Acceleration techniques for dependability simulation. M.S. Thesis

NASA Technical Reports Server (NTRS)

Barnette, James David

1995-01-01

As computer systems increase in complexity, the need to project system performance from the earliest design and development stages increases. We have to employ simulation for detailed dependability studies of large systems. However, as the complexity of the simulation model increases, the time required to obtain statistically significant results also increases. This paper discusses an approach that is application independent and can be readily applied to any process-based simulation model. Topics include background on classical discrete event simulation and techniques for random variate generation and statistics gathering to support simulation.

Inhibition of soluble epoxide hydrolase contributes to the anti-inflammatory effect of antimicrobial triclocarban in a murine model

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

Liu Junyan; Qiu Hong; Morisseau, Christophe

The increasing use of the antimicrobial triclocarban (TCC) in personal care products (PCPs) has resulted in concern regarding environmental pollution. TCC is a potent inhibitor of soluble epoxide hydrolase (sEH). Inhibitors of sEH (sEHIs) are anti-inflammatory, anti-hypertensive and cardio-protective in multiple animal models. However, the in vivo effects anticipated from a sEHI have not been reported for TCC. Here we demonstrated the anti-inflammatory effects in vivo of TCC in a murine model. TCC was employed in a lipopolysaccharide (LPS)-challenged murine model. Systolic blood pressure, plasma levels of several inflammatory cytokines and chemokine, and metabolomic profile of plasma oxylipins were determined.more » TCC significantly reversed LPS-induced morbid hypotension in a time-dependent manner. TCC significantly repressed the increased release of inflammatory cytokines and chemokine caused by LPS. Furthermore, TCC significantly shifted the oxylipin profile in vivo in a time-dependent manner towards resolution of inflammation as expected from a sEHI. These results demonstrated that at the doses used TCC is anti-inflammatory in the murine model. This study suggests that TCC may provide some benefits in humans in addition to its antimicrobial activities due to its potent inhibition of sEH. It may be a promising starting point for developing new low volume high value applications of TCC. However these biological effects also caution against the general over use of TCC in PCPs. - Graphical abstract: Display Omitted Research Highlights: > Anti-microbial triclocarban (TCC) is anti-inflammatory in a murine model. > TCC significantly shifted the oxylipin profile in vivo as expected from a sEHI. > TCC significantly reversed LPS-induced morbid hypotension in a time-dependent manner. > TCC significantly repressed LPS-induced increased release of inflammatory cytokines.« less

The Influence of the Brain on Overpopulation, Ageing and Dependency.

ERIC Educational Resources Information Center

Cape, Ronald D. T.

1989-01-01

With time, an increasing number in the world population is becoming old, and changes in the aging brain mean that a significant proportion of the aged are likely to be dependent on others. The devotion of resources to research into the aging brain could bring benefits far outweighing the investment. (Author/CW)

Superplastic Creep of Metal Nanowires from Rate-Dependent Plasticity Transition.

PubMed

Tao, Weiwei; Cao, Penghui; Park, Harold S

2018-05-22

Understanding the time-dependent mechanical behavior of nanomaterials such as nanowires is essential to predict their reliability in nanomechanical devices. This understanding is typically obtained using creep tests, which are the most fundamental loading mechanism by which the time-dependent deformation of materials is characterized. However, due to existing challenges facing both experimentalists and theorists, the time-dependent mechanical response of nanowires is not well-understood. Here, we use atomistic simulations that can access experimental time scales to examine the creep of single-crystal face-centered cubic metal (Cu, Ag, Pt) nanowires. We report that both Cu and Ag nanowires show significantly increased ductility and superplasticity under low creep stresses, where the superplasticity is driven by a rate-dependent transition in defect nucleation from twinning to trailing partial dislocations at the micro- or millisecond time scale. The transition in the deformation mechanism also governs a corresponding transition in the stress-dependent creep time at the microsecond (Ag) and millisecond (Cu) time scales. Overall, this work demonstrates the necessity of accessing time scales that far exceed those seen in conventional atomistic modeling for accurate insights into the time-dependent mechanical behavior and properties of nanomaterials.

[Effect of flooding time length on mycorrhizal colonization of three AM fungi in two wetland plants].

PubMed

Ma, Lei-Meng; Wang, Peng-Teng; Wang, Shu-Guang

2014-01-01

In order to provide information for elucidating effect of flooding on the formation and function of AM in wetland plants, three AM fungi (Glomus intraradices, Glomus versiforme, Glomus etunicatum) were used to investigate the effects of flooding time length on their colonization in cattail (Typha orientalis) and rice (Oryza sativa L. ). The results showed that the mycorrhizal colonization rate (MCR) presented downtrend with increasing flooding time length. In cattail, MCR of the fungus F3 was higher than those of fungi F1 and F2, but no significant difference in MCR was found between fungi F1 and F2. In rice, the MCRs of fungi F2 and F3 were higher than that of E1. In both plants, the proportional frequency of hyphae was the highest while the proportional frequency of arbuscules and vesicles was very low in all treatments, indicating that hyphal colonization was the main route for AM formation. The proportional frequency of hyphae in cattail increased with the flooding time length, but no significant trend was observed in rice plant. The proportional frequency of arhuscules decreased with the increase of flooding time, and was the highest in the treatment without flooding (treatment IV). The number of spores produced by AM fungi increased with increasing flooding time, and reached the highest in the treatment of long time flooding (treatment I). In the same treatment, the fungus F3 produced more spores than fungi F1 and F2. Changes in wet weight of the two plants showed that AM could increase cattail growth under flooding, hut little effect on rice growth was found. It is concluded that flooding time length significantly affected the mycorrhizal colonization rate and the proportional frequency of colonization. AM could enhance the growth of wetland plant, but this depends on the mycorrhizal dependence of host plant on AM fungi. Therefore, flooding time length should be considered in the inoculation of wetland plants with AM fungi.

Increased serum IL-6 level time-dependently regulates hyperalgesia and spinal mu opioid receptor expression during CFA-induced arthritis

PubMed Central

Tekieh, E.; Zaringhalam, Jalal; Manaheji, H.; Maghsoudi, N.; Alani, B.; Zardooz, H.

2011-01-01

Interleukin (IL)-6 is known to cause pro- and anti-inflammatory effects during different stages of inflammation. Recent therapeutic investigations have focused on treatment of various inflammatory disorders with anti-cytokine substances. As a result, the aim of this study was to further elucidate the influence of IL-6 in hyperalgesia and edema during different stages of Complete Freund's Adjuvant (CFA)-induced arthritis (AA) in male Wistar rats. AA was induced by a single subcutaneous injection of CFA into the rats' hindpaw. Anti-IL-6 was administered either daily or weekly during the 21 days of study. Spinal mu opioid receptor (mOR) expression was detected by Western blotting. Daily and weekly treatment with an anti-IL-6 antibody significantly decreased paw edema in the AA group compared to the AA control group. Additionally, daily and weekly anti-IL-6 administration significantly reduced hyperalgesia on day 7 in the AA group compared to the AA control group; however, there were significant increases in hyperalgesia in the antibody-treated group on days 14 and 21 compared to the AA control group. IL-6 antibody-induced increases in hyperalgesia on the 14th and 21st days after CFA injection correlated with a time-dependent, significant reduction in spinal mOR expression during anti-IL-6 treatment. Our study confirmed the important time-dependent relationship between serum IL-6 levels and hyperalgesia during AA. These results suggest that the stages of inflammation in AA must be considered for anti-hyperalgesic and anti-inflammatory interventions via anti-IL-6 antibody treatment. PMID:27857662

Increased serum IL-6 level time-dependently regulates hyperalgesia and spinal mu opioid receptor expression during CFA-induced arthritis.

PubMed

Tekieh, E; Zaringhalam, Jalal; Manaheji, H; Maghsoudi, N; Alani, B; Zardooz, H

2011-01-01

Interleukin (IL)-6 is known to cause pro- and anti-inflammatory effects during different stages of inflammation. Recent therapeutic investigations have focused on treatment of various inflammatory disorders with anti-cytokine substances. As a result, the aim of this study was to further elucidate the influence of IL-6 in hyperalgesia and edema during different stages of Complete Freund's Adjuvant (CFA)-induced arthritis (AA) in male Wistar rats. AA was induced by a single subcutaneous injection of CFA into the rats' hindpaw. Anti-IL-6 was administered either daily or weekly during the 21 days of study. Spinal mu opioid receptor (mOR) expression was detected by Western blotting. Daily and weekly treatment with an anti-IL-6 antibody significantly decreased paw edema in the AA group compared to the AA control group. Additionally, daily and weekly anti-IL-6 administration significantly reduced hyperalgesia on day 7 in the AA group compared to the AA control group; however, there were significant increases in hyperalgesia in the antibody-treated group on days 14 and 21 compared to the AA control group. IL-6 antibody-induced increases in hyperalgesia on the 14 th and 21 st days after CFA injection correlated with a time-dependent, significant reduction in spinal mOR expression during anti-IL-6 treatment. Our study confirmed the important time-dependent relationship between serum IL-6 levels and hyperalgesia during AA. These results suggest that the stages of inflammation in AA must be considered for anti-hyperalgesic and anti-inflammatory interventions via anti-IL-6 antibody treatment.

Modulation of CD4(+) T cell-dependent specific cytotoxic CD8(+) T cells differentiation and proliferation by the timing of increase in the pathogen load.

PubMed

Tzelepis, Fanny; Persechini, Pedro M; Rodrigues, Mauricio M

2007-04-25

Following infection with viruses, bacteria or protozoan parasites, naïve antigen-specific CD8(+) T cells undergo a process of differentiation and proliferation to generate effector cells. Recent evidences suggest that the timing of generation of specific effector CD8(+) T cells varies widely according to different pathogens. We hypothesized that the timing of increase in the pathogen load could be a critical parameter governing this process. Using increasing doses of the protozoan parasite Trypanosoma cruzi to infect C57BL/6 mice, we observed a significant acceleration in the timing of parasitemia without an increase in mouse susceptibility. In contrast, in CD8 deficient mice, we observed an inverse relationship between the parasite inoculum and the timing of death. These results suggest that in normal mice CD8(+) T cells became protective earlier, following the accelerated development of parasitemia. The evaluation of specific cytotoxic responses in vivo to three distinct epitopes revealed that increasing the parasite inoculum hastened the expansion of specific CD8(+) cytotoxic T cells following infection. The differentiation and expansion of T. cruzi-specific CD8(+) cytotoxic T cells is in fact dependent on parasite multiplication, as radiation-attenuated parasites were unable to activate these cells. We also observed that, in contrast to most pathogens, the activation process of T. cruzi-specific CD8(+) cytotoxic T cells was dependent on MHC class II restricted CD4(+) T cells. Our results are compatible with our initial hypothesis that the timing of increase in the pathogen load can be a critical parameter governing the kinetics of CD4(+) T cell-dependent expansion of pathogen-specific CD8(+) cytotoxic T cells.

Efficiency and cross-correlation in equity market during global financial crisis: Evidence from China

NASA Astrophysics Data System (ADS)

Ma, Pengcheng; Li, Daye; Li, Shuo

2016-02-01

Using one minute high-frequency data of the Shanghai Composite Index (SHCI) and the Shenzhen Composite Index (SZCI) (2007-2008), we employ the detrended fluctuation analysis (DFA) and the detrended cross correlation analysis (DCCA) with rolling window approach to observe the evolution of market efficiency and cross-correlation in pre-crisis and crisis period. Considering the fat-tail distribution of return time series, statistical test based on shuffling method is conducted to verify the null hypothesis of no long-term dependence. Our empirical research displays three main findings. First Shanghai equity market efficiency deteriorated while Shenzhen equity market efficiency improved with the advent of financial crisis. Second the highly positive dependence between SHCI and SZCI varies with time scale. Third financial crisis saw a significant increase of dependence between SHCI and SZCI at shorter time scales but a lack of significant change at longer time scales, providing evidence of contagion and absence of interdependence during crisis.

Effect of Time-Dependent Sorption on the Dissipation of Water-Extractable Pesticides in Soils.

PubMed

Motoki, Yutaka; Iwafune, Takashi; Seike, Nobuyasu; Inao, Keiya; Otani, Takashi

2016-06-08

The dissipation behavior of water-extractable pesticides in soils is important when assessing the phytoavailability of pesticides in soils. This process is less understood than pesticide extraction with organic solvents. To elucidate the dissipation behavior of water-extractable pesticides in soils, we conducted an incubation study using 27 pesticides and five Japanese soils. The rate of decrease of the level of pesticides in water extracts was faster in soils than that of total extracts (water extracts and acetone extracts). This suggests that time-dependent sorption contributed to the difference in the dissipation between the pesticides in water and total extracts from soils. Increased apparent sorption coefficients (Kd,app) with time were positively and significantly correlated with Kd,app values of a 0 day incubation [Kd,app(t0)]. This empirical relationship suggests that Kd,app(t0) values can predict the time-dependent increase in Kd,app and the dissipation of water-extractable pesticides in soils.

Cytosolic increased labile Zn2+ contributes to arrhythmogenic action potentials in left ventricular cardiomyocytes through protein thiol oxidation and cellular ATP depletion.

PubMed

Degirmenci, Sinan; Olgar, Yusuf; Durak, Aysegul; Tuncay, Erkan; Turan, Belma

2018-07-01

Intracellular labile (free) Zn 2+ -level ([Zn 2+ ] i ) is low and increases markedly under pathophysiological conditions in cardiomyocytes. High [Zn 2+ ] i is associated with alterations in excitability and ionic-conductances while exact mechanisms are not clarified yet. Therefore, we examined the elevated-[Zn 2+ ] i on some sarcolemmal ionic-mechanisms, which can mediate cardiomyocyte dysfunction. High-[Zn 2+ ] i induced significant changes in action potential (AP) parameters, including depolarization in resting membrane-potential and prolongations in AP-repolarizing phases. We detected also the time-dependent effects such as induction of spontaneous APs at the time of ≥ 3 min following [Zn 2+ ] i increases, a manner of cellular ATP dependent and reversible with disulfide-reducing agent dithiothreitol, DTT. High-[Zn 2+ ] i induced inhibitions in voltage-dependent K + -channel currents, such as transient outward K + -currents, I to , steady-state currents, I ss and inward-rectifier K + -currents, I K1 , reversible with DTT seemed to be responsible from the prolongations in APs. We, for the first time, demonstrated that lowering cellular ATP level induced significant decreaeses in both I ss and I K1 , while no effect on I to . However, the increased-[Zn 2+ ] i could induce marked activation in ATP-sensitive K + -channel currents, I KATP , depending on low cellular ATP and thiol-oxidation levels of these channels. The mRNA levels of Kv4.3, Kv1.4 and Kv2.1 were depressed markedly with increased-[Zn 2+ ] i with no change in mRNA level of Kv4.2, while the mRNA level of I KATP subunit, SUR2A was increased significantly with increased-[Zn 2+ ] i , being reversible with DTT. Overall we demonstrated that high-[Zn 2+ ] i, even if nanomolar levels, alters cardiac function via prolonged APs of cardiomyocytes, at most, due to inhibitions in voltage-dependent K + -currents, although activation of I KATP is playing cardioprotective role, through some biochemical changes in cellular ATP- and thiol-oxidation levels. It seems, a well-controlled [Zn 2+ ] i can be novel therapeutic target for cardiac complications under pathological conditions including oxidative stress. Copyright © 2018 Elsevier GmbH. All rights reserved.

Effect of advanced glycosylation end products (AGEs) on proliferation of human bone marrow mesenchymal stem cells (MSCs) in vitro.

PubMed

Lu, Yi-Qun; Lu, Yan; Li, Hui-Juan; Cheng, Xing-Bo

2012-10-01

This study aims to explore the effect of advanced glycosylation end products (AGEs) on proliferation of human bone marrow mesenchymal stem cells in vitro and the underlying mechanism. Bone marrow cell proliferation was determined by WST-8 assay using Cell Counting Kit-8 under the intervention of AGEs. In addition, the content of maldondialdehyde (MDA) and the activity of superoxide dismutase (SOD) were also measured. The proliferation activity of mesenchymal stem cells (MSCs) was significantly inhibited when AGEs were added to culture medium, and this effect was dose-dependent and time-dependent. As the concentration of AGEs-bovine serum albumin increased, the content of intracellular MDA was significantly increased, but the activity of SOD in cell homogenates was significantly suppressed, which also showed a dose-dependent manner. AGEs could significantly inhibit the proliferation of MSCs in vitro by improving the oxidative stress in MSCs and breaking the homeostasis of intracellular environment.

Memory effects of Aronia melanocarpa fruit juice in a passive avoidance test in rats.

PubMed

Valcheva-Kuzmanova, Stefka V; Eftimov, Miroslav Tz; Tashev, Roman E; Belcheva, Iren P; Belcheva, Stiliana P

2014-01-01

To study the effect of Aronia melanocarpa fruit juice on memory in male Wistar rats. The juice was administered orally for 7, 14, 21 and 30 days at doses of 2.5 ml/kg, 5 ml/kg and 10 ml/kg. Memory was assessed in the one-way passive avoidance task (step through) which consisted of one training session and two retention tests (3 hours and 24 hours after training). The variables measured were the latency time to step into the dark compartment of the apparatus and the learning criterion (remaining in the illuminated compartment for at least 180 sec). Oral administration of Aronia melanocarpa fruit juice for 7 and 14 days resulted in a dose-dependent tendency to increase the latency time and the learning criterion compared to saline-treated controls but the effect failed to reach statistical significance. After 21 days of treatment, the juice dose-dependently prolonged the latency time at the retention tests, the effect being significant at doses of 5 ml/kg and 10 ml/kg. Applied for 30 days, the juice in all the tested doses increased significantly the latency time at the retention tests and the dose of 10 ml/kg significantly increased the percentage of rats reaching the learning criterion. These findings suggest that Aronia melanocarpa fruit juice could improve memory in rats. The effect is probably due to the polyphenolic ingredients of the juice which have been shown to be involved in learning and memory processes.

The effect of UV-Vis to near-infrared light on the biological response of human dental pulp cells

NASA Astrophysics Data System (ADS)

Hadis, Mohammed A.; Cooper, Paul R.; Milward, Michael R.; Gorecki, Patricia; Tarte, Edward; Churm, James; Palin, William M.

2015-03-01

Human dental pulp cells (DPCs) were isolated and cultured in phenol-red-free α-MEM/10%-FCS at 37ºC in 5% CO2. DPCs at passages 2-4 were seeded (150μL; 25,000 cell/ml) in black 96-microwell plates with transparent bases. 24h post-seeding, cultures were irradiated using a bespoke LED array consisting of 60 LEDs (3.5mW/cm2) of wavelengths from 400-900nm (10 wavelengths, n=6) for time intervals of up to 120s. Metabolic and mitochondrial activity was assessed via a modified MTT assay. Statistical differences were identified using multi-factorial analysis of variance and post-hoc Tukey tests (P=0.05). The biological responses were significantly dependent upon post-irradiation incubation period, wavelength and exposure time (P<0.05). At shorter wavelength irradiances (400nm), a reduction in mitochondrial activity was detected although not significant, whereas longer wavelength irradiances (at 633, 656, 781 and 799nm) significantly increased mitochondrial activity (P<0.05) in DPCs. At these wavelengths, mitochondrial activity was generally increased for exposures less than 90s with 30s exposures being most effective with 24h incubation. Increasing the post-irradiation incubation period increased the measured response and identified further significance (P<0.05). The biological responses of human DPCs were wavelength, exposure-time and incubation period dependent. The optimisation of irradiation parameters will be key to the successful application of LLLT in dentistry.

The Estimation of Short Time Intervals as a Function of Age and Metronome Pacing.

ERIC Educational Resources Information Center

Kline, Donald W.; And Others

1980-01-01

The time judgments of the older participants were significantly and systematically determined by a metronome rate. Results are consistent with the notion of increased field-dependence among older persons and suggest that their greater social conformity and their inability to ignore irrelevant stimuli might also be explicable. (Author)

In vitro study of the effect of three hydrogen peroxide concentrations on the corrosion behavior and surface topography of alumina-reinforced dental ceramic.

PubMed

Abu-Eittah, Manal R; Mandour, Mona H

2011-10-01

This in vitro investigation studied the effect of three hydrogen peroxide (HP) concentrations (30%, 35%, 38% v/v) at two time intervals (1 and 2 hours) on the corrosion behavior and surface topography of a dental ceramic. A total of 62 Vitadur Alpha discs were constructed following manufacturer instructions. Specimens were divided into four main groups (n = 8). Group 1 (control): specimens were immersed in 4% acetic acid for 18 hours at 80°C. Groups 2, 3, and 4: specimens were immersed in 30%, 35%, and 38% HP concentrations, respectively. Each of the three groups was divided into two subgroups (a and b) according to the immersion time (1 and 2 hours, respectively). Specimens of subgroup a were further immersed in 4% acetic acid for 18 hours at 80°C and were designated as subgroup c. The corrosion behavior of the ceramic specimens were tested by solution analysis using the atomic absorption method, weight loss percent, and corrosion rate. Surface topography was investigated by surface roughness (Ra) measurements and scanning electron microscopy (SEM). Results were statistically analyzed. There was a significant increase for ions leached with the increase in time of immersion for all ions at 35% and 38% HP, while at 30% HP, ions of K(+) , Al(3+) , and Si(4+) did not increase significantly with time. The results also showed that at a fixed time of immersion, all ions released were dependent on the increase of HP concentration except for Al(3+) ions (p < 0.05). The combined treatment of specimens with HP followed by acetic acid had a significant effect on the increase of ions leached (p < 0.05). The surface roughness values for all specimens increased significantly with time of immersion as well as with the increase in concentration of HP (p < 0.05). These results were confirmed with SEM. The amount of released ions is directly proportional to HP concentration and time of immersion. Specimens exposed to both HP and acetic acid showed increased weight loss and a higher corrosion rate than those exposed to acetic acid only. Surface roughness values were time and HP concentration dependent. © 2011 by The American College of Prosthodontists.

Craving and subsequent opioid use among opioid dependent patients who initiate treatment with buprenorphine

PubMed Central

Tsui, Judith I.; Anderson, Bradley J.; Strong, David R.; Stein, Michael D.

2016-01-01

Background Few studies have directly assessed associations between craving and subsequent opioid use among treated patients. Our objective was to prospectively evaluate the relative utility of two craving questionnaires to predict opioid use among opioid dependent patients in treatment. Method Opioid dependent patients (n=147) initiating buprenorphine treatment were assessed for three months. Craving was measured using: 1) the Desires for Drug Questionnaire (DDQ) and 2) the Penn Alcohol-Craving Scale adapted for opioid craving (PCS) for this study. Multi-level logistic regression models estimated the effects of craving on the likelihood of opioid use after adjusting for gender, age, ethnicity, education, opioid of choice, frequency of use, pain and depression. In these analyses craving assessed at time t was entered as a time-varying predictor of opioid use at time t+1. Results In adjusted regression models, a 1-point increase in PCS scores (on a 7-point scale) was associated with a significant increase in the odds of opioid use at the subsequent assessment (OR = 1.27, 95% CI 1.08; 1.49, p < .01). The odds of opioid use at the subsequent follow-up assessment increased significantly as DDQ desire and intention scores increased (OR = 1.25, 95%CI 1.03; 1.51, p< .05), but was not associated significantly with DDQ negative reinforcement (OR = 1.01, 95%CI 0.88; 1.17, p > .05) or DDQ control (OR = 0.97, 95%CI 0.85; 1.11, p > .05) scores. Conclusion Self-reported craving for opioids was associated with subsequent lapse to opioid use among a cohort of patients treated with buprenorphine. PMID:24521036

Detection on emamectin benzoate-induced apoptosis and DNA damage in Spodoptera frugiperda Sf-9 cell line.

PubMed

Wu, Xiwei; Zhang, Lei; Yang, Chao; Zong, Mimi; Huang, Qingchun; Tao, Liming

2016-01-01

Emamectin benzoate (EMB), an important macrocyclic lactone insecticide that belongs to the avermectin family and possesses excellent potency in controlling pests, is non-carcinogenic and non-mutagenic conducted in rats and mice, but EMB-induced cytotoxicity and genotoxicity in arthropod insect have been seldom reported yet. In the present paper, we quantified the cytotoxicity of EMB through the detections on cell viability, DNA damage, and cell apoptosis in Spodoptera frugiperda Sf-9 cells in vitro. The results showed that EMB caused a concentration- and time-dependent reduction on the viability of Sf-9 cells, and the median inhibitory concentrations (IC50) were 3.34μM at 72h of exposure. The dual acridine orange/ethidium bromide staining showed that exposure to EMB induced a significant time- and concentration-dependent increase on cell apoptosis. The alkaline comet assay revealed that EMB induced significant increases on single-strand DNA breaks, and the percentage of γH2AX-positive cells represented a time- and concentration-dependent formation of DNA double-strand breaks in Sf-9 cells. Interestingly, the similar cytotoxic actions of EMB also went for the human cancerous HeLa cells as a control cell group. Data demonstrated the potential cytotoxic effect of EMB on Sf-9 cells that was significantly greater than the effect of hydrogen peroxide at the same concentrations. Copyright © 2015 Elsevier Inc. All rights reserved.

Comparison of the effects of acute fluvoxamine and desipramine administration on melatonin and cortisol production in humans.

PubMed Central

Skene, D J; Bojkowski, C J; Arendt, J

1994-01-01

1. Acute administration of the specific serotonin uptake inhibitor, fluvoxamine (100 mg at 16.00 h), markedly increased nocturnal plasma melatonin concentrations, with high levels extending into the morning hours. 2. Acute administration of the noradrenaline uptake inhibitor, desipramine (DMI) (100 mg at 16.00 h), increased evening plasma melatonin concentrations. 3. Both drug treatments increased the duration of melatonin secretion, fluvoxamine significantly delaying the offset time and DMI significantly advancing the onset time. 4. The stimulatory effect of DMI on plasma melatonin was mirrored by increased urinary 6-sulphatoxymelatonin (aMT6s) excretion. 5. On the contrary, there was no correlation between plasma melatonin and urinary aMT6s concentrations following fluvoxamine treatment, suggesting that fluvoxamine may inhibit the metabolism of melatonin. 6. Treatment with DMI increased plasma cortisol concentrations in the evening and early morning, treatment with fluvoxamine increased plasma cortisol at 03.00 h, 10.00 h and 11.00 h. 7. The drug treatments affected different aspects of the nocturnal plasma melatonin profile suggesting that the amplitude of the melatonin rhythm may depend upon serotonin availability and/or melatonin metabolism whilst the onset of melatonin production depends upon noradrenaline availability. PMID:8186063

Physiologic volume of phosphorus during hemodialysis: predictions from a pseudo one-compartment model.

PubMed

Leypoldt, John K; Akonur, Alp; Agar, Baris U; Culleton, Bruce F

2012-10-01

The kinetics of plasma phosphorus concentrations during hemodialysis (HD) are complex and cannot be described by conventional one- or two-compartment kinetic models. It has recently been shown by others that the physiologic (or apparent distribution) volume for phosphorus (Vr-P) increases with increasing treatment time and shows a large variation among patients treated by thrice weekly and daily HD. Here, we describe the dependence of Vr-P on treatment time and predialysis plasma phosphorus concentration as predicted by a novel pseudo one-compartment model. The kinetics of plasma phosphorus during conventional and six times per week daily HD were simulated as a function of treatment time per session for various dialyzer phosphate clearances and patient-specific phosphorus mobilization clearances (K(M)). Vr-P normalized to extracellular volume from these simulations were reported and compared with previously published empirical findings. Simulated results were relatively independent of dialyzer phosphate clearance and treatment frequency. In contrast, Vr-P was strongly dependent on treatment time per session; the increase in Vr-P with treatment time was larger for higher values of K(M). Vr-P was inversely dependent on predialysis plasma phosphorus concentration. There was significant variation among predicted Vr-P values, depending largely on the value of K(M). We conclude that a pseudo one-compartment model can describe the empirical dependence of the physiologic volume of phosphorus on treatment time and predialysis plasma phosphorus concentration. Further, the variation in physiologic volume of phosphorus among HD patients is largely due to differences in patient-specific phosphorus mobilization clearance. © 2012 The Authors. Hemodialysis International © 2012 International Society for Hemodialysis.

[Changes of telemetry electrical activity in the infralimbic cortex of morphine-dependent rats with extinguished drug-seeking behavior].

PubMed

Li, Jing; Pan, Qunwan; Zhu, Zaiman; Li, Min; Bai, Yu; Yu, Ran

2015-05-01

To investigate the changes of telemetry electrical activity in the infralimbic cortex (IL) of morphine-dependent rats with extinguished drug-seeking behavior. SD rats were randomly divided into model group and control group and received operations of brain stereotaxic electrode embedding in the IL. The rats in the model group were induced to acquire morphine dependence and then received subsequent extinction training, and the changes of electrical activity in the IL were recorded with a physical wireless telemetry system. In rats with morphine dependence, the time staying in the white box was significantly longer on days 1 and 2 after withdrawal than that before morphine injection and that of the control rats, but was obviously reduced on days 1 and 2 after extinction training to the control level. Compared with the control group, the morphine-dependent rats on day 2 following withdrawal showed significantly increased β wave and decreased δ wave when they stayed in the white box but significantly increased δ wave and decreased α wave and β wave when they shuttled from the black to the white box. On day 2 of extinction, the model rats, when staying in the white box, showed significantly decreased θ wave compared with that of the control rats group but decreased β wave and θ wave and increased δ wave compared with those in the withdrawal period. When they shuttled from black to white box, the model rats showed decreased δ wave and increased α wave and β wave compared with those in the withdrawal period. Morphine-dependent rats have abnormal changes of electrical activity in the IL in drug-seeking extinction to affect their drug-seeking motive and inhibit the expression and maintenance of drug-seeking behaviors.

Outcomes following surgical management of femoral neck fractures in elderly dialysis-dependent patients.

PubMed

Puvanesarajah, Varun; Amin, Raj; Qureshi, Rabia; Shafiq, Babar; Stein, Ben; Hassanzadeh, Hamid; Yarboro, Seth

2018-06-01

Proximal femur fractures are one of the most common fractures observed in dialysis-dependent patients. Given the large comorbidity burden present in this patient population, more information is needed regarding post-operative outcomes. The goal of this study was to assess morbidity and mortality following operative fixation of femoral neck fractures in the dialysis-dependent elderly. The full set of medicare data from 2005 to 2014 was retrospectively analyzed. Elderly patients with femoral neck fractures were selected. Patients were stratified based on dialysis dependence. Post-operative morbidity and mortality outcomes were compared between the two populations. Adjusted odds were calculated to determine the effect of dialysis dependence on outcomes. A total of 320,629 patients met the inclusion criteria. Of dialysis-dependent patients, 1504 patients underwent internal fixation and 2662 underwent arthroplasty. For both surgical cohorts, dialysis dependence was found to be associated with at least 1.9 times greater odds of mortality within 1 and 2 years post-operatively. Blood transfusions within 90 days and infections within 2 years were significantly increased in the dialysis-dependent study cohort. Dialysis dependence alone did not contribute to increased mechanical failure or major medical complications. Regardless of the surgery performed, dialysis dependence is a significant risk factor for major post-surgical morbidity and mortality after operative treatment of femoral neck fractures in this population. Increased mechanical failure in the internal fixation group was not observed. The increased risk associated with caring for this population should be understood when considering surgical intervention and counseling patients.

Does whole blood coagulation analysis reflect developmental haemostasis?

PubMed

Ravn, Hanne Berg; Andreasen, Jo Bønding; Hvas, Anne-Mette

2017-04-01

: Developmental haemostasis has been well documented over the last 3 decades and age-dependent reference ranges have been reported for a number of plasmatic coagulation parameters. With the increasing use of whole blood point-of-care tests like rotational thromboelastometry (ROTEM) and platelet function tests, an evaluation of age-dependent changes is warranted for these tests as well. We obtained blood samples from 149 children, aged 1 day to 5.9 years, and analysed conventional plasmatic coagulation tests, including activated partial prothrombin time, prothrombin time, and fibrinogen (functional). Whole blood samples were analysed using ROTEM to assess overall coagulation capacity and Multiplate analyzer to evaluate platelet aggregation. Age-dependent changes were analysed for all variables. We found age-dependent differences in all conventional coagulation tests (all P values < 0.05), but there was no sign of developmental changes in whole blood coagulation assessment when applying ROTEM, apart from clotting time in the EXTEM assay (P < 0.03). Despite marked differences in mean platelet aggregation between age groups, data did not reach statistical significance. Citrate-anticoagulated blood showed significantly reduced platelet aggregation compared with blood anticoagulated with heparin or hirudin (all P values < 0.003). We confirmed previous developmental changes in conventional plasmatic coagulation test. However, these age-dependent changes were not displayed in whole blood monitoring using ROTEM or Multiplate analyzer. Type of anticoagulant had a significant influence on platelet aggregation across all age groups.

Frequency-dependent acceleration of relaxation in mammalian heart: a property not relying on phospholamban and SERCA2a phosphorylation

PubMed Central

Valverde, Carlos A; Mundiña-Weilenmann, Cecilia; Said, Matilde; Ferrero, Paola; Vittone, Leticia; Salas, Margarita; Palomeque, Julieta; Petroff, Martín Vila; Mattiazzi, Alicia

2005-01-01

An increase in stimulation frequency causes an acceleration of myocardial relaxation (FDAR). Several mechanisms have been postulated to explain this effect, among which is the Ca2+–calmodulin-dependent protein kinase (CaMKII)-dependent phosphorylation of the Thr17 site of phospholamban (PLN). To gain further insights into the mechanisms of FDAR, we studied the FDAR and the phosphorylation of PLN residues in perfused rat hearts, cat papillary muscles and isolated cat myocytes. This allowed us to sweep over a wide range of frequencies, in species with either positive or negative force–frequency relationships, as well as to explore the FDAR under isometric (or isovolumic) and isotonic conditions. Results were compared with those produced by isoprenaline, an intervention known to accelerate relaxation (IDAR) via PLN phosphorylation. While IDAR occurs tightly associated with a significant increase in the phosphorylation of Ser16 and Thr17 of PLN, FDAR occurs without significant changes in the phosphorylation of PLN residues in the intact heart and cat papillary muscles. Moreover, in intact hearts, FDAR was not associated with any significant change in the CaMKII-dependent phosphorylation of sarcoplasmic/endoplasmic Ca2+ ATPase (SERCA2a), and was not affected by the presence of the CaMKII inhibitor, KN-93. In isolated myocytes, FDAR occurred associated with an increase in Thr17 phosphorylation. However, for a similar relaxant effect produced by isoprenaline, the phosphorylation of PLN (Ser16 and Thr17) was significantly higher in the presence of the β-agonist. Moreover, the time course of Thr17 phosphorylation was significantly delayed with respect to the onset of FDAR. In contrast, the time course of Ser16 phosphorylation, the first residue that becomes phosphorylated with isoprenaline, was temporally associated with IDAR. Furthermore, KN-93 significantly decreased the phosphorylation of Thr17 that was evoked by increasing the stimulation frequency, but failed to affect FDAR. Taken together, the results provide direct evidence indicating that CaMKII phosphorylation pathways are not involved in FDAR and that FDAR and IDAR do not share a common underlying mechanism. More likely, a CaMKII-independent mechanism could be involved, whereby increasing stimulation frequency would disrupt the SERCA2a–PLN interaction, leading to an increase in SR Ca2+ uptake and myocardial relaxation. PMID:15528241

Spatially varying density dependence drives a shifting mosaic of survival in a recovering apex predator (Canis lupus).

PubMed

O'Neil, Shawn T; Bump, Joseph K; Beyer, Dean E

2017-11-01

Understanding landscape patterns in mortality risk is crucial for promoting recovery of threatened and endangered species. Humans affect mortality risk in large carnivores such as wolves ( Canis lupus ), but spatiotemporally varying density dependence can significantly influence the landscape of survival. This potentially occurs when density varies spatially and risk is unevenly distributed. We quantified spatiotemporal sources of variation in survival rates of gray wolves ( C. lupus ) during a 21-year period of population recovery in the Upper Peninsula of Michigan, USA. We focused on mapping risk across time using Cox Proportional Hazards (CPH) models with time-dependent covariates, thus exploring a shifting mosaic of survival. Extended CPH models and time-dependent covariates revealed influences of seasonality, density dependence and experience, as well as individual-level factors and landscape predictors of risk. We used results to predict the shifting landscape of risk at the beginning, middle, and end of the wolf recovery time series. Survival rates varied spatially and declined over time. Long-term change was density-dependent, with landscape predictors such as agricultural land cover and edge densities contributing negatively to survival. Survival also varied seasonally and depended on individual experience, sex, and resident versus transient status. The shifting landscape of survival suggested that increasing density contributed to greater potential for human conflict and wolf mortality risk. Long-term spatial variation in key population vital rates is largely unquantified in many threatened, endangered, and recovering species. Variation in risk may indicate potential for source-sink population dynamics, especially where individuals preemptively occupy suitable territories, which forces new individuals into riskier habitat types as density increases. We encourage managers to explore relationships between adult survival and localized changes in population density. Density-dependent risk maps can identify increasing conflict areas or potential habitat sinks which may persist due to high recruitment in adjacent habitats.

Commonly used stimulants: Sleep problems, dependence and psychological distress.

PubMed

Ogeil, Rowan P; Phillips, James G

2015-08-01

Caffeine and nicotine are commonly used stimulants that enhance alertness and mood. Discontinuation of both stimulants is associated with withdrawal symptoms including sleep and mood disturbances, which may differ in males and females. The present study examines changes in sleep quality, daytime sleepiness and psychological distress associated with use and dependence on caffeine and nicotine. An online survey comprising validated tools to assess sleep quality, excessive daytime sleepiness and psychological distress was completed by 166 participants (74 males, 96 females) with a mean age of 28 years. Participants completed the study in their own time, and were not offered any inducements to participate. Sleep quality was poorer in those dependent upon caffeine or nicotine, and there were also significant interaction effects with gender whereby females reported poorer sleep despite males reporting higher use of both stimulants. Caffeine dependence was associated with poorer sleep quality, increased daytime dysfunction, and increased levels of night time disturbance, while nicotine dependence was associated with poorer sleep quality and increased use of sleep medication and sleep disturbances. There were strong links between poor sleep and diminished affect, with psychological distress found to co-occur in the context of disturbed sleep. Stimulants are widely used to promote vigilance and mood; however, dependence on commonly used drugs including caffeine and nicotine is associated with decrements in sleep quality and increased psychological distress, which may be compounded in female dependent users. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Mechanism of the melanogenesis stimulation activity of (-)-cubebin in murine B16 melanoma cells.

PubMed

Hirata, Noriko; Naruto, Shunsuke; Ohguchi, Kenji; Akao, Yukihiro; Nozawa, Yoshinori; Iinuma, Munekazu; Matsuda, Hideaki

2007-07-15

(-)-Cubebin showed a melanogenesis stimulation activity in a concentration-dependent manner in murine B16 melanoma cells without any significant effects on cell proliferation. Tyrosinase activity was increased at 24-72 h after addition of cubebin to B16 cells, and then intracellular melanin amount was increased at 48-96 h after the treatment. The expression levels of tyrosinase were time-dependently enhanced after the treatment with cubebin. At the same time, the expression levels of tyrosinase mRNA were also increased after addition of cubebin. Furthermore Western blot analysis revealed that cubebin elevated the level of phosphorylation of p38 mitogen-activated protein kinase (MAPK). SB203580, a selective inhibitor of p38 MAPK, completely blocked cubebin-induced expression of tyrosinase mRNA in B16 cells. These results suggested that cubebin increased melanogenesis in B16 cells through the enhancement of tyrosinase expression mediated by activation of p38 MAPK.

The organophosphate insecticide chlorpyrifos confers its genotoxic effects by inducing DNA damage and cell apoptosis.

PubMed

Li, Diqiu; Huang, Qingchun; Lu, Miaoqing; Zhang, Lei; Yang, Zhichuan; Zong, Mimi; Tao, Liming

2015-09-01

The organophosphate insecticide chlorpyrifos (CPF) is known to induce neurological effects, malformation and micronucleus formation, persistent developmental disorders, and maternal toxicity in rats and mice. The binding of chlorpyrifos with DNA to produce DNA adducts leads to an increasing social concern about the genotoxic risk of CPF in human, but CPF-induced cytotoxicity through DNA damage and cell apoptosis is not well understood. Here, we quantified the cytotoxicity and potential genotoxicity of CPF using the alkaline comet assay, γH2AX foci formation, and the DNA laddering assay in order to detect DNA damage and apoptosis in human HeLa and HEK293 cells in vitro. Drosophila S2 cells were used as a positive control. The alkaline comet assay showed that sublethal concentrations of CPF induced significant concentration-dependent increases in single-strand DNA breaks in the treated cells compared with the control. The percentage of γH2AX-positive HeLa cells revealed that CPF also causes DNA double-strand breaks in a time-dependent manner. Moreover, DNA fragmentation analysis demonstrated that exposure to CPF induced a significant concentration- and time-dependent increase in cell apoptosis. We conclude that CPF is a strongly genotoxic agent that induces DNA damage and cell apoptosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Significant enhancement of yellow-green light emission of ZnO nanorod arrays using Ag island films

NASA Astrophysics Data System (ADS)

Lin, Chin-An; Tsai, Dung-Sheng; Chen, Cheng-Ying; He-Hau, Jr.

2011-03-01

Surface plasmon (SP) mediated emission from ZnO nanorod arrays (NRAs)/Ag/Si structures has been investigated. The ratio of visible emission to UV emission can be increased by over 30 times via coupling with SP without deterioration of the crystal quality. The fact that the effect of SP crucially depends on the size of Ag island films provides the feasibility to significantly enhance the yellow-green emission of the ZnO nanostructures without sacrificing the crystallinity of ZnO.Surface plasmon (SP) mediated emission from ZnO nanorod arrays (NRAs)/Ag/Si structures has been investigated. The ratio of visible emission to UV emission can be increased by over 30 times via coupling with SP without deterioration of the crystal quality. The fact that the effect of SP crucially depends on the size of Ag island films provides the feasibility to significantly enhance the yellow-green emission of the ZnO nanostructures without sacrificing the crystallinity of ZnO. Electronic supplementary information (ESI) available. See DOI: 10.1039/c0nr00732c

Changes in Nutrition-Related Behaviors in Alcohol-Dependent Patients After Outpatient Detoxification: The Role of Chocolate.

PubMed

Stickel, Anna; Rohdemann, Maren; Landes, Tom; Engel, Katharina; Banas, Roman; Heinz, Andreas; Müller, Christian A

2016-01-01

Previous studies have reported changes in nutrition-related behaviors in alcohol-dependent patients after alcohol detoxification, but prospective studies assessing the effects of these changes on maintaining abstinence are lacking. To assess changes in craving and consumption of chocolate and other sweets over time up to six months after outpatient alcohol detoxification treatment and to detect differences in abstinent versus nonabstinent patients. One hundred and fifty alcohol-dependent patients were included in this prospective observational study. Participants completed self-report questionnaires on nutrition-related behaviors and craving before detoxification treatment (baseline, t1), one week (t2), one month (t3), and six months later (t4). Significant changes in craving for and consumption of chocolate as well as in craving for other sweets were observed over time. Increases were most prominent within the first month. Patients who remained abstinent until t3 consumed three times more chocolate than nonabstainers. One quarter of the patients switched from being rare (t1) to frequent (t3) chocolate eaters, and 84% of these remained abstinent until t3. No significant correlations were found between craving for alcohol and craving for or consumption of chocolate or other sweets. In the first month after outpatient alcohol detoxification treatment, significant changes in nutrition-related behaviors were observed. These changes were not associated with alcohol craving. For a subgroup, increasing the frequency of chocolate consumption might be a temporary protective factor with respect to alcohol relapse.

X-ray Variability Characteristics of the Narrow line SEYFERT 1 MKN 766 I: Energy Dependent Timing Properties

NASA Technical Reports Server (NTRS)

Markowitz, A.; Turner, T. J.; Papadakis, I.; Arevalo, P.; Reeves, J. N.; Miller, L.

2007-01-01

We present the energy-dependent power spectral density (PSD) and cross-spectral properties of Mkn 766 obtained from a six-revolution XMM-Newton observation in 2005. The resulting PSDs, which have highest temporal frequency resolution for an AGN PSD to date, show breaks which increase in temporal frequency as photon energy increases; break frequencies differ by an average of approx.0.4 in the log between the softest and hardest bands. The consistency of the 2001 and 2005 observations variability properties, namely PSD shapes and the linear rms-flux relation, suggests the 2005 observation is simply a low-flux extension of the 2001 observation. The coherence function is measured to be approx.0.6-0.9 at temporal frequencies below the PSD break, and is lower for relatively larger energy band separation; coherence also drops significantly towards zero above the PSD break frequency. Temporal frequency-dependent soft-to-hard time lags are detected in this object for the first time: lags increase towards longer time scales and as energy separation increases. Cross-spectral properties are the thus consistent with previous measurements for Mkn 766 (Vaughan & Fabian 2003) and other accreting black hole systems. The results are discussed in the context of several variability models, including those based on inwardly-propagating viscosity variations in the accretion disk.

Theoretical and Experimental Investigations on Droplet Evaporation and Droplet Ignition at High Pressures

NASA Technical Reports Server (NTRS)

Ristau, R.; Nagel, U.; Iglseder, H.; Koenig, J.; Rath, H. J.; Normura, H.; Kono, M.; Tanabe, M.; Sato, J.

1993-01-01

The evaporation of fuel droplets under high ambient pressure and temperature in normal gravity and microgravity has been investigated experimentally. For subcritical ambient conditions, droplet evaporation after a heat-up period follows the d(exp 2)-law. For all data the evaporation constant increases as the ambient temperature increases. At identical ambient conditions the evaporation constant under microgravity is smaller compared to normal gravity. This effect can first be observed at 1 bar and increases with ambient pressure. Preliminary experiments on ignition delay for self-igniting fuel droplets have been performed. Above a 1 s delay time, at identical ambient conditions, significant differences in the results of the normal and microgravity data are observed. Self-ignition occurs within different temperature ranges due to the influence of gravity. The time dependent behavior of the droplet is examined theoretically. In the calculations two different approaches for the gas phase are applied. In the first approach the conditions at the interface are given using a quasi steady theory approximation. The second approach uses a set of time dependent governing equations for the gas phase which are then evaluated. In comparison, the second model shows a better agreement with the drop tower experiments. In both cases a time dependent gasification rate is observed.

Dependence of spin dephasing on initial spin polarization in a high-mobility two-dimensional electron system

NASA Astrophysics Data System (ADS)

Stich, D.; Zhou, J.; Korn, T.; Schulz, R.; Schuh, D.; Wegscheider, W.; Wu, M. W.; Schüller, C.

2007-11-01

We have studied the spin dynamics of a high-mobility two-dimensional electron system in a GaAs/Al0.3Ga0.7As single quantum well by time-resolved Faraday rotation and time-resolved Kerr rotation in dependence on the initial degree of spin polarization, P , of the electrons. By increasing the initial spin polarization from the low- P regime to a significant P of several percent, we find that the spin dephasing time, T2* , increases from about 20to200ps . Moreover, T2* increases with temperature at small spin polarization but decreases with temperature at large spin polarization. All these features are in good agreement with theoretical predictions by Weng and Wu [Phys. Rev. B 68, 075312 (2003)]. Measurements as a function of spin polarization at fixed electron density are performed to further confirm the theory. A fully microscopic calculation is performed by setting up and numerically solving the kinetic spin Bloch equations, including the D’yakonov-Perel’ and the Bir-Aronov-Pikus mechanisms, with all the scattering explicitly included. We reproduce all principal features of the experiments, i.e., a dramatic decrease of spin dephasing with increasing P and the temperature dependences at different spin polarizations.

Factors affecting medication-order processing time.

PubMed

Beaman, M A; Kotzan, J A

1982-11-01

The factors affecting medication-order processing time at one hospital were studied. The order processing time was determined by directly observing the time to process randomly selected new drug orders on all three work shifts during two one-week periods. An order could list more than one drug for an individual patient. The observer recorded the nature, location, and cost of the drugs ordered, as well as the time to process the order. The time and type of interruptions also were noted. The time to process a drug order was classified as six dependent variables: (1) total time, (2) work time, (3) check time, (4) waiting time I--time from arrival on the dumbwaiter until work was initiated, (5) waiting time II--time between completion of the work and initiation of checking, and (6) waiting time III--time after the check was completed until the order left on the dumbwaiter. The significant predictors of each of the six dependent variables were determined using stepwise multiple regression. The total time to process a prescription order was 58.33 +/- 48.72 minutes; the urgency status of the order was the only significant determinant of total time. Urgency status also significantly predicted the three waiting-time variables. Interruptions and the number of drugs on the order were significant determinants of work time and check time. Each telephone interruption increased the work time by 1.72 minutes. While the results of this study cannot be generalized to other institutions, pharmacy managers can use the method of determining factors that affect medication-order processing time to identify problem areas in their institutions.

Development of a questionnaire for assessing dependence on electronic cigarettes among a large sample of ex-smoking E-cigarette users.

PubMed

Foulds, Jonathan; Veldheer, Susan; Yingst, Jessica; Hrabovsky, Shari; Wilson, Stephen J; Nichols, Travis T; Eissenberg, Thomas

2015-02-01

Electronic cigarettes (e-cigs) are becoming increasingly popular, but little is known about their dependence potential. This study aimed to assess ratings of dependence on electronic cigarettes and retrospectively compare them with rated dependence on tobacco cigarettes among a large sample of ex-smokers who switched to e-cigs. A total of 3,609 current users of e-cigs who were ex-cigarette smokers completed a 158-item online survey about their e-cig use, including 10 items designed to assess their previous dependence on cigarettes and 10 almost identical items, worded to assess their current dependence on e-cigs (range 0-20). Scores on the 10-item Penn State (PS) Cigarette Dependence Index were significantly higher than on the comparable PS Electronic Cigarette Dependence Index (14.5 vs. 8.1, p < .0001). In multivariate analysis, those who had used e-cigs longer had higher e-cig dependence scores, as did those using more advanced e-cigs that were larger than a cigarette and had a manual button. Those using zero nicotine liquid had significantly lower e-cig dependence scores than those using 1-12 mg/ml, who scored significantly lower than those using 13 or greater mg/ml nicotine liquid (p < .003). Current e-cigarette users reported being less dependent on e-cigarettes than they retrospectively reported having been dependent on cigarettes prior to switching. E-cig dependence appears to vary by product characteristics and liquid nicotine concentration, and it may increase over time. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Associations of prodynorphin sequence variation with alcohol dependence and related traits are phenotype-specific and sex-dependent

PubMed Central

Winham, Stacey J.; Preuss, Ulrich W.; Geske, Jennifer R.; Zill, Peter; Heit, John A.; Bakalkin, Georgy; Biernacka, Joanna M.; Karpyak, Victor M.

2015-01-01

We previously demonstrated that prodynorphin (PDYN) haplotypes and single nucleotide polymorphism (SNP) rs2281285 are associated with alcohol dependence and the propensity to drink in negative emotional states, and recent studies suggest that PDYN gene effects on substance dependence risk may be sex-related. We examined sex-dependent associations of PDYN variation with alcohol dependence and related phenotypes, including negative craving, time until relapse after treatment and the length of sobriety episodes before seeking treatment, in discovery and validation cohorts of European ancestry. We found a significant haplotype-by-sex interaction (p  =  0.03), suggesting association with alcohol dependence in males (p = 1E-4) but not females. The rs2281285 G allele increased risk for alcohol dependence in males in the discovery cohort (OR = 1.49, p = 0.002), with a similar trend in the validation cohort (OR = 1.35, p = 0.086). However, rs2281285 showed a trend towards association with increased negative craving in females in both the discovery (beta = 10.16, p = 0.045) and validation samples (OR = 7.11, p = 0.066). In the discovery cohort, rs2281285 was associated with time until relapse after treatment in females (HR = 1.72, p = 0.037); in the validation cohort, it was associated with increased length of sobriety episodes before treatment in males (beta = 13.49, p = 0.001). Our findings suggest that sex-dependent effects of PDYN variants in alcohol dependence are phenotype-specific. PMID:26502829

Associations of prodynorphin sequence variation with alcohol dependence and related traits are phenotype-specific and sex-dependent.

PubMed

Winham, Stacey J; Preuss, Ulrich W; Geske, Jennifer R; Zill, Peter; Heit, John A; Bakalkin, Georgy; Biernacka, Joanna M; Karpyak, Victor M

2015-10-27

We previously demonstrated that prodynorphin (PDYN) haplotypes and single nucleotide polymorphism (SNP) rs2281285 are associated with alcohol dependence and the propensity to drink in negative emotional states, and recent studies suggest that PDYN gene effects on substance dependence risk may be sex-related. We examined sex-dependent associations of PDYN variation with alcohol dependence and related phenotypes, including negative craving, time until relapse after treatment and the length of sobriety episodes before seeking treatment, in discovery and validation cohorts of European ancestry. We found a significant haplotype-by-sex interaction (p  =  0.03), suggesting association with alcohol dependence in males (p = 1E-4) but not females. The rs2281285 G allele increased risk for alcohol dependence in males in the discovery cohort (OR = 1.49, p = 0.002), with a similar trend in the validation cohort (OR = 1.35, p = 0.086). However, rs2281285 showed a trend towards association with increased negative craving in females in both the discovery (beta = 10.16, p = 0.045) and validation samples (OR = 7.11, p = 0.066). In the discovery cohort, rs2281285 was associated with time until relapse after treatment in females (HR = 1.72, p = 0.037); in the validation cohort, it was associated with increased length of sobriety episodes before treatment in males (beta = 13.49, p = 0.001). Our findings suggest that sex-dependent effects of PDYN variants in alcohol dependence are phenotype-specific.

Are elderly dependency ratios associated with general population suicide rates?

PubMed

Shah, Ajit

2011-05-01

The elderly population size is increasing worldwide due to falling birth rates and increasing life expectancy. It has been hypothesized that as the elderly dependency ratio (the ratio of those over the age of 65 years to those under 65) increases, there will be fewer younger people available to care for older people and this, in turn, will increase the burden on younger carers with increased levels of psychiatric morbidity leading to an increase in general population suicide rates. A cross-national study examining the relationship between elderly dependency ratios and general population suicide rates was conducted using data from the World Health Organization and the United Nations websites. The main findings were of a significant and independent positive correlation between elderly dependency ratios and general population suicide rates in both genders. The contribution of cross-national differences in psychiatric morbidity in younger carers on general population suicide rates requires further study. The prevalence of psychiatric morbidity in younger carers of older people should be examined by: (i) cross-national studies using standardized measures of psychiatric morbidity that are education-free, culture-fair and language-fair; and (ii) within-country longitudinal studies with changing elderly dependency ratios over time.

The Gut Microbiome Is Altered in a Letrozole-Induced Mouse Model of Polycystic Ovary Syndrome

PubMed Central

Kelley, Scott T.; Skarra, Danalea V.; Rivera, Alissa J.; Thackray, Varykina G.

2016-01-01

Women with polycystic ovary syndrome (PCOS) have reproductive and metabolic abnormalities that result in an increased risk of infertility, diabetes and cardiovascular disease. The large intestine contains a complex community of microorganisms (the gut microbiome) that is dysregulated in humans with obesity and type 2 diabetes. Using a letrozole-induced PCOS mouse model, we demonstrated significant diet-independent changes in the gut microbial community, suggesting that gut microbiome dysbiosis may also occur in PCOS women. Letrozole treatment was associated with a time-dependent shift in the gut microbiome and a substantial reduction in overall species and phylogenetic richness. Letrozole treatment also correlated with significant changes in the abundance of specific Bacteroidetes and Firmicutes previously implicated in other mouse models of metabolic disease in a time-dependent manner. Our results suggest that the hyperandrogenemia observed in PCOS may significantly alter the gut microbiome independently of diet. PMID:26731268

Smoking tobacco along with marijuana increases symptoms of cannabis dependence

PubMed Central

Ream, Geoffrey L.; Benoit, Ellen; Johnson, Bruce D.; Dunlap, Eloise

2008-01-01

Aim User practices/rituals that involve concurrent use of tobacco and marijuana – smoking blunts and “chasing” marijuana with tobacco – are hypothesized to increase cannabis dependence symptoms. Design Ethnographers administered group surveys to a diverse, purposive sample of marijuana users who appeared to be 17–35 years old. Setting New York City, including non-impoverished areas of Manhattan, the transitional area of East Village/Lower East Side, low-income areas of northern Manhattan and South Bronx, and diverse areas of Brooklyn and Queens. Participants 481 marijuana users ages 14–35, 57% male, 43% female; 27% White, 30% Black, 19% Latino, 5% Asian, 20% of other/multiple race. Measurements Among many other topics, group surveys measured cannabis dependence symptoms; frequencies of chasing, blunt smoking, joint/pipe smoking, using marijuana while alone, and general tobacco use; and demographic factors. Findings Blunt smoking and chasing marijuana with tobacco were each uniquely associated with five of the seven cannabis dependence symptoms. Across symptoms, predicted odds were 2.4–4.1 times greater for participants who smoked blunts on all 30 of the past 30 days than for participants who did not smoke blunts in the past 30 days. Significant increases in odds over the whole range of the five-point chasing frequency measure (from never to always) ranged from 3.4 times to 5.1 times. Conclusions Using tobacco with marijuana – smoking blunts and “chasing” marijuana with tobacco – contributes to cannabis dependence symptoms. Treatment for cannabis dependence may be more effective it addresses the issue of concurrent tobacco use. PMID:18339491

Age influences the effects of nicotine and monoamine oxidase inhibition on mood-related behaviors in rats.

PubMed

Villégier, Anne-Sophie; Gallager, Brittney; Heston, Jon; Belluzzi, James D; Leslie, Frances M

2010-03-01

Epidemiological studies have demonstrated a comorbidity of smoking with depression and anxiety, particularly during adolescence. However, few animal studies have considered possible synergistic interactions between nicotine and other tobacco smoke constituents, such as monoamine oxidase (MAO) inhibitors, in the regulation of mood. The aim of the study was to test the hypothesis that nicotine combined with the irreversible MAO inhibitor, tranylcypromine, will differentially affect depression- and anxiety-related behaviors in adolescent and adult rats. Nicotine (0, 0.05, 0.2 mg/kg, s.c.) and tranylcypromine (3 mg/kg, i.p.) were tested separately, or together, on male rats aged postnatal days 30 and 68, in three mood-related behavioral tests: forced swim test (FST), elevated plus maze (EPM), and open field. Nicotine (0.2 mg/kg) in adults significantly decreased floating time in the FST and increased time spent in the open arm of the EPM, with no change in locomotor activity. Tranylcypromine pretreatment combined with nicotine (0.2 mg/kg) significantly increased locomotor activity and time spent in the center of the open field. Whereas nicotine alone had no significant effect on adolescents, it significantly increased locomotor activity and decreased floating time in the FST when combined with tranylcypromine pretreatment. There is an age-dependent effect of nicotine, alone and in combination with MAO inhibition, on mood-related behaviors. Whereas nicotine alone induces mood improvement in adults, it has no effect on adolescents. Nicotine combined with tranylcypromine has unique, age-dependent effects. Thus, experimental studies of smoking should consider both age and other tobacco constituents, such as MAO inhibitors, as critical factors.

L-arginine supplementation enhances exhaled NO, breath condensate VEGF, and headache at 4,342 m.

PubMed

Mansoor, Jim K; Morrissey, Brian M; Walby, William F; Yoneda, Ken Y; Juarez, Maya; Kajekar, Radhika; Severinghaus, John W; Eldridge, Marlowe W; Schelegle, Edward S

2005-01-01

We examined the effect of dietary supplementation with L-arginine on breath condensate VEGF, exhaled nitric oxide (NO), plasma erythropoietin, symptoms of acute mountain sickness, and respiratory related sensations at 4,342 m through the course of 24 h in seven healthy male subjects. Serum L-arginine levels increased in treated subjects at time 0, 8, and 24 h compared with placebo, indicating the effectiveness of our treatment. L-arginine had no significant effect on overall Lake Louise scores compared with placebo. However, there was a significant increase in headache within the L-arginine treatment group at 12 h compared with time 0, a change not seen in the placebo condition between these two time points. There was a trend (p = 0.087) toward greater exhaled NO and significant increases in breath condensate VEGF with L-arginine treatment, but no L-arginine effect on serum EPO. These results suggest that L-arginine supplementation increases HIF-1 stabilization in the lung, possibly through a NO-dependent pathway. In total, our observations indicate that L-arginine supplementation is not beneficial in the prophylactic treatment of AMS.

[Effect of trampling disturbance on soil infiltration of biological soil crusts].

PubMed

Shi, Ya Fang; Zhao, Yun Ge; Li, Chen Hui; Wang, Shan Shan; Yang, Qiao Yun; Xie, Shen Qi

2017-10-01

The effect of trampling disturbance on soil infiltration of biological soil crusts was investigated by using simulated rainfall. The results showed that the trampling disturbance significantly increased soil surface roughness. The increasing extent depended on the disturbance intensity. Soil surface roughness values at 50% disturbance increased by 91% compared with the undisturbed treatment. The runoff was delayed by trampling disturbance. A linear increase in the time of runoff yield was observed along with the increasing disturbance intensity within 20%-50%. The time of runoff yield at 50% disturbance increased by 169.7% compared with the undisturbed treatment. Trampling disturbance increased soil infiltration and consequently decreased the runoff coefficient. The cumulative infiltration amount at 50% disturbance increased by 12.6% compared with the undisturbed treatment. Soil infiltration significant decreased when biocrusts were removed. The cumulative infiltration of the treatment of biocrusts removal decreased by 30.2% compared with the undisturbed treatment. Trampling disturbance did not significantly increase the soil loss when the distur bance intensity was lower than 50%, while the biocrusts removal resulted in 10 times higher in soil erosion modulus. The trampling disturbance of lower than 50% on biocrusts might improve soil infiltration and reduce the risk of runoff, thus might improve the soil moisture without obviously increa sing the soil loss.

Effect of ultrasonic treatment on reduction of Esherichia coli ATCC 25922 and egg quality parameters in experimentally contaminated hens' shell eggs.

PubMed

Sert, Durmus; Aygun, Ali; Torlak, Emrah; Mercan, Emin

2013-09-01

In this study, hen eggs which were experimentally contaminated with Esherichia coli ATCC 25922 were used. Contaminated eggs were washed statically (S5 to S30; 0 kHz) and by ultrasonic waves (U5 to U30; 35 kHz) for given applications of time (5, 15 and 30 min), then the eggs were stored at 22°C for 14 days. Depending on the time of ultrasonic application, a significant increase in egg shell strength (P < 0.01) was recorded. The highest value of the Haugh unit (67.93, 1 day) was observed on the eggs which were washed by ultrasonic waves. Yolk width values of ultrasonic washed eggs diminished. E. coli was completely removed by 30 min of ultrasonic application. During storage E. coli growth was not detected on the eggs which were washed by ultrasonic waves except the eggs in U5 group (2.04 log CFU eggshell⁻¹) on the first day of storage. Depending on the time of ultrasonic application a significant increase in egg quality parameters (shell strength, albumen height, Haugh units, and yolk height) were observed. The application of ultrasound led to a significant reduction in E. coli numbers on egg shells. © 2013 Society of Chemical Industry.

Working disability in Norwegian patients with vestibular schwannoma: vertigo predicts future dependence.

PubMed

Breivik, Cathrine Nansdal; Nilsen, Roy Miodini; Myrseth, Erling; Finnkirk, Monica Katrine; Lund-Johansen, Morten

2013-12-01

We examined whether reduced hearing, tinnitus, dizziness, and unsteadiness affected the patients' ability to maintain work within a time frame of 2-10 years after diagnosis. A total of 434 consecutive patients were followed at regular intervals. Data on symptoms were scored prospectively and dichotomized by visual analog scales for tinnitus and vertigo. Study design is retrospective. Hearing acuity was scored according to the Gardner-Robertson scale, and unsteadiness was measured on a balance platform. Patients were asked about working status, and scored as receiving governmental compensation for disability. Two hundred six patients were eligible for study. Of these, one died and nine were lost to follow-up. Ninety-seven patients received conservative management, 49 patients recieved gamma knife radiosurgery, and 50 patients were treated by microsurgery. Mean follow-up time was 58.7 months (range, 20-132 months). There was a significant increase in the number of individuals receiving compensation during the study period (P < 0.0001). At baseline, the proportion of pension receivers was within same range as that of the age- and sex-matched Norwegian population (5.61% vs. 6.91%; case-control odds ratio, 0.82; 95% confidence interval 0.45-1.49; P = 0.51, not significant). At the final time point, the increase in the number of receivers deviated significantly from the reference population (case-control odds ratio, 3.80; 95% confidence interval 2.71-5.33; P ≤ 0.001). Examining symptoms at first presentation as predictors of future dependence revealed that vertigo and higher mean age were associated with a higher risk (P < 0.001 and P = 0.015, respectively). No other symptoms were predictive of dependence. In a prospectively followed cohort of Norwegian patients with vestibular schwannoma, vestibular complaints were significant predictors for becoming dependant of disability pension. Copyright © 2013 Elsevier Inc. All rights reserved.

Evaluation of the cytogenetic status of human lymphocytes after exposure to a high concentration of bee venom in vitro.

PubMed

Garaj-Vrhovac, Verica; Gajski, Goran

2009-03-01

Several studies have reported radioprotective, antimutagenic, anti-inflammatory, antinociceptive, and anticancer effects of bee venom both in the cell and the whole organism. The aim of this study was to assess the effects of a single high dose of 100 microg mL(-1) of whole bee venom in human lymphocytes in vitro over a variety of time spans (from 10 min to 24 h). After the treatment, we used the comet assay and micronucleus test to see the effect of bee venom on the cell. The comet assay confirmed that the venom damaged the DNA molecule. Tail length, tail intensity, tail moment showed a significant increase (P < 0.05). The percentage of long-tailed nuclei (LTN) with the tail length exceeding the 95th percentile also increased in a time-dependent manner. The micronucleus parameters (number of micronuclei, nucleoplasmic bridges, and nuclear buds) also showed a significant time-dependent increase (P < 0.05). This research indicates that high concentrations of bee venom can lead to cellular instability. Further research is needed to understand the mechanism of action of bee venom and its components in human cells and to see if this natural product may find application in medicine.

Run-time parallelization and scheduling of loops

NASA Technical Reports Server (NTRS)

Saltz, Joel H.; Mirchandaney, Ravi; Crowley, Kay

1990-01-01

Run time methods are studied to automatically parallelize and schedule iterations of a do loop in certain cases, where compile-time information is inadequate. The methods presented involve execution time preprocessing of the loop. At compile-time, these methods set up the framework for performing a loop dependency analysis. At run time, wave fronts of concurrently executable loop iterations are identified. Using this wavefront information, loop iterations are reordered for increased parallelism. Symbolic transformation rules are used to produce: inspector procedures that perform execution time preprocessing and executors or transformed versions of source code loop structures. These transformed loop structures carry out the calculations planned in the inspector procedures. Performance results are presented from experiments conducted on the Encore Multimax. These results illustrate that run time reordering of loop indices can have a significant impact on performance. Furthermore, the overheads associated with this type of reordering are amortized when the loop is executed several times with the same dependency structure.

Acute haemodynamic effects of felodipine and verapamil in man, singly and with metoprolol.

PubMed

Rönn, O; Bengtsson, B; Edgar, B; Raner, S

1985-01-01

In a single-blind randomised study in 9 healthy men we compared the acute haemodynamic effects of the calcium antagonists felodipine and verapamil, singly and in combination with metoprolol. Three different cumulative intravenous doses of 0.25, 0.75 and 1.5 mg felodipine and of 2.0, 4.0 and 8.0 mg verapamil or placebo were given as constant infusions over 5 minutes on 3 occasions and were followed by intravenous metoprolol (15 mg). Felodipine caused a significant and dose-dependent decrease in the total peripheral resistance, and an increase in the forearm blood flow by 8, 48 and 163% with progressively increasing doses showing that the drug is a potent arteriolar vasodilator. A significant and dose-dependent increase in heart rate and a decrease in the pre-ejection period/left ventricular ejection time (PEP/LVET) ratio of up to 15% was also recorded, mainly reflecting a reflexogenic increase in the sympathetic tone. Total peripheral resistance, forearm blood flow, heart rate and the systolic time intervals were mainly unchanged after verapamil, whereas the PQ interval was prolonged. Metoprolol given after the 2 calcium antagonists caused a decrease in heart rate and blood flow and an increase in the total peripheral resistance and PEP/LVET ratio. The tolerability was good to all infusions.

Seismicity in a model governed by competing frictional weakening and healing mechanisms

NASA Astrophysics Data System (ADS)

Hillers, G.; Carlson, J. M.; Archuleta, R. J.

2009-09-01

Observations from laboratory, field and numerical work spanning a wide range of space and time scales suggest a strain dependent progressive evolution of material properties that control the stability of earthquake faults. The associated weakening mechanisms are counterbalanced by a variety of restrengthening mechanisms. The efficiency of the healing processes depends on local material properties and on rheologic, temperature, and hydraulic conditions. We investigate the relative effects of these competing non-linear feedbacks on seismogenesis in the context of evolving frictional properties, using a mechanical earthquake model that is governed by slip weakening friction. Weakening and strengthening mechanisms are parametrized by the evolution of the frictional control variable-the slip weakening rate R-using empirical relationships obtained from laboratory experiments. In our model, weakening depends on the slip of an earthquake and tends to increase R, following the behaviour of real and simulated frictional interfaces. Healing causes R to decrease and depends on the time passed since the last slip. Results from models with these competing feedbacks are compared with simulations using non-evolving friction. Compared to fixed R conditions, evolving properties result in a significantly increased variability in the system dynamics. We find that for a given set of weakening parameters the resulting seismicity patterns are sensitive to details of the restrengthening process, such as the healing rate b and a lower cutoff time, tc, up to which no significant change in the friction parameter is observed. For relatively large and small cutoff times, the statistics are typical of fixed large and small R values, respectively. However, a wide range of intermediate values leads to significant fluctuations in the internal energy levels. The frequency-size statistics of earthquake occurrence show corresponding non-stationary characteristics on time scales over which negligible fluctuations are observed in the fixed-R case. The progressive evolution implies that-except for extreme weakening and healing rates-faults and fault networks possibly are not well characterized by steady states on typical catalogue time scales, thus highlighting the essential role of memory and history dependence in seismogenesis. The results suggest that an extrapolation to future seismicity occurrence based on temporally limited data may be misleading due to variability in seismicity patterns associated with competing mechanisms that affect fault stability.

Profiling of Kidney Injury Biomarkers in Patients Receiving Cisplatin: Time-Dependent Changes in the Absence of Clinical Nephrotoxicity

PubMed Central

George, Blessy; Wen, Xia; Mercke, Nickie; Gomez, Madeleine; O’Bryant, Cindy; Bowles, Daniel W.; Hu, Yichun; Hogan, Susan L.

2016-01-01

The success of cisplatin-containing regimens to treat solid tumors is limited, in part, by nephrotoxicity. In rodents, several urinary proteins have emerged as more sensitive indicators of cisplatin-induced kidney injury. We sought to characterize time-dependent changes in the urinary concentrations of 12 proteins including KIM-1, calbindin, β2M, and TFF3 after cisplatin therapy. Urine was collected at baseline, 3 (range: 2-5), and 10 (range: 9-11) days from 57 patients with solid tumors receiving outpatient cisplatin therapy (≥ 25 mg/m2). Serum creatinine was largely unchanged after cisplatin infusion. However, compared to baseline values, several novel biomarkers were significantly increased in the urine including β2M, which was 3-fold higher by day 3 (p<0.0001). Urinary KIM-1 and TFF3 were elevated 2-fold by day 10 (p=0.002 and p=0.002, respectively) whereas calbindin levels were increased 8-fold (p<0.0001). We report novel time-dependent changes in the urinary excretion of noninvasive markers of subclinical kidney injury after cisplatin treatment. PMID:28002630

Humidity-dependent bacterial cells functional morphometry investigations using atomic force microscope.

PubMed

Nikiyan, Hike; Vasilchenko, Alexey; Deryabin, Dmitry

2010-01-01

The effect of a relative humidity (RH) in a range of 93-65% on morphological and elastic properties of Bacillus cereus and Escherichia coli cells was evaluated using atomic force microscopy. It is shown that gradual dehumidification of bacteria environment has no significant effect on cell dimensional features and considerably decreases them only at 65% RH. The increasing of the bacteria cell wall roughness and elasticity occurs at the same time. Observed changes indicate that morphological properties of B. cereus are rather stable in wide range of relative humidity, whereas E. coli are more sensitive to drying, significantly increasing roughness and stiffness parameters at RH

Learning enhances intrinsic excitability in a subset of lateral amygdala neurons

PubMed Central

Sehgal, Megha; Ehlers, Vanessa L.; Moyer, James R.

2014-01-01

Learning-induced modulation of neuronal intrinsic excitability is a metaplasticity mechanism that can impact the acquisition of new memories. Although the amygdala is important for emotional learning and other behaviors, including fear and anxiety, whether learning alters intrinsic excitability within the amygdala has received very little attention. Fear conditioning was combined with intracellular recordings to investigate the effects of learning on the intrinsic excitability of lateral amygdala (LA) neurons. To assess time-dependent changes, brain slices were prepared either immediately or 24-h post-conditioning. Fear conditioning significantly enhanced excitability of LA neurons, as evidenced by both decreased afterhyperpolarization (AHP) and increased neuronal firing. These changes were time-dependent such that reduced AHPs were evident at both time points whereas increased neuronal firing was only observed at the later (24-h) time point. Moreover, these changes occurred within a subset (32%) of LA neurons. Previous work also demonstrated that learning-related changes in synaptic plasticity are also evident in less than one-third of amygdala neurons, suggesting that the neurons undergoing intrinsic plasticity may be critical for fear memory. These data may be clinically relevant as enhanced LA excitability following fear learning could influence future amygdala-dependent behaviors. PMID:24554670

Serum biomarkers for acute hepatotoxicity of Echis pyramidum snake venom in rats.

PubMed

Asmari, Abdulrahman K Al; Khan, Haseeb A; Banah, Faisal A; Buraidi, Ahmed A Al; Manthiri, Rajamohammed A

2015-01-01

Echis pyramidum is a venomous viper responsible for most cases of envenomation in Arabian Peninsula. We determined the acute phase (3-6 h) changes in serum markers of liver function including alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT) and bilirubin in adult male Sprague Dawley rats injected with Echis pyramidum venom (EPV) in the doses of 0.00 (control), 0.25, 0.50 and 1.00 mg/kg bodyweight. We also analyzed markers of oxidative stress including superoxide dismutase (SOD), catalase (CAT), total thiols (T-SH) and thiobarbituric acids reactive substances (TBARS) in liver. The results showed significant and dose- and time-dependent increases in serum ALT, ALP and GGT activities after a single injection of EPV. Serum bilirubin was significantly increased by medium and high doses of EVP after 3 h post-injection and then decreased at 6 h. The low dose of EPV neither affected the activity of SOD nor altered the levels of liver T-SH and TBARS, however, it significantly decreased the activity of CAT at 6 h post-injection of EPV. The medium dose of EPV significantly reduced liver SOD activity after 6 h whereas the high dose significantly reduced the SOD activity at 3 h and 6 h post-dosing. Both medium and high doses of EPV caused significant as well as dose- and time-dependent reductions in liver CAT activities. The high dose significantly reduced T-SH and increased TBARS in rat liver. Further studies are warranted to test the pharmacological potential of early phase antioxidant therapy for neutralizing the toxic effects of EPV.

CO2 convective dissolution controlled by temporal changes in free-phase CO2 properties

NASA Astrophysics Data System (ADS)

Jafari Raad, S. M.; Emami-Meybodi, H.; Hassanzadeh, H.

2017-12-01

Understanding the factors that control CO2 convective dissolution, which is one of the permanent trapping mechanisms, in the deep saline aquifer is crucial in the long-term fate of the injected CO2. The present study investigates the effects of temporal changes in the solubility of CO2 at the free-phase CO2/brine interface on the onset of natural convection and the subsequent convective mixing by conducting linear stability analyses (LSA) and direct numerical simulations (DNS). A time-dependent concentration boundary is considered for the free-phase CO2/brine interface where the CO2 concentration first decreases with the time and then remains constant. The LSA results show that the temporal variation in the concentration increases the onset of natural convection up to two orders of magnitude. In addition, the critical Rayleigh number significantly increases as CO2 concentration decreases. In other words, size and pressure of the injected CO2 affect the commencement of convective mixing. Based on LSA results, several scaling relations are proposed to correlate critical Rayleigh number, critical time, and its corresponding wavenumbers with time-dependent boundary's parameters, such as concentration decline rate and equilibrium concentration ratio. The DNS results reveal that the convective fingering patterns are significantly influenced by the variation of CO2 concentration at the interface. These findings improve our understanding of CO2 solubility trapping and are particularly important in estimation of potential storage capacity, risk assessment, and storage sites characterization and screening. Keywords: CO2 sequestration; natural convection; solubility trapping; time-dependent boundary condition; numerical simulation; stability analysis

Statistical Analysis of Human Body Movement and Group Interactions in Response to Music

NASA Astrophysics Data System (ADS)

Desmet, Frank; Leman, Marc; Lesaffre, Micheline; de Bruyn, Leen

Quantification of time series that relate to physiological data is challenging for empirical music research. Up to now, most studies have focused on time-dependent responses of individual subjects in controlled environments. However, little is known about time-dependent responses of between-subject interactions in an ecological context. This paper provides new findings on the statistical analysis of group synchronicity in response to musical stimuli. Different statistical techniques were applied to time-dependent data obtained from an experiment on embodied listening in individual and group settings. Analysis of inter group synchronicity are described. Dynamic Time Warping (DTW) and Cross Correlation Function (CCF) were found to be valid methods to estimate group coherence of the resulting movements. It was found that synchronicity of movements between individuals (human-human interactions) increases significantly in the social context. Moreover, Analysis of Variance (ANOVA) revealed that the type of music is the predominant factor in both the individual and the social context.

Dynamics of threading dislocations in porous heteroepitaxial GaN films

NASA Astrophysics Data System (ADS)

Gutkin, M. Yu.; Rzhavtsev, E. A.

2017-12-01

Behavior of threading dislocations in porous heteroepitaxial gallium nitride (GaN) films has been studied using computer simulation by the two-dimensional discrete dislocation dynamics approach. A computational scheme, where pores are modeled as cross sections of cylindrical cavities, elastically interacting with unidirectional parallel edge dislocations, which imitate threading dislocations, is used. Time dependences of coordinates and velocities of each dislocation from dislocation ensembles under investigation are obtained. Visualization of current structure of dislocation ensemble is performed in the form of a location map of dislocations at any time. It has been shown that the density of appearing dislocation structures significantly depends on the ratio of area of a pore cross section to area of the simulation region. In particular, increasing the portion of pores surface on the layer surface up to 2% should lead to about a 1.5-times decrease of the final density of threading dislocations, and increase of this portion up to 15% should lead to approximately a 4.5-times decrease of it.

Mechanisms of angiotensin II stimulation of NCC are time-dependent in mDCT15 cells.

PubMed

Ko, Benjamin; Mistry, Abinash; Hanson, Lauren; Mallick, Rickta; Hoover, Robert S

2015-04-01

Angiotensin II (ANG II) increases thiazide-sensitive sodium-chloride cotransporter (NCC) activity both acutely and chronically. ANG II has been implicated as a switch that turns WNK4 from an inhibitor of NCC into an activator of NCC, and ANG II's effect on NCC appears to require WNK4. Chronically, ANG II stimulation of NCC results in an increase in total and phosphorylated NCC, but the role of NCC phosphorylation in acute ANG II actions is unclear. Here, using a mammalian cell model with robust native NCC activity, we corroborate the role that ANG II plays in WNK4 regulation and clarify the role of Ste20-related proline alanine-rich kinase (SPAK)-induced NCC phosphorylation in ANG II action. ANG II was noted to have a biphasic effect on NCC, with a peak increase in NCC activity in the physiologic range of 10(-11) M ANG II. This effect was apparent as early as 15 min and remained sustained through 120 min. These changes correlated with significant increases in NCC surface protein expression. Knockdown of WNK4 expression sharply attenuated the effect of ANG II. SPAK knockdown did not affect ANG II action at early time points (15 and 30 min), but it did attenuate the response at 60 min. Correspondingly, NCC phosphorylation did not increase at 15 or 30 min, but increased significantly at 60 min. We therefore conclude that within minutes of an increase in ANG II, NCC is rapidly trafficked to the cell surface in a phosphorylation-independent but WNK4-dependent manner. Then, after 60 min, ANG II induces SPAK-dependent phosphorylation of NCC.

Mechanisms of angiotensin II stimulation of NCC are time-dependent in mDCT15 cells

PubMed Central

Mistry, Abinash; Hanson, Lauren; Mallick, Rickta; Hoover, Robert S.

2015-01-01

Angiotensin II (ANG II) increases thiazide-sensitive sodium-chloride cotransporter (NCC) activity both acutely and chronically. ANG II has been implicated as a switch that turns WNK4 from an inhibitor of NCC into an activator of NCC, and ANG II's effect on NCC appears to require WNK4. Chronically, ANG II stimulation of NCC results in an increase in total and phosphorylated NCC, but the role of NCC phosphorylation in acute ANG II actions is unclear. Here, using a mammalian cell model with robust native NCC activity, we corroborate the role that ANG II plays in WNK4 regulation and clarify the role of Ste20-related proline alanine-rich kinase (SPAK)-induced NCC phosphorylation in ANG II action. ANG II was noted to have a biphasic effect on NCC, with a peak increase in NCC activity in the physiologic range of 10−11 M ANG II. This effect was apparent as early as 15 min and remained sustained through 120 min. These changes correlated with significant increases in NCC surface protein expression. Knockdown of WNK4 expression sharply attenuated the effect of ANG II. SPAK knockdown did not affect ANG II action at early time points (15 and 30 min), but it did attenuate the response at 60 min. Correspondingly, NCC phosphorylation did not increase at 15 or 30 min, but increased significantly at 60 min. We therefore conclude that within minutes of an increase in ANG II, NCC is rapidly trafficked to the cell surface in a phosphorylation-independent but WNK4-dependent manner. Then, after 60 min, ANG II induces SPAK-dependent phosphorylation of NCC. PMID:25651566

Transitions to regular smoking and to nicotine dependence in women using cannabis.

PubMed

Agrawal, Arpana; Madden, Pamela A F; Bucholz, Kathleen K; Heath, Andrew C; Lynskey, Michael T

2008-05-01

While there is substantial support in the literature for an increased prevalence of cannabis use in cigarette smokers, emerging studies allude to the possibility that cannabis users may, in turn, be at significantly elevated risk for rapid transitions in their cigarette smoking trajectories. If there is evidence in its favor, the increased rates of cigarette smoking in cannabis users may prove to be the most significant public health problem associated with cannabis use. In a sample of 3787 female twins (age range 18-29 years), we examined, using discrete-time survival analyses, whether women who reported cannabis use were at increased risk for regular cigarette smoking and progression to nicotine dependence. After controlling for a large number of potential covariates, we found that women who used cannabis were at 4.4 and 2.8 increased hazards for transitioning from initiation to regular smoking and from regular smoking to nicotine dependence, respectively. Cannabis use is associated with transitions to more involved stages of cigarette smoking in women. This is a source of public health concern, first due to the high mortality associated with cigarette smoking and second, due to the high prevalence of cannabis use in the general population.

Changes in Landscape Greenness and Climatic Factors over ...

EPA Pesticide Factsheets

Monitoring and quantifying changes in vegetation cover over large areas using remote sensing can be achieved using the Normalized Difference Vegetation Index (NDVI), an indicator of greenness. However, distinguishing gradual shifts in NDVI (e.g. climate change) versus direct and rapid changes (e.g., fire, land development) is challenging as changes can be confounded by time-dependent patterns, and variation associated with climatic factors. In the present study we leveraged a method, that we previously developed for a pilot study, to address these confounding factors by evaluating NDVI change using autoregression techniques that compare results from univariate (NDVI vs. time) and multivariate analyses (NDVI vs. time and climatic factors) for ~7,660,636 1-km2 pixels comprising the 48 contiguous states of the USA, over a 25-year period (1989−2013). NDVI changed significantly for 48% of the nation over the 25-year in the univariate analyses where most significant trends (85%) indicated an increase in greenness over time. By including climatic factors in the multivariate analyses of NDVI over time, the detection of significant NDVI trends increased to 53% (an increase of 5%). Comparisons of univariate and multivariate analyses for each pixel showed that less than 4% of the pixels had a significant NDVI trend attributable to gradual climatic changes while the remainder of pixels with a significant NDVI trend indicated that changes were due to direct factors. Whi

Effect of dimethyl sulfoxide on dentin collagen.

PubMed

Mehtälä, P; Pashley, D H; Tjäderhane, L

2017-08-01

Infiltration of adhesive on dentin matrix depends on interaction of surface and adhesive. Interaction depends on dentin wettability, which can be enhanced either by increasing dentin surface energy or lowering the surface energy of adhesive. The objective was to examine the effect of dimethyl sulfoxide (DMSO) on demineralized dentin wettability and dentin organic matrix expansion. Acid-etched human dentin was used for sessile drop contact angle measurement to test surface wetting on 1-5% DMSO-treated demineralized dentin surface, and linear variable differential transformer (LVDT) to measure expansion/shrinkage of dentinal matrix. DMSO-water binary liquids were examined for surface tension changes through concentrations from 0 to 100% DMSO. Kruskal-Wallis and Mann-Whitney tests were used to test the differences in dentin wettability, expansion and shrinkage, and Spearman test to test the correlation between DMSO concentration and water surface tension. The level of significance was p<0.05. Pretreatment with 1-5% DMSO caused statistically significant concentration-dependent increase in wetting: the immediate contact angles decreased by 11.8% and 46.6% and 60s contact angles by 9.5% and 47.4% with 1% and 5% DMSO, respectively. DMSO-water mixtures concentration-dependently expanded demineralized dentin samples less than pure water, except with high (≥80%) DMSO concentrations which expanded demineralized dentin more than water. Drying times of LVDT samples increased significantly with the use of DMSO. Increased dentin wettability may explain the previously demonstrated increase in adhesive penetration with DMSO-treated dentin, and together with the expansion of collagen matrix after drying may also explain previously observed increase in dentin adhesive bonding. Copyright © 2017 The Academy of Dental Materials. Published by Elsevier Ltd. All rights reserved.

How do dual practitioners divide their time? The cases of three African capital cities.

PubMed

McPake, Barbara; Russo, Giuliano; Tseng, Fu-Min

2014-12-01

Health professionals dual practice has received increasing attention, particularly in the context of the universal health coverage movement. This paper explores the determinants of doctors' choices to become a dual practitioner and of dual practitioners' choices to allocate time to the private sector in the capital cities of Mozambique, Guinea Bissau and Cape Verde. The data are drawn from a survey conducted in 2012 among 329 physicians. We use a two-part model to analyse the decision of both public and private practitioners to become dual practitioners, and to allocate time between public and private sectors. We impute potential earnings in public and private practice by using nearest-neighbour propensity score matching. Our results show that hourly wage in the private sector, number of dependents, length of time as a physician, work outside city, and being a specialist with or without technology all have a positive association with the probability of being a dual physician, while number of dependents displays a negative sign. Level of salaries in the public sector are not associated with dual practice engagement, with important implications for attempts aimed at retaining professionals in the public sector through wage increases. As predicted by theory that recognises doctors' role in price setting, earnings rates are not significant predictors of private sector time allocation; personal characteristics of physicians appear more important, such as age, number of dependents, specialist without technology, specialist with technology, and three reasons for not working more hours in the private sector. Answers to questions about the factors that limit working hours in the private sector have significant predictive power, suggesting that type of employment in the private sector may be an underlying determinant of both dual practice engagement and time allocation decisions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Time-Dependent Decline in Serum Phenytoin Concentration with Heightened Convulsive Seizure Risk by Prolonged Administration of Fosphenytoin in Japanese: A Retrospective Study.

PubMed

Ohno, Yuta; Niwa, Takashi; Hirai, Keita; Suzuki, Keiko; Yamada, Yuto; Hayashi, Yuichi; Hayashi, Hideki; Suzuki, Akio; Itoh, Yoshinori

2018-04-20

Because clinical data to confirm the safety and effectiveness of fosphenytoin, a prodrug of phenytoin, are insufficient, the length of administration of fosphenytoin is restricted. Nevertheless, some cases require fosphenytoin administration for more than a few days. The aim of this study was to retrospectively investigate the serum concentration of phenytoin in adult Japanese patients who received intravenous fosphenytoin therapy for more than 3 days. Patients injected with intravenous fosphenytoin for more than 3 days at Gifu University Hospital between January 2012 and September 2014 were enrolled. Individual pharmacokinetic parameters were predicted by Bayesian estimation using NONMEM software, and the maintenance dose of fosphenytoin required to maintain the therapeutic trough concentration (10-20 μg/mL) was calculated from the parameters. Among a total of 8 patients, the serum trough concentration of phenytoin decreased with each day after repeated injection of fosphenytoin. The incidence rate of significant convulsive seizures was increased time-dependently (0% on day 1, 12.5% on day 2, 25% on day 3, and 66.7% on day 4 and after). Phenytoin clearance showed a time-dependent increase. The maintenance dose of fosphenytoin required to maintain the therapeutic trough concentration was simulated to be 779.8 ± 316.8 mg/day, a dose that was markedly higher than the actual maintenance dose (414.1 ± 55.7 mg/day). Prolonged use of fosphenytoin for such patients as those with autoimmune-mediated encephalopathy accompanied with reflux disease and/or ileus time-dependently decreased the serum concentration of phenytoin and increased the risk of convulsion. Therefore, the maintenance dose should be increased to maintain the therapeutic serum concentration.

The influence of temperature on brittle creep in sandstones

NASA Astrophysics Data System (ADS)

Heap, M. J.; Baud, P.; Meredith, P. G.; Vinciguerra, S.

2009-04-01

The characterization of time-dependent brittle rock deformation is fundamental to understanding the long-term evolution and dynamics of the Earth's upper crust. The presence of water promotes time-dependent deformation through environment-dependent stress corrosion cracking that allows rocks to deform at stresses far below their short-term failure stress. Here we report results from an experimental study of the influence of an elevated temperature on time-dependent brittle creep in water-saturated samples of Darley Dale (initial porosity of 13%), Bentheim (23%) and Crab Orchard (4%) sandstones. We present results from both conventional creep experiments (or ‘static fatigue' tests) and stress-stepping creep experiments performed under 20°C and 75°C and an effective confining pressure of 30 MPa (50 MPa confining pressure and a 20 MPa pore fluid pressure). The evolution of crack damage was monitored throughout each experiment by measuring the three proxies for damage (1) axial strain (2) pore volume change and (3) the output of AE energy. Conventional creep experiments have demonstrated that, for any given applied differential stress, the time-to-failure is dramatically reduced and the creep strain rate is significantly increased by application of an elevated temperature. Stress-stepping creep experiments have allowed us to investigate the influence of temperature in detail. Results from these experiments show that the creep strain rate for Darley Dale and Bentheim sandstones increases by approximately 3 orders of magnitude, and for Crab Orchard sandstone increases by approximately 2 orders of magnitude, as temperature is increased from 20°C to 75°C at a fixed effective differential stress. We discuss these results in the context of the different mineralogical and microstructural properties of the three rock types and the micro-mechanical and chemical processes operating on them.

Direction dependence of displacement time for two-fluid electroosmotic flow.

PubMed

Lim, Chun Yee; Lam, Yee Cheong

2012-03-01

Electroosmotic flow that involves one fluid displacing another fluid is commonly encountered in various microfludic applications and experiments, for example, current monitoring technique to determine zeta potential of microchannel. There is experimentally observed anomaly in such flow, namely, the displacement time is flow direction dependent, i.e., it depends if it is a high concentration fluid displacing a low concentration fluid, or vice versa. Thus, this investigation focuses on the displacement flow of two fluids with various concentration differences. The displacement time was determined experimentally with current monitoring method. It is concluded that the time required for a high concentration solution to displace a low concentration solution is smaller than the time required for a low concentration solution to displace a high concentration solution. The percentage displacement time difference increases with increasing concentration difference and independent of the length or width of the channel and the voltage applied. Hitherto, no theoretical analysis or numerical simulation has been conducted to explain this phenomenon. A numerical model based on finite element method was developed to explain the experimental observations. Simulations showed that the velocity profile and ion distribution deviate significantly from a single fluid electroosmotic flow. The distortion of ion distribution near the electrical double layer is responsible for the displacement time difference for the two different flow directions. The trends obtained from simulations agree with the experimental findings.

Direction dependence of displacement time for two-fluid electroosmotic flow

PubMed Central

Lim, Chun Yee; Lam, Yee Cheong

2012-01-01

Electroosmotic flow that involves one fluid displacing another fluid is commonly encountered in various microfludic applications and experiments, for example, current monitoring technique to determine zeta potential of microchannel. There is experimentally observed anomaly in such flow, namely, the displacement time is flow direction dependent, i.e., it depends if it is a high concentration fluid displacing a low concentration fluid, or vice versa. Thus, this investigation focuses on the displacement flow of two fluids with various concentration differences. The displacement time was determined experimentally with current monitoring method. It is concluded that the time required for a high concentration solution to displace a low concentration solution is smaller than the time required for a low concentration solution to displace a high concentration solution. The percentage displacement time difference increases with increasing concentration difference and independent of the length or width of the channel and the voltage applied. Hitherto, no theoretical analysis or numerical simulation has been conducted to explain this phenomenon. A numerical model based on finite element method was developed to explain the experimental observations. Simulations showed that the velocity profile and ion distribution deviate significantly from a single fluid electroosmotic flow. The distortion of ion distribution near the electrical double layer is responsible for the displacement time difference for the two different flow directions. The trends obtained from simulations agree with the experimental findings. PMID:22662083

Analysis of Accelerometer Data from a Woven Inflatable Creep Burst Test

NASA Technical Reports Server (NTRS)

James, George H.; Grygier, Michael; Selig, Molly M.

2015-01-01

Accelerometers were used to montor an inflatable test article during a creep test to failure. The test article experienced impulse events that were classified based on the response of the sensors and their time-dependent manifestation. These impulse events required specialized techniques to process the structural dynamics data. However, certain phenomena were defined as worthy of additional study. An assessment of one phenomena (a frequency near 1000Hz) showed a time dependent frequency and an amplitude that increased significantly near the end of the test. Hence, these observations are expected to drive future understanding of and utility in inflatable space structures.

Stress response in rat brain after different durations of noise exposure.

PubMed

Samson, James; Sheeladevi, Rathinasamy; Ravindran, Rajan; Senthilvelan, Manohar

2007-01-01

The alteration in the levels of plasma corticosterone, brain norepinephrine (NE), and expression of brain heat shock proteins (Hsp70) after different durations of noise exposure (acute, 1 day; sub-acute, 15 days; chronic, 30 days) has been studied to analyze their role in combating time-dependent stress effects of noise. Broadband white noise (100dB) exposure to male Wistar albino rats significantly increased the levels of plasma corticosterone and NE in all three durations of noise exposure. The sustained increase observed in their levels in the chronic group suggests that animals are not getting adapted to noise even after 30 days of exposure. The important role of Hsp70 in combating noise induced stress is evident from the significant increase in its expression after chronic exposure, while there was a reciprocal decrease in the NE and corticosterone when compared with their levels after acute and sub-acute noise exposure. This clearly indicates that the time-dependent stress response to noise exposure is a complex mechanism involving highly interconnected systems such as hypothalamo-pituitary-adrenal (HPA) axis, heat shock proteins and may have serious implications in vital organs, particularly in the brain when there is a prolonged noise exposure.

HIV Treatment Outcomes Among HIV-Infected, Opioid-Dependent Patients Receiving Buprenorphine/Naloxone Treatment within HIV Clinical Care Settings: Results From a Multisite Study

PubMed Central

Altice, Frederick L.; Bruce, R. Douglas; Lucas, Gregory M.; Lum, Paula J.; Korthuis, P. Todd; Flanigan, Timothy P.; Cunningham, Chinazo O.; Sullivan, Lynn E.; Vergara-Rodriguez, Pamela; Fiellin, David A.; Cajina, Adan; Botsko, Michael; Nandi, Vijay; Gourevitch, Marc N.; Finkelstein, Ruth

2012-01-01

Background Having opioid dependence and HIV infection are associated with poor HIV-related treatment outcomes. Methods HIV-infected, opioid-dependent subjects (N = 295) recruited from 10 clinical sites initiated buprenorphine/naloxone (BUP/NX) and were assessed at baseline and quarterly for 12 months. Primary outcomes included receiving antiretroviral therapy (ART), HIV-1 RNA suppression, and mean changes in CD4 lymphocyte count. Analyses were stratified for the 119 subjects not on ART at baseline. Generalized estimating equations were deployed to examine time-dependent correlates for each outcome. Results At baseline, subjects on ART (N = 176) were more likely than those not on ART (N = 119) to be older, heterosexual, have lower alcohol addiction severity scores, and lower HIV-1 RNA levels; they were less likely to be homeless and report sexual risk behaviors. Subjects initiating BUP/NX (N = 295) were significantly more likely to initiate or remain on ART and improve CD4 counts over time compared with baseline; however, these improvements were not significantly improved by longer retention on BUP/NX. Retention on BUP/NX for three or more quarters was, however, significantly associated with increased likelihood of initiating ART (β = 1.34 [1.18, 1.53]) and achieve viral suppression (β = 1.25 [1.10, 1.42]) for the 64 of 119 (54%) subjects not on ART at baseline compared with the 55 subjects not retained on BUP/NX. In longitudinal analyses, being on ART was positively associated with increasing time of observation from baseline and higher mental health quality of life scores (β = 1.25 [1.06, 1.46]) and negatively associated with being homo- or bisexual (β = 0.55 [0.35, 0.97]), homeless (β = 0.58 [0.34, 0.98]), and increasing levels of alcohol addiction severity (β = 0.17 [0.03, 0.88]). The strongest correlate of achieving viral suppression was being on ART (β = 10.27 [5.79, 18.23]). Female gender (β = 1.91 [1.07, 3.41]), Hispanic ethnicity (β = 2.82 [1.44, 5.49]), and increased general health quality of life (β = 1.02 [1.00,1.04]) were also independently correlated with viral suppression. Improvements in CD4 lymphocyte count were significantly associated with being on ART and increased over time. Conclusions Initiating BUP/NX in HIV clinical care settings is feasible and correlated with initiation of ART and improved CD4 lymphocyte counts. Longer retention on BPN/NX was not associated with improved prescription of ART, viral suppression, or CD4 lymphocyte counts for the overall sample in which the majority was already prescribed ART at baseline. Among those retained on BUP/NX, HIV treatment outcomes did not worsen and were sustained. Increasing time on BUP/NX, however, was especially important for improving HIV treatment outcomes for those not on ART at baseline, the group at highest risk for clinical deterioration. Retaining subjects on BUP/NX is an important goal for sustaining HIV treatment outcomes for those on ART and improving them for those who are not. Comorbid substance use disorders (especially alcohol), mental health problems, and quality–of-life indicators independently contributed to HIV treatment outcomes among HIV-infected persons with opioid dependence, suggesting the need for multidisciplinary treatment strategies for this population. PMID:21317590

Spatial aspects of tree mortality strongly differ between young and old-growth forests.

PubMed

Larson, Andrew J; Lutz, James A; Donato, Daniel C; Freund, James A; Swanson, Mark E; HilleRisLambers, Janneke; Sprugel, Douglas G; Franklin, Jerry F

2015-11-01

Rates and spatial patterns of tree mortality are predicted to change during forest structural development. In young forests, mortality should be primarily density dependent due to competition for light, leading to an increasingly spatially uniform pattern of surviving trees. In contrast, mortality in old-growth forests should be primarily caused by contagious and spatially autocorrelated agents (e.g., insects, wind), causing spatial aggregation of surviving trees to increase through time. We tested these predictions by contrasting a three-decade record of tree mortality from replicated mapped permanent plots located in young (< 60-year-old) and old-growth (> 300-year-old) Abies amabilis forests. Trees in young forests died at a rate of 4.42% per year, whereas trees in old-growth forests died at 0.60% per year. Tree mortality in young forests was significantly aggregated, strongly density dependent, and caused live tree patterns to become more uniform through time. Mortality in old-growth forests was spatially aggregated, but was density independent and did not change the spatial pattern of surviving trees. These results extend current theory by demonstrating that density-dependent competitive mortality leading to increasingly uniform tree spacing in young forests ultimately transitions late in succession to a more diverse tree mortality regime that maintains spatial heterogeneity through time.

Allelic association of a dopamine transporter gene polymorphism with antisocial behaviour in heroin-dependent patients.

PubMed

Gerra, Gilberto; Garofano, Luciano; Pellegrini, Caterina; Bosari, Silvano; Zaimovic, Amir; Moi, Gabriele; Avanzini, Paola; Talarico, Enrica; Gardini, Federica; Donnini, Claudia

2005-09-01

Polymorphism of a variable number of tandem repeats (VNTR) in the 3' untranslated region of exon 15 of the SLC6A3 gene, coding for the dopamine transporter (DAT), was analysed to test whether length variation contributes to differences in the individual susceptibility to aggressive - criminal behaviour and liability to heroin dependence. The repeat number of the DAT polymorphism was assessed in 125 healthy subjects and 104 heroin-dependent subjects (including 52 addicted individuals with violent behaviour and criminal records). There was no significant difference in the frequencies of genotypes and alleles between heroin-dependent subjects and control subjects. On the contrary, there was a significant difference between offenders and non-offenders, p = 0.004 and p = 0.002, respectively, among heroin-dependent subjects. No association was found between DAT polymorphism and history of suicide. Buss - Durkee Hostility Inventory (BDHI) mean total scores were significantly higher in heroin addicts than in controls (p < 0.001) and in antisocial - violent heroin addicts in comparison with addicted individuals without antisocial behaviour (p < 0.005). The regression analysis of BDHI subscales, performed to provide an estimate of the magnitude of any potential effect on the risk of aggressiveness associated with the variants in DAT VNTR, showed that the presence of the 9 - 9 genotype significantly increases the risk of irritability and direct aggressiveness more than six and 10 times with respect to the 9 - 10 genotype. Our findings suggest that the 9-repeat allele of the DAT polymorphism confers increased susceptibility to antisocial - violent behaviour and aggressiveness, rather than drug dependence per se in heroin-dependent males.

Satiety and eating patterns in two species of constricting snakes.

PubMed

Nielsen, Torben P; Jacobsen, Magnus W; Wang, Tobias

2011-01-10

Satiety has been studied extensively in mammals, birds and fish but very little information exists on reptiles. Here we investigate time-dependent satiation in two species of constricting snakes, ball pythons (Python regius) and yellow anacondas (Eunectes notaeus). Satiation was shown to depend on both fasting time and prey size. In the ball pythons fed with mice of a relative prey mass RPM (mass of the prey/mass of the snake×100) of 15%, we observed a satiety response that developed between 6 and 12h after feeding, but after 24h pythons regained their appetite. With an RPM of 10% the pythons kept eating throughout the experiment. The anacondas showed a non-significant tendency for satiety to develop between 6 and 12h after ingesting a prey of 20% RPM. Unlike pythons, anacondas remained satiated after 24h. Handling time (from strike until prey swallowed) increased with RPM. We also found a significant decrease in handling time between the first and the second prey and a positive correlation between handling time and the mass of the snake. 2010 Elsevier Inc. All rights reserved.

Thermal ablation of an aluminium film upon absorption of a femtosecond laser pulse

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

Bezhanov, S G; Kanavin, A P; Uryupin, S A

We have found the time dependence of the ablation depth of aluminium irradiated by a femtosecond laser pulse. It is shown to what extent an increase in the radiation energy flux density leads to an increase in the quasi-stationary value of the ablation depth. By reducing the aluminium film thickness down to one hundred nanometres and less, the ablation depth significantly increases. At the same time, the quasi-stationary value of the ablation depth of a thin film is obtained due to the removal of heat from the focal spot region. (interaction of laser radiation with matter. laser plasma)

Effect of beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitors and antioxidant vitamins on free radical lipid oxidation in rat liver.

PubMed

Lankin, V Z; Ivanova, M V; Konovalova, G G; Tikhaze, A K; Kaminnyi, A I; Kukharchuk, V V

2007-04-01

We studied the effects of two inhibitors of beta-hydroxy-beta-methylglutaryl coenzyme A reductase, simvastatin and lovastatin, on the lag phase of ascorbate-dependent lipid oxidation in rat liver. Oxidizability of liver biological membranes significantly increased in intact animals and rats with induced hypercholesterolemia after peroral administration of these statins. The lag phase of ascorbate-dependent lipid oxidation in liver biomembranes decreased by 2.1 times in hypercholesterolemic rats. In animals of the lovastatin group this parameter decreased by 4.4 times compared to the control. In intact rats receiving simvastatin, the lag phase of oxidation in biomembranes from the liver decreased practically by 2 times. At the same time, in animals receiving simvastatin in combination with antioxidant vitamins (vitamins E and C, provitamin A) and selenium, the period of induction of oxidation increased by 3.3 times. Our results indicate that beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitors produce a prooxidant effect on the liver, which can be prevented by administration of antioxidant agents.

Bioactive compounds from crocodile (Crocodylus siamensis) white blood cells induced apoptotic cell death in hela cells.

PubMed

Patathananone, Supawadee; Thammasirirak, Sompong; Daduang, Jureerut; Chung, Jing Gung; Temsiripong, Yosapong; Daduang, Sakda

2016-08-01

Crocodile (Crocodylus siamensis) white blood cell extracts (WBCex) were examined for anticancer activity in HeLa cell lines using the MTT assay. The percentage viability of HeLa cells significantly deceased after treatment with WBCex in a dose- and time-dependent manner. The IC50 dose was suggested to be approximately 225 μg/mL protein. Apoptotic cell death occurred in a time-dependent manner based on investigation by flow cytometry using annexin V-FITC and PI staining. DAPI nucleic acid staining indicated increased chromatin condensation. Caspase-3, -8 and -9 activities also increased, suggesting the induction of the caspase-dependent apoptotic pathway. Furthermore, the mitochondrial membrane potential (ΔΨm ) of HeLa cells was lost as a result of increasing levels of Bax and reduced levels of Bcl-2, Bcl-XL, Bcl-Xs, and XIAP. The decreased ΔΨm led to the release of cytochrome c and the activation of caspase-9 and -3. Apoptosis-inducing factor translocated into the nuclei, and endonuclease G (Endo G) was released from the mitochondria. These results suggest that anticancer agents in WBCex can induce apoptosis in HeLa cells via both caspase-dependent and -independent pathways. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 986-997, 2016. © 2015 Wiley Periodicals, Inc.

Progression of spinal deformity in wheelchair-dependent patients with Duchenne muscular dystrophy who are not treated with steroids: coronal plane (scoliosis) and sagittal plane (kyphosis, lordosis) deformity.

PubMed

Shapiro, F; Zurakowski, D; Bui, T; Darras, B T

2014-01-01

We determined the frequency, rate and extent of development of scoliosis (coronal plane deformity) in wheelchair-dependent patients with Duchenne muscular dystrophy (DMD) who were not receiving steroid treatment. We also assessed kyphosis and lordosis (sagittal plane deformity). The extent of scoliosis was assessed on sitting anteroposterior (AP) spinal radiographs in 88 consecutive non-ambulatory patients with DMD. Radiographs were studied from the time the patients became wheelchair-dependent until the time of spinal fusion, or the latest assessment if surgery was not undertaken. Progression was estimated using a longitudinal mixed-model regression analysis to handle repeated measurements. Scoliosis ≥ 10° occurred in 85 of 88 patients (97%), ≥ 20° in 78 of 88 (89%) and ≥ 30° in 66 of 88 patients (75%). The fitted longitudinal model revealed that time in a wheelchair was a highly significant predictor of the magnitude of the curve, independent of the age of the patient (p < 0.001). Scoliosis developed in virtually all DMD patients not receiving steroids once they became wheelchair-dependent, and the degree of deformity deteriorated over time. In general, scoliosis increased at a constant rate, beginning at the time of wheelchair-dependency (p < 0.001). In some there was no scoliosis for as long as three years after dependency, but scoliosis then developed and increased at a constant rate. Some patients showed a rapid increase in the rate of progression of the curve after a few years - the clinical phenomenon of a rapidly collapsing curve over a few months. A sagittal plane kyphotic deformity was seen in 37 of 60 patients (62%) with appropriate radiographs, with 23 (38%) showing lumbar lordosis (16 (27%) abnormal and seven (11%) normal). This study provides a baseline to assess the effects of steroids and other forms of treatment on the natural history of scoliosis in patients with DMD, and an approach to assessing spinal deformity in the coronal and sagittal planes in wheelchair-dependent patients with other neuromuscular disorders.

Three-dimensional collagenous niche and azacytidine selectively promote time-dependent cardiomyogenesis from human bone marrow-derived MSC spheroids.

PubMed

Joshi, Jyotsna; Mahajan, Gautam; Kothapalli, Chandrasekhar R

2018-04-17

Endogenous adult cardiac regenerative machinery is not capable of replacing the lost cells following myocardial infarction, often leading to permanent alterations in structure-function-mechanical properties. Regenerative therapies based on delivering autologous stem cells within an appropriate 3D milieu could meet such demand, by enabling homing and directed differentiation of the transplanted cells into lost specialized cell populations. Since type I collagen is the predominant cardiac tissue matrix protein, we here optimized the 3D niche which could promote time-dependent evolution of cardiomyogenesis from human bone marrow-derived mesenchymal stem cells (BM-MSC). 3D collagen gel physical and mechanical characteristics were assessed using SEM and AFM, respectively, while the standalone and combined effects of collagen concentration, culture duration, and 5-azacytidine (aza) dose on the phenotype and genotype of MSC spheroids were quantified using immunofluorescence labeling and RT-PCR analysis. Increasing collagen concentration led to a significant increase in Young's modulus (p < 0.01) but simultaneous decrease in the mean pore size, resulting in stiffer gels. Spheroid formation significantly modulated MSC differentiation and genotype, mostly due to better cell-cell interactions. Among the aza dosages tested, 10 μM appears to be optimal, while 3 mg/ml gels resulted in significantly lower cell viability compared to 1 or 2 mg/ml gels. Stiffer gels (2 and 3 mg/ml) and exposure to 10 μM aza upregulated early and late cardiac marker expressions in a time-dependent fashion. On the other hand, cell-cell signaling within the MSC spheroids seem to have a strong role in influencing mature cardiac markers expression, since neither aza nor gel stiffness seem to significantly improve their expression. Western blot analysis suggested that canonical Wnt/β-catenin signaling pathway might be primarily mediating the observed benefits of aza on cardiac differentiation of MSC spheroids. In conclusion, 2 mg/ml collagen and 10 μM aza appears to offer optimal 3D microenvironment in terms of cell viability and time-dependent evolution of cardiomyogenesis from human BM-MSCs, with significant applications in cardiac tissue engineering and stem cell transplantation for regenerating lost cardiac tissue. © 2018 Wiley Periodicals, Inc.

Humidity-Dependent Bacterial Cells Functional Morphometry Investigations Using Atomic Force Microscope

PubMed Central

Nikiyan, Hike; Vasilchenko, Alexey; Deryabin, Dmitry

2010-01-01

The effect of a relative humidity (RH) in a range of 93–65% on morphological and elastic properties of Bacillus cereus and Escherichia coli cells was evaluated using atomic force microscopy. It is shown that gradual dehumidification of bacteria environment has no significant effect on cell dimensional features and considerably decreases them only at 65% RH. The increasing of the bacteria cell wall roughness and elasticity occurs at the same time. Observed changes indicate that morphological properties of B. cereus are rather stable in wide range of relative humidity, whereas E. coli are more sensitive to drying, significantly increasing roughness and stiffness parameters at RH ≤ 84% RH. It is discussed the dependence of the response features on differences in cell wall structure of gram-positive and gram-negative bacterial cells. PMID:20652040

The Influence of Pituitary Size on Outcome After Transsphenoidal Hypophysectomy in a Large Cohort of Dogs with Pituitary-Dependent Hypercortisolism.

PubMed

van Rijn, S J; Galac, S; Tryfonidou, M A; Hesselink, J W; Penning, L C; Kooistra, H S; Meij, B P

2016-07-01

Transsphenoidal hypophysectomy is one of the treatment strategies in the comprehensive management of dogs with pituitary-dependent hypercortisolism (PDH). To describe the influence of pituitary size at time of pituitary gland surgery on long-term outcome. Three-hundred-and-six dogs with PDH. Survival and disease-free fractions were analyzed and related to pituitary size; dogs with and without recurrence were compared. Four weeks after surgery, 91% of dogs were alive and remission was confirmed in 92% of these dogs. The median survival time was 781 days, median disease-free interval was 951 days. Over time, 27% of dogs developed recurrence of hypercortisolism after a median period of 555 days. Dogs with recurrence had significantly higher pituitary height/brain area (P/B) ratio and pre-operative basal urinary corticoid-to-creatinine ratio (UCCR) than dogs without recurrence. Survival time and disease-free interval of dogs with enlarged pituitary glands was significantly shorter than that of dogs with a non-enlarged pituitary gland. Pituitary size at the time of surgery significantly increased over the 20-year period. Although larger tumors have a less favorable prognosis, outcome in larger tumors improved over time. Transsphenoidal hypophysectomy is an effective treatment for PDH in dogs, with an acceptable long-term outcome. Survival time and disease-free fractions are correlated negatively with pituitary gland size, making the P/B ratio an important pre-operative prognosticator. However, with increasing experience, and for large tumors, pituitary gland surgery remains an option to control the pituitary mass and hypercortisolism. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

Dynamic Torque and Vertical Force Analysis during Nickel-titanium Rotary Root Canal Preparation with Different Modes of Reciprocal Rotation.

PubMed

Tokita, Daisuke; Ebihara, Arata; Nishijo, Miki; Miyara, Kana; Okiji, Takashi

2017-10-01

The purpose of the present study was to compare 2 modes of reciprocal movement (torque-sensitive and time-dependent reciprocal rotation) with continuous rotation in terms of torque and apical force generation during nickel-titanium rotary root canal instrumentation. A custom-made automated root canal instrumentation and torque/force analyzing device was used to prepare simulated canals in resin blocks and monitor the torque and apical force generated in the blocks during preparation. Experimental groups (n = 7, each) consisted of (1) torque-sensitive reciprocal rotation with torque-sensitive vertical movement (group TqR), (2) time-dependent reciprocal rotation with time-dependent vertical movement (group TmR), and (3) continuous rotation with time-dependent vertical movement (group CR). The canals were instrumented with TF Adaptive SM1 and SM2 rotary files (SybronEndo, Orange, CA), and the torque and apical force were measured during instrumentation with SM2. The mean and maximum torque and apical force values were statistically analyzed using 1-way analysis of variance and the Tukey test (α = 0.05). The recordings showed intermittent increases of upward apical force and clockwise torque, indicating the generation and release of screw-in forces. The maximum upward apical force values in group TmR were significantly smaller than those in group CR (P < .05). The maximum torque values in clockwise and counterclockwise directions in groups TqR and TmR were significantly smaller than those in group CR (P < .05). Under the present experimental conditions using TF Adaptive instruments, both torque-sensitive and time-dependent reciprocal rotation generated significantly lower maximum torque and may have advantages in reducing stress generation caused by screw-in forces when compared with continuous rotation. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

Tendon Contraction After Cyclic Elongation Is an Age-Dependent Phenomenon: In Vitro and In Vivo Comparisons.

PubMed

Lavagnino, Michael; Bedi, Asheesh; Walsh, Christopher P; Sibilsky Enselman, Elizabeth R; Sheibani-Rad, Shahin; Arnoczky, Steven P

2014-06-01

Tendons are viscoelastic tissues that deform (elongate) in response to cyclic loading. However, the ability of a tendon to recover this elongation is unknown. Tendon length significantly increases after in vivo or in vitro cyclic loading, and the ability to return to its original length through a cell-mediated contraction mechanism is an age-dependent phenomenon. Controlled laboratory study. In vitro, rat tail tendon fascicles (RTTfs) from Sprague-Dawley rats of 3 age groups (1, 3, and 12 months) underwent 2% cyclic strain at 0.17 Hz for 2 hours, and the percentages of elongation were determined. After loading, the RTTfs were suspended for 3 days under tissue culture conditions and photographed daily to determine the amount of length contraction. In vivo, healthy male participants (n = 29; age, 19-49 years) had lateral, single-legged weightbearing radiographs taken of the knee at 60° of flexion immediately before, immediately after, and 24 hours after completing eccentric quadriceps loading exercises on the dominant leg to fatigue. Measurements of patellar tendon length were taken from the radiographs, and the percentages of tendon elongation and subsequent contraction were calculated. In vitro, cyclic loading increased the length of all RTTfs, with specimens from younger (1 and 3 months) rats demonstrating significantly greater elongation than those from older (12 months) rats (P = .009). The RTTfs contracted to their original length significantly faster (P < .001) and in an age-dependent fashion, with younger animals contracting faster. In vivo, repetitive eccentric loading exercises significantly increased patellar tendon length (P < .001). Patellar tendon length decreased 24 hours after exercises (P < .001) but did not recover completely (P < .001). There was a weak but significant (R (2) = 0.203, P = .014) linear correlation between the amount of tendon contraction and age, with younger participants (<30 years) demonstrating significantly more contraction (P = .014) at 24 hours than older participants (>30 years). Cyclic tendon loading results in a significant increase in tendon elongation under both in vitro and in vivo conditions. Tendons in both conditions demonstrated an incomplete return to their original length after 24 hours, and the extent of this return was age dependent. The age- and time-dependent contraction of tendons, elongated after repetitive loading, could result in transient alterations in the mechanobiological environment of tendon cells. This, in turn, could induce the onset of catabolic changes associated with the pathogenesis of tendinopathy. These results suggest the importance of allowing time for contraction between bouts of repetitive exercise and may explain why age is a predisposing factor in tendinopathy. © 2014 The Author(s).

Load and Time Dependence of Interfacial Chemical Bond-Induced Friction at the Nanoscale.

PubMed

Tian, Kaiwen; Gosvami, Nitya N; Goldsby, David L; Liu, Yun; Szlufarska, Izabela; Carpick, Robert W

2017-02-17

Rate and state friction (RSF) laws are widely used empirical relationships that describe the macroscale frictional behavior of a broad range of materials, including rocks found in the seismogenic zone of Earth's crust. A fundamental aspect of the RSF laws is frictional "aging," where friction increases with the time of stationary contact due to asperity creep and/or interfacial strengthening. Recent atomic force microscope (AFM) experiments and simulations found that nanoscale silica contacts exhibit aging due to the progressive formation of interfacial chemical bonds. The role of normal load (and, thus, normal stress) on this interfacial chemical bond-induced (ICBI) friction is predicted to be significant but has not been examined experimentally. Here, we show using AFM that, for nanoscale ICBI friction of silica-silica interfaces, aging (the difference between the maximum static friction and the kinetic friction) increases approximately linearly with the product of the normal load and the log of the hold time. This behavior is attributed to the approximately linear dependence of the contact area on the load in the positive load regime before significant wear occurs, as inferred from sliding friction measurements. This implies that the average pressure, and thus the average bond formation rate, is load independent within the accessible load range. We also consider a more accurate nonlinear model for the contact area, from which we extract the activation volume and the average stress-free energy barrier to the aging process. Our work provides an approach for studying the load and time dependence of contact aging at the nanoscale and further establishes RSF laws for nanoscale asperity contacts.

Load and Time Dependence of Interfacial Chemical Bond-Induced Friction at the Nanoscale

NASA Astrophysics Data System (ADS)

Tian, Kaiwen; Gosvami, Nitya N.; Goldsby, David L.; Liu, Yun; Szlufarska, Izabela; Carpick, Robert W.

2017-02-01

Rate and state friction (RSF) laws are widely used empirical relationships that describe the macroscale frictional behavior of a broad range of materials, including rocks found in the seismogenic zone of Earth's crust. A fundamental aspect of the RSF laws is frictional "aging," where friction increases with the time of stationary contact due to asperity creep and/or interfacial strengthening. Recent atomic force microscope (AFM) experiments and simulations found that nanoscale silica contacts exhibit aging due to the progressive formation of interfacial chemical bonds. The role of normal load (and, thus, normal stress) on this interfacial chemical bond-induced (ICBI) friction is predicted to be significant but has not been examined experimentally. Here, we show using AFM that, for nanoscale ICBI friction of silica-silica interfaces, aging (the difference between the maximum static friction and the kinetic friction) increases approximately linearly with the product of the normal load and the log of the hold time. This behavior is attributed to the approximately linear dependence of the contact area on the load in the positive load regime before significant wear occurs, as inferred from sliding friction measurements. This implies that the average pressure, and thus the average bond formation rate, is load independent within the accessible load range. We also consider a more accurate nonlinear model for the contact area, from which we extract the activation volume and the average stress-free energy barrier to the aging process. Our work provides an approach for studying the load and time dependence of contact aging at the nanoscale and further establishes RSF laws for nanoscale asperity contacts.

Stress generation in a developmental context: the role of youth depressive symptoms, maternal depression, the parent-child relationship, and family stress.

PubMed

Chan, Priscilla T; Doan, Stacey N; Tompson, Martha C

2014-02-01

The present study examined stress generation in a developmental and family context among 171 mothers and their preadolescent children, ages 8-12 years, at baseline (Time 1) and 1-year follow-up (Time 2). In the current study, we examined the bidirectional relationship between children's depressive symptoms and dependent family stress. Results suggest that children's baseline level of depressive symptoms predicted the generation of dependent family stress 1 year later. However, baseline dependent family stress did not predict an increase in children's depressive symptoms 1 year later. In addition, we examined whether a larger context of both child chronic strain (indicated by academic, behavioral, and peer stress) and family factors, including socioeconomic status and parent-child relationship quality, would influence the stress generation process. Although both chronic strain and socioeconomic status were not associated with dependent family stress at Time 2, poorer parent-child relationship quality significantly predicted greater dependent family stress at Time 2. Child chronic strain, but neither socioeconomic status nor parent-child relationship quality, predicted children's depression symptoms at Time 2. Finally, gender, maternal depression history, and current maternal depressive symptoms did not moderate the relationship between level of dependent family stress and depressive symptoms. Overall, findings provide partial support for a developmental stress generation model operating in the preadolescent period.

Time-dependent effect of composted tannery sludge on the chemical and microbial properties of soil.

PubMed

de Sousa, Ricardo Silva; Santos, Vilma Maria; de Melo, Wanderley Jose; Nunes, Luis Alfredo Pinheiro Leal; van den Brink, Paul J; Araújo, Ademir Sérgio Ferreira

2017-12-01

Composting has been suggested as an efficient method for tannery sludge recycling before its application to the soil. However, the application of composted tannery sludge (CTS) should be monitored to evaluate its effect on the chemical and microbial properties of soil. This study evaluated the time-dependent effect of CTS on the chemical and microbial properties of soil. CTS was applied at 0, 2.5, 5, 10, and 20 Mg ha -1 and the soil chemical and microbial properties were evaluated at 0, 45, 75, 150, and 180 days. Increased CTS rates increased the levels of Ca, Cr, and Mg. While Soil pH, organic C, and P increased with the CTS rates initially, this effect decreased over time. Soil microbial biomass, respiration, metabolic quotient, and dehydrogenase increased with the application of CTS, but decreased over time. Analysis of the Principal Response Curve showed a significant effect of CTS rate on the chemical and microbial properties of the soil over time. The weight of each variable indicated that all soil properties, except β-glucosidase, dehydrogenase and microbial quotient, increased due to the CTS application. However, the highest weights were found for Cr, pH, Ca, P, phosphatase and total organic C. The application of CTS in the soil changed the chemical and microbial properties over time, indicating Cr, pH, Ca, phosphatase, and soil respiration as the more responsive chemical and microbial variables by CTS application.

Nicotine dependence matters: examining longitudinal association between smoking and physical activity among Canadian adults.

PubMed

Azagba, Sunday; Asbridge, Mark

2013-11-01

A number of studies point to the inverse relationship between physical activity and smoking; however, none has examined the role of nicotine dependence in physical activity participation among smokers. This study examined whether levels of nicotine dependence modify the association between leisure time physical activity and smoking status. The study used longitudinal data on 6795 adults from the Canadian National Population Health Survey (2004-2010). Generalized estimating equations were used to examine the association between physical activity, smoking, and nicotine dependence. We found that nicotine dependent smokers were significantly less likely to be physically active compared to non-smokers. Specifically, using the Fagerstrom Test for Nicotine Dependence, nicotine dependent smokers (OR 0.65, 95% CI 0.55-0.76) were less likely to be physically active while no significant difference was found for non-dependent smokers (OR 0.90, 95% CI 0.80-1.02) compared to non-smokers. Nicotine dependence matters in shaping engagement in physical activity among daily smokers. Efforts directed at promoting smoking cessation through nicotine dependence treatment intervention may provide additional benefits to health and well-being through an increased participation in physical activity. © 2013.

Do health care workforce, population, and service provision significantly contribute to the total health expenditure? An econometric analysis of Serbia.

PubMed

Santric-Milicevic, M; Vasic, V; Terzic-Supic, Z

2016-08-15

In times of austerity, the availability of econometric health knowledge assists policy-makers in understanding and balancing health expenditure with health care plans within fiscal constraints. The objective of this study is to explore whether the health workforce supply of the public health care sector, population number, and utilization of inpatient care significantly contribute to total health expenditure. The dependent variable is the total health expenditure (THE) in Serbia from the years 2003 to 2011. The independent variables are the number of health workers employed in the public health care sector, population number, and inpatient care discharges per 100 population. The statistical analyses include the quadratic interpolation method, natural logarithm and differentiation, and multiple linear regression analyses. The level of significance is set at P < 0.05. The regression model captures 90 % of all variations of observed dependent variables (adjusted R square), and the model is significant (P < 0.001). Total health expenditure increased by 1.21 standard deviations, with an increase in health workforce growth rate by 1 standard deviation. Furthermore, this rate decreased by 1.12 standard deviations, with an increase in (negative) population growth rate by 1 standard deviation. Finally, the growth rate increased by 0.38 standard deviation, with an increase of the growth rate of inpatient care discharges per 100 population by 1 standard deviation (P < 0.001). Study results demonstrate that the government has been making an effort to control strongly health budget growth. Exploring causality relationships between health expenditure and health workforce is important for countries that are trying to consolidate their public health finances and achieve universal health coverage at the same time.

Melanins as biomarkers of ovarian follicular atresia in the catfish Heteropneustes fossilis: biochemical and histochemical characterization, seasonal variation and hormone effects.

PubMed

Kumar, Ravi; Joy, Keerikkattil P

2015-06-01

Follicular atresia is a common feature of the vertebrate ovary that occurs at different stages of folliculogenesis and ovarian regression. It has physiological significance to maintain homeostasis and control fecundity, and ensure removal of post-ovulatory follicular remnants for preparing the ovary for the next cycle. Pigments appear late in the atretic process as indigestible waste formed out of the degradation of the oocytes, follicle wall and granulocytes. In the present study, pigment accumulation was demonstrated by Schmorl's and Perls' staining methods in the atretic ovarian follicles of Heteropneustes fossilis during follicular development and regression. Melanins were characterized spectrophotometrically for the first time in fish ovary. The predominant form is eumelanin, followed by pheomelanin and alkali-soluble melanin. Melanins showed significant seasonal variations with levels low in gonad resting phase, increasing to the peak in the post-spawning phase. The concentration of melanins increased time-dependently in post-ovulated ovary after human chorionic gonadotropin treatment. In the spawning phase, in vitro incubation of ovary slices with estradiol-17β or dexamethasone for 8 or 16 h decreased both eumelanin and pheomelanin levels time-dependently. The alkali-soluble melanin showed a significant decrease only in the dexamethasone group at 16 h. The results show that melanin assay can be used as a biomarker of follicular atresia in fish ovary, natural or induced by environmental toxicants.

Inoculation of Scrapie with the Self-Assembling RADA-Peptide Disrupts Prion Accumulation and Extends Hamster Survival

USDA-ARS?s Scientific Manuscript database

Intercerebral inoculation of 263K Scrapie brain homogenate (PrPsc) with a self-assembling RADA-peptide (RADA) significantly delayed disease onset and increased hamster survival. Time of survival was dependent on the dose of RADA and pre-incubation with PrPsc prior to inoculation. RADA treatment resu...

CFTR-dependent chloride efflux in cystic fibrosis mononuclear cells is increased by ivacaftor therapy.

PubMed

Guerra, Lorenzo; D'Oria, Susanna; Favia, Maria; Castellani, Stefano; Santostasi, Teresa; Polizzi, Angela M; Mariggiò, Maria A; Gallo, Crescenzio; Casavola, Valeria; Montemurro, Pasqualina; Leonetti, Giuseppina; Manca, Antonio; Conese, Massimo

2017-07-01

The Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) potentiator ivacaftor (Kalydeco®) improves clinical outcome in G551D cystic fibrosis (CF) patients. Here, we have investigated whether ivacaftor has a clinical impact on non-G551D gating mutations and function of circulating leukocytes as well. Seven patients were treated with ivacaftor and evaluated at baseline, and at 1-3 and 6 months. Besides clinical and systemic inflammatory parameters, circulating mononuclear cells (MNC) were evaluated for CFTR-dependent chloride efflux by spectrofluorimetry, neutrophils for oxidative burst by cytofluorimetry and HVCN1 mRNA expression by real time PCR. Ivacaftor determined a significant decrease in sweat chloride concentrations at all time points during treatment. Body mass index (BMI), FEV 1 , and FVC showed an increasing trend. While C-reactive protein decreased significantly at 2 months, the opposite behavior was noticed for circulating monocytes. CFTR activity in MNC was found to increase significantly at 3 and 6 months. Neutrophil oxidative burst peaked at 2 months and then decreased to baseline. HVCN1 mRNA expression was significantly higher than baseline at 1-3 months and decreased after 6 months of treatment. The chloride efflux in MNC correlated positively with both FEV 1 and FVC. On the other hand, sweat chloride correlated positively with CRP and WBC, and negatively with both respiratory function tests. A cluster analysis confirmed that sweat chloride, FEV 1 , FVC, BMI, and MNC chloride efflux behaved as a single entity over time. In patients with non-G551D mutations, ivacaftor improved both chloride transport in sweat ducts and chloride efflux in MNC, that is, functions directly imputed to CFTR. © 2017 Wiley Periodicals, Inc.

Days with pain and substance use disorders: is there an association?

PubMed

Edlund, Mark J; Sullivan, Mark D; Han, Xiaotong; Booth, Brenda M

2013-08-01

We investigated possible associations between pain frequency and the 5 most common substance use disorders: alcohol abuse/dependence, cocaine abuse/dependence, methamphetamine abuse/dependence, opioid abuse/dependence, and marijuana abuse/dependence. We used data from the Rural Stimulant Study, a longitudinal (7 waves), observational study of at-risk stimulant users (cocaine and methamphetamine) in Arkansas and Kentucky (n=462). In fixed-effects logistic regression models, we regressed our measures of substance use disorders on the number of days with pain in the past 30 days and depression severity. Time periods when individuals had 1 to 15 days [odds ratio (OR)=1.85, P<0.001] or 16+ days (OR=2.18, P<0.001) with pain in the past 30 days were more likely to have a diagnosis of alcohol abuse/dependence, compared with time periods when individuals had no days with pain. Compared with time periods when individuals had no pain days in the past 30 days, time periods when individuals had 16+ pain days were more likely to have a diagnosis of opioid abuse/dependence (OR=3.32, P=0.02). Number of days with pain was not significantly associated with other substance use disorders. Pain frequency seems to be associated with an increased risk for alcohol abuse/dependence and opioid abuse/dependence in this population, and the magnitude of the association is medium to large. Further research is needed to investigate this in more representative populations and to determine causal relationships.

Dynamics of shear-induced ATP release from red blood cells.

PubMed

Wan, Jiandi; Ristenpart, William D; Stone, Howard A

2008-10-28

Adenosine triphosphate (ATP) is a regulatory molecule for many cell functions, both for intracellular and, perhaps less well known, extracellular functions. An important example of the latter involves red blood cells (RBCs), which help regulate blood pressure by releasing ATP as a vasodilatory signaling molecule in response to the increased shear stress inside arterial constrictions. Although shear-induced ATP release has been observed widely and is believed to be triggered by deformation of the cell membrane, the underlying mechanosensing mechanism inside RBCs is still controversial. Here, we use an in vitro microfluidic approach to investigate the dynamics of shear-induced ATP release from human RBCs with millisecond resolution. We demonstrate that there is a sizable delay time between the onset of increased shear stress and the release of ATP. This response time decreases with shear stress, but surprisingly does not depend significantly on membrane rigidity. Furthermore, we show that even though the RBCs deform significantly in short constrictions (duration of increased stress <3 ms), no measurable ATP is released. This critical timescale is commensurate with a characteristic membrane relaxation time determined from observations of the cell deformation by using high-speed video. Taken together our results suggest a model wherein the retraction of the spectrin-actin cytoskeleton network triggers the mechanosensitive ATP release and a shear-dependent membrane viscosity controls the rate of release.

Agglomeration, sedimentation, and cellular toxicity of alumina nanoparticles in cell culture medium

NASA Astrophysics Data System (ADS)

Yoon, Dokyung; Woo, Daekwang; Kim, Jung Heon; Kim, Moon Ki; Kim, Taesung; Hwang, Eung-Soo; Baik, Seunghyun

2011-06-01

The cytotoxicity of alumina nanoparticles (NPs) was investigated for a wide range of concentration (25-200 μg/mL) and incubation time (0-72 h) using floating cells (THP-1) and adherent cells (J774A.1, A549, and 293). Alumina NPs were gradually agglomerated over time although a significant portion of sedimentation occurred at the early stage within 6 h. A decrease of the viability was found in floating (THP-1) and adherent (J774A.1 and A549) cells in a dose-dependent manner. However, the time-dependent decrease in cell viability was observed only in adherent cells (J774A.1 and A549), which is predominantly related with the sedimentation of alumina NPs in cell culture medium. The uptake of alumina NPs in macrophages and an increased cell-to-cell adhesion in adherent cells were observed. There was no significant change in the viability of 293 cells. This in vitro test suggests that the agglomeration and sedimentation of alumina NPs affected cellular viability depending on cell types such as monocytes (THP-1), macrophages (J774A.1), lung carcinoma cells (A549), and embryonic kidney cells (293).

Retinoblastoma protein (pRB) was significantly phosphorylated through a Ras-to-MAPK pathway in mutant K-ras stably transfected human adrenocortical cells.

PubMed

Chen, Y-F; Chiu, H-H; Wu, C-H; Wang, J-Y; Chen, F-M; Tzou, W-H; Shin, S-J; Lin, S-R

2003-10-01

Our previous studies have shown that the cell proliferation rate, mRNA levels of p450scc, p450c17, and 3betaHSD, and secretion of cortisol were significantly increased in human adrenocortical cells stably transfected with mutated K-ras expression plasmid "pK568MRSV" after being inducted with IPTG. In addition, the increased level was a time-dependent manner. However, the levels of p450, p450scc, p450c17, 3betaHSD, cortisol, and cell proliferation rate were inhibited by a MEK phospholation inhibitor, PD098059. The above results prove that mutated K-ras oncogene is able to regulate tumorigenesis and steroidogenesis through a Ras-RAF-MEK-MAPK signal transduction pathway. The aim of this study was to investigate regulated factors in this pathway and also examine whether the other signal transduction pathways or other moles involved in tumorigenesis or steroidogenesis. In the first year, we analyzed gene profiles of mutant K-ras-transfected adrenocortical cells by DNA microarray to determine the gene expression related to cell cycle, signal transduction, apoptosis, tumorigenesis, steroidogenesis, and other expressed sequence tag. After being affected by the K-ras mutant, gene expression was significantly increased in some upregulated genes. Human zinc-finger protein 22 increased by 28.5 times, Osteopontin increased by 5.8 times, LIM domain Kinase 2 (LIMK2) increased by 3.3 times, Homo sapiens dual-specificity tyrosine-(Y)-phosphorylation regulated Kinase 2 (DYRK2) increased by 2.2 times, and human syntaxin 3 increased by two times. On the other hand, significant decreases in gene expression were also observed in some downregulated genes. Retinoblastoma binding protein 1 (RBBP1) decreased by four times, Homo sapiens craniofacial development protein 1 (CFDP1) decreased by 2.4 times, DAP Kinase-related apoptosis-inducing protein Kinase 1 (DRAK1) decreased by 2.3 times, SKI-interacting protein (SKIP) decreased by 2.2 times, and human poly(A)-Binding protein (PABP) decreased by 2.1 times. In all significant differentially expressed genes, preliminary analysis by bioinformatics revealed that after induced K-ras mutant expression by isopropyl thiogalctoside (IPTG), the downregulation of RBBP1 gene was most correlated to cell proliferation. RBBP1 can bind with RB/E2F to form a mSIN3-HDAC complex, which induces cell cycle arrest in the G1/G0 stage by repressing transcription of E2F-regulated genes. The result of a Northern blot showed that RBBP1 were inhibited after an induction of IPTG for 36 h. Another Northern blot analysis proved that mRNA levels of cyclin D1 and c-myc increased in proportion to K-ras expression. Finally, Western blot was carried out, and the results showed that phosphorylated pRB also increased. Taken together, we infer that the mutant K-ras oncogene promoted the cells to proceed to the G1/S stage by the inhibiting the formation of RB/RBBP1-dependent repressor complex from binding with the SIN3-HDAC complex, which resulted in the acetylation of histone to active transcription of E2F-regulated genes. However, the roles of the other differentially expressed genes involved in cell proliferation, cell morphologic change, tumorigenesis, or steroidogenesis still need further investigation.

Solution of 3-dimensional time-dependent viscous flows. Part 3: Application to turbulent and unsteady flows

NASA Technical Reports Server (NTRS)

Weinberg, B. C.; Mcdonald, H.

1982-01-01

A numerical scheme is developed for solving the time dependent, three dimensional compressible viscous flow equations to be used as an aid in the design of helicopter rotors. In order to further investigate the numerical procedure, the computer code developed to solve an approximate form of the three dimensional unsteady Navier-Stokes equations employing a linearized block implicit technique in conjunction with a QR operator scheme is tested. Results of calculations are presented for several two dimensional boundary layer flows including steady turbulent and unsteady laminar cases. A comparison of fourth order and second order solutions indicate that increased accuracy can be obtained without any significant increases in cost (run time). The results of the computations also indicate that the computer code can be applied to more complex flows such as those encountered on rotating airfoils. The geometry of a symmetric NACA four digit airfoil is considered and the appropriate geometrical properties are computed.

Internet Use and Its Impact on Engagement in Leisure Activities in China

PubMed Central

Zhou, Ronggang; Fong, Patrick S. W.; Tan, Peking

2014-01-01

Introduction Internet use has become an increasingly common leisure time activity among Chinese citizens. The association between Internet use and engagement in leisure activities is especially unclear among China population. This study aims to investigate Internet usage and to determine whether active Internet use is a marker for low or high levels of leisure time activities. Methods/Principal Findings With the use of a face-to-face structured questionnaire interview, a total of 2,400 respondents who met all screening requirements were surveyed to answer the questions in eight major cities in China. 66.2% (n = 1,589) of all respondents were identified as Internet users. Of these Internet users, 30.0%, 24.1%, 26.4%, and 19.6% were clustered as “informative or instrumental users,” “entertainment users,” “communication users,” and “advanced users,” respectively. Regarding time spent on Internet use in leisure time, more than 96% reported going online in non-work situations, and 26.2% (n = 416) were classified as “heavy Internet users.” A logistic regression analysis revealed that there were significant differences in some leisure activities between non-Internet users and Internet users, with an observed one-unit increase in the leisure time dependence category increasing the probability of engaging in mental or social activities. In contrast, Internet users were less engaged in physical exercise-related activities. In addition, advanced Internet users were generally more active in leisure time activities than non-Internet users and other types of users. Conclusion/Significance Internet use is one of very common leisure activities in Chinese citizens, and age, gender, income, and education are the key factors affecting Internet access. According to different types of leisure activities, Internet usage has different impacts on leisure activity engagement. High Internet dependence has no significant negative influence on engagement in mental or social leisure activities, but this group respondent tended to be less engaged in physical activities. PMID:24586902

Atmospheric carbon dioxide and chlorofluoromethanes - Combined effects on stratospheric ozone, temperature, and surface temperature

NASA Technical Reports Server (NTRS)

Callis, L. B.; Natarajan, M.

1981-01-01

The effects of combined CO2 and CFCl3 and CF2Cl2 time-dependent scenarios on atmospheric O3 and temperature are described; the steady-state levels of O3 and surface temperature, to which the chlorofluoromethane scenario tends in the presence of twice and four time ambient CO2, are examined; and surface temperature changes, caused by the combined effects, are established. A description of the model and of the experiments is presented. Results indicate that (1) the total ozone time history is significantly different from that due to the chlorofluoromethane alone; (2) a local ozone minimum occurs in the upper stratosphere about 45 years from the present with a subsequent ozone increase, then decline; and (3) steady-state solutions indicate that tropospheric temperature and water vapor increases, associated with increased infrared opacity, cause significant changes in tropospheric ozone levels for 2 x CO2 and 4 x CO2, without the addition of chlorofluoromethanes.

Two-stage unified stretched-exponential model for time-dependence of threshold voltage shift under positive-bias-stresses in amorphous indium-gallium-zinc oxide thin-film transistors

NASA Astrophysics Data System (ADS)

Jeong, Chan-Yong; Kim, Hee-Joong; Hong, Sae-Young; Song, Sang-Hun; Kwon, Hyuck-In

2017-08-01

In this study, we show that the two-stage unified stretched-exponential model can more exactly describe the time-dependence of threshold voltage shift (ΔV TH) under long-term positive-bias-stresses compared to the traditional stretched-exponential model in amorphous indium-gallium-zinc oxide (a-IGZO) thin-film transistors (TFTs). ΔV TH is mainly dominated by electron trapping at short stress times, and the contribution of trap state generation becomes significant with an increase in the stress time. The two-stage unified stretched-exponential model can provide useful information not only for evaluating the long-term electrical stability and lifetime of the a-IGZO TFT but also for understanding the stress-induced degradation mechanism in a-IGZO TFTs.

Ethanol Dose- and Time-dependently Increases α and β Subunits of Mitochondrial ATP Synthase of Cultured Neonatal Rat Cardiomyocytes.

PubMed

Mashimo, Keiko; Arthur, Peter G; Ohno, Youkichi

2015-01-01

Mitochondria are target subcellular organelles of ethanol. In this study, the effects of ethanol on protein composition was examined with 2-dimensional electrophoresis of protein extracts from cultured neonatal rat cardiomyocytes exposed to 100 mM ethanol for 24 hours. A putative β subunit of mitochondrial ATP synthase was increased, which was confirmed by Western blot. The cellular protein abundances in the α and β subunits of ATP synthase increased in dose (0, 10, 50, and 100 mM) - and time (0.5 hour and 24 hours) -dependent manners. The DNA microarray analysis of total RNA extract demonstrated that gene expression of the corresponding messenger RNAs of these subunit proteins did not significantly alter due to 24-hour ethanol exposure. Therefore, protein expression of these nuclear-encoded mitochondrial proteins may be regulated at the translational, rather than the transcriptional, level. Alternatively, degradation of these subunit proteins might be decreased. Additionally, cellular ATP content of cardiomyocytes scarcely decreased following 24-hour exposure to any examined concentrations of ethanol. Previous studies, together with this study, have demonstrated that protein abundance of the α subunit or β subunit or both subunits of ATP synthase after ethanol exposure or dysfunctional conditions might differ according to tissue: significant increases in heart but decreases in liver and brain. Thus, it is suggested that the abundance of subunit proteins of mitochondrial ATP synthase in the ethanol-exposed heart, being different from that in the liver and brain, should increase dose-dependently through either translational upregulation or decreased degradation or both to maintain ATP production, as the heart requires much more energy than other tissues for continuing sustained contractions.

RAFT-synthesized Graft Copolymers that Enhance pH-dependent Membrane Destabilization and Protein Circulation Times

PubMed Central

Crownover, Emily; Duvall, Craig L.; Convertine, Anthony; Hoffman, Allan S.; Stayton, Patrick S.

2012-01-01

Here we describe a new graft copolymer architecture of poly(propylacrylic acid) (polyPAA) that displays potent pH-dependent, membrane-destabilizing activity and in addition is shown to enhance protein blood circulation kinetics. PolyPAA containing a single telechelic alkyne functionality was prepared via reversible addition-fragmentation chain transfer (RAFT) polymerization with an alkyne-functional chain transfer agent (CTA) and coupled to RAFT polymerized poly(azidopropyl methacrylate) (polyAPMA) through azide-alkyne [3+2] Huisgen cycloaddition. The graft copolymers become membrane destabilizing at endosomal pH values and are active at significantly lower concentrations than the linear polyPAA. A biotin terminated polyPAA graft copolymer was prepared by grafting PAA onto polyAPMA polymerized with a biotin functional RAFT CTA. The blood circulation time and biodistribution of tritium labeled avidin conjugated to the polyPAA graft copolymer was characterized along with a clinically utilized 40 kDa branched polyethylene glycol (PEG) also possessing biotin functionalization. The linear and graft polyPAA increase the area under the curve (AUC) over avidin alone by 9 and 12 times, respectively. Furthermore, polyPAA graft copolymer conjugates accumulated in tumor tissue significantly more than the linear polyPAA and the branched PEG conjugates. The collective data presented in this report indicate that the polyPAA graft copolymers exhibit robust pH-dependent, membrane-destabilizing activity, low cytotoxicity and significantly enhance blood circulation time and tumor accumulation. PMID:21699931

[Unplanned extubation in ICU, and the relevance of non-dependent patient variables the quality of care].

PubMed

González-Castro, A; Peñasco, Y; Blanco, C; González-Fernández, C; Domínguez, M J; Rodríguez-Borregán, J C

2014-01-01

To evaluate, for a consecutive year, the magnitude of unplanned extubation, looking for non-dependent patient variables. Prospective, observational study of cases and controls in a mixed intensive care unit within in a tertiary hospital. Patients were considered cases with more than 24 hours who had an episode of unplanned extubation. Prospective collection of variables case as time of unplanned extubation (collection time), identification of the box where the patient was admitted, presence and type of physical restraint, development of ventilator-associated pneumonia (VAP) and death. There were 17 unplanned extubation in 15 patients, 1.21 unplanned extubation per 100 days of MV. The unplanned extubation had an inhomogeneous spatial distribution (number of boxes). The time distribution of cases compared with controls showed significant differences in time distribution (P=.02). The comparative analysis between cases and controls, showed increased mortality, increased length of ICU stay, longer hospital stay and increased risk for VAP when patients suffer an episode of unplanned extubation. Unplanned extubation occurs most frequently in a given time slot of the day, may play a role in the spatial location of the patient; occurs most often in patients who are in the process of weaning from mechanical ventilation, and develop greater VAP. Copyright © 2014 SECA. Published by Elsevier Espana. All rights reserved.

Wave-vector and polarization dependent impedance model for a hexagonal periodic metasurface exemplified through finite-difference time-domain simulations.

PubMed

Ding, Yi S; He, Yang

2017-08-21

An isotropic impedance sheet model is proposed for a loop-type hexagonal periodic metasurface. Both frequency and wave-vector dispersion are considered near the resonance frequency. Therefore both the angle and polarization dependences of the metasurface impedance can be properly and simultaneously described in our model. The constitutive relation of this model is transformed into auxiliary differential equations which are integrated into the finite-difference time-domain algorithm. Finally, a finite large metasurface sample under oblique illumination is used to test the model and the algorithm. Our model and algorithm can significantly increase the accuracy of the homogenization methods for modeling periodic metasurfaces.

Seismic hazard assessment over time: Modelling earthquakes in Taiwan

NASA Astrophysics Data System (ADS)

Chan, Chung-Han; Wang, Yu; Wang, Yu-Ju; Lee, Ya-Ting

2017-04-01

To assess the seismic hazard with temporal change in Taiwan, we develop a new approach, combining both the Brownian Passage Time (BPT) model and the Coulomb stress change, and implement the seismogenic source parameters by the Taiwan Earthquake Model (TEM). The BPT model was adopted to describe the rupture recurrence intervals of the specific fault sources, together with the time elapsed since the last fault-rupture to derive their long-term rupture probability. We also evaluate the short-term seismicity rate change based on the static Coulomb stress interaction between seismogenic sources. By considering above time-dependent factors, our new combined model suggests an increased long-term seismic hazard in the vicinity of active faults along the western Coastal Plain and the Longitudinal Valley, where active faults have short recurrence intervals and long elapsed time since their last ruptures, and/or short-term elevated hazard levels right after the occurrence of large earthquakes due to the stress triggering effect. The stress enhanced by the February 6th, 2016, Meinong ML 6.6 earthquake also significantly increased rupture probabilities of several neighbouring seismogenic sources in Southwestern Taiwan and raised hazard level in the near future. Our approach draws on the advantage of incorporating long- and short-term models, to provide time-dependent earthquake probability constraints. Our time-dependent model considers more detailed information than any other published models. It thus offers decision-makers and public officials an adequate basis for rapid evaluations of and response to future emergency scenarios such as victim relocation and sheltering.

Drop-on-demand drop formation of polyethylene oxide solutions

NASA Astrophysics Data System (ADS)

Yan, Xuejia; Carr, Wallace W.; Dong, Hongming

2011-10-01

The dynamics of drop-on-demand (DOD) drop formation for solutions containing polyethylene oxide (PEO) have been studied experimentally. Using a piezoelectrical actuated inkjet printhead with the nozzle orifice diameter of 53 μm, experiments were conducted for a series of PEO aqueous solutions with molecular weights ranging from 14 to 1000 kg/mol, polydispersity from 1.02 to 2.5, and concentrations from 0.005 to 10 wt. %. The addition of a small amount of PEO can have a significant effect on the DOD drop formation process, increasing breakup time, decreasing primary drop speed, and decreasing the number of satellite drops in some cases. The effects depend on both molecular weight and concentration. At lower molecular weights (14 and 35 kg/mol), the effect of PEO over the dilute solution regime is insignificant even at concentrations large enough that the solution does not fall in the dilute regime. As PEO molecular weight increased, the effects became significant. For monodispersed PEO solutions, breakup time and primary drop speed closely correlated with effective relaxation time but not for polydispersed PEO. Effective relaxation time depended greatly on molecular weight distribution. Viscosity-average molecular weight, used in calculating effective relaxation time for polydispersed PEO solutions, did not adequately account for high molecular fractions in the molecular weight distribution of the polydispersed PEOs. A mixture rule was developed to calculate the effective relaxation times for aqueous solutions containing mixtures of monodispersed PEO, and breakup times and primary drop speeds correlated well with effective relaxation times. For our experiments, DOD drop formation was limited to Deborah number ≲ 23.

Charge trapping in detector grade thallium bromide and cadmium zinc telluride: Measurement and theory

NASA Astrophysics Data System (ADS)

Elshazly, Ezzat S.; Tepper, Gary; Burger, Arnold

2010-08-01

Carrier trapping times were measured in detector grade thallium bromide (TlBr) and cadmium zinc telluride (CZT) from 300 to 110 K and the experimental data were analyzed using a trapping model. In CZT, because the majority carrier concentration is close to the intrinsic carrier concentration, the trapping time increases exponentially as the temperature decreases below about 160 K. In TlBr, the majority carrier concentration is many orders of magnitude greater than the intrinsic carrier concentration and the trapping time followed a (1/ T) 1/2 temperature dependence over the range of temperatures studied. The results of the model suggest that a moderately deep compensation center could be used to significantly increase the room temperature trapping time in TlBr.

Diuretic effects of medetomidine compared with xylazine in healthy dogs.

PubMed

Talukder, Md Hasanuzzaman; Hikasa, Yoshiaki

2009-07-01

This study aimed to investigate and compare the effects of medetomidine and xylazine on diuretic and hormonal variables in healthy dogs. Five dogs, used in each of 11 groups, were injected intramuscularly with physiological saline solution (control), 5, 10, 20, 40, and 80 microg/kg of medetomidine, and 0.25, 0.5, 1, 2, and 4 mg/kg of xylazine. Urine and blood samples were taken 11 times over 24 h. Both medetomidine and xylazine increased urine production in a dose-dependent manner up to 4 h after injection, but the increase was much less with medetomidine than with xylazine at the tested doses. Urine specific gravity, pH, osmolality, and concentrations of creatinine, sodium, potassium, chloride, and arginine vasopressin (AVP) were decreased in a dose-dependent manner with both medetomidine and xylazine. Plasma osmolality and concentrations of sodium, potassium, and chloride were increased significantly with both drugs. Total amounts of urine AVP excreted and plasma AVP concentrations were significantly decreased by higher doses of medetomidine but were not significantly decreased by xylazine. Higher doses of both drugs significantly increased the plasma concentration of atrial natriuretic peptide (ANP), but the effect was greater with medetomidine than with xylazine. The results revealed that both drugs induce a profound diuresis, but medetomidine's effect is less dose-dependent than xylazine's effect. Although changes in plasma concentrations of AVP and ANP may partially influence the diuresis induced by medetomidine, other factors may be involved in the mechanism of the diuretic response to both drugs. Thus, both agents can be used clinically for transient but effective diuresis accompanied by sedation.

Dynamics of optical matter creation and annihilation in colloidal liquids controlled by laser trapping power.

PubMed

Liu, Jin; Dai, Qiao-Feng; Huang, Xu-Guang; Wu, Li-Jun; Guo, Qi; Hu, Wei; Yang, Xiang-Bo; Lan, Sheng; Gopal, Achanta Venu; Trofimov, Vyacheslav A

2008-11-15

We investigate the dynamics of optical matter creation and annihilation in a colloidal liquid that was employed to construct an all-optical switch. It is revealed that the switching-on process can be characterized by the Fermi-Dirac distribution function, while the switching-off process can be described by a steady state followed by a single exponential decay. The phase transition times exhibit a strong dependence on trapping power. With an increasing trapping power, while the switching-on time decreases rapidly, the switch-off time increases significantly, indicating the effects of optical binding and van der Waals force on the lifetime of the optical matter.

Groundwater-level trends in the U.S. glacial aquifer system, 1964-2013

USGS Publications Warehouse

Hodgkins, Glenn A.; Dudley, Robert W.; Nielsen, Martha G.; Renard, Benjamin; Qi, Sharon L.

2017-01-01

The glacial aquifer system in the United States is a major source of water supply but previous work on historical groundwater trends across the system is lacking. Trends in annual minimum, mean, and maximum groundwater levels for 205 monitoring wells were analyzed across three regions of the system (East, Central, West Central) for four time periods: 1964-2013, 1974-2013, 1984-2013, and 1994-2013. Trends were computed separately for wells in the glacial aquifer system with low potential for human influence on groundwater levels and ones with high potential influence from activities such as groundwater pumping. Generally there were more wells with significantly increasing groundwater levels (levels closer to ground surface) than wells with significantly decreasing levels. The highest numbers of significant increases for all four time periods were with annual minimum and/or mean levels. There were many more wells with significant increases from 1964 to 2013 than from more recent periods, consistent with low precipitation in the 1960s. Overall there were low numbers of wells with significantly decreasing trends regardless of time period considered; the highest number of these were generally for annual minimum groundwater levels at wells with likely human influence. There were substantial differences in the number of wells with significant groundwater-level trends over time, depending on whether the historical time series are assumed to be independent, have short-term persistence, or have long-term persistence. Mean annual groundwater levels have significant lag-one-year autocorrelation at 26.0% of wells in the East region, 65.4% of wells in the Central region, and 100% of wells in the West Central region. Annual precipitation across the glacial aquifer system, on the other hand, has significant autocorrelation at only 5.5% of stations, about the percentage expected due to chance.

Long-term energy capture and the effects of optimizing wind turbine operating strategies

NASA Technical Reports Server (NTRS)

Miller, A. H.; Formica, W. J.

1982-01-01

Methods of increasing energy capture without affecting the turbine design were investigated. The emphasis was on optimizing the wind turbine operating strategy. The operating strategy embodies the startup and shutdown algorithm as well as the algorithm for determining when to yaw (rotate) the axis of the turbine more directly into the wind. Using data collected at a number of sites, the time-dependent simulation of a MOD-2 wind turbine using various, site-dependent operating strategies provided evidence that site-specific fine tuning can produce significant increases in long-term energy capture as well as reduce the number of start-stop cycles and yawing maneuvers, which may result in reduced fatigue and subsequent maintenance.

Behavioral responses of wolves to roads: scale-dependent ambivalence

PubMed Central

Nelson, Lindsey; Wabakken, Petter; Sand, Håkan; Liberg, Olof

2014-01-01

Throughout their recent recovery in several industrialized countries, large carnivores have had to cope with a changed landscape dominated by human infrastructure. Population growth depends on the ability of individuals to adapt to these changes by making use of new habitat features and at the same time to avoid increased risks of mortality associated with human infrastructure. We analyzed the summer movements of 19 GPS-collared resident wolves (Canis lupus L.) from 14 territories in Scandinavia in relation to roads. We used resource and step selection functions, including >12000 field-checked GPS-positions and 315 kill sites. Wolves displayed ambivalent responses to roads depending on the spatial scale, road type, time of day, behavioral state, and reproductive status. At the site scale (approximately 0.1 km2), they selected for roads when traveling, nearly doubling their travel speed. Breeding wolves moved the fastest. At the patch scale (10 km2), house density rather than road density was a significant negative predictor of wolf patch selection. At the home range scale (approximately 1000 km2), breeding wolves increased gravel road use with increasing road availability, although at a lower rate than expected. Wolves have adapted to use roads for ease of travel, but at the same time developed a cryptic behavior to avoid human encounters. This behavioral plasticity may have been important in allowing the successful recovery of wolf populations in industrialized countries. However, we emphasize the role of roads as a potential cause of increased human-caused mortality. PMID:25419085

Behavioral responses of wolves to roads: scale-dependent ambivalence.

PubMed

Zimmermann, Barbara; Nelson, Lindsey; Wabakken, Petter; Sand, Håkan; Liberg, Olof

2014-11-01

Throughout their recent recovery in several industrialized countries, large carnivores have had to cope with a changed landscape dominated by human infrastructure. Population growth depends on the ability of individuals to adapt to these changes by making use of new habitat features and at the same time to avoid increased risks of mortality associated with human infrastructure. We analyzed the summer movements of 19 GPS-collared resident wolves ( Canis lupus L.) from 14 territories in Scandinavia in relation to roads. We used resource and step selection functions, including >12000 field-checked GPS-positions and 315 kill sites. Wolves displayed ambivalent responses to roads depending on the spatial scale, road type, time of day, behavioral state, and reproductive status. At the site scale (approximately 0.1 km 2 ), they selected for roads when traveling, nearly doubling their travel speed. Breeding wolves moved the fastest. At the patch scale (10 km 2 ), house density rather than road density was a significant negative predictor of wolf patch selection. At the home range scale (approximately 1000 km 2 ), breeding wolves increased gravel road use with increasing road availability, although at a lower rate than expected. Wolves have adapted to use roads for ease of travel, but at the same time developed a cryptic behavior to avoid human encounters. This behavioral plasticity may have been important in allowing the successful recovery of wolf populations in industrialized countries. However, we emphasize the role of roads as a potential cause of increased human-caused mortality.

Interval Management with Spacing to Parallel Dependent Runways (IMSPIDR) Experiment and Results

NASA Technical Reports Server (NTRS)

Baxley, Brian T.; Swieringa, Kurt A.; Capron, William R.

2012-01-01

An area in aviation operations that may offer an increase in efficiency is the use of continuous descent arrivals (CDA), especially during dependent parallel runway operations. However, variations in aircraft descent angle and speed can cause inaccuracies in estimated time of arrival calculations, requiring an increase in the size of the buffer between aircraft. This in turn reduces airport throughput and limits the use of CDAs during high-density operations, particularly to dependent parallel runways. The Interval Management with Spacing to Parallel Dependent Runways (IMSPiDR) concept uses a trajectory-based spacing tool onboard the aircraft to achieve by the runway an air traffic control assigned spacing interval behind the previous aircraft. This paper describes the first ever experiment and results of this concept at NASA Langley. Pilots flew CDAs to the Dallas Fort-Worth airport using airspeed calculations from the spacing tool to achieve either a Required Time of Arrival (RTA) or Interval Management (IM) spacing interval at the runway threshold. Results indicate flight crews were able to land aircraft on the runway with a mean of 2 seconds and less than 4 seconds standard deviation of the air traffic control assigned time, even in the presence of forecast wind error and large time delay. Statistically significant differences in delivery precision and number of speed changes as a function of stream position were observed, however, there was no trend to the difference and the error did not increase during the operation. Two areas the flight crew indicated as not acceptable included the additional number of speed changes required during the wind shear event, and issuing an IM clearance via data link while at low altitude. A number of refinements and future spacing algorithm capabilities were also identified.

Elevation of Hippocampal Neurogenesis Induces a Temporally Graded Pattern of Forgetting of Contextual Fear Memories.

PubMed

Gao, Aijing; Xia, Frances; Guskjolen, Axel J; Ramsaran, Adam I; Santoro, Adam; Josselyn, Sheena A; Frankland, Paul W

2018-03-28

Throughout life neurons are continuously generated in the subgranular zone of the hippocampus. The subsequent integration of newly generated neurons alters patterns of dentate gyrus input and output connectivity, potentially rendering memories already stored in those circuits harder to access. Consistent with this prediction, we previously showed that increasing hippocampal neurogenesis after training induces forgetting of hippocampus-dependent memories, including contextual fear memory. However, the brain regions supporting contextual fear memories change with time, and this time-dependent memory reorganization might regulate the sensitivity of contextual fear memories to fluctuations in hippocampal neurogenesis. By virally expressing the inhibitory designer receptor exclusively activated by designer drugs, hM4Di, we first confirmed that chemogenetic inhibition of dorsal hippocampal neurons impairs retrieval of recent (day-old) but not remote (month-old) contextual fear memories in male mice. We then contrasted the effects of increasing hippocampal neurogenesis at recent versus remote time points after contextual fear conditioning in male and female mice. Increasing hippocampal neurogenesis immediately following training reduced conditioned freezing when mice were replaced in the context 1 month later. In contrast, when hippocampal neurogenesis was increased time points remote to training, conditioned freezing levels were unaltered when mice were subsequently tested. These temporally graded forgetting effects were observed using both environmental and genetic interventions to increase hippocampal neurogenesis. Our experiments identify memory age as a boundary condition for neurogenesis-mediated forgetting and suggest that, as contextual fear memories mature, they become less sensitive to changes in hippocampal neurogenesis levels because they no longer depend on the hippocampus for their expression. SIGNIFICANCE STATEMENT New neurons are generated in the hippocampus throughout life. As they integrate into the hippocampus, they remodel neural circuitry, potentially making information stored in those circuits harder to access. Consistent with this, increasing hippocampal neurogenesis after learning induces forgetting of the learnt information. The current study in mice asks whether these forgetting effects depend on the age of the memory. We found that post-training increases in hippocampal neurogenesis only impacted recently acquired, and not remotely acquired, hippocampal memories. These experiments identify memory age as a boundary condition for neurogenesis-mediated forgetting, and suggest remote memories are less sensitive to changes in hippocampal neurogenesis levels because they no longer depend critically on the hippocampus for their expression. Copyright © 2018 the authors 0270-6474/18/383190-09$15.00/0.

The effect of polar caps on obliquity

NASA Technical Reports Server (NTRS)

Lindner, B. L.

1993-01-01

Rubincam has shown that the Martian obliquity is dependent on the seasonal polar caps. In particular, Rubincam analytically derived this dependence and showed that the change in obliquity is directly proportional to the seasonal polar cap mass. Rubincam concludes that seasonal friction does not appear to have changed Mars' climate significantly. Using a computer model for the evolution of the Martian atmosphere, Haberle et al. have made a convincing case for the possibility of huge polar caps, about 10 times the mass of the current polar caps, that exist for a significant fraction of the planet's history. Since Rubincam showed that the effect of seasonal friction on obliquity is directly proportional to polar cap mass, a scenario with a ten-fold increase in polar cap mass over a significant fraction of the planet's history would result in a secular increase in Mars' obliquity of perhaps 10 degrees. Hence, the Rubincam conclusion of an insignificant contribution to Mars' climate by seasonal friction may be incorrect. Furthermore, if seasonal friction is an important consideration in the obliquity of Mars, this would significantly alter the predictions of past obliquity.

Strengthening of synthetic quartz-rich sediments during time-dependent compaction due to pressure solution-precipitation compaction creep

NASA Astrophysics Data System (ADS)

Noda, H.; Okazaki, K.; Katayama, I.

2013-12-01

During diagenesis, incohesive sediments are compacted and gain strength against shear deformation for a geologically long time scale. The evolution of shear strength as well as the change in the mechanical and hydraulic characteristics under shear deformation is of significant importance in considering deformation at shallow part of the subduction zones and in accretionary prisms. Sediments after induration due to time-dependent diagenesis process probably deform with increases in porosity and permeability much more significantly than normally compacted incohesive sediments. An active fault in a shallow incohesive medium may favor thermal pressurization of pore fluid when slid rapidly, while the lack of time-dependent healing effect may cause stable (e.g., rate-strengthening) frictional property there. On the other hand, indurated sediments may deform with significant post-failure weakening, and thus exhibit localization of deformation or unstable behavior. In order to investigate how the time-dependent compaction and induration affect the mechanical and hydraulic characteristics of sediments under deformation, we have conducted a series of compaction experiments under hydrothermal conditions (at temperatures from R.T. to 500 °C, 200 MPa confining pressure, 100 MPa pore water pressure, and for various time), and following triaxial deformation experiments for the compacted samples, with monitoring permeability and storage capacity with pore pressure oscillation method [Fischer and Paterson, 1992]. Previous work [e.g., Niemeijer et at., 2003] reported that under the adopted conditions, quartz aggregate deforms by pressure solution-precipitation creep. The initial synthetic sediments have been prepared by depositing commercially available crushed quartzite the grain size of which is about 6 μm on average. 4 cm long samples have been extracted from the middle of 10 cm long deposited columns. The experiments have been performed with a gas-medium apparatus in Hiroshima University. As the compaction time and temperature increases, compressional strain increases and the synthetic sediments gain shear strength, flow stress during triaxial deformation tests. An uncooked sample yielded immediately on application of differential stress, and showed strengthening during triaxial deformation test with σ1-σ3 about 150 MPa at 0.1 compressional strain. On the other hand, a sample compacted at 500 °C for 5 hours (about 0.1 of isotropic compressional strain) deformed mainly elastically up to about 100 MPa differential stress. At 0.02 compressional strain σ1-σ3 reached 200 MPa which is the experimental limitation due to compressional strength of porous alumina spacers. In the presentation, we will focus on the relation between mechanical behavior under shear and the compressional strain during preceding compaction experiments.

Genetic effects and correlations between production and fertility traits and their dependency on the lactation-stage in Holstein Friesians

PubMed Central

2012-01-01

Background This study focused on the dynamics of genome-wide effects on five milk production and eight fertility traits as well as genetic correlations between the traits. For 2,405 Holstein Friesian bulls, estimated breeding values (EBVs) were used. The production traits were additionally assessed in 10-day intervals over the first 60 lactation days, as this stage is physiologically the most crucial time in milk production. Results SNPs significantly affecting the EBVs of the production traits could be separated into three groups according to the development of the size of allele effects over time: 1) increasing effects for all traits; 2) decreasing effects for all traits; and 3) increasing effects for all traits except fat yield. Most of the significant markers were found within 22 haplotypes spanning on average 135,338 bp. The DGAT1 region showed high density of significant markers, and thus, haplotype blocks. Further functional candidate genes are proposed for haplotype blocks of significant SNPs (KLHL8, SICLEC12, AGPAT6 and NID1). Negative genetic correlations were found between yield and fertility traits, whilst content traits showed positive correlations with some fertility traits. Genetic correlations became stronger with progressing lactation. When correlations were estimated within genotype classes, correlations were on average 0.1 units weaker between production and fertility traits when the yield increasing allele was present in the genotype. Conclusions This study provides insight into the expression of genetic effects during early lactation and suggests possible biological explanations for the presented time-dependent effects. Even though only three markers were found with effects on fertility, the direction of genetic correlations within genotype classes between production and fertility traits suggests that alleles increasing the milk production do not affect fertility in a more negative way compared to the decreasing allele. PMID:23244492

Sense of place in outdoor-pursuits trip groups

Treesearch

Sharon L. Todd; Anderson B. Young; Lynn S. Anderson; Timothy S. O' Connell; Mary Breunig

2009-01-01

Studies have revealed that sense of community and group cohesion increase significantly over time in outdoor-pursuits trip groups. This study sought to understand similar development of sense of place. Do people simultaneously become more attached to or dependent on the natural environment as they grow closer to each other? Results from a study of college students...

Effects of Copper on Hemocyte Apoptosis, ROS Production, and Gene Expression in White Shrimp Litopenaeus vannamei.

PubMed

Guo, Hui; Li, Kexu; Wang, Wei; Wang, Chenggui; Shen, Yuchun

2017-10-01

Copper, a common chemical contaminant in aquatic environment, is known to be toxic to aquatic life at high concentrations. In the present study, we evaluated the apoptotic cell ratio and ROS production in hemocytes of the white shrimp Litopenaeus vannamei exposed to 1 or 5 mg L -1 Cu for 0, 3, 6, 12, 24, and 48 h. The expression changes of antioxidant biomarker genes, i.e., copper-zinc superoxide dismutase (Cu-Zn SOD) and catalase (CAT), apoptosis-related genes, i.e., caspase-3 and inhibitor of apoptosis protein (IAP), and a specific biomarker gene of heavy metal pollution, i.e., metallothionein (MT), were also determined in hemocytes. Significant increases in ROS production were observed in both treatment groups at each time points. The apoptotic cell ratios were significantly increased at 6-48 h among shrimp exposed to 1 mg L -1 Cu and at each time points in 5 mg L -1 Cu group. These results indicated that Cu would induce oxidative stress and apoptosis in the hemocyte of L. vannamei. Quantitative real-time PCR analysis revealed that the relative expression levels of Cu-Zn SOD, CAT, caspase-3, IAP, and MT were upregulated in a dose-dependent and time-dependent manner, suggesting the involvement of these genes in stress response against Cu exposure.

Time of Day Does Not Modulate Improvements in Motor Performance following a Repetitive Ballistic Motor Training Task

PubMed Central

Sale, Martin V.; Ridding, Michael C.; Nordstrom, Michael A.

2013-01-01

Repetitive performance of a task can result in learning. The neural mechanisms underpinning such use-dependent plasticity are influenced by several neuromodulators. Variations in neuromodulator levels may contribute to the variability in performance outcomes following training. Circulating levels of the neuromodulator cortisol change throughout the day. High cortisol levels inhibit neuroplasticity induced with a transcranial magnetic stimulation (TMS) paradigm that has similarities to use-dependent plasticity. The present study investigated whether performance changes following a motor training task are modulated by time of day and/or changes in endogenous cortisol levels. Motor training involving 30 minutes of repeated maximum left thumb abduction was undertaken by twenty-two participants twice, once in the morning (8 AM) and once in the evening (8 PM) on separate occasions. Saliva was assayed for cortisol concentration. Motor performance, quantified by measuring maximum left thumb abduction acceleration, significantly increased by 28% following training. Neuroplastic changes in corticomotor excitability of abductor pollicis brevis, quantified with TMS, increased significantly by 23% following training. Training-related motor performance improvements and neuroplasticity were unaffected by time of day and salivary cortisol concentration. Although similar neural elements and processes contribute to motor learning, training-induced neuroplasticity, and TMS-induced neuroplasticity, our findings suggest that the influence of time of day and cortisol differs for these three interventions. PMID:23577271

Modeling of thermal lensing in a [1 1 1]-cut Nd:YAG rod with temperature-dependent parameters and different pumping profiles

NASA Astrophysics Data System (ADS)

Bričkus, D.; Dement'ev, A. S.

2017-05-01

Temperature dependences of the thermo-optical coefficients of YAG crystals are often neglected when thermal lensing in laser rods is investigated, though their influence is very significant. It is especially significant for transversally non-uniform thermal loading. An analytical solution of the heat transfer equation with only the radial heat flow is found in the integral form, which is very convenient for numerical simulations. Uniform, top-hat, parabolic, Gaussian, super-Gaussian and annular heat source distributions are used in the calculations. The generalization of the thermally-induced refractive index change for long enough [1 1 1]-cut YAG rods to the case of temperature-dependent YAG parameters is developed and applied to the calculation of the corresponding optical path differences. Different definitions of the optical power of the aberrated thermal lens (TL) are discussed in detail. It is shown that for each of the heat source distributions, the temperature dependences of the YAG parameters significantly increase (1.5-1.8 times) the paraxial optical power of the induced TL.

Plasma cannabinoid concentrations during dronabinol pharmacotherapy for cannabis dependence.

PubMed

Milman, Garry; Bergamaschi, Mateus M; Lee, Dayong; Mendu, Damodara R; Barnes, Allan J; Vandrey, Ryan; Huestis, Marilyn A

2014-04-01

Recently, high-dose oral synthetic delta-9-tetrahydrocannabinol (THC) was shown to alleviate cannabis withdrawal symptoms. The present data describe cannabinoid pharmacokinetics in chronic, daily cannabis smokers who received high-dose oral THC pharmacotherapy and later a smoked cannabis challenge. Eleven daily cannabis smokers received 0, 30, 60, or 120 mg/d THC for four 5-day medication sessions, each separated by 9 days of ad libitum cannabis smoking. On the fifth day, participants were challenged with smoking one 5.9% THC cigarette. Plasma collected on the first and fifth days was quantified by two-dimensional gas chromatography mass spectrometer for THC, 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH). Linear ranges (ng/mL) were 0.5-100 for THC, 1-50 for 11-OH-THC, and 0.5-200 for THCCOOH. During placebo dosing, THC, 11-OH-THC, and THCCOOH concentrations consistently decreased, whereas all cannabinoids increased dose dependently during active dronabinol administration. THC increase over time was not significant after any dose, 11-OH-THC increased significantly during the 60- and 120-mg/d doses, and THCCOOH increased significantly only during the 120-mg/d dose. THC, 11-OH-THC, and THCCOOH concentrations peaked within 0.25 hours after cannabis smoking, except after 120 mg/d THC when THCCOOH peaked 0.5 hours before smoking. The significant withdrawal effects noted during placebo dronabinol administration were supported by significant plasma THC and 11-OH-THC concentration decreases. During active dronabinol dosing, significant dose-dependent increases in THC and 11-OH-THC concentrations support withdrawal symptom suppression. THC concentrations after cannabis smoking were only distinguishable from oral THC doses for 1 hour, too short a period to feasibly identify cannabis relapse. THCCOOH/THC ratios were higher 14 hours after overnight oral dronabinol abstinence but cannot distinguish oral THC dosing from the smoked cannabis intake.

Plasma Cannabinoid Concentrations during Dronabinol Pharmacotherapy for Cannabis Dependence

PubMed Central

Milman, Garry; Bergamaschi, Mateus M.; Lee, Dayong; Mendu, Damodara R.; Barnes, Allan J.; Vandrey, Ryan; Huestis, Marilyn A.

2013-01-01

Background Recently, high-dose oral synthetic delta-9-tetrahydrocannabinol (THC) was shown to alleviate cannabis withdrawal symptoms. The present data describe cannabinoid pharmacokinetics in chronic daily cannabis smokers who received high-dose oral THC pharmacotherapy and later, a smoked cannabis challenge. Methods 11 daily cannabis smokers received 0, 30, 60, or 120 mg/day THC for four 5-day medication sessions, each separated by 9-days of ad-libitum cannabis smoking. On the 5th day, participants were challenged with smoking one 5.9% THC cigarette. Plasma collected on the 1st and 5th days was quantified by GC-GC-MS for THC, 11-hydroxy-THC (11-OH-THC), and 11-nor-9-carboxy-THC (THCCOOH). Linear ranges (ng/mL) were 0.5–100 for THC, 1–50 11-OH-THC, and 0.5–200 THCCOOH. Results During placebo dosing, THC, 11-OH-THC and THCCOOH concentrations consistently decreased, while all cannabinoids increased dose-dependently during active dronabinol administration. THC increase over time was not significant after any dose, 11-OH-THC increased significantly during 60 and 120 mg/day doses, and THCCOOH increased significantly only during the 120 mg/day dose. THC and 11-OH-THC, and THCCOOH concentrations peaked within 0.25 h after cannabis smoking, except after 120 mg/day THC when THCCOOH peaked 0.5 h before smoking. Conclusions The significant withdrawal effects noted during placebo dronabinol administration were supported by significant plasma THC and 11-OH-THC concentration decreases. During active dronabinol dosing, significant dose-dependent increases in THC and 11-OH-THC concentrations support withdrawal symptom suppression. THC concentrations after cannabis smoking were only distinguishable from oral THC doses for 1 h, too short a period to feasibly identify cannabis relapse. THCCOOH/THC ratios were higher 14 h after overnight oral dronabinol abstinence, but cannot distinguish oral THC dosing from smoked cannabis intake. PMID:24067260

Skeletal muscle tensile strain dependence: hyperviscoelastic nonlinearity

PubMed Central

Wheatley, Benjamin B; Morrow, Duane A; Odegard, Gregory M; Kaufman, Kenton R; Donahue, Tammy L Haut

2015-01-01

Introduction Computational modeling of skeletal muscle requires characterization at the tissue level. While most skeletal muscle studies focus on hyperelasticity, the goal of this study was to examine and model the nonlinear behavior of both time-independent and time-dependent properties of skeletal muscle as a function of strain. Materials and Methods Nine tibialis anterior muscles from New Zealand White rabbits were subject to five consecutive stress relaxation cycles of roughly 3% strain. Individual relaxation steps were fit with a three-term linear Prony series. Prony series coefficients and relaxation ratio were assessed for strain dependence using a general linear statistical model. A fully nonlinear constitutive model was employed to capture the strain dependence of both the viscoelastic and instantaneous components. Results Instantaneous modulus (p<0.0005) and mid-range relaxation (p<0.0005) increased significantly with strain level, while relaxation at longer time periods decreased with strain (p<0.0005). Time constants and overall relaxation ratio did not change with strain level (p>0.1). Additionally, the fully nonlinear hyperviscoelastic constitutive model provided an excellent fit to experimental data, while other models which included linear components failed to capture muscle function as accurately. Conclusions Material properties of skeletal muscle are strain-dependent at the tissue level. This strain dependence can be included in computational models of skeletal muscle performance with a fully nonlinear hyperviscoelastic model. PMID:26409235

Impacts of parameterized orographic drag on the Northern Hemisphere winter circulation

PubMed Central

Bechtold, Peter; Beljaars, Anton; Bozzo, Alessio; Pithan, Felix; Shepherd, Theodore G.; Zadra, Ayrton

2016-01-01

Abstract A recent intercomparison exercise proposed by the Working Group for Numerical Experimentation (WGNE) revealed that the parameterized, or unresolved, surface stress in weather forecast models is highly model‐dependent, especially over orography. Models of comparable resolution differ over land by as much as 20% in zonal mean total subgrid surface stress (τtot). The way τtot is partitioned between the different parameterizations is also model‐dependent. In this study, we simulated in a particular model an increase in τtot comparable with the spread found in the WGNE intercomparison. This increase was simulated in two ways, namely by increasing independently the contributions to τtot of the turbulent orographic form drag scheme (TOFD) and of the orographic low‐level blocking scheme (BLOCK). Increasing the parameterized orographic drag leads to significant changes in surface pressure, zonal wind and temperature in the Northern Hemisphere during winter both in 10 day weather forecasts and in seasonal integrations. However, the magnitude of these changes in circulation strongly depends on which scheme is modified. In 10 day forecasts, stronger changes are found when the TOFD stress is increased, while on seasonal time scales the effects are of comparable magnitude, although different in detail. At these time scales, the BLOCK scheme affects the lower stratosphere winds through changes in the resolved planetary waves which are associated with surface impacts, while the TOFD effects are mostly limited to the lower troposphere. The partitioning of τtot between the two schemes appears to play an important role at all time scales. PMID:27668040

Impacts of parameterized orographic drag on the Northern Hemisphere winter circulation

NASA Astrophysics Data System (ADS)

Sandu, Irina; Bechtold, Peter; Beljaars, Anton; Bozzo, Alessio; Pithan, Felix; Shepherd, Theodore G.; Zadra, Ayrton

2016-03-01

A recent intercomparison exercise proposed by the Working Group for Numerical Experimentation (WGNE) revealed that the parameterized, or unresolved, surface stress in weather forecast models is highly model-dependent, especially over orography. Models of comparable resolution differ over land by as much as 20% in zonal mean total subgrid surface stress (τtot). The way τtot is partitioned between the different parameterizations is also model-dependent. In this study, we simulated in a particular model an increase in τtot comparable with the spread found in the WGNE intercomparison. This increase was simulated in two ways, namely by increasing independently the contributions to τtot of the turbulent orographic form drag scheme (TOFD) and of the orographic low-level blocking scheme (BLOCK). Increasing the parameterized orographic drag leads to significant changes in surface pressure, zonal wind and temperature in the Northern Hemisphere during winter both in 10 day weather forecasts and in seasonal integrations. However, the magnitude of these changes in circulation strongly depends on which scheme is modified. In 10 day forecasts, stronger changes are found when the TOFD stress is increased, while on seasonal time scales the effects are of comparable magnitude, although different in detail. At these time scales, the BLOCK scheme affects the lower stratosphere winds through changes in the resolved planetary waves which are associated with surface impacts, while the TOFD effects are mostly limited to the lower troposphere. The partitioning of τtot between the two schemes appears to play an important role at all time scales.

Increased gray matter density in the parietal cortex of mathematicians: a voxel-based morphometry study.

PubMed

Aydin, K; Ucar, A; Oguz, K K; Okur, O O; Agayev, A; Unal, Z; Yilmaz, S; Ozturk, C

2007-01-01

The training to acquire or practicing to perform a skill, which may lead to structural changes in the brain, is called experience-dependent structural plasticity. The main purpose of this cross-sectional study was to investigate the presence of experience-dependent structural plasticity in mathematicians' brains, which may develop after long-term practice of mathematic thinking. Twenty-six volunteer mathematicians, who have been working as academicians, were enrolled in the study. We applied an optimized method of voxel-based morphometry in the mathematicians and the age- and sex-matched control subjects. We assessed the gray and white matter density differences in mathematicians and the control subjects. Moreover, the correlation between the cortical density and the time spent as an academician was investigated. We found that cortical gray matter density in the left inferior frontal and bilateral inferior parietal lobules of the mathematicians were significantly increased compared with the control subjects. Furthermore, increase in gray matter density in the right inferior parietal lobule of the mathematicians was strongly correlated with the time spent as an academician (r = 0.84; P < .01). Left-inferior frontal and bilateral parietal regions are involved in arithmetic processing. Inferior parietal regions are also involved in high-level mathematic thinking, which requires visuospatial imagery, such as mental creation and manipulation of 3D objects. The voxel-based morphometric analysis of mathematicians' brains revealed increased gray matter density in the cortical regions related to mathematic thinking. The correlation between cortical density increase and the time spent as an academician suggests experience-dependent structural plasticity in mathematicians' brains.

Arsenic induced progesterone production in a caspase-3-dependent manner and changed redox status in preovulatory granulosa cells.

PubMed

Yuan, Xiao-Hua; Lu, Cai-Ling; Yao, Nan; An, Li-Sha; Yang, Bai-Qing; Zhang, Chuan-Ling; Ma, Xu

2012-01-01

Arsenic contamination is a principal environmental health threat throughout the world. However, little is known about the effect of arsenic on steroidogenesis in granulosa cells (GCs). We found that the treatment of preovulatory GCs with arsenite stimulated progesterone production. A significant increase in serum level of progesterone was observed in female Sprague-Dawley rats following arsenite treatment at a dose of 10 mg/L/rat/day for 7 days. Further experiments demonstrated that arsenite treatment did not change the level of intracellular cyclic AMP (cAMP) or phosphorylated ERK1/2 in preovulatory GCs; however, progesterone production was significantly decreased when cAMP-dependent protein kinase (PKA) or ERK1/2 pathway was inhibited. This implied that the effect of arsenite on progesterone production may require cAMP/PKA and ERK1/2 signaling but not depend on them. Furthermore, we found that arsenite decreased intracellular reactive oxygen species (ROS) but increased the antioxidant glutathione (GSH) levels and mitochondrial membrane potential (ΔΨm) in parallel to the changes in progesterone production. Progesterone antagonist blocked the arsenic-stimulated increase of GSH levels. Arsenite treatment induced caspase-3 activation, although no apoptosis was observed. Inhibition of caspase-3 activity significantly decreased progesterone production stimulated by arsenite or follicle-stimulating hormone (FSH). GSH depletion with buthionine sulfoximine led to cell apoptosis in response to arsenite treatment. Collectively, this study demonstrated for the first time that arsenite stimulates progesterone production through cleaved/active caspase-3-dependent pathway, and the increase of GSH level promoted by progesterone production may protect GCs against apoptosis and maintain the steroidogenesis of GCs in response to arsenite treatment. Copyright © 2011 Wiley Periodicals, Inc.

Optimization of temperature and time for drying and carbonization to increase calorific value of coconut shell using Taguchi method

NASA Astrophysics Data System (ADS)

Musabbikhah, Saptoadi, H.; Subarmono, Wibisono, M. A.

2016-03-01

Fossil fuel still dominates the needs of energy in Indonesia for the past few years. The increasing scarcity of oil and gas from non-renewable materials results in an energy crisis. This condition turns to be a serious problem for society which demands immediate solution. One effort which can be taken to overcome this problem is the utilization and processing of biomass as renewable energy by means of carbonization. Thus, it can be used as qualified raw material for production of briquette. In this research, coconut shell is used as carbonized waste. The research aims at improving the quality of coconut shell as the material for making briquettes as cheap and eco-friendly renewable energy. At the end, it is expected to decrease dependence on oil and gas. The research variables are drying temperature and time, carbonization time and temperature. The dependent variable is calorific value of the coconut shell. The method used in this research is Taguchi Method. The result of the research shows thus variables, have a significant contribution on the increase of coconut shell's calorific value. It is proven that the higher thus variables are higher calorific value. Before carbonization, the average calorific value of coconut shell reaches 4,667 call/g, and a significant increase is notable after the carbonization. The optimization is parameter setting of A2B3C3D3, which means that the drying temperature is 105 °C, the drying time is 24 hours, the carbonization temperature is 650 °C and carbonization time is 120 minutes. The average calorific value is approximately 7,744 cal/g. Therefore, the increase of the coconut shell's calorific value after the carbonization is 3,077 cal/g or approximately 60 %. The charcoal of carbonized coconut shell has met the requirement of SNI, thus it can be used as raw material in making briquette which can eventually be used as cheap and environmental friendly fuel.

Heavy quark energy loss in nuclear medium

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

Zhang, Benr-Wei; Wang, Enke; Wang, Xin-Nian

2003-09-16

Multiple scattering, modified fragmentation functions and radiative energy loss of a heavy quark propagating in a nuclear medium are investigated in perturbative QCD. Because of the quark mass dependence of the gluon formation time, the medium size dependence of heavy quark energy loss is found to change from a linear to a quadratic form when the initial energy and momentum scale are increased relative to the quark mass. The radiative energy loss is also significantly suppressed relative to a light quark due to the suppression of collinear gluon emission by a heavy quark.

The effect of locally delivered recombinant human bone morphogenetic protein-2 with hydroxyapatite/tri-calcium phosphate on the biomechanical properties of bone in diabetes-related osteoporosis.

PubMed

Liporace, Frank A; Breitbart, Eric A; Yoon, Richard S; Doyle, Erin; Paglia, David N; Lin, Sheldon

2015-06-01

Recombinant human bone morphogenetic protein-2 (rhBMP-2) is particularly effective in improving osteogenesis in patients with diminished bone healing capabilities, such as individuals with type 1 diabetes mellitus (T1DM) who have impaired bone healing capabilities and increased risk of developing osteoporosis. This study measured the effects of rhBMP-2 treatment on osteogenesis by observing the dose-dependent effect of localized delivery of rhBMP-2 on biomechanical parameters of bone using a hydroxyapatite/tri-calcium phosphate (HA/TCP) carrier in a T1DM-related osteoporosis animal model. Two different doses of rhBMP-2 (LD low dose, HD high dose) with a HA/TCP carrier were injected into the femoral intramedullary canal of rats with T1DM-related osteoporosis. Two more diabetic rat groups were injected with saline alone and with HA/TCP carrier alone. Radiographs and micro-computed tomography were utilized for qualitative assessment of bone mineral density (BMD). Biomechanical testing occurred at 4- and 8-week time points; parameters tested included torque to failure, torsional rigidity, shear stress, and shear modulus. At the 4-week time point, the LD and HD groups both exhibited significantly higher BMD than controls; at the 8-week time point, the HD group exhibited significantly higher BMD than controls. Biomechanical testing revealed dose-dependent, higher trends in all parameters tested at the 4- and 8-week time points, with minimal significant differences. Groups treated with rhBMP-2 demonstrated improved bone mineral density at both 4 and 8 weeks compared to control saline groups, in addition to strong trends towards improvement of intrinsic and extrinsic biomechanical properties when compared to control groups. Data revealed trends toward dose-dependent increases in peak torque, torsional rigidity, shear stress, and shear modulus 4 weeks after rhBMP-2 treatment. Not applicable.

Effects of high temperature frying of Spinach leaves in sunflower oil on carotenoids, chlorophylls and tocopherol composition

NASA Astrophysics Data System (ADS)

Zeb, Alam; Nisar, Parveen

2017-03-01

Spinach is one of the highly consumed vegetable, with significant nutritional and beneficial properties. This study revealed for the first time, the effects of high temperature frying on the carotenoids, chlorophylls and tocopherol contents of spinach leaves. Spinach leaves were thermally processed in the sunflower oil for 15, 30, 45 and 60 min at 250 °C. HPLC-DAD results revealed a total of eight carotenoids, four chlorophylls and α-tocopherol in the spinach leaves. Lutein, neoxanthin, violaxanthin and β-carotene-5,6-epoxide were the major carotenoids, while chlorophyll a and b' were present in higher amounts. Frying of spinach leaves increased significantly the amount of α-tocopherol, β-carotene-5,6-epoxide, luteoxanthin, lutein and its Z-isomers and chlorophyll b' isomer. There was a dose dependent decrease in the amounts of neoxanthin, violaxanthin, chlorophyll b, b' and chlorophyll a with increase of frying time. The increase of frying time increased the total phenolic contents in spinach leaves and fried sunflower oil samples. Chemical characteristics such as peroxide values, free fatty acids, conjugated dienes, conjugated trienes and radical scavenging activity were significantly affected by frying, while spinach leaves increased the stability of the frying oil. This study can be used to improve the quality of fried vegetable leaves or their products at high temperature frying in food industries for increasing consumer acceptability.

Time-Dependent Alterations of MMPs, TIMPs and Tendon Structure in Human Achilles Tendons after Acute Rupture

PubMed Central

Minkwitz, Susann; Schmock, Aysha; Kurtoglu, Alper; Tsitsilonis, Serafeim; Manegold, Sebastian; Klatte-Schulz, Franka

2017-01-01

A balance between matrix metalloproteinases (MMPs) and their inhibitors (TIMPs) is required to maintain tendon homeostasis. Variation in this balance over time might impact on the success of tendon healing. This study aimed to analyze structural changes and the expression profile of MMPs and TIMPs in human Achilles tendons at different time-points after rupture. Biopsies from 37 patients with acute Achilles tendon rupture were taken at surgery and grouped according to time after rupture: early (2–4 days), middle (5–6 days), and late (≥7 days), and intact Achilles tendons served as control. The histological score increased from the early to the late time-point after rupture, indicating the progression towards a more degenerative status. In comparison to intact tendons, qRT-PCR analysis revealed a significantly increased expression of MMP-1, -2, -13, TIMP-1, COL1A1, and COL3A1 in ruptured tendons, whereas TIMP-3 decreased. Comparing the changes over time post rupture, the expression of MMP-9, -13, and COL1A1 significantly increased, whereas MMP-3 and -10 expression decreased. TIMP expression was not significantly altered over time. MMP staining by immunohistochemistry was positive in the ruptured tendons exemplarily analyzed from early and late time-points. The study demonstrates a pivotal contribution of all investigated MMPs and TIMP-1, but a minor role of TIMP-2, -3, and -4, in the early human tendon healing process. PMID:29053586

Sex- and dose-dependency in the pharmacokinetics and pharmacodynamics of (+)-methamphetamine and its metabolite (+)-amphetamine in rats

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

Milesi-Halle, Alessandra; Hendrickson, Howard P.; Laurenzana, Elizabeth M.

These studies investigated how (+)-methamphetamine (METH) dose and rat sex affect the pharmacological response to METH in Sprague-Dawley rats. The first set of experiments determined the pharmacokinetics of METH and its pharmacologically active metabolite (+)-amphetamine (AMP) in male and female Sprague-Dawley rats after 1.0 and 3.0 mg/kg METH doses. The results showed significant sex-dependent changes in METH pharmacokinetics, and females formed significantly lower amounts of AMP. While the area under the serum concentration-time curve in males increased proportionately with the METH dose, the females showed a disproportional increase. The sex differences in systemic clearance, renal clearance, volume of distribution, andmore » percentage of unchanged METH eliminated in the urine suggested dose-dependent pharmacokinetics in female rats. The second set of studies sought to determine the behavioral implications of these pharmacokinetic differences by quantifying locomotor activity in male and female rats after saline, 1.0, and 3.0 mg/kg METH. The results showed sex- and dose-dependent differences in METH-induced locomotion, including profound differences in the temporal profile of effects at higher dose. These findings show that the pharmacokinetic and metabolic profile of METH (slower METH clearance and lower AMP metabolite formation) plays a significant role in the differential pharmacological response to METH in male and female rats.« less

[Trigger factor dependent refolding of bacterial luciferases in Escherichia coli cells: kinetics, efficiency and effect of the bichaperone system, DnaKJE-ClpB].

PubMed

Mel'kina, O E; Gorianin, I I; Manukhov, I V; Zavil'gel'skiĭ, G B

2013-01-01

Here were determined the basic parameters of the Tigger Factor (TF) -dependent refolding of thermal inactivated bacterial luciferases. The TF-dependent refolding is less efficient and requires more time than DnaKJE-dependent refolding. The increase in the intracellular concentration of TF leads to an apparent decrease in the level of the thermal inactivated bacterial luciferase refolding. For thermolabile luciferases, the level of TF-dependent refolding is significantly higher, than for thermostable luciferases: 30-40%--for the thermolabile Aliivibrio fischeri and Photobacterium leiognathi luciferases, and 10 and 0.5% for the thermostable Vibrio harveyi and Photorhabdus luminescens luciferases, respectively. The negative effect of the ClpB protein on the TF-dependent refolding was shown: in Escherichia coli clpB::kan TF-dependent refolding is more efficient than in the E. coli clpB+.

Formal methods for dependable real-time systems

NASA Technical Reports Server (NTRS)

Rushby, John

1993-01-01

The motivation for using formal methods to specify and reason about real time properties is outlined and approaches that were proposed and used are sketched. The formal verifications of clock synchronization algorithms are concluded as showing that mechanically supported reasoning about complex real time behavior is feasible. However, there was significant increase in the effectiveness of verification systems since those verifications were performed, at it is to be expected that verifications of comparable difficulty will become fairly routine. The current challenge lies in developing perspicuous and economical approaches to the formalization and specification of real time properties.

PM2.5-induced alterations of cell cycle associated gene expression in lung cancer cells and rat lung tissues.

PubMed

Zhao, Hui; Yang, Biao; Xu, Jia; Chen, Dong-Mei; Xiao, Chun-Ling

2017-06-01

The aim of the current study was to investigate the expression of cell cycle-associated genes induced by fine particulate matter (PM 2.5 ) in lung cancer cell line and tissues. The pulmonary lymph node metastasis cells (H292) were treated with PM 2.5 in vitro. Wistar rats were used to perform an in vivo study. Rats were randomly assigned to experiment and control groups and those in the experiment group were exposed to PM 2.5 once every 15 d, while those in the control group were exposed to normal saline. The cell cycle-associated genes expression was analyzed by real-time PCR. Trachea and lung tissues of rats were processed for scanning electron microscopic (SEM) examinations. Exposure of H292 cells to PM 2.5 dramatically increased the expressions of p53 and cyclin-dependent kinase 2 (CDK2) after 24h of exposure (p<0.01) and markedly increased the expressions of the cell division cycle 2 (Cdc2) and cyclin B after 48h of exposure (p<0.01), while those genes expressions were significantly reduced after 72h of exposure, at which time the expression of p21 was predominant (p<0.01). In vivo studies further demonstrated these results. The results of SEM suggested that both of the trachea and lung tissues were damaged and the degree of damage was time-dependent. In conclusion, PM 2.5 can induce significantly alterations of p53 and CDK2 in the early phase, Cdc2 and cyclin B in mid-term and p21 in long-term exposure. The degree of PM 2.5 -induced damage to the trachea and lung tissue was time-dependent. Copyright © 2017. Published by Elsevier B.V.

Extracellular purines' action on glomerular albumin permeability in isolated rat glomeruli: insights into the pathogenesis of albuminuria.

PubMed

Kasztan, Małgorzata; Piwkowska, Agnieszka; Kreft, Ewelina; Rogacka, Dorota; Audzeyenka, Irena; Szczepanska-Konkel, Mirosława; Jankowski, Maciej

2016-07-01

Purinoceptors (adrengeric receptors and P2 receptors) are expressed on the cellular components of the glomerular filtration barrier, and their activation may affect glomerular permeability to albumin, which may ultimately lead to albuminuria, a well-established risk factor for the progression of chronic kidney disease and development of cardiovascular diseases. We investigated the mechanisms underlying the in vitro and in vivo purinergic actions on glomerular filter permeability to albumin by measuring convectional albumin permeability (Palb) in a single isolated rat glomerulus based on the video microscopy method. Primary cultured rat podocytes were used for the analysis of Palb, cGMP accumulation, PKG-Iα dimerization, and immunofluorescence. In vitro, natural nucleotides (ATP, ADP, UTP, and UDP) and nonmetabolized ATP analogs (2-meSATP and ATP-γ-S) increased Palb in a time- and concentration-dependent manner. The effects were dependent on P2 receptor activation, nitric oxide synthase, and cytoplasmic guanylate cyclase. ATP analogs significantly increased Palb, cGMP accumulation, and subcortical actin reorganization in a PKG-dependent but nondimer-mediated route in cultured podocytes. In vivo, 2-meSATP and ATP-γ-S increased Palb but did not significantly affect urinary albumin excretion. Both agonists enhanced the clathrin-mediated endocytosis of albumin in podocytes. A product of adenine nucleotides hydrolysis, adenosine, increased the permeability of the glomerular barrier via adrenergic receptors in a dependent and independent manner. Our results suggest that the extracellular nucleotides that stimulate an increase of glomerular Palb involve nitric oxide synthase and cytoplasmic guanylate cyclase with actin reorganization in podocytes. Copyright © 2016 the American Physiological Society.

Modeling impurity production and transport during ELM transients in a DIII-D lower single null configuration.

NASA Astrophysics Data System (ADS)

Hogan, J.; Fenstermacher, M.; Groth, M.; West, P.; Coster, D.; Thomas, P.

2003-10-01

Better understanding of carbon production and eventual pathways is an important need for ITER. ELM events can provide a significant carbon source, and small scale experiments predict significant dependence of C production rates on incident deuterium flux and surface temperature, quantities which change significantly during an ELM event. Thus, development of better quantitative models has been hampered by lack of sufficient time resolution during ELMs. Recent progress on DIII-D has significantly improved the spectroscopic resolution [1, 2]. Measured CIII evolution during low- and high-density DIII-D LSN ELMy H-modes (type I and type I-III, respectively) has been compared with modeling using the solps5.0/Eirene99 coupled edge code, and the CASTEM- 2000 3-D, time dependent thermal analysis code. The latter provides time-resolved absolute surface temperature distributions for the cases described in [2]. Comparison with observations using the Roth et al annealing model for chemical sputtering finds qualitative agreement. However, the transition in ELM type/frequency as density increases is the most important factor, and this is an input to the calculation given the present state of first principles ELM models. [1] M Fenstermacher et al EPS2003 [2] M Groth et al J Nucl Mater 2003

Chiral tunneling modulated by a time-periodic potential on the surface states of a topological insulator

PubMed Central

Li, Yuan; Jalil, Mansoor B. A.; Tan, S. G.; Zhao, W.; Bai, R.; Zhou, G. H.

2014-01-01

Time-periodic perturbation can be used to modify the transport properties of the surface states of topological insulators, specifically their chiral tunneling property. Using the scattering matrix method, we study the tunneling transmission of the surface states of a topological insulator under the influence of a time-dependent potential and finite gate bias voltage. It is found that perfect transmission is obtained for electrons which are injected normally into the time-periodic potential region in the absence of any bias voltage. However, this signature of Klein tunneling is destroyed when a bias voltage is applied, with the transmission probability of normally incident electrons decreasing with increasing gate bias voltage. Likewise, the overall conductance of the system decreases significantly when a gate bias voltage is applied. The characteristic left-handed helicity of the transmitted spin polarization is also broken by the finite gate bias voltage. In addition, the time-dependent potential modifies the large-angle transmission profile, which exhibits an oscillatory or resonance-like behavior. Finally, time-dependent transport modes (with oscillating potential in the THz frequency) can result in enhanced overall conductance, irrespective of the presence or absence of the gate bias voltage. PMID:24713634

Selective Rac1 inhibition protects renal tubular epithelial cells from oxalate-induced NADPH oxidase-mediated oxidative cell injury

PubMed Central

Thamilselvan, Vijayalakshmi; Menon, Mani

2013-01-01

Oxalate-induced oxidative cell injury is one of the major mechanisms implicated in calcium oxalate nucleation, aggregation and growth of kidney stones. We previously demonstrated that oxalate-induced NADPH oxidase-derived free radicals play a significant role in renal injury. Since NADPH oxidase activation requires several regulatory proteins, the primary goal of this study was to characterize the role of Rac GTPase in oxalate-induced NADPH oxidase-mediated oxidative injury in renal epithelial cells. Our results show that oxalate significantly increased membrane translocation of Rac1 and NADPH oxidase activity of renal epithelial cells in a time-dependent manner. We found that NSC23766, a selective inhibitor of Rac1, blocked oxalate-induced membrane translocation of Rac1 and NADPH oxidase activity. In the absence of Rac1 inhibitor, oxalate exposure significantly increased hydrogen peroxide formation and LDH release in renal epithelial cells. In contrast, Rac1 inhibitor pretreatment, significantly decreased oxalate-induced hydrogen peroxide production and LDH release. Furthermore, PKC α and δ inhibitor, oxalate exposure did not increase Rac1 protein translocation, suggesting that PKC resides upstream from Rac1 in the pathway that regulates NADPH oxidase. In conclusion, our data demonstrate for the first time that Rac1-dependent activation of NADPH oxidase might be a crucial mechanism responsible for oxalate-induced oxidative renal cell injury. These findings suggest that Rac1 signaling plays a key role in oxalate-induced renal injury, and may serve as a potential therapeutic target to prevent calcium oxalate crystal deposition in stone formers and reduce recurrence. PMID:21814770

Estimation of Coda Wave Attenuation in Northern Morocco

NASA Astrophysics Data System (ADS)

Boulanouar, Abderrahim; Moudnib, Lahcen El; Padhy, Simanchal; Harnafi, Mimoun; Villaseñor, Antonio; Gallart, Josep; Pazos, Antonio; Rahmouni, Abdelaali; Boukalouch, Mohamed; Sebbani, Jamal

2018-03-01

We studied the attenuation of coda waves and its frequency and lapse-time dependence in northern Morocco. We analysed coda waves of 66 earthquakes recorded in this region during 2008 for four lapse time windows of length 30, 40, 50, and 60 s, and at five frequency bands with central frequency in the range of 0.75-12 Hz. We determined the frequency dependent Q c relation for the horizontal (NS and EW) and vertical (Z) component seismograms. We analyzed three-component broadband seismograms of 66 local earthquakes for determining coda-Q based on the single back-scattering model. The Q c values show strong frequency dependence in 1.5-12 Hz that is related to high degree of heterogeneity of the medium. The lapse time dependence of Q c shows that Q 0 ( Q c at 1 Hz) significantly increases with lapse time that is related to the depth dependence of attenuation and hence of the level of heterogeneity of the medium. The average frequency-dependent Q c( f) values are Qc = (143.75 ± 1.09)f^{(0.864 ± 0.006)}, Qc = (149.12 ± 1.08)f^{(0.85 ± 0.005)} and Qc = (140.42 ± 1.81)f^{(0.902 ± 0.004)} for the vertical, north-south and east-west components of motion, respectively. The frequency-dependent Q c(f) relations are useful for evaluating source parameters (Singh et al. 2001), which are the key inputs for seismic hazard assessment of the region.

The impact of the 2007-2009 recession on workers' health coverage.

PubMed

Fronstin, Paul

2011-04-01

IMPACT OF THE RECESSION: The 2007-2009 recession has taken its toll on the percentage of the population with employment-based health coverage. While, since 2000, there has been a slow erosion in the percentage of individuals under age 65 with employment-based health coverage, 2009 was the first year in which the percentage fell below 60 percent, and marked the largest one-year decline in coverage. FEWER WORKERS WITH COVERAGE: The percentage of workers with coverage through their own job fell from 53.2 percent in 2008 to 52 percent in 2009, a 2.4 percent decline in the likelihood that a worker has coverage through his or her own job. The percentage of workers with coverage as a dependent fell from 17 percent in 2008 to 16.3 percent in 2009, a 4.5 percent drop in the likelihood that a worker has coverage as a dependent. These declines occurred as the unemployment rate increased from an average of 5.8 percent in 2008 to 9.3 percent in 2009 (and reached a high of 10.1 percent during 2009). FIRM SIZE/INDUSTRY: The decline in the percentage of workers with coverage from their own job affected workers in private-sector firms of all sizes. Among public-sector workers, the decline from 73.4 percent to 73 percent was not statistically significant. Workers in all private-sector industries experienced a statistically significant decline in coverage between 2008 and 2009. HOURS WORKED: Full-time workers experienced a decline in coverage that was statistically significant while part-time workers did not. Among full-time workers, those employed full year experienced a statistically significant decline in coverage from their own job. Those employed full time but for only part of the year did not experience a statistically significant change in coverage. Among part-time workers, those employed full year experienced a statistically significant increase in the likelihood of having coverage in their own name, as did part-time workers employed for only part of the year. ANNUAL EARNINGS: The decline in the percentage of workers with coverage through their own job was limited to workers with lower annual earnings. Statistically significant declines were not found among any group of workers with annual earnings of at least $40,000. Workers with a high school education or less experienced a statistically significant decline in the likelihood of having coverage. Neither workers with a college degree nor those with a graduate degree experienced a statistically significant decline in coverage through their own job. Workers of all races experienced statistically significant declines in coverage between 2008 and 2009. Both men and women experienced a statistically significant decline in the percentage with health coverage through their own job. IMPACT OF STRUCTURAL CHANGES TO THE WORK FORCE: The movement of workers from the manufacturing industry to the service sector continued between 2008 and 2009. The percentage of workers employed on a full-time basis decreased while the percentage working part time increased. While there was an overall decline in the percentage of full-time workers, that decline was limited to workers employed full year. The percentage of workers employed on a full-time, part-year basis increased between 2008 and 2009. The distribution of workers by annual earnings shifted from middle-income workers to lower-income workers between 2008 and 2009.

Physiological relevance of LL-37 induced bladder inflammation and mast cells.

PubMed

Oottamasathien, Siam; Jia, Wanjian; Roundy, Lindsi McCoard; Zhang, Jianxing; Wang, Li; Ye, Xiangyang; Hill, A Cameron; Savage, Justin; Lee, Wong Yong; Hannon, Ann Marie; Milner, Sylvia; Prestwich, Glenn D

2013-10-01

We established the physiological relevance of LL-37 induced bladder inflammation. We hypothesized that 1) human urinary LL-37 is increased in pediatric patients with spina bifida, 2) LL-37 induced inflammation occurs in our mouse model via urothelial binding and is dose dependent and 3) LL-37 induced inflammation involves mast cells. To test our first hypothesis, we obtained urine samples from 56 pediatric patients with spina bifida and 22 normal patients. LL-37 was measured by enzyme-linked immunosorbent assay. Our second hypothesis was tested in C57Bl/6 mice challenged with 7 LL-37 concentrations intravesically for 1 hour. At 24 hours tissues were examined histologically and myeloperoxidase assay was done to quantitate inflammation. In separate experiments fluorescent LL-37 was instilled and tissues were obtained immediately (time = 0) and at 24 hours (time = 24). To test our final hypothesis, we performed immunohistochemistry for mast cell tryptase and evaluated 5 high power fields per bladder to determine the mean number of mast cells per mm(2). Urinary LL-37 was 89-fold higher in patients with spina bifida. Mouse LL-37 dose escalation experiments revealed increased inflammation at higher LL-37 concentrations. Fluorescent LL-37 demonstrated global urothelial binding at time = 0 but was not visible at time = 24. Immunohistochemistry for tryptase revealed mast cell infiltration in all tissue layers. At higher concentrations the LL-37 challenge led to significantly greater mast cell infiltration. Urinary LL-37 was significantly increased in pediatric patients with spina bifida. To our knowledge we report for the first time that LL-37 can elicit profound, dose dependent bladder inflammation involving the urothelium. Finally, inflammation propagation involves mast cells. Copyright © 2013 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Physiological Relevance of LL-37 Induced Bladder Inflammation and Mast Cells

PubMed Central

Roundy, Lindsi McCoard; Zhang, Jianxing; Wang, Li; Ye, Xiangyang; Hill, A. Cameron; Savage, Justin; Lee, Wong Yong; Hannon, Ann Marie; Milner, Sylvia; Prestwich, Glenn D.

2014-01-01

Purpose We established the physiological relevance of LL-37 induced bladder inflammation. We hypothesized that 1) human urinary LL-37 is increased in pediatric patients with spina bifida, 2) LL-37 induced inflammation occurs in our mouse model via urothelial binding and is dose dependent and 3) LL-37 induced inflammation involves mast cells. Materials and Methods To test our first hypothesis, we obtained urine samples from 56 pediatric patients with spina bifida and 22 normal patients. LL-37 was measured by enzyme-linked immunosorbent assay. Our second hypothesis was tested in C57Bl/6 mice challenged with 7 LL-37 concentrations intravesically for 1 hour. At 24 hours tissues were examined histologically and myeloperoxidase assay was done to quantitate inflammation. In separate experiments fluorescent LL-37 was instilled and tissues were obtained immediately (time = 0) and at 24 hours (time = 24). To test our final hypothesis, we performed immunohistochemistry for mast cell tryptase and evaluated 5 high power fields per bladder to determine the mean number of mast cells per mm2. Results Urinary LL-37 was 89-fold higher in patients with spina bifida. Mouse LL-37 dose escalation experiments revealed increased inflammation at higher LL-37 concentrations. Fluorescent LL-37 demonstrated global urothelial binding at time = 0 but was not visible at time = 24. Immunohistochemistry for tryptase revealed mast cell infiltration in all tissue layers. At higher concentrations the LL-37 challenge led to significantly greater mast cell infiltration. Conclusions Urinary LL-37 was significantly increased in pediatric patients with spina bifida. To our knowledge we report for the first time that LL-37 can elicit profound, dose dependent bladder inflammation involving the urothelium. Finally, inflammation propagation involves mast cells. PMID:23313203

Smad, PI3K/Akt, and Wnt-dependent signaling pathways are involved in BMP-4-induced ESC self-renewal.

PubMed

Lee, Min Young; Lim, Hyun Woo; Lee, Sang Hun; Han, Ho Jae

2009-08-01

It is known that bone morphogenetic protein 4 (BMP-4) has a diverse effect on ESCs. However, its precise mechanism in mouse ESCs is not fully understood. We evaluated the effect of BMP-4 on ESC proliferation and its related signal cascades in this study. BMP-4 significantly increased the level of [(3)H]-thymidine incorporation in time- (> or =8 hours) and dose- (> or =10 ng/ml) dependent manners. Additionally, BMP-4 increased cyclin D1 and decreased p27(kip1) expression values in a time-dependent manner. The increases in BMP-4-induced [(3)H]-thymidine incorporation and cyclin D1 expression were inhibited by the BMP-4 receptor antagonist noggin. BMP-4 increased Wnt1 expression. Wnt1 expression was attenuated by Smad4 small interfering RNA (siRNA), and BMP-4-induced cyclin D1 expression was inhibited by Smad4 and Wnt1 siRNAs. BMP-4 also activated beta-catenin, which was blocked by Smad4 and Wnt1 siRNAs. In addition, BMP-4 induced Akt phosphorylation. BMP-4-induced beta-catenin activation and cyclin D1 expression were attenuated by phosphatidyl inositol 3-kinase (PI3K) siRNA and Akt inhibitor. Additionally, downregulation of Smad4, Wnt1, and PI3K expression by siRNA decreased the levels of pluripotency marker mRNAs of ESCs, including Oct4, Sox2, and FoxD3. Our results suggested that BMP-4-induced [(3)H]-thymidine incorporation was significantly attenuated by Smad4, Wnt1, and PI3K knockdown. In conclusion, BMP-4 contributed to the maintenance of cell proliferation and the pluripotent state by Smad, PI3K/Akt, and Wnt1/beta-catenin in mouse ESCs.

Stress dependence of permeability of intact and fractured shale cores.

NASA Astrophysics Data System (ADS)

van Noort, Reinier; Yarushina, Viktoriya

2016-04-01

Whether a shale acts as a caprock, source rock, or reservoir, understanding fluid flow through shale is of major importance for understanding fluid flow in geological systems. Because of the low permeability of shale, flow is thought to be largely confined to fractures and similar features. In fracking operations, fractures are induced specifically to allow for hydrocarbon exploration. We have constructed an experimental setup to measure core permeabilities, using constant flow or a transient pulse. In this setup, we have measured the permeability of intact and fractured shale core samples, using either water or supercritical CO2 as the transporting fluid. Our measurements show decreasing permeability with increasing confining pressure, mainly due to time-dependent creep. Furthermore, our measurements show that for a simple splitting fracture, time-dependent creep will also eliminate any significant effect of this fracture on permeability. This effect of confinement on fracture permeability can have important implications regarding the effects of fracturing on shale permeability, and hence for operations depending on that.

Controls on the time-scales of mantle mixing

NASA Astrophysics Data System (ADS)

Crameri, F.; Cagney, N.; Lithgow-Bertelloni, C. R.; Whitehead, J. A.

2016-12-01

Understanding the processes controlling the mantle mixing is crucial to our geochemical interpretation of basalts, and our understanding of the mantle heterogeneity. We investigate the influence of various mantle conditions on the time scales of mixing using numerical simulations. We examine the effects of Rayleigh number (Ra), depth- and temperature-dependent rheology and internal heating, as well as the role of Prandtl number (Pr), in order to assess how mixing in the early magma ocean and experiments (where Pr tends to be 103) differs from that in the present-day mantle (Pr 1025). We use the "coarse grained density" method to quantify the mixing state and determine the mixing time. The mixing time is found to be strongly affected by the Rayleigh number, scaling with Ra-0.65, in agreement with previous studies. In contrast, when Ra is held constant, the temperature-dependent rheology has a weak effect. The depth-dependent rheology also has a negligible effect on the mixing time, as material that is initially viscous is transported to the low viscosity near the surface where it undergoes fast mixing. The internal heating rate does not affect the mixing time, provided that it does not increase the fluid temperature above that of the boundary condition. In this case, the decrease in mixing time is shown to be a result of an increase in the effective Ra. Finally, we show that for moderate and low Pr, the mixing time increases with Pr0.45. However, for all Pr greater than about 100, the mixing time is the same at the infinite-Pr value. Our results have several implications for the mantle: (1) Ra is the controlling factor on mantle mixing. (2) The non-Newtonian rheology of the mantle has a very weak effect on mantle mixing and can be neglected. (3) A dramatic increase in viscosity in the deep mantle has been proposed at a cause of regions of unmixed `primitive' mantle. Our results show that this hypothesis is unlikely, as depth dependent rheology does not increase in the mixing time. (4) Pr does not have a significant effect, for Pr > 100. This implies that the same processes govern mixing in the magma ocean and the solid mantle. (5) Using an appropriate estimate for the Rayleigh of the early magma ocean, we show that the degree of mixing achieved throughout the history of the solid mantle is less than that achieved in a single year in the magma ocean.

Effects of storage time and temperature on pH, specific gravity, and crystal formation in urine samples from dogs and cats.

PubMed

Albasan, Hasan; Lulich, Jody P; Osborne, Carl A; Lekcharoensuk, Chalermpol; Ulrich, Lisa K; Carpenter, Kathleen A

2003-01-15

To determine effects of storage temperature and time on pH and specific gravity of and number and size of crystals in urine samples from dogs and cats. Randomized complete block design. 31 dogs and 8 cats. Aliquots of each urine sample were analyzed within 60 minutes of collection or after storage at room or refrigeration temperatures (20 vs 6 degrees C [68 vs 43 degrees F]) for 6 or 24 hours. Crystals formed in samples from 11 of 39 (28%) animals. Calcium oxalate (CaOx) crystals formed in vitro in samples from 1 cat and 8 dogs. Magnesium ammonium phosphate (MAP) crystals formed in vitro in samples from 2 dogs. Compared with aliquots stored at room temperature, refrigeration increased the number and size of crystals that formed in vitro; however, the increase in number and size of MAP crystals in stored urine samples was not significant. Increased storage time and decreased storage temperature were associated with a significant increase in number of CaOx crystals formed. Greater numbers of crystals formed in urine aliquots stored for 24 hours than in aliquots stored for 6 hours. Storage time and temperature did not have a significant effect on pH or specific gravity. Urine samples should be analyzed within 60 minutes of collection to minimize temperature- and time-dependent effects on in vitro crystal formation. Presence of crystals observed in stored samples should be validated by reevaluation of fresh urine.

Anomalous and non-Gaussian diffusion in Hertzian spheres

NASA Astrophysics Data System (ADS)

Ouyang, Wenze; Sun, Bin; Sun, Zhiwei; Xu, Shenghua

2018-09-01

By means of molecular dynamics simulations, we study the non-Gaussian diffusion in the fluid of Hertzian spheres. The time dependent non-Gaussian parameter, as an indicator of the dynamic heterogeneity, is increased with the increasing of temperature. When the temperature is high enough, the dynamic heterogeneity becomes very significant, and it seems counterintuitive that the maximum of non-Gaussian parameter and the position of its peak decrease monotonically with the increasing of density. By fitting the curves of self intermediate scattering function, we find that the character relaxation time τα is surprisingly not coupled with the time τmax where the non-Gaussian parameter reaches to a maximum. The intriguing features of non-Gaussian diffusion at high enough temperatures can be associated with the weakly correlated mean-field behavior of Hertzian spheres. Especially the time τmax is nearly inversely proportional to the density at extremely high temperatures.

Different methods to analyze stepped wedge trial designs revealed different aspects of intervention effects.

PubMed

Twisk, J W R; Hoogendijk, E O; Zwijsen, S A; de Boer, M R

2016-04-01

Within epidemiology, a stepped wedge trial design (i.e., a one-way crossover trial in which several arms start the intervention at different time points) is increasingly popular as an alternative to a classical cluster randomized controlled trial. Despite this increasing popularity, there is a huge variation in the methods used to analyze data from a stepped wedge trial design. Four linear mixed models were used to analyze data from a stepped wedge trial design on two example data sets. The four methods were chosen because they have been (frequently) used in practice. Method 1 compares all the intervention measurements with the control measurements. Method 2 treats the intervention variable as a time-independent categorical variable comparing the different arms with each other. In method 3, the intervention variable is a time-dependent categorical variable comparing groups with different number of intervention measurements, whereas in method 4, the changes in the outcome variable between subsequent measurements are analyzed. Regarding the results in the first example data set, methods 1 and 3 showed a strong positive intervention effect, which disappeared after adjusting for time. Method 2 showed an inverse intervention effect, whereas method 4 did not show a significant effect at all. In the second example data set, the results were the opposite. Both methods 2 and 4 showed significant intervention effects, whereas the other two methods did not. For method 4, the intervention effect attenuated after adjustment for time. Different methods to analyze data from a stepped wedge trial design reveal different aspects of a possible intervention effect. The choice of a method partly depends on the type of the intervention and the possible time-dependent effect of the intervention. Furthermore, it is advised to combine the results of the different methods to obtain an interpretable overall result. Copyright © 2016 Elsevier Inc. All rights reserved.

A Factorial Data Rate and Dwell Time Experiment in the National Transonic Facility

NASA Technical Reports Server (NTRS)

DeLoach, R.

2000-01-01

This report is an introductory tutorial on the application of formal experiment design methods to wind tunnel testing, for the benefit of aeronautical engineers with little formal experiment design training. It also describes the results of a Study to determine whether increases in the sample rate and dwell time of the National Transonic Facility data system Would result in significant changes in force and moment data. Increases in sample rate from 10 samples per second to 50 samples per second were examined, as were changes in dwell time from one second per data point to two seconds. These changes were examined for a representative aircraft model in a range of tunnel operating conditions defined by angles of attack from 0 deg to 3.8 degrees, total pressure from 15.0 psi to 24.1 psi, and Mach numbers from 0.52 to 0.82. No statistically significant effect was associated with the change in sample rate. The change in dwell time from one second to two seconds affected axial force measurements, and to a lesser degree normal force measurements. This dwell effect comprises a "rectification error" caused by incomplete cancellation of the positive and negative elements of certain low frequency dynamic components that are not rejected by the one-Hz low-pass filters of the data system. These low frequency effects may be due to tunnel circuit phenomena and other sources. The magnitude of the dwell effect depends on dynamic pressure, with angle of attack and Mach number influencing the strength of this dependence. An analysis is presented which suggests that the magnitude of the rectification error depends on the ratio of measurement dwell time to the period of the low-frequency dynamics, as well as the amplitude of the dynamics The essential conclusion of this analysis is that extending the dwell time (or, equivalently, replicating short-dwell data points) reduces the rectification error.

Na+/Ca2+ exchange in cardiac myocytes. Effect of ouabain on voltage dependence.

PubMed

Lee, H C; Clusin, W T

1987-02-01

Sarcolemmal sodium/calcium exchange activity was examined in individual chick embryonic myocardial cell aggregates that were loaded with quin 2. The baseline [Ca2+]i was 68 +/- 4 nM (n = 29). Abrupt superfusion with sodium-free lithium solution produced a fourfold increase in steady-state [Ca2+]i to 290 +/- 19 nM, which was reversible upon sodium restitution. Other methods of increasing [Ca2+]i such as KCl-depolarization or caffeine produced a dose-dependent increase in quin 2 fluorescence, accompanied by sustained contracture. The [Ca2+]i increase in zero sodium was linear, and its half-time (t1/2) of 15.1 +/- 0.1 s was similar to that of the sodium-free contracture (t1/2 = 14.4 +/- 0.5 s) under the same conditions. The sodium-dependent [Ca2+]i increase was not significantly greater when potassium served as the sodium substitute instead of lithium. This suggests that sodium/calcium exchange has little voltage dependence in this situation. However, in aggregates pretreated with ouabain (2.5 microM), the [Ca2+]i increase was almost threefold greater with potassium than with lithium (P less than 0.007). Ouabain therefore potentiated the effect of membrane potential on calcium influx. We propose that elevation of [Na2+]i is a prerequisite for voltage dependence of the sodium/calcium exchange under the conditions studied. Sodium loading will then drastically increase calcium influx during the action potential while inducing an outward membrane current that could accelerate repolarization.

Convection links biomass burning to increased tropical ozone: However, models will tend to overpredict O3

NASA Astrophysics Data System (ADS)

Chatfield, Robert B.; Delany, Anthony C.

1990-10-01

Biomass burning throughout the inhabited portions of the tropics generates precursors which lead to significant local atmospheric ozone pollution. Several simulations show how this smog could be only an easily observed, local manifestation of a much broader increase in tropospheric ozone. We illustrate basic processes with a one-dimensional time-dependent model that is closer to true meteorological motions than commonly used eddy diffusion models. Its application to a representative region of South America gives reasonable simulations of the local pollutants measured there. Three illustrative simulations indicate the importance of dilution, principally due to vertical transport, in increasing the efficiency of ozone production, possibly enough for high ozone to be apparent on a very large, intercontinental scale. In the first, cook-then-mix, simulation the nitrogen oxides and other burning-produced pollutants are confined to a persistently subsident fair weather boundary layer for several days, and the resultant ozone is found to have only a transient influence on the whole column of tropospheric ozone. In the second, mix-then-cook, simulation the effect of typical cumulonimbus convection, which vents an actively polluted boundary layer, is to make a persistent increase in the tropical ozone column. Such a broadly increased ozone column is observed over the the populated "continental" portion of the tropics. A third simulation averages all emission, transport, and deposition parameters, representing one column in a global tropospheric model that does not simulate individual weather events. This "oversmoothing" simulation produces 60% more ozone than observed or otherwise modeled. Qualitatively similar overprediction is suggested for all models which average significantly in time or space, as all need do. Clearly, simulating these O3 levels will depend sensitively on knowledge of the timing of emissions and transport.

Mitochondrial impairment increases FL-PINK1 levels by calcium-dependent gene expression☆

PubMed Central

Gómez-Sánchez, Rubén; Gegg, Matthew E.; Bravo-San Pedro, José M.; Niso-Santano, Mireia; Alvarez-Erviti, Lydia; Pizarro-Estrella, Elisa; Gutiérrez-Martín, Yolanda; Alvarez-Barrientos, Alberto; Fuentes, José M.; González-Polo, Rosa Ana; Schapira, Anthony H.V.

2014-01-01

Mutations of the PTEN-induced kinase 1 (PINK1) gene are a cause of autosomal recessive Parkinson's disease (PD). This gene encodes a mitochondrial serine/threonine kinase, which is partly localized to mitochondria, and has been shown to play a role in protecting neuronal cells from oxidative stress and cell death, perhaps related to its role in mitochondrial dynamics and mitophagy. In this study, we report that increased mitochondrial PINK1 levels observed in human neuroblastoma SH-SY5Y cells after carbonyl cyanide m-chlorophelyhydrazone (CCCP) treatment were due to de novo protein synthesis, and not just increased stabilization of full length PINK1 (FL-PINK1). PINK1 mRNA levels were significantly increased by 4-fold after 24 h. FL-PINK1 protein levels at this time point were significantly higher than vehicle-treated, or cells treated with CCCP for 3 h, despite mitochondrial content being decreased by 29%. We have also shown that CCCP dissipated the mitochondrial membrane potential (Δψm) and induced entry of extracellular calcium through L/N-type calcium channels. The calcium chelating agent BAPTA-AM impaired the CCCP-induced PINK1 mRNA and protein expression. Furthermore, CCCP treatment activated the transcription factor c-Fos in a calcium-dependent manner. These data indicate that PINK1 expression is significantly increased upon CCCP-induced mitophagy in a calcium-dependent manner. This increase in expression continues after peak Parkin mitochondrial translocation, suggesting a role for PINK1 in mitophagy that is downstream of ubiquitination of mitochondrial substrates. This sensitivity to intracellular calcium levels supports the hypothesis that PINK1 may also play a role in cellular calcium homeostasis and neuroprotection. PMID:24184327

Energy survey - What can R&D do by 1985. [fossil fuel utilization

NASA Technical Reports Server (NTRS)

Copps, S. L.

1975-01-01

Research and development in the field of energy is generally recognized as requiring long lead times before the results are felt. Near term relief from foreign oil dependence will be achieved by reducing energy consumption through conservation and by increasing domestic energy supply through expanded exploration and drilling for oil and natural gas, and by increased coal production. This paper describes the results of an informal survey performed by NASA within its own agency to determine if any research and development activities might be an exception to the general rule of long lead times and thus have significant impact by 1985 on oil and natural gas consumption.

Variability of the hemodynamic response as a function of age and frequency of epileptic discharge in children with epilepsy.

PubMed

Jacobs, Julia; Hawco, Colin; Kobayashi, Eliane; Boor, Rainer; LeVan, Pierre; Stephani, Ulrich; Siniatchkin, Michael; Gotman, Jean

2008-04-01

EEG-fMRI is a non-invasive tool to investigate epileptogenic networks in patients with epilepsy. Different patterns of BOLD responses have been observed in children as compared to adults. A high intra- and intersubject variability of the hemodynamic response function (HRF) to epileptic discharges has been observed in adults. The actual HRF to epileptic discharges in children and its dependence on age are unknown. We analyzed 64 EEG-fMRI event types in 37 children (3 months to 18 years), 92% showing a significant BOLD response. HRFs were calculated for each BOLD cluster using a Fourier basis set. After excluding HRFs with a low signal-to-noise ratio, 126 positive and 98 negative HRFs were analyzed. We evaluated age-dependent changes as well as the effect of increasing numbers of spikes. Peak time, amplitude and signal-to-noise ratio of the HRF and the t-statistic score of the cluster were used as dependent variables. We observed significantly longer peak times of the HRF in the youngest children (0 to 2 years), suggesting that the use of multiple HRFs might be important in this group. A different coupling between neuronal activity and metabolism or blood flow in young children may cause this phenomenon. Even if the t-value increased with frequent spikes, the amplitude of the HRF decreased significantly with spike frequency. This reflects a violation of the assumptions of the General Linear Model and therefore the use of alternative analysis techniques may be more appropriate with high spiking rates, a common situation in children.

Variability of the hemodynamic response as a function of age and frequency of epileptic discharge in children with epilepsy

PubMed Central

Jacobs, Julia; Hawco, Colin; Kobayashi, Eliane; Boor, Rainer; LeVan, Pierre; Stephani, Ulrich; Siniatchkin, Michael; Gotman, Jean

2013-01-01

EEG-fMRI is a non-invasive tool to investigate epileptogenic networks in patients with epilepsy. Different patterns of BOLD responses have been observed in children as compared to adults. A high intra- and intersubject variability of the hemodynamic response function (HRF) to epileptic discharges has been observed in adults. The actual HRF to epileptic discharges in children and its dependence on age are unknown. We analyzed 64 EEG-fMRI event types in 37 children (3 months to 18 years), 92% showing a significant BOLD response. HRFs were calculated for each BOLD cluster using a Fourier basis set. After excluding HRFs with a low signal-to-noise ratio, 126 positive and 98 negative HRFs were analyzed. We evaluated age-dependent changes as well as the effect of increasing numbers of spikes. Peak time, amplitude and signal-to-noise ratio of the HRF and the t-statistic score of the cluster were used as dependent variables. We observed significantly longer peak times of the HRF in the youngest children (0 to 2 years), suggesting that the use of multiple HRFs might be important in this group. A different coupling between neuronal activity and metabolism or blood flow in young children may cause this phenomenon. Even if the t-value increased with frequent spikes, the amplitude of the HRF decreased significantly with spike frequency. This reflects a violation of the assumptions of the General Linear Model and therefore the use of alternative analysis techniques may be more appropriate with high spiking rates, a common situation in children. PMID:18221891

Differential Changes in Expression of Stress- and Metabolic-Related Neuropeptides in the Rat Hypothalamus during Morphine Dependence and Withdrawal

PubMed Central

Núnez, Cristina; Zelei, Edina; Polyák, Ágnes; Milanés, M. Victoria

2013-01-01

Chronic morphine treatment and naloxone precipitated morphine withdrawal activates stress-related brain circuit and results in significant changes in food intake, body weight gain and energy metabolism. The present study aimed to reveal hypothalamic mechanisms underlying these effects. Adult male rats were made dependent on morphine by subcutaneous implantation of constant release drug pellets. Pair feeding revealed significantly smaller weight loss of morphine treated rats compared to placebo implanted animals whose food consumption was limited to that eaten by morphine implanted pairs. These results suggest reduced energy expenditure of morphine-treated animals. Chronic morphine exposure or pair feeding did not significantly affect hypothalamic expression of selected stress- and metabolic related neuropeptides - corticotropin-releasing hormone (CRH), urocortin 2 (UCN2) and proopiomelanocortin (POMC) compared to placebo implanted and pair fed animals. Naloxone precipitated morphine withdrawal resulted in a dramatic weight loss starting as early as 15–30 min after naloxone injection and increased adrenocorticotrophic hormone, prolactin and corticosterone plasma levels in morphine dependent rats. Using real-time quantitative PCR to monitor the time course of relative expression of neuropeptide mRNAs in the hypothalamus we found elevated CRH and UCN2 mRNA and dramatically reduced POMC expression. Neuropeptide Y (NPY) and arginine vasopressin (AVP) mRNA levels were transiently increased during opiate withdrawal. These data highlight that morphine withdrawal differentially affects expression of stress- and metabolic-related neuropeptides in the rat hypothalamus, while relative mRNA levels of these neuropeptides remain unchanged either in rats chronically treated with morphine or in their pair-fed controls. PMID:23805290

A prediction model for colon cancer surveillance data.

PubMed

Good, Norm M; Suresh, Krithika; Young, Graeme P; Lockett, Trevor J; Macrae, Finlay A; Taylor, Jeremy M G

2015-08-15

Dynamic prediction models make use of patient-specific longitudinal data to update individualized survival probability predictions based on current and past information. Colonoscopy (COL) and fecal occult blood test (FOBT) results were collected from two Australian surveillance studies on individuals characterized as high-risk based on a personal or family history of colorectal cancer. Motivated by a Poisson process, this paper proposes a generalized nonlinear model with a complementary log-log link as a dynamic prediction tool that produces individualized probabilities for the risk of developing advanced adenoma or colorectal cancer (AAC). This model allows predicted risk to depend on a patient's baseline characteristics and time-dependent covariates. Information on the dates and results of COLs and FOBTs were incorporated using time-dependent covariates that contributed to patient risk of AAC for a specified period following the test result. These covariates serve to update a person's risk as additional COL, and FOBT test information becomes available. Model selection was conducted systematically through the comparison of Akaike information criterion. Goodness-of-fit was assessed with the use of calibration plots to compare the predicted probability of event occurrence with the proportion of events observed. Abnormal COL results were found to significantly increase risk of AAC for 1 year following the test. Positive FOBTs were found to significantly increase the risk of AAC for 3 months following the result. The covariates that incorporated the updated test results were of greater significance and had a larger effect on risk than the baseline variables. Copyright © 2015 John Wiley & Sons, Ltd.

Effect of time, injury, age and ethanol on interpatient variability in valproic acid pharmacokinetics after traumatic brain injury.

PubMed

Anderson, Gail D; Temkin, Nancy R; Awan, Asaad B; Winn, H Richard; Winn, Richard H

2007-01-01

Traumatic brain injury (TBI) results in an increase in hepatic metabolism. The increased metabolism is in significant contrast to a large body of in vitro and in vivo data demonstrating that activation of the host-defence response downregulates hepatic metabolism. Theoretically, this occurs because of activation of the pro-inflammatory cytokines tumour necrosis factor-alpha, interferon-gamma, interleukin (IL)-1 and IL-6. As part of a large double-blind, placebo-controlled clinical trial evaluating the use of valproic acid for prophylaxis of post-traumatic seizures, we obtained extensive valproic acid concentration-time data. Valproic acid is a hepatically metabolised, low extraction-ratio drug. Therefore, unbound clearance (CL(u)) is equal to intrinsic or metabolic clearance. The objective of this study was to evaluate the time-dependent effects of TBI on the pharmacokinetics of total and unbound valproic acid with the goal of identifying patient factors that may predict changes in total clearance (CL) and CL(u). In addition, by determining the factors that influence the magnitude and time course of induction of hepatic metabolism and understanding their interaction with the host-defence mediators, we can further our insight into the mechanism(s) responsible for the changes in CL and CL(u). Valproic acid plasma concentration data were obtained from 158 TBI patients. Unbound valproic acid plasma concentrations were estimated using total valproic acid plasma and albumin concentrations following a Scatchard equation binding model previously developed in a subset of TBI patients. The effect of 13 patient factors on CL and CL(u) was evaluated initially in a univariate analysis. The significant factors were then included in a multiple linear regression analysis by use of step-wise selection and forward selection procedures. CL and CL(u) were significantly increased after TBI in a time-dependent manner. The average increase was >75% by weeks 2 and 3 post-injury. The magnitude of the induction of CL was increased with decreased albumin concentrations, in addition to the presence of ethanol on admission, increased severity of head injury, tube feeding and total parenteral nutrition (TPN). The magnitude of induction of CL(u) was increased by older age, presence of ethanol on admission, increased severity of head injury, tube feeding, TPN, and if the patient had a post-injury neurosurgical procedure. The time to normalisation of CL(u) was significantly longer in patients with head injury plus other injuries compared with those with head injury alone. As has been reported with other drugs, TBI results in a significant increase in the metabolism of valproic acid. The patient factors identified in this study that resulted in an increase in the magnitude and time course of the induction of CL(u) (ethanol, older age, presence of a neurosurgical procedure, severity of TBI and presence of multiple non-TBI injuries) have all been reported to cause a shift to the anti-inflammatory mediators IL-4 and IL-10. This suggests that the increase in hepatic metabolism after TBI may be due to the increased presence of anti-inflammatory mediators in contrast to the inhibition effect of the pro-inflammatory mediators in non-TBI inflammation and infection.

Hormetic effects of noncoplanar PCB exposed to human lung fibroblast cells (HELF) and possible role of oxidative stress.

PubMed

Hashmi, Muhammad Zaffar; Khan, Kiran Yasmin; Hu, Jinxing; Naveedullah; Su, Xiaomei; Abbas, Ghulam; Yu, Chunna; Shen, Chaofeng

2015-12-01

Hormesis, a biphasic dose-response phenomenon, which is characterized by stimulation of an end point at a low-dose and inhibition at a high-dose. In the present study we used human lungs fibroblast (HELF) cells as a test model to evaluate the role of oxidative stress (OS) in hormetic effects of non coplanar PCB 101. Results from 3-(4,5-dime-thylthiazol-2-yl)-2,5-diphenyltetrazo-lium bromide (MTT) assay indicated that PCB101 at lower concentrations (10(-5) to 10(-1) μg mL(-1) ) stimulated HELF cell proliferation and inhibited at high concentrations (1, 5, 10, and 20 μg mL(-1) ) in a dose- and time-dependent manner. Reactive oxygen species (ROS), malondialdehyde (MDA) and superoxide dismutase (SOD) (except 48 h) showed a significant increase at higher concentrations of PCB 101 than those at the lower concentrations with the passage of time. Antioxidant enzymes such as glutathione peroxidase (GSH-Px) exhibited decreasing trends in dose and time dependent manner. Lipid peroxidation assay resulted in a significant increase (P < 0.05) of MDA level in PCB 101-treated HELF cells compared with controls, suggesting that OS plays a key role in PCB 101-induced toxicity. Comet assay indicated a significant increase in genotoxicity at higher concentrations of PCB 101 exposure compared to lower concentrations. Overall, we found that HELF cell proliferation was higher at low ROS level and vice versa, which revealed activation of cell signaling-mediated hormetic mechanisms. The results suggested that PCB 101 has hormetic effects to HELF cells and these were associated with oxidative stress. © 2014 Wiley Periodicals, Inc.

Ultraviolet absorption spectra of shock-heated carbon dioxide and water between 900 and 3050 K

NASA Astrophysics Data System (ADS)

Schulz, C.; Koch, J. D.; Davidson, D. F.; Jeffries, J. B.; Hanson, R. K.

2002-03-01

Spectrally resolved UV absorption cross-sections between 190 and 320 nm were measured in shock-heated CO 2 between 880 and 3050 K and H 2O between 1230 and 2860 K. Absorption spectra were acquired with 10 μs time resolution using a unique kinetic spectrograph, thereby enabling comparisons with time-dependent chemical kinetic modeling of post-shock thermal decomposition and chemical reactions. Although room temperature CO 2 is transparent (σ<10 -22 cm2) at wavelengths longer than 200 nm, hot CO 2 has significant absorption (σ>10 -20 cm2) extending to wavelengths longer than 300 nm. The temperature dependence of CO 2 absorption strongly suggests sharply increased transition probabilities from excited vibrational levels.

Systematic pain assessment in nursing homes: a cluster-randomized trial using mixed-methods approach.

PubMed

Mamhidir, Anna-Greta; Sjölund, Britt-Marie; Fläckman, Birgitta; Wimo, Anders; Sköldunger, Anders; Engström, Maria

2017-02-28

Chronic pain affects nursing home residents' daily life. Pain assessment is central to adequate pain management. The overall aim was to investigate effects of a pain management intervention on nursing homes residents and to describe staffs' experiences of the intervention. A cluster-randomized trial and a mixed-methods approach. Randomized nursing home assignment to intervention or comparison group. The intervention group after theoretical and practical training sessions, performed systematic pain assessments using predominately observational scales with external and internal facilitators supporting the implementation. No measures were taken in the comparison group; pain management continued as before, but after the study corresponding training was provided. Resident data were collected baseline and at two follow-ups using validated scales and record reviews. Nurse group interviews were carried out twice. Primary outcome measures were wellbeing and proxy-measured pain. Secondary outcome measures were ADL-dependency and pain documentation. Using both non-parametric statistics on residential level and generalized estimating equation (GEE) models to take clustering effects into account, the results revealed non-significant interaction effects for the primary outcome measures, while for ADL-dependency using Katz-ADL there was a significant interaction effect. Comparison group (n = 66 residents) Katz-ADL values showed increased dependency over time, while the intervention group demonstrated no significant change over time (n = 98). In the intervention group, 13/44 residents showed decreased pain scores over the period, 14/44 had no pain score changes ≥ 30% in either direction measured with Doloplus-2. Furthermore, 17/44 residents showed increased pain scores ≥ 30% over time, indicating pain/risk for pain; 8 identified at the first assessment and 9 were new, i.e. developed pain over time. No significant changes in the use of drugs was found in any of the groups. Nursing pain related documentation was sparse. In general, nurses from the outset were positive regarding pain assessments. Persisting positive attitudes seemed strengthened by continued assessment experiences and perceptions of improved pain management. The implementation of a systematic work approach to pain issues in nursing homes indicates that an increased awareness, collaboration across and shared understanding among the team members of the pain assessment results can improve pain management and lead to decreased physical deterioration or the maintenance of physical and functional abilities among NH residents. However, pain (proxy-measured) and wellbeing level did not reveal any interaction effects between the groups over time. The study was registered in ISRCTN71142240 in September 2012, retrospectively registered.

Dynamic shear-stress-enhanced rates of nutrient consumption in gas-liquid semi-continuous-flow suspensions

NASA Astrophysics Data System (ADS)

Belfiore, Laurence A.; Volpato, Fabio Z.; Paulino, Alexandre T.; Belfiore, Carol J.

2011-12-01

The primary objective of this investigation is to establish guidelines for generating significant mammalian cell density in suspension bioreactors when stress-sensitive kinetics enhance the rate of nutrient consumption. Ultra-low-frequency dynamic modulations of the impeller (i.e., 35104 Hz) introduce time-dependent oscillatory shear into this transient analysis of cell proliferation under semi-continuous creeping flow conditions. Greater nutrient consumption is predicted when the amplitude A of modulated impeller rotation increases, and stress-kinetic contributions to nutrient consumption rates increase linearly at higher modulation frequency via an application of fluctuation-dissipation response. Interphase mass transfer is required to replace dissolved oxygen as it is consumed by aerobic nutrient consumption in the liquid phase. The theory and predictions described herein could be important at small length scales in the creeping flow regime where viscous shear is significant at the interface between the nutrient medium and isolated cells in suspension. Two-dimensional flow around spherically shaped mammalian cells, suspended in a Newtonian culture medium, is analyzed to calculate the surface-averaged magnitude of the velocity gradient tensor and modify homogeneous rates of nutrient consumption that are stimulated by viscous shear, via the formalism of stress-kinetic reciprocal relations that obey Curie's theorem in non-equilibrium thermodynamics. Time constants for stress-free free and stress-sensitive stress nutrient consumption are defined and quantified to identify the threshold (i.e., stress,threshold) below which the effect of stress cannot be neglected in accurate predictions of bioreactor performance. Parametric studies reveal that the threshold time constant for stress-sensitive nutrient consumption stress,threshold decreases when the time constant for stress-free nutrient consumption free is shorter. Hence, stress,threshold depends directly on free. In other words, the threshold rate of stress-sensitive nutrient consumption is higher when the stress-free rate of nutrient consumption increases. Modulated rotation of the impeller, superimposed on steady shear, increases stress,threshold when free is constant, and stress,threshold depends directly on the amplitude A of these angular velocity modulations.

Comparative Evaluation of Partial α2 -Adrenoceptor Agonist and Pure α2 -Adrenoceptor Antagonist on the Behavioural Symptoms of Withdrawal after Chronic Alcohol Administration in Mice.

PubMed

Arora, Shivani; Vohora, Divya

2016-08-01

As an addictive drug, alcohol produces withdrawal symptoms if discontinued abruptly after chronic use. Clonidine (CLN), a partial α2 -adrenergic agonist, and mirtazapine (MRT), an antagonist of α2 -adrenoceptor, both clinically aid alcohol withdrawal. Considering different mechanisms of action of the two drugs, this study was designed to see how far these two mechanistically different drugs differ in their ability to decrease the severity of ethanol withdrawal syndrome. The effect of CLN and MRT on ethanol withdrawal-induced anxiety, depression and memory impairment was analysed using EPM, FST and PAR tests, respectively. Animals received distilled water, ethanol and/or either of the drugs (CLN and MRT) in different doses. Relapse to alcohol use was analysed by CPP test. Animals received ethanol as a conditioning drug and distilled water, CLN or MRT as test drug. CLN and MRT both alleviated anxiety in a dose-dependent manner. MRT (4 mg/kg) was more effective than CLN (0.1 mg/kg) in ameliorating the anxiogenic effect of alcohol withdrawal. However, CLN treatment increased depression. It significantly decreased swimming time and increased immobility time, whereas MRT treatment decreased immobility time and increased climbing and swimming time during abstinence. The effect was dose dependent for both drugs. The results of PAR test show that CLN treatment worsens working memory. Significant increase in SDE and TSZ and decrease in SDL were observed in CLN-treated animals. MRT treatment, on the other hand, improved working memory at both doses. Further, both CLN and MRT alleviated craving. A significant decrease in time spent in the ethanol-paired chamber was seen. MRT treatment at both doses showed better effect than CLN in preventing the development of preference in CPP test. These findings indicate a potential therapeutic use and better profile of mirtazapine over clonidine in improving memory, as well as in alleviating depression, anxiety and craving associated with alcohol withdrawal. © 2016 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).

Time distributions of solar energetic particle events: Are SEPEs really random?

NASA Astrophysics Data System (ADS)

Jiggens, P. T. A.; Gabriel, S. B.

2009-10-01

Solar energetic particle events (SEPEs) can exhibit flux increases of several orders of magnitude over background levels and have always been considered to be random in nature in statistical models with no dependence of any one event on the occurrence of previous events. We examine whether this assumption of randomness in time is correct. Engineering modeling of SEPEs is important to enable reliable and efficient design of both Earth-orbiting and interplanetary spacecraft and future manned missions to Mars and the Moon. All existing engineering models assume that the frequency of SEPEs follows a Poisson process. We present analysis of the event waiting times using alternative distributions described by Lévy and time-dependent Poisson processes and compared these with the usual Poisson distribution. The results show significant deviation from a Poisson process and indicate that the underlying physical processes might be more closely related to a Lévy-type process, suggesting that there is some inherent “memory” in the system. Inherent Poisson assumptions of stationarity and event independence are investigated, and it appears that they do not hold and can be dependent upon the event definition used. SEPEs appear to have some memory indicating that events are not completely random with activity levels varying even during solar active periods and are characterized by clusters of events. This could have significant ramifications for engineering models of the SEP environment, and it is recommended that current statistical engineering models of the SEP environment should be modified to incorporate long-term event dependency and short-term system memory.

Diuretic effects of medetomidine compared with xylazine in healthy dogs

PubMed Central

Talukder, Md. Hasanuzzaman; Hikasa, Yoshiaki

2009-01-01

This study aimed to investigate and compare the effects of medetomidine and xylazine on diuretic and hormonal variables in healthy dogs. Five dogs, used in each of 11 groups, were injected intramuscularly with physiological saline solution (control), 5, 10, 20, 40, and 80 μg/kg of medetomidine, and 0.25, 0.5, 1, 2, and 4 mg/kg of xylazine. Urine and blood samples were taken 11 times over 24 h. Both medetomidine and xylazine increased urine production in a dose-dependent manner up to 4 h after injection, but the increase was much less with medetomidine than with xylazine at the tested doses. Urine specific gravity, pH, osmolality, and concentrations of creatinine, sodium, potassium, chloride, and arginine vasopressin (AVP) were decreased in a dose-dependent manner with both medetomidine and xylazine. Plasma osmolality and concentrations of sodium, potassium, and chloride were increased significantly with both drugs. Total amounts of urine AVP excreted and plasma AVP concentrations were significantly decreased by higher doses of medetomidine but were not significantly decreased by xylazine. Higher doses of both drugs significantly increased the plasma concentration of atrial natriuretic peptide (ANP), but the effect was greater with medetomidine than with xylazine. The results revealed that both drugs induce a profound diuresis, but medetomidine’s effect is less dose-dependent than xylazine’s effect. Although changes in plasma concentrations of AVP and ANP may partially influence the diuresis induced by medetomidine, other factors may be involved in the mechanism of the diuretic response to both drugs. Thus, both agents can be used clinically for transient but effective diuresis accompanied by sedation. PMID:19794896

Do climate model predictions agree with long-term precipitation trends in the arid southwestern United States?

NASA Astrophysics Data System (ADS)

Elias, E.; Rango, A.; James, D.; Maxwell, C.; Anderson, J.; Abatzoglou, J. T.

2016-12-01

Researchers evaluating climate projections across southwestern North America observed a decreasing precipitation trend. Aridification was most pronounced in the cold (non-monsoonal) season, whereas downward trends in precipitation were smaller in the warm (monsoonal) season. In this region, based upon a multimodel mean of 20 Coupled Model Intercomparison Project 5 models using a business-as-usual (Representative Concentration Pathway 8.5) trajectory, midcentury precipitation is projected to increase slightly during the monsoonal time period (July-September; 6%) and decrease slightly during the remainder of the year (October-June; -4%). We use observed long-term (1915-2015) monthly precipitation records from 16 weather stations to investigate how well measured trends corroborate climate model predictions during the monsoonal and non-monsoonal timeframe. Running trend analysis using the Mann-Kendall test for 15 to 101 year moving windows reveals that half the stations showed significant (p≤0.1), albeit small, increasing trends based on the longest term record. Trends based on shorter-term records reveal a period of significant precipitation decline at all stations representing the 1950s drought. Trends from 1930 to 2015 reveal significant annual, monsoonal and non-monsoonal increases in precipitation (Fig 1). The 1960 to 2015 time window shows no significant precipitation trends. The more recent time window (1980 to 2015) shows a slight, but not significant, increase in monsoonal precipitation and a larger, significant decline in non-monsoonal precipitation. GCM precipitation projections are consistent with more recent trends for the region. Running trends from the most recent time window (mid-1990s to 2015) at all stations show increasing monsoonal precipitation and decreasing Oct-Jun precipitation, with significant trends at 6 of 16 stations. Running trend analysis revealed that the long-term trends were not persistent throughout the series length, but depended on the period examined. Recent trends in Southwest precipitation are directionally consistent with anthropogenic climate change.

Effects of yohimbine and drug cues on impulsivity and attention in cocaine-dependent men and women and sex-matched controls.

PubMed

Moran-Santa Maria, M M; Baker, N L; McRae-Clark, A L; Prisciandaro, J J; Brady, K T

2016-05-01

Deficits in executive function have been associated with risk for relapse. Data from previous studies suggest that relapse may be triggered by stress and drug-paired cues and that there are significant sex differences in the magnitude of these responses. The aim of this study was to examine the impact of the pharmacological stressor and alpha-2 adrenergic receptor antagonist yohimbine and cocaine cues on executive function in cocaine-dependent men and women. In a double-blind placebo controlled cross-over study, cocaine-dependent men (n=12), cocaine-dependent women (n=27), control men (n=31) and control women (n=25) received either yohimbine or placebo prior to two cocaine cue exposure sessions. Participants performed the Connors' Continuous Performance Test II prior to medication/placebo administration and immediately after each cue exposure session Healthy controls had a significant increase in commission errors under the yohimbine condition [RR (95% CI)=1.1 (1.0-1.3), χ(2)1=2.0, p=0.050]. Cocaine-dependent individuals exhibited a significant decrease in omission errors under the yohimbine condition [RR (95% CI)=0.6 (0.4-0.8), χ(2)1=8.6, p=0.003]. Cocaine-dependent women had more omission errors as compared to cocaine-dependent men regardless of treatment [RR (95% CI)=7.2 (3.6-14.7), χ(2)1=30.1, p<0.001]. Cocaine-dependent women exhibited a slower hit reaction time as compared to cocaine-dependent men [Female 354 ± 13 vs. Male 415 ± 14; t89=2.6, p=0.012]. These data add to a growing literature demonstrating significant sex differences in behaviors associated with relapse in cocaine-dependent individuals. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

A hazard rate analysis of fertility using duration data from Malaysia.

PubMed

Chang, C

1988-01-01

Data from the Malaysia Fertility and Family Planning Survey (MFLS) of 1974 were used to investigate the effects of biological and socioeconomic variables on fertility based on the hazard rate model. Another study objective was to investigate the robustness of the findings of Trussell et al. (1985) by comparing the findings of this study with theirs. The hazard rate of conception for the jth fecundable spell of the ith woman, hij, is determined by duration dependence, tij, measured by the waiting time to conception; unmeasured heterogeneity (HETi; the time-invariant variables, Yi (race, cohort, education, age at marriage); and time-varying variables, Xij (age, parity, opportunity cost, income, child mortality, child sex composition). In this study, all the time-varying variables were constant over a spell. An asymptotic X2 test for the equality of constant hazard rates across birth orders, allowing time-invariant variables and heterogeneity, showed the importance of time-varying variables and duration dependence. Under the assumption of fixed effects heterogeneity and the Weibull distribution for the duration of waiting time to conception, the empirical results revealed a negative parity effect, a negative impact from male children, and a positive effect from child mortality on the hazard rate of conception. The estimates of step functions for the hazard rate of conception showed parity-dependent fertility control, evidence of heterogeneity, and the possibility of nonmonotonic duration dependence. In a hazard rate model with piecewise-linear-segment duration dependence, the socioeconomic variables such as cohort, child mortality, income, and race had significant effects, after controlling for the length of the preceding birth. The duration dependence was consistant with the common finding, i.e., first increasing and then decreasing at a slow rate. The effects of education and opportunity cost on fertility were insignificant.

Eotaxin increases monolayer permeability of human coronary artery endothelial cells.

PubMed

Jamaluddin, Md Saha; Wang, Xinwen; Wang, Hao; Rafael, Cubas; Yao, Qizhi; Chen, Changyi

2009-12-01

The objective of this study was to determine the effects and molecular mechanisms of eotaxin, a newly discovered chemokine (CCL11), on endothelial permeability in the human coronary artery endothelial cells (HCAECs). Cells were treated with eotaxin, and the monolayer permeability was studied by using a costar transwell system with a Texas Red-labeled dextran tracer. Eotaxin significantly increased monolayer permeability in a concentration-dependent manner. In addition, eotaxin treatment significantly decreased the mRNA and protein levels of endothelial junction molecules including zonula occludens-1 (ZO-1), occludin, and claudin-1 in a concentration-dependent manner as determined by real-time RT-PCR and Western blot analysis, respectively. Increased oxidative stress was observed in eotaxin-treated HCAECs by analysis of cellular glutathione levels. Furthermore, eotaxin treatment substantially activated the phosphorylation of MAPK p38. HCAECs expressed CCR3. Consequently, antioxidants (ginkgolide B and MnTBAP), specific p38 inhibitor SB203580, and anti-CCR3 antibody effectively blocked the eotaxin-induced permeability increase in HCAECs. Eotaxin also increased the phosphorylation of Stat3 and nuclear translocation of NF-kappaB in HCAECs. Eotaxin increases vascular permeability through CCR3, the downregulation of tight junction proteins, increase of oxidative stress, and activation of MAPK p38, Stat3, and NF-kB pathways in HCAECs.

Postseismic viscoelastic deformation and stress. Part 2: Stress theory and computation; dependence of displacement, strain, and stress on fault parameters

NASA Technical Reports Server (NTRS)

Cohen, S. C.

1979-01-01

A viscoelastic model for deformation and stress associated with earthquakes is reported. The model consists of a rectangular dislocation (strike slip fault) in a viscoelastic layer (lithosphere) lying over a viscoelastic half space (asthenosphere). The time dependent surface stresses are analyzed. The model predicts that near the fault a significant fraction of the stress that was reduced during the earthquake is recovered by viscoelastic softening of the lithosphere. By contrast, the strain shows very little change near the fault. The model also predicts that the stress changes associated with asthenospheric flow extend over a broader region than those associated with lithospheric relaxation even though the peak value is less. The dependence of the displacements, stresses on fault parameters studied. Peak values of strain and stress drop increase with increasing fault height and decrease with fault depth. Under many circumstances postseismic strains and stresses show an increase with decreasing depth to the lithosphere-asthenosphere boundary. Values of the strain and stress at distant points from the fault increase with fault area but are relatively insensitive to fault depth.

Chronic agmatine treatment prevents behavioral manifestations of nicotine withdrawal in mice.

PubMed

Kotagale, Nandkishor R; Chopde, Chandrabhan T; Umekar, Milind J; Taksande, Brijesh G

2015-05-05

Smoking cessation exhibits an aversive withdrawal syndrome characterized by both increases in somatic signs and affective behaviors including anxiety and depression. In present study, abrupt withdrawal of daily nicotine injections (2mg/kg, s.c., four times daily, for 10 days) significantly increased somatic signs viz. rearing, grooming, jumping, genital licking, leg licking, head shakes with associated depression (increased immobility in forced swim test) as well as anxiety (decreased the number of entries and time spent in open arm in elevated plus maze) in nicotine dependent animals. The peak effect was observed at 24h time point of nicotine withdrawal. Repeated administration of agmatine (40-80µg/mouse, i.c.v.) before the first daily dose of nicotine from day 5 to 10 attenuated the elevated scores of somatic signs and abolished the depression and anxiety like behavior induced by nicotine withdrawal in dependent animals. However, in separate groups, its acute administration 30min before behavior analysis of nicotine withdrawal was ineffective. This result clearly shows the role of agmatine in development of nicotine dependence and its withdrawal. In extension to behavioral experiments, brain agmatine analyses, carried out at 24h time point of nicotine withdrawal demonstrated marked decrease in basal brain agmatine concentration as compared to control animals. Taken together, these data support the role of agmatine as common biological substrate for somatic signs and affective symptoms of nicotine withdrawal. This data may project therapies based on agmatine in anxiety, depression and mood changes associated with tobacco withdrawal. Copyright © 2015 Elsevier B.V. All rights reserved.

Ventricular Repolarization Adaptation to Abrupt Changes in Heart Rate after Microgravity Simulation by 5-Day Head-Down Bed Rest

NASA Astrophysics Data System (ADS)

Bolea, J.; Almeida, R.; Pueyo, E.; Laguna, P.; Caiani, E. G.

2013-02-01

Microgravity exposure for long periods of time leads to body deconditioning and it increases the risk of experiencing life-threatening arrhythmias. The study of ventricular repolarization dependence on heart rate has been used to stratify patients according to their arrhythmic risk. The QTp adaptation to HR changes is characterized by M90 (90% of the adaptation). The QTp=HR , after compensation for the adaptation lag, is modeled using a set of regression functions (a , kind of slope of relationship). Subjects with lower orthostatic tolerance time showed a non significant decrease in the adaptation lag (M90 from 148 to 108 beats), which may be due to an extra deconditioning in the sympathovagal response. Nevertheless an increase in the QTp=HR adaptation lag (M90 from 108 to 117 beats with a p = 0.06) and a significant reduction in the slope (a from 0.53 to 0.35 with a p < 0.005), which in previous studies have been correlated with an increased arrhytimic risk, were observed for subjects with higher orthostatic tolerance time.

Size and Temperature Dependence of Electron Transfer between CdSe Quantum Dots and a TiO 2 Nanobelt

DOE PAGES

Tafen, De Nyago; Prezhdo, Oleg V.

2015-02-24

Understanding charge transfer reactions between quantum dots (QD) and metal oxides is fundamental for improving photocatalytic, photovoltaic and electronic devices. The complexity of these processes makes it difficult to find an optimum QD size with rapid charge injection and low recombination. We combine time-domain density functional theory with nonadiabatic molecular dynamics to investigate the size and temperature dependence of the experimentally studied electron transfer and charge recombination at CdSe QD-TiO 2 nanobelt (NB) interfaces. The electron injection rate shows strong dependence on the QD size, increasing for small QDs. The rate exhibits Arrhenius temperature dependence, with the activation energy ofmore » the order of millielectronvolts. The charge recombination process occurs due to coupling of the electronic subsystem to vibrational modes of the TiO 2 NB. Inelastic electron-phonon scattering happens on a picosecond time scale, with strong dependence on the QD size. Our simulations demonstrate that the electron-hole recombination rate decreases significantly as the QD size increases, in excellent agreement with experiments. The temperature dependence of the charge recombination rates can be successfully modeled within the framework of the Marcus theory through optimization of the electronic coupling and the reorganization energy. Our simulations indicate that by varying the QD size, one can modulate the photoinduced charge separation and charge recombination, fundamental aspects of the design principles for high efficiency devices.« less

Abdominal Manual Therapy Repairs Interstitial Cells of Cajal and Increases Colonic c-Kit Expression When Treating Bowel Dysfunction after Spinal Cord Injury

PubMed Central

Zhang, Wenyi; Zhu, Zhaojin; Xie, Bin; Yu, Jun

2017-01-01

Background This study aimed to evaluate the therapeutic effects of abdominal manual therapy (AMT) on bowel dysfunction after spinal cord injury (SCI), investigating interstitial cells of Cajal (ICCs) and related c-kit expression. Methods Model rats were divided as SCI and SCI with drug treatment (intragastric mosapride), low-intensity (SCI + LMT; 50 g, 50 times/min), and high-intensity AMT (SCI + HMT; 100 g, 150 times/min). After 14 days of treatment, weight, improved Basso-Beattie-Bresnahan (BBB) locomotor score, and intestinal movement were evaluated. Morphological structure of spinal cord and colon tissues were examined. Immunostaining, RT-PCR, and western blot were used to assess c-kit expression. Results In SCI rats, AMT could not restore BBB, but it significantly increased weight, shortened time to defecation, increased feces amounts, and improved fecal pellet traits and colon histology. AMT improved the number, distribution, and ultrastructure of colonic ICCs, increasing colonic c-kit mRNA and protein levels. Compared with the SCI + Drug and SCI + LMT groups, the SCI + HMT group showed better therapeutic effect in improving intestinal transmission function and promoting c-kit expression. Conclusions AMT is an effective therapy for recovery of intestinal transmission function. It could repair ICCs and increase c-kit expression in colon tissues after SCI, in a frequency-dependent and pressure-dependent manner. PMID:29349063

Predictors of the Nicotine Dependence Behavior Time to the First Cigarette in a Multiracial Cohort.

PubMed

Branstetter, Steven A; Mercincavage, Melissa; Muscat, Joshua E

2015-07-01

The time to first cigarette of the day (TTFC) is a strong indicator of nicotine dependence behaviors such as nicotine uptake and quit success in young and older smokers. There are substantial differences in levels of nicotine dependence by race and ethnic group. Data from Wave III of the multiracial National Longitudinal Study of Adolescent Health were analyzed for young smokers between the ages of 21 and 28 (N = 1,425). Time to first cigarette data was compared between Hispanic, White, Black, Native American, and Asian smokers. Black smokers were significantly more likely to smoke within 5min of waking than White, Hispanic, and Asian smokers. Lower personal income predicted smoking within 5min of waking for both White and Black smokers. For White smokers, increased number of cigarettes per day and increased years of smoking also predicted smoking within 5min of waking. The number of days smoked or number of cigarettes per day did not predict smoking within 5min of waking among smokers. The higher prevalence of early TTFC among Blacks indicates increased nicotine and carcinogen exposure, and may help explain the increased lung cancer rates and failed cessation attempts among Black smokers. TTFC may be an important screening item, independent of cigarettes per day, for clinicians and interventions to identify those at highest risk for cessation failure and disease risk. © The Author 2014. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Time-dependent crack growth behavior of alloy 617 and alloy 230 at elevated temperatures

NASA Astrophysics Data System (ADS)

Roy, Shawoon Kumar

2011-12-01

Two Ni-base solid-solution-strengthened superalloys: INCONEL 617 and HAYNES 230 were studied to check sustained loading crack growth (SLCG) behavior at elevated temperatures appropriate for Next Generation Nuclear Plant (NGNP) applictaions with constant stress intensity factor (Kmax= 27.75 MPa✓m) in air. The results indicate a time-dependent rate controlling process which can be characterized by a linear elastic fracture mechanics (LEFM) parameter -- stress intensity factor (K). At elevated temperatures, the crack growth mechanism was best described using a damage zone concept. Based on results and study, SAGBOE (stress accelerated grain boundary oxidation embrittlement) is considered the primary reason for time-dependent SLCG. A thermodynamic equation was considered to correlate all the SLCG results to determine the thermal activation energy in the process. A phenomenological model based on a time-dependent factor was developed considering the previous researcher's time-dependent fatigue crack propagation (FCP) results and current SLCG results to relate cycle-dependent and time-dependent FCP for both alloys. Further study includes hold time (3+300s) fatigue testing and no hold (1s) fatigue testing with various load ratios (R) at 700°C with a Kmax of 27.75 MPa✓m. Study results suggest an interesting point: crack growth behavior is significantly affected with the change in R value in cycle-dependent process whereas in time-dependent process, change in R does not have any significant effect. Fractography study showed intergranular cracking mode for all time-dependent processes and transgranular cracking mode for cycle-dependent processes. In Alloy 230, SEM images display intergranular cracking with carbide particles, dense oxides and dimple mixed secondary cracks for time-dependent 3+300s FCP and SLCG test. In all cases, Alloy 230 shows better crack growth resistance compared to Alloy 617.

Epigallocatechin activates haem oxygenase-1 expression via protein kinase Cδ and Nrf2

PubMed Central

Ogborne, Richard M.; Rushworth, Stuart A.; O’Connell, Maria A.

2008-01-01

The Nrf2/anti-oxidant response element (ARE) pathway plays an important role in regulating cellular anti-oxidants, including haem oxygenase-1 (HO-1). Various kinases have been implicated in the pathways leading to Nrf2 activation. Here, we investigated the effect of epigallocatechin (EGC) on ARE-mediated gene expression in human monocytic cells. EGC time and dose dependently increased HO-1 mRNA and protein expression but had minimal effect on expression of other ARE-regulated genes, including NAD(P)H:quinone oxidoreductase 1, glutathione cysteine ligase and ferritin. siRNA knock down of Nrf2 significantly inhibited EGC-induced HO-1 expression. Furthermore, inhibition of PKC by Ro-31-8220 dose dependently decreased EGC-induced HO-1 mRNA expression, whereas MAP kinase and phosphatidylinositol-3-kinase pathway inhibitors had no significant effect. EGC stimulated phosphorylation of PKCαβ and δ in THP-1 cells. PKCδ inhibition significantly decreased EGC-induced HO-1 mRNA expression, whereas PKCα- and β-specific inhibitors had no significant effect. These results demonstrate for the first time that EGC-induced HO-1 expression occurs via PKCδ and Nrf2. PMID:18586007

Chronic Ethanol Exposure Produces Time- and Brain Region-Dependent Changes in Gene Coexpression Networks

PubMed Central

Osterndorff-Kahanek, Elizabeth A.; Becker, Howard C.; Lopez, Marcelo F.; Farris, Sean P.; Tiwari, Gayatri R.; Nunez, Yury O.; Harris, R. Adron; Mayfield, R. Dayne

2015-01-01

Repeated ethanol exposure and withdrawal in mice increases voluntary drinking and represents an animal model of physical dependence. We examined time- and brain region-dependent changes in gene coexpression networks in amygdala (AMY), nucleus accumbens (NAC), prefrontal cortex (PFC), and liver after four weekly cycles of chronic intermittent ethanol (CIE) vapor exposure in C57BL/6J mice. Microarrays were used to compare gene expression profiles at 0-, 8-, and 120-hours following the last ethanol exposure. Each brain region exhibited a large number of differentially expressed genes (2,000-3,000) at the 0- and 8-hour time points, but fewer changes were detected at the 120-hour time point (400-600). Within each region, there was little gene overlap across time (~20%). All brain regions were significantly enriched with differentially expressed immune-related genes at the 8-hour time point. Weighted gene correlation network analysis identified modules that were highly enriched with differentially expressed genes at the 0- and 8-hour time points with virtually no enrichment at 120 hours. Modules enriched for both ethanol-responsive and cell-specific genes were identified in each brain region. These results indicate that chronic alcohol exposure causes global ‘rewiring‘ of coexpression systems involving glial and immune signaling as well as neuronal genes. PMID:25803291

Temperature-dependent inotropic and lusitropic indices based on half-logistic time constants for four segmental phases in isovolumic left ventricular pressure-time curve in excised, cross-circulated canine heart.

PubMed

Mizuno, Ju; Mohri, Satoshi; Yokoyama, Takeshi; Otsuji, Mikiya; Arita, Hideko; Hanaoka, Kazuo

2017-02-01

Varying temperature affects cardiac systolic and diastolic function and the left ventricular (LV) pressure-time curve (PTC) waveform that includes information about LV inotropism and lusitropism. Our proposed half-logistic (h-L) time constants obtained by fitting using h-L functions for four segmental phases (Phases I-IV) in the isovolumic LV PTC are more useful indices for estimating LV inotropism and lusitropism during contraction and relaxation periods than the mono-exponential (m-E) time constants at normal temperature. In this study, we investigated whether the superiority of the goodness of h-L fits remained even at hypothermia and hyperthermia. Phases I-IV in the isovolumic LV PTCs in eight excised, cross-circulated canine hearts at 33, 36, and 38 °C were analyzed using h-L and m-E functions and the least-squares method. The h-L and m-E time constants for Phases I-IV significantly shortened with increasing temperature. Curve fitting using h-L functions was significantly better than that using m-E functions for Phases I-IV at all temperatures. Therefore, the superiority of the goodness of h-L fit vs. m-E fit remained at all temperatures. As LV inotropic and lusitropic indices, temperature-dependent h-L time constants could be more useful than m-E time constants for Phases I-IV.

How can mortality increase population size? A test of two mechanistic hypotheses.

PubMed

McIntire, Kristina M; Juliano, Steven A

2018-05-03

Overcompensation occurs when added mortality increases survival to the next life-cycle stage. Overcompensation can contribute to the Hydra Effect, wherein added mortality increases equilibrium population size. One hypothesis for overcompensation is that added mortality eases density-dependence, increasing survival to adulthood ("temporal separation of mortality and density dependence"). Mortality early in the life cycle is therefore predicted to cause overcompensation, whereas mortality later in the life cycle is not. Another hypothesis for overcompensation is that threat of mortality (e.g., from predation) causes behavioral changes that reduce overexploitation of resources, allowing resource recovery, and increasing production of adults ("prudent resource exploitation"). Behaviorally active predation cues alone are therefore predicted to cause overcompensation. We tested these predictions in two experiments with larvae of two species of Aedes. As predicted, early mortality yielded greater production of adults, and of adult females, and greater estimated rate of population increase than did later mortality. Addition of water-borne predation cues usually reduced browsing on surfaces in late-stage larvae, but contrary to prediction, resulted in neither significantly greater production of adult mosquitoes nor significantly greater estimated rate of increase. Thus we have strong evidence that timing of mortality contributes to overcompensation and the Hydra effect in mosquitoes. Evidence that predation cues alone can result in overcompensation via prudent resource exploitation is lacking. We expect the overcompensation in response to early mortality will be common in organisms with complex life cycles, density dependence among juveniles, and developmental control of populations. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

PGE(2) activation of apical membrane Cl(-) channels in A6 epithelia: impedance analysis.

PubMed Central

Păunescu, T G; Helman, S I

2001-01-01

Measurements of transepithelial electrical impedance of continuously short-circuited A6 epithelia were made at audio frequencies (0.244 Hz to 10.45 kHz) to investigate the time course and extent to which prostaglandin E(2) (PGE(2)) modulates Cl(-) transport and apical membrane capacitance in this cell-cultured model epithelium. Apical and basolateral membrane resistances were determined by nonlinear curve-fitting of the impedance vectors at relatively low frequencies (<50 Hz) to equations (Păunescu, T. G., and S. I. Helman. 2001. Biophys. J. 81:838--851) where depressed Nyquist impedance semicircles were characteristic of the membrane impedances under control Na(+)-transporting and amiloride-inhibited conditions. In all tissues (control, amiloride-blocked, and amiloride-blocked and furosemide-pretreated), PGE(2) caused relatively small (< approximately 3 microA/cm(2)) and rapid (<60 s) maximal increase of chloride current due to activation of a rather large increase of apical membrane conductance that preceded significant activation of Na(+) transport through amiloride-sensitive epithelial Na(+) channels (ENaCs). Apical membrane capacitance was frequency-dependent with a Cole-Cole dielectric dispersion whose relaxation frequency was near 150 Hz. Analysis of the time-dependent changes of the complex frequency-dependent equivalent capacitance of the cells at frequencies >1.5 kHz revealed that the mean 9.8% increase of capacitance caused by PGE(2) was not correlated in time with activation of chloride conductance, but rather correlated with activation of apical membrane Na(+) transport. PMID:11463630

Dielectric analysis of depth dependent curing behavior of dental resin composites.

PubMed

Steinhaus, Johannes; Moeginger, Bernhard; Grossgarten, Mandy; Rosentritt, Martin; Hausnerova, Berenika

2014-06-01

The aim of this study is to investigate depth dependent changes of polymerization process and kinetics of visible light-curing (VLC) dental composites in real-time. The measured quantity - "ion viscosity" determined by dielectric analysis (DEA) - provides the depth dependent reaction rate which is correlated to the light intensity available in the corresponding depths derived from light transmission measurements. The ion viscosity curves of two composites (VOCO Arabesk Top and Grandio) were determined during irradiation of 40s with a light-curing unit (LCU) in specimen depths of 0.5/0.75/1.0/1.25/1.5/1.75 and 2.0mm using a dielectric cure analyzer (NETZSCH DEA 231 with Mini IDEX sensors). The thickness dependent light transmission was measured by irradiation composite specimens of various thicknesses on top of a radiometer setup. The shape of the ion viscosity curves depends strongly on the specimen thickness above the sensor. All curves exhibit a range of linear time dependency of the ion viscosity after a certain initiation time. The determined initiation times, the slopes of the linear part of the curves, and the ion viscosities at the end of the irradiation differ significantly with depth within the specimen. The slopes of the ion viscosity curves as well as the light intensity values decrease with depth and fit to the Lambert-Beer law. The corresponding attenuation coefficients are determined for Arabesk Top OA2 to 1.39mm(-1) and 1.48mm(-1), respectively, and for Grandio OA2 with 1.17 and 1.39mm(-1), respectively. For thicknesses exceeding 1.5mm a change in polymerization behavior is observed as the ion viscosity increases subsequent to the linear range indicating some kind of reaction acceleration. The two VLC composites and different specimen thicknesses discriminate significantly in their ion viscosity evolution allowing for a precise characterization of the curing process even with respect to the polymerization mechanism. Copyright © 2014. Published by Elsevier Ltd.

Effect of water on structure and dynamics of [BMIM][PF6] ionic liquid: An all-atom molecular dynamics simulation investigation.

PubMed

Sharma, Anirban; Ghorai, Pradip Kr

2016-03-21

Composition dependent structural and dynamical properties of aqueous hydrophobic 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF6]) ionic liquid (IL) have been investigated by using all-atom molecular dynamics simulation. We observe that addition of water does not increase significant number of dissociated ions in the solution over the pure state. As a consequence, self-diffusion coefficient of the cation and anion is comparable to each other at all water concentration similar to that is observed for the pure state. Voronoi polyhedra analysis exhibits strong dependence on the local environment of IL concentration. Void and neck distributions in Voronoi tessellation are approximately Gaussian for pure IL but upon subsequent addition of water, we observe deviation from the Gaussian behaviour with an asymmetric broadening with long tail of exponential decay at large void radius, particularly at higher water concentrations. The increase in void space and neck size at higher water concentration facilitates ionic motion, thus, decreasing dynamical heterogeneity and IL reorientation time and increases self-diffusion coefficient significantly.

Effect of water on structure and dynamics of [BMIM][PF{sub 6}] ionic liquid: An all-atom molecular dynamics simulation investigation

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

Sharma, Anirban; Ghorai, Pradip Kr., E-mail: pradip@iiserkol.ac.in

2016-03-21

Composition dependent structural and dynamical properties of aqueous hydrophobic 1-butyl-3-methylimidazolium hexafluorophosphate ([BMIM][PF{sub 6}]) ionic liquid (IL) have been investigated by using all-atom molecular dynamics simulation. We observe that addition of water does not increase significant number of dissociated ions in the solution over the pure state. As a consequence, self-diffusion coefficient of the cation and anion is comparable to each other at all water concentration similar to that is observed for the pure state. Voronoi polyhedra analysis exhibits strong dependence on the local environment of IL concentration. Void and neck distributions in Voronoi tessellation are approximately Gaussian for pure ILmore » but upon subsequent addition of water, we observe deviation from the Gaussian behaviour with an asymmetric broadening with long tail of exponential decay at large void radius, particularly at higher water concentrations. The increase in void space and neck size at higher water concentration facilitates ionic motion, thus, decreasing dynamical heterogeneity and IL reorientation time and increases self-diffusion coefficient significantly.« less

Effects of a Multi-Ingredient Energy Supplement on Cognitive Performance and Cerebral-Cortical Activation.

PubMed

Daou, Marcos; Sassi, Julia Montagner; Miller, Matthew W; Gonzalez, Adam M

2018-03-13

This study assessed whether a multi-ingredient energy supplement (MIES) could enhance cerebral-cortical activation and cognitive performance during an attention-switching task. Cerebral-cortical activation was recorded in 24 young adults (12 males, 12 females; 22.8 ± 3.8 yrs) via electroencephalography (EEG) both at rest and during the attention-switching task before (pretest) and 30 min after (posttest) consumption of a single serving of a MIES (MIES-1), two servings of a MIES (MIES-2), or a placebo (PL) in a double-blinded, randomized crossover experimental design. EEG upper-alpha power was assessed at rest and during the task, wherein d' (Z[hit rate]-Z[false alarm rate]) and median reaction time (RT) for correct responses to targets on attention-hold and attention-switch trials were analyzed. For both d' and RT, the Session (MIES-1, MIES-2, PL) × Time (pretest, posttest) interaction approached statistical significance (p = .07, η 2 p = 0.106). Exploring these interactions with linear contrasts, a significant linear effect of supplement dose on the linear effect of time was observed (ps ≤.034), suggesting the pretest-to-posttest improvement in sensitivity to task target stimuli (d') and RT increased as a function of supplement dose. With respect to upper-alpha power, the Session × Time interaction was significant (p < .001, η 2 p = 0.422). Exploring this interaction with linear contrasts, a significant linear effect of supplement dose on the linear effect of time was observed (p < .001), suggesting pretest-to-posttest increases in cerebral-cortical activation were a function of supplement dose. In conclusion, our findings suggest that MIES can increase cerebral-cortical activation and RT during task performance while increasing sensitivity to target stimuli in a dose-dependent manner.

Chlorine gas exposure disrupts nitric oxide homeostasis in the pulmonary vasculature

PubMed Central

Honavar, Jaideep; Bradley, Eddie; Bradley, Kelley; Oh, Joo Yeun; Vallejo, Matthew O.; Kelley, Eric E.; Cantu-Medellin, Nadiezhda; Doran, Stephen; Dell’italia, Louis J.; Matalon, Sadis; Patel, Rakesh P.

2014-01-01

Exposure to chlorine (Cl2) gas during industrial accidents or chemical warfare leads to significant airway and distal lung epithelial injury that continues post exposure. While lung epithelial injury is prevalent, relatively little is known about whether Cl2 gas also promotes injury to the pulmonary vasculature. To determine this, rats were subjected to a sub-lethal Cl2 gas exposure (400ppm, 30min) and then brought back to room air. Pulmonary arteries (PA) were isolated from rats at various times post-exposure and contractile (phenylephrine) and nitric oxide (NO)-dependent vasodilation (acetylcholine and mahmanonoate) responses measured ex-vivo. PA contractility did not change, however significant inhibition of NO-dependent vasodilation was observed that was maximal at 24–48 hours post exposure. Superoxide dismutase restored NO-dependent vasodilation suggesting a role for increased superoxide formation. This was supported by ~2-fold increase in superoxide formation (measured using 2-hydroethidine oxidation to 2-OH-E+) from PA isolated from Cl2 exposed rats. We next measured PA pressures in anesthetized rats. Surprisingly, PA pressures were significantly (~4mmHg) lower in rats that had been exposed to Cl2 gas 24 hours earlier suggesting that deficit in NO-signaling observed in isolated PA experiments did not manifest as increased PA pressures in vivo. Administration of the iNOS selective inhibitor 1400W, restored PA pressures to normal in Cl2 exposed, but not control rats suggesting that any deficit in NO-signaling due to increased superoxide formation in the PA, is offset by increased NO-formation from iNOS. These data indicate that disruption of endogenous NO-signaling mechanisms that maintain PA tone is an important aspect of post-Cl2 gas exposure toxicity. PMID:24769334

Surface microhardness of a resin composite exposed to a "first-generation" LED curing lamp, in vitro.

PubMed

Keogh, Pauraic; Ray, Noel J; Lynch, Christopher D; Burke, Francis M; Hannigan, Ailish

2004-12-01

This investigation determined the minimum exposure times consistent with optimised surface microhardness parameters for a commercial resin composite cured using a "first-generation" light-emitting diode activation lamp. Disk specimens were exposed and surface microhardness numbers measured at the top and bottom surfaces for elapsed times of 1 hour and 24 hours. Bottom/top microhardness number ratios were also calculated. Most microhardness data increased significantly over the elapsed time interval but microhardness ratios (bottom/top) were dependent on exposure time only. A minimum exposure of 40 secs is appropriate to optimise microhardness parameters for the combination of resin composite and lamp investigated.

Time- and dose-dependent differential regulation of copper-zinc superoxide dismutase and manganese superoxide dismutase enzymatic activity and mRNA level by vitamin E in rat blood cells.

PubMed

Hajiani, Maliheh; Razi, Farideh; Golestani, Aboualfazl; Frouzandeh, Mehdi; Owji, Ali Akbar; Khaghani, Shahnaz; Ghannadian, Naghmeh; Shariftabrizi, Ahmad; Pasalar, Parvin

2012-01-01

Vitamin E is the most important lipid-soluble antioxidant. Recently, it has been proposed as a gene regulator, and its gene modulation effects have been observed at different levels of gene expression and cell signaling. This study was performed to investigate the effects of vitamin E on the activity and expression of the most important endogenous antioxidant enzyme, superoxide dismutase (SOD), in rat plasma. Twenty-eight male Sprauge-Dawley rats were divided into four groups: control group and three dosing groups. The control group received the vehicle (liquid paraffin), and the dosing groups received twice-weekly intraperitoneal injections of 10, 30, and 100 mg/kg of vitamin E ((±)-α-Tocopherol) for 6 weeks. Quantitative real-time reverse transcription-polymerase chain reaction and enzyme assays were used to assess the levels of Cu/Zn-SOD and Mn-SOD mRNA and enzyme activity levels in blood cells at 0, 2, 4, and 6 weeks following vitamin E administration. Catalase enzyme activity and total antioxidant capacity were also assessed in plasma at the same time intervals. Mn-SOD activity was significantly increased in the 100 and 30 mg/kg dosing groups after 4 and 6 weeks, with corresponding significant increase in their mRNA levels. Cu/Zn-SOD activity was not significantly changed in response to vitamin E administration at any time points, whereas Cu/Zn-SOD mRNA levels were significantly increased after longer time points with high doses (30 and 100 mg/kg) of vitamin E. Catalase enzyme activity was transiently but significantly increased after 4 weeks of vitamin E treatment in 30 and 100 mg/kg dosing groups. Total antioxidant status was significantly increased after 4 and 6 weeks in the 100 mg/kg dosing group. Only the chronic administration of higher doses of alpha-tocopherol is associated with the increased activity and expression of Mn-SOD in rats. Cu/Zn-SOD activity and expression does not dramatically change in response to vitamin E.

DOI Determination by Rise Time Discrimination in Single-Ended Readout for TOF PET Imaging

PubMed Central

Wiener, R.I.; Surti, S.; Karp, J.S.

2013-01-01

Clinical TOF PET systems achieve detection efficiency using thick crystals, typically of thickness 2–3cm. The resulting dispersion in interaction depths degrades spatial resolution for increasing radial positions due to parallax error. Furthermore, interaction depth dispersion results in time pickoff dispersion and thus in degraded timing resolution, and is therefore of added concern in TOF scanners. Using fast signal digitization, we characterize the timing performance, pulse shape and light output of LaBr3:Ce, CeBr3 and LYSO. Coincidence timing resolution is shown to degrade by ~50ps/cm for scintillator pixels of constant cross section and increasing length. By controlling irradiation depth in a scintillator pixel, we show that DOI-dependence of time pickoff is a significant factor in the loss of timing performance in thick detectors. Using the correlated DOI-dependence of time pickoff and charge collection, we apply a charge-based correction to the time pickoff, obtaining improved coincidence timing resolution of <200ps for a uniform 4×4×30mm3 LaBr3 pixel. In order to obtain both DOI identification and improved timing resolution, we design a two layer LaBr3[5%Ce]/LaBr3[30%Ce] detector of total size 4×4×30mm3, exploiting the dependence of scintillator rise time on [Ce] in LaBr3:Ce. Using signal rise time to determine interaction layer, excellent interaction layer discrimination is achieved, while maintaining coincidence timing resolution of <250ps and energy resolution <7% using a R4998 PMT. Excellent layer separation and timing performance is measured with several other commercially-available TOF photodetectors, demonstrating the practicality of this design. These results indicate the feasibility of rise time discrimination as a technique for measuring event DOI while maintaining sensitivity, timing and energy performance, in a well-known detector architecture. PMID:24403611

DOI Determination by Rise Time Discrimination in Single-Ended Readout for TOF PET Imaging.

PubMed

Wiener, R I; Surti, S; Karp, J S

2013-06-01

Clinical TOF PET systems achieve detection efficiency using thick crystals, typically of thickness 2-3cm. The resulting dispersion in interaction depths degrades spatial resolution for increasing radial positions due to parallax error. Furthermore, interaction depth dispersion results in time pickoff dispersion and thus in degraded timing resolution, and is therefore of added concern in TOF scanners. Using fast signal digitization, we characterize the timing performance, pulse shape and light output of LaBr 3 :Ce, CeBr 3 and LYSO. Coincidence timing resolution is shown to degrade by ~50ps/cm for scintillator pixels of constant cross section and increasing length. By controlling irradiation depth in a scintillator pixel, we show that DOI-dependence of time pickoff is a significant factor in the loss of timing performance in thick detectors. Using the correlated DOI-dependence of time pickoff and charge collection, we apply a charge-based correction to the time pickoff, obtaining improved coincidence timing resolution of <200ps for a uniform 4×4×30mm 3 LaBr 3 pixel. In order to obtain both DOI identification and improved timing resolution, we design a two layer LaBr 3 [5%Ce]/LaBr 3 [30%Ce] detector of total size 4×4×30mm 3 , exploiting the dependence of scintillator rise time on [Ce] in LaBr 3 :Ce. Using signal rise time to determine interaction layer, excellent interaction layer discrimination is achieved, while maintaining coincidence timing resolution of <250ps and energy resolution <7% using a R4998 PMT. Excellent layer separation and timing performance is measured with several other commercially-available TOF photodetectors, demonstrating the practicality of this design. These results indicate the feasibility of rise time discrimination as a technique for measuring event DOI while maintaining sensitivity, timing and energy performance, in a well-known detector architecture.

Kinetics of moisture loss and oil uptake during deep fat frying of Gethi (Dioscorea kamoonensis Kunth) strips.

PubMed

Manjunatha, S S; Ravi, N; Negi, P S; Raju, P S; Bawa, A S

2014-11-01

Investigation was carried out to study kinetics of moisture loss, oil uptake and tristimulus colour during deep fat frying of Gethi (Dioscorea kamoonensis kunth) strips. Deep fat frying of Gethi strips of size 6 × 6 × 40 mm was carried out in a laboratory scale fryer at different temperatures ranging from 120 to 180 °C. The investigation showed that the moisture loss and oil uptake followed the first order kinetics equation (r > 0.95, p < 0.05). The kinetic coefficients for moisture loss and oil uptake increased significantly (p < 0.05) with temperature from 0.166 to 0.889 min(-1) and 0.139 to 0.430 min(-1) respectively. The temperature dependency of rate constants for moisture loss and oil uptake values was described using Arrhenius equation (r > 0.99, p < 0.01). The activation energies for moisture loss and oil uptake were found to be 41.53 KJ/mol and 27.12 KJ/mol respectively. The hunter colour parameters were significantly affected by frying temperature and frying time. The hunter lightness (L) value increased with respect to frying time initially, followed by decline and same trend was observed at higher temperatures of frying with elevated rate, whereas hunter redness (a) value increased significantly (p < 0.01) with time as well as temperature of frying and obeyed zero order rate equation. The temperature dependency kinetic coefficients of Hunter (a) value were described by Arrhenius equation and the energy of activation for change in hunter redness was found to be 42.41 KJ/mol (r > 0.99, p < 0.01). The other hunter colour parameters such as chroma, hue angle and total colour difference were markedly affected by frying temperature as well as frying time.

Interferon-γ regulates chemokine expression and release in the human mast cell line HMC1: role of nitric oxide

PubMed Central

Gilchrist, M; Befus, A D

2008-01-01

Mast cells (MCs) are critical immune effector cells that release cytokines and chemokines involved in both homeostasis and disease. Interferon-γ (IFN-γ) is a pleiotropic cytokine that regulates multiple cellular activities. IFN-γ modulates rodent MC responsiveness via production of nitric oxide (NO), although the effects in human MC populations is unknown. We sought to investigate the effects of IFN-γ on expression of the chemokines interleukin-8 (IL-8) and CCL1 (I-309) in a human mast cell line (HMC1) and to determine the underlying regulatory mechanism. Nitric oxide synthase (NOS), IL-8 and CCL1 expression was determined using real-time polymerase chain reaction (PCR). NOS protein expression was analysed using western blot. NOS activity was determined using the citrulline assay. IL-8 and CCL1 release was measured by specific enzyme-linked immunosorbent assay (ELISA). IFN-γ inhibited phorbol 12-myristate 13-acetate (PMA)-induced release of IL-8 and CCL1 (by 47 and 38%). Real-time PCR analysis of IFN-γ-treated HMC1 showed a significant (P < 0·05) time-dependent increase in NOS1 and NOS3 mRNA. NOS3 protein was significantly increased at 18 hr, which correlated with a significant (P < 0·05) increase in constitutive NOS (cNOS) activity. IFN-γ-induced inhibition of chemokine expression and release was NO dependent, as treatment with the NOS inhibitor NG-nitro-l-arginine methyl ester (l-NAME) reduced the IFN-γ inhibitory effect on IL-8 and CCL1 mRNA expression. NO donors mimicked the IFN-γ effect. IFN-γ inhibited PMA-induced cAMP response element binding protein (CREB) phosphorylation and DNA-binding activity. Our observations indicate for the first time that IFN-γ enhances endogenous NO formation through NOS3 activity, and that NO regulates the transcription and release of IL-8 and CCL1 in a human MC line. PMID:17662042

Time-dependent postural control adaptations following a neuromuscular warm-up in female handball players: a randomized controlled trial.

PubMed

Steib, Simon; Zahn, Peter; Zu Eulenburg, Christine; Pfeifer, Klaus; Zech, Astrid

2016-01-01

Female handball athletes are at a particular risk of sustaining lower extremity injuries. The study examines time-dependent adaptations of static and dynamic balance as potential injury risk factors to a specific warm-up program focusing on neuromuscular control. Fourty one (24.0 ± 5.9 years) female handball athletes were randomized to an intervention or control group. The intervention group implemented a 15-min specific neuromuscular warm-up program, three times per week for eleven weeks, whereas the control group continued with their regular warm-up. Balance was assessed at five time points. Measures included the star excursion balance test (SEBT), and center of pressure (COP) sway velocity during single-leg standing. No baseline differences existed between groups in demographic data. Adherence to neuromuscular warm-up was 88.7 %. Mean COP sway velocity decreased significantly over time in the intervention group (-14.4 %; p  < .001), but not in the control group (-6.2 %; p  = 0.056). However, these effects did not differ significantly between groups ( p  = .098). Mean changes over time in the SEBT score were significantly greater ( p  = .014) in the intervention group (+5.48) compared to the control group (+3.45). Paired t-tests revealed that the first significant balance improvements were observed after 6 weeks of training. A neuromuscular warm-up positively influences balance variables associated with an increased risk of lower extremity injuries in female handball athletes. The course of adaptations suggests that a training volume of 15 min, three times weekly over at least six weeks produces measurable changes. Retrospectively registered on 4th October 2016. Registry: clinicaltrials.gov. Trial number: NCT02925377.

Assessment of time-dependent density functional theory with the restricted excitation space approximation for excited state calculations of large systems

NASA Astrophysics Data System (ADS)

Hanson-Heine, Magnus W. D.; George, Michael W.; Besley, Nicholas A.

2018-06-01

The restricted excitation subspace approximation is explored as a basis to reduce the memory storage required in linear response time-dependent density functional theory (TDDFT) calculations within the Tamm-Dancoff approximation. It is shown that excluding the core orbitals and up to 70% of the virtual orbitals in the construction of the excitation subspace does not result in significant changes in computed UV/vis spectra for large molecules. The reduced size of the excitation subspace greatly reduces the size of the subspace vectors that need to be stored when using the Davidson procedure to determine the eigenvalues of the TDDFT equations. Furthermore, additional screening of the two-electron integrals in combination with a reduction in the size of the numerical integration grid used in the TDDFT calculation leads to significant computational savings. The use of these approximations represents a simple approach to extend TDDFT to the study of large systems and make the calculations increasingly tractable using modest computing resources.

The Magnitude and Time Course of IOP Change in Response to Body Position Change in Nonhuman Primates Measured Using Continuous IOP Telemetry

PubMed Central

Turner, Daniel C.; Samuels, Brian C.; Huisingh, Carrie; Girkin, Christopher A.

2017-01-01

Purpose To study the effect and time course of body position changes on IOP in nonhuman primates. Methods We recorded continuous bilateral IOP measurements with a wireless telemetry implant in three rhesus macaques in seven different body positions. IOP measurements were acquired in the seated-upright, standing, prone, supine, right and left lateral decubitus positions (LDPs), and head-down inverted positions. Continuous IOP was recorded for 90 seconds in each position before returning to a supine reference position until IOP stabilized; measurements were averaged after IOP stabilized at each position. Results Head-down inversion increased IOP an average of 8.9 mm Hg, compared to the supine reference. In the LDP, IOP decreased an average of 0.5 mm Hg in the nondependent eye (i.e., the higher eye), while the fellow dependent (i.e., lower) eye increased an average of 0.5 mm Hg, compared to supine reference. Standing and seated positions decreased IOP 1.5 and 2.2 mm Hg, respectively, compared with supine reference. IOP changes occurred within 4 to 15 seconds of a body position change, and timing was affected by the speed at which body position was changed. Compared to the IOP in the supine position, the IOP in the inverted, prone, and seated positions was significantly different (P = 0.0313 for all). The IOP in the standing position was not statistically different from the IOP in the supine position (P = 0.094). In addition, the IOP was significantly different between the nondependent eye and the dependent eye in the LDPs compared to the supine position (P = 0.0313). Conclusions Body position has a significant effect on IOP and those changes persist over time. PMID:29228251

A phthalide derivative isolated from endophytic fungi Pestalotiopsis photiniae induces G1 cell cycle arrest and apoptosis in human HeLa cells.

PubMed

Chen, C; Yang, R L

2013-08-01

MP [4-(3',3'-dimethylallyloxy)-5-methyl-6-methoxyphthalide] was obtained from liquid culture of Pestalotiopsis photiniae isolated from the Chinese Podocarpaceae plant Podocarpus macrophyllus. MP significantly inhibited the proliferation of HeLa tumor cell lines. After treatment with MP, characteristic apoptotic features such as DNA fragmentation and chromatin condensation were observed in DAPI-stained HeLa cells. Flow cytometry showed that MP induced G1 cell cycle arrest and apoptosis in a dose-dependent manner. Western blotting and real-time reverse transcription-polymerase chain reaction were used to investigate protein and mRNA expression. MP caused significant cell cycle arrest by upregulating the cyclin-dependent kinase inhibitor p27(KIP1) protein and p21(CIP1) mRNA levels in HeLa cells. The expression of p73 protein was increased after treatment with various MP concentrations. mRNA expression of the cell cycle-related genes, p21(CIP1), p16(INK4a) and Gadd45α, was significantly upregulated and mRNA levels demonstrated significantly increased translation of p73, JunB, FKHR, and Bim. The results indicate that MP may be a potential treatment for cervical cancer.

Necroptosis contributes to methamphetamine-induced cytotoxicity in rat cortical neurons.

PubMed

Xiong, Kun; Liao, Huidan; Long, Lingling; Ding, Yanjun; Huang, Jufang; Yan, Jie

2016-09-01

Necroptosis, a programmed necrosis, is involved in various types of neurodegenerative diseases. In this study, we investigated whether necroptosis contributed to neuronal damage in a methamphetamine injury model. Primary cultures of embryonic cortical neurons from Sprague-Dawley rats were subjected to different doses of methamphetamine with/without pre-treatment with a specific necroptosis inhibitor, Necrostatin-1. Necrosis was assessed by determining lactate dehydrogenase release and by Annexin V/propidium iodide double staining, while the neuronal ultra-structure was examined by electron microscopy. Tumor necrosis factor-α protein levels were determined by enzyme-linked immunosorbent assay. At early stages (12h) of post-treatment with methamphetamine, significant necrosis occurred and the viability of neurons decreased in a dose- and time-dependent manner in this model of acute neuronal injury. Pretreatment with Necrostatin-1 led to significant neuronal preservation compared with the methamphetamine-treated groups. Furthermore, tumor necrosis factor-α expression increased in a dose-dependent manner following methamphetamine exposure. Methamphetamine induced necrosis in rat cortical neurons in vitro, both time and dose dependently, and necroptosis may be an important newly identified mode of cortical neuronal death caused by single high-dose methamphetamine administration. Copyright © 2016 Elsevier B.V. All rights reserved.

Anaplerotic input is sufficient to induce time-dependent potentiation of insulin release in rat pancreatic islets.

PubMed

Gunawardana, Subhadra C; Liu, Yi-Jia; Macdonald, Michael J; Straub, Susanne G; Sharp, Geoffrey W G

2004-11-01

Nutrients that induce biphasic insulin release, such as glucose and leucine, provide acetyl-CoA and anaplerotic input in the beta-cell. The first phase of release requires increased ATP production leading to increased intracellular Ca(2+) concentration ([Ca(2+)](i)). The second phase requires increased [Ca(2+)](i) and anaplerosis. There is strong evidence to indicate that the second phase is due to augmentation of Ca(2+)-stimulated release via the K(ATP) channel-independent pathway. To test whether the phenomenon of time-dependent potentiation (TDP) has similar properties to the ATP-sensitive K(+) channel-independent pathway, we monitored the ability of different agents that provide acetyl-CoA and anaplerotic input or both of these inputs to induce TDP. The results show that anaplerotic input is sufficient to induce TDP. Interestingly, among the agents tested, the nonsecretagogue glutamine, the nonhydrolyzable analog of leucine aminobicyclo[2.2.1]heptane-2-carboxylic acid, and succinic acid methyl ester all induced TDP, and all significantly increased alpha-ketoglutarate levels in the islets. In conclusion, anaplerosis that enhances the supply and utilization of alpha-ketoglutarate in the tricarboxylic acid cycle appears to play an essential role in the generation of TDP.

Slow-Down in Diffusion in Crowded Protein Solutions Correlates with Transient Cluster Formation.

PubMed

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.

Time-dependence of lung injury in mice acutely exposed to cylindrospermopsin.

PubMed

Oliveira, V R; Carvalho, G M C; Avila, M B; Soares, R M; Azevedo, S M F O; Ferreira, T S; Valença, S S; Faffe, D S; Zin, Walter Araujo

2012-10-01

Cylindrospermopsin is a cyanobacterial toxin of increasing environmental importance, as it can lead to disease if orally or intravenously absorbed. However, its in vivo lung impairment has not been documented. Thus, we aimed at verifying whether cylindrospermopsin can induce lung injury and establish its putative dependence on the time elapsed since exposure. BALB/c mice were intratracheally injected with either saline (NaCl 0.9%, 50 μL, SAL group, n = 12) or a sublethal dose (70 μg/kg) of semi-purified extract of cylindrospermopsin (CYN groups, n = 52). Lung mechanics, histological and biochemical analyses, and cylindrospermopsin presence in lungs and liver were determined in independent groups at 2, 8, 24, 48, and 96 h after cylindrospermopsin instillation. There was a significant increase in static elastance at 24 and 48 h after exposure to cylindrospermopsin, while viscoelastic component of elastance and viscoelastic pressure rose at 48 h. Alveolar collapse augmented in CYN groups at 8 h. A significant increase in polymorphonuclear influx into lung parenchyma, as well as a higher myeloperoxidase activity started off at 24 h. Exposure to cylindrospermopsin increased lipid peroxidation and superoxide dismutase activity and reduced catalase activity in CYN groups. The toxin was detected in lungs and liver of all CYN mice. In conclusion, cylindrospermopsin exposure impaired lung mechanics, which was preceded by lung parenchyma inflammation and oxidative stress. Copyright © 2012 Elsevier Ltd. All rights reserved.

Environmentally realistic concentrations of the antibiotic Trimethoprim affect haemocyte parameters but not antioxidant enzyme activities in the clam Ruditapes philippinarum.

PubMed

Matozzo, Valerio; De Notaris, Chiara; Finos, Livio; Filippini, Raffaella; Piovan, Anna

2015-11-01

Several biomarkers were measured to evaluate the effects of Trimethoprim (TMP; 300, 600 and 900 ng/L) in the clam Ruditapes philippinarum after exposure for 1, 3 and 7 days. The actual TMP concentrations were also measured in the experimental tanks. The total haemocyte count significantly increased in 7 day-exposed clams, whereas alterations in haemocyte volume were observed after 1 and 3 days of exposure. Haemocyte proliferation was increased significantly in animals exposed for 1 and 7 days, whereas haemocyte lysate lysozyme activity decreased significantly after 1 and 3 days. In addition, TMP significantly increased haemolymph lactate dehydrogenase activity after 3 and 7 days. Regarding antioxidant enzymes, only a significant time-dependent effect on CAT activity was recorded. This study demonstrated that environmentally realistic concentrations of TMP affect haemocyte parameters in clams, suggesting that haemocytes are a useful cellular model for the assessment of the impact of TMP on bivalves. Copyright © 2015 Elsevier Ltd. All rights reserved.

Time-dependent fracture probability of bilayer, lithium-disilicate-based glass-ceramic molar crowns as a function of core/veneer thickness ratio and load orientation

PubMed Central

Anusavice, Kenneth J.; Jadaan, Osama M.; Esquivel–Upshaw, Josephine

2013-01-01

Recent reports on bilayer ceramic crown prostheses suggest that fractures of the veneering ceramic represent the most common reason for prosthesis failure. Objective The aims of this study were to test the hypotheses that: (1) an increase in core ceramic/veneer ceramic thickness ratio for a crown thickness of 1.6 mm reduces the time-dependent fracture probability (Pf) of bilayer crowns with a lithium-disilicate-based glass-ceramic core, and (2) oblique loading, within the central fossa, increases Pf for 1.6-mm-thick crowns compared with vertical loading. Materials and methods Time-dependent fracture probabilities were calculated for 1.6-mm-thick, veneered lithium-disilicate-based glass-ceramic molar crowns as a function of core/veneer thickness ratio and load orientation in the central fossa area. Time-dependent fracture probability analyses were computed by CARES/Life software and finite element analysis, using dynamic fatigue strength data for monolithic discs of a lithium-disilicate glass-ceramic core (Empress 2), and ceramic veneer (Empress 2 Veneer Ceramic). Results Predicted fracture probabilities (Pf) for centrally-loaded 1,6-mm-thick bilayer crowns over periods of 1, 5, and 10 years are 1.2%, 2.7%, and 3.5%, respectively, for a core/veneer thickness ratio of 1.0 (0.8 mm/0.8 mm), and 2.5%, 5.1%, and 7.0%, respectively, for a core/veneer thickness ratio of 0.33 (0.4 mm/1.2 mm). Conclusion CARES/Life results support the proposed crown design and load orientation hypotheses. Significance The application of dynamic fatigue data, finite element stress analysis, and CARES/Life analysis represent an optimal approach to optimize fixed dental prosthesis designs produced from dental ceramics and to predict time-dependent fracture probabilities of ceramic-based fixed dental prostheses that can minimize the risk for clinical failures. PMID:24060349

The Pro-Proliferative Effects of Nicotine and Its Underlying Mechanism on Rat Airway Smooth Muscle Cells

PubMed Central

He, Fang; Li, Bing; Zhao, Zhuxiang; Zhou, Yumin; Hu, Guoping; Zou, Weifeng; Hong, Wei; Zou, Yimin; Jiang, Changbin; Zhao, Dongxing; Ran, Pixin

2014-01-01

Recent studies have shown that nicotine, a major component of cigarette smoke, can stimulate the proliferation of non-neuronal cells. Cigarette smoking can promote a variety of pulmonary and cardiovascular diseases, such as chronic obstructive pulmonary disease (COPD), atherosclerosis, and cancer. A predominant feature of COPD is airway remodeling, which includes increased airway smooth muscle (ASM) mass. The mechanisms underlying ASM remodeling in COPD have not yet been fully elucidated. Here, we show that nicotine induces a profound and time-dependent increase in DNA synthesis in rat airway smooth muscle cells (RASMCs) in vitro. Nicotine also significantly increased the number of RASMCs, which was associated with the increased expression of Cyclin D1, phosphorylation of the retinoblastoma protein (RB) and was dependent on the activation of Akt. The activation of Akt by nicotine occurred within minutes and depended upon the nicotinic acetylcholine receptors (nAchRs). Activated Akt increased the phosphorylation of downstream substrates such as GSK3β. Our data suggest that the binding of nicotine to the nAchRs on RASMCs can regulate cellular proliferation by activating the Akt pathway. PMID:24690900

Platelet-, leucocyte- and red cell-derived microparticles in stored whole blood, with and without leucofiltration, with and without ionising radiation.

PubMed

Saito, Shunnichi; Nollet, Kenneth E; Ngoma, Alain M; Ono, Takako; Ohto, Hitoshi

2018-02-01

Storage lesion, including microparticle formation, has been partially characterised in whole blood, but not in all combinations of pre-storage leucofiltration and/or irradiation. Single-donor whole blood products were processed into four subunits: with and without leucofiltration, with and without X-irradiation (25 Gy). Platelet-, leucocyte-, and erythrocyte-derived microparticles and free haemoglobin were measured periodically throughout 42 days of storage. Pre-storage leucofiltration substantially reduced platelet- and leucocyte-derived microparticle counts throughout storage. Irradiation, in contrast, had no significant effect on microparticle counts. A gate for all microparticles showed a substantial time-dependent increase in unfiltered whole blood. A time-dependent increase in free haemoglobin was greatest in unfiltered, irradiated whole blood. This study indicates that leucofiltration can prevent the formation of leucocyte- and platelet-derived microparticles, and might reduce haemolysis in irradiated whole blood, either by removing factors that provoke haemolysis, or by selective retention of senescent or effete red cells most prone to haemolysis.

The influence of chronic hypoxia upon chemoreception

PubMed Central

Powell, Frank L.

2007-01-01

Carotid body chemoreceptors are essential for time-dependent changes in ventilatory control during chronic hypoxia. Early theories of ventilatory acclimatization to hypoxia focused on time-dependent changes in known ventilatory stimuli, such as small changes in arterial pH that may play a significant role in some species. However, plasticity in the cellular and molecular mechanisms of carotid body chemoreception play a major role in ventilatory acclimatization to hypoxia in all species studied. Chronic hypoxia causes changes in (a) ion channels (potassium, sodium, calcium) to increase glomus cell excitability, and (b) neurotransmitters (dopamine, acetylcholine, ATP) and neuromodulators (endothelin-1) to increase carotid body afferent activity for a given PO2 and optimize O2-sensitivity. O2-sensing heme-containing molecules in the carotid body have not been studied in chronic hypoxia. Plasticity in medullary respiratory centers processing carotid body afferent input also contributes to ventilatory acclimatization to hypoxia. It is not known if the same mechanisms occur in patients with chronic hypoxemia from lung disease or high altitude natives. PMID:17291837

Impact of grade separator on pedestrian risk taking behavior.

PubMed

Khatoon, Mariya; Tiwari, Geetam; Chatterjee, Niladri

2013-01-01

Pedestrians on Delhi roads are often exposed to high risks. This is because the basic needs of pedestrians are not recognized as a part of the urban transport infrastructure improvement projects in Delhi. Rather, an ever increasing number of cars and motorized two-wheelers encourage the construction of large numbers of flyovers/grade separators to facilitate signal free movement for motorized vehicles, exposing pedestrians to greater risk. This paper describes the statistical analysis of pedestrian risk taking behavior while crossing the road, before and after the construction of a grade separator at an intersection of Delhi. A significant number of pedestrians are willing to take risks in both before and after situations. The results indicate that absence of signals make pedestrians behave independently, leading to increased variability in their risk taking behavior. Variability in the speeds of all categories of vehicles has increased after the construction of grade separators. After the construction of the grade separator, the waiting time of pedestrians at the starting point of crossing has increased and the correlation between waiting times and gaps accepted by pedestrians show that after certain time of waiting, pedestrians become impatient and accepts smaller gap size to cross the road. A Logistic regression model is fitted by assuming that the probability of road crossing by pedestrians depends on the gap size (in s) between pedestrian and conflicting vehicles, sex, age, type of pedestrians (single or in a group) and type of conflicting vehicles. The results of Logistic regression explained that before the construction of the grade separator the probability of road crossing by the pedestrian depends on only the gap size parameter; however after the construction of the grade separator, other parameters become significant in determining pedestrian risk taking behavior. Copyright © 2012 Elsevier Ltd. All rights reserved.

Glucocorticoids enhance and suppress heart rate and behaviour in time dependent manner in greylag geese (Anser anser).

PubMed

Kralj-Fiser, Simona; Scheiber, Isabella B R; Kotrschal, Kurt; Weiss, Brigitte M; Wascher, Claudia A F

2010-06-16

Stress responses involve autonomic, endocrine and behavioural changes. Each of these responses has been studied thoroughly in avian species, but hardly in an integrative way, in free-living birds. This is necessary to reveal the temporal dynamics of the stress response. Towards that goal, we recorded heart rate (HR) and behaviour in free-ranging male greylag geese (Anser anser) simultaneously over 2h. The geese were subjected to (a) unmanipulated control condition, (b) capture, handling and injection of ACTH, and (c) capture, handling and injection of a saline solution (SHAM). Fecal samples for the non-invasive determination of immuno-reactive glucocorticoid metabolite (BM) concentrations were collected for 7h thereafter. The SHAM control caused a significant BM increase, a transient increase in HR, an initial increase of preening behaviour and a delay in feeding. ACTH treatment, relative to SHAM, produced significantly higher BM concentrations, and activation of "displacement behaviours" such as wing flapping, body shaking and preening. Also, feeding activity as well as resting was postponed and/or lower for a longer period of time after ACTH than after SHAM. ACTH injection had a greater effect than SHAM injection on HR increase in the first hour, but particularly on HR decline in the second hour following the injection. Hence, glucocorticoids had time- and dose-dependent stimulatory and suppressive effects on cardiovascular activity and behaviour. HR dynamics after ACTH actually matched with behavioural dynamics: both were first enhanced and later suppressed, which is in alignment with adaptive stress management involving the fight-flight response and recovery from stress, respectively. (c) 2010 Elsevier Inc. All rights reserved.

Dynamics of exciton magnetic polarons in CdMnSe/CdMgSe quantum wells: Effect of self-localization

NASA Astrophysics Data System (ADS)

Akimov, I. A.; Godde, T.; Kavokin, K. V.; Yakovlev, D. R.; Reshina, I. I.; Sedova, I. V.; Sorokin, S. V.; Ivanov, S. V.; Kusrayev, Yu. G.; Bayer, M.

2017-04-01

We study the exciton magnetic polaron (EMP) formation in (Cd,Mn)Se/(Cd,Mg)Se diluted-magnetic-semiconductor quantum wells by using time-resolved photoluminescence (PL). The magnetic-field and temperature dependencies of this dynamics allow us to separate the nonmagnetic and magnetic contributions to the exciton localization. We deduce the EMP energy of 14 meV, which is in agreement with time-integrated measurements based on selective excitation and the magnetic-field dependence of the PL circular polarization degree. The polaron formation time of 500 ps is significantly longer than the corresponding values reported earlier. We propose that this behavior is related to strong self-localization of the EMP, accompanied with a squeezing of the heavy-hole envelope wave function. This conclusion is also supported by the decrease of the exciton lifetime from 600 ps to 200-400 ps with increasing magnetic field and temperature.

Trends in the suspended-sediment yields of coastal rivers of northern California, 1955–2010

USGS Publications Warehouse

Warrick, J.A.; Madej, Mary Ann; Goñi, M. A.; Wheatcroft, R.A.

2013-01-01

Time-dependencies of suspended-sediment discharge from six coastal watersheds of northern California – Smith River, Klamath River, Trinity River, Redwood Creek, Mad River, and Eel River – were evaluated using monitoring data from 1955 to 2010. Suspended-sediment concentrations revealed time-dependent hysteresis and multi-year trends. The multi-year trends had two primary patterns relative to river discharge: (i) increases in concentration resulting from both land clearing from logging and the flood of record during December 1964 (water year 1965), and (ii) continual decreases in concentration during the decades following this flood. Data from the Eel River revealed that changes in suspended-sediment concentrations occurred for all grain-size fractions, but were most pronounced for the sand fraction. Because of these changes, the use of bulk discharge-concentration relationships (i.e., “sediment rating curves”) without time-dependencies in these relationships resulted in substantial errors in sediment load estimates, including 2.5-fold over-prediction of Eel River sediment loads since 1979. We conclude that sediment discharge and sediment discharge relationships (such as sediment rating curves) from these coastal rivers have varied substantially with time in response to land use and climate. Thus, the use of historical river sediment data and sediment rating curves without considerations for time-dependent trends may result in significant errors in sediment yield estimates from the globally-important steep, small watersheds.

Effects of DETANONOate, a nitric oxide donor, on hemostasis in rabbits: an in vitro and in vivo thrombelastographic analysis.

PubMed

Nielsen, V G; Geary, B T; Baird, M S

2000-03-01

The purpose of this study was to determine if whole blood thrombelastographic variables (reaction time, K, alpha, and maximum amplitude) would be adversely effected by exposure to the nitric oxide (NO) donor, DETANONOate, in vitro or after alveolar instillation in vivo. Conscious rabbits (n = 10) had blood sampled from ear arteries anticoagulated with sodium citrate. The blood was then incubated with 0, 1, 5, 10, or 20 mmol/L DETANONOate for 30 minutes. Arterial blood from anesthetized rabbits (n = 4) was obtained and anticoagulated before and 60 minutes after 1 mmol/L DETANONOate (2 mL/kg) was instilled into the right lung. After incubation, all samples were placed in a thrombelastograph and recalcified, with thrombelastographic variables measured for 45 minutes. In vitro, 10 mmol/L DETANONOate significantly (P < .05) increased reaction time, K, and decreased alpha compared with values observed after incubation with 0, 1, and 5 mmol/L DETANONOate. Twenty mmol/L DETANONOate significantly (P < .05) increased reaction time, K, and decreased alpha and maximum amplitude values compared with all other concentrations. In vivo, DETANONOate administration did not significantly affect thrombelastographic variables. DETANONOate significantly decreased hemostatic function in vitro in a dose-dependent fashion but did not significantly affect hemostatic function in vivo.

The Pursuit of Romantic Alternatives Online: Social Media Friends as Potential Alternatives.

PubMed

Abbasi, Irum Saeed; Alghamdi, Nawal G

2018-01-02

What causes some marriages to stand the test of time while others fail? Marital commitment is the key force underlying the stability, quality, and longevity of the romantic relationship. Commitment is strengthened in the presence of marital satisfaction, the absence of alternative attractions, and steady investments made in the relationship. Commitment is also a consequence of increasing dependence. When partners are emotionally engaged with their virtual connections, their dependence on the significant other decreases. On the contrary, dependence on the partner increases when people feel satisfied with their relationship, think unfavorably about the quality of available alternatives, and feel that they have made great investments in their relationship. Technological advancements of the present era have spawned a wide array of social networking sites (SNSs) that display boastfully curated profiles of virtual connections. These overly glossed profiles may lead social media users to feel deficient in their lives. Previous research has shown that Facebook use can reduce relationship satisfaction by providing potential romantic alternatives and deflecting time and emotional investments away from the committed relationship. This article examines the commitment literature and discusses how commitment is undermined in the contemporary era. Finally, marital therapy is addressed with suggestions for future areas of exploration.

Structure and phylogenetic diversity of post-fire ectomycorrhizal communities of maritime pine.

PubMed

Rincón, A; Santamaría, B P; Ocaña, L; Verdú, M

2014-02-01

Environmental disturbances define the diversity and assemblage of species, affecting the functioning of ecosystems. Fire is a major disturbance of Mediterranean pine forests. Pines are highly dependent on the ectomycorrhizal (EM) fungal symbiosis, which is critical for tree recruitment under primary succession. To determine the effects of time since fire on the structure and recovery of EM fungal communities, we surveyed the young Pinus pinaster regenerate in three sites differing in the elapsed time after the last fire event. Pine roots were collected, and EM fungi characterized by sequencing the internal transcribed spacer (ITS) and the large subunit (LSU) regions of the nuclear ribosomal (nr)-DNA. The effects of the elapsed time after fire on the EM community structure (richness, presence/absence of fungi, phylogenetic diversity) and on soil properties were analysed.Fungal richness decreased with the elapsed time since the fire; although, the phylogenetic diversity of the EM community increased. Soil properties were different depending on the elapsed time after fire and particularly, the organic matter, carbon-to-nitrogen (C/N) ratio, nitrogen and iron significantly correlated with the assemblage of fungal species. Ascomycetes, particularly Tuberaceae and Pezizales, were significantly over-represented on saplings in the burned site. On seedlings, a significant over-representation of Rhizopogonaceae and Atheliaceae was observed in the most recently burned site, while other fungi (i.e. Cortinariaceae) were significantly under-represented. Our results are consistent with the hypothesis that fire can act as a selective agent by printing a phylogenetic signal on the EM fungal communities associated with naturally regenerated pines, pointing out to some groups as potential fire-adapted fungi.

Computational Examination of Orientation-Dependent Morphological Evolution during the Electrodeposition and Electrodissolution of Magnesium

DOE PAGES

DeWitt, S.; Hahn, N.; Zavadil, K.; ...

2015-12-30

Here a new model of electrodeposition and electrodissolution is developed and applied to the evolution of Mg deposits during anode cycling. The model captures Butler-Volmer kinetics, facet evolution, the spatially varying potential in the electrolyte, and the time-dependent electrolyte concentration. The model utilizes a diffuse interface approach, employing the phase field and smoothed boundary methods. Scanning electron microscope (SEM) images of magnesium deposited on a gold substrate show the formation of faceted deposits, often in the form of hexagonal prisms. Orientation-dependent reaction rate coefficients were parameterized using the experimental SEM images. Three-dimensional simulations of the growth of magnesium deposits yieldmore » deposit morphologies consistent with the experimental results. The simulations predict that the deposits become narrower and taller as the current density increases due to the depletion of the electrolyte concentration near the sides of the deposits. Increasing the distance between the deposits leads to increased depletion of the electrolyte surrounding the deposit. Two models relating the orientation-dependence of the deposition and dissolution reactions are presented. Finally, the morphology of the Mg deposit after one deposition-dissolution cycle is significantly different between the two orientation-dependence models, providing testable predictions that suggest the underlying physical mechanisms governing morphology evolution during deposition and dissolution.« less

Density-dependent changes of the pore properties of the P2X2 receptor channel

PubMed Central

Fujiwara, Yuichiro; Kubo, Yoshihiro

2004-01-01

Ligand-gated ion channels underlie and play important roles in synaptic transmission, and it is generally accepted that the ion channel pores have a rigid structure that enables strict regulation of ion permeation. One exception is the P2X ATP-gated channel. After application of ATP, the ion selectivity of the P2X2 channel time-dependently changes, i.e. permeability to large cations gradually increases, and there is significant cell-to-cell variation in the intensity of inward rectification. Here we show P2X2 channel properties are correlated with the expression level: increasing P2X2 expression level in oocytes increases permeability to large cations, decreases inward rectification and increases ligand sensitivity. We also observed that the inward rectification changed in a dose-dependent manner, i.e. when low concentration of ATP was applied to an oocyte with a high expression level, the intensity of inward rectification of the evoked current was weak. Taken together, these results show that the pore properties of P2X2 channel are not static but change dynamically depending on the open channel density. Furthermore, we identified by mutagenesis study that Ile328 located at the outer mouth of the pore is critical for the density-dependent changes of P2X2. Our findings suggest synaptic transmission can be modulated by the local density-dependent changes of channel properties caused, for example, by the presence of clustering molecules. PMID:15107474

Cognitive vulnerability to depression in Canadian and Chinese adolescents.

PubMed

Auerbach, Randy P; Eberhart, Nicole K; Abela, John R Z

2010-01-01

The goal of the current study was to compare diathesis-stress and transactional models of cognitive vulnerability to depression in samples of Canadian (n = 118) and Chinese (n = 405) adolescents. We utilized a six-month multi-wave, longitudinal design in order to examine whether (a) perceived control moderated the association between the occurrence of dependent interpersonal stressors and subsequent increases in depressive symptoms (i.e., a diathesis-stress perspective) and (b) dependent interpersonal stressors mediated the association between perceived control and subsequent increases in depressive symptoms (i.e., a transactional perspective). Results from idiographic, time-lagged, hierarchical linear modeling analyses indicated that for Canadian adolescents both diathesis-stress and transactional models were significant predictors of depressive symptomology. When examining the diathesis-stress model, boys, but not girls, who reported lower perceived control, reported higher levels of depressive symptoms following the occurrence of dependent interpersonal stress. Gender differences, however, were not present in the transactional model. In contrast, transactional, but not diathesis-stress, models were significant in Chinese adolescents, and gender differences did not emerge. Overall, these results may reflect culturally-relevant differences in the etiology of depression in Canadian and Chinese adolescents.

Histological, molecular and biochemical detection of renal injury after Echis pyramidum snake envenomation in rats

PubMed Central

Al-Johany, Awadh M.; Al-Sadoon, Mohamed K.; Abdel Moneim, Ahmed E.; Bauomy, Amira A.; Diab, Marwa S.M.

2014-01-01

Nephrotoxicity is a common sign of snake envenomation. The present work aimed to clarify the effect of intraperitoneal injection of 1/8 LD50 and 1/4 LD50 doses of Echis pyramidum snake venom on the renal tissue of rats after 2, 4 and 6 h from envenomation. Histopathological examination showed intense dose and time dependent abnormalities, including swelling glomerulus and tubular necrosis and damage as well as signs of intertubular medullary hemorrhage at early stages of envenomation. However, at late stages of envenomation by any of the doses under investigation, no intact renal corpuscles were recorded and complete lysis in renal corpuscles with ruptured Bowman’s capsules was observed. Immunohistochemistry by immunohistochemical staining was used to test the protein expression of Bax in renal tissue of rats. The result showed that the expression of Bax in renal tissue sections of envenomated rats was increased according to dose and time-dependant manner. The isolation of DNA from the renal cells of envenomed rats pointed out to the occurrence of DNA fragmentation, which is another indicator for renal tissue injury especially after 6 h of 1/4 LD50 of E. pyramidum envenomation. Oxidative stress biomarkers malondialdehyde and nitrite/nitrate levels, antioxidant parameters; glutathione, total antioxidant capacity and catalase were assayed in renal tissue homogenates. The venom induced significant increase in the levels of malondialdehyde and nitrite/nitrate while the levels of glutathione, total antioxidant capacity and catalase were significantly decreased, especially after 6 h of envenomation. The results revealed that the E. pyramidum induced dose and time-dependant significant disturbances in the physiological parameters in the kidney. We conclude that the use of the immunohistochemical techniques, the detection of DNA integrity and oxidative stress marker estimations are more specific tools that can clarify cellular injury and could point out to the defense activity of the renal tissue at envenomation. PMID:25972751

Histological, molecular and biochemical detection of renal injury after Echis pyramidum snake envenomation in rats.

PubMed

Al-Johany, Awadh M; Al-Sadoon, Mohamed K; Abdel Moneim, Ahmed E; Bauomy, Amira A; Diab, Marwa S M

2015-05-01

Nephrotoxicity is a common sign of snake envenomation. The present work aimed to clarify the effect of intraperitoneal injection of 1/8 LD50 and 1/4 LD50 doses of Echis pyramidum snake venom on the renal tissue of rats after 2, 4 and 6 h from envenomation. Histopathological examination showed intense dose and time dependent abnormalities, including swelling glomerulus and tubular necrosis and damage as well as signs of intertubular medullary hemorrhage at early stages of envenomation. However, at late stages of envenomation by any of the doses under investigation, no intact renal corpuscles were recorded and complete lysis in renal corpuscles with ruptured Bowman's capsules was observed. Immunohistochemistry by immunohistochemical staining was used to test the protein expression of Bax in renal tissue of rats. The result showed that the expression of Bax in renal tissue sections of envenomated rats was increased according to dose and time-dependant manner. The isolation of DNA from the renal cells of envenomed rats pointed out to the occurrence of DNA fragmentation, which is another indicator for renal tissue injury especially after 6 h of 1/4 LD50 of E. pyramidum envenomation. Oxidative stress biomarkers malondialdehyde and nitrite/nitrate levels, antioxidant parameters; glutathione, total antioxidant capacity and catalase were assayed in renal tissue homogenates. The venom induced significant increase in the levels of malondialdehyde and nitrite/nitrate while the levels of glutathione, total antioxidant capacity and catalase were significantly decreased, especially after 6 h of envenomation. The results revealed that the E. pyramidum induced dose and time-dependant significant disturbances in the physiological parameters in the kidney. We conclude that the use of the immunohistochemical techniques, the detection of DNA integrity and oxidative stress marker estimations are more specific tools that can clarify cellular injury and could point out to the defense activity of the renal tissue at envenomation.

Time-dependent probability density functions and information geometry in stochastic logistic and Gompertz models

NASA Astrophysics Data System (ADS)

Tenkès, Lucille-Marie; Hollerbach, Rainer; Kim, Eun-jin

2017-12-01

A probabilistic description is essential for understanding growth processes in non-stationary states. In this paper, we compute time-dependent probability density functions (PDFs) in order to investigate stochastic logistic and Gompertz models, which are two of the most popular growth models. We consider different types of short-correlated multiplicative and additive noise sources and compare the time-dependent PDFs in the two models, elucidating the effects of the additive and multiplicative noises on the form of PDFs. We demonstrate an interesting transition from a unimodal to a bimodal PDF as the multiplicative noise increases for a fixed value of the additive noise. A much weaker (leaky) attractor in the Gompertz model leads to a significant (singular) growth of the population of a very small size. We point out the limitation of using stationary PDFs, mean value and variance in understanding statistical properties of the growth in non-stationary states, highlighting the importance of time-dependent PDFs. We further compare these two models from the perspective of information change that occurs during the growth process. Specifically, we define an infinitesimal distance at any time by comparing two PDFs at times infinitesimally apart and sum these distances in time. The total distance along the trajectory quantifies the total number of different states that the system undergoes in time, and is called the information length. We show that the time-evolution of the two models become more similar when measured in units of the information length and point out the merit of using the information length in unifying and understanding the dynamic evolution of different growth processes.

Logarithmic contact time dependence of adhesion force and its dominant role among the effects of AFM experimental parameters under low humidity

NASA Astrophysics Data System (ADS)

Lai, Tianmao; Meng, Yonggang

2017-10-01

The influences of contact time, normal load, piezo velocity, and measurement number of times on the adhesion force between two silicon surfaces were studied with an atomic force microscope (AFM) at low humidity (17-15%). Results show that the adhesion force is time-dependent and increases logarithmically with contact time until saturation is reached, which is related with the growing size of a water bridge between them. The contact time plays a dominant role among these parameters. The adhesion forces with different normal loads and piezo velocities can be quantitatively obtained just by figuring out the length of contact time, provided that the contact time dependence is known. The time-dependent adhesion force with repeated contacts at one location usually increases first sharply and then slowly with measurement number of times until saturation is reached, which is in accordance with the contact time dependence. The behavior of the adhesion force with repeated contacts can be adjusted by the lengths of contact time and non-contact time. These results may help facilitate the anti-adhesion design of silicon-based microscale systems working under low humidity.

Time-dependent friction and the mechanics of stick-slip

USGS Publications Warehouse

Dieterich, J.H.

1978-01-01

Time-dependent increase of static friction is characteristic of rock friction undera variety of experimental circumstances. Data presented here show an analogous velocity-dependent effect. A theor of friction is proposed that establishes a common basis for static and sliding friction. Creep at points of contact causes increases in friction that are proportional to the logarithm of the time that the population of points of contact exist. For static friction that time is the time of stationary contact. For sliding friction the time of contact is determined by the critical displacement required to change the population of contacts and the slip velocity. An analysis of a one-dimensional spring and slider system shows that experimental observations establishing the transition from stable sliding to stick-slip to be a function of normal stress, stiffness and surface finish are a consequence of time-dependent friction. ?? 1978 Birkha??user Verlag.

Curcumin induces apoptosis and cell cycle arrest via the activation of reactive oxygen species-independent mitochondrial apoptotic pathway in Smad4 and p53 mutated colon adenocarcinoma HT29 cells.

PubMed

Agarwal, Ayushi; Kasinathan, Akiladdevi; Ganesan, Ramamoorthi; Balasubramanian, Akhila; Bhaskaran, Jahnavi; Suresh, Samyuktha; Srinivasan, Revanth; Aravind, K B; Sivalingam, Nageswaran

2018-03-01

Curcumin is a natural dietary polyphenol compound that has various pharmacological activities such as antiproliferative and cancer-preventive activities on tumor cells. Indeed, the role reactive oxygen species (ROS) generated by curcumin on cell death and cell proliferation inhibition in colon cancer is poorly understood. In the present study, we hypothesized that curcumin-induced ROS may promote apoptosis and cell cycle arrest in colon cancer. To test this hypothesis, the apoptosis-inducing potential and cell cycle inhibition effect of ROS induced by curcumin was investigated in Smd4 and p53 mutated HT-29 colon adenocarcinoma cells. We found that curcumin treatment significantly increased the level of ROS in HT-29 cells in a dose- and time-dependent manner. Furthermore, curcumin treatment markedly decreased the cell viability and proliferation potential of HT-29 cells in a dose- and time-dependent manner. Conversely, generation of ROS and inhibitory effect of curcumin on HT-29 cells were abrogated by N-acetylcysteine treatment. In addition, curcumin treatment did not show any cytotoxic effects on HT-29 cells. Furthermore, curcumin-induced ROS generation caused the DNA fragmentation, chromatin condensation, and cell nuclear shrinkage and significantly increased apoptotic cells in a dose- and time-dependent manner in HT-29 cells. However, pretreatment of N-acetylcysteine inhibited the apoptosis-triggering effect of curcumin-induced ROS in HT-29 cells. In addition, curcumin-induced ROS effectively mediated cell cycle inhibition in HT-29 cells. In conclusion, our data provide the first evidence that curcumin induces ROS independent apoptosis and cell cycle arrest in colon cancer cells that carry mutation on Smad4 and p53. Copyright © 2018. Published by Elsevier Inc.

Study of damage to red blood cells exposed to different doses of γ-ray irradiation.

PubMed

Xu, Deyi; Peng, Mingxi; Zhang, Zhe; Dong, Guofei; Zhang, Yiqin; Yu, Hongwei

2012-07-01

The aims of this research were to study alterations in the ultrastructure of red blood cells, the changes in concentrations of plasma electrolytes and the killing effect of lymphocytes in samples of blood exposed to different doses of γ-ray irradiation. Blood samples were treated with different doses of γ-ray irradiation and then preserved for different periods. Specimens were prepared for standard electron microscopy and transmission electron microscopy. At the same time, changes in the concentrations of Na(+), K(+) and Cl(-) and pH values in the plasma as well as Fas and FasL expression of lymphocytes before and after irradiation were determined. The proportions of reversibly and irreversibly transformed cells, for example, echinocytes, sphero-echinocytes, and degenerated forms, increased with increasing doses of irradiation and storage period, while the number of discocyte shaped red blood cells decreased. The change in K(+) concentration was greater than that of Na+ or Cl(-) after irradiation and was dosage-dependent. Plasma pH was influenced by different doses of radiation and storage time. After exposure to (137)Cs γ-irradiation, the expression of both Fas and FasL in lymphocytes differed significantly from that in the control group: the expression was positively correlated with irradiation dose (r=0.95, 0.96), but no significant difference in the Fas/FasL ratio was observed (P>0.05). We conclude that the ultrastructure of red blood cells is not changed obviously by irradiation with some doses of γ-rays and various periods of storage. However, irradiation does have some dose-dependent and time-dependent adverse effects on the erythrocytes.

Time-of-Day Dependent Neuronal Injury After Ischemic Stroke: Implication of Circadian Clock Transcriptional Factor Bmal1 and Survival Kinase AKT.

PubMed

Beker, Mustafa Caglar; Caglayan, Berrak; Yalcin, Esra; Caglayan, Ahmet Burak; Turkseven, Seyma; Gurel, Busra; Kelestemur, Taha; Sertel, Elif; Sahin, Zafer; Kutlu, Selim; Kilic, Ulkan; Baykal, Ahmet Tarik; Kilic, Ertugrul

2018-03-01

Occurrence of stroke cases displays a time-of-day variation in human. However, the mechanism linking circadian rhythm to the internal response mechanisms against pathophysiological events after ischemic stroke remained largely unknown. To this end, temporal changes in the susceptibility to ischemia/reperfusion (I/R) injury were investigated in mice in which the ischemic stroke induced at four different Zeitgeber time points with 6-h intervals (ZT0, ZT6, ZT12, and ZT18). Besides infarct volume and brain swelling, neuronal survival, apoptosis, ischemia, and circadian rhythm related proteins were examined using immunohistochemistry, Western blot, planar surface immune assay, and liquid chromatography-mass spectrometry tools. Here, we present evidence that midnight (ZT18; 24:00) I/R injury in mice resulted in significantly improved infarct volume, brain swelling, neurological deficit score, neuronal survival, and decreased apoptotic cell death compared with ischemia induced at other time points, which were associated with increased expressions of circadian proteins Bmal1, PerI, and Clock proteins and survival kinases AKT and Erk-1/2. Moreover, ribosomal protein S6, mTOR, and Bad were also significantly increased, while the levels of PRAS40, negative regulator of AKT and mTOR, and phosphorylated p53 were decreased at this time point compared to ZT0 (06:00). Furthermore, detailed proteomic analysis revealed significantly decreased CSKP, HBB-1/2, and HBA levels, while increased GNAZ, NEGR1, IMPCT, and PDE1B at midnight as compared with early morning. Our results indicate that nighttime I/R injury results in less severe neuronal damage, with increased neuronal survival, increased levels of survival kinases and circadian clock proteins, and also alters the circadian-related proteins.

Internet use and its impact on engagement in leisure activities in China.

PubMed

Zhou, Ronggang; Fong, Patrick S W; Tan, Peking

2014-01-01

Internet use has become an increasingly common leisure time activity among Chinese citizens. The association between Internet use and engagement in leisure activities is especially unclear among China population. This study aims to investigate Internet usage and to determine whether active Internet use is a marker for low or high levels of leisure time activities. With the use of a face-to-face structured questionnaire interview, a total of 2,400 respondents who met all screening requirements were surveyed to answer the questions in eight major cities in China. 66.2% (n = 1,589) of all respondents were identified as Internet users. Of these Internet users, 30.0%, 24.1%, 26.4%, and 19.6% were clustered as "informative or instrumental users," "entertainment users," "communication users," and "advanced users," respectively. Regarding time spent on Internet use in leisure time, more than 96% reported going online in non-work situations, and 26.2% (n = 416) were classified as "heavy Internet users." A logistic regression analysis revealed that there were significant differences in some leisure activities between non-Internet users and Internet users, with an observed one-unit increase in the leisure time dependence category increasing the probability of engaging in mental or social activities. In contrast, Internet users were less engaged in physical exercise-related activities. In addition, advanced Internet users were generally more active in leisure time activities than non-Internet users and other types of users. Internet use is one of very common leisure activities in Chinese citizens, and age, gender, income, and education are the key factors affecting Internet access. According to different types of leisure activities, Internet usage has different impacts on leisure activity engagement. High Internet dependence has no significant negative influence on engagement in mental or social leisure activities, but this group respondent tended to be less engaged in physical activities.

Measuring trends of outpatient antibiotic use in Europe: jointly modelling longitudinal data in defined daily doses and packages.

PubMed

Bruyndonckx, Robin; Hens, Niel; Aerts, Marc; Goossens, Herman; Molenberghs, Geert; Coenen, Samuel

2014-07-01

To complement analyses of the linear trend and seasonal fluctuation of European outpatient antibiotic use expressed in defined daily doses (DDD) by analyses of data in packages, to assess the agreement between both measures and to study changes in the number of DDD per package over time. Data on outpatient antibiotic use, aggregated at the level of the active substance (WHO version 2011) were collected from 2000 to 2007 for 31 countries and expressed in DDD and packages per 1000 inhabitants per day (DID and PID, respectively). Data expressed in DID and PID were analysed separately using non-linear mixed models while the agreement between these measurements was analysed through a joint non-linear mixed model. The change in DDD per package over time was studied with a linear mixed model. Total outpatient antibiotic and penicillin use in Europe and their seasonal fluctuation significantly increased in DID, but not in PID. The use of combinations of penicillins significantly increased in DID and in PID. Broad-spectrum penicillin use did not increase significantly in DID and decreased significantly in PID. For all but one subgroup, country-specific deviations moved in the same direction whether measured in DID or PID. The correlations are not perfect. The DDD per package increased significantly over time for all but one subgroup. Outpatient antibiotic use in Europe shows contrasting trends, depending on whether DID or PID is used as the measure. The increase of the DDD per package corroborates the recommendation to adopt PID to monitor outpatient antibiotic use in Europe. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Pyrethroid Insecticides Directly Activate Microglia Through Interaction With Voltage-Gated Sodium Channels.

PubMed

Hossain, Muhammad M; Liu, Jason; Richardson, Jason R

2017-01-01

Microglia are considered to be the resident immune cells of the central nervous system and contribute significantly to ongoing neuroinflammation in a variety of neurodegenerative diseases. Recently, we and others identified that voltage-gated sodium channels (VGSC) are present on microglia cells and contribute to excessive accumulation of intracellular Na +  and release of major pro-inflammatory cytokine tumor necrosis factor alpha (TNF-α). Based on this finding and the fact that pyrethroid pesticides act on VGSC, we hypothesized that exposure of microglia to the pyrethroid pesticides, permethrin and deltamethrin, would activate microglia and increase the release of TNF-α. BV2 cells or primary microglia were treated with 0-5 µM deltamethrin or permethrin in the presence or absence of tetrodotoxin (TTX), a VGSC blocker for 24-48 h. Both pyrethroids caused a rapid Na +  influx and increased accumulation of intracellular sodium [(Na + )i] in the microglia in a dose- and time-dependent manner, which was significantly reduced by TTX. Furthermore, deltamethrin and permethrin increased the release of TNF-α in a dose- and time-dependent manner, which was significantly reduced by pre-treatment of cells with TTX. These results demonstrate that pyrethroid pesticides may directly activate microglial cells through their interaction with microglial VGSC. Because neuroinflammation plays a key role in many neurodegenerative diseases, these data provide an additional mechanism by which exposure to pyrethroid insecticides may contribute to neurodegeneration. © 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.

A significant increase in both basal and maximal calcineurin activity in the rat pilocarpine model of status epilepticus.

PubMed

Kurz, J E; Sheets, D; Parsons, J T; Rana, A; Delorenzo, R J; Churn, S B

2001-07-01

This study focused on the effects of status epilepticus on the activity of calcineurin, a neuronally enriched, calcium-dependent phosphatase. Calcineurin is an important modulator of many neuronal processes, including learning and memory, induction of apoptosis, receptor function and neuronal excitability. Therefore, a status epilepticus-induced alteration of the activity of this important phosphatase would have significant physiological implications. Status epilepticus was induced by pilocarpine injection and allowed to continue for 60 min. Brain region homogenates were then assayed for calcineurin activity by dephosphorylation of p-nitrophenol phosphate. A significant status epilepticus-dependent increase in both basal and Mn(2+)-dependent calcineurin activity was observed in homogenates isolated from the cortex and hippocampus, but not the cerebellum. This increase was resistant to 150 nM okadaic acid, but sensitive to 50 microM okadaic acid. The increase in basal activity was also resistant to 100 microM sodium orthovanadate. Both maximal dephosphorylation rate and substrate affinity were increased following status epilepticus. However, the increase in calcineurin activity was not found to be due to an increase in calcineurin enzyme levels. Finally, increase in calcineurin activity was found to be NMDA-receptor activation dependent. The data demonstrate that status epilepticus resulted in a significant increase in both basal and maximal calcineurin activity.

Effect of salt on turbulent drag reduction of xanthan gum.

PubMed

Hong, Cheng Hai; Choi, Hyoung Jin; Zhang, Ke; Renou, Frederic; Grisel, Michel

2015-05-05

The turbulent flow of an aqueous KCl solution driven by a rotating disc in a closed chamber showed significant drag reduction (DR) when a small amount of xanthan gum (XG) was added. The effects of the experimental parameters (XG and KCl concentrations, and time) on the drag reduction efficiency were examined. While the DR efficiency of XG decreased with increasing salt (KCl) concentration, the time-dependent DR efficiency was found to be fitted well using Brostow model equation. Copyright © 2014 Elsevier Ltd. All rights reserved.

Active eye fixation performance in 940 young men: effects of IQ, schizotypy, anxiety and depression.

PubMed

Smyrnis, N; Kattoulas, E; Evdokimidis, I; Stefanis, N C; Avramopoulos, D; Pantes, G; Theleritis, C; Stefanis, C N

2004-05-01

A total of 940 young men performed a task in which they actively maintained fixation for 50 s in three conditions: a). on a visual target, b). on a visual target while distracting targets appeared briefly on the periphery and c). with no visual target present. The same individuals completed psychometric evaluation tests measuring IQ, schizotypy and current state-dependent psychopathology. The proportion of fixation time decreased and saccade frequency increased in condition b compared wih condition a, and sequentially in condition c compared with condition b. A trend towards a decrease in proportion of fixation time and increase in saccade frequency was found as the subjects maintained fixation during the task and this time-dependent deterioration of performance was again most pronounced in condition c, less so in condition b and absent in condition a. Psychometric test scores were significantly correlated with fixation performance in the population. Worse performance in all three fixation conditions was observed for individuals with lower IQ scores. A deterioration of fixation performance with time in condition b was correlated with disorganization characteristics of schizotypy, suggesting that these individuals had difficulty maintaining active fixation in the presence of increased inhibitory load. A connection of such a difficulty with the frontal lobes and their role in the control of voluntary inhibitory functions is discussed.

The expression of intermediate filament protein nestin and its association with cyclin-dependent kinase 5 in the glomeruli of rats with diabetic nephropathy.

PubMed

Liu, Wei; Zhang, Yue; Liu, Shuxia; Liu, Qingjuan; Hao, Jun; Shi, Yonghong; Zhao, Song; Duan, Huijun

2013-06-01

Podocyte injury plays a crucial role in the development of diabetic nephropathy (DN), but its underlying mechanism remains poorly understood. Emerging evidences suggest that the cytoskeleton disruption is related to podocyte injury. The aim of this study was to investigate whether nestin, a cytoskeleton-associated intermediate filament protein, is involved in the development of DN. Rat diabetes was induced by intraperitoneal injection of streptozotocin. The renal histological changes were investigated by light microscopy and transmission electron microscopy. The location of nestin and vimentin in renal tissues was observed by immunohistochemistry. The protein or messenger RNA levels of nestin and cyclin-dependent kinase 5 (Cdk5) were detected by Western blot and real-time polymerase chain reaction. The relationship between nestin and vimentin was detected by co-immunoprecipitation. Compared with controls, diabetic rats showed significant characteristics of renal damage. The expression of nestin and vimentin in the glomeruli was increased at the early stage of diabetes, which then gradually decreased. Co-immunoprecipitation assays demonstrated that nestin disassembled with vimentin in diabetic rats. The expression of Cdk5 was increased in a time-dependent manner in diabetic rats. The degree of albuminuria in diabetic rats was negatively correlated with nestin and positively correlated with Cdk5. Roscovitine, a Cdk5 inhibitor, reduced the degradation of nestin. Moreover, podocyte injuries were significantly ameliorated by treatment with roscovitine. The intermediate filament protein nestin is associated with development of DN. Blockage of Cdk5 increases the level of nestin and attenuates renal damage, which would provide a useful target for DN therapy.

Pleiotrophin modulates morphine withdrawal but has no effects on morphine-conditioned place preference.

PubMed

Gramage, Esther; Vicente-Rodríguez, Marta; Herradón, Gonzalo

2015-09-14

Pleiotrophin (PTN) is a neurotrophic factor with important functions in addiction and neurodegenerative disorders. Morphine administration induces an increase in the expression of PTN and Midkine (MK), the only other member of this family of cytokines, in brain areas related with the addictive effects of drug of abuse, like the Ventral Tegmental Area or the hippocampus. In spite of previous studies showing that PTN modulates amphetamine and ethanol rewarding effects, and that PTN is involved in morphine-induced analgesia, it was still unknown if the rewarding effects of morphine may be regulated by endogenous PTN. Thus, we aim to study the role of PTN in the reward and physical dependence induced by morphine. We used the Conditioned Place Preference (CPP) paradigm in PTN genetically deficient (PTN-/-) and wild type (WT) mice to assess the rewarding effects of morphine in absence of endogenous PTN. Second, to study if PTN may be involved in morphine physical dependence, naloxone-precipitated withdrawal syndrome was induced in PTN-/- and WT morphine dependent mice. Although the increase in the time spent in the morphine-paired compartment after conditioning tended to be more pronounced in PTN-/- mice, statistical significance was not achieved. The data suggest that PTN does not exert an important role in morphine reward. However, our results clearly indicate that PTN-/- mice develop a more severe withdrawal syndrome than WT mice, characterized as a significant increase in the time standing and in the total incidences of forepaw licking, forepaw tremors, wet dog shake and writhing. The data presented here suggest that PTN is a novel genetic factor that plays a role in morphine withdrawal syndrome. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

The impact of pneumolysin on the macrophage response to Streptococcus pneumoniae is strain-dependent.

PubMed

Harvey, Richard M; Hughes, Catherine E; Paton, Adrienne W; Trappetti, Claudia; Tweten, Rodney K; Paton, James C

2014-01-01

Streptococcus pneumoniae is the world's leading cause of pneumonia, bacteremia, meningitis and otitis media. A major pneumococcal virulence factor is the cholesterol-dependent cytolysin, which has the defining property of forming pores in cholesterol-containing membranes. In recent times a clinically significant and internationally successful serotype 1 ST306 clone has been found to express a non-cytolytic variant of Ply (Ply306). However, while the pneumococcus is a naturally transformable organism, strains of the ST306 clonal group have to date been virtually impossible to transform, severely restricting efforts to understand the role of non-cytolytic Ply in the success of this clone. In this study isogenic Ply mutants were constructed in the D39 background and for the first time in the ST306 background (A0229467) to enable direct comparisons between Ply variants for their impact on the immune response in a macrophage-like cell line. Strains that expressed cytolytic Ply were found to induce a significant increase in IL-1β release from macrophage-like cells compared to the non-cytolytic and Ply-deficient strains in a background-independent manner, confirming the requirement for pore formation in the Ply-dependent activation of the NLRP3 inflammasome. However, cytolytic activity in the D39 background was found to induce increased expression of the genes encoding GM-CSF (CSF2), p19 subunit of IL-23 (IL23A) and IFNβ (IFNB1) compared to non-cytolytic and Ply-deficient D39 mutants, but had no effect in the A0229467 background. The impact of Ply on the immune response to the pneumococcus is highly dependent on the strain background, thus emphasising the importance of the interaction between specific virulence factors and other components of the genetic background of this organism.

The Impact of Pneumolysin on the Macrophage Response to Streptococcus pneumoniae is Strain-Dependent

PubMed Central

Paton, Adrienne W.; Trappetti, Claudia; Tweten, Rodney K.; Paton, James C.

2014-01-01

Streptococcus pneumoniae is the world's leading cause of pneumonia, bacteremia, meningitis and otitis media. A major pneumococcal virulence factor is the cholesterol-dependent cytolysin, which has the defining property of forming pores in cholesterol-containing membranes. In recent times a clinically significant and internationally successful serotype 1 ST306 clone has been found to express a non-cytolytic variant of Ply (Ply306). However, while the pneumococcus is a naturally transformable organism, strains of the ST306 clonal group have to date been virtually impossible to transform, severely restricting efforts to understand the role of non-cytolytic Ply in the success of this clone. In this study isogenic Ply mutants were constructed in the D39 background and for the first time in the ST306 background (A0229467) to enable direct comparisons between Ply variants for their impact on the immune response in a macrophage-like cell line. Strains that expressed cytolytic Ply were found to induce a significant increase in IL-1β release from macrophage-like cells compared to the non-cytolytic and Ply-deficient strains in a background-independent manner, confirming the requirement for pore formation in the Ply-dependent activation of the NLRP3 inflammasome. However, cytolytic activity in the D39 background was found to induce increased expression of the genes encoding GM-CSF (CSF2), p19 subunit of IL-23 (IL23A) and IFNβ (IFNB1) compared to non-cytolytic and Ply-deficient D39 mutants, but had no effect in the A0229467 background. The impact of Ply on the immune response to the pneumococcus is highly dependent on the strain background, thus emphasising the importance of the interaction between specific virulence factors and other components of the genetic background of this organism. PMID:25105894

Analysis of the hologram recording on the novel chloride photo-thermo-refractive glass

NASA Astrophysics Data System (ADS)

Ivanov, S. A.; Nikonorov, N. V.; Dubrovin, V. D.; Krykova, V. A.

2017-05-01

In this research, we present new holographic material based on fluoride photo-thermo-refractive glass(PTR) - chloride PTR glass. One of the benefit of this type of PTR glass is positive refractive index change. During this work, for the first-time volume Bragg gratings were recorded in this kind of material. The first experiments revealed that such gratings are mixed i.e. possess both absorption and phase components. Complex analysis shows that both refractive index and absorption coefficient are modulated inside the grating structure. We found out that at first there is no strict dependence of the refractive index change from dosage, but as we continue the process of thermal treatment - dependence is appear. Exposure influence on the refractive index change for this glass differs from fluoride one and shows some sort of saturation after the exposure of 4-6 J/cm2 . We distinguished refractive index change and absorption coefficient change and observed both behavior with increasing thermal treatment time. We found out that the increase of thermal treatment time results in the significant refractive index change. At the same time the absorption does `not practically change. It was found that maximum modulation of refractive index is comparable with fluoride PTR glass and achieves value of 1600 ppm. The modulation of absorption is equal to induced absorption caused by silver nanoparticles and depends from reading wavelength. Our study shows that almost all absorption is modulated inside the grating.

The protective effect of autophagy on mouse spermatocyte derived cells exposure to 1800MHz radiofrequency electromagnetic radiation.

PubMed

Liu, Kaijun; Zhang, Guowei; Wang, Zhi; Liu, Yong; Dong, Jianyun; Dong, Xiaomei; Liu, Jinyi; Cao, Jia; Ao, Lin; Zhang, Shaoxiang

2014-08-04

The increasing exposure to radiofrequency (RF) radiation emitted from mobile phone use has raised public concern regarding the biological effects of RF exposure on the male reproductive system. Autophagy contributes to maintaining intracellular homeostasis under environmental stress. To clarify whether RF exposure could induce autophagy in the spermatocyte, mouse spermatocyte-derived cells (GC-2) were exposed to 1800MHz Global System for Mobile Communication (GSM) signals in GSM-Talk mode at specific absorption rate (SAR) values of 1w/kg, 2w/kg or 4w/kg for 24h, respectively. The results indicated that the expression of LC3-II increased in a dose- and time-dependent manner with RF exposure, and showed a significant change at the SAR value of 4w/kg. The autophagosome formation and the occurrence of autophagy were further confirmed by GFP-LC3 transient transfection assay and transmission electron microscopy (TEM) analysis. Furthermore, the conversion of LC3-I to LC3-II was enhanced by co-treatment with Chloroquine (CQ), indicating autophagic flux could be enhanced by RF exposure. Intracellular ROS levels significantly increased in a dose- and time-dependent manner after cells were exposed to RF. Pretreatment with anti-oxidative NAC obviously decreased the conversion of LC3-I to LC3-II and attenuated the degradation of p62 induced by RF exposure. Meanwhile, phosphorylated extracellular-signal-regulated kinase (ERK) significantly increased after RF exposure at the SAR value of 2w/kg and 4w/kg. Moreover, we observed that RF exposure did not increase the percentage of apoptotic cells, but inhibition of autophagy could increase the percentage of apoptotic cells. These findings suggested that autophagy flux could be enhanced by 1800MHz GSM exposure (4w/kg), which is mediated by ROS generation. Autophagy may play an important role in preventing cells from apoptotic cell death under RF exposure stress. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Investigating the dependence of BOLD contrast on oxidative metabolism.

PubMed

Schwarzbauer, C; Heinke, W

1999-03-01

Most functional magnetic resonance imaging (fMRI) studies are based on measuring the changes in the blood oxygenation level-dependent (BOLD) contrast that arise from a complex interplay between cerebral hemodynamics and oxidative metabolism. To separate these effects, we consecutively applied two different stimuli: visual stimulation (black/white checkerboard alternating with a frequency of 8 Hz) and hypercapnia (inspiration of 5% CO2). Changes in cerebral blood flow (deltaCBF) and the effective transverse relaxation time (T2*) were measured in an interleaved manner by combining a previously described spin-labeling technique with BOLD-based fMRI. In six healthy volunteers, T2* was significantly longer during hypercapnia than during visual stimulation, whereas the corresponding deltaCBF values were the same at the given level of significance (P<0.01). This finding is explained by a significant increase in oxygen consumption under visual stimulation. The average T2* changes in the visual cortex related to cerebral hemodynamics and oxidative metabolism were 10.6+/-3.0% and -4.7+/-1.2%, respectively, resulting in a net increase of 5.9+/-2.3%. Although the hemodynamic effect is dominant, the increase in oxidative metabolism gives rise to a significant decrease in BOLD contrast. The calculated average change in the cerebral metabolic rate of oxygen (CMRO2), 4.4+/-1.1% (N = 6), is in excellent agreement with previous results obtained by positron emission tomography.

Anesthetic activity of plant essential oils on Cyprinus carpio (koi carp).

PubMed

Khumpirapang, Nattakanwadee; Pikulkaew, Surachai; Anuchapreeda, Songyot; Okonogi, Siriporn

2018-03-19

The aims of this study were to investigate the anesthetic and cytotoxic effects of essential oils (EOs) of Ocimum basilicum (OBO), O. canum (OCO), and O. sanctum (OSO) on Cyprinus carpio (koi carp). For anesthetic effect, induction time to surgical anesthesia and recovery time were determined. For cytotoxicity effect, viability of fish peripheral blood nuclear cells (PBMCs) was investigated. Results indicated that increasing oil concentration caused significant (p < 0.01) decrease of induction time. OSO at 100, 200, and 300 mg/L gave the induction time of 169.5 ± 10.2, 62.8 ± 2.3, 45.3 ± 2.2 sec, respectively, significantly shorter than OCO, and OBO. The recovery time of anesthetized fish was dose dependent (p <0.01). Among them, OCO showed the longest recovery time of 313.0 ± 8.1, 420.7 ± 12.6, 616.6 ± 12.1 sec for concentrations of 100, 200, and 300 mg/L, respectively, followed by OSO and OBO, respectively. Within 10 min contact time of the EOs and fish PBMCs, the fish PBMC viability was higher than 80%. Increase contact time and EO concentration caused an increase in cytotoxicity to fish PBMC. OBO showed less toxic than OSO and OCO. Based on the desired induction and recovery times for anesthetizing koi carp, OBO, OCO, and OSO at 300, 200, and 100 mg/L, respectively were suggested to be the most suitable. It was concluded that OBO, OCO, and OSO can be used as natural anesthetics for fish.

A Perishable Inventory Model with Return

NASA Astrophysics Data System (ADS)

Setiawan, S. W.; Lesmono, D.; Limansyah, T.

2018-04-01

In this paper, we develop a mathematical model for a perishable inventory with return by assuming deterministic demand and inventory dependent demand. By inventory dependent demand, it means that demand at certain time depends on the available inventory at that time with certain rate. In dealing with perishable items, we should consider deteriorating rate factor that corresponds to the decreasing quality of goods. There are also costs involved in this model such as purchasing, ordering, holding, shortage (backordering) and returning costs. These costs compose the total costs in the model that we want to minimize. In the model we seek for the optimal return time and order quantity. We assume that after some period of time, called return time, perishable items can be returned to the supplier at some returning costs. The supplier will then replace them in the next delivery. Some numerical experiments are given to illustrate our model and sensitivity analysis is performed as well. We found that as the deteriorating rate increases, returning time becomes shorter, the optimal order quantity and total cost increases. When considering the inventory-dependent demand factor, we found that as this factor increases, assuming a certain deteriorating rate, returning time becomes shorter, optimal order quantity becomes larger and the total cost increases.

The survival benefit of dual dispatch of EMS and fire-fighters in out-of-hospital cardiac arrest may differ depending on population density--a prospective cohort study.

PubMed

Nordberg, Per; Jonsson, Martin; Forsberg, Sune; Ringh, Mattias; Fredman, David; Riva, Gabriel; Hasselqvist-Ax, Ingela; Hollenberg, Jacob

2015-05-01

Outcome after out-of-hospital cardiac arrest (OHCA) varies between contexts. Dual dispatching of fire-fighters or police in addition to emergency medical services (EMS) has the potential to increase survival, but the effect in urban vs. rural areas is unknown. The aim of this study was to determine the effects of dual dispatching on response times and outcome in regions with different population density. The study design was a prospective cohort study of EMS-treated OHCAs from 2004 (historical controls, only EMS dispatch) and 2006-2009 (intervention, dual dispatch of EMS and fire-fighters), with data on exact geographical coordinates. Patients were divided into four subgroups depending on population density: rural (<250 persons/km2), suburban (250-2999/km2), urban (3000-5999/km2) and downtown (≥6000/km2). Totally, 2513 OHCAs were included (historical controls, n=571 and intervention, n=1942). Median time to arrival of first unit shortened significantly in all subgroups, ranging from 0.8 to 3.2 min, with the main time gain in the rural area. There were significant differences in 30-day survival between the historical controls vs. the intervention group in the suburban population (3.1% vs. 7.0%, p=0.02) and in downtown (4.1 vs. 14.6, p=0.04). In the urban population the difference was 2.7 vs. 6.9% (p=0.06) and in the rural population (4.7 vs. 5.3, p=0.82). Dual dispatch of fire-fighters and EMS in OHCA significantly reduced response times in all studied regions. The 30-day survival increased significantly in the downtown and suburban populations, while a limited impact was seen in the rural areas. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Cancer detection rates following enrolment in a disease management programme for type 2 diabetes.

PubMed

Geier, A S; Wellmann, J; Wellmann, I; Kajüter, H; Heidinger, O; Hempel, G; Hense, H W

2013-09-01

Recent prospective studies found an elevated cancer risk shortly after diabetes diagnosis, and this was probably due to increased ascertainment. This study investigated whether site-specific cancer risks are also raised following enrolment in a disease management programme for type 2 diabetes mellitus (DMP-DM2). We linked records from a DMP-DM2 to population cancer registry data. The study period was from June 2003 to December 2009. Standardised incidence ratios (SIRs) were calculated for time intervals following DMP enrolment using the cancer incidence rates of the general source population. Additionally, Poisson regression with natural splines was used to assess time-dependent cancer incidence by diabetes duration. There were 2,034 first invasive cancer cases identified over 163,738 person-years of follow-up. Pancreatic cancer risk was significantly increased mainly in the first year after enrolment (SIR 1.62); the increment was only seen for patients in whom diabetes had been diagnosed less than 1 year before DMP-DM2 enrolment. Risk of endometrial cancer was similarly raised in the first year after DMP-DM2 enrolment among individuals newly diagnosed with diabetes but decreased rapidly thereafter. There was no time dependence in the incidence of cancers of the liver, lung, colon, breast and prostate. Enrolment in a DMP-DM2 did not appear to induce ascertainment bias for most cancers. Cancer risks were initially increased, especially for pancreatic cancer, potentially as a result of reverse causality. Ascertainment bias and time-dependent incidence of cancer appear to be less of a problem in settings using DMP-like structures for the study of the association between diabetes duration, glucose-lowering medication and cancer incidence.

Damage Recovery in Carrara Marble

NASA Astrophysics Data System (ADS)

Meyer, G.; Brantut, N.; Mitchell, T. M.; Meredith, P. G.

2017-12-01

We investigate the effect of confining pressure on the recovery of elastic wave velocities following deformation episodes in Carrara Marble. Dry Carrara Marble cores were deformed in the ductile regime (Pc = 40 MPa) up to 3% axial strain. After deformation, samples were held at constant stress conditions for extended periods of time (5-8 days) whilst continuously recording volumetric strain and seismic wave velocities. The velocity data were used to invert for microcrack densities using an effective medium approach. Finally, thin sections were produced to characterise the microstructures after recovery. During deformation, elastic wave speeds decreased with increasing strain by more than 30% of the value for the intact rock due to the formation of distributed microcracks. Under constant hydrostatic pressure, wave speeds progressively recovered 12-90% of the initial drop, depending on the applied confining pressure. In contrast, the strain recovery (deformation towards the initial shape of the sample) during holding time is negligible (of the order of 10-4). Tests performed under nonhydrostatic (triaxial) stress conditions during recovery showed some time-dependent creep deformation together with very significant recovery of wave velocities. The recovery is interpreted as a progressive reduction in crack density within the sample. The process is highly dependent on confining pressure, which favours it. We propose that the driving process for wave speed recovery is the time-dependent increase of contact area between crack surfaces due to the formation and growth of asperity contacts. We develop a micromechanical model for crack closure driven by asperity creep, which shows a good fit to the experimental data. Most of the recovery is achieved in the initial few hours, implying it is the fastest recovery or healing process, and thus occurs prior to any chemical healing or mineral precipitation. Our data corroborate field observations of post-seismic fault behavior.

ACA dependent coverage provision reduced high out-of-pocket health care spending for young adults.

PubMed

Busch, Susan H; Golberstein, Ezra; Meara, Ellen

2014-08-01

Since September 2010 the Affordable Care Act (ACA) has required that insurers allow children to remain as dependents on their parents' private insurance plans until age twenty-six. Studies have shown that this provision increased coverage rates among young adults. In this article we analyze whether the provision also protected young adults from large and uncertain out-of-pocket expenses. We found that the policy was associated with a statistically significant reduction in the share of young adults facing annual out-of-pocket expenditures greater than $1,500 (decreasing from 4.2 percent to 2.9 percent), compared to an increase in the proportion of their slightly older peers facing such expenditures (increasing from 4.4 percent to 5.4 percent), a net difference of -2.4 percentage points, or 57 percent. We conclude that the dependent coverage provision in the ACA provides financial protection for young adults at a time when they often face high debt burden but low wages. Project HOPE—The People-to-People Health Foundation, Inc.

Site-Dependent Fluorescence Decay of Malachite Green Doped in Onion Cell

NASA Astrophysics Data System (ADS)

Nakatsuka, Hiroki; Sekine, Masaya; Suzuki, Yuji; Hattori, Toshiaki

1999-03-01

Time-resolved fluorescence measurements of malachite green dye moleculesdoped in onion cells were carried out.The fluorescence decay time was dependent on the individual cell and on theposition of the dye in a cell, which reflect the microscopic dynamics of each boundsite.Upon cooling, the decay time increased and this increase was accelerated ataround the freezing point of the onion cell.

Time dependent effect of chronic embryonic exposure to ethanol on zebrafish: Morphology, biochemical and anxiety alterations.

PubMed

Ramlan, Nurul Farhana; Sata, Nurul Syafida Asma Mohd; Hassan, Siti Norhidayah; Bakar, Noraini Abu; Ahmad, Syahida; Zulkifli, Syaizwan Zahmir; Abdullah, Che Azurahanim Che; Ibrahim, Wan Norhamidah Wan

2017-08-14

Exposure to ethanol during critical period of development can cause severe impairments in the central nervous system (CNS). This study was conducted to assess the neurotoxic effects of chronic embryonic exposure to ethanol in the zebrafish, taking into consideration the time dependent effect. Two types of exposure regimen were applied in this study. Withdrawal exposure group received daily exposure starting from gastrulation until hatching, while continuous exposure group received daily exposure from gastrulation until behavioural assessment at 6dpf (days post fertilization). Chronic embryonic exposure to ethanol decreased spontaneous tail coiling at 24hpf (hour post fertilization), heart rate at 48hpf and increased mortality rate at 72hpf. The number of apoptotic cells in the embryos treated with ethanol was significantly increased as compared to the control. We also measured the morphological abnormalities and the most prominent effects can be observed in the treated embryos exposed to 1.50% and 2.00%. The treated embryos showed shorter body length, larger egg yolk, smaller eye diameter and heart edema as compared to the control. Larvae received 0.75% continuous ethanol exposure exhibited decreased swimming activity and increased anxiety related behavior, while withdrawal ethanol exposure showed increased swimming activity and decreased anxiety related behavior as compared to the respective control. Biochemical analysis exhibited that ethanol exposure for both exposure regimens altered proteins, lipids, carbohydrates and nucleic acids of the zebrafish larvae. Our results indicated that time dependent effect of ethanol exposure during development could target the biochemical processes thus leading to induction of apoptosis and neurobehavioral deficits in the zebrafish larvae. Thus it raised our concern about the safe limit of alcohol consumption for pregnant mother especially during critical periods of vulnerability for developing nervous system. Copyright © 2017 Elsevier B.V. All rights reserved.

Eotaxin Increases Monolayer Permeability of Human Coronary Artery Endothelial Cells

PubMed Central

Jamaluddin, Md Saha; Wang, Xinwen; Wang, Hao; Rafael, Cubas; Yao, Qizhi; Chen, Changyi

2009-01-01

Objective The objective of this study was to determine the effects and molecular mechanisms of eotaxin, a newly discovered chemokine (CCL11), on endothelial permeability in the human coronary artery endothelial cells (HCAECs). Methods and Results Cells were treated with eotaxin, and the monolayer permeability was studied by using a costar transwell system with a Texas-Red-labeled dextran tracer. Eotaxin significantly increased monolayer permeability in a concentration-dependent manner. In addition, eotaxin treatment significantly decreased the mRNA and protein levels of endothelial junction molecules including zonula occludens-1 (ZO-1), occludin and claudin-1 in a concentration-dependent manner as determined by real time RT-PCR and Western blot analysis, respectively. Increased oxidative stress was observed in eotaxin-treated HCAECs by analysis of cellular glutathione levels. Furthermore, eotaxin treatment substantially activated the phosphorylation of MAPK p38. HCAECs expressed CCR3. Consequently, antioxidants (ginkgolide B and MnTBAP), specific p38 inhibitor SB203580 and anti-CCR3 antibody effectively blocked the eotaxin-induced permeability increase in HCAECs. Eotaxin also increased phosphorylation of Stat3 and nuclear translocation of NF-κB in HCAECs. Conclusions Eotaxin increases vascular permeability through CCR3, the down regulation of tight junction proteins, increase of oxidative stress and activation of MAPK p38, Stat3 and NF-kB pathways in HCAECs. PMID:19778943

The pH dependence of cocaine interaction with cardiac sodium channels.

PubMed

Crumb, W J; Clarkson, C W

1995-09-01

Previous in vitro and in vivo studies have provided evidence implicating cocaine block of cardiac sodium channels as a putative mechanism for cocaine-induced arrhythmias and sudden death. Cocaine also has been shown to cause seizures which can result in respiratory and/or metabolic acidosis. In this study we investigated how changes in both internal pH (pHi) and external pH (pHo) over the range of 6.6 to 9.2 modify the sodium channel blocking properties of cocaine in isolated guinea pig ventricular myocytes by using the whole-cell variant of the patch clamp technique. Use-dependent block produced by a train of 1-sec pulses to -20 mV was not affected by changes in pHi, but both the amplitude and time constant for approaching steady-state block were significantly affected by changes in pHo. Characterization of the time course of cocaine binding during a depolarizing pulse indicated that the kinetics of drug interaction with inactivated channels were independent of pHi, but were significantly affected by changes in pHo. The rate of recovery from channel block at a holding potential of -140 mV also was independent of pHi, but strongly dependent on pHo, with the unblocking time constant decreasing exponentially as pHo was increased. The results of this study indicate that cocaine's effect on cardiac sodium channels can be modulated significantly by changes in pHo, and provide further support for previously poorly tested assumptions of the modulated receptor hypothesis.

Programmed Cell Death in the Honey Bee (Apis mellifera) (Hymenoptera: Apidae) Worker Brain Induced by Imidacloprid.

PubMed

Wu, Yan-Yan; Zhou, Ting; Wang, Qiang; Dai, Ping-Li; Xu, Shu-Fa; Jia, Hui-Ru; Wang, Xing

2015-08-01

Honey bees are at an unavoidable risk of exposure to neonicotinoid pesticides, which are used worldwide. Compared with the well-studied roles of these pesticides in nontarget site (including midgut, ovary, or salivary glands), little has been reported in the target sites, the brain. In the current study, laboratory-reared adult worker honey bees (Apis mellifera L.) were treated with sublethal doses of imidacloprid. Neuronal apoptosis was detected using the TUNEL technique for DNA labeling. We observed significantly increased apoptotic markers in dose- and time-dependent manners in brains of bees exposed to imidacloprid. Neuronal activated caspase-3 and mRNA levels of caspase-1, as detected by immunofluorescence and real-time quantitative PCR, respectively, were significantly increased, suggesting that sublethal doses of imidacloprid may induce the caspase-dependent apoptotic pathway. Additionally, the overlap of apoptosis and autophagy in neurons was confirmed by transmission electron microscopy. It further suggests that a relationship exists between neurotoxicity and behavioral changes induced by sublethal doses of imidacloprid, and that there is a need to determine reasonable limits for imidacloprid application in the field to protect pollinators. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Dual Effects of N,N-dimethylformamide on Cell Proliferation and Apoptosis in Breast Cancer

PubMed Central

Zhang, Jihong; Zhou, Daibing; Zhang, Lingyun; Lin, Qunbo; Ren, Weimin; Zhang, Jinguo; Nadeem, Lubna; Xu, Guoxiong

2017-01-01

N,N-dimethylformamide (DMF) has been widely used as an organic solvent in industries. DMF is a potential medication. However, the antitumorigenic role of DMF in breast cancer remains unclear. Here, we examined dose-dependent effects of DMF on proliferation and apoptosis in breast cancer MCF-7 and nontumorous MCF-12A cells. We found that DMF had a growth inhibitory effect in MCF-12A cells in a dose-dependent manner. By contrast, however, DMF had dual effects on cell proliferation and apoptosis in MCF-7 cells. DMF at a high dose (100 mM) significantly inhibited MCF-7 cell growth while at a low dose (1 mM) significantly stimulated MCF-7 cell growth (both P < .05). The inhibitory effect of DMF on cell proliferation was accompanied by the decrease of cyclin D1 and cyclin E1 protein expression, leading to the cell cycle arrest at the G0/G1 phase. Furthermore, a high-dose DMF significantly increased the number of early apoptotic cells by increasing cleaved caspase-9 and proapoptotic protein Bax expression and decreased the ratio of Bcl-xL/Bax (P < .01). Thus, our data demonstrated for the first time that DMF has dual effects on breast cancer cell behaviors depending upon its dose. Caution must be warranted in determining its effective dose for targeting breast cancer. PMID:29238273

Effect of Methamphetamine Dependence on Heart Rate Variability

PubMed Central

Henry, Brook L.; Minassian, Arpi; Perry, William

2010-01-01

Background Methamphetamine (METH) is an increasing popular and highly addictive stimulant associated with autonomic nervous system (ANS) dysfunction, cardiovascular pathology, and neurotoxicity. Heart rate variability (HRV) has been used to assess autonomic function and predict mortality in cardiac disorders and drug intoxication, but has not been characterized in METH use. We recorded HRV in a sample of currently abstinent individuals with a history of METH dependence compared to age- and gender-matched drug-free comparison subjects. Method HRV was assessed using time domain, frequency domain, and nonlinear entropic analyses in 17 previously METH-dependent and 21 drug-free comparison individuals during a 5 minute rest period. Results The METH-dependent group demonstrated significant reduction in HRV, reduced parasympathetic activity, and diminished heartbeat complexity relative to comparison participants. More recent METH use was associated with increased sympathetic tone. Conclusion Chronic METH exposure may be associated with decreased HRV, impaired vagal function, and reduction in heart rate complexity as assessed by multiple methods of analysis. We discuss and review evidence that impaired HRV may be related to the cardiotoxic or neurotoxic effects of prolonged METH use. PMID:21182570

The Effect of Lactobacillus casei 32G on the Mouse Cecum Microbiota and Innate Immune Response Is Dose and Time Dependent

PubMed Central

Aktas, Busra; De Wolfe, Travis J.; Tandee, Kanokwan; Safdar, Nasia; Darien, Benjamin J.; Steele, James L.

2015-01-01

Lactobacilli have been associated with a variety of immunomodulatory effects and some of these effects have been related to changes in gastrointestinal microbiota. However, the relationship between probiotic dose, time since probiotic consumption, changes in the microbiota, and immune system requires further investigation. The objective of this study was to determine if the effect of Lactobacillus casei 32G on the murine gastrointestinal microbiota and immune function are dose and time dependent. Mice were fed L. casei 32G at doses of 106, 107, or 108 CFU/day/mouse for seven days and were sacrificed 0.5h, 3.5h, 12h, or 24h after the last administration. The ileum tissue and the cecal content were collected for immune profiling by qPCR and microbiota analysis, respectively. The time required for L. casei 32G to reach the cecum was monitored by qPCR and the 32G bolus reaches the cecum 3.5h after the last administration. L. casei 32G altered the cecal microbiota with the predominance of Lachnospiraceae IS, and Oscillospira decreasing significantly (p < 0.05) in the mice receiving 108 CFU/mouse 32G relative to the control mice, while a significant (p < 0.05) increase was observed in the prevalence of lactobacilli. The lactobacilli that increased were determined to be a commensal lactobacilli. Interestingly, no significant difference in the overall microbiota composition, regardless of 32G doses, was observed at the 12h time point. A likely explanation for this observation is the level of feed derived-nutrients resulting from the 12h light/dark cycle. 32G results in consistent increases in Clec2h expression and reductions in TLR-2, alpha-defensins, and lysozyme. Changes in expression of these components of the innate immune system are one possible explanation for the observed changes in the cecal microbiota. Additionally, 32G administration was observed to alter the expression of cytokines (IL-10rb and TNF-α) in a manner consistent with an anti-inflammatory response. PMID:26714177

Stainless steel leaches nickel and chromium into foods during cooking.

PubMed

Kamerud, Kristin L; Hobbie, Kevin A; Anderson, Kim A

2013-10-02

Toxicological studies show that oral doses of nickel and chromium can cause cutaneous adverse reactions such as dermatitis. Additional dietary sources, such as leaching from stainless steel cookware during food preparation, are not well characterized. This study examined stainless steel grades, cooking time, repetitive cooking cycles, and multiple types of tomato sauces for their effects on nickel and chromium leaching. Trials included three types of stainless steels and a stainless steel saucepan, cooking times of 2-20 h, 10 consecutive cooking cycles, and four commercial tomato sauces. After a simulated cooking process, samples were analyzed by ICP-MS for Ni and Cr. After 6 h of cooking, Ni and Cr concentrations in tomato sauce increased up to 26- and 7-fold, respectively, depending on the grade of stainless steel. Longer cooking durations resulted in additional increases in metal leaching, where Ni concentrations increased 34-fold and Cr increased approximately 35-fold from sauces cooked without stainless steel. Cooking with new stainless steel resulted in the largest increases. Metal leaching decreases with sequential cooking cycles and stabilized after the sixth cooking cycle, although significant metal contributions to foods were still observed. The tenth cooking cycle resulted in an average of 88 μg of Ni and 86 μg of Cr leached per 126 g serving of tomato sauce. Stainless steel cookware can be an overlooked source of nickel and chromium, where the contribution is dependent on stainless steel grade, cooking time, and cookware usage.

Stainless Steel Leaches Nickel and Chromium into Foods During Cooking

PubMed Central

Kamerud, Kristin L.; Hobbie, Kevin A.; Anderson, Kim A.

2014-01-01

Toxicological studies show that oral doses of nickel and chromium can cause cutaneous adverse reactions such as dermatitis. Additional dietary sources, such as leaching from stainless steel cookware during food preparation, are not well characterized. This study examined stainless steel grades, cooking time, repetitive cooking cycles, and multiple types of tomato sauces for their effects on nickel and chromium leaching. Trials included three types of stainless steels and a stainless steel saucepan; cooking times of 2 to 20 hours, ten consecutive cooking cycles, and four commercial tomato sauces. After a simulated cooking process, samples were analyzed by ICP-MS for Ni and Cr. After six hours of cooking, Ni and Cr concentrations in tomato sauce increased up to 26- and 7-fold respectively, depending on the grade of stainless steel. Longer cooking durations resulted in additional increases in metal leaching, where Ni concentrations increased 34 fold and Cr increased approximately 35 fold from sauces cooked without stainless steel. Cooking with new stainless steel resulted in the largest increases. Metal leaching decreases with sequential cooking cycles and stabilized after the sixth cooking cycle, though significant metal contributions to foods were still observed. The tenth cooking cycle, resulted in an average of 88 μg of Ni and 86 μg of Cr leached per 126 g serving of tomato sauce. Stainless steel cookware can be an overlooked source of nickel and chromium, where the contribution is dependent on stainless steel grade, cooking time, and cookware usage. PMID:23984718

Cell Specific Cytotoxicity and Uptake of Graphene Nanoribbons

PubMed Central

Chowdhury, Sayan Mullick; Lalwani, Gaurav; Zhang, Kevin; Yang, Jeong Yun; Neville, Kayla; Sitharaman, Balaji

2012-01-01

The synthesis of oxidized graphene nanoribbons (O-GNR) via longitudinal unzipping of carbon nanotubes opens avenues for their further development for a variety of biomedical applications. Evaluation of the cyto- and bio-compatibility is necessary to develop any new material for in vivo biomedical applications. In this study, we report the cytotoxicity screening of O-GNRs water-solubilized with PEG-DSPE (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)]), using six different assays, in four representative cell lines; Henrietta Lacks cells (HeLa) derived from cervical cancer tissue, National Institute of Health 3T3 mouse fibroblast cells (NIH-3T3), Sloan Kettering breast cancer cells (SKBR3) and Michigan cancer foundation-7 breast cancer cells (MCF7). These cell lines significantly differed in their response to O-GNR-PEG-DSPE formulations; assessed and evaluated using various endpoints (lactate dehydrogenase (LDH) release, cellular metabolism, lysosomal integrity and cell proliferation) for cytotoxicity. In general, all the cells showed a dose-dependent (10–400 μg/ml) and time-dependent (12–48 h) decrease in cell viability. However, the degree of cytotoxicity was significantly lower in MCF7 or SKBR3 cells compared to HeLa cells. These cells were 100% viable upto 48 hours, when incubated at 10μg/ml O-GNR-PEG-DSPE concentration, and showed decrease in cell viability above this concentration with ~78% of cells viable at the highest concentration (400 μg/ml). In contrast, significant cell death (5–25% cell death depending on the time point, and the assay) was observed for HeLa cells even at a low concentration of 10μg/ml. The decrease in cell viability was steep with increase in concentration with the CD50 values ≥ 100μg/ml depending on the assay, and time point. Transmission electron microscopy of the various cells treated with the O-GNR solutions show higher uptake of the O-GNR-PEG-DSPEs into HeLa cells compared to other cell types. Additional analysis indicates that this increased uptake is the dominant cause of the significantly higher toxicity exhibited by HeLa cells. The results suggest that water-solubilized O-GNR-PEG-DSPEs have a heterogeneous cell-specific cytotoxicity, and have significantly different cytotoxicity profile compared to graphene nanoparticles prepared by the modified Hummer’s method (graphene nanoparticles prepared by oxidation of graphite, and its mechanical exfoliation) or its variations. PMID:23072942

Cell specific cytotoxicity and uptake of graphene nanoribbons.

PubMed

Mullick Chowdhury, Sayan; Lalwani, Gaurav; Zhang, Kevin; Yang, Jeong Y; Neville, Kayla; Sitharaman, Balaji

2013-01-01

The synthesis of oxidized graphene nanoribbons (O-GNR) via longitudinal unzipping of carbon nanotubes opens avenues for their further development for a variety of biomedical applications. Evaluation of the cyto- and bio-compatibility is necessary to develop any new material for in vivo biomedical applications. In this study, we report the cytotoxicity screening of O-GNRs water-solubilized with PEG-DSPE (1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)]), using six different assays, in four representative cell lines; Henrietta Lacks cells (HeLa) derived from cervical cancer tissue, National Institute of Health 3T3 mouse fibroblast cells (NIH-3T3), Sloan Kettering breast cancer cells (SKBR3) and Michigan cancer foundation-7 breast cancer cells (MCF7). These cell lines significantly differed in their response to O-GNR-PEG-DSPE formulations; assessed and evaluated using various endpoints (lactate dehydrogenase (LDH) release, cellular metabolism, lysosomal integrity and cell proliferation) for cytotoxicity. In general, all the cells showed a dose-dependent (10-400 μg/ml) and time-dependent (12-48 h) decrease in cell viability. However, the degree of cytotoxicity was significantly lower in MCF7 or SKBR3 cells compared to HeLa cells. These cells were 100% viable upto 48 h, when incubated at 10 μg/ml O-GNR-PEG-DSPE concentration, and showed decrease in cell viability above this concentration with ~78% of cells viable at the highest concentration (400 μg/ml). In contrast, significant cell death (5-25% cell death depending on the time point, and the assay) was observed for HeLa cells even at a low concentration of 10 μg/ml. The decrease in cell viability was steep with increase in concentration with the CD(50) values ≥ 100 μg/ml depending on the assay, and time point. Transmission electron microscopy of the various cells treated with the O-GNR solutions show higher uptake of the O-GNR-PEG-DSPEs into HeLa cells compared to other cell types. Additional analysis indicates that this increased uptake is the dominant cause of the significantly higher toxicity exhibited by HeLa cells. The results suggest that water-solubilized O-GNR-PEG-DSPEs have a heterogenous cell-specific cytotoxicity, and have significantly different cytotoxicity profile compared to graphene nanoparticles prepared by the modified Hummer's method (graphene nanoparticles prepared by oxidation of graphite, and its mechanical exfoliation) or its variations. Copyright © 2012 Elsevier Ltd. All rights reserved.

Relationship of mechanical characteristics and microstructural features to the time-dependent edge notch sensitivity of inconel 718 sheet

NASA Technical Reports Server (NTRS)

Wilson, D. J.

1971-01-01

Time-dependent notch sensitivity of Inconel 718 sheet was observed at 900 F to 1200 F (482 - 649 C). It occurred when edge-notched specimens were loaded below the yield strength and smooth specimen tests showed that small amounts of creep consumed large rupture life fractions. The severity of the notch sensitivity was reduced by decreasing the solution temperature, increasing the time and/or temperature of aging and increasing the test temperature to 1400 F (760 C). Elimination of time-dependent notch sensitivity correlated with a change in dislocation motion mechanism from shearing to by-passing precipitate particles.

Assessing the Temporal Stability of a Cigarette Purchase Task After an Excise Tax Increase for Factory-Made and Roll-Your-Own Smokers.

PubMed

Grace, Randolph C; Kivell, Bronwyn M; Laugesen, Murray

2015-11-01

Cigarette purchase tasks (CPTs) are used increasingly to measure simulated demand curves for tobacco. However, there is currently limited information about the temporal stability of demand curves obtained from these tasks. We interviewed a sample (N = 210) of smokers in New Zealand both before and after a 10% increase in the tobacco excise tax that took effect on January 1, 2013. Participants were interviewed in November-December 2012 (wave 1) and February-March 2013 (wave 2). At each interview, participants completed a high-resolution CPT with 64 prices ranging from NZ $0.00 to NZ $5.00/cigarette, and questionnaires regarding their smoking habit. Roll-your-own smokers had higher levels of nicotine dependence and tobacco demand based on CPT responses than factory-made smokers. Although demand curves for waves 1 and 2 were similar, intentions to purchase cigarettes were significantly less at wave 2 for three prices (NZ $0.85, NZ $0.90, and NZ $0.95) that were just higher than the actual price after the tax increase, for both roll-your-own and factory-made smokers. Measures of elasticity (α) derived from Hursh and Silberberg's model were significantly greater at wave 2 than wave 1, and there was a significant reduction in smoking habit as measured by cigarettes/day and the Fagerström Test for Nicotine Dependence at wave 2. Purchase tasks can discriminate between smokers based on their tobacco preference, and although results are relatively stable over time, they depend on contextual factors such as the current real price for tobacco. © The Author 2015. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

A metabolomics-driven approach reveals metabolic responses and mechanisms in the rat heart following myocardial infarction.

PubMed

Nam, Miso; Jung, Youngae; Ryu, Do Hyun; Hwang, Geum-Sook

2017-01-15

Myocardial infarction (MI) is caused by myocardial necrosis resulting from prolonged ischemia. However, the biological mechanisms underlying MI remain unclear. We evaluated metabolic and lipidomic changes in rat heart tissue from sham and MI at 1h, 1day and 10day after coronary ligation, using global profiling based on metabolomics. A time-dependent increase or decrease in polar and lipid metabolite levels was measured. The S-adenosylmethionine (SAM) concentration and the SAM/S-adenosylhomocysteine (SAH) ratio gradually decreased in a time-dependent manner and were significantly downregulated 10days after MI. Transcriptome analysis revealed that the levels of coenzyme Q (Coq)-3 and Coq5, both of which are SAM-dependent methyltransferases, were decreased in the MI groups. These results suggested that dysregulation of SAM may be related to down regulated COQ biosynthetic pathway. In addition, short-chain (C3) and medium-chain (C4-C12) acylcarnitine levels gradually decreased, whereas long-chain acylcarnitine (C14-18) levels increased, owing to a defect in β-oxidation during ischemia. These changes are related to energy-dependent metabolic pathways, and a subsequent decrease in adenosine triphosphate concentration was observed. The comprehensive integration of various omics data provides a novel means of understanding the underlying pathophysiological mechanisms of MI. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

Kaur, Gurpreet; Ly-Huynh, Jennifer D.; Jans, David A., E-mail: David.Jans@monash.edu

Highlights: • High intracellular calcium inhibits Impα/β1- or Impβ1-dependent nuclear protein import. • The effect of Ca{sup 2+} on nuclear import does not relate to changes in the nuclear pore. • High intracellular calcium can result in mislocalisation of Impβ1, Ran and RCC1. - Abstract: We previously showed that increased intracellular calcium can modulate Importin (Imp)β1-dependent nuclear import of SRY-related chromatin remodeling proteins. Here we extend this work to show for the first time that high intracellular calcium inhibits Impα/β1- or Impβ1-dependent nuclear protein import generally. The basis of this relates to the mislocalisation of the transport factors Impβ1 andmore » Ran, which show significantly higher nuclear localization in contrast to various other factors, and RCC1, which shows altered subnuclear localisation. The results here establish for the first time that intracellular calcium modulates conventional nuclear import through direct effects on the nuclear transport machinery.« less

Anisotropic thermal conductivity in carbon honeycomb

NASA Astrophysics Data System (ADS)

Chen, Xue-Kun; Liu, Jun; Du, Dan; Xie, Zhong-Xiang; Chen, Ke-Qiu

2018-04-01

Carbon honeycomb, a new kind of 3D carbon allotrope experimentally synthesized recently, has received much attention for its fascinating applications in electronic device and energy storage. In the present work, we perform equilibrium molecular dynamics (EMD) to study the thermal transport properties of carbon honeycombs with different chirality. It is found that the thermal conductivity along the honeycomb axis ({κx} ) is three times larger than that normal to the axis ({κz} ), which shows strong anisotropy reflecting their geometric anisotropy. Lattice dynamics calculations reveal that this anisotropy stems from the orientation-dependent phonon group velocities. Moreover, when ambient temperature (T ) increases from 200 K to 800 K, the {{T}-1} dependence of κ is observed due to the enhanced Umklapp scattering. The detailed phonon spectra analyses indicate phonon group velocities are insensitive to the variation of ambient temperature, and the temperature dependence of the relaxation times of low-frequency phonons (<20 THz) follows ∼ {{T}-1} behavior. Our results have a certain guiding significance to develop carbon honeycomb for effective thermal channeling devices.

Run-time parallelization and scheduling of loops

NASA Technical Reports Server (NTRS)

Saltz, Joel H.; Mirchandaney, Ravi; Crowley, Kay

1991-01-01

Run-time methods are studied to automatically parallelize and schedule iterations of a do loop in certain cases where compile-time information is inadequate. The methods presented involve execution time preprocessing of the loop. At compile-time, these methods set up the framework for performing a loop dependency analysis. At run-time, wavefronts of concurrently executable loop iterations are identified. Using this wavefront information, loop iterations are reordered for increased parallelism. Symbolic transformation rules are used to produce: inspector procedures that perform execution time preprocessing, and executors or transformed versions of source code loop structures. These transformed loop structures carry out the calculations planned in the inspector procedures. Performance results are presented from experiments conducted on the Encore Multimax. These results illustrate that run-time reordering of loop indexes can have a significant impact on performance.

Effects of length of abstinence on decision-making and craving in methamphetamine abusers.

PubMed

Wang, Guibin; Shi, Jie; Chen, Na; Xu, Lingzhi; Li, Jiali; Li, Peng; Sun, Yan; Lu, Lin

2013-01-01

The majority of drug abusers are incapable of sustaining abstinence over any length of time. Accumulating evidence has linked intense and involuntary craving, Impulsive decision-making and mood disturbances to risk for relapse. However, little is known about temporal changes of these neuropsychological functions in methamphetamine (METH)-dependent individuals. To investigate the effect of length of abstinence on decision-making, craving (baseline and cue-induced), and emotional state in METH-addicted individuals. In this cross-sectional study, 183 adult METH-dependent patients at an addiction rehabilitation center who were abstinent for 6 days (n = 37), 14 days (n = 33), 1 month (n = 31), 3 months (n = 30), 6 months (n = 26), or 1 year (n = 30) and 39 healthy subjects were administered the Iowa Gambling Task (IGT) to assess decision-making performance. Depression, anxiety, and impulsivity were also examined. One hundred thirty-nine METH abusers who were abstinent for the aforementioned times then underwent a cue session, and subjective and physiological measures were assessed. METH dependent individuals who were abstinent for longer periods of time exhibited better decision-making than those who were abstinent for shorter periods of time. And self-reported emotional symptoms improved with abstinence. METH abusers' ratings of craving decreased with the duration of abstinence, while cue-induced craving increased until 3 months of abstinence and decreased at 6 months and 1 year of abstinence. We present time-dependent alterations in decision-making, emotional state, and the incubation of cue-induced craving in METH-dependent individuals, which might have significant clinical implications for the prevention of relapse.

Mean platelet volume (MPV) predicts middle distance running performance.

PubMed

Lippi, Giuseppe; Salvagno, Gian Luca; Danese, Elisa; Skafidas, Spyros; Tarperi, Cantor; Guidi, Gian Cesare; Schena, Federico

2014-01-01

Running economy and performance in middle distance running depend on several physiological factors, which include anthropometric variables, functional characteristics, training volume and intensity. Since little information is available about hematological predictors of middle distance running time, we investigated whether some hematological parameters may be associated with middle distance running performance in a large sample of recreational runners. The study population consisted in 43 amateur runners (15 females, 28 males; median age 47 years), who successfully concluded a 21.1 km half-marathon at 75-85% of their maximal aerobic power (VO2max). Whole blood was collected 10 min before the run started and immediately thereafter, and hematological testing was completed within 2 hours after sample collection. The values of lymphocytes and eosinophils exhibited a significant decrease compared to pre-run values, whereas those of mean corpuscular volume (MCV), platelets, mean platelet volume (MPV), white blood cells (WBCs), neutrophils and monocytes were significantly increased after the run. In univariate analysis, significant associations with running time were found for pre-run values of hematocrit, hemoglobin, mean corpuscular hemoglobin (MCH), red blood cell distribution width (RDW), MPV, reticulocyte hemoglobin concentration (RetCHR), and post-run values of MCH, RDW, MPV, monocytes and RetCHR. In multivariate analysis, in which running time was entered as dependent variable whereas age, sex, blood lactate, body mass index, VO2max, mean training regimen and the hematological parameters significantly associated with running performance in univariate analysis were entered as independent variables, only MPV values before and after the trial remained significantly associated with running time. After adjustment for platelet count, the MPV value before the run (p = 0.042), but not thereafter (p = 0.247), remained significantly associated with running performance. The significant association between baseline MPV and running time suggest that hyperactive platelets may exert some pleiotropic effects on endurance performance.

GABA promotes elastin synthesis and elastin fiber formation in normal human dermal fibroblasts (HDFs).

PubMed

Uehara, Eriko; Hokazono, Hideki; Hida, Mariko; Sasaki, Takako; Yoshioka, Hidekatsu; Matsuo, Noritaka

2017-06-01

The multiple physiological effects of γ-aminobutyric acid (GABA) as a functional food component have been recently reported. We previously reported that GABA upregulated the expression of type I collagen in human dermal fibroblasts (HDFs), and that oral administration of GABA significantly increased skin elasticity. However, details of the regulatory mechanism still remain unknown. In this study, we further examined the effects of GABA on elastin synthesis and elastin fiber formation in HDFs. Real-time PCR indicated that GABA significantly increased the expression of tropoelastin transcript in a dose-dependent manner. Additionally, the expression of fibrillin-1, fibrillin-2, and fibulin-5/DANCE, but not lysyl oxidase and latent transforming factor-β-binding protein 4, were also significantly increased in HDFs. Finally, immunohistochemical analysis confirmed that treatment with GABA dramatically increased the formation of elastic fibers in HDFs. Taken together, our results showed that GABA improves skin elasticity in HDFs by upregulating elastin synthesis and elastin fiber formation.

Extracellular visfatin activates gluconeogenesis in HepG2 cells through the classical PKA/CREB-dependent pathway.

PubMed

Choi, Y J; Choi, S-E; Ha, E S; Kang, Y; Han, S J; Kim, D J; Lee, K W; Kim, H J

2014-04-01

Adipokines reportedly affect hepatic gluconeogenesis, and the adipokine visfatin is known to be related to insulin resistance and type 2 diabetes. However, whether visfatin contributes to hepatic gluconeogenesis remains unclear. Visfatin, also known as nicotinamide phosphoribosyltransferase (NAMPT), modulates sirtuin1 (SIRT1) through the regulation of nicotinamide adenine dinucleotide (NAD). Therefore, we investigated the effect of extracellular visfatin on glucose production in HepG2 cells, and evaluated whether extracellular visfatin affects hepatic gluconeogenesis via an NAD+-SIRT1-dependent pathway. Treatment with visfatin significantly increased glucose production and the mRNA expression and protein levels of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) in HepG2 cells in a time- and concentration-dependent manner. Knockdown of SIRT1 had no remarkable effect on the induction of gluconeogenesis by visfatin. Subsequently, we evaluated if extracellular visfatin stimulates the production of gluconeogenic enzymes through the classical protein kinase A (PKA)/cyclic AMP-responsive element (CRE)-binding protein (CREB)-dependent process. The phosphorylation of CREB and PKA increased significantly in HepG2 cells treated with visfatin. Additionally, knockdown of CREB and PKA inhibited visfatin-induced gluconeogenesis in HepG2 cells. In summary, extracellular visfatin modulates glucose production in HepG2 cells through the PKA/CREB pathway, rather than via SIRT1 signaling. © Georg Thieme Verlag KG Stuttgart · New York.

Modelling possible causality in the associations between unemployment, cannabis use, and alcohol misuse.

PubMed

Boden, Joseph M; Lee, Jungeun Olivia; Horwood, L John; Grest, Carolina Villamil; McLeod, Geraldine F H

2017-02-01

There has been considerable interest in the extent to which substance use and unemployment may be related, particularly the causal pathways that may be involved in these associations. It has been argued that these associations may reflect social causation, in which unemployment influences substance use, or that they may reflect social selection, in which substance use increases the risk of becoming and remaining unemployed. The present study sought to test these competing explanations. Data from the Christchurch Health and Development Study, featuring a longitudinal birth cohort, were used to model the associations between unemployment and both cannabis and alcohol. Data on patterns of unemployment, involvement with cannabis, and symptoms of alcohol use disorder were examined from ages 18-35 years. The associations between unemployment and both cannabis dependence and alcohol use disorder (AUD) were modelled using conditional fixed-effects regression models, augmented by time-dynamic covariate factors. The analyses showed evidence of possible reciprocal causal processes in the association between unemployment and cannabis dependence, in which unemployment of at least three months' duration significantly (p < 0.0001) increased the risk of cannabis dependence, and cannabis dependence significantly (p < 0.0001) increased the risk of being unemployed. Similar evidence was found for the associations between unemployment and AUD, although these associations were smaller in magnitude. The present findings support both social causation and social selection arguments, by indicating that unemployment plays a causal role in substance misuse, and that it is also likely that a reverse causal process whereby substance misuse increases the risk of unemployment. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effects of T'ai Chi on Serotonin, Nicotine Dependency, Depression, and Anger in Hospitalized Alcohol-Dependent Patients.

PubMed

Oh, Chung-Uk; Kim, Nam-Cho

2016-12-01

The aim of this study was to investigate the effects of t'ai chi on blood serotonin levels, nicotine dependence, depression, and anger in hospitalized alcohol-dependent patients. This study followed an experimental and nonequivalent control group in a non-synchronized design. It was performed in a hospital located in Young Ju city, Korea, from April to August 2013. Thirty-eight patients who were hospitalized with alcohol dependence were included. They were randomly divided into an experimental and a control group, with 19 patients in each group. Patients in the experimental group practiced the 24-posture yang style t'ai chi for 50 min three times per week for 8 weeks as part of the routine hospital rehabilitation program, and those in the control group followed only the routine hospital rehabilitation program. The effect of treatment was measured using blood serotonin levels and a questionnaire on nicotine dependence, depression, and anger. Both measurements were performed before and after 8 weeks of intervention. Data were analyzed using the t-test, chi-square test, and paired t-tests. The experimental group showed a significantly increased blood serotonin level (p = 0.001) and significantly reduced nicotine dependence, depression, and anger (p = 0.001) than the control group did after 8 weeks of treatment. T'ai chi was shown to be an effective nursing intervention in hospitalized alcohol-dependent patients.

Exercise training improves heart rate variability after methamphetamine dependency.

PubMed

Dolezal, Brett Andrew; Chudzynski, Joy; Dickerson, Daniel; Mooney, Larissa; Rawson, Richard A; Garfinkel, Alan; Cooper, Christopher B

2014-06-01

Heart rate variability (HRV) reflects a healthy autonomic nervous system and is increased with physical training. Methamphetamine dependence (MD) causes autonomic dysfunction and diminished HRV. We compared recently abstinent methamphetamine-dependent participants with age-matched, drug-free controls (DF) and also investigated whether HRV can be improved with exercise training in the methamphetamine-dependent participants. In 50 participants (MD = 28; DF = 22), resting heart rate (HR; R-R intervals) was recorded over 5 min while seated using a monitor affixed to a chest strap. Previously reported time domain (SDNN, RMSSD, pNN50) and frequency domain (LFnu, HFnu, LF/HF) parameters of HRV were calculated with customized software. MD were randomized to thrice-weekly exercise training (ME = 14) or equal attention without training (MC = 14) over 8 wk. Groups were compared using paired and unpaired t-tests. Statistical significance was set at P ≤ 0.05. Participant characteristics were matched between groups (mean ± SD): age = 33 ± 6 yr; body mass = 82.7 ± 12 kg, body mass index = 26.8 ± 4.1 kg·min. Compared with DF, the MD group had significantly higher resting HR (P < 0.05), LFnu, and LF/HF (P < 0.001) as well as lower SDNN, RMSSD, pNN50, and HFnu (all P < 0.001). At randomization, HRV indices were similar between ME and MC groups. However, after training, the ME group significantly (all P < 0.001) increased SDNN (+14.7 ± 2.0 ms, +34%), RMSSD (+19.6 ± 4.2 ms, +63%), pNN50 (+22.6% ± 2.7%, +173%), HFnu (+14.2 ± 1.9, +60%), and decreased HR (-5.2 ± 1.1 bpm, -7%), LFnu (-9.6 ± 1.5, -16%), and LF/HF (-0.7 ± 0.3, -19%). These measures did not change from baseline in the MC group. HRV, based on several conventional indices, was diminished in recently abstinent, methamphetamine-dependent individuals. Moreover, physical training yielded a marked increase in HRV, representing increased vagal modulation or improved autonomic balance.

Absence of equifinality of hand position in a double-step unloading task.

PubMed

Norouzi-Gheidari, Nahid; Archambault, Philippe

2010-08-01

Equifinality, during arm reaching movements, relates to the capacity of the neuromuscular system to attain the same final position in the presence or absence of transient perturbations. There have been several controversies regarding equifinality in the literature. A brief elastic perturbation, applied during a fast arm movement or just before its initiation, typically does not affect final arm position. On the other hand, several experiments have shown that velocity-dependent perturbations, such as Coriolis force or negative damping, while transient in nature, have a significant effect on final arm position when compared to unperturbed movements. In this study, an unloading paradigm was used to study the role of reflexes with respect to equifinality. The effects on final arm position of suddenly decreasing a static load maintained by fourteen subjects were analyzed. Subjects maintained an initial load produced by a double-joint manipulandum moving in the horizontal plane. The load was suddenly decreased, either in one or in two successive steps with different time intervals, resulting in a rapid reflex-mediated change in arm position. Unloading led to short-latency changes in the activity of shoulder and elbow muscles and significant variations in tonic activity. It was found that the final hand position was shorter for double- versus single-step unloading if the time between two successive changes in load was greater than 100 ms. With a shorter time interval, the final hand positions were the same. This difference in final hand positions was inversely proportional to the hand velocity at the time of the second change in load. Further, agonist/antagonist co-activation increased in double-step unloading. Thus, the change in both the load and the movement velocity may influence the magnitude of the unloading reflex. This may be indicative of a dependence of stretch reflexes on velocity. Perturbation may cause a reflex-mediated increase in joint stiffness, which could explain why equifinality is not preserved after some perturbations, such as velocity-dependant external forces.

Dynamic rheological properties of dough as affected by amylases from various sources.

PubMed

Doğan, Ismail S

2002-12-01

The effect of alpha-amylases from cereal, fungal, and bacterial sources on dough dynamic rheological properties was investigated. Dynamic rheological study of flour-and-water doughs during resting period showed significant changes in dough rheological properties as a function of alpha-amylases. Addition of alpha-amylases caused a time-dependent decrease in G', storage modulus. The enzyme action on starch during baking increased viscous flow properties. These changes were temperature-dependent. The thermal inactivation temperature of alpha-amylase plays an important role in modification of starch. Rheological changes in dough will alter the machinability of the dough and the quality of end products.

Antiproliferative effect of Antrodia camphorata polysaccharides encapsulated in chitosan-silica nanoparticles strongly depends on the metabolic activity type of the cell line

NASA Astrophysics Data System (ADS)

Kong, Zwe-Ling; Chang, Jenq-Sheng; Chang, Ke Liang B.

2013-09-01

Chitosan molecules interact with silica and encapsulate the Antrodia camphorata extract (ACE) polysaccharides to form composite nanoparticles. The nanoparticle suspensions of ACE polysaccharides encapsulated in silica-chitosan and silica nanoparticles approach an average particle size of 210 and 294 nm in solution, respectively. The encapsulation efficiencies of ACE polysaccharides are 66 and 63.5 %, respectively. Scanning electron micrographs confirm the formation of near-spherical nanoparticles. ACE polysaccharides solution had better antioxidative capability than ACE polysaccharides encapsulated in silica or silica-chitosan nanoparticles suspensions. The antioxidant capacity of nanoparticles increases with increasing dissolution time. The antitumor effects of ACE polysaccharides, ACE polysaccharides encapsulated in silica, or silica-chitosan nanoparticles increased with increasing concentration of nanoparticles. This is the first report demonstrating the potential of ACE polysaccharides encapsulated in chitosan-silica nanoparticles for cancer chemoprevention. Furthermore, this study suggests that antiproliferative effect of nanoparticle-encapsulated bioactive could significantly depend on the metabolic activity type of the cell line.

Paeonol protects rat vascular endothelial cells from ox-LDL-induced injury in vitro via downregulating microRNA-21 expression and TNF-α release

PubMed Central

Liu, Ya-rong; Chen, Jun-jun; Dai, Min

2014-01-01

Aim: Paeonol (2′-hydroxy-4′-methoxyacetophenone) from Cortex moutan root is a potential therapeutic agent for atherosclerosis. This study sought to investigate the mechanisms underlying anti-inflammatory effects of paeonol in rat vascular endothelial cells (VECs) in vitro. Methods: VECs were isolated from rat thoracic aortas. The cells were pretreated with paeonol for 24 h, and then stimulated with ox-LDL for another 24 h. The expression of microRNA-21 (miR-21) and PTEN in VECs was analyzed using qRT-PCR. The expression of PTEN protein was detected by Western blotting. TNF-α release by VECs was measured by ELISA. Results: Ox-LDL treatment inhibited VEC growth in dose- and time-dependent manners (the value of IC50 was about 20 mg/L at 24 h). Furthermore, ox-LDL (20 mg/L) significantly increased miR-21 expression and inhibited the expression of PTEN, one of downstream target genes of miR-21 in VECs. In addition, ox-LDL (20 mg/L) significantly increased the release of TNF-α from VECs. Pretreatment with paeonol increased the survival rate of ox-LDL-treated VECs in dose- and time-dependent manners. Moreover, paeonol (120 μmol/L) prevented ox-LDL-induced increases in miR-21 expression and TNF-α release, and ox-LDL-induced inhibition in PTEN expression. A dual-luciferase reporter assay showed that miR-21 bound directly to PTEN's 3′-UTR, thus inhibiting PTEN expression. In ox-LDL treated VECs, transfection with a miR-21 mimic significantly increased miR-21 expression and inhibited PTEN expression, and attenuated the protective effects of paeonol pretreatment, whereas transfection with an miR-21 inhibitor significantly decreased miR-21 expression and increased PTEN expression, thus enhanced the protective effects of paeonol pretreatment. Conclusion: miR-21 is an important target of paeonol for its protective effects against ox-LDL-induced VEC injury, which may play critical roles in development of atherosclerosis. PMID:24562307

Adipose tissue uncoupling protein 1 levels and function are increased in a mouse model of developmental obesity induced by maternal exposure to high-fat diet.

PubMed

Bytautiene Prewit, E; Porter, C; La Rosa, M; Bhattarai, N; Yin, H; Gamble, P; Kechichian, T; Sidossis, L S

2018-05-17

With brown adipose tissue (BAT) becoming a possible therapeutic target to counteract obesity, the prenatal environment could represent a critical window to modify BAT function and browning of white AT. We investigated if levels of uncoupling protein 1 (UCP1) and UCP1-mediated thermogenesis are altered in offspring exposed to prenatal obesity. Female CD-1 mice were fed a high-fat (HF) or standard-fat (SF) diet for 3 months before breeding. After weaning, all pups were placed on SF. UCP1 mRNA and protein levels were quantified using quantitative real-time PCR and Western blot analysis, respectively, in brown (BAT), subcutaneous (SAT) and visceral (VAT) adipose tissues at 6 months of age. Total and UCP1-dependent mitochondrial respiration were determined by high-resolution respirometry. A Student's t-test and Mann-Whitney test were used (significance: P<0.05). UCP1 mRNA levels were not different between the HF and SF offspring. UCP1 protein levels, total mitochondrial respiration and UCP1-dependent respiration were significantly higher in BAT from HF males (P=0.02, P=0.04, P=0.005, respectively) and females (P=0.01, P=0.04, P=0.02, respectively). In SAT, the UCP1 protein was significantly lower in HF females (P=0.03), and the UCP1-dependent thermogenesis was significantly lower from HF males (P=0.04). In VAT, UCP1 protein levels and UCP1-dependent respiration were significantly lower only in HF females (P=0.03, P=0.04, respectively). There were no differences in total respiration in SAT and VAT. Prenatal exposure to maternal obesity leads to significant increases in UCP1 levels and function in BAT in offspring with little impact on UCP1 levels and function in SAT and VAT.

Photothermal stress triggered by near-infrared-irradiated carbon nanotubes up-regulates osteogenesis and mineral deposition in tooth-extracted sockets.

PubMed

Kajiya, Hiroshi; Katsumata, Yuri; Sasaki, Mina; Tsutsumi, Takashi; Kawaguchi, Minoru; Fukushima, Tadao

2015-01-01

The bone regenerative healing process is often prolonged, with a high risk of infection particularly in elderly and diseased patients. A reduction in healing process time usually requires mechanical stress devices, chemical cues, or laser/thermal therapies. Although these approaches have been used extensively for the reduction of bone healing time, the exact mechanisms involved in thermal stress-induced bone regeneration remain unclear. Photothermal stress (PTS) stimulation was carried out using a novel photothermal device, composed of an alginate gel (AG) including carbon nanotubes (CNT-AGs) and their irradiator with near-infrared (NIR) light. We investigated the effects of optimal hyperthermia on osteogenesis, its signalling pathway in vitro and mineral deposition in tooth-extracted sockets in vivo. The PTS (10 min at 42 °C, every day), triggered by NIR-induced CNT, increased the activity of alkaline phosphatase (ALP) in mouse osteoblast MC3T3-E1 cells in a time-dependent manner compared with the non-thermal stress control. PTS significantly induced the expression of osteogenic-related molecules such as ALP, RUNX2 and Osterix in a time-dependent manner with phosphorylated mitogen-activated protein kinases (MAPK). PTS increased the expression of heat shock factor (HSF) 2, but not HSF1, resulting in activation of heat shock protein 27. PTS significantly up-regulated mineral deposition in tooth-extracted sockets in normal and ovariectomised osteoporotic model mice in vivo. Our novel CNT-based PTS up-regulated osteogenesis via activation of heat shock-related molecules, resulting in promotion of mineral deposition in enhanced tooth-extracted sockets.

Early postnatal changes in respiratory activity in rat in vitro and modulatory effects of substance P.

PubMed

Shvarev, Y N; Lagercrantz, H

2006-10-01

Developmental changes in the respiratory activity and its modulation by substance P (SP) were studied in the neonatal rat brainstem-spinal cord preparation from the day of birth to day 3 (P0-P3). The respiratory network activity in the ventrolateral medulla was represented by two types of bursts: basic regular bursts with typical decrementing shape and biphasic bursts appearing after augmented biphasic discharges in inspiratory neurons. With advancing postnatal age the respiratory output was considerably modified; the basic rhythm became faster by 20%, whereas the biphasic burst rate, which was originally 15 times slower, declined further by 180% and the C4 burst duration significantly decreased by 20% due to reduced decay time without preceding changes in the central inspiratory drive. SP had an age-dependent excitatory effect on respiratory activity. In the basic rhythm, SP could induce transient rhythm cessations on P0-P2 but not on P3. For the biphasic burst frequency, the sensitivity to SP significantly decreased from P0 to P3, whereas the range of SP-induced changes increased. In both types of bursts, SP prolonged C4 burst duration due to increasing decay time. This effect was three times greater on P3 and did not depend on the central inspiratory drive. Our results suggest that the potency of SP to regulate the respiratory activity elevates during the early postnatal period. The developmental changes in the respiratory activity appear to represent the transient stage in the maturation of rhythm and pattern generation mechanisms facilitating adaptive behavior of a quickly growing organism.

Effects of task and age on the magnitude and structure of force fluctuations: insights into underlying neuro-behavioral processes.

PubMed

Vieluf, Solveig; Temprado, Jean-Jacques; Berton, Eric; Jirsa, Viktor K; Sleimen-Malkoun, Rita

2015-03-13

The present study aimed at characterizing the effects of increasing (relative) force level and aging on isometric force control. To achieve this objective and to infer changes in the underlying control mechanisms, measures of information transmission, as well as magnitude and time-frequency structure of behavioral variability were applied to force-time-series. Older adults were found to be weaker, more variable, and less efficient than young participants. As a function of force level, efficiency followed an inverted-U shape in both groups, suggesting a similar organization of the force control system. The time-frequency structure of force output fluctuations was only significantly affected by task conditions. Specifically, a narrower spectral distribution with more long-range correlations and an inverted-U pattern of complexity changes were observed with increasing force level. Although not significant older participants displayed on average a less complex behavior for low and intermediate force levels. The changes in force signal's regularity presented a strong dependence on time-scales, which significantly interacted with age and condition. An inverted-U profile was only observed for the time-scale relevant to the sensorimotor control process. However, in both groups the peak was not aligned with the optimum of efficiency. Our results support the view that behavioral variability, in terms of magnitude and structure, has a functional meaning and affords non-invasive markers of the adaptations of the sensorimotor control system to various constraints. The measures of efficiency and variability ought to be considered as complementary since they convey specific information on the organization of control processes. The reported weak age effect on variability and complexity measures suggests that the behavioral expression of the loss of complexity hypothesis is not as straightforward as conventionally admitted. However, group differences did not completely vanish, which suggests that age differences can be more or less apparent depending on task properties and whether difficulty is scaled in relative or absolute terms.

Prenatal methylmercury exposure hampers glutathione antioxidant system ontogenesis and causes long-lasting oxidative stress in the mouse brain

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

Stringari, James; Nunes, Adriana K.C.; Franco, Jeferson L.

2008-02-15

During the perinatal period, the central nervous system (CNS) is extremely sensitive to metals, including methylmercury (MeHg). Although the mechanism(s) associated with MeHg-induced developmental neurotoxicity remains obscure, several studies point to the glutathione (GSH) antioxidant system as an important molecular target for this toxicant. To extend our recent findings of MeHg-induced GSH dyshomeostasis, the present study was designed to assess the developmental profile of the GSH antioxidant system in the mouse brain during the early postnatal period after in utero exposure to MeHg. Pregnant mice were exposed to different doses of MeHg (1, 3 and 10 mg/l, diluted in drinkingmore » water, ad libitum) during the gestational period. After delivery, pups were killed at different time points - postnatal days (PND) 1, 11 and 21 - and the whole brain was used for determining biochemical parameters related to the antioxidant GSH system, as well as mercury content and the levels of F{sub 2}-isoprostane. In control animals, cerebral GSH levels significantly increased over time during the early postnatal period; gestational exposure to MeHg caused a dose-dependent inhibition of this developmental event. Cerebral glutathione peroxidase (GPx) and glutathione reductase (GR) activities significantly increased over time during the early postnatal period in control animals; gestational MeHg exposure induced a dose-dependent inhibitory effect on both developmental phenomena. These adverse effects of prenatal MeHg exposure were corroborated by marked increases in cerebral F{sub 2}-isoprostanes levels at all time points. Significant negative correlations were found between F{sub 2}-isoprostanes and GSH, as well as between F{sub 2}-isoprostanes and GPx activity, suggesting that MeHg-induced disruption of the GSH system maturation is related to MeHg-induced increased lipid peroxidation in the pup brain. In utero MeHg exposure also caused a dose-dependent increase in the cerebral levels of mercury at birth. Even though the cerebral mercury concentration decreased to nearly basal levels at postnatal day 21, GSH levels, GPx and GR activities remained decreased in MeHg-exposed mice, indicating that prenatal exposure to MeHg affects the cerebral GSH antioxidant systems by inducing biochemical alterations that endure even when mercury tissue levels decrease and become indistinguishable from those noted in pups born to control dams. This study is the first to show that prenatal exposure to MeHg disrupts the postnatal development of the glutathione antioxidant system in the mouse brain, pointing to an additional molecular mechanism by which MeHg induces pro-oxidative damage in the developing CNS. Moreover, our experimental observation corroborates previous reports on the permanent functional deficits observed after prenatal MeHg exposure.« less

Prenatal methylmercury exposure hampers glutathione antioxidant system ontogenesis and causes long-lasting oxidative stress in the mouse brain

PubMed Central

Stringari, James; Nunes, Adriana KC; Franco, Jeferson L; Bohrer, Denise; Garcia, Solange C; Dafre, Alcir L; Milatovic, Dejan; Souza, Diogo O; Rocha, João BT; Aschner, Michael; Farina, Marcelo

2010-01-01

During the perinatal period, the central nervous system (CNS) is extremely sensitive to metals, including methylmercury (MeHg). Although the mechanism(s) associated with MeHg-induced developmental neurotoxicity remains obscure, several studies point to the glutathione (GSH) antioxidant system as an important molecular target for this toxicant. To extend our recent findings of MeHg-induced GSH dyshomeostasis, the present study was designed to assess the developmental profile of the GSH antioxidant system in the mouse brain during the early postnatal period after in utero exposure to MeHg. Pregnant mice were exposed to different doses of MeHg (1, 3 and 10 mg/L, diluted in drinking water, ad libitum) during the gestational period. After delivery, pups were killed at different time points - postnatal days (PNDs) 1, 11 and 21 - and the whole brain was used for determining biochemical parameters related to the antioxidant GSH system, as well as mercury content and the levels of F2-isoprostane. In control animals, cerebral GSH levels significantly increased over time during the early postnatal period; gestational exposure to MeHg caused a dose-dependent inhibition of this developmental event. Cerebral glutathione peroxidase (GPx) and glutathione reductase (GR) activities significantly increased over time during the early postnatal period in control animals; gestational MeHg exposure induced a dose-dependent inhibitory effect on both developmental phenomena. These adverse effects of prenatal MeHg exposure were corroborated by marked increases in cerebral F2-isoprostanes levels at all time points. Significant negative correlations were found between F2-isoprostanes and GSH, as well as between F2-isoprostanes and GPx activity, suggesting that MeHg-induced disruption of the GSH system maturation is related to MeHg-induced increased lipid peroxidation in the pup brain. In utero MeHg exposure also caused a dose-dependent increase in the cerebral levels of mercury at birth. Even though the cerebral mercury concentration decreased to nearly basal levels at postnatal day 21, GSH levels, GPx and GR activities remained decreased in MeHg-exposed mice, indicating that prenatal exposure to MeHg affects the cerebral GSH antioxidant systems by inducing biochemical alterations that endure even when mercury tissue levels decrease and become indistinguishable from those noted in pups born to control dams. This study is the first to show that prenatal exposure to MeHg disrupts the postnatal development of the glutathione antioxidant system in the mouse brain, pointing to an additional molecular mechanism by which MeHg induces pro-oxidative damage in the developing CNS. Moreover, our experimental observation corroborates previous reports on the permanent functional deficits observed after prenatal MeHg exposure. PMID:18023834

Objective assessment of gait in xylazine-induced ataxic horses.

PubMed

Nout-Lomas, Y S; Page, K M; Kang, H G; Aanstoos, M E; Greene, H M

2017-05-01

There is poor agreement between observers of equine neurological gait abnormalities using the modified Mayhew grading scale. To stimulate a dose-dependent ataxia in horses through xylazine administration and identify quantifiable relevant gait parameters. Balanced, randomised, 2-way crossover design. Eight horses were assessed before and after administration of xylazine (low dose and high dose). Gait analyses performed before and after xylazine administration included: 1) kinematic data collected on an equine high-speed treadmill (flat and 10% decline) and from accelerometers placed on head and sacrum; and 2) kinetic data collected on a force plate. All horses developed dose-dependent ataxia. Horses developed a dose-dependent increased stride time, stride length, and time of contact (P<0.0001), and a decreased stride frequency (P<0.0002) after administration of xylazine. Although pelvic acceleration increased in the mediolateral direction (P<0.05) in horses walked on the treadmill, this movement decreased when walking over ground after administration of xylazine (P<0.05). Furthermore, centre of pressure and path length indices changed significantly in horses following administration of xylazine (P<0.05). This study examined one breed of horse (Arabian), all of similar height and weight. Accelerometers were attached to skin, not bone; no correction was made for artefacts from skin displacement. The sedative drug effect is of certain duration, limiting the data collection period. Administration of xylazine induced a dose-dependent ataxia in horses and resulted in significant changes of gait parameters, pelvic accelerations, and stabilographic variables, some of which changed in a dose-dependent fashion. Some of the altered gait parameters in this model were probably a result of overall slowing down of the stride cycle secondary to the sedative effect. Continued efforts to discover and evaluate quantifiable gait parameters that are susceptible to change following development of clinical neurological disease in horses is warranted. © 2016 EVJ Ltd.

Europe. An analysis of changes in the consumption of alcoholic beverages: the interaction among consumption, related harms, contextual factors and alcoholic beverage control policies.

PubMed

Allamani, Allaman; Pepe, Pasquale; Baccini, Michela; Massini, Giulia; Voller, Fabio

2014-10-01

This AMPHORA study's aim was to investigate selected factors potentially affecting changes in consumption of alcoholic beverages in 12 European countries during the 1960s-2008 (an average increase in beer, decreases in wine and spirits, total alcohol drinking decrease). Both time series and artificial neural networks-based analyses were used. Results indicated that selected socio-demographic and economic factors showed an overall major impact on consumption changes; particularly urbanization, increased income, and older mothers' age at their childbirths were significantly associated with consumption increase or decrease, depending on the country. Alcoholic beverage control policies showed an overall minor impact on consumption changes: among them, permissive availability measures were significantly associated with consumption increases, while drinking and driving limits and availability restrictions were correlated with consumption decreases, and alcohol taxation and prices of the alcoholic beverages were not significantly correlated with consumption. Population ageing, older mother's age at childbirths, increased income and increases in female employment, as well as drink driving limitations were associated with the decrease of transport mortality. Study's limitations are noted.

[Cross-sectional study of informal caregiver burden and the determinants related to the care of dependent persons].

PubMed

Rodríguez-González, Ana María; Rodríguez-Míguez, Eva; Duarte-Pérez, Ana; Díaz-Sanisidro, Eduardo; Barbosa-Álvarez, Ángel; Clavería, Ana

2017-03-01

To describe the burden of informal carers of dependent people and to identify related variables. Descriptive observational cross-sectional study. Primary Health Care in the southern area of Pontevedra. 97 caregivers of dependent persons. We collected socioeconomic data and health conditions from caregivers and dependent persons, time spent on the daily care and caregiver burden (Zarit abbreviate) through a personal interview. Besides the description of the sample-including their burden level-, a contrast mean was used to identify characteristics that influenced in punctuation of Zarit scale. A logistic regression was used to analyse characteristics that increase the likelihood to experiment burden. 61.9% of caregivers are subject to intense burden. The item on the scale which contributes most to the caregiver burden is the lack of time for oneself, followed by the negative effects of interpersonal relationships. Contrast means shows that degree of relationship, number of care hours, caregiver health and aggressiveness of dependent persons produce significant differences in Zarit scale. Physic and psychological health of caregivers and aggressiveness of dependent persons is associated with the likelihood of developing caregiver burden. Informal caregivers of dependent persons show a high level of burden, both related to their characteristics and those of the dependent persons. Caregiver burden rethinks the need for public policies focused on dependence to adopt an integrative caregiver-dependent vision. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Behavioral, physiological, and endocrine responses of starlings to acute increases in density.

PubMed

Nephew, Benjamin C; Romero, L Michael

2003-09-01

One potential stressor to vertebrates both in the wild and in captivity is the presence of numerous individuals in a confined space. To examine the effects of increased conspecific density in birds, we simultaneously measured cardiac, behavioral, and endocrine responses of European starlings (Sturnus vulgaris) to acute crowding. A cage containing a resident bird was outfitted with a trap door that allowed for the introduction of intruder birds (one, three, or five birds) without human interference. The resident bird was implanted with a subcutaneous heart rate (HR) transmitter, behavior was videotaped through a two-way mirror, and blood samples were taken at the end of each treatment to determine plasma corticosterone (CORT) concentrations. Resident starlings significantly increased both general activity and aggressive behaviors while decreasing preening following the initiation of elevated conspecific density. Intruder starlings increased feeding, drinking, and aggressive pecking rates, but postintrusion feeding rates decreased as intruder number increased. Preening decreased in both residents and intruders following the intrusion. HR increased in the resident starlings at the time of intruder introduction, with an increase in the magnitude of this response directly correlating with increasing intruder number. The CORT response to increased density was dependent on social role (resident or intruder), since increasing density did not alter CORT levels in resident birds, but resulted in elevated CORT 30 min following the five-intruder introduction in the intruder birds. Together, these data suggest that increased conspecific density is a significant acute stressor in starlings which is capable of inducing aggression in both residents and intruders. Furthermore, it elicits different responses from different physiological and behavioral systems, and behavioral responses such as feeding and general activity may be density-dependent. The data specifically illustrate that cardiac and behavioral activation can be independent of CORT release, and the CORT response of starlings to increased conspecific density is dependent on social role and degree of the increase in density.

Acute high-caffeine exposure increases autophagic flux and reduces protein synthesis in C2C12 skeletal myotubes.

PubMed

Hughes, M A; Downs, R M; Webb, G W; Crocker, C L; Kinsey, S T; Baumgarner, Bradley L

2017-04-01

Caffeine is a highly catabolic dietary stimulant. High caffeine concentrations (1-10 mM) have previously been shown to inhibit protein synthesis and increase protein degradation in various mammalian cell lines. The purpose of this study was to examine the effect of short-term caffeine exposure on cell signaling pathways that regulate protein metabolism in mammalian skeletal muscle cells. Fully differentiated C2C12 skeletal myotubes either received vehicle (DMSO) or 5 mM caffeine for 6 h. Our analysis revealed that caffeine promoted a 40% increase in autolysosome formation and a 25% increase in autophagic flux. In contrast, caffeine treatment did not significantly increase the expression of the skeletal muscle specific ubiquitin ligases MAFbx and MuRF1 or 20S proteasome activity. Caffeine treatment significantly reduced mTORC1 signaling, total protein synthesis and myotube diameter in a CaMKKβ/AMPK-dependent manner. Further, caffeine promoted a CaMKII-dependent increase in myostatin mRNA expression that did not significantly contribute to the caffeine-dependent reduction in protein synthesis. Our results indicate that short-term caffeine exposure significantly reduced skeletal myotube diameter by increasing autophagic flux and promoting a CaMKKβ/AMPK-dependent reduction in protein synthesis.

Measurement of In Vitro Single Cell Temperature by Novel Thermocouple Nanoprobe in Acute Lung Injury Models.

PubMed

Wang, Xing; Chen, Qiuhua; Tian, Wenjuan; Wang, Jianqing; Cheng, Lu; Lu, Jun; Chen, Mingqi; Pei, Yinhao; Li, Can; Chen, Gong; Gu, Ning

2017-01-01

Energy metabolism may alter pattern differences in acute lung injury (ALI) as one of the causes but the detailed features at single-cellular level remain unclear. Changes in intercellular temperature and adenosine triphosphate (ATP) concentration within the single cell may help to understand the role of energy metabolism in causing ALI. ALI in vitro models were established by treating mice lung epithelial (MLE-12) cells with lipopolysaccharide (LPS), hydrogen peroxide (H2O2), hydrochloric acid (HCl) and cobalt chloride (CoCl2, respectively. 100 nm micro thermocouple probe (TMP) was inserted into the cytosol by micromanipulation system and thermoelectric readings were recorded to calculate the intracellular temperature based on standard curve. The total ATP contents for the MLE-12 cells were evaluated at different time intervals after treatments. A significant increase of intracellular temperature was observed after 10 or 20 μg/L LPS and HCl treatments. The HCl increased the temperature in a dose-dependent manner. On the contrary, H2O2 induced a significant decline of intracellular temperature after treatment. No significant difference in intracellular temperature was observed after CoCl2 exposure. The intracellular ATP levels decreased in a time-dependent manner after treatment with H2O2 and HCl, while the LPS and CoCl2 had no significant effect on ATP levels. The intracellular temperature responses varied in different ALI models. The concentration of ATP in the MLE-12 cells played part in the intracellular temperature changes. No direct correlation was observed between the intracellular temperature and concentration of ATP in the MLE-12 cells.

Prognostic impact of peritonitis in hemodialysis patients: A national-wide longitudinal study in Taiwan

PubMed Central

Lee, Cheng-Chia; Wu, Patricia W.; Chang, Chee-Jen; Tian, Ya-Chung; Yang, Chih-Wei

2017-01-01

Background Peritonitis has been independently associated with increased morbidity and mortality in peritoneal dialysis patients. However, there are few reports on peritonitis in hemodialysis patients. We aim at investigating both the risk profiles and prognostic impact of peritonitis in hemodialysis patients. Methods This nation-wide longitudinal study uses claims data obtained from the Taiwan National Health Insurance Research Database. A total of 80,733 incident hemodialysis patients of age ≥ 20 years without a history of peritonitis were identified between January 1, 1998 and December 31, 2009. Predictors of peritonitis events were estimated using Cox proportional hazard models. Time-dependent Cox proportional hazard models were used to estimate hazard ratio for mortality attributed to peritonitis exposure. Results Of 80,733 incident hemodialysis patients over a 13-year study period, peritonitis was diagnosed in 935 (1.16%), yielding an incidence rate of 2.91 per 1000 person-years. Female gender, liver cirrhosis and polycystic kidney disease were three of the most significant factors for peritonitis in both non-diabetic and diabetic hemodialysis patients. The cumulative survival rate of patients with peritonitis was 38.8% at 1 year and 10.1% at 5 years. A time-dependent Cox multivariate analysis showed that peritonitis had significantly increased hazard ratio for all cause mortality. Additionally, the risk of mortality remained significantly higher for non-diabetic hemodialysis patients that experienced peritonitis. Conclusions The risk of peritonitis in hemodialysis patients is higher in female gender, liver cirrhosis and polycystic kidney disease. Although peritonitis is a rare condition, it is associated with significantly poorer outcome in hemodialysis patients. PMID:28301536

Prognostic impact of peritonitis in hemodialysis patients: A national-wide longitudinal study in Taiwan.

PubMed

Lu, Yueh-An; Tu, Kun-Hua; Lee, Cheng-Chia; Wu, Patricia W; Chang, Chee-Jen; Tian, Ya-Chung; Yang, Chih-Wei; Chu, Pao-Hsien

2017-01-01

Peritonitis has been independently associated with increased morbidity and mortality in peritoneal dialysis patients. However, there are few reports on peritonitis in hemodialysis patients. We aim at investigating both the risk profiles and prognostic impact of peritonitis in hemodialysis patients. This nation-wide longitudinal study uses claims data obtained from the Taiwan National Health Insurance Research Database. A total of 80,733 incident hemodialysis patients of age ≥ 20 years without a history of peritonitis were identified between January 1, 1998 and December 31, 2009. Predictors of peritonitis events were estimated using Cox proportional hazard models. Time-dependent Cox proportional hazard models were used to estimate hazard ratio for mortality attributed to peritonitis exposure. Of 80,733 incident hemodialysis patients over a 13-year study period, peritonitis was diagnosed in 935 (1.16%), yielding an incidence rate of 2.91 per 1000 person-years. Female gender, liver cirrhosis and polycystic kidney disease were three of the most significant factors for peritonitis in both non-diabetic and diabetic hemodialysis patients. The cumulative survival rate of patients with peritonitis was 38.8% at 1 year and 10.1% at 5 years. A time-dependent Cox multivariate analysis showed that peritonitis had significantly increased hazard ratio for all cause mortality. Additionally, the risk of mortality remained significantly higher for non-diabetic hemodialysis patients that experienced peritonitis. The risk of peritonitis in hemodialysis patients is higher in female gender, liver cirrhosis and polycystic kidney disease. Although peritonitis is a rare condition, it is associated with significantly poorer outcome in hemodialysis patients.

Potential Protective Effects of Ursolic Acid against Gamma Irradiation-Induced Damage Are Mediated through the Modulation of Diverse Inflammatory Mediators

PubMed Central

Wang, Hong; Sim, Meng-Kwoon; Loke, Weng Keong; Chinnathambi, Arunachalam; Alharbi, Sulaiman Ali; Tang, Feng Ru; Sethi, Gautam

2017-01-01

This study was aimed to evaluate the possible protective effects of ursolic acid (UA) against gamma radiation induced damage both in vitro as well as in vivo. It was observed that the exposure to gamma radiation dose- and time-dependently caused a significant decrease in the cell viability, while the treatment of UA attenuated this cytotoxicity. The production of free radicals including reactive oxygen species (ROS) and NO increased significantly post-irradiation and further induced lipid peroxidation and oxidative DNA damage in cells. These deleterious effects could also be effectively blocked by UA treatment. In addition, UA also reversed gamma irradiation induced inflammatory responses, as indicated by the decreased production of TNF-α, IL-6, and IL-1β. NF-κB signaling pathway has been reported to be a key mediator involved in gamma radiation-induced cellular damage. Our results further demonstrated that gamma radiation dose- and time-dependently enhanced NF-κB DNA binding activity, which was significantly attenuated upon UA treatment. The post-irradiation increase in the expression of both phospho-p65, and phospho-IκBα was also blocked by UA. Moreover, the treatment of UA was found to significantly prolong overall survival in mice exposed to whole body gamma irradiation, and reduce the excessive inflammatory responses. Given its radioprotective efficacy as described here, UA as an antioxidant and NF-κB pathway blocker, may function as an important pharmacological agent in protecting against gamma irradiation-induced injury. PMID:28670276

Licochalcone-A Induces Intrinsic and Extrinsic Apoptosis via ERK1/2 and p38 Phosphorylation-mediated TRAIL Expression in Head and Neck Squamous Carcinoma FaDu Cells

PubMed Central

Park, Mi-Ra; Kim, Su-Gwan; Cho, In-A; Oh, Dahye; Kang, Kyeong-Rok; Lee, Sook-Young; Moon, Sung-Min; Cho, Seung Sik; Yoon, Goo; Kim, Chun Sung; Oh, Ji-Su; You, Jae-Seek; Kim, Do Kyung; Seo, Yo-Seob; Im, Hee-Jeong; Kim, Jae-Sung

2015-01-01

We investigated Licochalcone-A (Lico-A)-induced apoptosis and the pathway underlying its activity in a pharyngeal squamous carcinoma FaDu cell line. Lico-A purified from root of Glycyrrhiza inflata had cytotoxic effects, significantly increasing cell death in FaDu cells. Using a cell viability assay, we determined that the IC50 value of Lico-A in FaDu cells was approximately 100 µM. Chromatin condensation was observed in FaDu cells treated with Lico-A for 24 h. Consistent with this finding, the number of apoptotic cells increased in a time-dependent manner when FaDu cells were treated with Lico-A. TRAIL was significantly up-regulated in Lico-A-treated FaDu cells in a dose-dependent manner. Apoptotic factors such as caspases and PARP polymerase were subsequently activated in a caspase-dependent manner. In addition, levels of pro-apoptotic factors increased significantly in response to Lico-A treatment, while levels of anti-apoptotic factors decreased. Lico-A-induced TRAIL expression was mediated in part by a MAPK signaling pathway involving ERK1/2 and p38. Lastly, in an in vivo xenograft mouse model, Lico-A treatment effectively suppressed the growth of FaDu cell xenografts by activating caspase-3, without affecting the body weight of mice. Taken together, these data suggest that Lico-A has potential chemopreventive effects and should therefore be developed as a chemotherapeutic agent for pharyngeal squamous carcinoma. PMID:25572524

Effect of interfacial slip on the thin film drainage time for two equal-sized, surfactant-free drops undergoing a head-on collision: A scaling analysis

NASA Astrophysics Data System (ADS)

Ramachandran, A.; Leal, L. G.

2016-10-01

Using a scaling analysis, we assess the impact of interfacial slip on the time required for the thin liquid film between two drops undergoing a head-on collision to drain to the critical thickness for rupture by van der Waals forces. Interfacial slip is included in our continuum development using a Navier slip boundary condition, with the slip coefficient modeled using previous theories [Helfand and Tagami, J. Chem. Phys. 57, 1812 (1972), 10.1063/1.1678491; Goveas and Fredrickson, Eur. Phys. J. B 2, 79 (1998), 10.1007/s100510050228]. Slip decreases hydrodynamic resistance and speeds up film drainage. It renders the dependence of the drainage time on capillary number stronger in the spherical-film regime, but, interestingly, this dependence is altered only weakly in the dimpled-film regime. A subtle effect of slip is that it increases the range of capillary numbers in which the film remains predominantly spherical in shape during drainage (as opposed to being dimpled), leading to significantly faster drainage for these capillary numbers. Slip also leads to an increase in the critical capillary number beyond which coalescence is not possible in a head-collision.

Effects of Alcohol on Performance on a Distraction Task During Simulated Driving

PubMed Central

Allen, Allyssa J.; Meda, Shashwath A.; Skudlarski, Pawel; Calhoun, Vince; Astur, Robert; Ruopp, Kathryn C.; Pearlson, Godfrey D.

2009-01-01

Background Prior studies report that accidents involving intoxicated drivers are more likely to occur during performance of secondary tasks. We studied this phenomenon, using a dual-task paradigm, involving performance of a visual oddball (VO) task while driving in an alcohol challenge paradigm. Previous functional MRI (fMRI) studies of the VO task have shown activation in the anterior cingulate, hippocampus, and prefrontal cortex. Thus, we predicted dose-dependent decreases in activation of these areas during VO performance. Methods Forty healthy social drinkers were administered 3 different doses of alcohol, individually tailored to their gender and weight. Participants performed a VO task while operating a virtual reality driving simulator in a 3T fMRI scanner. Results Analysis showed a dose-dependent linear decrease in Blood Oxygen Level Dependent activation during task performance, primarily in hippocampus, anterior cingulate, and dorsolateral prefrontal areas, with the least activation occurring during the high dose. Behavioral analysis showed a dose-dependent linear increase in reaction time, with no effects associated with either correct hits or false alarms. In all dose conditions, driving speed decreased significantly after a VO stimulus. However, at the high dose this decrease was significantly less. Passenger-side line crossings significantly increased at the high dose. Conclusions These results suggest that driving impairment during secondary task performance may be associated with alcohol-related effects on the above brain regions, which are involved with attentional processing/decision-making. Drivers with high blood alcohol concentrations may be less able to orient or detect novel or sudden stimuli during driving. PMID:19183133

Involvement of the bax and bcl-2 system in the induction of germ cell apoptosis is correlated with the time of reperfusion after testicular ischemia in a rat model.

PubMed

Sukhotnik, Igor; Voskoboinik, Katya; Lurie, Michael; Bejar, Yakov; Coran, Arnold G; Mogilner, Jorge G

2009-10-01

The objective of this study was to examine the relationship between time of reperfusion and bax/bcl-2-dependent germ cell apoptosis after testicular ischemia-reperfusion injury in the rat. In ischemic testis, bax/bcl-2 ratio did not change significantly, and the elevation of germ cell apoptosis was not marked; in the contralateral testis, germ cell apoptosis increased after 6 hours of reperfusion, achieved statistical significance after 24 hours, and decreased after 72 hours of reperfusion and was initiated by decreased bcl-2 messenger RNA levels and elevated bax/bcl-2 ratio within the first 6 hours of reperfusion.

Pepsi® or Coke®? Influence of acid on dasatinib absorption.

PubMed

Knoebel, Randall W; Larson, Richard A

2018-03-01

Dasatinib is a second generation ABL kinase inhibitor used in the management of chronic myeloid leukemia or Philadelphia chromosome positive acute lymphoblastic leukemia (Ph+ ALL). Dasatinib's bioavailability is highly dependent on gastric pH. When proton-pump inhibitors (PPIs) are co-administered with dasatinib, absorption is significantly reduced. Cola intake at the time of drug administration has been demonstrated to lead to relevant increases in the bioavailability for other acid labile drugs during PPI treatment. This manuscript reviews the relevant literature supporting a strategy of temporarily lowering the gastric pH with a carbonated beverage at the time of drug administration. The use of cola provides an easy to implement way to significantly improve dasatinib bioavailability, especially during concomitant use of a PPI.

Cytosolic NADP+-dependent isocitrate dehydrogenase plays a key role in lipid metabolism.

PubMed

Koh, Ho-Jin; Lee, Su-Min; Son, Byung-Gap; Lee, Soh-Hyun; Ryoo, Zae Young; Chang, Kyu-Tae; Park, Jeen-Woo; Park, Dong-Chan; Song, Byoung J; Veech, Richard L; Song, Hebok; Huh, Tae-Lin

2004-09-17

NADPH is an essential cofactor for many enzymatic reactions including glutathione metabolism and fat and cholesterol biosynthesis. We have reported recently an important role for mitochondrial NADP(+)-dependent isocitrate dehydrogenase in cellular defense against oxidative damage by providing NADPH needed for the regeneration of reduced glutathione. However, the role of cytosolic NADP(+)-dependent isocitrate dehydrogenase (IDPc) is still unclear. We report here for the first time that IDPc plays a critical role in fat and cholesterol biosynthesis. During differentiation of 3T3-L1 adipocytes, both IDPc enzyme activity and its protein content were increased in parallel in a time-dependent manner. Increased expression of IDPc by stable transfection of IDPc cDNA positively correlated with adipogenesis of 3T3-L1 cells, whereas decreased IDPc expression by an antisense IDPc vector retarded adipogenesis. Furthermore, transgenic mice with overexpressed IDPc exhibited fatty liver, hyperlipidemia, and obesity. In the epididymal fat pads of the transgenic mice, the expressions of adipocyte-specific genes including peroxisome proliferator-activated receptor gamma were markedly elevated. The hepatic and epididymal fat pad contents of acetyl-CoA and malonyl-CoA in the transgenic mice were significantly lower, whereas the total triglyceride and cholesterol contents were markedly higher in the liver and serum of transgenic mice compared with those measured in wild type mice, suggesting that the consumption rate of those lipogenic precursors needed for fat biosynthesis must be increased by elevated IDPc activity. Taken together, our findings strongly indicate that IDPc would be a major NADPH producer required for fat and cholesterol synthesis.

Influence of Temperature on the Colloidal Stability of Polymer-Coated Gold Nanoparticles in Cell Culture Media.

PubMed

Zyuzin, Mikhail V; Honold, Tobias; Carregal-Romero, Susana; Kantner, Karsten; Karg, Matthias; Parak, Wolfgang J

2016-04-06

The temperature-dependence of the hydrodynamic diameter and colloidal stability of gold-polymer core-shell particles with temperature-sensitive (poly(N-isopropylacrylamide)) and temperature-insensitive shells (polyallylaminine hydrochloride/polystyrensulfonate, poly(isobutylene-alt-maleic anhydride)-graft-dodecyl) are investigated in various aqueous media. The data demonstrate that for all nanoparticle agglomeration, i.e., increase in effective nanoparticle size, the presence of salts or proteins in the dispersion media has to be taken into account. Poly(N-isopropylacrylamide) coated nanoparticles show a reversible temperature-dependent increase in size above the volume phase transition of the polymer shell when they are dispersed in phosphate buffered saline or in media containing protein. In contrast, the nanoparticles coated with temperature-insensitive polymers show a time-dependent increase in size in phosphate buffered saline or in medium containing protein. This is due to time-dependent agglomeration, which is particularly strong in phosphate buffered saline, and induces a time-dependent, irreversible increase in the hydrodynamic diameter of the nanoparticles. This demonstrates that one has to distinguish between temperature- and time-induced agglomerations. Since the size of nanoparticles regulates their uptake by cells, temperature-dependent uptake of thermosensitive and non-thermosensitive nanoparticles by cells lines is compared. No temperature-specific difference between both types of nanoparticles could be observed. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Electron transfer beyond the static picture: A TDDFT/TD-ZINDO study of a pentacene dimer

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

Reslan, Randa; Lopata, Kenneth; Arntsen, Christopher

2012-12-14

We use time-dependent density functional theory and time-dependent ZINDO (a semi-empirical method) to study transfer of an extra electron between a pair of pentacene molecules. A measure of the electronic transfer integral is computed in a dynamic picture via the vertical excitation energy from a delocalized anionic ground state. With increasing dimer separation, this dynamical measurement of charge transfer is shown to be significantly larger than the commonly used static approximation (i.e., LUMO+1–LUMO of the neutral dimer, or HOMO–LUMO of the charged dimer), up to an order of magnitude higher at 6 Å. These results offer a word of cautionmore » for calculations involving large separations, as in organic photovoltaics, where care must be taken when using a static picture to model charge transfer.« less

Electron transfer beyond the static picture: A TDDFT/TD-ZINDO study of a pentacene dimer

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

Reslan, Randa; Lopata, Kenneth A.; Arntsen, Christopher D.

2012-12-14

We use time-dependent density functional theory and time-dependent ZINDO (a semi-empirical method) to study transfer of an extra electron between a pair of pentacene dimers. A measure of the electronic transfer integral is computed in a dynamic picture via the vertical excitation energy from a delocalized anionic ground state. With increasing dimer separation, this dynamical measurement of charge transfer is shown to be significantly larger than the commonly used static approximation (i.e., LUMO+1 - LUMO of the neutral dimer, or HOMO - LUMO of the charged dimer), up to an order of magnitude higher at 6 Å. These results offermore » a word of caution for calculations involving large separations, as in organic photovoltaics, where care must be taken when using a static picture to model charge transfer.« less

Modulation of inward rectifier potassium channel by toosendanin, a presynaptic blocker.

PubMed

Wang, Z F; Shi, Y L

2001-07-01

The effect of toosendanin, a presynaptic blocker, on the inward rectifier potassium channel (K(Kir)) of hippocampal CA1 pyramidal neurons of rats was studied by the single-channel patch-clamp technique. The results showed that toosendanin had an inhibitory effect on K(Kir) in an excised inside-out patch of the neuron under a symmetrical 150 mM K(+) condition. By decreasing the slower open time constant and increasing the slower close time constant, toosendanin (1x10(-6)-1x10(-4) g/ml) significantly reduced the open probability of the channel in a concentration-dependent manner. Meanwhile, a dose-dependent reduction in unitary conductance of the channel was also detected after toosendanin application. These data offer an explanation for toosendanin-induced facilitation of neurotransmitter release and antibotulismic effect of the drug.

Folding time dependence of the motions of a molecular motor in an amorphous medium

NASA Astrophysics Data System (ADS)

Ciobotarescu, Simona; Bechelli, Solene; Rajonson, Gabriel; Migirditch, Samuel; Hester, Brooke; Hurduc, Nicolae; Teboul, Victor

2017-12-01

We investigate the dependence of the displacements of a molecular motor embedded inside a glassy material on its folding characteristic time τf. We observe two different time regimes. For slow foldings (regime I) the diffusion evolves very slowly with τf, while for rapid foldings (regime II) the diffusion increases strongly with τf(D ≈τf-2 ), suggesting two different physical mechanisms. We find that in regime I the motor's displacement during the folding process is counteracted by a reverse displacement during the unfolding, while in regime II this counteraction is much weaker. We notice that regime I behavior is reminiscent of the scallop theorem that holds for larger motors in a continuous medium. We find that the difference in the efficiency of the motor's motion explains most of the observed difference between the two regimes. For fast foldings the motor trajectories differ significantly from the opposite trajectories induced by the following unfolding process, resulting in a more efficient global motion than for slow foldings. This result agrees with the fluctuation theorems expectation for time reversal mechanisms. In agreement with the fluctuation theorems we find that the motors are unexpectedly more efficient when they are generating more entropy, a result that can be used to increase dramatically the motor's motion.

Single-particle fusion of influenza viruses reveals complex interactions with target membranes

NASA Astrophysics Data System (ADS)

van der Borg, Guus; Braddock, Scarlett; Blijleven, Jelle S.; van Oijen, Antoine M.; Roos, Wouter H.

2018-05-01

The first step in infection of influenza A virus is contact with the host cell membrane, with which it later fuses. The composition of the target bilayer exerts a complex influence on both fusion efficiency and time. Here, an in vitro, single-particle approach is used to study this effect. Using total internal reflection fluorescence (TIRF) microscopy and a microfluidic flow cell, the hemifusion of single virions is visualized. Hemifusion efficiency and kinetics are studied while altering target bilayer cholesterol content and sialic-acid donor. Cholesterol ratios tested were 0%, 10%, 20%, and 40%. Sialic-acid donors GD1a and GYPA were used. Both cholesterol ratio and sialic-acid donors proved to have a significant effect on hemifusion efficiency. Furthermore, comparison between GD1a and GYPA conditions shows that the cholesterol dependence of the hemifusion time is severely affected by the sialic-acid donor. Only GD1a shows a clear increasing trend in hemifusion efficiency and time with increasing cholesterol concentration of the target bilayer with maximum rates for GD1A and 40% cholesterol. Overall our results show that sialic acid donor and target bilayer composition should be carefully chosen, depending on the desired hemifusion time and efficiency in the experiment.

FORESHOCKS AND TIME-DEPENDENT EARTHQUAKE HAZARD ASSESSMENT IN SOUTHERN CALIFORNIA.

USGS Publications Warehouse

Jones, Lucile M.

1985-01-01

The probability that an earthquake in southern California (M greater than equivalent to 3. 0) will be followed by an earthquake of larger magnitude within 5 days and 10 km (i. e. , will be a foreshock) is 6 plus or minus 0. 5 per cent (1 S. D. ), and is not significantly dependent on the magnitude of the possible foreshock between M equals 3 and M equals 5. The probability that an earthquake will be followed by an M greater than equivalent to 5. 0 main shock, however, increases with magnitude of the foreshock from less than 1 per cent at M greater than equivalent to 3 to 6. 5 plus or minus 2. 5 per cent (1 S. D. ) at M greater than equivalent to 5. The main shock will most likely occur in the first hour after the foreshock, and the probability that a main shock will occur in the first hour decreases with elapsed time from the occurrence of the possible foreshock by approximately the inverse of time. Thus, the occurrence of an earthquake of M greater than equivalent to 3. 0 in southern California increases the earthquake hazard within a small space-time window several orders of magnitude above the normal background level.

First-in-man-proof of concept study with molidustat: a novel selective oral HIF-prolyl hydroxylase inhibitor for the treatment of renal anaemia.

PubMed

Böttcher, M; Lentini, S; Arens, E R; Kaiser, A; van der Mey, D; Thuss, U; Kubitza, D; Wensing, G

2018-07-01

Insufficient erythropoietin (EPO) synthesis is a relevant cause of renal anaemia in patients with chronic kidney disease. Molidustat, a selective hypoxia-inducible factor prolyl hydroxylase (HIF-PH) inhibitor, increases endogenous EPO levels dose dependently in preclinical models. We examined the pharmacokinetics, safety, tolerability and effect on EPO levels of single oral doses of molidustat in healthy male volunteers. This was a single-centre, randomized, single-blind, placebo-controlled, group-comparison, dose-escalation study. Molidustat was administered at doses of 5, 12.5, 25, 37.5 or 50 mg as a polyethylene glycol-based solution. In total, 45 volunteers received molidustat and 14 received placebo. Molidustat was absorbed rapidly, and the mean maximum plasma concentration and area under the concentration-time curve increased dose dependently. The mean terminal half-life was 4.64-10.40 h. A significant increase in endogenous EPO was observed following single oral doses of molidustat of 12.5 mg and above. Geometric mean peak EPO levels were 14.8 IU l -1 (90% confidence interval 13.0, 16.9) for volunteers who received placebo and 39.8 IU l -1 (90% confidence interval: 29.4, 53.8) for those who received molidustat 50 mg. The time course of EPO levels resembled the normal diurnal variation in EPO. Maximum EPO levels were observed approximately 12 h postdose and returned to baseline after approximately 24-48 h. All doses of molidustat were well tolerated and there were no significant changes in vital signs or laboratory safety parameters. Oral administration of molidustat to healthy volunteers elicited a dose-dependent increase in endogenous EPO. These results support the ongoing development of molidustat as a potential new treatment for patients with renal anaemia. © 2018 The British Pharmacological Society.

Autonomic, neuroendocrine, and immunological effects of ayahuasca: a comparative study with d-amphetamine.

PubMed

Dos Santos, Rafael G; Valle, Marta; Bouso, José Carlos; Nomdedéu, Josep F; Rodríguez-Espinosa, José; McIlhenny, Ethan H; Barker, Steven A; Barbanoj, Manel J; Riba, Jordi

2011-12-01

Ayahuasca is an Amazonian psychotropic plant tea combining the 5-HT2A agonist N,N-dimethyltryptamine (DMT) and monoamine oxidase-inhibiting β-carboline alkaloids that render DMT orally active. The tea, obtained from Banisteriopsis caapi and Psychotria viridis, has traditionally been used for religious, ritual, and medicinal purposes by the indigenous peoples of the region. More recently, the syncretistic religious use of ayahuasca has expanded to the United States and Europe. Here we conducted a double-blind randomized crossover clinical trial to investigate the physiological impact of ayahuasca in terms of autonomic, neuroendocrine, and immunomodulatory effects. An oral dose of encapsulated freeze-dried ayahuasca (1.0 mg DMT/kg body weight) was compared versus a placebo and versus a positive control (20 mg d-amphetamine) in a group of 10 healthy volunteers. Ayahuasca led to measurable DMT plasma levels and distinct subjective and neurophysiological effects that were absent after amphetamine. Both drugs increased pupillary diameter, with ayahuasca showing milder effects. Prolactin levels were significantly increased by ayahuasca but not by amphetamine, and cortisol was increased by both, with ayahuasca leading to the higher peak values. Ayahuasca and amphetamine induced similar time-dependent modifications in lymphocyte subpopulations. Percent CD4 and CD3 were decreased, whereas natural killer cells were increased. Maximum changes occurred around 2 hours, returning to baseline levels at 24 hours. In conclusion, ayahuasca displayed moderate sympathomimetic effects, significant neuroendocrine stimulation, and a time-dependent modulatory effect on cell-mediated immunity. Future studies on the health impact of long-term ayahuasca consumption should consider the assessment of immunological status in regular users.

Impact of partial sleep deprivation on immune markers.

PubMed

Wilder-Smith, A; Mustafa, F B; Earnest, A; Gen, L; Macary, P A

2013-10-01

Sleep quality is considered to be an important predictor of immunity. Lack of sleep therefore may reduce immunity, thereby increasing the susceptibility to respiratory pathogens. A previous study showed that reduced sleep duration was associated with an increased likelihood of the common cold. It is important to understand the role of sleep in altering immune responses to understand how sleep deprivation leads to an increased susceptibility to the common cold or other respiratory infections. We sought to examine the impact of partial sleep deprivation on various immune markers. Fifty-two healthy volunteers were partially sleep deprived for one night. We took blood samples before the sleep deprivation, immediately after, and 4 and 7 days after sleep deprivation. We measured various immune markers and used a generalized estimating equation (GEE) to examine the differences in the repeated measures. CD4, CD8, CD14, and CD16 all showed significant time-dependent changes, but CD3 did not. The most striking time-dependent change was observed for the mitogen proliferation assay and for HLA-DR. There was a significant decrease in the mitogen proliferation values and HLA-DR immediately after the sleep deprivation experiment, which started to rise again on day 4 and normalized by day 7. The transiently impaired mitogen proliferation, the decreased HLA-DR, the upregulated CD14, and the variations in CD4 and CD8 that we observed in temporal relationship with partial sleep deprivation could be one possible explanation for the increased susceptibility to respiratory infections reported after reduced sleep duration. Copyright © 2013 Elsevier B.V. All rights reserved.

Four Transgenerational Demographic Performance of Moina macrocopa Exposed to Chronic Levels of Cadmium.

PubMed

Gama-Flores, José Luis; Huidobro-Salas, María Elena; Sarma, S S S; Nandini, S

2017-01-01

In this study, we quantified intergenerational, demographic variability of Moina macrocopa subjected to cadmium stress. Exposure of M macrocopa to cadmium (0.2, 0.3, and 0.4 mg/L as CdCl 2 ) through 4 consecutive generations revealed changes in demographic responses not only in survivorship variables but also in reproductive parameters. Long-term demographic responses varied differently, depending on the demographic trait and the concentration of heavy metal in the medium. With the exception of generation time, all life history traits were significantly and adversely influenced due to increase in Cd concentrations. The average life span of M macrocopa varied up to 40% depending on Cd level and the generation of exposure. The highest gross reproductive rates were recorded in controls, while the lowest (∼30% less) were recorded at the highest Cd level. Survival-weighted net reproductive rates were reduced by nearly 50% due to Cd toxicity. The rate of population increase per day of M macrocopa was also significantly affected (∼25%) by Cd as compared to controls. This cladoceran showed a dose-response to Cd toxicity with a significance in both magnitude and frequency of offspring production.

Four Transgenerational Demographic Performance of Moina macrocopa Exposed to Chronic Levels of Cadmium

PubMed Central

Gama-Flores, José Luis; Huidobro-Salas, María Elena; Sarma, S.S.S.; Nandini, S.

2017-01-01

In this study, we quantified intergenerational, demographic variability of Moina macrocopa subjected to cadmium stress. Exposure of M macrocopa to cadmium (0.2, 0.3, and 0.4 mg/L as CdCl2) through 4 consecutive generations revealed changes in demographic responses not only in survivorship variables but also in reproductive parameters. Long-term demographic responses varied differently, depending on the demographic trait and the concentration of heavy metal in the medium. With the exception of generation time, all life history traits were significantly and adversely influenced due to increase in Cd concentrations. The average life span of M macrocopa varied up to 40% depending on Cd level and the generation of exposure. The highest gross reproductive rates were recorded in controls, while the lowest (∼30% less) were recorded at the highest Cd level. Survival-weighted net reproductive rates were reduced by nearly 50% due to Cd toxicity. The rate of population increase per day of M macrocopa was also significantly affected (∼25%) by Cd as compared to controls. This cladoceran showed a dose–response to Cd toxicity with a significance in both magnitude and frequency of offspring production. PMID:28835748

Improved statistical analysis of moclobemide dose effects on panic disorder treatment.

PubMed

Ross, Donald C; Klein, Donald F; Uhlenhuth, E H

2010-04-01

Clinical trials with several measurement occasions are frequently analyzed using only the last available observation as the dependent variable [last observation carried forward (LOCF)]. This ignores intermediate observations. We reanalyze, with complete data methods, a clinical trial previously reported using LOCF, comparing placebo and five dosage levels of moclobemide in the treatment of outpatients with panic disorder to illustrate the superiority of methods using repeated observations. We initially analyzed unprovoked and situational, major and minor attacks as the four dependent variables, by repeated measures maximum likelihood methods. The model included parameters for linear and curvilinear time trends and regression of measures during treatment on baseline measures. Significance tests using this method take into account the structure of the error covariance matrix. This makes the sphericity assumption irrelevant. Missingness is assumed to be unrelated to eventual outcome and the residuals are assumed to have a multivariate normal distribution. No differential treatment effects for limited attacks were found. Since similar results were obtained for both types of major attack, data for the two types of major attack were combined. Overall downward linear and negatively accelerated downward curvilinear time trends were found. There were highly significant treatment differences in the regression slopes of scores during treatment on baseline observations. For major attacks, all treatment groups improved over time. The flatter regression slopes, obtained with higher doses, indicated that higher doses result in uniformly lower attack rates regardless of initial severity. Lower doses do not lower the attack rate of severely ill patients to those achieved in the less severely ill. The clinical implication is that more severe patients require higher doses to attain best benefit. Further, the significance levels obtained by LOCF analyses were only in the 0.05-0.01 range, while significance levels of <0.00001 were obtained by these repeated measures analyses indicating increased power. The greater sensitivity to treatment effect of this complete data method is illustrated. To increase power, it is often recommended to increase sample size. However, this is often impractical since a major proportion of the cost per subject is due to the initial evaluation. Increasing the number of repeated observations increases power economically and also allows detailed longitudinal trajectory analyses.

Effects of the new imidazopyridine CL 86-02-01 on isolated papillary muscle of guinea-pig hearts.

PubMed

Studenik, C; Lemmens-Gruber, R; Heistracher, P

1998-06-01

Inotropic activity and the effect of CL 86-02-01 (2-(3-methoxy-5-methylsulfinyl-2-thienyl)-1H-imidazo[4,5-c]pyridine hydrochloride, CAS 109 792-24-7) on membrane resting and action potentials were studied in isolated guinea-pig papillary muscles. Membrane resting potential and action potential parameters were not significantly changed, while CL 86-02-01 exerted a concentration-dependent inotropic effect by increasing the maximum rate of force development and maximum rate of force relaxation. Time to peak force, relaxation time and total contraction time were reduced. These effects are similar to those of beta-adrenergic drugs and phosphodiesterase inhibitors, but markedly differ from those described for other positive inotropic agents like cardiac glycosides, calcium agonists, alpha-adrenergic drugs or increased extracellular calcium concentration.

The effect of time-dependent macromolecular crowding on the kinetics of protein aggregation: a simple model for the onset of age-related neurodegenerative disease

NASA Astrophysics Data System (ADS)

Minton, Allen

2014-08-01

A linear increase in the concentration of "inert" macromolecules with time is incorporated into simple excluded volume models for protein condensation or fibrillation. Such models predict a long latent period during which no significant amount of protein aggregates, followed by a steep increase in the total amount of aggregate. The elapsed time at which these models predict half-conversion of model protein to aggregate varies by less than a factor of two when the intrinsic rate constant for condensation or fibril growth of the protein is varied over many orders of magnitude. It is suggested that this concept can explain why the symptoms of neurodegenerative diseases associated with the aggregation of very different proteins and peptides appear at approximately the same advanced age in humans.

Characterizing the Developmental Trajectory of Sirolimus Clearance in Neonates and Infants

PubMed Central

Emoto, C; Mizuno, T; Schniedewind, B; Christians, Uwe; Adams, DM; Vinks, AA

2016-01-01

Sirolimus is increasingly being used in neonates and infants, but the mechanistic basis of age‐dependent changes in sirolimus disposition has not been fully addressed yet. In order to characterize the age‐dependent changes, serial sirolimus clearance (CL) estimates in individual young pediatric patients were collected and analyzed by population modeling analysis. In addition, sirolimus metabolite formation was also investigated to further substantiate the corresponding age‐dependent change in CYP3A activity. The increasing pattern over time of allometrically size‐normalized sirolimus CL estimates vs. age was well described by a sigmoidal Emax model. This age‐dependent increase was also observed within each individual patient over a 4‐year study period. CYP3A‐dependent sirolimus metabolite formation changed in a similar fashion. This study clearly demonstrates the rapid increase of sirolimus CL over time in neonates and infants, indicating the developmental change. This developmental pattern can be explained by a parallel increase in CYP3A metabolic activity. PMID:27501453

The Role of Gender in Neuropsychological Assessment in Healthy Adolescents.

PubMed

Mormile, Megan Elizabeth Evelyn; Langdon, Jody L; Hunt, Tamerah Nicole

2018-01-01

Research in college athletes has revealed significant gender differences in areas of verbal memory, visual memory, and reaction time. Additionally, research has focused on differences in neuropsychological components and gender in college populations; however, such differences in gender have not been documented in healthy adolescent populations. To identify potential differences between males and females using different components of a common computerized neuropsychological test. A computerized neuropsychological test battery (ImPACT®) was administered to 662 high-school age adolescent athletes (male: n = 451 female: n = 262). Differences between genders were calculated using a 1-way ANOVA. All statistical analyses were conducted using SPSS 23.0. Significance levels were set a priori at P < .05. A 1-way ANOVA revealed statistically significant differences between males and females for composite reaction time (F 1,660  = 10.68, P = .001) and total symptom score (F 1,660  = 81.20, P < .001). However, no statistically significant differences were found between males and females in composite verbal memory, visual memory, visual motor, or impulse control (P > .05). Significant differences between males and females were discovered for composite reaction time and total symptom scores, with females reporting more symptoms and slower reaction times at a baseline assessment. Increased symptom reporting by females may be attributed to both hormonal differences and increased honesty. Quicker reaction times in males may support theories that repetition of activities and quicker muscle contraction are gender dependent. However, additional research is necessary to understand gender differences in adolescent athletes during periods of cognitive and physical maturation.

Bayesian hierarchical modelling of North Atlantic windiness

NASA Astrophysics Data System (ADS)

Vanem, E.; Breivik, O. N.

2013-03-01

Extreme weather conditions represent serious natural hazards to ship operations and may be the direct cause or contributing factor to maritime accidents. Such severe environmental conditions can be taken into account in ship design and operational windows can be defined that limits hazardous operations to less extreme conditions. Nevertheless, possible changes in the statistics of extreme weather conditions, possibly due to anthropogenic climate change, represent an additional hazard to ship operations that is less straightforward to account for in a consistent way. Obviously, there are large uncertainties as to how future climate change will affect the extreme weather conditions at sea and there is a need for stochastic models that can describe the variability in both space and time at various scales of the environmental conditions. Previously, Bayesian hierarchical space-time models have been developed to describe the variability and complex dependence structures of significant wave height in space and time. These models were found to perform reasonably well and provided some interesting results, in particular, pertaining to long-term trends in the wave climate. In this paper, a similar framework is applied to oceanic windiness and the spatial and temporal variability of the 10-m wind speed over an area in the North Atlantic ocean is investigated. When the results from the model for North Atlantic windiness is compared to the results for significant wave height over the same area, it is interesting to observe that whereas an increasing trend in significant wave height was identified, no statistically significant long-term trend was estimated in windiness. This may indicate that the increase in significant wave height is not due to an increase in locally generated wind waves, but rather to increased swell. This observation is also consistent with studies that have suggested a poleward shift of the main storm tracks.

A phthalide derivative isolated from endophytic fungi Pestalotiopsis photiniae induces G1 cell cycle arrest and apoptosis in human HeLa cells

PubMed Central

Chen, C.; Yang, R.L.

2013-01-01

MP [4-(3′,3′-dimethylallyloxy)-5-methyl-6-methoxyphthalide] was obtained from liquid culture of Pestalotiopsis photiniae isolated from the Chinese Podocarpaceae plant Podocarpus macrophyllus. MP significantly inhibited the proliferation of HeLa tumor cell lines. After treatment with MP, characteristic apoptotic features such as DNA fragmentation and chromatin condensation were observed in DAPI-stained HeLa cells. Flow cytometry showed that MP induced G1 cell cycle arrest and apoptosis in a dose-dependent manner. Western blotting and real-time reverse transcription-polymerase chain reaction were used to investigate protein and mRNA expression. MP caused significant cell cycle arrest by upregulating the cyclin-dependent kinase inhibitor p27KIP1 protein and p21CIP1 mRNA levels in HeLa cells. The expression of p73 protein was increased after treatment with various MP concentrations. mRNA expression of the cell cycle-related genes, p21CIP1, p16INK4a and Gadd45α, was significantly upregulated and mRNA levels demonstrated significantly increased translation of p73, JunB, FKHR, and Bim. The results indicate that MP may be a potential treatment for cervical cancer. PMID:23903687

Shorter Exposures to Harder X-Rays Trigger Early Apoptotic Events in Xenopus laevis Embryos

PubMed Central

Dong, JiaJia; Mury, Sean P.; Drahos, Karen E.; Moscovitch, Marko

2010-01-01

Background A long-standing conventional view of radiation-induced apoptosis is that increased exposure results in augmented apoptosis in a biological system, with a threshold below which radiation doses do not cause any significant increase in cell death. The consequences of this belief impact the extent to which malignant diseases and non-malignant conditions are therapeutically treated and how radiation is used in combination with other therapies. Our research challenges the current dogma of dose-dependent induction of apoptosis and establishes a new parallel paradigm to the photoelectric effect in biological systems. Methodology/Principal Findings We explored how the energy of individual X-ray photons and exposure time, both factors that determine the total dose, influence the occurrence of cell death in early Xenopus embryo. Three different experimental scenarios were analyzed and morphological and biochemical hallmarks of apoptosis were evaluated. Initially, we examined cell death events in embryos exposed to increasing incident energies when the exposure time was preset. Then, we evaluated the embryo's response when the exposure time was augmented while the energy value remained constant. Lastly, we studied the incidence of apoptosis in embryos exposed to an equal total dose of radiation that resulted from increasing the incoming energy while lowering the exposure time. Conclusions/Significance Overall, our data establish that the energy of the incident photon is a major contributor to the outcome of the biological system. In particular, for embryos exposed under identical conditions and delivered the same absorbed dose of radiation, the response is significantly increased when shorter bursts of more energetic photons are used. These results suggest that biological organisms display properties similar to the photoelectric effect in physical systems and provide new insights into how radiation-mediated apoptosis should be understood and utilized for therapeutic purposes. PMID:20126466

Two-year follow-up of changes in bite force and occlusal contact area after intraoral vertical ramus osteotomy with and without Le Fort I osteotomy.

PubMed

Choi, Y J; Lim, H; Chung, C J; Park, K H; Kim, K H

2014-06-01

This study was performed to examine the longitudinal changes in bite force and occlusal contact area after mandibular setback surgery via intraoral vertical ramus osteotomy (IVRO). Patients with mandibular prognathism who underwent IVRO (surgical group: 39 men and 39 women) were compared with subjects with class I skeletal and dental relationships (control group; 32 men and 35 women). The surgical group was divided into two subgroups: 1-jaw surgery (n = 30) and 2-jaw surgery (n = 48). Bite force and contact area were measured in maximum intercuspation with the Dental Prescale System before treatment, within 1 month before surgery, and at 1, 3, 6, 9, 12, and 24 months postsurgery. A linear mixed model was used to investigate the time-dependent changes and associated factors. Bite force and contact area decreased during presurgical orthodontic treatment, were minimal at 1 month postsurgery, and increased gradually thereafter. The 1-jaw and 2-jaw subgroups showed no significant differences in bite force. The time-dependent changes in bite force were significantly different according to the contact area (P < 0.05). The results of this study suggest that bite force and occlusal contact area gradually increase throughout the postsurgical evaluation period. Increasing the occlusal contact area may be essential for improving bite force after surgery. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Extreme Unconditional Dependence Vs. Multivariate GARCH Effect in the Analysis of Dependence Between High Losses on Polish and German Stock Indexes

NASA Astrophysics Data System (ADS)

Rokita, Pawel

Classical portfolio diversification methods do not take account of any dependence between extreme returns (losses). Many researchers provide, however, some empirical evidence for various assets that extreme-losses co-occur. If the co-occurrence is frequent enough to be statistically significant, it may seriously influence portfolio risk. Such effects may result from a few different properties of financial time series, like for instance: (1) extreme dependence in a (long-term) unconditional distribution, (2) extreme dependence in subsequent conditional distributions, (3) time-varying conditional covariance, (4) time-varying (long-term) unconditional covariance, (5) market contagion. Moreover, a mix of these properties may be present in return time series. Modeling each of them requires different approaches. It seams reasonable to investigate whether distinguishing between the properties is highly significant for portfolio risk measurement. If it is, identifying the effect responsible for high loss co-occurrence would be of a great importance. If it is not, the best solution would be selecting the easiest-to-apply model. This article concentrates on two of the aforementioned properties: extreme dependence (in a long-term unconditional distribution) and time-varying conditional covariance.

Theoretical Prediction of Si 2–Si 33 Absorption Spectra

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

Zhao, Li -Zhen; Lu, Wen -Cai; Qin, Wei

Here, the optical absorption spectra of Si 2–Si 33 clusters were systematically studied by a time-dependent density functional theory approach. The calculations revealed that the absorption spectrum becomes significantly broad with increasing cluster size, stretching from ultraviolet to the infrared region. The absorption spectra are closely related to the structural motifs. With increasing cluster size, the absorption intensity of cage structures gradually increases, but the absorption curves of the prolate and the Y-shaped structures are very sensitive to cluster size. If the transition energy reaches ~12 eV, it is noted that all the clusters have remarkable absorption in deep ultravioletmore » region of 100–200 nm, and the maximum absorption intensity is ~100 times that in the visible region. Further, the optical responses to doping in the Si clusters were studied.« less

Theoretical Prediction of Si 2–Si 33 Absorption Spectra

DOE PAGES

Zhao, Li -Zhen; Lu, Wen -Cai; Qin, Wei; ...

2017-07-07

Here, the optical absorption spectra of Si 2–Si 33 clusters were systematically studied by a time-dependent density functional theory approach. The calculations revealed that the absorption spectrum becomes significantly broad with increasing cluster size, stretching from ultraviolet to the infrared region. The absorption spectra are closely related to the structural motifs. With increasing cluster size, the absorption intensity of cage structures gradually increases, but the absorption curves of the prolate and the Y-shaped structures are very sensitive to cluster size. If the transition energy reaches ~12 eV, it is noted that all the clusters have remarkable absorption in deep ultravioletmore » region of 100–200 nm, and the maximum absorption intensity is ~100 times that in the visible region. Further, the optical responses to doping in the Si clusters were studied.« less

Investigation of the effect of a panel of model hepatotoxins on the Nrf2-Keap1 defence response pathway in CD-1 mice.

PubMed

Randle, Laura E; Goldring, Chris E P; Benson, Craig A; Metcalfe, Peter N; Kitteringham, Neil R; Park, B Kevin; Williams, Dominic P

2008-01-20

The Keap1-Nrf2-ARE signalling pathway has emerged as an important regulator of the mammalian defence system to enable detoxification and clearance of foreign chemicals. Recent studies by our group using paracetamol (APAP), diethylmaleate and buthionine sulphoximine have shown that for a given xenobiotic molecule, Nrf2 induction in the murine liver is associated with protein reactivity and glutathione depletion. Here, we have investigated, in vivo, whether the ability of four murine hepatotoxins, paracetamol, bromobenzene (BB), carbon tetrachloride (CCl4) and furosemide (FS) to deplete hepatic glutathione (GSH) is related to induction of hepatic Nrf2 nuclear translocation and Nrf2-dependent gene expression. Additionally, we studied whether hepatic Nrf2 nuclear translocation is a general response during the early stages of acute hepatic chemical stress in vivo. Male CD-1 mice were administered APAP (3.5 mmol/kg), FS (1.21 mmol/kg), BB (4.8 mmol/kg) and CCl4 (1 mmol/kg) for 1, 5 and 24h. Each compound elicited significant serum ALT increases after 24h (ALT U/L: APAP, 3036+/-1462; BB, 5308+/-2210; CCl4, 5089+/-1665; FS, 2301+/-1053), accompanied by centrilobular damage as assessed by histopathology. Treatment with APAP also elicited toxicity at a much earlier time point (5h) than the other hepatotoxins (ALT U/L: APAP, 1780+/-661; BB, 161+/-15; CCl4, 90+/-23; FS, 136+/-27). Significant GSH depletion was seen with APAP (9.6+/-1.7% of control levels) and BB (52.8+/-6.2% of control levels) 1h after administration, but not with FS and CCl4. Western Blot analysis revealed an increase in nuclear Nrf2, 1h after administration of BB (209+/-10% control), CCl4 (146+/-3% control) and FS (254+/-41% control), however this was significantly lower than the levels observed in the APAP-treated mice (462+/-36% control). The levels of Nrf2-dependent gene induction were also analysed by quantitative real-time PCR and Western blotting. Treatment with APAP for 1h caused a significant increase in the levels of haem oxygenase-1 (HO-1; 2.85-fold) and glutamate cysteine ligase (GCLC; 1.62-fold) mRNA. BB and FS did not affect the mRNA levels of either gene after 1h of treatment; however CCl4 significantly increased HO-1 mRNA at this time point. After 24h treatment with the hepatotoxins, there was evidence for the initiation of a late defence response. BB significantly increased both HO-1 and GCLC protein at this time point, CCl4 increased GCLC protein alone, although FS did not alter either of these proteins. In summary, we have demonstrated that the hepatotoxins BB, CCl4 and FS can induce a small but significant increase in Nrf2 accumulation in hepatic nuclei. However, this was associated with modest changes in hepatic GSH, a delayed development of toxicity and was insufficient to activate an early functional adaptive response to these hepatotoxins.

Exploring variable patterns of density-dependent larval settlement among corals with distinct and shared functional traits

NASA Astrophysics Data System (ADS)

Doropoulos, Christopher; Gómez-Lemos, Luis A.; Babcock, Russell C.

2018-03-01

Coral settlement is a key process for the recovery and maintenance of coral reefs, yet interspecific variations in density-dependent settlement are unknown. Settlement of the submassive Goniastrea retiformis and corymbose Acropora digitifera and A. millepora was quantified at densities ranging from 1 to 50 larvae per 20 mL from 110 to 216 h following spawning. Settlement patterns were distinct for each species. Goniastrea settlement was rapid and increased linearly with time, whereas both Acropora spp. hardly settled until crustose coralline algae was provided. Both Goniastrea and A. digitifera showed positive density-dependent settlement, but the relationship was exponential for Goniastrea but linear for A. digitifera. Settlement was highest but density independent in A. millepora. Our results suggest that larval density can have significant effects on settler replenishment, and highlight variability in density-dependent settlement among corals with distinct functional traits as well as those with similar functional forms.

High glucose condition increases NADPH oxidase activity in endothelial microparticles that promote vascular inflammation.

PubMed

Jansen, Felix; Yang, Xiaoyan; Franklin, Bernardo S; Hoelscher, Marion; Schmitz, Theresa; Bedorf, Jörg; Nickenig, Georg; Werner, Nikos

2013-04-01

Diabetes is a major risk factor for cardiovascular diseases. Circulating endothelial microparticles (EMP) are increased in diabetic patients, but their potential contribution in atherogenesis is unclear. We sought to determine the role of EMP derived under high glucose conditions in the development of atherosclerosis. EMP were generated from human coronary endothelial cells (HCAEC) exposed to high glucose concentrations in order to mimic diabetic conditions. These EMP were defined as 'injured' EMP (iEMP) and their effects were compared with EMP generated from 'healthy' untreated HCAEC. iEMP injection significantly impaired endothelial function in ApoE(-/-) mice compared with EMP and vehicle treatment. Immunofluorescent experiments showed increased macrophage infiltration and adhesion protein expression in atherosclerotic lesions of iEMP-treated ApoE(-/-) mice compared with controls. To further investigate the underlying mechanism of iEMP-induced vascular inflammation, additional in vitro experiments were performed. iEMP, but not EMP, induced activation of HCAEC in a time- and dose-dependent manner and increased monocyte adhesion. Further experiments demonstrated that iEMP induced activation of HCAEC by phosphorylation of p38 into its biologically active form phospho-p38. Inhibition of p38 activation abrogated iEMP-dependent induction of adhesion proteins and monocyte adhesion on HCAEC. Moreover, we could demonstrate that iEMP show increased NADPH oxidase activity and contain significantly higher level of reactive oxygen species (ROS) than EMP. iEMP triggered ROS production in HCAEC and thereby activate p38 in an ROS-dependent manner. High glucose condition increases NADPH oxidase activity in endothelial microparticles that amplify endothelial inflammation and impair endothelial function by promoting activation of the endothelium. These findings provide new insights into the pathogenesis of diabetes-associated atherosclerosis.

Complex effect of hydroxyapatite nanoparticles on the differentiation and functional activity of human pre-osteoclastic cells.

PubMed

Costa-Rodrigues, João; Silva, Ana; Santos, Catarina; Almeida, Maria Margarida; Costa, Maria Elisabete; Fernandes, Maria Helena

2014-12-01

Nanosized hydroxyapatite (HA) is a promising material in clinical applications targeting the bone tissue. NanoHA is able to modulate bone cellular events, which accounts for its potential utility, but also raises safety concerns regarding the maintenance of the bone homeostasis. This work analyses the effects of HA nanoparticles (HAnp) on osteoclastic differentiation and activity, an issue that has been barely addressed. Rod-like HAnp, produced by a hydrothermal precipitation method, were tested on peripheral blood mononuclear cells (PBMC), which contains the CD14+ osteoclastic precursors, in unstimulated or osteoclastogenic-induced conditions. HAnp were added at three time-points during the osteoclastic differentiation pathway, and cell response was evaluated for osteoclastic related parameters. Results showed that HAnp modulated the differentiation and function of osteoclastic cells in a dose- and time-dependent manner. In addition, the effects were dependent on the stage of osteoclastic differentiation. In unstimulated PBMC, HAnp significantly increased osteoclastogenesis, leading to the formation of mature osteoclasts, as evident by the significant increase of TRAP activity, number of TRAP-positive multinucleated cells, osteoclastic gene expression and resorbing ability. However, in a population of mature osteoclasts (formed in osteoclastogenic-induced PBMC cultures), HAnp caused a dose-dependent decrease on the osteoclastic-related parameters. These results highlight the complex effects of HAnp in osteoclastic differentiation and activity, and suggest the possibility of HAnp to modulate/disrupt osteoclastic behavior, with eventual imbalances in the bone metabolism. This should be carefully considered in bone-related and other established and prospective biomedical applications of HAnp.

Involvement of riboflavin transporter RFVT2/Slc52a2 in hepatic homeostasis of riboflavin in mice.

PubMed

Yao, Yoshiaki; Yonezawa, Atsushi; Yoshimatsu, Hiroki; Omura, Tomohiro; Masuda, Satohiro; Matsubara, Kazuo

2013-08-15

Riboflavin (vitamin B2) acts as an intermediary during various biochemical oxidation-reduction reactions in the liver. Hepatic riboflavin homeostasis is suggested to be maintained through its transporter(s). Riboflavin transporters, RFVT2/Slc52a2 and RFVT3/Slc52a3, have been identified in rodents. However, the role of each RFVT in the hepatic homeostasis of riboflavin has not yet been fully clarified. In this study, we assessed the contribution of each RFVT to riboflavin uptake into the liver using in vitro and in vivo studies. The uptake of riboflavin by mouse primary hepatocytes increased in a time-dependent and a concentration-dependent manner. Riboflavin transport was independent of extracellular Na(+). However, the uptake decreased slightly along with the extracellular pH increases. Real-time PCR analysis revealed that the mRNA level of Slc52a2, or coding for mouse (m)RFVT2, in the mouse liver was 10 times higher than that of Slc52a3 (coding for mRFVT3). The uptake of riboflavin at pH 7.4 by primary hepatocytes was significantly decreased by the transfection of Slc52a2-small interfering RNA (siRNA), but not Slc52a3-siRNA. Furthermore, we also confirmed the contribution of riboflavin transporters in vivo. The riboflavin concentrations in plasma, but not in the liver, were significantly decreased in mice fed on a riboflavin-deficient diet for 8 weeks. The expression of Slc52a2 mRNA was significantly upregulated by riboflavin deprivation. These results strongly suggest that mRFVT2 was involved in hepatic riboflavin homeostasis. © 2013 Elsevier B.V. All rights reserved.

One-Year Efficacy Testing of Enabling Mothers to Prevent Pediatric Obesity Through Web-Based Education and Reciprocal Determinism (EMPOWER) Randomized Control Trial.

PubMed

Knowlden, Adam; Sharma, Manoj

2016-02-01

The purpose of this study was to evaluate the efficacy of the Enabling Mothers to Prevent Pediatric Obesity through Web-Based Education and Reciprocal Determinism (EMPOWER) intervention at 1-year, postintervention follow-up. A mixed between-within subjects design was used to evaluate the trial. Independent variables included a two-level, group assignment: EMPOWER (experimental intervention) based on social cognitive theory (SCT) as well as a knowledge-based intervention Healthy Lifestyles (active control intervention). Dependent variables were evaluated across four levels of time: baseline (Week 0), posttest (Week 4), 1-month follow-up (Week 8), and 1-year follow-up (Week 60). Dependent variables included five maternal-facilitated SCT constructs (environment, emotional coping, expectations, self-control, and self-efficacy) as well as four child behaviors (minutes of child physical activity, cups of fruits and vegetables consumed, 8-ounce glasses of sugar-sweetened beverages consumed, and minutes of screen time). Null hypotheses implied no significant group-by-time interactions for the dependent variables under investigation. A significant group-by-time interaction for child fruit and vegetable consumption was found in the experimental group (p = .012) relative to the control group. At 1 year, results suggested an overall increase of 1.847 cups of fruits and vegetables (95% confidence interval = 1.207-2.498) in the experimental group (p < .001). Analysis suggested changes in the maternal-facilitated home environment accounted for 13.3% of the variance in the change in child fruit and vegetable consumption. Improvements in child physical activity, sugar-free beverage intake, and screen time first detected at 1-month follow-up in both groups were no longer significant at 1-year follow-up. An online family-and-home-based intervention was efficacious for improving child fruit and vegetable consumption. Follow-up booster sessions may assist in maintaining treatment effects. © 2015 Society for Public Health Education.

The effect on endothelial function of vitamin C during methionine induced hyperhomocysteinaemia.

PubMed

Hanratty, C G; McGrath, L T; McAuley, D F; Young, I S; Johnston, D G

2001-01-01

Manipulation of total homocysteine concentration with oral methionine is associated with impairment of endothelial-dependent vasodilation. This may be caused by increased oxidative stress. Vitamin C is an aqueous phase antioxidant vitamin and free radical scavenger. We hypothesised that if the impairment of endothelial function related to experimental hyperhomocysteinaemia was free radically mediated then co-administration of vitamin C should prevent this. Ten healthy adults took part in this crossover study. Endothelial function was determined by measuring forearm blood flow (FBF) in response to intra-arterial infusion of acetylcholine (endothelial-dependent) and sodium nitroprusside (endothelial-independent). Subjects received methionine (100 mg/Kg) plus placebo tablets, methionine plus vitamin C (2 g orally) or placebo drink plus placebo tablets. Study drugs were administered at 9 am on each study date, a minimum of two weeks passed between each study. Homocysteine (tHcy) concentration was determined at baseline and after 4 hours. Endothelial function was determined at 4 hours. Responses to the vasoactive substances are expressed as the area under the curve of change in FBF from baseline. Data are mean plus 95% Confidence Intervals. Following oral methionine tHcy concentration increased significantly versus placebo. At this time endothelial-dependent responses were significantly reduced compared to placebo (31.2 units [22.1-40.3] vs. 46.4 units [42.0-50.8], p < 0.05 vs. Placebo). Endothelial-independent responses were unchanged. Co-administration of vitamin C did not alter the increase in homocysteine or prevent the impairment of endothelial-dependent responses (31.4 [19.5-43.3] vs. 46.4 units [42.0-50.8], p < 0.05 vs. Placebo) This study demonstrates that methionine increased tHcy with impairment of the endothelial-dependent vasomotor responses. Administration of vitamin C did not prevent this impairment and our results do not support the hypothesis that the endothelial impairment is mediated by adverse oxidative stress.

A microarray analysis of the effects of moderate hypothermia and rewarming on gene expression by human hepatocytes (HepG2).

PubMed

Sonna, Larry A; Kuhlmeier, Matthew M; Khatri, Purvesh; Chen, Dechang; Lilly, Craig M

2010-09-01

The gene expression changes produced by moderate hypothermia are not fully known, but appear to differ in important ways from those produced by heat shock. We examined the gene expression changes produced by moderate hypothermia and tested the hypothesis that rewarming after hypothermia approximates a heat-shock response. Six sets of human HepG2 hepatocytes were subjected to moderate hypothermia (31 degrees C for 16 h), a conventional in vitro heat shock (43 degrees C for 30 min) or control conditions (37 degrees C), then harvested immediately or allowed to recover for 3 h at 37 degrees C. Expression analysis was performed with Affymetrix U133A gene chips, using analysis of variance-based techniques. Moderate hypothermia led to distinct time-dependent expression changes, as did heat shock. Hypothermia initially caused statistically significant, greater than or equal to twofold changes in expression (relative to controls) of 409 sequences (143 increased and 266 decreased), whereas heat shock affected 71 (35 increased and 36 decreased). After 3 h of recovery, 192 sequences (83 increased, 109 decreased) were affected by hypothermia and 231 (146 increased, 85 decreased) by heat shock. Expression of many heat shock proteins was decreased by hypothermia but significantly increased after rewarming. A comparison of sequences affected by thermal stress without regard to the magnitude of change revealed that the overlap between heat and cold stress was greater after 3 h of recovery than immediately following thermal stress. Thus, while some overlap occurs (particularly after rewarming), moderate hypothermia produces extensive, time-dependent gene expression changes in HepG2 cells that differ in important ways from those induced by heat shock.

The influence of anaesthetists' experience on workload, performance and visual attention during simulated critical incidents.

PubMed

Schulz, Christian M; Schneider, Erich; Kohlbecher, Stefan; Hapfelmeier, Alexander; Heuser, Fabian; Wagner, Klaus J; Kochs, Eberhard F; Schneider, Gerhard

2014-10-01

Development of accurate Situation Awareness (SA) depends on experience and may be impaired during excessive workload. In order to gain adequate SA for decision making and performance, anaesthetists need to distribute visual attention effectively. Therefore, we hypothesized that in more experienced anaesthetists performance is better and increase of physiological workload is less during critical incidents. Additionally, we investigated the relation between physiological workload indicators and distribution of visual attention. In fifteen anaesthetists, the increase of pupil size and heart rate was assessed in course of a simulated critical incident. Simulator log files were used for performance assessment. An eye-tracking device (EyeSeeCam) provided data about the anaesthetists' distribution of visual attention. Performance was assessed as time until definitive treatment. T tests and multivariate generalized linear models (MANOVA) were used for retrospective statistical analysis. Mean pupil diameter increase was 8.1% (SD ± 4.3) in the less experienced and 15.8% (±10.4) in the more experienced subjects (p = 0.191). Mean heart rate increase was 10.2% (±6.7) and 10.5% (±8.3, p = 0.956), respectively. Performance did not depend on experience. Pupil diameter and heart rate increases were associated with a shift of visual attention from monitoring towards manual tasks (not significant). For the first time, the following four variables were assessed simultaneously: physiological workload indicators, performance, experience, and distribution of visual attention between "monitoring" and "manual" tasks. However, we were unable to detect significant interactions between these variables. This experimental model could prove valuable in the investigation of gaining and maintaining SA in the operation theatre.

APL-UW Deep Water Propagation 2015-2017: Philippine Sea Data Analysis

DTIC Science & Technology

independent Monte Carlo parabolic equation simulations . The autospectrum of normalized intensity had an excellent match to that of a time-dependent Monte...ambient noise; systems along the Aleutian chain have either no significant trendor a slight increasing trend; systems in the central Pacific Ocean...At the end of the grant, it was determined that the Kauai cable had suffered a break in the shallow near-shore region. Additional contractual

Temperature Dependence of Uranium and Vanadium Adsorption on Amidoxime-Based Adsorbents in Natural Seawater

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

Kuo, Li-Jung; Gill, Gary A.; Tsouris, Costas

The apparent enthalpy and entropy of the complexation of uranium (VI) and vanadium (V) with amidoxime ligands grafted onto polyethylene fiber was determined using time series measurements of adsorption capacities in natural seawater at three different temperatures. The complexation of uranium was highly endothermic, while the complexation of vanadium showed minimal temperature sensitivity. Amidoxime-based polymeric adsorbents exhibit significantly increased uranium adsorption capacities and selectivity in warmer waters.

Orthographic versus semantic matching in visual search for words within lists.

PubMed

Léger, Laure; Rouet, Jean-François; Ros, Christine; Vibert, Nicolas

2012-03-01

An eye-tracking experiment was performed to assess the influence of orthographic and semantic distractor words on visual search for words within lists. The target word (e.g., "raven") was either shown to participants before the search (literal search) or defined by its semantic category (e.g., "bird", categorical search). In both cases, the type of words included in the list affected visual search times and eye movement patterns. In the literal condition, the presence of orthographic distractors sharing initial and final letters with the target word strongly increased search times. Indeed, the orthographic distractors attracted participants' gaze and were fixated for longer times than other words in the list. The presence of semantic distractors related to the target word also increased search times, which suggests that significant automatic semantic processing of nontarget words took place. In the categorical condition, semantic distractors were expected to have a greater impact on the search task. As expected, the presence in the list of semantic associates of the target word led to target selection errors. However, semantic distractors did not significantly increase search times any more, whereas orthographic distractors still did. Hence, the visual characteristics of nontarget words can be strong predictors of the efficiency of visual search even when the exact target word is unknown. The respective impacts of orthographic and semantic distractors depended more on the characteristics of lists than on the nature of the search task.

Characterization of a Strain Rate Transient Along the San Andreas and San Jacinto Faults Following the October 1999 Hector Mine Earthquake.

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.

Advanced Glycation End Products Inhibit the Proliferation of Human Umbilical Vein Endothelial Cells by Inhibiting Cathepsin D.

PubMed

Li, Yuan; Chang, Ye; Ye, Ning; Dai, Dongxue; Chen, Yintao; Zhang, Naijin; Sun, Guozhe; Sun, Yingxian

2017-02-17

We aimed to investigate the effect of advanced glycation end products (AGEs) on the proliferation and migration ability of human umbilical vein endothelial cells (HUVECs). Cell proliferation was detected by methyl thiazolyl tetrazolium (MTT) assay, real-time cell analyzer and 5-Ethynyl-2'-deoxyuridine (EdU) staining. Cell migration was detected by wound-healing and transwell assay. AGEs significantly inhibited the proliferation and migration of HUVECs in a time-and dose-dependent way. Western blotting revealed that AGEs dramatically increased the expression of microtubule-associated protein 1 light chain 3 (LC3) II/I and p62. Immunofluorescence of p62 and acridine orange staining revealed that AGEs significantly increased the expression of p62 and the accumulation of autophagic vacuoles, respectively. Chloroquine (CQ) could further promote the expression of LC3 II/I and p62, increase the accumulation of autophagic vacuoles and promote cell injury induced by AGEs. In addition, AGEs reduced cathepsin D (CTSD) expression in a time-dependent way. Overexpression of wild-type CTSD significantly decreased the ratio of LC 3 II/I as well as p62 accumulation induced by AGEs, but overexpression of catalytically inactive mutant CTSD had no such effects. Only overexpression of wild-type CTSD could restore the proliferation of HUVECs inhibited by AGEs. However, overexpression of both wild-type CTSD and catalytically inactive mutant CTSD could promote the migration of HUVECs inhibited by AGEs. Collectively, our study found that AGEs inhibited the proliferation and migration in HUVECs and promoted autophagic flux, which in turn played a protective role against AGEs-induced cell injury. CTSD, in need of its catalytic activity, may promote proliferation in AGEs-treated HUVECs independent of the autophagy-lysosome pathway. Meanwhile, CTSD could improve the migration of AGEs-treated HUVECs regardless of its enzymatic activity.

Advanced Glycation End Products Inhibit the Proliferation of Human Umbilical Vein Endothelial Cells by Inhibiting Cathepsin D

PubMed Central

Li, Yuan; Chang, Ye; Ye, Ning; Dai, Dongxue; Chen, Yintao; Zhang, Naijin; Sun, Guozhe; Sun, Yingxian

2017-01-01

We aimed to investigate the effect of advanced glycation end products (AGEs) on the proliferation and migration ability of human umbilical vein endothelial cells (HUVECs). Cell proliferation was detected by methyl thiazolyl tetrazolium (MTT) assay, real-time cell analyzer and 5-Ethynyl-2′-deoxyuridine (EdU) staining. Cell migration was detected by wound-healing and transwell assay. AGEs significantly inhibited the proliferation and migration of HUVECs in a time-and dose-dependent way. Western blotting revealed that AGEs dramatically increased the expression of microtubule-associated protein 1 light chain 3 (LC3) II/I and p62. Immunofluorescence of p62 and acridine orange staining revealed that AGEs significantly increased the expression of p62 and the accumulation of autophagic vacuoles, respectively. Chloroquine (CQ) could further promote the expression of LC3 II/I and p62, increase the accumulation of autophagic vacuoles and promote cell injury induced by AGEs. In addition, AGEs reduced cathepsin D (CTSD) expression in a time-dependent way. Overexpression of wild-type CTSD significantly decreased the ratio of LC 3 II/I as well as p62 accumulation induced by AGEs, but overexpression of catalytically inactive mutant CTSD had no such effects. Only overexpression of wild-type CTSD could restore the proliferation of HUVECs inhibited by AGEs. However, overexpression of both wild-type CTSD and catalytically inactive mutant CTSD could promote the migration of HUVECs inhibited by AGEs. Collectively, our study found that AGEs inhibited the proliferation and migration in HUVECs and promoted autophagic flux, which in turn played a protective role against AGEs-induced cell injury. CTSD, in need of its catalytic activity, may promote proliferation in AGEs-treated HUVECs independent of the autophagy-lysosome pathway. Meanwhile, CTSD could improve the migration of AGEs-treated HUVECs regardless of its enzymatic activity. PMID:28218663

Effects of acetaminophen and ibuprofen in children with migraine receiving preventive treatment with magnesium.

PubMed

Gallelli, Luca; Avenoso, Tiziana; Falcone, Daniela; Palleria, Caterina; Peltrone, Francesco; Esposito, Maria; De Sarro, Giovambattista; Carotenuto, Marco; Guidetti, Vincenzo

2014-02-01

The purpose of this study was to evaluate both the effects of ibuprofen and/or acetaminophen for the acute treatment of primary migraine in children in or out prophylactic treatment with magnesium. Children ranging from the ages of 5 to 16 years with at least 4 attack/month of primary migraine were eligible for participation the study. A visual analog scale was used to evaluate pain intensity at the moment of admission to the study (start of the study) and every month up to 18 months later (end of the study). One hundred sixty children of both sexes aged 5-16 years were enrolled and assigned in 4 groups to receive a treatment with acetaminophen or ibuprofen without or with magnesium. Migraine pain endurance and monthly frequency were similar in the 4 groups. Both acetaminophen and ibuprofen induced a significant decrease in pain intensity (P < .01), without a time-dependent correlation, but did not modify its frequency. Magnesium pretreatment induced a significant decrease in pain intensity (P < .01) without a time-dependent correlation in both acetaminophen- and ibuprofen-treated children and also significantly reduced (P < .01) the pain relief timing during acetaminophen but not during ibuprofen treatment (P < .01). In both acetaminophen and ibuprofen groups, magnesium pretreatment significantly reduced the pain frequency (P < .01). Magnesium increased the efficacy of ibuprofen and acetaminophen with not age-related effects. © 2013 American Headache Society.

Progressive levels of physical dependence to tobacco coincide with changes in the anterior cingulum bundle microstructure.

PubMed

Huang, Wei; DiFranza, Joseph R; Kennedy, David N; Zhang, Nanyin; Ziedonis, Douglas; Ursprung, Sanouri; King, Jean A

2013-01-01

The tobacco withdrawal syndrome indicates the development of neurophysiologic dependence. Clinical evidence indicates that neurophysiologic dependence develops through a set sequence of symptom presentation that can be assessed with a new 3-item survey measure of wanting, craving, and needing tobacco, the Level of Physical Dependence (PD). This study sought to determine if advancing neurophysiologic dependence as measured by the Level of PD correlates with characteristics of white matter structure measured by Fractional Anisotropy (FA). Diffusion-MRI based FA and diffusion tensor imaging probabilistic tractography were used to evaluate 11 smokers and 10 nonsmokers. FA was also examined in relation to two additional measures of dependence severity, the Hooked on Nicotine Checklist (HONC), and the Fagerström Test for Nicotine Dependence (FTND). Among smokers, FA in the left anterior cingulate bundle (ACb) correlated negatively with the Level of PD (r = -0.68, p = 0.02) and HONC scores (r = -0.65, p = 0.03), but the correlation for the FTND did not reach statistical significance (r = -49, p = 0.12). With advancing Levels of PD, the density of streamlines between the ACb and precuneus increased (r = -0.67, p<0.05) and those between the ACb and white matter projecting to the superior-frontal cortex (r = -0.86, p = 0.0006) decreased significantly. The correlations between neural structure and both the clinical Level of PD survey measure and the HONC suggest that the Level of PD and the HONC may reflect the microstructural integrity of white matter, as influenced by tobacco abuse. Given that the Level of PD is measuring a sequence of symptoms of neurophysiologic dependence that develops over time, the correlation between the Level of PD and neural structure suggests that these features might represent neuroplastic changes that develop over time to support the development of neurophysiologic dependence.

Postural Stability in Cigarette Smokers and During Abstinence from Alcohol

PubMed Central

Schmidt, Thomas Paul; Pennington, David Louis; Durazzo, Timothy Craig; Meyerhoff, Dieter Johannes

2014-01-01

Background Static postural instability is common in alcohol dependent individuals (ALC). Chronic alcohol consumption has deleterious effects on the neural and perceptual systems subserving postural stability. However, little is known about the effects of chronic cigarette smoking on postural stability and its changes during abstinence from alcohol. Methods A modified Fregly ataxia battery was administered to a total of 115 smoking (sALC) and non-smoking ALC (nsALC) and to 74 smoking (sCON) and non-smoking light/non-drinking controls (nsCON). Subgroups of abstinent ALC were assessed at 3 time points (approximately 1 week, 5 weeks, 34 weeks of abstinence from alcohol); a subset of nsCON was re-tested at 40 weeks. We tested if cigarette smoking affects postural stability in CON and in ALC during extended abstinence from alcohol, and we used linear mixed effects modeling to measure change across time points within ALC. Results Chronic smoking was associated with reduced performance on the Sharpened Romberg eyes-closed task in abstinent ALC at all three time points and in CON. The test performance of nsALC increased significantly between 1 and 32 weeks of abstinence, whereas the corresponding increases for sALC between 1 and 35 weeks was non-significant. With long-term abstinence from alcohol, nsALC recovered into the range of nsCON and sALC recovered into the range of sCON. Static postural stability decreased with age and correlated with smoking variables but not with drinking measures. Conclusions Chronic smoking was associated with reduced static postural stability with eyes closed and with lower increases of postural stability during abstinence from alcohol. Smoking cessation in alcohol dependence treatment may facilitate recovery from static postural instability during abstinence. PMID:24721012

Time-dependent mobility and recombination of the photoinduced charge carriers in conjugated polymer/fullerene bulk heterojunction solar cells

NASA Astrophysics Data System (ADS)

Mozer, A. J.; Dennler, G.; Sariciftci, N. S.; Westerling, M.; Pivrikas, A.; Österbacka, R.; Juška, G.

2005-07-01

Time-dependent mobility and recombination in the blend of poly[2-methoxy-5-(3,7-dimethyloctyloxy)-phenylene vinylene] (MDMO-PPV) and 1-(3-methoxycarbonyl)propyl-1-phenyl-(6,6)- C61 (PCBM) is studied simultaneously using the photoinduced charge carrier extraction by linearly increasing voltage technique. The charge carriers are photogenerated by a strongly absorbed, 3 ns laser flash, and extracted by the application of a reverse bias voltage pulse after an adjustable delay time (tdel) . It is found that the mobility of the extracted charge carriers decreases with increasing delay time, especially shortly after photoexcitation. The time-dependent mobility μ(t) is attributed to the energy relaxation of the charge carriers towards the tail states of the density of states distribution. A model based on a dispersive bimolecular recombination is formulated, which properly describes the concentration decay of the extracted charge carriers at all measured temperatures and concentrations. The calculated bimolecular recombination coefficient β(t) is also found to be time-dependent exhibiting a power law dependence as β(t)=β0t-(1-γ) with increasing slope (1-γ) with decreasing temperatures. The temperature dependence study reveals that both the mobility and recombination of the photogenerated charge carriers are thermally activated processes with activation energy in the range of 0.1 eV. Finally, the direct comparison of μ(t) and β(t) shows that the recombination of the long-lived charge carriers is controlled by diffusion.

Effect of a zinc L-carnosine compound on acid-induced injury in canine gastric mucosa ex vivo.

PubMed

Hill, Tracy L; Blikslager, Anthony T

2012-05-01

To examine whether a zinc L-carnosine compound used for treatment of suspected gastric ulcers in dogs ameliorates acid-induced injury in canine gastric mucosa. Gastric mucosa from 6 healthy dogs. Mucosa from the gastric antrum was harvested from 6 unadoptable shelter dogs immediately after euthanasia and mounted on Ussing chambers. The tissues were equilibrated for 30 minutes in neutral Ringer's solution prior to incubation with acidic Ringer's solution (HCl plus Ringer's solution [final pH, 1.5 to 2.5]), acidic Ringer's solution plus zinc L-carnosine compound, or zinc L-carnosine compound alone. Tissues were maintained for 180 minutes in Ussing chambers, during which permeability was assessed by measurement of transepithelial electrical resistance. After the 180-minute treatment period, tissues were removed from Ussing chambers and labeled with immunofluorescent anti-active caspase-3 antibody as an indicator of apoptosis. Permeability of the gastric mucosa was significantly increased in a time-dependent manner by addition of HCl, whereas control tissues maintained viability for the study period. Change in permeability was detected within the first 15 minutes after acid application and progressed over the subsequent 150 minutes. The zinc L-carnosine compound had no significant effect on this increase in permeability. Apoptosis was evident in acid-treated tissues but not in control tissues. The zinc L-carnosine compound did not protect against development of apoptosis. Addition of HCl caused a dose-dependent increase in gastric permeability over time and apparent induction of apoptosis as determined on the basis of immunofluorescence. However, there was no significant protective effect of a zinc L-carnosine compound. Nonetheless, results suggested the utility of this method for further studies of canine gastric injury.

Effect of Mn doping on the temperature-dependent anomalous giant dielectric behavior of CaCu3Ti4O12

NASA Astrophysics Data System (ADS)

Kim, C. H.; Jang, Y. H.; Seo, S. J.; Song, C. H.; Son, J. Y.; Yang, Y. S.; Cho, J. H.

2012-06-01

We report dielectric properties and dielectric relaxation behaviors of Mn-substituted CaCu3Ti4O12 (CCTO) on Cu sites. While CCTO exhibits the giant dielectric constant and low dielectric loss in a wide temperature range, drastic suppression of the dielectric constant in Mn-doped CCTO (CCMTO) samples have been observed in temperature and frequency dependencies of dielectric properties with two possible origins as Mn doping increases. The observed suppression of dielectric response in the low Mn doping differs from the heavy doping of Mn in CCMTO samples. The low-Mn-doped CCMTO samples (x=0.01 and 0.02) show that the relaxation time and the activation energy Ea were slightly reduced due to a decreased contribution from the density of the dipolar effect. However, in heavily doped CCMTO samples (x=0.03, 0.04, and 0.05), the dielectric response, relaxation time, and Ea were significantly decreased, suggesting Mn doping plays a significant role in the destruction of the intrinsic dipolar effect.

Tanshinones extend chronological lifespan in budding yeast Saccharomyces cerevisiae.

PubMed

Wu, Ziyun; Song, Lixia; Liu, Shao Quan; Huang, Dejian

2014-10-01

Natural products with anti-aging property have drawn great attention recently but examples of such compounds are exceedingly scarce. By applying a high-throughput assay based on yeast chronological lifespan measurement, we screened the anti-aging activity of 144 botanical materials and found that dried roots of Salvia miltiorrhiza Bunge have significant anti-aging activity. Tanshinones isolated from the plant including cryptotanshione, tanshinone I, and tanshinone IIa, are the active components. Among them, cryptotanshinone can greatly extend the budding yeast Saccharomyces cerevisiae chronological lifespan (up to 2.5 times) in a dose- and the-time-of-addition-dependent manner at nanomolar concentrations without disruption of cell growth. We demonstrate that cryptotanshinone prolong chronological lifespan via a nutrient-dependent regime, especially essential amino acid sensing, and three conserved protein kinases Tor1, Sch9, and Gcn2 are required for cryptotanshinone-induced lifespan extension. In addition, cryptotanshinone significantly increases the lifespan of SOD2-deleted mutants. Altogether, those data suggest that cryptotanshinone might be involved in the regulation of, Tor1, Sch9, Gcn2, and Sod2, these highly conserved longevity proteins modulated by nutrients from yeast to humans.

In vivo gamma-rays induced initial DNA damage and the effect of famotidine in mouse leukocytes as assayed by the alkaline comet assay.

PubMed

Mozdarani, Hossein; Nasirian, Borzo; Haeri, S Abolghasem

2007-03-01

Ionizing radiation induces a variety of lesions in DNA, each of which can be used as a bio-indicator for biological dosimetry or the study of the radioprotective effects of substances. To assess gamma ray-induced DNA damage in vivo in mouse leukocytes at various doses and the effect of famotidine, blood was collected from Balb/c male mice after irradiation with 4 Gy gamma-rays at different time intervals post-irradiation. To assess the response, mice were irradiated with doses of gamma-rays at 1 to 4 Grays. Famotidine was injected intra-peritoneally (i.p) at a dose of 5 mg/kg at various time intervals before irradiation. Four slides were prepared from each sample and alkaline comet assay was performed using standard protocols. Results obtained show that radiation significantly increases DNA damage in leukocytes in a dose dependent manner (p < 0.01) when using appropriate sampling time after irradiation, because increasing sampling time after irradiation resulted in a time dependent disappearance of DNA damage. Treatment with only 5 mg/kg famotidine before 4 Gy irradiation led to almost 50% reduction in DNA damage when compared with those animals which received radiation alone. The radioprotective capability of famotidine might be attributed to radical scavenging properties and an anti-oxidation mechanism.

Femtosecond dynamics of energetic electrons in high intensity laser-matter interactions

NASA Astrophysics Data System (ADS)

Pompili, R.; Anania, M. P.; Bisesto, F.; Botton, M.; Castellano, M.; Chiadroni, E.; Cianchi, A.; Curcio, A.; Ferrario, M.; Galletti, M.; Henis, Z.; Petrarca, M.; Schleifer, E.; Zigler, A.

2016-10-01

Highly energetic electrons are generated at the early phases of the interaction of short-pulse high-intensity lasers with solid targets. These escaping particles are identified as the essential core of picosecond-scale phenomena such as laser-based acceleration, surface manipulation, generation of intense magnetic fields and electromagnetic pulses. Increasing the number of the escaping electrons facilitate the late time processes in all cases. Up to now only indirect evidences of these important forerunners have been recorded, thus no detailed study of the governing mechanisms was possible. Here we report, for the first time, direct time-dependent measurements of energetic electrons ejected from solid targets by the interaction with a short-pulse high-intensity laser. We measured electron bunches up to 7 nanocoulombs charge, picosecond duration and 12 megaelectronvolts energy. Our ’snapshots’ capture their evolution with an unprecedented temporal resolution, demonstrat- ing a significant boost in charge and energy of escaping electrons when increasing the geometrical target curvature. These results pave the way toward significant improvement in laser acceleration of ions using shaped targets allowing the future development of small scale laser-ion accelerators.

A small amount can make a difference: a prospective human study of the paradoxical coagulation characteristics of hemothorax.

PubMed

Smith, W Zachary; Harrison, Hannah B; Salhanick, Marc A; Higgins, Russell A; Ortiz, Alfonso; Olson, John D; Schwacha, Martin G; Harrison, Chantal R; Aydelotte, Jayson D; Stewart, Ronald M; Dent, Daniel L

2013-12-01

The evacuated hemothorax has been poorly described because it varies with time, it has been found to be incoagulable, and its potential effect on the coagulation cascade during autotransfusion is largely unknown. This is a prospective descriptive study of adult patients with traumatic chest injury necessitating tube thoracostomy. Pleural and venous samples were analyzed for coagulation, hematology, and electrolytes at 1 to 4 hours after drainage. Pleural samples were also analyzed for their effect on the coagulation cascade via mixing studies. Thirty-four subjects were enrolled with a traumatic hemothorax. The following measured coagulation factors were significantly depleted compared with venous blood: international normalized ratio (>9 vs 1.1) (P < .001) and activated partial thromboplastin time (aPTT) (>180 vs 24.5 seconds) (P < .001). Mixing studies showed a dose-dependent increase in coagulation dilutions through 1:8 (P < .05). An evacuated hemothorax does not vary in composition significantly with time and is incoagulable alone. Mixing studies with hemothorax plasma increased coagulation, raising safety concerns. Copyright © 2013 Elsevier Inc. All rights reserved.

A significant increase in both basal and maximal calcineurin activity following fluid percussion injury in the rat.

PubMed

Kurz, Jonathan E; Parsons, J Travis; Rana, Aniruddha; Gibson, Cynthia J; Hamm, Robert J; Churn, Severn B

2005-04-01

Calcineurin, a neuronally enriched, calcium-stimulated phosphatase, is an important modulator of many neuronal processes, including several that are physiologically related to the pathology of traumatic brain injury. This study examined the effects of moderate, central fluid percussion injury on the activity of this important neuronal enzyme. Animals were sacrificed at several time-points postinjury and cortical, hippocampal, and cerebellar homogenates were assayed for calcineurin activity by dephosphorylation of p-nitrophenol phosphate. A significant brain injury-dependent increase was observed in both hippocampal and cortical homogenates under both basal and maximally-stimulated reaction conditions. This increase persisted 2-3 weeks post-injury. Brain injury did not alter substrate affinity, but did induce a significant increase in the apparent maximal dephosphorylation rate. Unlike the other brain regions, no change in calcineurin activity was observed in the cerebellum following brain injury. No brain region tested displayed a significant change in calcineurin enzyme levels as determined by Western blot, demonstrating that increased enzyme synthesis was not responsible for the observed increase in activity. The data support the conclusion that fluid percussion injury results in increased calcineurin activity in the rat forebrain. This increased activity has broad physiological implications, possibly resulting in altered cellular excitability or a greater likelihood of neuronal cell death.

Time course of right ventricular pressure-overload induced myocardial fibrosis: relationship to changes in fibroblast postsynthetic procollagen processing.

PubMed

Baicu, Catalin F; Li, Jiayu; Zhang, Yuhua; Kasiganesan, Harinath; Cooper, George; Zile, Michael R; Bradshaw, Amy D

2012-11-01

Myocardial fibrillar collagen is considered an important determinant of increased ventricular stiffness in pressure-overload (PO)-induced cardiac hypertrophy. Chronic PO was created in feline right ventricles (RV) by pulmonary artery banding (PAB) to define the time course of changes in fibrillar collagen content after PO using a nonrodent model and to determine whether this time course was dependent on changes in fibroblast function. Total, soluble, and insoluble collagen (hydroxyproline), collagen volume fraction (CVF), and RV end-diastolic pressure were assessed 2 days and 1, 2, 4, and 10 wk following PAB. Fibroblast function was assessed by quantitating the product of postsynthetic processing, insoluble collagen, and levels of SPARC (secreted protein acidic and rich in cysteine), a protein that affects procollagen processing. RV hypertrophic growth was complete 2 wk after PAB. Changes in RV collagen content did not follow the same time course. Two weeks after PAB, there were elevations in total collagen (control RV: 8.84 ± 1.03 mg/g vs. 2-wk PAB: 11.50 ± 0.78 mg/g); however, increased insoluble fibrillar collagen, as measured by CVF, was not detected until 4 wk after PAB (control RV CVF: 1.39 ± 0.25% vs. 4-wk PAB: 4.18 ± 0.87%). RV end-diastolic pressure was unchanged at 2 wk, but increased until 4 wk after PAB. RV fibroblasts isolated after 2-wk PAB had no changes in either insoluble collagen or SPARC expression; however, increases in insoluble collagen and in levels of SPARC were detected in RV fibroblasts from 4-wk PAB. Therefore, the time course of PO-induced RV hypertrophy differs significantly from myocardial fibrosis and diastolic dysfunction. These temporal differences appear dependent on changes in fibroblast function.

Time course of right ventricular pressure-overload induced myocardial fibrosis: relationship to changes in fibroblast postsynthetic procollagen processing

PubMed Central

Baicu, Catalin F.; Li, Jiayu; Zhang, Yuhua; Kasiganesan, Harinath; Cooper, George; Zile, Michael R.

2012-01-01

Myocardial fibrillar collagen is considered an important determinant of increased ventricular stiffness in pressure-overload (PO)-induced cardiac hypertrophy. Chronic PO was created in feline right ventricles (RV) by pulmonary artery banding (PAB) to define the time course of changes in fibrillar collagen content after PO using a nonrodent model and to determine whether this time course was dependent on changes in fibroblast function. Total, soluble, and insoluble collagen (hydroxyproline), collagen volume fraction (CVF), and RV end-diastolic pressure were assessed 2 days and 1, 2, 4, and 10 wk following PAB. Fibroblast function was assessed by quantitating the product of postsynthetic processing, insoluble collagen, and levels of SPARC (secreted protein acidic and rich in cysteine), a protein that affects procollagen processing. RV hypertrophic growth was complete 2 wk after PAB. Changes in RV collagen content did not follow the same time course. Two weeks after PAB, there were elevations in total collagen (control RV: 8.84 ± 1.03 mg/g vs. 2-wk PAB: 11.50 ± 0.78 mg/g); however, increased insoluble fibrillar collagen, as measured by CVF, was not detected until 4 wk after PAB (control RV CVF: 1.39 ± 0.25% vs. 4-wk PAB: 4.18 ± 0.87%). RV end-diastolic pressure was unchanged at 2 wk, but increased until 4 wk after PAB. RV fibroblasts isolated after 2-wk PAB had no changes in either insoluble collagen or SPARC expression; however, increases in insoluble collagen and in levels of SPARC were detected in RV fibroblasts from 4-wk PAB. Therefore, the time course of PO-induced RV hypertrophy differs significantly from myocardial fibrosis and diastolic dysfunction. These temporal differences appear dependent on changes in fibroblast function. PMID:22942178

Alamar blue reagent interacts with cell-culture media giving different fluorescence over time: potential for false positives.

PubMed

Munshi, Soumyabrata; Twining, Robert C; Dahl, Russell

2014-01-01

The cell viability assay by alamar blue is based on the principle of reduction of the non-fluorescent reagent (resazurin) to a fluorescent compound (resarufin) by the intracellular reducing environment of living cells over time. In the present study, we have for the first time shown that even in the absence of cells, there occurs significant interaction between alamar blue and cell-culture media causing an increase in fluorescence. We have used Opti-MEM, DMEM and 1:1 DMEM:Opti-MEM as three different media and determined the changes in their relative fluorescence units (RFUs) over time after the addition of 10% (v/v) alamar blue using two-way repeated measures analysis of variance (RM-ANOVA) followed by Tukey's post-hoc test. Our results show that upon the addition of alamar blue, there occurs a significant increase in RFUs in all the three media over time along with a significantly higher RFU for the Opti-MEM overall (p<0.05). We also show that the time-dependent change in RFU of 1:1 DMEM:Opti-MEM was more gradual compared to that of the other two media. These findings indicate that the reagent can itself interact with the media causing significantly different fluorescence over time in a manner independent from the effect of intracellular reducing environment of living cells on alamar blue. In addition our results indicate that fluorescence varies as a function of incubation time with the reagent. These findings signify the need for routine subtraction of the background fluorescence of media-only with alamar blue reagent during measurement of cell viability by this method in order to determine an accurate measurement of cell viability. Copyright © 2014 Elsevier Inc. All rights reserved.

Anti-Alzheimer activity of isolated karanjin from Pongamia pinnata (L.) pierre and embelin from Embelia ribes Burm.f.

PubMed

Saini, Prachi; Lakshmayya, L; Bisht, Vinod Singh

2017-01-01

The aim of this study is to find out the anti-Alzheimer's activity of isolated karanjin and embelin. Karanjin isolated from Pongamia pinnata (L.) pierre and embelin from Embelia ribes Burm.f. and their purity was confirmed by ultraviolet spectrophotometric and Thin layer chromatography based study. Anti-Alzheimer's activity of isolated compounds were evaluated through elevated plus maze and Morris water maze model on Swiss albino mice. Diazepam (1 mg/kg body weight, intraperitoneally) was used for the induction of Alzheimer's like effects (amnesia) on Swiss albino mice and piracetam (200 mg/kg body weight, oral) used as a standard treatment. In EPM, embelin and karanjin decrease the transfer latency time in dose dependent manner and escape latency time in MWM method. A significant ( P < 0.01) reduction in amnesia with an anti-Alzheimer's effect found when results of isolated compounds were compared with standard and vehicle control. Diazepam (1 mg/kg) treated group showed significant increase in escape latency and transfer latency when compared with vehicle control; which indicates impairment in learning and memory. Both isolated compounds and standard significantly reversed the amnesia induced by diazepam and improved learning and memory of mice in dose and time dependent manner. This study supports the ethnobotanical use of these two plants in India for the management of nerve or brain related problems.

In vitro profiling of toxicity and endocrine disrupting effects of bisphenol analogues by employing MCF-7 cells and two-hybrid yeast bioassay.

PubMed

Lei, Bingli; Xu, Jie; Peng, Wei; Wen, Yu; Zeng, Xiangying; Yu, Zhiqiang; Wang, Yipei; Chen, Tian

2017-01-01

The potentially adverse health implications of bisphenol A (BPA) have led to increasing use of alternative bisphenols (BPs). However, little is known about the toxicity of alternative BPs. In this study, the cytotoxicity, genotoxicity, intracellular ROS formation, and Ca 2+ fluctuation effects of BPs on MCF-7 cells were evaluated. At the same time, the estrogenic and thyroidal hormone effect potentials of six BPs were also evaluated using two-hybrid yeast bioassay. The results showed that most BPs at 0.01-1 μM significantly increased cell viability in MCF-7 cells and at higher exposure concentrations of 25-100 μM, they caused a significant decrease of cell viability. At the same time, these BPs also at 25-100 μM significantly increased LDH release of MCF-7 cells. In addition, several BPs at 10-50 μM resulted in a significantly concentration-depended increase in DNA-damaging effect on MCF-7 cells and elevated ROS production. Most BPs at 0.0001-10 μM significantly increased intracellular Ca 2+ level. These results showed that bisphenol AF (BPAF) and thiodiphenol (TDP) exerted cell biological effect, estrogenic, and thyroidal effect potentials greater than those of BPA. The cytotoxicity and endocrine disrupting effects of other BPs are similar to or slightly lower than those of BPA. Therefore, as potential alternatives to BPA, endocrine disrupting effects and potential health harm of alternative BPs to human can also not be ignored. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 278-289, 2017. © 2016 Wiley Periodicals, Inc.

Adaptive mesh strategies for the spectral element method

NASA Technical Reports Server (NTRS)

Mavriplis, Catherine

1992-01-01

An adaptive spectral method was developed for the efficient solution of time dependent partial differential equations. Adaptive mesh strategies that include resolution refinement and coarsening by three different methods are illustrated on solutions to the 1-D viscous Burger equation and the 2-D Navier-Stokes equations for driven flow in a cavity. Sharp gradients, singularities, and regions of poor resolution are resolved optimally as they develop in time using error estimators which indicate the choice of refinement to be used. The adaptive formulation presents significant increases in efficiency, flexibility, and general capabilities for high order spectral methods.

Development and in vitro/in vivo evaluation of Zn-pectinate microparticles reinforced with chitosan for the colonic delivery of progesterone.

PubMed

Gadalla, Hytham H; Soliman, Ghareb M; Mohammed, Fergany A; El-Sayed, Ahmed M

2016-09-01

The colon is a promising target for drug delivery owing to its long transit time of up to 78 h, which is likely to increase the time available for drug absorption. Progesterone has a short elimination half-life and undergoes extensive first-pass metabolism, which results in very low oral bioavailability (∼25%). To overcome these shortcomings, we developed an oral multiparticulate system for the colonic delivery of progesterone. Zn-pectinate/chitosan microparticles were prepared by ionotropic gelation and characterized for their size, shape, weight, drug entrapment efficiency, mucoadhesion and swelling behavior. The effect of cross-linking pH, cross-linking time and chitosan concentration on progesterone release were also studied. Spherical microparticles having a diameter of 580-720 µm were obtained. Drug entrapment efficiency of ∼75-100% was obtained depending on the microparticle composition. Microparticle mucoadhesive properties were dependent on the pectin concentration, as well as the cross-linking pH. Progesterone release in simulated gastric fluids was minimal (3-9%), followed by burst release at pH 6.8 and a sustained phase at pH 7.4. The in vivo study revealed that the microparticles significantly increased progesterone residence time in the plasma and increased its relative bioavailability to ∼168%, compared to the drug alone. This study confirms the potential of Zn-pectinate/chitosan microparticles as a colon-specific drug delivery system able to enhance the oral bioavailability of progesterone or similar drugs.

Formulation development of smart gel periodontal drug delivery system for local delivery of chemotherapeutic agents with application of experimental design.

PubMed

Dabhi, Mahesh R; Nagori, Stavan A; Gohel, Mukesh C; Parikh, Rajesh K; Sheth, Navin R

2010-01-01

Smart gel periodontal drug delivery systems (SGPDDS) containing gellan gum (0.1-0.8% w/v), lutrol F127 (14, 16, and 18% w/v), and ornidazole (1% w/v) were designed for the treatment of periodontal diseases. Each formulation was characterized in terms of in vitro gelling capacity, viscosity, rheology, content uniformity, in vitro drug release, and syringeability. In vitro gelation time and the nature of the gel formed in simulated saliva for prepared formulations showed polymeric concentration dependency. Drug release data from all formulations was fitted to different kinetic models and the Korsemeyer-Peppas model was the best fit model. Drug release was significantly decreased as the concentration of each polymer component was increased. Increasing the concentration of each polymeric component significantly increased viscosity, syringeability, and time for 50%, 70%, and 90% drug release. In conclusion, the formulations described offer a wide range of physical and drug release characteristics. The formulation containing 0.8% w/v of gellan gum and 16% w/v of lutrol F127 exhibited superior physical characteristics.

A charged particle in a homogeneous magnetic field accelerated by a time-periodic Aharonov-Bohm flux

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

Kalvoda, T.; Stovicek, P., E-mail: stovicek@kmlinux.fjfi.cvut.cz

2011-10-15

We consider a nonrelativistic quantum charged particle moving on a plane under the influence of a uniform magnetic field and driven by a periodically time-dependent Aharonov-Bohm flux. We observe an acceleration effect in the case when the Aharonov-Bohm flux depends on time as a sinusoidal function whose frequency is in resonance with the cyclotron frequency. In particular, the energy of the particle increases linearly for large times. An explicit formula for the acceleration rate is derived with the aid of the quantum averaging method, and then it is checked against a numerical solution and a very good agreement is found.more » - Highlights: > A nonrelativistic quantum charged particle on a plane. > A homogeneous magnetic field and a periodically time-dependent Aharonov-Bohm flux. > The quantum averaging method applied to a time-dependent system. > A resonance of the AB flux with the cyclotron frequency. > An acceleration with linearly increasing energy; a formula for the acceleration rate.« less

Motherhood and drug-dependency: the attributes of full-time versus part-time responsibility for child care.

PubMed

Jackson, M R; Berry, G L

1994-10-01

This study examined differences between the maternal characteristics of African-American drug-dependent mothers who have full-time responsibility for child care and those having part-time responsibility. The study revealed that full-time mothers have significantly higher levels of maternal adaptation than part-time mothers. For part-time mothers, the level of maternal adaptation or self-esteem did not fluctuate, regardless of whether she saw the child 4 days a week or once a month. The article identifies variables that may facilitate better maternal behaviors among drug-dependent mothers.

Temperature dependence of proton NMR relaxation times at earth's magnetic field

NASA Astrophysics Data System (ADS)

Niedbalski, Peter; Kiswandhi, Andhika; Parish, Christopher; Ferguson, Sarah; Cervantes, Eduardo; Oomen, Anisha; Krishnan, Anagha; Goyal, Aayush; Lumata, Lloyd

The theoretical description of relaxation processes for protons, well established and experimentally verified at conventional nuclear magnetic resonance (NMR) fields, has remained untested at low fields despite significant advances in low field NMR technology. In this study, proton spin-lattice relaxation (T1) times in pure water and water doped with varying concentrations of the paramagnetic agent copper chloride have been measured from 6 to 92oC at earth's magnetic field (1700 Hz). Results show a linear increase of T1 with temperature for each of the samples studied. Increasing the concentration of the copper chloride greatly reduced T1 and reduced dependence on temperature. The consistency of the results with theory is an important confirmation of past results, while the ability of an ultra-low field NMR system to do contrast-enhanced magnetic resonance imaging (MRI) is promising for future applicability to low-cost medical imaging and chemical identification. This work is supported by US Dept of Defense Award No. W81XWH-14-1-0048 and the Robert A. Welch Foundation Grant No. AT-1877.

Platelet-, leucocyte- and red cell-derived microparticles in stored whole blood, with and without leucofiltration, with and without ionising radiation

PubMed Central

Saito, Shunnichi; Ngoma, Alain M.; Ono, Takako; Ohto, Hitoshi

2018-01-01

Background Storage lesion, including microparticle formation, has been partially characterised in whole blood, but not in all combinations of pre-storage leucofiltration and/or irradiation. Materials and methods Single-donor whole blood products were processed into four subunits: with and without leucofiltration, with and without X-irradiation (25 Gy). Platelet-, leucocyte-, and erythrocyte-derived microparticles and free haemoglobin were measured periodically throughout 42 days of storage. Results Pre-storage leucofiltration substantially reduced platelet- and leucocyte-derived microparticle counts throughout storage. Irradiation, in contrast, had no significant effect on microparticle counts. A gate for all microparticles showed a substantial time-dependent increase in unfiltered whole blood. A time-dependent increase in free haemoglobin was greatest in unfiltered, irradiated whole blood. Discussion This study indicates that leucofiltration can prevent the formation of leucocyte- and platelet-derived microparticles, and might reduce haemolysis in irradiated whole blood, either by removing factors that provoke haemolysis, or by selective retention of senescent or effete red cells most prone to haemolysis. PMID:27893349

Evaluation of different fast melting disintegrants by means of a central composite design.

PubMed

Di Martino, Piera; Martelli, Sante; Wehrlé, Pascal

2005-01-01

Fast-disintegration technologies have encountered increased interest from industries in the past decades. In order to orientate the formulators to the choice of the best disintegrating agent, the most common disintegrants were selected and their ability to quickly disintegrate direct compressed tablets was evaluated. For this study, a central composite design was used. The main factors included were the concentration of disintegrant (X1) and the compression force (X2). These factors were studied for tablets containing either Zeparox or Pearlitol 200 as soluble diluents and six different disintegrants: L-HPC LH11 and LH31, Lycatab PGS, Vivasol, Kollidon CL, and Explotab. Their micromeritics properties were previously determined. The response variables were disintegration time (Y1), tensile strength (Y2), and porosity (Y3). Whatever the diluent, the longest disintegration time is obtained with Vivasol as the disintegrant, while Kollidon CL leads to the shortest disintegration times. Exception for Lycatab PGS and L-HPC LH11, formulations with Pearlitol 200 disintegrate faster. Almost the same results are obtained with porosity: no relevant effect of disintegrant concentration is observed, since porosity is mainly correlated to the compression force. In particular, highest values are obtained with Zeparox as the diluent when compared to Pearlitol 200 and, as the type of disintegrant is concerned, no difference is observed. Tensile strength models have been all statistically validated and are all highly dependent on the compression force. Lycatab PGS concentration does not affect disintegration time, mainly increased by the increase of compression pressure. When Pearlitol 200 is used with Vivasol, disintegration time is more influenced by the disintegrant concentration than by the compression pressure, an increase in concentration leading to a significant and relevant increase of the disintegration time. With Zeparox, the interaction between the two controlled variables is more complex: there is no effect of compression force on the disintegration time for a small amount of disintegrant, but a significant increase for higher concentrations. With Kollidon CL, the main factor influencing the disintegration time is the compression force, rather than the disintegrant concentration. Increasing both the compression force and the disintegrant concentration leads to an increase of the disintegration time. For lower Kollidon CL percentages, the compression pressure increases dramatically the tablet disintegration. With the Explotab, whatever the increase of compression force, the disintegrant concentration leads to an increase of the disintegration time. According to Student's t-test, only the compression force significantly and strongly influences the disintegration time when Pearlitol 200 is used. A slight interaction and some trends nevertheless appear: above 150 MPa, increasing the disintegrant concentration leads to a shortened disintegration time, below this limit the opposite effect is observed.

[Assertiveness and peripheral intravenous catheters dwell time with ultrasonography-guided insertion in children and adolescents].

PubMed

Avelar, Ariane Ferreira Machado; Peterlini, Maria Angélica Sorgini; da Pedreira, Mavilde Luz Gonçalves

2013-06-01

Randomized controlled trial which aimed to verify whether the use of vascular ultrasound (VUS) increases assertiveness in the use of peripheral venous catheter in children, and the catheter dwell time, when compared to traditional puncture. Data were collected after approval of theethical merit. Children and adolescents undergoing VUS-guided peripheral intravenous (GVUS) or puncture guided by clinical assessment of the venous conditions(CG) were included in the study. Significance level was set at p< or =0.05. The sample was composed of 382 punctures, 188 (49.2%) in VUS Gand 194 (50.8%) in CG, performed in 335 children. Assertiveness was found in 73 (71.6%) GVUS catheters and in 84(71.8%) of the CG (p=0.970), and catheter dwell time presented a median of less than one day in both groups (p=0.121), showing nostatistically significant difference. VUS did not significantly influence the results of the dependent variables investigated. ClinicalTrials.govNCT00930254.

Terrestrial nitrous oxide cycles and atmospheric effects

NASA Technical Reports Server (NTRS)

Whitten, R. C.; Lawless, J. G.; Banin, A.

1984-01-01

The basic processes that cause N2O emission from soils are briefly discussed, and the rate of the processes is shown to vary widely in space and time, depending on soil, climate, and agrotechnical conditions. Although significant amounts of N2O are indeed emitted from the land, the complexity of the soil processes involved and the wide variation of measured rates still prevents the quantitative evaluation, global budgeting, and reliable prediction of atmospheric N2O. Increased atmospheric N2O abundance increases the levels of odd-nitrogen in the stratosphere, which, in turn, decreases the stratospheric ozone density via a catalytic cycle. Using appropriate atmospheric models and current chemical kinetic data, it has been found that the dependence of ozone reduction on N2O increase is nearly linear; a simulated doubling of N2O leads to a predicted decrease of about 14 percent in total ozone column density. A 10 percent increase in N2O yields a predicted increase in nonmelanoma skin cancer of several percent, and a possible raising of surface temperature of 0.03 K.

Modeling time-dependent corrosion fatigue crack propagation in 7000 series aluminum alloys

NASA Technical Reports Server (NTRS)

Mason, Mark E.; Gangloff, Richard P.

1994-01-01

Stress corrosion cracking and corrosion fatigue experiments were conducted with the susceptible S-L orientation of AA7075-T651, immersed in acidified and inhibited NaCl solution, to provide a basis for incorporating environmental effects into fatigue crack propagation life prediction codes such as NASA FLAGRO. This environment enhances da/dN by five to ten-fold compared to fatigue in moist air. Time-based crack growth rates from quasi-static load experiments are an order of magnitude too small for accurate linear superposition prediction of da/dN for loading frequencies above 0.001 Hz. Alternate methods of establishing da/dt, based on rising-load or ripple-load-enhanced crack tip strain rate, do not increase da/dt and do not improve linear superposition. Corrosion fatigue is characterized by two regimes of frequency dependence; da/dN is proportional to f(exp -1) below 0.001 Hz and to F(exp 0) to F(exp -0.1) for higher frequencies. Da/dN increases mildly both with increasing hold-time at K(sub max) and with increasing rise-time for a range of loading waveforms. The mild time-dependence is due to cycle-time-dependent corrosion fatigue growth. This behavior is identical for S-L nd L-T crack orientations. The frequency response of environmental fatigue in several 7000 series alloys is variable and depends on undefined compositional or microstructural variables. Speculative explanations are based on the effect of Mg on occluded crack chemistry and embritting hydrogen uptake, or on variable hydrogen diffusion in the crack tip process zone. Cracking in the 7075/NaCl system is adequately described for life prediction by linear superposition for prolonged load-cycle periods, and by a time-dependent upper bound relationship between da/dN and delta K for moderate loading times.

Different storage conditions influence biocompatibility and physicochemical properties of iron oxide nanoparticles.

PubMed

Zaloga, Jan; Janko, Christina; Agarwal, Rohit; Nowak, Johannes; Müller, Robert; Boccaccini, Aldo R; Lee, Geoffrey; Odenbach, Stefan; Lyer, Stefan; Alexiou, Christoph

2015-04-24

Superparamagnetic iron oxide nanoparticles (SPIONs) have attracted increasing attention in many biomedical fields. In magnetic drug targeting SPIONs are injected into a tumour supplying artery and accumulated inside the tumour with a magnet. The effectiveness of this therapy is thus dependent on magnetic properties, stability and biocompatibility of the particles. A good knowledge of the effect of storage conditions on those parameters is of utmost importance for the translation of the therapy concept into the clinic and for reproducibility in preclinical studies. Here, core shell SPIONs with a hybrid coating consisting of lauric acid and albumin were stored at different temperatures from 4 to 45 °C over twelve weeks and periodically tested for their physicochemical properties over time. Surprisingly, even at the highest storage temperature we did not observe denaturation of the protein or colloidal instability. However, the saturation magnetisation decreased by maximally 28.8% with clear correlation to time and storage temperature. Furthermore, the biocompatibility was clearly affected, as cellular uptake of the SPIONs into human T-lymphoma cells was crucially dependent on the storage conditions. Taken together, the results show that the particle properties undergo significant changes over time depending on the way they are stored.

Continuous opioid treatment for chronic noncancer pain: a time for moderation in prescribing.

PubMed

Colameco, Stephen; Coren, Joshua S; Ciervo, Carman A

2009-07-01

Physicians have embraced the concept of long-term opioid treatment for chronic noncancer pain (CNCP), as evidenced by increased prescribing. Many patients have benefited from more liberal opioid prescribing, but many have not, and prescription opioid abuse has risen significantly coincident with increased prescribing. Because of the potentially serious adverse effects of opioids, physicians must balance potential benefits against risks, especially in individuals at risk for opioid misuse, abuse, or dependence. This article reviews long-term, continuous opioid treatment of CNCP, current treatment guidelines, addiction risk stratification, opioid-induced hyperalgesia, and endocrine dysfunction.

Transient features in nanosecond pulsed electric fields differentially modulate mitochondria and viability.

PubMed

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.

Global patterns of the dynamics of soil carbon and nitrogen stocks following afforestation: a meta-analysis.

PubMed

Li, Dejun; Niu, Shuli; Luo, Yiqi

2012-07-01

• Afforestation has been proposed as an effective method of carbon (C) sequestration; however, the magnitude and direction of soil carbon accumulation following afforestation and its regulation by soil nitrogen (N) dynamics are still not well understood. • We synthesized the results from 292 sites and carried out a meta-analysis to evaluate the dynamics of soil C and N stocks following afforestation. • Changes in soil C and N stocks were significantly correlated and had a similar temporal pattern. Significant C and N stock increases were found 30 and 50 yr after afforestation, respectively. Before these time points, C and N stocks were either depleted or unchanged. Carbon stock increased following afforestation on cropland and pasture, and in tropical, subtropical and boreal zones. The soil N stock increased in the subtropical zone. The soil C stock increased after afforestation with hardwoods such as Eucalyptus, but did not change after afforestation with softwoods such as pine. Soil N stocks increased and decreased, respectively, after afforestation with hardwoods (excluding Eucalyptus) and pine. • These results indicate that soil C and N stocks both increase with time after afforestation, and that C sequestration through afforestation depends on prior land use, climate and the tree species planted. © 2012 The Authors. New Phytologist © 2012 New Phytologist Trust.

Time-dependent dissociation of cocaine dose–response effects on sucrose craving and locomotion

PubMed Central

Grimm, Jeffrey W.; Buse, Carl; Manaois, Meghan; Osincup, Dan; Fyall, Amber; Wells, Barbara

2010-01-01

In the present study, rats self-administered sucrose 6 h/day for 10 days. Separate groups of rats were then tested on day 1 or day 30 of forced abstinence. After they had responded to near extinction, rats were injected with either saline or cocaine (2.5, 5, 10, or 20 mg/kg intraperitoneal) and then allowed to respond to a sucrose-paired stimulus. Locomotor activity was assessed during testing. Rats pressed more during the extinction responding phase of testing on day 30 than on day 1 of forced abstinence, and this incubation of craving was accompanied by a time-dependent increase in locomotor activity. Compared with saline, cocaine increased responding for the sucrose-paired cue on day 1 of forced abstinence at the 5 mg/kg dose only. In contrast, responding on day 30 was increased at the 10 and 20 mg/kg doses. Locomotor activity increased dose-dependently at both forced-abstinence time points, suggesting a dissociation between cocaine-induced locomotion and cocaine-elevated responding for a sucrose-paired stimulus. These results also indicate that there are time-dependent changes in how cocaine affects sucrose craving. PMID:16495722

Replacing Escherichia coli NAD-dependent glyceraldehyde 3-phosphate dehydrogenase (GAPDH) with a NADP-dependent enzyme from Clostridium acetobutylicum facilitates NADPH dependent pathways.

PubMed

Martínez, Irene; Zhu, Jiangfeng; Lin, Henry; Bennett, George N; San, Ka-Yiu

2008-11-01

Reactions requiring reducing equivalents, NAD(P)H, are of enormous importance for the synthesis of industrially valuable compounds such as carotenoids, polymers, antibiotics and chiral alcohols among others. The use of whole-cell biocatalysis can reduce process cost by acting as catalyst and cofactor regenerator at the same time; however, product yields might be limited by cofactor availability within the cell. Thus, our study focussed on the genetic manipulation of a whole-cell system by modifying metabolic pathways and enzymes to improve the overall production process. In the present work, we genetically engineered an Escherichia coli strain to increase NADPH availability to improve the productivity of products that require NADPH in its biosynthesis. The approach involved an alteration of the glycolysis step where glyceraldehyde-3-phosphate (GAP) is oxidized to 1,3 bisphophoglycerate (1,3-BPG). This reaction is catalyzed by NAD-dependent endogenous glyceraldehyde-3-phosphate dehydrogenase (GAPDH) encoded by the gapA gene. We constructed a recombinant E. coli strain by replacing the native NAD-dependent gapA gene with a NADP-dependent GAPDH from Clostridium acetobutylicum, encoded by the gene gapC. The beauty of this approach is that the recombinant E. coli strain produces 2 mol of NADPH, instead of NADH, per mole of glucose consumed. Metabolic flux analysis showed that the flux through the pentose phosphate (PP) pathway, one of the main pathways that produce NADPH, was reduced significantly in the recombinant strain when compared to that of the parent strain. The effectiveness of the NADPH enhancing system was tested using the production of lycopene and epsilon-caprolactone as model systems using two different background strains. The recombinant strains, with increased NADPH availability, consistently showed significant higher productivity than the parent strains.

Morning surge of ventricular arrhythmias in a new arrhythmogenic canine model of chronic heart failure is associated with attenuation of time-of-day dependence of heart rate and autonomic adaptation, and reduced cardiac chaos.

PubMed

Zhu, Yujie; Hanafy, Mohamed A; Killingsworth, Cheryl R; Walcott, Gregory P; Young, Martin E; Pogwizd, Steven M

2014-01-01

Patients with chronic heart failure (CHF) exhibit a morning surge in ventricular arrhythmias, but the underlying cause remains unknown. The aim of this study was to determine if heart rate dynamics, autonomic input (assessed by heart rate variability (HRV)) and nonlinear dynamics as well as their abnormal time-of-day-dependent oscillations in a newly developed arrhythmogenic canine heart failure model are associated with a morning surge in ventricular arrhythmias. CHF was induced in dogs by aortic insufficiency & aortic constriction, and assessed by echocardiography. Holter monitoring was performed to study time-of-day-dependent variation in ventricular arrhythmias (PVCs, VT), traditional HRV measures, and nonlinear dynamics (including detrended fluctuations analysis α1 and α2 (DFAα1 & DFAα2), correlation dimension (CD), and Shannon entropy (SE)) at baseline, as well as 240 days (240 d) and 720 days (720 d) following CHF induction. LV fractional shortening was decreased at both 240 d and 720 d. Both PVCs and VT increased with CHF duration and showed a morning rise (2.5-fold & 1.8-fold increase at 6 AM-noon vs midnight-6 AM) during CHF. The morning rise in HR at baseline was significantly attenuated by 52% with development of CHF (at both 240 d & 720 d). Morning rise in the ratio of low frequency to high frequency (LF/HF) HRV at baseline was markedly attenuated with CHF. DFAα1, DFAα2, CD and SE all decreased with CHF by 31, 17, 34 and 7%, respectively. Time-of-day-dependent variations in LF/HF, CD, DFA α1 and SE, observed at baseline, were lost during CHF. Thus in this new arrhythmogenic canine CHF model, attenuated morning HR rise, blunted autonomic oscillation, decreased cardiac chaos and complexity of heart rate, as well as aberrant time-of-day-dependent variations in many of these parameters were associated with a morning surge of ventricular arrhythmias.

Morning Surge of Ventricular Arrhythmias in a New Arrhythmogenic Canine Model of Chronic Heart Failure Is Associated with Attenuation of Time-Of-Day Dependence of Heart Rate and Autonomic Adaptation, and Reduced Cardiac Chaos

PubMed Central

Zhu, Yujie; Hanafy, Mohamed A.; Killingsworth, Cheryl R.; Walcott, Gregory P.; Young, Martin E.; Pogwizd, Steven M.

2014-01-01

Patients with chronic heart failure (CHF) exhibit a morning surge in ventricular arrhythmias, but the underlying cause remains unknown. The aim of this study was to determine if heart rate dynamics, autonomic input (assessed by heart rate variability (HRV)) and nonlinear dynamics as well as their abnormal time-of-day-dependent oscillations in a newly developed arrhythmogenic canine heart failure model are associated with a morning surge in ventricular arrhythmias. CHF was induced in dogs by aortic insufficiency & aortic constriction, and assessed by echocardiography. Holter monitoring was performed to study time-of-day-dependent variation in ventricular arrhythmias (PVCs, VT), traditional HRV measures, and nonlinear dynamics (including detrended fluctuations analysis α1 and α2 (DFAα1 & DFAα2), correlation dimension (CD), and Shannon entropy (SE)) at baseline, as well as 240 days (240d) and 720 days (720d) following CHF induction. LV fractional shortening was decreased at both 240d and 720d. Both PVCs and VT increased with CHF duration and showed a morning rise (2.5-fold & 1.8-fold increase at 6 AM-noon vs midnight-6 AM) during CHF. The morning rise in HR at baseline was significantly attenuated by 52% with development of CHF (at both 240d & 720d). Morning rise in the ratio of low frequency to high frequency (LF/HF) HRV at baseline was markedly attenuated with CHF. DFAα1, DFAα2, CD and SE all decreased with CHF by 31, 17, 34 and 7%, respectively. Time-of-day-dependent variations in LF/HF, CD, DFA α1 and SE, observed at baseline, were lost during CHF. Thus in this new arrhythmogenic canine CHF model, attenuated morning HR rise, blunted autonomic oscillation, decreased cardiac chaos and complexity of heart rate, as well as aberrant time-of-day-dependent variations in many of these parameters were associated with a morning surge of ventricular arrhythmias. PMID:25140699

Effect of Detector Dead Time on the Performance of Optical Direct-Detection Communication Links

NASA Technical Reports Server (NTRS)

Chen, C.-C.

1988-01-01

Avalanche photodiodes (APDs) operating in the Geiger mode can provide a significantly improved single-photon detect ion sensitivity over conventional photodiodes. However, the quenching circuit required to remove the excess charge carriers after each photon event can introduce an undesirable dead time into the detection process. The effect of this detector dead time on the performance of a binary pulse-position-modulted (PPM) channel is studied by analyzing the error probability. It is shown that, when back- ground noise is negligible, the performance of the detector with dead time is similar to that o f a quantum-limited receiver. For systems with increasing background intensities, the error rate of the receiver starts to degrade rapidly with increasing dead time. The power penalty due to detector dead time is also evaluated and shown to depend critically on background intensity as well as dead time. Given the expected background strength in an optical channel, therefore, a constraint must be placed on the bandwidth of the receiver to limit the amount of power penalty due to detector dead time.

Effect of detector dead time on the performance of optical direct-detection communication links

NASA Astrophysics Data System (ADS)

Chen, C.-C.

1988-05-01

Avalanche photodiodes (APDs) operating in the Geiger mode can provide a significantly improved single-photon detection sensitivity over conventional photodiodes. However, the quenching circuit required to remove the excess charge carriers after each photon event can introduce an undesirable dead time into the detection process. The effect of this detector dead time on the performance of a binary pulse-position-modulated (PPM) channel is studied by analyzing the error probability. It is shown that, when background noise is negligible, the performance of the detector with dead time is similar to that of a quantum-limited receiver. For systems with increasing background intensities, the error rate of the receiver starts to degrade rapidly with increasing dead time. The power penalty due to detector dead time is also evaluated and shown to depend critically on badkground intensity as well as dead time. Given the expected background strength in an optical channel, therefore, a constraint must be placed on the bandwidth of the receiver to limit the amount of power penalty due to detector dead time.

Fabrication and characterization of carbon nanotube turfs

NASA Astrophysics Data System (ADS)

Qiu, Anqi

Carbon nanotube turfs are vertically aligned, slightly tortuous and entangled functional nanomaterials that exhibit high thermal and electrical properties. CNT turfs exhibit unique combinations of thermal and electrical conductivity, energy absorbing capability, low density and adhesive behavior. The objective of this study is to fabricate, measure, manipulate and characterize CNT turfs and thus determine the relationship between a turf's properties and its morphology, and provide guidance for developing links between turf growth conditions and of the subsequent turf properties. Nanoindentation was utilized to determine the mechanical and in situ electrical properties of CNT turfs. Elastic properties do not vary significantly laterally within a single turf, quantifying for the first time the ability to treat the turf as a mechanical continuum throughout. The use of the average mechanical properties for any given turf should be suitable for design purpose without the necessity of accounting for lateral spatial variation in structure. Properties variation based on time dependency, rate dependency, adhesive behavior and energy absorption and dissipation behavior have been investigated for these CNT turfs. Electrical properties measurements of CNT turfs have been carried out and show that a constant electrical current at a constant penetration depth indicates that a constant number of CNTs in contact with the tip; combining with the results that adhesive load increased with an increasing penetration hold time, thus we conclude that during a hold period of nanoindentation, individual tubes increase their individual attachment to the tip. CNT turfs show decreased adhesion and modulus after exposure to an electron beam due to carbon deposition and subsequent oxidation. To increase the modulus of the turf, axial compression and solvent capillary were used to increase the density of the turf by up to 15 times. Structure-property relationships were determined from the density and tortuosity measurements carried out through in situ electrical measurements and directionality measurements. Increasing density increases the mechanical properties as well as electrical conductivity. The modulus increased with a lower tortuosity, which may be related to the compressive buckling positioning.

Nonautonomous dark soliton solutions in two-component Bose—Einstein condensates with a linear time-dependent potential

NASA Astrophysics Data System (ADS)

Li, Qiu-Yan; Wang, Shuang-Jin; Li, Zai-Dong

2014-06-01

We report the analytical nonautonomous soliton solutions (NSSs) for two-component Bose—Einstein condensates with the presence of a time-dependent potential. These solutions show that the time-dependent potential can affect the velocity of NSS. The velocity shows the characteristic of both increasing and oscillation with time. A detailed analysis for the asymptotic behavior of NSSs demonstrates that the collision of two NSSs of each component is elastic.

Soil Solution Phosphorus Status and Mycorrhizal Dependency in Leucaena leucocephala.

PubMed

Habte, M; Manjunath, A

1987-04-01

A phosphorus sorption isotherm was used to establish concentrations of P in a soil solution ranging from 0.002 to 0.807 mug/ml. The influence of P concentration on the symbiotic interaction between the tropical tree legume Leucaena leucocephala and the vesicular-arbuscular mycorrhizal (VAM) fungus Glomus fasciculatum was evaluated in pot experiments. The level of mycorrhizal infection in Leucaena roots increased as the concentration of P was raised from 0.002 to 0.153 mug/ml. Higher levels of P depressed mycorrhizal infection, but the level of infection never declined below 50%. Periodic monitoring of P contents of Leucaena subleaflets indicated that significant mycorrhizal activity was detected as early as 17 days after planting, with the activity peaking 12 to 16 days thereafter. The highest level of mycorrhizal activity was associated with a soil solution P level of 0.021 mug/ml. Even though the mycorrhizal inoculation effect diminished as the concentration of P in the soil solution was increased, mycorrhizal inoculation significantly increased P uptake and dry-matter yield of Leucaena at all levels of soil solution P examined. The concentration of P required by nonmycorrhizal L. leucocephala for maximum yield was 27 to 38 times higher than that required by mycorrhizal L. leucocephala. The results illustrate the very high dependence of L. leucocephala on VAM fungi and the significance of optimizing soil solution phosphorus for enhancing the benefits of the VAM symbiosis.

Pulsed magnetic field enhances therapeutic efficiency of mesenchymal stem cells in chronic neuropathic pain model.

PubMed

Mert, Tufan; Kurt, Akif Hakan; Altun, İdiris; Celik, Ahmet; Baran, Furkan; Gunay, Ismail

2017-05-01

Cell-based or magnetic field therapies as alternative approaches to pain management have been tested in several experimental pain models. The aim of this study therefore was to investigate the actions of the cell-based therapy (adipose tissue derived mesenchymal stem cells; ADMSC) or pulsed magnetic field (PMF) therapy and magneto-cell therapy (combination of ADMSC and PMF) in chronic constriction nerve injury model (CCI). The actions of individual ADMSC (route dependent [systemic or local], time-dependent [a day or a week after surgery]), or PMF and their combination (magneto-cell) therapies on hyperalgesia and allodynia were investigated by using thermal plantar test and a dynamic plantar aesthesiometer, respectively. In addition, various cytokine levels (IL-1β, IL-6, and IL-10) of rat sciatic nerve after CCI were analyzed. Following the CCI, both latency and threshold significantly decreased. ADMSC or PMF significantly increased latencies and thresholds. The combination of ADMSC with PMF even more significantly increased latency and threshold when compared with ADMSC alone. However, ADMSC-induced decrease in pro-inflammatory or increase in anti-inflammatory cytokines levels were partially prevented by PMF treatments. Present findings may suggest that both cell-based and magnetic therapies can effectively attenuate chronic neuropathic pain symptoms. Combined magneto-cell therapy may also efficiently reverse neuropathic signs. Bioelectromagnetics. 38:255-264, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Site-specific differences of insulin action in adipose tissue derived from normal prepubertal children.

PubMed

Grohmann, Malcolm; Stewart, Claire; Welsh, Gavin; Hunt, Linda; Tavaré, Jeremy; Holly, Jeff; Shield, Julian; Sabin, Matt; Crowne, Elizabeth

2005-08-15

Body fat distribution determines obesity-related morbidity in adults but little is known of the aetiology or pathophysiology in children. This study investigates differences in insulin-mediated metabolism in primary cell cultures of subcutaneous and visceral preadipocytes derived from prepubertal children. The impact of differentiation and responses to TNFalpha exposure was also investigated. Proliferation rates were greater in subcutaneous versus visceral preadipocytes (41 h3 versus 69 h4; P=0.008). Insulin caused a dose-dependent increase in GSK-3 phosphorylation and an increase in MAPK phosphorylation over time, with increased sensitivity in subcutaneous preadipocytes. Post-differentiation, dose-dependent increases in GSK-3 phosphorylation were maintained, while MAPK phosphorylation was identical in both subtypes. No changes were observed in insulin receptor abundance pre-/post-differentiation. GLUT4 abundance was significantly increased in visceral versus subcutaneous adipocytes by 76(4)%; P=0.03), coincidental with increased insulin-stimulated 2-deoxy-glucose transport (+150(26)% versus +79(10)%; P=0.014) and further elevated by acute exposure to TNFalpha (+230(52)%; P=0.019 versus +123(24)%; P=0.025, respectively). TNFalpha also significantly increased basal glucose transport rates (+44(14)%; P=0.006 versus +34(11)%; P=0.007) and GLUT1 localisation to the plasma membrane. These data establish site-specific differences in subcutaneous and visceral fat cells from children. Responses to insulin varied with differentiation and TNFalpha exposure in the two depots, consistent with parallel changes in GLUT1/4 abundance and localisation.

A prospective study of posturography in normal older people.

PubMed

Baloh, R W; Corona, S; Jacobson, K M; Enrietto, J A; Bell, T

1998-04-01

To follow posturographic measurements over time in a group of normal older subjects to see if sway increases with aging and if sway is greater in those with deteriorating balance and falls. Seventy-two community-dwelling older people (age range 79-91 years), who initially had normal neurological evaluations, were followed with three yearly follow-up examinations. Amplitude and velocity of sway on static and dynamic posturography, Tinetti gait and balance score, reports of falls. Velocity of sway on dynamic tests increased significantly during the 3 years of follow-up. The percentage increase in sway was about the same in the anterior-posterior and medial-lateral directions and with eyes open and eyes closed. Subjects with low Tinetti scores had higher sway amplitude and velocity, particularly on dynamic tests, but no measure of sway was significantly different in those who reported falls compared with those who did not report falls. Sway increases in normal subjects over time, and sway is greater in older subjects with deteriorating balance compared with those with normal balance. Sway was not greater in those who fell compared with those who did not fall, probably because falls are highly dependent on individual behavior.

Ursodeoxycholic acid increases low-density lipoprotein binding, uptake and degradation in isolated hamster hepatocytes.

PubMed Central

Bouscarel, B; Fromm, H; Ceryak, S; Cassidy, M M

1991-01-01

Ursodeoxycholic acid (UDCA), in contrast to both chenodeoxycholic acid (CDCA), its 7 alpha-epimer, and lithocholic acid, enhanced receptor-dependent low-density lipoprotein (LDL) uptake and degradation in isolated hamster hepatocytes. The increase in cell-associated LDL was time- and concentration-dependent, with a maximum effect observed at approx. 60 min with 1 mM-UDCA. This increase was not associated with a detergent effect of UDCA, as no significant modifications were observed either in the cellular release of lactate dehydrogenase or in Trypan Blue exclusion. The effect of UDCA was not due to a modification of the LDL particle, but rather was receptor-related. UDCA (1 mM) maximally increased the number of 125I-LDL-binding sites (Bmax.) by 35%, from 176 to 240 ng/mg of protein, without a significant modification of the binding affinity. Furthermore, following proteolytic degradation of the LDL receptor with Pronase, specific LDL binding decreased to the level of non-specific binding, and the effect of UDCA was abolished. Conversely, the trihydroxy 7 beta-hydroxy bile acid ursocholic acid and its 7 alpha-epimer, cholic acid, induced a significant decrease in LDL binding by approx. 15%. The C23 analogue of UDCA (nor-UDCA) and CDCA did not affect LDL binding. On the other hand, UDCA conjugated with either glycine (GUDCA) or taurine (TUDCA), increased LDL binding to the same extent as did the free bile acid. The half maximum time (t1/2) to reach the full effect was 1-2 min for UDCA and TUDCA, while GUDCA had a much slower t1/2 of 8.3 min. Ketoconazole (50 microM), an antifungal agent, increased LDL binding, but this effect was not additive when tested in the presence of 0.7 mM-UDCA. The results of the studies indicate that, in isolated hamster hepatocytes, the UDCA-induced increase in receptor-dependent LDL binding and uptake represents a direct effect of this bile acid. The action of the bile acid is closely related to its specific structural conformation, since UDCA and its conjugates are the only bile acids shown to express this ability thus far. However, certain agents other than bile acids, such as ketoconazole, have a similar effect. Finally, the studies suggest that the recruitment of LDL receptors from a latent pool in the hepatocellular membrane may be the mechanism by which UDCA exerts its direct effect. Images Fig. 6. PMID:1764022

Changes in glutamate receptor subunits within the medulla in goats after section of the carotid sinus nerves

PubMed Central

Miller, Justin Robert; Neumueller, Suzanne; Muere, Clarissa; Olesiak, Samantha; Pan, Lawrence; Bukowy, John D.; Daghistany, Asem O.; Hodges, Matthew R.

2014-01-01

The mechanisms which contribute to the time-dependent recovery of resting ventilation and the ventilatory CO2 chemoreflex after carotid body denervation (CBD) are poorly understood. Herein we tested the hypothesis that there are time-dependent changes in the expression of specific AMPA, NMDA, and/or neurokinin-1 (NK1R) receptors within respiratory-related brain stem nuclei acutely or chronically after CBD in adult goats. Brain stem tissues were collected acutely (5 days) or chronically (30 days) after sham or bilateral CBD, immunostained with antibodies targeting AMPA (GluA1 or GluA2), NMDA (GluN1), or NK-1 receptors, and optical density (OD) compared. Physiological measurement confirmed categorization of each group and showed ventilatory effects consistent with bilateral CBD (Miller et al. J Appl Physiol 115: 1088–1098, 2013). Acutely after CBD, GluA1 OD was unchanged or slightly increased, but GluA2 and GluN1 OD were reduced 15–30% within the nucleus tractus solitarius (NTS) and in other medullary respiratory nuclei. Chronically after CBD, GluA1 was reduced (P < 0.05) within the caudal NTS and in other nuclei, but there was significant recovery of GluA2 and GluN1 OD. NK1 OD was not significantly different from control after CBD. We conclude that the initial decrease in GluA2 and GluN1 after CBD likely contributes to hypoventilation and the reduced CO2 chemoreflex. The partial recovery of ventilation and the CO2 chemoreflex after CBD parallel a time-dependent return of these receptors to near control levels but likely depend upon additional initiating and maintenance factors for neuroplasticity. PMID:24790015

Temporal trends and variability of colonoscopy performance in a gastroenterology practice.

PubMed

le Clercq, Chantal M C; Mooi, Rick J; Winkens, Bjorn; Salden, Bouke N H; Bakker, C Minke; van Nunen, Annick B; Keulen, Eric P T; de Ridder, Rogier J; Masclee, Ad A M; Sanduleanu, Silvia

2016-03-01

Quality measures for colonoscopy are operator dependent and vary. It is unclear whether quality measures change over time. In this study, time-dependent variation in colonoscopy performance was examined in a gastroenterology practice. Colonoscopy and histopathology records that were collected at three hospitals (one university and two non-university hospitals) over three time periods (2007, 2010, and 2013) were reviewed. Data from colonoscopists performing at least 100 procedures per year were analyzed. Inter-colonoscopist variation in performance (i. e. adjusted cecal intubation rate [aCIR], adenoma detection rate [ADR], advanced ADR, mean adenomas per procedure [MAP], proximal ADR, nonpolypoid ADR, and serrated polyp detection rate) were examined using coefficients of variation. Logistic regression analyses were also performed, adjusting for covariates. A total of 23 colonoscopists performing 6400 procedures were included. Overall, the mean aCIR, ADR, MAP, and proximal ADR improved significantly over time, from 91.9 %, 22.5 %, 0.37, and 10.2 % in 2007 to 95.3 %, 25.8 %, 0.45, and 13.4 %, respectively, in 2013 (P < 0.05). The inter-colonoscopist variation in ADR decreased from 37 % in 2007 to 15 % in 2013 (P < 0.05). In the non-university hospitals, mean values for quality measures increased significantly over time, whereas they remained stable in the university hospital. Variability in performance among colonoscopists decreased significantly within the gastroenterology clinical practice. Core quality measures improved over time, mainly through improvement of the lower performers. Measurement of inter-colonoscopist variation in performance helps to identify factors that stimulate or hinder performance, and forms the basis for interventions. http://www.trialregister.nl. © Georg Thieme Verlag KG Stuttgart · New York.

Pharmacologic characterization of the oxytocin receptor in human uterine smooth muscle cells

PubMed Central

Tahara, Atsuo; Tsukada, Junko; Tomura, Yuichi; Wada, Koh-ichi; Kusayama, Toshiyuki; Ishii, Noe; Yatsu, Takeyuki; Uchida, Wataru; Tanaka, Akihiro

2000-01-01

[3H]-oxytocin was used to characterize the oxytocin receptor found in human uterine smooth muscle cells (USMC). Specific binding of [3H]-oxytocin to USMC plasma membranes was dependent upon time, temperature and membrane protein concentration. Scatchard plot analysis of equilibrium binding data revealed the existence of a single class of high-affinity binding sites with an apparent equilibrium dissociation constant (Kd) of 0.76 nM and a maximum receptor density (Bmax) of 153 fmol mg−1 protein. The Hill coefficient (nH) did not differ significantly from unity, suggesting binding to homogenous, non-interacting receptor populations. Competitive inhibition of [3H]-oxytocin binding showed that oxytocin and vasopressin (AVP) receptor agonists and antagonists displaced [3H]-oxytocin in a concentration-dependent manner. The order of potencies for peptide agonists and antagonists was: oxytocin>[Asu1,6]-oxytocin>AVP= atosiban>d(CH2)5Tyr(Me)AVP>[Thr4,Gly7]-oxytocin>dDAVP, and for nonpeptide antagonists was: L-371257>YM087>SR 49059>OPC-21268>SR 121463A>OPC-31260. Oxytocin significantly induced concentration-dependent increase in intracellular Ca2+ concentration ([Ca2+]i) and hyperplasia in USMC. The oxytocin receptor antagonists, atosiban and L-371257, potently and concentration-dependently inhibited oxytocin-induced [Ca2+]i increase and hyperplasia. In contrast, the V1A receptor selective antagonist, SR 49059, and the V2 receptor selective antagonist, SR 121463A, did not potently inhibit oxytocin-induced [Ca2+]i increase and hyperplasia. The potency order of antagonists in inhibiting oxytocin-induced [Ca2+]i increase and hyperplasia was similar to that observed in radioligand binding assays. In conclusion, these data provide evidence that the high-affinity [3H]-oxytocin binding site found in human USMC is a functional oxytocin receptor coupled to [Ca2+]i increase and cell growth. Thus human USMC may prove to be a valuable tool in further investigation of the physiologic and pathophysiologic roles of oxytocin in the uterus. PMID:10694212

Antenatal retinoic acid administration increases trophoblastic retinol-binding protein dependent retinol transport in the nitrofen model of congenital diaphragmatic hernia.

PubMed

Kutasy, Balazs; Friedmacher, Florian; Pes, Lara; Coyle, David; Doi, Takashi; Paradisi, Francesca; Puri, Prem

2016-04-01

Low pulmonary retinol levels and disrupted retinoid signaling pathway (RSP) have been implicated in the pathogenesis of congenital diaphragmatic hernia (CDH) and associated pulmonary hypoplasia (PH). It has been demonstrated that nitrofen disturbs the main retinol-binding protein (RBP)-dependent trophoblastic retinol transport. Several studies have demonstrated that prenatal treatment with retinoic acid (RA) can reverse PH in the nitrofen-induced CDH model. We hypothesized that maternal administration of RA can increase trophoblastic RBP-dependent retinol transport in a nitrofen model of CDH. Pregnant rats were treated with nitrofen or vehicle on gestational day 9 (D9) and sacrificed on D21. RA was given i.p. on D18, D19, and D20. Retinol and RA levels were measured using high-performance liquid chromatography. Immunohistochemistry was performed to evaluate trophoblastic expression of RBP. Expression levels of the primary RSP genes were determined using quantitative real-time PCR and immunohistochemistry. Markedly increased trophoblastic RBP immunoreactivity was observed in CDH+RA compared to CDH. Significantly increased serum and pulmonary retinol and RA levels were detected in CDH+RA compared to CDH. Pulmonary expression of RSP genes and proteins were increased in CDH+RA compared to CDH. Increased trophoblastic RBP expression and retinol transport after antenatal administration of RA suggest that retinol-triggered RSP activation may attenuate CDH-associated PH by elevating serum and pulmonary retinol levels.

[Site of prelingual cochlear stimulation and its effect on electrically evoked compound action potentials and refractory using the Nucleus 24 standard].

PubMed

Ma, R Y; Li, W; Jiang, X J

2016-12-01

Objective: To investigate the correlation between the site of prelingual cochlear stimulation and its effect on electrically evoked compound action potentials. Method: Recordings of auditory nerve responses were conducted in 32 prelingual subjects to demonstrate the feasibility of ECAP recordings using the nerve response telemetry(NRT) feature of the Nucleus CI24R(CA) system software. These recordings were then analyzed based on the site of cochlear stimulation defined as basal, middle and apical to determine if the amplitude, threshold and slope of the amplitude growth function and the refractory time differs depending on the region of stimulation. Result: Findings of our prelingual children showed significant differences in the ECAP recordings depending on the stimulation site. Comparing the apical with the basal region, on average higher amplitudes, lower thresholds and steeper slopes of the amplitude growth function hadbeen observed. The refractory time showed an overall dependence on cochlear region; however post-hoc tests showed no significant effect between individual regions. Conclusion: Obtaining ECAP recordings is also possible in the most apical region of the cochlea. However, differences can be observed depending on the region of the cochlea stimulated. Specifically, significant higher ECAP amplitude, lower thresholds and steeper amplitude growth function slopes have been observed in the apical region. These differences between prelingual children and adults could be explained by the location of the stimulating electrode with respect to the neural tissue in the cochlea, a higher density, or an increased neural survival rate of neural tissue in the apex. Copyright© by the Editorial Department of Journal of Clinical Otorhinolaryngology Head and Neck Surgery.

Recharge characteristics of an unconfined aquifer from the rainfall-water table relationship

NASA Astrophysics Data System (ADS)

Viswanathan, M. N.

1984-02-01

The determination of recharge levels of unconfined aquifers, recharged entirely by rainfall, is done by developing a model for the aquifer that estimates the water-table levels from the history of rainfall observations and past water-table levels. In the present analysis, the model parameters that influence the recharge were not only assumed to be time dependent but also to have varying dependence rates for various parameters. Such a model is solved by the use of a recursive least-squares method. The variable-rate parameter variation is incorporated using a random walk model. From the field tests conducted at Tomago Sandbeds, Newcastle, Australia, it was observed that the assumption of variable rates of time dependency of recharge parameters produced better estimates of water-table levels compared to that with constant-recharge parameters. It was observed that considerable recharge due to rainfall occurred on the very same day of rainfall. The increase in water-table level was insignificant for subsequent days of rainfall. The level of recharge very much depends upon the intensity and history of rainfall. Isolated rainfalls, even of the order of 25 mm day -1, had no significant effect on the water-table levels.

Effect of detomidine on visceral and somatic nociception and duodenal motility in conscious adult horses.

PubMed

Elfenbein, Johanna R; Sanchez, L Chris; Robertson, Sheilah A; Cole, Cynthia A; Sams, Richard

2009-03-01

To evaluate the effects of detomidine on visceral and somatic nociception, heart and respiratory rates, sedation, and duodenal motility and to correlate these effects with serum detomidine concentrations. Nonrandomized, experimental trial. Five adult horses, each with a permanent gastric cannula weighing 534 +/- 46 kg. Visceral nociception was evaluated by colorectal (CRD) and duodenal distension (DD). The duodenal balloon was used to assess motility. Somatic nociception was assessed via thermal threshold (TT). Nose-to-ground (NTG) height was used as a measure of sedation. Serum was collected for pharmacokinetic analysis. Detomidine (10 or 20 microg kg(-1)) was administered intravenously. Data were analyzed by means of a three-factor anova with fixed factors of treatment and time and random factor of horse. When a significant time x treatment interaction was detected, differences were compared with a simple t-test or Bonferroni t-test. Significance was set at p < 0.05. Detomidine produced a significant, dose-dependent decrease in NTG height, heart rate, and skin temperature and a significant, nondose-dependent decrease in respiratory rate. Colorectal distension threshold was significantly increased with 10 microg kg(-1) for 15 minutes and for at least 165 minutes with 20 microg kg(-1). Duodenal distension threshold was significantly increased at 15 minutes for the 20 microg kg(-1) dose. A significant change in TT was not observed at either dose. A marked, immediate decrease in amplitude of duodenal contractions followed detomidine administration at both doses for 50 minutes. Detomidine caused a longer period of visceral anti-nociception as determined by CRD but a shorter period of anti-nociception as determined by DD than has been previously reported. The lack of somatic anti-nociception as determined by TT testing may be related to the marked decrease in skin temperature, likely caused by peripheral vasoconstriction and the low temperature cut-off of the testing device.

Substance P promotes expansion of human mesenteric preadipocytes through proliferative and antiapoptotic pathways.

PubMed

Gross, Kara; Karagiannides, Iordanes; Thomou, Thomas; Koon, Hon Wai; Bowe, Collin; Kim, Ho; Giorgadze, Nino; Tchkonia, Tamara; Pirtskhalava, Tamara; Kirkland, James L; Pothoulakis, Charalabos

2009-05-01

White adipose tissue is intimately involved in the regulation of immunity and inflammation. We reported that human mesenteric preadipocytes express the substance P (SP)-mediated neurokinin-1 receptor (NK-1R), which signals proinflammatory responses. Here we tested the hypothesis that SP promotes proliferation and survival of human mesenteric preadipocytes and investigated responsible mechanism(s). Preadipocytes were isolated from mesenteric fat biopsies during gastric bypass surgery. Proliferative and antiapoptotic responses were delineated in 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS), bromodeoxyuridine (BrdU), caspase-3, and TUNEL assays, as well as Western immunoanalysis. SP (10(-7) M) increased MTS and proliferation (BrdU) and time dependently (15-30 min) induced Akt, EGF receptor, IGF receptor, integrin alphaVbeta3, phosphatidylinositol 3-kinase, and PKC-theta phosphorylation. Furthermore, pharmacological antagonism of Akt and PKC-theta activation significantly attenuated SP-induced preadipocyte proliferation. Exposure of preadipocytes to the proapoptotic Fas ligand (FasL, 100 microM) resulted in nuclear DNA fragmentation (TUNEL assay), as well as increased cleaved poly (ADP-ribose) polymerase, cleaved caspase-7, and caspase-3 expression. Cotreatment with SP almost completely abolished these responses in a NK-1R-dependent fashion. SP (10(-7) M) also time dependently stimulated expression 4E binding protein 1 and phosphorylation of p70 S6 kinase, which increased protein translation efficiency. SP increases preadipocyte viability, reduces apoptosis, and stimulates proliferation, possibly via cell cycle upregulation and increased protein translation efficiency. SP-induced proliferative and antiapoptotic pathways in fat depots may contribute to development of the creeping fat and inflammation characteristic of Crohn's disease.

Pharmacologic activation of peroxisome proliferator-activating receptor-α accelerates hepatic fatty acid oxidation in neonatal pigs

PubMed Central

Shim, Kwanseob; Jacobi, Sheila; Odle, Jack; Lin, Xi

2018-01-01

Up-regulation of peroxisome proliferator-activating receptor-α (PPARα) and increasing fatty acid oxidation are important for reducing pre-weaning mortality of pigs. We examined the time-dependent regulatory effects of PPARα activation via oral postnatal clofibrate administration (75 mg/(kg-BW·d) for up to 7 days) on mitochondrial and peroxisomal fatty acid oxidation in pigs, a species with limited hepatic fatty acid oxidative capacity due to low ketogenesis. Hepatic oxidation was increased by 44-147% (depending on fatty acid chain-length) and was attained after only 4 days of clofibrate treatment. Acyl-CoA oxidase (ACO) and carnitine palmitoyltransferase I (CPTI) activities accelerated in parallel. The increase in CPTI activity was accompanied by a rapid reduction in the sensitivity of CPTI to malonyl-CoA inhibition. The mRNA abundance of CPTI and ACO, as well as peroxisomal keto-acyl-CoA thiolase (KetoACoA) and mitochondrial malonyl-CoA decarboxylase (MCD), also were augmented greatly. However, the increase in ACO activity and MCD expression were different from CPTI, and significant interactions were observed between postnatal age and clofibrate administration. Furthermore, the expression of acetyl-CoA carboxylase β (ACCβ) decreased with postnatal age and clofibrate had no effect on its expression. Collectively these results demonstrate that the expression of PPARα target genes and the increase in fatty acid oxidation induced by clofibrate are time- and age-dependent in the liver of neonatal pigs. Although the induction patterns of CPTI, MCD, ACO, KetoACoA, and ACCβ are different during the early postnatal period, 4 days of exposure to clofibrate were sufficient to robustly accelerate fatty acid oxidation.

Drying kinetic of industrial cassava flour: Experimental data in view.

PubMed

Odetunmibi, Oluwole A; Adejumo, Oluyemisi A; Oguntunde, Pelumi E; Okagbue, Hilary I; Adejumo, Adebowale O; Suleiman, Esivue A

2017-12-01

In this data article, laboratory experimental investigation results on drying kinetic properties: the drying temperature ( T ), drying air velocity ( V ) and dewatering time (Te), each of the factors has five levels, and the experiment was replicated three times and the output: drying rate and drying time obtained, were observed. The experiment was conducted at National Centre for Agricultural Mechanization (NCAM) for a period of eight months, in 2014. Analysis of variance was carried out using randomized complete block design with factorial experiment on each of the outputs: drying rate and drying times of the industrial cassava flour. A clear picture on each of these outputs was provided separately using tables and figures. It was observed that all the main factors as well as two and three ways interactions are significant at 5% level for both drying time and rate. This also implies that the rate of drying grated unfermented cassava mash, to produce industrial cassava flour, depend on the dewatering time (the initial moisture content), temperature of drying, velocity of drying air as well as the combinations of these factors altogether. It was also discovered that all the levels of each of these factors are significantly difference from one another. In summary, the time of drying is a function of the dewatering time which was responsible for the initial moisture content. The higher the initial moisture content the longer the time of drying, and the lower the initial moisture content, the lower the time of drying. Also, the higher the temperature of drying the shorter the time of drying and vice versa. Also, the air velocity effect on the drying process was significant. As velocity increases, rate of drying also increases and vice versa. Finally, it can be deduced that the drying kinetics are influenced by these processing factors.

Nanosilica induced dose-dependent cytotoxicity and cell type-dependent multinucleation in HepG2 and L-02 cells

NASA Astrophysics Data System (ADS)

Yu, Yongbo; Duan, Junchao; Li, Yang; Yu, Yang; Hu, Hejing; Wu, Jing; Zhang, Yannan; Li, Yanbo; CaixiaGuo; Zhou, Xianqing; Sun, Zhiwei

2016-11-01

The prevalent exposure to nanosilica gained concerns about health effects of these particles on human beings. Although nanosilica-induced multinucleation has been confirmed previously, the underlying mechanism was still not clear; this study was to investigate the origination of multinucleated cells caused by nanosilica (62 nm) in both HepG2 and L-02 cells. Cell viability and cellular uptake was determined by MTT assay and transmission electron microscope (TEM), respectively. Giemsa staining was applied to detect multinucleation. To clarify the origination of multinucleated cells, fluorescent probes, PKH26 and PKH67, time-lapse observation were further conducted by confocal microscopy. Results indicated that nanosilica particles were internalized into cells and induced cytotoxicity in a dose-dependent manner. Quantification analysis showed that nanosilica significantly increased the rates of binucleated and multinucleated cells, which suggested mitotic catastrophe induction. Moreover, dynamic visualization verified that multinucleation resulted from cell fusion in HepG2 cells not in L-02 cells after nanosilica exposure, suggesting cell type-dependent multinucleation formation. Both multinucleation and cell fusion were involved in genetic instability, which emphasized the significance to explore the multinucleation induced by nanosilica via environmental, occupational and consumer product exposure.

Effect of bacterial stimulants on release of reactive oxygen metabolites from peripheral blood neutrophils in periodontitis.

PubMed

Zekonis, Gediminas; Zekonis, Jonas

2004-01-01

The aim of the present investigation was to explore the oxidative activity of peripheral blood polymorphonuclear neutrophils of periodontitis patients and of healthy subjects stimulated with non-opsonized E. coli and lipopolysaccharide of E. coli. The leukocytes for this study were obtained from peripheral venous blood of 22 parodontitis patients and 16 healthy subjects. Oxidative activity of peripheral blood polymorphonuclear neutrophils was measured by method of the luminol-dependent chemiluminescence. The luminol-dependent chemiluminescence of stimulated neutrophils of periodontitis patients with non-opsonized E. coli increased less significantly (p<0.001) as compared to analogous chemiluminescence of control subjects (147126+/-8386 cpm and 189247+/-9134 cpm, respectively). However, the luminol-dependent chemiluminescence of stimulated neutrophils of periodontitis patients with lipopolysaccharide was five times higher than that of the subjects with intact periodontal tissues and comprised 13261+/-1251 cpm and 2627+/-638 cpm, respectively. Our study results show a complex dependence of oxidative function of peripheral polymorphonuclear neutrophils of periodontitis patients upon the nature of stimulants. Therefore further attempts should be made to evaluate its significance in the etiopathogenesis of periodontal tissue diseases of inflammatory origin.

Asthma exacerbations in children immediately following stressful life events: a Cox's hierarchical regression.

PubMed

Sandberg, S; Järvenpää, S; Penttinen, A; Paton, J Y; McCann, D C

2004-12-01

A recent prospective study of children with asthma employing a within subject, over time analysis using dynamic logistic regression showed that severely negative life events significantly increased the risk of an acute exacerbation during the subsequent 6 week period. The timing of the maximum risk depended on the degree of chronic psychosocial stress also present. A hierarchical Cox regression analysis was undertaken to examine whether there were any immediate effects of negative life events in children without a background of high chronic stress. Sixty children with verified chronic asthma were followed prospectively for 18 months with continuous monitoring of asthma by daily symptom diaries and peak flow measurements, accompanied by repeated interview assessments of life events. The key outcome measures were asthma exacerbations and severely negative life events. An immediate effect evident within the first 2 days following a severely negative life event increased the risk of a new asthma attack by a factor of 4.69, 95% confidence interval 2.33 to 9.44 (p<0.001) [corrected] In the period 3-10 days after a severe event there was no increased risk of an asthma attack (p = 0.5). In addition to the immediate effect, an increased risk of 1.81 (95% confidence interval 1.24 to 2.65) [corrected] was found 5-7 weeks after a severe event (p = 0.002). This is consistent with earlier findings. There was a statistically significant variation due to unobserved factors in the incidence of asthma attacks between the children. The use of statistical methods capable of investigating short time lags showed that stressful life events significantly increase the risk of a new asthma attack immediately after the event; a more delayed increase in risk was also evident 5-7 weeks later.

Effect of accelerated crucible rotation on melt composition in high-pressure vertical Bridgman growth of cadmium zinc telluride

NASA Astrophysics Data System (ADS)

Yeckel, Andrew; Derby, Jeffrey J.

2000-02-01

Three-dimensional axisymmetric, time-dependent simulations of the high-pressure vertical Bridgman growth of large-diameter cadmium zinc telluride are performed to study the effect of accelerated crucible rotation (ACRT) on crystal growth dynamics. The model includes details of heat transfer, melt convection, solid-liquid interface shape, and dilute zinc segregation. Application of ACRT greatly improves mixing in the melt, but causes an overall increased deflection of the solid-liquid interface. The flow exhibits a Taylor-Görtler instability at the crucible sidewall, which further enhances melt mixing. The rate of mixing depends strongly on the length of the ACRT cycle, with an optimum half-cycle length between 2 and 4 Ekman time units. Significant melting of the crystal occurs during a portion of the rotation cycle, caused by periodic reversal of the secondary flow at the solid-liquid interface, indicating the possibility of compositional striations.

Ion guiding accompanied by formation of neutrals in polyethylene terephthalate polymer nanocapillaries: Further insight into a self-organizing process

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

Juhasz, Z.; Sulik, B.; Racz, R.

2010-12-15

A relatively large yield of neutralized atoms was observed when 3 keV Ar{sup 7+} ions were guided trough polyethylene terephthalate nanocapillaries. Time and deposited-charge dependence of the angular distribution of both the guided ions and the neutrals was measured simultaneously using a two-dimensional multichannel plate detector. The yield of neutrals increased significantly faster than that of guided ions and saturated typically at a few percent level. In accordance with earlier observations, both the yield and the mean emission angle of the guided ions exhibited strong oscillations. For the atoms, the equilibrium was achieved not only faster, but also without significantmore » oscillations in yield and angular position. A phase analysis of these time dependencies provides insight into the dynamic features of the self-organizing mechanisms, which leads to ion guiding in insulating nanocapillaries.« less

Amplitude analysis of four-body decays using a massively-parallel fitting framework

NASA Astrophysics Data System (ADS)

Hasse, C.; Albrecht, J.; Alves, A. A., Jr.; d'Argent, P.; Evans, T. D.; Rademacker, J.; Sokoloff, M. D.

2017-10-01

The GooFit Framework is designed to perform maximum-likelihood fits for arbitrary functions on various parallel back ends, for example a GPU. We present an extension to GooFit which adds the functionality to perform time-dependent amplitude analyses of pseudoscalar mesons decaying into four pseudoscalar final states. Benchmarks of this functionality show a significant performance increase when utilizing a GPU compared to a CPU. Furthermore, this extension is employed to study the sensitivity on the {{{D}}}0-{\\bar{{{D}}}}0 mixing parameters x and y in a time-dependent amplitude analysis of the decay D0 → K+π-π+π-. Studying a sample of 50 000 events and setting the central values to the world average of x = (0.49 ± 0.15)% and y = (0.61 ± 0.08)%, the statistical sensitivities of x and y are determined to be σ(x) = 0.019 % and σ(y) = 0.019 %.

Magnetic storms and variations in hormone levels among residents of North Polar area - Svalbard

NASA Astrophysics Data System (ADS)

Breus, T. K.; Boiko, E. R.; Zenchenko, T. A.

2015-01-01

In the present work four examinations (January, March, June, October 1991-1992) of the blood concentration of adrenal hormones (cortisol) and thyroid hormones (triiodothyronine (T3) and thyroxine T4) and their dependence on space and terrestrial weather parameters have been done for large groups of healthy inhabitants of high latitudes (Svalbard, the most northerly in the world year-round inhabited settlements). The aim of this study was to find the possible sensitivity of these biochemical parameters to variations of external natural factors at high latitudes in three independent groups of people living in this region (miners and people working underground (364 samples), the men working on the ground (274 samples) and women working on the ground (280 samples)). The obtained data indicate that the most expressed dependence of concentration of the three studied hormones is on the level of geomagnetic activity (GMA) - Kp, Ap, Kpmax - 3h. For two of the four seasons (June and October) with increasing levels of GMA a significant (p < 0.05) increase in cortisol concentration in all three independent groups of people was observed. Range of increases in cortisol concentration in different groups were about 30% of the observed variation in the average intragroup concentration in June and from 16% to 38% in October. For T3 dependence was found only in June: drop in hormone secretion with increasing levels of GMA from 18 to 30% of the average range of intragroup variations. Thus it was shown for the first time that at high geographical latitudes with increased level of GMA a significant change in the level of secretion of several hormones leads to the type of adaptive stress reaction.

Magnetic storms and variations in hormone levels among residents of North Polar area--Svalbard.

PubMed

Breus, T K; Boiko, E R; Zenchenko, T A

2015-01-01

In the present work four examinations (January, March, June, October 1991-1992) of the blood concentration of adrenal hormones (cortisol) and thyroid hormones (triiodothyronine (T3) and thyroxine T4) and their dependence on space and terrestrial weather parameters have been done for large groups of healthy inhabitants of high latitudes (Svalbard, the most northerly in the world year-round inhabited settlements). The aim of this study was to find the possible sensitivity of these biochemical parameters to variations of external natural factors at high latitudes in three independent groups of people living in this region (miners and people working underground (364 samples), the men working on the ground (274 samples) and women working on the ground (280 samples)). The obtained data indicate that the most expressed dependence of concentration of the three studied hormones is on the level of geomagnetic activity (GMA) - Kp, Ap, Kpmax - 3h. For two of the four seasons (June and October) with increasing levels of GMA a significant (p<0.05) increase in cortisol concentration in all three independent groups of people was observed. Range of increases in cortisol concentration in different groups were about 30% of the observed variation in the average intragroup concentration in June and from 16% to 38% in October. For T3 dependence was found only in June: drop in hormone secretion with increasing levels of GMA from 18 to 30% of the average range of intragroup variations. Thus it was shown for the first time that at high geographical latitudes with increased level of GMA a significant change in the level of secretion of several hormones leads to the type of adaptive stress reaction. Copyright © 2014 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

MOLD-SHAPED, NANOFIBER SCAFFOLD-BASED CARTILAGE ENGINEERING USING HUMAN MESENCHYMAL STEM CELLS AND BIOREACTOR

PubMed Central

Janjanin, Sasa; Li, Wan-Ju; Morgan, Meredith T.; Shanti, Rabie M.; Tuan, Rocky S.

2008-01-01

Background Mesenchymal stem cell (MSC)-based tissue engineering is a promising future alternative to autologous cartilage grafting. This study evaluates the potential of using MSCs, seeded into electrospun, biodegradable polymeric nanofibrous scaffolds, to engineer cartilage with defined dimensions and shape, similar to grafts used for subcutaneous implantation in plastic and reconstructive surgery. Materials and methods Human bone marrow derived MSCs seeded onto nanofibrous scaffolds and placed in custom-designed molds were cultured for up to 42 days in bioreactors. Chondrogenesis was induced with either transforming growth factor-β1 (TGF-β1) alone or in combination with insulin-like growth factor-I (IGF-I). Results Constructs exhibited hyaline cartilage histology with desired thickness and shape as well as favorable tissue integrity and shape retention, suggesting the presence of elastic tissue. Time-dependent increase in cartilage matrix gene expression was seen in both types of culture; at Day 42, TGF-β1/IGF-I treated cultures showed higher collagen type II and aggrecan expression. Both culture conditions showed significant time-dependent increase in sulfated glycosaminoglycan and hydroxyproline contents. TGF-β1/IGF-I treated samples were significantly stiffer; with equilibrium compressive Young’s modulus values reaching 17 kPa by Day 42. Conclusions The successful ex vivo development of geometrically defined cartilaginous construct using customized molding suggests the potential of cell-based cartilage tissue for reconstructive surgery. PMID:18316094

A long term study of pulmonary function among US refractory ceramic fibre workers

PubMed Central

LeMasters, Grace K; Hilbert, Timothy J; Levin, Linda S; Rice, Carol H; Borton, Eric K; Lockey, James E

2010-01-01

Background Cross-sectional studies have shown declines in lung function among refractory ceramic fibre (RCF) workers with increasing fibre exposure. This study followed current and former workers (n=1396) for up to 17 years and collected 5243 pulmonary function tests. Methods Cumulative fibre exposure and production years were categorised into exposure levels at five manufacturing locations. Conventional longitudinal models did not adequately partition age-related changes from other time-dependent variables. Therefore, a restricted cubic spline model was developed to account for the non-linear decline with age. Results Cumulative fibre >60 fibre-months/cc showed a significant loss in lung function at the first test. When results were examined longitudinally, cumulative exposure was confounded with age as workers with the highest cumulative exposure were generally older. A longitudinal model adjusted by age groups was implemented to control for this confounding. No consistent longitudinal loss in lung function was observed with RCF exposure. Smoking, initial weight and weight increase were significant factors. Conclusion No consistent decline was observed longitudinally with exposure to RCF, although cross-sectional and longitudinal findings were discordant. Confounding and accelerated lung function declines with ageing and the correlation of multiple time-dependent variables should be considered in order to minimise error and maximise precision. An innovative statistical methodology for these types of data is described. PMID:20798015

Predation and fragmentation portrayed in the statistical structure of prey time series

PubMed Central

Hendrichsen, Ditte K; Topping, Chris J; Forchhammer, Mads C

2009-01-01

Background Statistical autoregressive analyses of direct and delayed density dependence are widespread in ecological research. The models suggest that changes in ecological factors affecting density dependence, like predation and landscape heterogeneity are directly portrayed in the first and second order autoregressive parameters, and the models are therefore used to decipher complex biological patterns. However, independent tests of model predictions are complicated by the inherent variability of natural populations, where differences in landscape structure, climate or species composition prevent controlled repeated analyses. To circumvent this problem, we applied second-order autoregressive time series analyses to data generated by a realistic agent-based computer model. The model simulated life history decisions of individual field voles under controlled variations in predator pressure and landscape fragmentation. Analyses were made on three levels: comparisons between predated and non-predated populations, between populations exposed to different types of predators and between populations experiencing different degrees of habitat fragmentation. Results The results are unambiguous: Changes in landscape fragmentation and the numerical response of predators are clearly portrayed in the statistical time series structure as predicted by the autoregressive model. Populations without predators displayed significantly stronger negative direct density dependence than did those exposed to predators, where direct density dependence was only moderately negative. The effects of predation versus no predation had an even stronger effect on the delayed density dependence of the simulated prey populations. In non-predated prey populations, the coefficients of delayed density dependence were distinctly positive, whereas they were negative in predated populations. Similarly, increasing the degree of fragmentation of optimal habitat available to the prey was accompanied with a shift in the delayed density dependence, from strongly negative to gradually becoming less negative. Conclusion We conclude that statistical second-order autoregressive time series analyses are capable of deciphering interactions within and across trophic levels and their effect on direct and delayed density dependence. PMID:19419539

ANTIPROLIFERATIVE EFFECT OF INOSITOL HEXAPHOSPHATE ON HUMAN SKIN MELANOMA CELLS IN VITRO.

PubMed

Wawszczyk, Joanna; Kapral, Małgorzata; Lodowska, Jolanta; Jesse, Katarzyna; Hollek, Andrzej; Węglarz, Ludmiła

2015-01-01

Human malignant melanoma is a highly metastatic tumor with poor prognosis. The majority of metastatic melanomas are resistant to diverse chemotherapeutic agents. Consequently, the search for novel antimelanoma agents continues. In recent years, the interest in plants and their biologically active constituents as a source of novel potential drugs significantly increased. Inositol hexaphosphate (IP6) is a naturally occurring compound that has been shown to inhibit the growth of a wide variety of tumor cells in multiple experimental model systems. The aim of this study was to evaluate the antiproliferative and cytotoxic influence of IP6 on melanotic melanoma cells in vitro. The A2058 cells used as a model of human skin melanoma malignum were exposed to different concentrations of IP6 (0.1-5 mM) for a various period of time and their growth was determined by sulforhodamine B assay after 24, 48 and 72 h. The cytotoxicity of IP6 was measured at 24 and 72 h by XTT assay. IP6 has been found to cause dose-dependent growth suppression of A2058 melanoma cells. At low concentrations (0.1 and 0.5 mM) it did not exert any influence on the cell proliferation as compared to control cultures. Higher concentrations of IP6 (from 1 to 5 mM) had a statistically significant, suppressive effect on cell proliferation after 24 h incubation. When the experimental time period was increased up to 72 h, statistically significant inhibition of cell proliferation was monitored at all IP6 concentrations used. Data obtained from XTT assay indicated that IP6 had dose- and time-dependent cytotoxic effect on melanoma cells. The results demonstrate the antiproliferative and cytotoxic properties of IP6 in a wide range of concentrations on human A2058 melanoma cells. Hence, it can be suggested that IP6 could have a promising therapeutic significance in treating cancer.

Exposure to As-, Cd-, and Pb-mixture induces Aβ, amyloidogenic APP processing and cognitive impairments via oxidative stress-dependent neuroinflammation in young rats.

PubMed

Ashok, Anushruti; Rai, Nagendra Kumar; Tripathi, Sachin; Bandyopadhyay, Sanghamitra

2015-01-01

Environmental pollutants act as risk factors for Alzheimer's disease (AD), mainly affecting the aging population. We investigated early manifestations of AD-like pathology by a mixture of arsenic (As), cadmium (Cd), and lead (Pb), reported to impair neurodevelopment. We treated rats with As+Cd+Pb at their concentrations detected in groundwater of India, ie, 0.38, 0.098, and 0.22 ppm or 10 times of each, respectively, from gestation-05 to postnatal day-180. We identified dose-dependent increase in amyloid-beta (Aβ) in frontal cortex and hippocampus as early as post-weaning. The effect was strongly significant during early-adulthood, reaching levels comparable to an Aβ-infused AD-like rat model. The metals activated the proamyloidogenic pathway, mediated by increase in amyloid precursor protein (APP), and subsequent beta secretase (BACE) and presenilin (PS)-mediated APP-processing. Investigating the mechanism of Aβ-induction revealed an augmentation in oxidative stress-dependent neuroinflammation that stimulated APP expression through interleukin-responsive-APP-mRNA 5'-untranslated region. We then examined the effects of individual metals and binary mixtures in comparison with the tertiary. Among individual metals, Pb triggered maximum induction of Aβ, whereas individual As or Cd had a relatively non-significant effect on Aβ despite enhanced APP, owing to reduced induction of BACE and PS. Interestingly, when combined the metals demonstrated synergism, with a major contribution by As. The synergistic effect was significant and consistent in tertiary mixture, resulting in the augmentation of Aβ. Eventually, increase in Aβ culminated in cognitive impairments in the young rats. Together, our data demonstrate that exposure to As+Cd+Pb induces premature manifestation of AD-like pathology that is synergistic, and oxidative stress and inflammation dependent. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Antimutagenic effects of garlic extract on chromosomal aberrations.

PubMed

Shukla, Yogeshwer; Taneja, Pankaj

2002-02-08

Garlic (Allium sativum) has been used since ancient times, as a spice and also for its medicinal properties. In present set of investigations antimutagenic effect of garlic extract (GE) has been evaluated using 'in vivo chromosomal aberration assay' in Swiss albino mice. Cyclophosphamide (CP), a well-known mutagen, was given at a single dose of 25 mg/kg b.w. intraperitoneally. Pretreatment with 1, 2.5 and 5% of freshly prepared GE was given through oral intubation for 5 days prior to CP administration. Animals from all the groups were sacrificed at sampling times of 24 and 48 h and their bone marrow tissue was analyzed for chromosomal damage. The animals of the positive control group (CP alone) shows a significant increase in chromosomal aberrations both at 24 and 48 h sampling time. GE, alone did not significantly induced aberrations at either sampling time, confirming its non-mutagenicity. However in the GE pre-treated and CP post-treated groups, a dose dependent decrease in cytogenetic damage was recorded. A significant suppression in the chromosomal aberrations was recorded following pretreatment with 2.5 and 5% GE administration. The anticytotoxic effects of GE were also evident, as observed by significant increase in mitotic index, when compared to positive control group. Reduction in CP induced clastogenicity by GE was evident at 24 h and to a much greater extent at 48 h of cell cycle. Thus results of the present investigations revealed that GE has chemopreventive potential against CP induced chromosomal mutations in Swiss albino mice.

Influence of humic acid addition on the degradation of pharmaceuticals by biofilms in effluent wastewater.

PubMed

Tang, Kai; Escola Casas, Monica; Ooi, Gordon T H; Kaarsholm, Kamilla M S; Bester, Kai; Andersen, Henrik R

2017-05-01

The degradation of organic micropollutants in wastewater treatment is suspected to depend on co-degradation i.e. be dependent on concentrations of substrate. This complicates predicting and modelling their fate. The effect of humic acid, as a model for complex organic substrate, was investigated in relation to the biodegradation of pharmaceuticals by suspended biofilm carriers adapted to polishing effluent water from a tertiary sewage treatment plant. Twelve out of 22 investigated pharmaceuticals were significantly biodegradable. The biodegradation rate constants of ten of those compounds were increasing with increased humic acid concentrations. At the highest humic acid concentration (30mgC/L), the biodegradation rate constants were four times higher than the biodegradation rate constants without added humic acid. This shows that the presence of complex substrate stimulates degradation via a co-metabolism-like mechanism and competitive inhibition does not occur. Increases of rate constant per mgC/L are tentatively calculated. Copyright © 2017 Elsevier GmbH. All rights reserved.

Asbestos-induced endothelial cell activation and injury. Demonstration of fiber phagocytosis and oxidant-dependent toxicity.

PubMed

Garcia, J G; Gray, L D; Dodson, R F; Callahan, K S

1988-10-01

Vascular endothelial cell injury is important in the development of a variety of chronic interstitial lung disorders. However, the involvement of such injury in the inflammatory response associated with the inhalation of asbestos fibers is unclear and the mechanism of asbestos fiber cytotoxicity remains unknown. In the present study, human umbilical vein endothelial cells were challenged with amosite asbestos and several parameters of cellular function were examined. Electron microscopic examination revealed that endothelial cell exposure to asbestos resulted in active phagocytosis of these particulates. Biochemical evidence of dose-dependent asbestos-mediated endothelial cell activation was indicated by increased metabolism of arachidonic acid. For example, amosite asbestos (500 micrograms/ml) produced a ninefold increase in prostacyclin (PGI2) levels over those levels in non-exposed cells. Incubation of human endothelial cells with asbestos fibers induced specific 51Cr release in both a dose- and time-dependent fashion indicative of cellular injury. Injury induced by amosite asbestos was not significantly attenuated by treatment of the endothelial cell monolayer with either the iron chelator deferoxamine, which prevents hydroxyl radical (.OH) formation, or by the superoxide anion (O2-) scavenger, superoxide dismutase. However, significant dose-dependent protection was observed with the hydrogen peroxide (H2O2) scavenger, catalase. Chelation of elemental iron present within amosite asbestos fibers by deferoxamine produced a 33% reduction in asbestos cytotoxicity, suggesting a potential role for hydroxyl radical-mediated injury via the iron-catalyzed Haber-Weiss reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Effects of cognitive and experiential group therapy on self-efficacy and perceptions of employability of chemically dependent women.

PubMed

Washington, O

1999-01-01

This quasi-experimental study assessed effects of cognitive and experiential group therapy on self-efficacy and perceptions of employability for 52 chemically dependent adult women. The sample was 98% African American. Therapy consisted of six 90-min group sessions held twice weekly. The participants were pre- and posttested with the Self-Efficacy Scale (M. Sherer et al., 1982) and the Ghiselli Self-Description Inventory (E. E. Ghiselli, 1975). After the intervention, the cognitive group had significantly higher levels than the experiential group of social self-efficacy and need for self-actualization, an indicator of aspiration for employment. General self-efficacy and decisiveness, indicators of employability, significantly increased over time for both groups. Interventions to enhance people's belief in their ability to successfully perform tasks and control outcomes, promote personal growth, teach responsibility, and enhance self-awareness could be used to develop employability skills that reduce recidivism.

The impact of peritoneal dialysis-related peritonitis on mortality in peritoneal dialysis patients.

PubMed

Ye, Hongjian; Zhou, Qian; Fan, Li; Guo, Qunying; Mao, Haiping; Huang, Fengxian; Yu, Xueqing; Yang, Xiao

2017-06-05

Results concerning the association between peritoneal dialysis-related peritonitis and mortality in peritoneal dialysis patients are inconclusive, with one potential reason being that the time-dependent effect of peritonitis has rarely been considered in previous studies. This study aimed to evaluate whether peritonitis has a negative impact on mortality in a large cohort of peritoneal dialysis patients. We also assessed the changing impact of peritonitis on patient mortality with respect to duration of follow-up. This retrospective cohort study included incident patients who started peritoneal dialysis from 1 January 2006 to 31 December 2011. Episodes of peritonitis were recorded at the time of onset, and peritonitis was parameterized as a time-dependent variable for analysis. We used the Cox regression model to assess whether peritonitis has a negative impact on mortality. A total of 1321 patients were included. The mean age was 48.1 ± 15.3 years, 41.3% were female, and 23.5% with diabetes mellitus. The median (interquartile) follow-up time was 34 (21-48) months. After adjusting for confounders, peritonitis was independently associated with 95% increased risk of all-cause mortality (hazard ratio, 1.95; 95% confidence interval: 1.46-2.60), 90% increased risk of cardiovascular mortality (hazard ratio, 1.90; 95% confidence interval: 1.28-2.81) and near 4-fold increased risk of infection-related mortality (hazard ratio, 4.94; 95% confidence interval: 2.47-9.86). Further analyses showed that peritonitis was not significantly associated with mortality within 2 years of peritoneal dialysis initiation, but strongly influenced mortality in patients dialysed longer than 2 years. Peritonitis was independently associated with higher risk of all-cause, cardiovascular and infection-related mortality in peritoneal dialysis patients, and its impact on mortality was more significant in patients with longer peritoneal dialysis duration.

Fluorescence resonance energy transfer in microemulsions composed of tripled-chain surface active ionic liquids, RTILs, and biological solvent: an excitation wavelength dependence study.

PubMed

Banerjee, Chiranjib; Kundu, Niloy; Ghosh, Surajit; Mandal, Sarthak; Kuchlyan, Jagannath; Sarkar, Nilmoni

2013-08-15

In this article we have reported the fluorescence resonance energy transfer (FRET) study in our earlier characterized surface active ionic liquids (SAILs)-containing microemulsion, i.e., N-methyl-N-propylpyrrolidinium bis(trifluoromethanesulfonyl)imide ([P13][Tf2N])/[CTA][AOT]/isopropyl myristate ([IPM]) and N,N,N-trimethyl-N-propylammonium bis(trifluoromethanesulfonyl)imide ([N3111][Tf2N])/[CTA][AOT]/[IPM] microemulsions (Banerjee, C.; Mandal, S.; Ghosh, S.; Kuchlyan, J.; Kundu, N.; Sarkar, N. J. Phys. Chem. B 2013, 117, 3927-3934). The occurrence of effective FRET from the donor, coumarin-153 (C-153) to the acceptor rhodamine 6G (R6G) is evident from the decrease in the steady state fluorescence intensity of the donor with addition of acceptor and subsequent increase in the fluorescence intensity of the acceptor in the presence of donor. The excitation wavelength dependent FRET from C-153 to R6G has also been performed to assess the dynamic heterogeneity of these confined systems. In time-resolved experiments, the significant rise time of the acceptor in the presence of the donor further confirms the occurrence of FRET. The multiple donor-acceptor (D-A) distances, for various microemulsions, obtained from the rise times of the acceptor emission in the presence of a donor can be rationalized from the varying distribution of the donor, C-153, in the different regions of the microemulsion. Time-resolved measurement reveals that with increasing excitation wavelength from 408 to 440 nm, the contribution of the faster rise component of FRET increases significantly due to the close proximity of the C-153 and R6G in the polar region of the microemulsion where occurrence of FRET is very high. Moreover, we have also studied the FRET with variation of R (R = [room temperature ionic liquids (RTILs)]/[surfactant]) and shown that the effect of excitation wavelength on FRET is similar irrespective of R values.

Energy-dependent angular shifts in the photoelectron momentum distribution for atoms in elliptically polarized laser pulses

NASA Astrophysics Data System (ADS)

Xie, Hui; Li, Min; Luo, Siqiang; Li, Yang; Zhou, Yueming; Cao, Wei; Lu, Peixiang

2017-12-01

We measure the photoelectron momentum distributions from atoms ionized by strong elliptically polarized laser fields at the wavelengths of 400 and 800 nm, respectively. The momentum distributions show distinct angular shifts, which sensitively depend on the electron energy. We find that the deflection angle with respect to the major axis of the laser ellipse decreases with the increase of the electron energy for large ellipticities. This energy-dependent angular shift is well reproduced by both numerical solutions of the time-dependent Schrödinger equation and the classical-trajectory Monte Carlo model. We show that the ionization time delays among the electrons with different energies are responsible for the energy-dependent angular shifts. On the other hand, for small ellipticities, we find the deflection angle increases with increasing the electron energy, which might be caused by electron rescattering in the elliptically polarized fields.

Decreased circulation time offsets increased efficacy of PEGylated nanocarriers targeting folate receptors of glioma

NASA Astrophysics Data System (ADS)

McNeeley, Kathleen M.; Annapragada, Ananth; Bellamkonda, Ravi V.

2007-09-01

Liposomal and other nanocarrier based drug delivery vehicles can localize to tumours through passive and/or active targeting. Passively targeted liposomal nanocarriers accumulate in tumours via 'leaky' vasculature through the enhanced permeability and retention (EPR) effect. Passive accumulation depends upon the circulation time and the degree of tumour vessel 'leakiness'. After extravasation, actively targeted liposomal nanocarriers efficiently deliver their payload by receptor-mediated uptake. However, incorporation of targeting moieties can compromise circulation time in the blood due to recognition and clearance by the reticuloendothelial system, decreasing passive accumulation. Here, we compare the efficacy of passively targeted doxorubicin-loaded PEGylated liposomal nanocarriers to that of actively targeted liposomal nanocarriers in a rat 9L brain tumour model. Although folate receptor (FR)-targeted liposomal nanocarriers had significantly reduced blood circulation time compared to PEGylated liposomal nanocarriers; intratumoural drug concentrations both at 20 and 50 h after administration were equal for both treatments. Both treatments significantly increased tumour inoculated animal survival by 60-80% compared to non-treated controls, but no difference in survival was observed between FR-targeted and passively targeted nanocarriers. Therefore, alternate approaches allowing for active targeting without compromising circulation time may be important for fully realizing the benefits of receptor-mediated active targeting of gliomas.

Behavioral stress may increase the rewarding valence of cocaine-associated cues through a dynorphin/kappa-opioid receptor-mediated mechanism without affecting associative learning or memory retrieval mechanisms.

PubMed

Schindler, Abigail G; Li, Shuang; Chavkin, Charles

2010-08-01

Stress exposure increases the risk of addictive drug use in human and animal models of drug addiction by mechanisms that are not completely understood. Mice subjected to repeated forced swim stress (FSS) before cocaine develop significantly greater conditioned place preference (CPP) for the drug-paired chamber than unstressed mice. Analysis of the dose dependency showed that FSS increased both the maximal CPP response and sensitivity to cocaine. To determine whether FSS potentiated CPP by enhancing associative learning mechanisms, mice were conditioned with cocaine in the absence of stress, then challenged after association was complete with the kappa-opioid receptor (KOR) agonist U50,488 or repeated FSS, before preference testing. Mice challenged with U50,488 60 min before CPP preference testing expressed significantly greater cocaine-CPP than saline-challenged mice. Potentiation by U50,488 was dose and time dependent and blocked by the KOR antagonist norbinaltorphimine (norBNI). Similarly, mice subjected to repeated FSS before the final preference test expressed significantly greater cocaine-CPP than unstressed controls, and FSS-induced potentiation was blocked by norBNI. Novel object recognition (NOR) performance was not affected by U50,488 given 60 min before assay, but was impaired when given 15 min before NOR assay, suggesting that KOR activation did not potentiate CPP by facilitating memory retrieval or expression. The results from this study show that the potentiation of cocaine-CPP by KOR activation does not result from an enhancement of associative learning mechanisms and that stress may instead enhance the rewarding valence of cocaine-associated cues by a dynorphin-dependent mechanism.

The role of peroxisome proliferator-activated receptor-{beta}/{delta} in epidermal growth factor-induced HaCaT cell proliferation

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

Liang Pengfei; Jiang Bimei; Yang Xinghua

2008-10-15

Epidermal growth factor (EGF) has been shown to be a potent mitogen for epidermal cells both in vitro and in vivo, thus contributing to the development of an organism. It has recently become clear that peroxisome proliferator-activated receptor-{beta}/{delta} (PPAR{beta}/{delta}) expression and activation is involved in the cell proliferation. However, little is known about the role of PPAR{beta}/{delta} in EGF-induced proliferation of HaCaT keratinocytes. In this study, HaCaT cells were cultured in the presence and absence of EGF and we identified that EGF induced an increase of PPAR{beta}/{delta} mRNA and protein level expression in time-dependent and dose-dependent manner, and AG1487, anmore » EGF receptor (EGFR) special inhibitor, caused attenuation of PPAR{beta}/{delta} protein expression. Electrophoretic mobility shift assay (EMSA) revealed that EGF significantly increased PPAR{beta}/{delta} binding activity in HaCaT keratinocytes. Antisense phosphorothioate oligonucleotides (asODNs) against PPAR{beta}/{delta} caused selectively inhibition of PPAR{beta}/{delta} protein content induced by EGF and significantly attenuated EGF-mediated cell proliferation. Treatment of the cells with L165041, a specific synthetic ligand for PPAR{beta}/{delta}, significantly enhanced EGF-mediated cell proliferation. Finally, c-Jun ablation inhibited PPAR{beta}/{delta} up-regulation induced by EGF, and chromatin immunoprecipitation (ChIP) showed that c-Jun bound to the PPAR{beta}/{delta} promoter and the binding increased in EGF-stimulated cells. These results demonstrate that EGF induces PPAR{beta}/{delta} expression in a c-Jun-dependent manner and PPAR{beta}/{delta} plays a vital role in EGF-stimulated proliferation of HaCaT cells.« less

The effectiveness of national guidance in changing analgesic prescribing in primary care from 2002 to 2009: An observational database study

PubMed Central

Bedson, J; Belcher, J; Martino, OI; Ndlovu, M; Rathod, T; Walters, K; Dunn, KM; Jordan, KP

2013-01-01

Background Numerous national guidelines have been issued to assist general practitioners’ safe analgesic prescribing. Their effectiveness is unclear. The objective of this study was to examine trends in general practitioners’ prescribing behaviour in relation to national guidelines. Methods This was a retrospective observational database study of registered adult patients prescribed an analgesic (2002–2009) from the Consultations in Primary Care Archive – 12 North Staffordshire general practices. Prescribing guidance from the UK Medicines Regulatory Health Authority (MHRA) regarding non-steroidal anti-inflammatory drugs (NSAIDs) and co-proxamol, and the National Institute for Health and Clinical Excellence (NICE) osteoarthritis (OA) management guidelines were considered. Analgesic prescribing rates were examined, arranged according to a classification of six equipotent medication groups: (1) basic analgesics; (2)–(5) increasingly potent opioids and (6) NSAIDs. In each quarter from 2002 to 2009, the number of patients per 10,000 registered population receiving a prescription for the first time from each group was determined. Quarters associated with significant changes in the underlying prescribing trend were determined using joinpoint regression. Results A significant decrease in incident co-proxamol and Cox-2 prescribing occurred around the time of the first MHRA advice to stop using them and were rarely prescribed thereafter. The new prescribing of weak analgesics (e.g., co-codamol 8/500) increased at this same time. Initiating topical NSAIDs significantly increased around the time of the NICE OA guidelines. Conclusions Significant prescribing changes occurred when national advice and guidelines were issued. The effectiveness of this advice may vary depending upon the content and method of dissemination. Further evaluation of the optimal methods for delivering prescribing guidance is required. PMID:22865816

Characterization of the Exradin W1 scintillator for use in radiotherapy.

PubMed

Carrasco, P; Jornet, N; Jordi, O; Lizondo, M; Latorre-Musoll, A; Eudaldo, T; Ruiz, A; Ribas, M

2015-01-01

To evaluate the main characteristics of the Exradin W1 scintillator as a dosimeter and to estimate measurement uncertainties when used in radiotherapy. We studied the calibration procedure, energy and modality dependence, short-term repeatability, dose-response linearity, angular dependence, temperature dependence, time to reach thermal equilibrium, dose-rate dependence, water-equivalent depth of the effective measurement point, and long-term stability. An uncertainty budget was derived for relative and absolute dose measurements in photon and electron beams. Exradin W1 showed a temperature dependence of -0.225% °C(-1). The loss of sensitivity with accumulated dose decreased with use. The sensitivity of Exradin W1 was energy independent for high-energy photon and electron beams. All remaining dependencies of Exradin W1 were around or below 0.5%, leading to an uncertainty budget of about 1%. When a dual channel electrometer with automatic trigger was not used, timing effects became significant, increasing uncertainties by one order of magnitude. The Exradin W1 response is energy independent for high energy x-rays and electron beams, and only one calibration coefficient is needed. A temperature correction factor should be applied to keep uncertainties around 2% for absolute dose measurements and around 1% for relative measurements in high-energy photon and electron beams. The Exradin W1 scintillator is an excellent alternative to detectors such as diodes for relative dose measurements.

Hyperthermically induced changes in high spectral and spatial resolution MR images of tumor tissue—a pilot study

NASA Astrophysics Data System (ADS)

Foxley, Sean; Fan, Xiaobing; River, Jonathan; Zamora, Marta; Markiewicz, Erica; Sokka, Shunmugavelu; Karczmar, Gregory S.

2012-05-01

This pilot study investigated the feasibility of using MRI based on BOLD (blood-oxygen-level-dependent) contrast to detect physiological effects of locally induced hyperthermia in a rodent tumor model. Nude mice bearing AT6.1 rodent prostate tumors inoculated in the hind leg were imaged using a 9.4 T scanner using a multi-gradient echo pulse sequence to acquire high spectral and spatial resolution (HiSS) data. Temperature increases of approximately 6 °C were produced in tumor tissue using fiber-optic-guided light from a 250 W halogen lamp. HiSS data were acquired over three slices through the tumor and leg both prior to and during heating. Water spectra were produced from these datasets for each voxel at each time point. Time-dependent changes in water resonance peak width were measured during 15 min of localized tumor heating. The results demonstrated that hyperthermia produced both significant increases and decreases in water resonance peak width. Average decreases in peak width were significantly larger in the tumor rim than in normal muscle (p = 0.04). The effect of hyperthermia in tumor was spatially heterogeneous, i.e. the standard deviation of the change in peak width was significantly larger in the tumor rim than in normal muscle (p = 0.005). Therefore, mild hyperthermia produces spatially heterogeneous changes in water peak width in both tumor and muscle. This may reflect heterogeneous effects of hyperthermia on local oxygenation. The peak width changes in tumor and muscle were significantly different, perhaps due to abnormal tumor vasculature and metabolism. Response to hyperthermia measured by MRI may be useful for identifying and/or characterizing suspicious lesions as well as guiding the development of new hyperthermia protocols.

Reinforcement and substitution in humans: a multiple-response analysis1

PubMed Central

Bernstein, Daniel J.; Ebbesen, Ebbe B.

1978-01-01

Three adult human subjects engaged in activities such as reading, sewing, artwork, and candlemaking while living alone in a laboratory apartment 24 hours per day for several weeks. After a baseline period in which the activities were fully available, access to a particular activity (contingent response) was made dependent on engaging in another less-preferred activity (instrumental response). The contingencies produced substantial increases in instrumental responding, and responding decreased toward baseline levels when the dependency was removed. Under the contingent conditions, time earned for the concurrent activity was always less than the baseline level. To determine the contribution of this reduction to the instrumental increase, access to the contingent activity was restricted in the absence of any dependency. The results indicated that increases among responses that filled the newly available time could be selective, e.g., artwork increased when reading was restricted but candlemaking did not. It was concluded that the reductions in the contingent response that accompany contingencies usually do not exclusively determine instrumental increases, but selective increases can contribute to the increase in time devoted to the instrumental response. PMID:16812105

Measurements of Time-Dependent CP Asymmetries in b->s Penguin Dominated Hadronic B Decays at BABAR

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

Biassoni, Pietro

2010-02-10

We report measurements of Time-Dependent CP asymmetries in several b->s penguin dominated hadronic B decays, where New Physics contributions may appear. We find no significant discrepancies with respect to the Standard Model expectations.

The impact of multiple memory formation on dendritic complexity in the hippocampus and anterior cingulate cortex assessed at recent and remote time points

PubMed Central

Wartman, Brianne C.; Holahan, Matthew R.

2014-01-01

Consolidation processes, involving synaptic and systems level changes, are suggested to stabilize memories once they are formed. At the synaptic level, dendritic structural changes are associated with long-term memory storage. At the systems level, memory storage dynamics between the hippocampus and anterior cingulate cortex (ACC) may be influenced by the number of sequentially encoded memories. The present experiment utilized Golgi-Cox staining and neuron reconstruction to examine recent and remote structural changes in the hippocampus and ACC following training on three different behavioral procedures. Rats were trained on one hippocampal-dependent task only (a water maze task), two hippocampal-dependent tasks (a water maze task followed by a radial arm maze task), or one hippocampal-dependent and one non-hippocampal-dependent task (a water maze task followed by an operant conditioning task). Rats were euthanized recently or remotely. Brains underwent Golgi-Cox processing and neurons were reconstructed using Neurolucida software (MicroBrightField, Williston, VT, USA). Rats trained on two hippocampal-dependent tasks displayed increased dendritic complexity compared to control rats, in neurons examined in both the ACC and hippocampus at recent and remote time points. Importantly, this behavioral group showed consistent, significant structural differences in the ACC compared to the control group at the recent time point. These findings suggest that taxing the demand placed upon the hippocampus, by training rats on two hippocampal-dependent tasks, engages synaptic and systems consolidation processes in the ACC at an accelerated rate for recent and remote storage of spatial memories. PMID:24795581

Analysis of epothilone B-induced cell death in normal ovarian cells.

PubMed

Rogalska, Aneta; Gajek, Arkadiusz; Marczak, Agnieszka

2013-12-01

We have investigated the mode of cell death induced by a new microtubule-stabilizing agent, epothilone B (EpoB, patupilone), and a clinically used medicine, paclitaxel (PTX), in normal ovarian cells. Using fluorescence microscopy, polyacrylamide gel electrophoresis preceding Western blot analysis, as well as spectrofluorimetric and colorimetric detection, we demonstrate that, compared to EpoB, PTX induced high time-dependent morphological and biochemical changes typical of apoptosis. Induction of apoptosis followed an early increase in p53 levels. Apoptosis reached its maximum at 24-48 h. At the same time, there was a significant increase in caspase-9 and -3 activity and PARP fragmentation, which suggests that an intrinsic path was involved. Apoptosis in MM14 cells was increased more by PTX than EpoB, and also induced more necrosis responsible for inflammation (1.4-fold) than EpoB. © 2013 International Federation for Cell Biology.

Photodetachment dynamics in a time-dependent oscillating electric field

NASA Astrophysics Data System (ADS)

Wang, De-hua; Xu, Qin-feng; Du, Jie

2017-03-01

Using the time-dependent form of closed orbit theory, as developed by Haggerty and Delos [M.R. Haggerty, J.B. Delos, Phys. Rev. A 61, 053406 (2000)], and by Yang and Robicheaux [B.C. Yang, F. Robicheaux, Phys. Rev. A 93, 053413 (2016)], we study the photodetachment dynamics of a hydrogen negative ion in a time-dependent oscillating electric field. Compared to the photodetachment in a static electric field, the photodetachment dynamics of a negative ion in the time-dependent oscillating electric field become much more complicated but more interesting. Since the applied electric field is oscillating with time, the photodetachment cross section of the negative ion in the oscillating electric field is time-dependent. In a time-dependent framework, we put forward an analytical formula for calculating the instantaneous photodetachment cross section of this system. Our study suggests that the instantaneous photodetachment cross section exhibits oscillatory structure, which depends sensitively on the frequency of the oscillating electric field. With increasing frequency of the oscillating electric field, the number of closed orbits increases and the oscillatory structure in the photodetachment cross section becomes much more complicated. The connection between the detached electron's closed orbit with the oscillating cross section is analyzed quantitatively. This study provides a clear and intuitive picture for the photodetachment processes of a negative ion in the presence of an oscillating electric field. We hope that our work will be useful in guiding future experimental research.

Application of CRAFT (complete reduction to amplitude frequency table) in nonuniformly sampled (NUS) 2D NMR data processing.

PubMed

Krishnamurthy, Krish; Hari, Natarajan

2017-09-15

The recently published CRAFT (complete reduction to amplitude frequency table) technique converts the raw FID data (i.e., time domain data) into a table of frequencies, amplitudes, decay rate constants, and phases. It offers an alternate approach to decimate time-domain data, with minimal preprocessing step. It has been shown that application of CRAFT technique to process the t 1 dimension of the 2D data significantly improved the detectable resolution by its ability to analyze without the use of ubiquitous apodization of extensively zero-filled data. It was noted earlier that CRAFT did not resolve sinusoids that were not already resolvable in time-domain (i.e., t 1 max dependent resolution). We present a combined NUS-IST-CRAFT approach wherein the NUS acquisition technique (sparse sampling technique) increases the intrinsic resolution in time-domain (by increasing t 1 max), IST fills the gap in the sparse sampling, and CRAFT processing extracts the information without loss due to any severe apodization. NUS and CRAFT are thus complementary techniques to improve intrinsic and usable resolution. We show that significant improvement can be achieved with this combination over conventional NUS-IST processing. With reasonable sensitivity, the models can be extended to significantly higher t 1 max to generate an indirect-DEPT spectrum that rivals the direct observe counterpart. Copyright © 2017 John Wiley & Sons, Ltd.

Kinetic changes in tetanic Ca2+ transients in enzymatically dissociated muscle fibres under repetitive stimulation

PubMed Central

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

Year-long upregulation of connexin43 in rabbit hearts by heavy ion irradiation.

PubMed

Amino, Mari; Yoshioka, Koichiro; Fujibayashi, Daisuke; Hashida, Tadashi; Furusawa, Yoshiya; Zareba, Wojciech; Ikari, Yuji; Tanaka, Etsuro; Mori, Hidezo; Inokuchi, Sadaki; Kodama, Itsuo; Tanabe, Teruhisa

2010-03-01

A previous study from our laboratory has shown that a single targeted heavy ion irradiation (THIR; 15 Gy) to rabbit hearts increases connexin43 (Cx43) expression for 2 wk in association with an improvement of conduction, a decrease of the spatial inhomogeneity of repolarization, and a reduction of vulnerability to ventricular arrhythmias after myocardial infarction. This study investigated the time- and dose-dependent effects of THIR (5-15 Gy) on Cx43 expression in normal rabbit hearts (n = 45). Five rabbits without THIR were used as controls. A significant upregulation of Cx43 protein and mRNA in the ventricular myocardium was recognized by immunohistochemistry, Western blotting, and real-time PCR from 2 wk up to 1 yr after a single THIR at 15 Gy. THIR > or =10 Gy caused a significant dose-dependent increase of Cx43 protein and mRNA 2 wk after THIR. Anterior, lateral, and posterior free wall of the left ventricle, interventricular septum, and right ventricular free wall were affected similarly by THIR in terms of Cx43 upregulation. The radiation-induced increase of immunolabeled Cx43 was observed not only at the intercalated disk region but also at the lateral surface of ventricular myocytes. The increase of immunoreactive Cx43 protein was predominant in the membrane fraction insoluble in Triton X-100, that is the Cx43 in the sarcolemma. In vivo examinations of the rabbits 1 yr after THIR (15 Gy) revealed no significant changes in ECGs and echocardiograms (left ventricular dimensions, contractility, and diastolic function), indicating no apparent late radiation injury. A single application of THIR causes upregulation and altered cellular distribution of Cx43 in the ventricles lasting for at least 1 yr. This long-lasting remodeling effect on gap junctions may open the pathway to novel therapy against life threatening ventricular arrhythmias in structural heart disease.

Exercise activates the phosphatidylinositol 3-kinase pathway.

PubMed

Chen, Michael J; Russo-Neustadt, Amelia A

2005-04-27

Physical exercise is known to enhance psychological well-being and coping capacity. Voluntary physical exercise in rats also robustly and rapidly up-regulates hippocampal brain-derived neurotrophic factor (BDNF) mRNA levels, which are potentiated following a regimen of chronic antidepressant treatment. Increased BDNF levels are associated with enhanced activity of cyclic AMP response element binding protein (CREB). So far, relatively little is known about the intracellular signaling mechanisms mediating this effect of exercise. We wished to explore the possibility that exercise and/or antidepressant treatment activate the hippocampal phosphatidylinositol-3 (PI-3) kinase pathway, which mediates cellular survival. In young male Sprague-Dawley rats, we examined the effects of 2 weeks of daily voluntary wheel-running activity and/or tranylcypromine (n = 7 per group) on the levels of the active forms of protein-dependent kinase-1 (PDK-1), PI-3 kinase, phospho-thr308-Akt, phospho-ser473-Akt, and phospho-glycogen synthase kinase-3beta (GSK3beta; inactive form), as well as BDNF, activated CREB, and the phospho-Trk receptor, in the rat hippocampus, and compared these with sedentary saline-treated controls. Immunoblotting analyses revealed that in exercising rats, there was a significant increase in PI-3 kinase expression (4.61 times that of controls, P = 0.0161) and phosphorylation of PDK-1 (2.73 times that of controls, P = 0.0454), thr308-Akt (2.857 times that of controls, P = 0.0082), CREB (60.27 times that of controls, P = 0.05), and Trk (35.3 times that of controls, P < 0.0001) in the hippocampi of exercising animals; BDNF was also increased (3.2 times that of controls), but this was not statistically significant. In rats receiving both exercise and tranylcypromine, BDNF (4.51 times that of controls, P = 0.0068) and PI-3 kinase (4.88 times that of controls, P = 0.0103), and the phospho- forms of Trk (13.67 times that of controls, P = 0.0278), thr308-Akt (3.644 times that of controls, P = 0.0004), GSK-3beta (2.93 times that of controls, P = 0.026), and CREB (88.97 times that of controls, P = 0.0053) were significantly increased. These results suggest that the exercise-induced expression of BDNF is associated with the increased expression of several key intermediates of the PI-3 kinase/Akt pathway, which is known for its role in enhancing neuronal survival.

Leucemia inhibitory factor; investigating the time-dependent effect on viability of vitrified bovine embryos.

PubMed

Kocyigit, A; Cevik, M

2017-12-01

Leucemia inhibitory factor (LIF) is involved in various reproductive processes, including sperm development, regulation of ovulation, as well as blastocyst formation, hatching and implantation in embryos. Moreover, LIF has also been shown significantly to enhance the blastocyst formation rates of bovine embryos, a finding that remains controversial. Our purpose was to investigate time-dependent effect of LIF on bovine embryo culture, especially in terms of addition timing. Presumptive zygotes were cultured in five different groups. In this study, 100 ng/ml LIF was added to the culture medium were as follows; control: SOF alone, group A: at day 0 (fertilization day), group B: at day 4 post-insemination (p.i.), group C: at day 4 to 7 (p.i. before vitrification) and group D: at day 8 (p.i. after thawing). Addition of LIF to the culture medium at day 4 significantly increased the percentage of blastocyst rate when compared day 0, day 4 at 6/7 and control group (41.8% versus 24.3%, 19.7%, 34.6%). In conclusion, the addition of LIF only on day 4 (p.i.) to the culture medium was found to be beneficial for bovine embryonic development based on several measures, including blastocysts rate, re-expansion rate and cellular cryotolerance after vitrification. © 2017 Blackwell Verlag GmbH.

Electromagnetic-field dependence of the internal excited state of the polaron and the qubit in quantum dot with thickness

NASA Astrophysics Data System (ADS)

Bai, Xu-Fang; Xin, Wei; Yin, Hong-Wu; Eerdunchaolu

2017-06-01

The electromagnetic-field dependence of the ground and the first excited-state (GFES) energy eigenvalues and eigenfunctions of the strong-coupling polaron in a quantum dot (QD) was studied for various QD thicknesses by using the variational method of the Pekar type (VMPT). On this basis, we construct a qubit in the quantum dot (QQD) by taking a two-level structure of the polaron as the carrier. The results of numerical calculations indicate that the oscillation period of the qubit, {itT}{in0}, increases with increasing the thickness of the quantum dot (TQD) {itL}, but decreases with increasing the cyclotron frequency of the magnetic field (CFMF) ω{in{itc}}, electric-field strength {itF}, and electron-phonon coupling strength (EPCS) α. The probability density of the qubit |Ψ({itρ}, {itz}, {itt})|{su2} presents a normal distribution of the electronic transverse coordinate ρ, significantly influenced by the TQD and effective radius of the quantum dot (ERQD) {itR}{in0}, and shows a periodic oscillation with variations in the electronic longitudinal coordinate {itz}, polar angle φ and time {itt}. The decoherence time τ and the quality factor {itQ} of the free rotation increase with increasing the CFMF ω{in{itc}}, dispersion coefficient η, and EPCS α, but decrease with increasing the electric-field strength {itF}, TQD {itL}, and ERQD {itR}{in0}. The TQD is an important parameter of the qubit. Theoretically, the target, which is to regulate the oscillation period, decoherence time and quality factor of the free rotation of the qubit, can be achieved by designing different TQDs and regulating the strength of the electromagnetic field.

Gating by Cyclic Gmp and Voltage in the α Subunit of the Cyclic Gmp–Gated Channel from Rod Photoreceptors

PubMed Central

Benndorf, Klaus; Koopmann, Rolf; Eismann, Elisabeth; Kaupp, U. Benjamin

1999-01-01

Gating by cGMP and voltage of the α subunit of the cGMP-gated channel from rod photoreceptor was examined with a patch-clamp technique. The channels were expressed in Xenopus oocytes. At low [cGMP] (<20 μM), the current displayed strong outward rectification. At low and high (700 μM) [cGMP], the channel activity was dominated by only one conductance level. Therefore, the outward rectification at low [cGMP] results solely from an increase in the open probability, P o. Kinetic analysis of single-channel openings revealed two exponential distributions. At low [cGMP], the larger P o at positive voltages with respect to negative voltages is caused by an increased frequency of openings in both components of the open-time distribution. In macroscopic currents, depolarizing voltage steps, starting from −100 mV, generated a time-dependent current that increased with the step size (activation). At low [cGMP] (20 μM), the degree of activation was large and the time course was slow, whereas at saturating [cGMP] (7 mM) the respective changes were small and fast. The dose–response relation at −100 mV was shifted to the right and saturated at significantly lower P o values with respect to that at +100 mV (0.77 vs. 0.96). P o was determined as function of the [cGMP] (at +100 and −100 mV) and voltage (at 20, 70, and 700 μM, and 7 mM cGMP). Both relations could be fitted with an allosteric state model consisting of four independent cGMP-binding reactions and one voltage-dependent allosteric opening reaction. At saturating [cGMP] (7 mM), the activation time course was monoexponential, which allowed us to determine the individual rate constants for the allosteric reaction. For the rapid rate constants of cGMP binding and unbinding, lower limits are determined. It is concluded that an allosteric model consisting of four independent cGMP-binding reactions and one voltage-dependent allosteric reaction, describes the cGMP- and voltage-dependent gating of cGMP-gated channels adequately. PMID:10498668

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

Zhu Lingling; Zaidi, Samir; Peng Yuanzhen

Strontium ranelate, a new agent for the treatment of osteoporosis, has been shown stimulate bone formation in various experimental models. This study examines the effect of strontium ranelate on gene expression in osteoblasts, as well as the formation of mineralized (von Kossa-positive) colony-forming unit-osteoblasts (CFU-obs). Bone marrow-derived stromal cells cultured for 21 days under differentiating conditions, when exposed to strontium ranelate, displayed a significant time- and concentration-dependent increase in the expression of the master gene, Runx2, as well as bone sialoprotein (BSP), but interestingly without effects on osteocalcin. This was associated with a significant increase in the formation of CFU-obsmore » at day 21 of culture. In U-33 pre-osteoblastic cells, strontium ranelate significantly enhanced the expression of Runx2 and osteocalcin, but not BSP. Late, more mature osteoblastic OB-6 cells showed significant elevations in BSP and osteocalcin, but with only minimal effects on Runx2. In conclusion, strontium ranelate stimulates osteoblast differentiation, but the induction of the program of gene expression appears to be cell type-specific. The increased osteoblastic differentiation is the likely basis underlying the therapeutic bone-forming actions of strontium ranelate.« less

Leucine modulates dynamic phosphorylation events in insulin signaling pathway and enhances insulin-dependent glycogen synthesis in human skeletal muscle cells

PubMed Central

2014-01-01

Background Branched-chain amino acids, especially leucine, are known to interact with insulin signaling pathway and glucose metabolism. However, the mechanism by which this is exerted, remain to be clearly defined. In order to examine the effect of leucine on muscle insulin signaling, a set of experiments was carried out to quantitate phosphorylation events along the insulin signaling pathway in human skeletal muscle cell cultures. Cells were exposed to insulin, leucine or both, and phosphorylation events of key insulin signaling molecules were tracked over time so as to monitor time-related responses that characterize the signaling events and could be missed by a single sampling strategy limited to pre/post stimulus events. Results Leucine is shown to increase the magnitude of insulin-dependent phosphorylation of protein kinase B (AKT) at Ser473 and glycogen synthase kinase (GSK3β) at Ser21-9. Glycogen synthesis follows the same pattern of GSK3β, with a significant increase at 100 μM leucine plus insulin stimulus. Moreover, data do not show any statistically significant increase of pGSK3β and glycogen synthesis at higher leucine concentrations. Leucine is also shown to increase the magnitude of insulin-mediated extracellularly regulated kinase (ERK) phosphorylation; however, differently from AKT and GSK3β, ERK shows a transient behavior, with an early peak response, followed by a return to the baseline condition. Conclusions These experiments demonstrate a complementary effect of leucine on insulin signaling in a human skeletal muscle cell culture, promoting insulin-activated GSK3β phosphorylation and glycogen synthesis. PMID:24646332

[Inhibitive effect of matrine modification X on the growth of human nasopharyngeal carcinoma CNE2 cell xenografts in nude mice].

PubMed

Shi, Shujing; Tang, Anzhou; Yin, Shaolin; Wang, Lisheng; Xie, Mao; Yi, Xiang

2014-11-01

To evaluate the inhibitive effect of matrine modification X on the growth of human nasopharyngeal carcinoma CNE2 cell xenografts in nude mice. Tumor model was established by subcutaneous inoculation of nasopharyngeal carcinoma cell CNE2 into nude mice, which was used to evaluate the antitumor effect of matrine modification X in vivo. The expression levels of Bax, Bcl-2, Caspase3 were detected by real-time PCR and western blot. The growth of xenografts in nude mice was significantly suppressed after application of matrine modification X in a dose-dependent manner. The inhibition rates were 32.55% and 44.89% when treated at medium and high dose respectively. Real-time fluorescence quantitative-PCR and Western Blot results showed that the expression of Bax and Caspase3 increased, while the expression of Bcl-2 decreased in a dose-dependent manner. The change of high dose group was obvious, and the difference was statistically significant (P < 0.05). Matrine modification X could significantly inhibit the growth of human nasopharyngeal carcinoma CNE2 cell xenografts in nude mice, probably by inducing the apoptosis of nasopharyngeal carcinoma cells, and the possible mechanism is related to regulating the expression level of Bax/Bcl-2 and Casepase3.

Is children's listening effort in background noise influenced by the speaker's voice quality?

PubMed

Sahlén, Birgitta; Haake, Magnus; von Lochow, Heike; Holm, Lucas; Kastberg, Tobias; Brännström, K Jonas; Lyberg-Åhlander, Viveka

2018-07-01

The present study aims at exploring the influence of voice quality on listening effort in children performing a language comprehension test with sentences of increasing difficulty. Listening effort is explored in relation to gender ( = cisgender). The study has a between-groups design. Ninety-three mainstreamed children aged 8;2 to 9;3 with typical language development participated. The children were randomly assigned to two groups (n = 46/47) with equal allocation of boys and girls and for the analysis to four groups depending of gender and voice condition. Working memory capacity and executive functions were tested in quiet. A digital version of a language comprehension test (the TROG-2) was used to measure the effect of voice quality on listening effort, measured as response time in a forced-choice paradigm. The groups listened to sentences through recordings of the same female voice, one group with a typical voice and one with a dysphonic voice, both in competing multi-talker babble noise. Response times were logged after a time buffer between the sentence-ending and indication of response. There was a significant increase in response times with increased task difficulty and response times between the two voice conditions differed significantly. The girls in the dysphonic condition were slower with increasing task difficulty. A dysphonic voice clearly adds to the noise burden and listening effort is greater in girls than in boys when the teacher speaks with dysphonic voice in a noisy background. These findings might mirror gender differences as for coping strategies in challenging contexts and have important implications for education.

The Mechanical Properties and Modeling of Creep Behavior of UHMWPE/Nano-HA Composites

NASA Astrophysics Data System (ADS)

Li, Fan; Gao, Lilan; Gao, Hong; Cui, Yun

2017-09-01

Composites with different levels of hydroxyapatite (HA) content and ultra-high molecular weight polyethylene (UHMWPE) were prepared in this work. Mechanical properties of the composites were examined here, and to evaluate the effect of HA particles on the time-dependent behavior of the pure matrix, the creep and recovery performance of composites at various stress levels were also researched. As expected, the addition of HA influenced the time-dependent response of the UHMWPE and the effect had a strong dependence on the HA content. The creep and recovery strain of the composites significantly decreased with increasing HA content, and tensile properties were also impaired, which was due to the concentration of HA fillers. The mechanism and effect of HA dispersed into the UHMWPE matrix were examined by scanning electron microscopy. Additionally, since variations in the adjusted parameters revealed the impact of HA on the creep behavior of the UHMWPE matrix, Findley's model was employed. The results indicated that the analytical model was accurate for the prediction of creep of the pure matrix and its composites.

Anisotropic thermal conductivity in carbon honeycomb.

PubMed

Chen, Xue-Kun; Liu, Jun; Du, Dan; Xie, Zhong-Xiang; Chen, Ke-Qiu

2018-04-18

Carbon honeycomb, a new kind of 3D carbon allotrope experimentally synthesized recently, has received much attention for its fascinating applications in electronic device and energy storage. In the present work, we perform equilibrium molecular dynamics (EMD) to study the thermal transport properties of carbon honeycombs with different chirality. It is found that the thermal conductivity along the honeycomb axis ([Formula: see text]) is three times larger than that normal to the axis ([Formula: see text]), which shows strong anisotropy reflecting their geometric anisotropy. Lattice dynamics calculations reveal that this anisotropy stems from the orientation-dependent phonon group velocities. Moreover, when ambient temperature ([Formula: see text]) increases from 200 K to 800 K, the [Formula: see text] dependence of [Formula: see text] is observed due to the enhanced Umklapp scattering. The detailed phonon spectra analyses indicate phonon group velocities are insensitive to the variation of ambient temperature, and the temperature dependence of the relaxation times of low-frequency phonons (<20 THz) follows [Formula: see text] behavior. Our results have a certain guiding significance to develop carbon honeycomb for effective thermal channeling devices.

Frequency-dependent hydrodynamic interaction between two solid spheres

NASA Astrophysics Data System (ADS)

Jung, Gerhard; Schmid, Friederike

2017-12-01

Hydrodynamic interactions play an important role in many areas of soft matter science. In simulations with implicit solvent, various techniques such as Brownian or Stokesian dynamics explicitly include hydrodynamic interactions a posteriori by using hydrodynamic diffusion tensors derived from the Stokes equation. However, this equation assumes the interaction to be instantaneous which is an idealized approximation and only valid on long time scales. In the present paper, we go one step further and analyze the time-dependence of hydrodynamic interactions between finite-sized particles in a compressible fluid on the basis of the linearized Navier-Stokes equation. The theoretical results show that at high frequencies, the compressibility of the fluid has a significant impact on the frequency-dependent pair interactions. The predictions of hydrodynamic theory are compared to molecular dynamics simulations of two nanocolloids in a Lennard-Jones fluid. For this system, we reconstruct memory functions by extending the inverse Volterra technique. The simulation data agree very well with the theory, therefore, the theory can be used to implement dynamically consistent hydrodynamic interactions in the increasingly popular field of non-Markovian modeling.

Non-linear dielectric signatures of entropy changes in liquids subject to time dependent electric fields

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

Richert, Ranko

2016-03-21

A model of non-linear dielectric polarization is studied in which the field induced entropy change is the source of polarization dependent retardation time constants. Numerical solutions for the susceptibilities of the system are obtained for parameters that represent the dynamic and thermodynamic behavior of glycerol. The calculations for high amplitude sinusoidal fields show a significant enhancement of the steady state loss for frequencies below that of the low field loss peak. Also at relatively low frequencies, the third harmonic susceptibility spectrum shows a “hump,” i.e., a maximum, with an amplitude that increases with decreasing temperature. Both of these non-linear effectsmore » are consistent with experimental evidence. While such features have been used to conclude on a temperature dependent number of dynamically correlated particles, N{sub corr}, the present result demonstrates that the third harmonic susceptibility display a peak with an amplitude that tracks the variation of the activation energy in a model that does not involve dynamical correlations or spatial scales.« less

Dextran sulphate sodium (DSS) causes intestinal histopathology and inflammatory changes consistent with increased gut leakiness in chickens.

PubMed

Zou, X; Ji, J; Wang, J; Qu, H; Shu, D M; Guo, F Y; Luo, C L

2018-04-01

1. The clinical severity, histological changes, indicators of gut leakiness and inflammatory cytokine profiles were studied in chickens with dextran sulphate sodium (DSS)-induced intestinal inflammation. 2. The experimental groups (1.25%, 1.5% and 2.5% DSS) showed clinical signs, such as loose stools and weight loss, which increased with additional treatment days and, as expected, the effects of DSS-induced intestinal inflammation were time and dose-dependent. 3. After 10 d, histological manifestations were evident, including goblet cell depletion, mucus layer loss, significantly shorter villi and a thinner total ileal mucosa. 4. The d(-)-lactate value, which was used as a gut leakiness indicator, was significantly increased in the 2.5% DSS group. 5. Expression of the inflammatory cytokines interleukin-1Beta, tumour necrosis factor alpha and interleukin-10 in the serum significantly increased with DSS treatment. 6. This study indicates that the experimental intestinal inflammation induced by DSS is an ideal model to study the pathogenic mechanisms of intestinal inflammation in chickens and to test the efficacy of therapies.

Role of CYP1A1 in modulating the vascular and blood pressure benefits of omega-3 polyunsaturated fatty acids.

PubMed

Agbor, Larry N; Wiest, Elani F; Rothe, Michael; Schunck, Wolf-Hagen; Walker, Mary K

2014-12-01

The mechanisms that mediate the cardiovascular protective effects of omega 3 (n-3) polyunsaturated fatty acids (PUFAs) have not been fully elucidated. Cytochrome P450 1A1 efficiently metabolizes n-3 PUFAs to potent vasodilators. Thus, we hypothesized that dietary n-3 PUFAs increase nitric oxide (NO)-dependent blood pressure regulation and vasodilation in a CYP1A1-dependent manner. CYP1A1 wild-type (WT) and knockout (KO) mice were fed an n-3 or n-6 PUFA-enriched diet for 8 weeks and were analyzed for tissue fatty acids and metabolites, NO-dependent blood pressure regulation, NO-dependent vasodilation of acetylcholine (ACh) in mesenteric resistance arterioles, and endothelial NO synthase (eNOS) and phospho-Ser1177-eNOS expression in the aorta. All mice fed the n-3 PUFA diet showed significantly higher levels of n-3 PUFAs and their metabolites, and significantly lower levels of n-6 PUFAs and their metabolites. In addition, KO mice on the n-3 PUFA diet accumulated significantly higher levels of n-3 PUFAs in the aorta and kidney without a parallel increase in the levels of their metabolites. Moreover, KO mice exhibited significantly less NO-dependent regulation of blood pressure on the n-3 PUFA diet and significantly less NO-dependent, ACh-mediated vasodilation in mesenteric arterioles on both diets. Finally, the n-3 PUFA diet significantly increased aortic phospho-Ser1177-eNOS/eNOS ratio in the WT compared with KO mice. These data demonstrate that CYP1A1 contributes to eNOS activation, NO bioavailability, and NO-dependent blood pressure regulation mediated by dietary n-3 PUFAs. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

Irradiation of silver and agar/silver nanoparticles with argon, oxygen glow discharge plasma, and mercury lamp.

PubMed

Ahmad, Mahmoud M; Abdel-Wahab, Essam A; El-Maaref, A A; Rawway, Mohammed; Shaaban, Essam R

2014-01-01

The irradiation effect of argon, oxygen glow discharge plasma, and mercury lamp on silver and agar/silver nanoparticle samples is studied. The irradiation time dependence of the synthesized silver and agar/silver nanoparticle absorption spectra and their antibacterial effect are studied and compared. In the agar/silver nanoparticle sample, as the irradiation time of argon glow discharge plasma or mercury lamp increases, the peak intensity and the full width at half maximum, FWHM, of the surface plasmon resonance absorption band is increased, however a decrease of the peak intensity with oxygen glow plasma has been observed. In the silver nanoparticle sample, as the irradiation time of argon, oxygen glow discharge plasma or mercury lamp increases, the peak intensity of the surface plasmon resonance absorption band is increased, however, there is no significant change in the FWHM of the surface plasmon resonance absorption band. The SEM results for both samples showed nanoparticle formation with mean size about 50 nm and 40 nm respectively. Throughout the irradiation time with the argon, oxygen glow discharge plasma or mercury lamp, the antibacterial activity of several kinds of Gram-positive and Gram-negative bacteria has been examined.

Further study on the solar activity variation of daytime NmF2

NASA Astrophysics Data System (ADS)

Chen, Yiding; Liu, Libo

2010-12-01

The ionosonde observations in the East Asia-Australia sector are collected to further investigate the solar activity variation of daytime (0800 ˜ 1600 LT) NmF2. The linear increase rate of NmF2 with F10.7 at lower solar activity levels is remarkably dependent on latitude, season, and local time. The rate is largest in equinoxes (with an equinoctial asymmetry) and higher in the morning (afternoon) in local winter (summer) at geomagnetic midlatitudes; particularly, the maximum rates in local winter are obviously larger than those in local summer at northern midlatitudes. In the equatorial ionization anomaly (EIA) crest regions, the rates in equinoxes and December (June) solstice are remarkably higher than those in June (December) solstice at the northern (southern) EIA crest, and the rate grows from the morning sector to the afternoon sector. The variation trend of NmF2 with F10.7 also shows latitudinal, seasonal, and local time dependences. The saturation effect dominates in all seasons in the EIA regions; at midlatitudes, NmF2 nearly increases linearly with F10.7 in local winter so that a linear fit is a good approximation for NmF2 modeling, while the saturation effect still dominates in other seasons. The saturation effect is more significant in the afternoon, and the strongest saturation effect appears at the EIA crest latitudes in equinox afternoon. Discussions indicate that the variations of neutral atmosphere and hmF2 are responsible for the seasonal and local time dependences of the linear increase rate of NmF2 with F10.7 at midlatitudes, and the seasonal variation of neutral atmosphere is the primary reason for the seasonal dependence of the variation trend of NmF2 with F10.7, while dynamics processes are the more important factors controlling the linear increase rate and the variation trend of NmF2 with F10.7 at low latitudes. Furthermore, dynamics processes are important for the saturation effect, and the fountain effect is related to the strongest saturation effect appearing at the EIA crests.

Duration-dependent effects of clinically relevant oral alendronate doses on cortical bone toughness in beagle dogs

PubMed Central

Burr, David B.; Liu, Ziyue; Allen, Matthew R.

2014-01-01

Bisphosphonates (BPs) have been shown to significantly reduce bone toughness in vertebrae within one year when given at clinical doses to dogs. Although BPs also reduce toughness in cortical bone when given at high doses, their effect on cortical bone material properties when given at clinical doses is less clear. In part, this may be due to the use of small sample sizes that were powered to demonstrate differences in bone mineral density rather than bone’s material properties. Our lab has conducted several studies in which dogs were treated with alendronate at a clinically relevant dose. The goal of this study was to examine these published and unpublished data collectively to determine whether there is a significant time-dependent effect of alendronate on toughness of cortical bone. This analysis seemed particularly relevant given the recent occurrence of atypical femoral fractures in humans. Differences in the toughness of ribs taken from dogs derived from five separate experiments were measured. The dogs were orally administered saline (CON, 1 ml/kg/day) or alendronate (ALN) at a clinical dose (0.2 mg/kg/day). Treatment duration ranged from 3 months to 3 years. Groups were compared using ANOVA, and time trends analyzed with linear regression analysis. Linear regressions of the percent difference in toughness between CON and ALN at each time point revealed a significant reduction in toughness with longer exposure to ALN. The downward trend was primarily driven by a downward trend in post-yield toughness, whereas toughness in the pre-yield region was not changed relative to CON. These data suggest that a longer duration of treatment with clinical doses of ALN results in deterioration of cortical bone toughness in a time-dependent manner. As the duration of treatment is lengthened, the cortical bone exhibits increasingly brittle behavior. This may be important in assessing the role that long-term BP treatments play in the risk of atypical fractures of femoral cortical bone in humans. PMID:25445446

Linear response of mutans streptococci to increasing frequency of xylitol chewing gum use: a randomized controlled trial [ISRCTN43479664].

PubMed

Ly, Kiet A; Milgrom, Peter; Roberts, Marilyn C; Yamaguchi, David K; Rothen, Marilynn; Mueller, Greg

2006-03-24

Xylitol is a naturally occurring sugar substitute that has been shown to reduce the level of mutans streptococci in plaque and saliva and to reduce tooth decay. It has been suggested that the degree of reduction is dependent on both the amount and the frequency of xylitol consumption. For xylitol to be successfully and cost-effectively used in public health prevention strategies dosing and frequency guidelines should be established. This study determined the reduction in mutans streptococci levels in plaque and unstimulated saliva to increasing frequency of xylitol gum use at a fixed total daily dose of 10.32 g over five weeks. Participants (n = 132) were randomized to either active groups (10.32 g xylitol/day) or a placebo control (9.828 g sorbitol and 0.7 g maltitol/day). All groups chewed 12 pieces of gum per day. The control group chewed 4 times/day and active groups chewed xylitol gum at a frequency of 2 times/day, 3 times/day, or 4 times/day. The 12 gum pieces were evenly divided into the frequency assigned to each group. Plaque and unstimulated saliva samples were taken at baseline and five-weeks and were cultured on modified Mitis Salivarius agar for mutans streptococci enumeration. There were no significant differences in mutans streptococci level among the groups at baseline. At five-weeks, mutans streptococci levels in plaque and unstimulated saliva showed a linear reduction with increasing frequency of xylitol chewing gum use at the constant daily dose. Although the difference observed for the group that chewed xylitol 2 times/day was consistent with the linear model, the difference was not significant. There was a linear reduction in mutans streptococci levels in plaque and saliva with increasing frequency of xylitol gum use at a constant daily dose. Reduction at a consumption frequency of 2 times per day was small and consistent with the linear-response line but was not statistically significant.

Lanthanum Affects Bell Pepper Seedling Quality Depending on the Genotype and Time of Exposure by Differentially Modifying Plant Height, Stem Diameter and Concentrations of Chlorophylls, Sugars, Amino Acids, and Proteins.

PubMed

García-Jiménez, Atonaltzin; Gómez-Merino, Fernando C; Tejeda-Sartorius, Olga; Trejo-Téllez, Libia I

2017-01-01

Lanthanum (La) is considered a beneficial element, capable of inducing hormesis. Hormesis is a dose-response relationship phenomenon characterized by low-dose stimulation and high-dose inhibition. Herein we tested the effect of 0 and 10 μM La on growth and biomolecule concentrations of seedlings of four sweet bell pepper ( Capsicum annuum L.) varieties, namely Sven, Sympathy, Yolo Wonder, and Zidenka. Seedling evaluations were performed 15 and 30 days after treatment applications (dat) under hydroponic greenhouse conditions. Seedling height was significantly increased by La, growing 20% taller in Yolo Wonder plants, in comparison to the control. Similarly, La significantly enhanced shoot diameter, with increases of 9 and 9.8% in measurements performed 15 and 30 dat, respectively, as compared to the control. Likewise, La-treated seedlings had a higher number of flower buds than the control. An increase in the number of leaves because of La application was observed in Yolo Wonder seedlings, both 15 and 30 dat, while leaf area was augmented in this variety only 30 dat. Nevertheless, La did not affect dry biomass accumulation. La effects on biomolecule concentration were differential over time. In all varieties, La stimulated the biosynthesis of chlorophyll a, b and total 15 dat, though 30 dat only the varieties Sympathy and Yolo Wonder showed enhanced concentrations of these molecules because of La. Total soluble sugars increased in La-treated seedlings 30 dat. Interestingly, while most varieties exposed to La showed a reduction in amino acid concentration 15 dat, the opposite trend was observed 30 dat. Importantly, in all varieties evaluated, La stimulated soluble protein concentration 30 dat. It is important to note that while chlorophyll concentrations increased in all varieties exposed to La, both 15 and 30 dat, those of soluble sugars and proteins consistently increased only 30 dat, but not 15 dat. Our results confirm that La may improve seedling quality by enhancing some growth parameters and biomolecule concentrations, depending on the genotype, and time of exposure.

Real-Time Measurements of Aft Dome Insulation Erosion on Space Shuttle Reusable Solid Rocket Motor

NASA Technical Reports Server (NTRS)

McWhorter, Bruce; Ewing, Mark; Albrechtsen, Kevin; Noble, Todd; Longaker, Matt

2004-01-01

Real-time erosion of aft dome internal insulation was measured with internal instrumentation on a static test of a lengthened version of the Space Shuffle Reusable Solid Rocket Motor (RSRM). This effort marks the first time that real-time aft dome insulation erosion (Le., erosion due to the combined effects of thermochemical ablation and mechanical abrasion) was measured in this kind of large motor static test [designated as Engineering Test Motor number 3 (ETM3)I. This paper presents data plots of the erosion depth versus time. The data indicates general erosion versus time behavior that is in contrast to what would be expected from earlier analyses. Engineers have long known that the thermal environment in the aft dome is severe and that the resulting aft dome insulation erosion is significant. Models of aft dome erosion involve a two-step process of computational fluid dynamics (CFD) modeling and material ablation modeling. This modeling effort is complex. The time- dependent effects are difficult to verify with only prefire and postfire insulation measurements. Nozzle vectoring, slag accumulation, and changing boundary conditions will affect the time dependence of aft dome erosion. Further study of this data and continued measurements on future motors will increase our understanding of the aft dome flow and erosion environment.

Effect of long-time immersion of soft denture liners in water on viscoelastic properties.

PubMed

Iwasaki, Naohiko; Yamaki, Chisato; Takahashi, Hidekazu; Oki, Meiko; Suzuki, Tetsuya

2017-09-26

Aim of this study was to investigate the effect of long-time immersion of soft denture liners in 37°C water on viscoelastic properties. Six silicone-based and two acrylic resin-based soft denture liners were selected. Cylindrical specimens were stored in distilled water at 37°C for 6 months. Viscoelastic properties, which were instantaneous and delayed elastic displacements, viscous flow, and residual displacement, were determined using a creep meter, and analyzed with 2-way analysis of variance and Tukey's comparison (α=0.05). Viscoelastic properties and their time-dependent changes were varied among materials examined. The observed viscoelastic properties of three from six silicone-based liners did not significantly change after 6-month immersion, but those of two acrylic resin-based liners significantly changed with the increase of immersion time. However, the sum of initial instantaneous elastic displacement and delayed elastic displacement of two acrylic resin-based liners during 6-month immersion changed less than 10%, which might indicate clinically sufficient elastic performance.

Volkov basis for simulation of interaction of strong laser pulses and solids

NASA Astrophysics Data System (ADS)

Kidd, Daniel; Covington, Cody; Li, Yonghui; Varga, Kálmán

2018-01-01

An efficient and accurate basis comprised of Volkov states is implemented and tested for time-dependent simulations of interactions between strong laser pulses and crystalline solids. The Volkov states are eigenstates of the free electron Hamiltonian in an electromagnetic field and analytically represent the rapidly oscillating time-dependence of the orbitals, allowing significantly faster time propagation than conventional approaches. The Volkov approach can be readily implemented in plane-wave codes by multiplying the potential energy matrix elements with a simple time-dependent phase factor.

Serum amyloid A induction of cytokines in monocytes/macrophages and lymphocytes.

PubMed

Song, Changjie; Hsu, Kenneth; Yamen, Eric; Yan, Weixing; Fock, Jianyi; Witting, Paul K; Geczy, Carolyn L; Freedman, S Ben

2009-12-01

Serum amyloid A (SAA) is a biomarker of inflammation. Elevated blood levels in cardiovascular disease and local deposition in atheroma implies a role of SAA as a mediator rather than just a marker of inflammation. This study explored SAA-induced cytokine production and secretion by mononuclear cells. RT-PCR showed that SAA time-dependently induced cytokine mRNAs in peripheral blood mononuclear cells (PBMC) and THP-1 monocytoid cells, and dramatically increased IL-1beta, MCP-1, IL-6, IL-8, IL-10, GM-CSF, TNF, and MIP-1alpha secretion by PBMC to levels 28 to 25,000 fold above baseline, as measured with Bio-Plex kits; monocytes were the principle source. SAA induction of cytokines in monocyte-derived macrophages (MDM) was significantly higher than from monocytes from the same donors. SAA time-dependently induced transient and significant upregulation of NF-kappaB1 mRNA; inhibitor studies indicate that activation of NF-kappaB through the ERK1/2, p38 and JNK MAPKs and the PI3K pathway was involved. PBMC from 10 patients with coronary artery disease (CAD) spontaneously secreted higher levels of IL-6 and MIP-1alpha after 24h incubation than PBMC from normal controls, whereas SAA-induced levels of all cytokines were similar to controls. Aortic and coronary sinus sampling in 23 CAD patients indicated significant SAA release into the coronary circulation, not evident in 11 controls. SAA can increase monocyte and macrophage cytokine production, possibly at sites of atherosclerosis, thereby contributing to the pro-inflammatory state in coronary artery disease.

Serum Bicarbonate and Mortality in Stage 3 and Stage 4 Chronic Kidney Disease

PubMed Central

Schold, Jesse D.; Arrigain, Susana; Jolly, Stacey E.; Wehbe, Edgard; Raina, Rupesh; Simon, James F.; Srinivas, Titte R.; Jain, Anil; Schreiber, Martin J.; Nally, Joseph V.

2011-01-01

Summary Background and objectives The incidence and prevalence of metabolic acidosis increase with declining kidney function. We studied the associations of both low and high serum bicarbonate levels with all-cause mortality among stage 3 and 4 chronic kidney disease (CKD) patients. Design, setting, participants, & measurements We examined factors associated with low (<23 mmol/L) and high (>32 mmol/L) serum bicarbonate levels using logistic regression models and associations between bicarbonate and all-cause mortality using Cox-proportional hazard models, Kaplan–Meier survival curves, and time-dependent analysis. Results Out of 41,749 patients, 13.9% (n = 5796) had low and 1.6% (n = 652) had high serum bicarbonate levels. After adjusting for relevant covariates, there was a significant association between low serum bicarbonate and all-cause mortality (hazard ratio [HR] 1.23, 95% CI 1.16, 1.31). This association was not statistically significant among patients with stage 4 CKD and diabetes. The time-dependent analysis demonstrated a significant mortality risk associated with a decline from normal to low bicarbonate level (HR 1.59, 95% CI 1.49, 1.69). High serum bicarbonate levels were associated with death irrespective of the level of kidney function (HR 1.74, 95% CI 1.52, 2.00). When serum bicarbonate was examined as a continuous variable, a J-shaped relationship was noted between serum bicarbonate and mortality. Conclusions Low serum bicarbonate levels are associated with increased mortality among stage 3 CKD patients and patients without diabetes. High serum bicarbonate levels are associated with mortality in both stage 3 and stage 4 CKD patients. PMID:21885787

Experimental evaluation of the pressure and temperature dependence of ion-induced nucleation.

PubMed

Munir, Muhammad Miftahul; Suhendi, Asep; Ogi, Takashi; Iskandar, Ferry; Okuyama, Kikuo

2010-09-28

An experimental system for the study of ion-induced nucleation in a SO(2)/H(2)O/N(2) gas mixture was developed, employing a soft x-ray at different pressure and temperature levels. The difficulties associated with these experiments included the changes in physical properties of the gas mixture when temperature and pressure were varied. Changes in the relative humidity (RH) as a function of pressure and temperature also had a significant effect on the different behaviors of the mobility distributions of particles. In order to accomplish reliable measurement and minimize uncertainties, an integrated on-line control system was utilized. As the pressure decreased in a range of 500-980 hPa, the peak concentration of both ions and nanometer-sized particles decreased, which suggests that higher pressure tended to enhance the growth of particles nucleated by ion-induced nucleation. Moreover, the modal diameters of the measured particle size distributions showed a systematic shift to larger sizes with increasing pressure. However, in the temperature range of 5-20 °C, temperature increases had no significant effects on the mobility distribution of particles. The effects of residence time, RH (7%-70%), and SO(2) concentration (0.08-6.7 ppm) on ion-induced nucleation were also systematically investigated. The results show that the nucleation and growth were significantly dependent on the residence time, RH, and SO(2) concentration, which is in agreement with both a previous model and previous observations. This research will be inevitable for a better understanding of the role of ions in an atmospheric nucleation mechanism.

Acute toxicity, biochemical and histopathological responses of endosulfan in Chanos chanos.

PubMed

Kumar, Neeraj; Ambasankar, K; Krishnani, K K; Gupta, S K; Bhushan, Shashi; Minhas, P S

2016-09-01

This study investigated 96h median lethal concentration of endosulfan (99%, pure α: β ratio of 7:3) by conducting static non-renewable acute toxicity bio-assay in Chanos chanos juvenile with average weight (110±5.65g). Further, the effect of different definitive doses (18.5, 19.5, 20.5, 21.5 and 22.5µg/L) of endosulfan on metabolic, heamato-immunoligcal and histopathological response were probed. Anti-oxidative enzymes CAT, SOD and GST showed significant (p<0.01) increase of activity in the liver, gill and brain during exposure to endosulfan in a dose and time dependent manner. The brain AChE activity showed significant (p<0.01) inhibition from 18.5 to 22.5µg/L exposure of endosulfan than the control group. LDH and MDH activity gradually increased with consequent increasing dose of endosulfan exposure in the liver, gill and brain. Similarly, ALT, AST and G6PDH activities in both liver and gill increased with consequent increases in the dose of endosulfan exposure. Immunological profile such as blood glucose and serum cortisol level significantly enhanced while respiratory burst activity declined with consequent increasing doses of endosulfan exposure. Histopathological alteration in the gill demonstrated curling of secondary lamellae, thickening of primary epithelium, shorting of secondary lamellae, epithelial hyperplasia, fusion of secondary lamellae, aneurism, and collapsed secondary lamellae due to dose dependent exposure of endosulfan. Liver histology illustrated cloudy swelling and necrosis with pyknotic nuclei to the moderate dose of endosulfan, whereas higher dose of endosulfan (21.5µg/L) displayed severe necrosis of hepatic cells. Overall results clearly indicate that acute exposure of endosulfan led to pronounced deleterious alterations on biochemical, heamato-immunological, and histopathological responses of C. chanos juvenile. Copyright © 2016 Elsevier Inc. All rights reserved.

Observed increase in extreme daily rainfall in the French Mediterranean

NASA Astrophysics Data System (ADS)

Ribes, Aurélien; Thao, Soulivanh; Vautard, Robert; Dubuisson, Brigitte; Somot, Samuel; Colin, Jeanne; Planton, Serge; Soubeyroux, Jean-Michel

2018-04-01

We examine long-term trends in the historical record of extreme precipitation events occurring over the French Mediterranean area. Extreme events are considered in terms of their intensity, frequency, extent and precipitated volume. Changes in intensity are analysed via an original statistical approach where the annual maximum rainfall amounts observed at each measurement station are aggregated into a univariate time-series according to their dependence. The mean intensity increase is significant and estimated at + 22% (+ 7 to + 39% at the 90% confidence level) over the 1961-2015 period. Given the observed warming over the considered area, this increase is consistent with a rate of about one to three times that implied by the Clausius-Clapeyron relationship. Changes in frequency and other spatial features are investigated through a Generalised Linear Model. Changes in frequency for events exceeding high thresholds (about 200 mm in 1 day) are found to be significant, typically near a doubling of the frequency, but with large uncertainties in this change ratio. The area affected by severe events and the water volume precipitated during those events also exhibit significant trends, with an increase by a factor of about 4 for a 200 mm threshold, again with large uncertainties. All diagnoses consistently point toward an intensification of the most extreme events over the last decades. We argue that it is difficult to explain the diagnosed trends without invoking the human influence on climate.

Temperature-dependent sorption of naphthalene, phenanthrene, and pyrene to low organic carbon aquifer sediments

USGS Publications Warehouse

Piatt, Joseph J.; Backhus, Debera A.; Capel, Paul D.; Eisenreich, Steven J.

1996-01-01

Sorption experiments were conducted with naphthalene, phenanthrene, and pyrene on low organic carbon sediments at 4 and 26 °C using batch and column techniques. Experimental controls ensured the absence of biologic and photolytic activity and colloid-free solution supernatants. Equilibrium distribution coefficients (Kd) increased 1.1−1.6 times with a decrease in temperature of 22 °C. Fraction instantaneous sorption (F) values did not change significantly with a decrease in temperature of 22 °C. Desorption rate constants (k2) decreased 1.2−2.6 times with a decrease in temperature of 22 °C. Times to equilibrium were at least 40 h. The magnitude of observed Kd and k2 values and the effect of temperature on Kd (e.g., low enthalpy of sorption) are consistent with sorbate partitioning between the aqueous phase and small amounts of organic matter (foc = 0.02%) on the sediments. The temperature dependence of Kd and k2 may be small as compared to the effects of heterogeneities in field-scale aquifer systems. Thus, thermal gradients may not be of major importance in most saturated subsurface regimes when predicting solute transport. However, aquifer remediation pump-and-treat times could be decreased because increased temperature decreases both retardation and tailing.

Tests of nonuniversality of the stock return distributions in an emerging market

NASA Astrophysics Data System (ADS)

Mu, Guo-Hua; Zhou, Wei-Xing

2010-12-01

There is convincing evidence showing that the probability distributions of stock returns in mature markets exhibit power-law tails and both the positive and negative tails conform to the inverse cubic law. It supports the possibility that the tail exponents are universal at least for mature markets in the sense that they do not depend on stock market, industry sector, and market capitalization. We investigate the distributions of intraday returns at different time scales ( Δt=1 , 5, 15, and 30 min) of all the A-share stocks traded in the Chinese stock market, which is the largest emerging market in the world. We find that the returns can be well fitted by the q -Gaussian distribution and the tails have power-law relaxations with the exponents increasing with Δt and being well outside the Lévy stable regime for individual stocks. We provide statistically significant evidence showing that, at small time scales Δt<15min , the exponents logarithmically decrease with the turnover rate and increase with the market capitalization. When Δt>15min , no conclusive evidence is found for a possible dependence of the tail exponent on the turnover rate or the market capitalization. Our findings indicate that the intraday return distributions at small time scales are not universal in emerging stock markets but might be universal at large time scales.

Dynamic Properties of the Alkaline Vesicle Population at Hippocampal Synapses

PubMed Central

Röther, Mareike; Brauner, Jan M.; Ebert, Katrin; Welzel, Oliver; Jung, Jasmin; Bauereiss, Anna; Kornhuber, Johannes; Groemer, Teja W.

2014-01-01

In compensatory endocytosis, scission of vesicles from the plasma membrane to the cytoplasm is a prerequisite for intravesicular reacidification and accumulation of neurotransmitter molecules. Here, we provide time-resolved measurements of the dynamics of the alkaline vesicle population which appears upon endocytic retrieval. Using fast perfusion pH-cycling in live-cell microscopy, synapto-pHluorin expressing rat hippocampal neurons were electrically stimulated. We found that the relative size of the alkaline vesicle population depended significantly on the electrical stimulus size: With increasing number of action potentials the relative size of the alkaline vesicle population expanded. In contrast to that, increasing the stimulus frequency reduced the relative size of the population of alkaline vesicles. Measurement of the time constant for reacification and calculation of the time constant for endocytosis revealed that both time constants were variable with regard to the stimulus condition. Furthermore, we show that the dynamics of the alkaline vesicle population can be predicted by a simple mathematical model. In conclusion, here a novel methodical approach to analyze dynamic properties of alkaline vesicles is presented and validated as a convenient method for the detection of intracellular events. Using this method we show that the population of alkaline vesicles is highly dynamic and depends both on stimulus strength and frequency. Our results implicate that determination of the alkaline vesicle population size may provide new insights into the kinetics of endocytic retrieval. PMID:25079223

Aggregation of model amyloid insulin protein in crowding environments and under ac-electric fields

NASA Astrophysics Data System (ADS)

Zheng, Zhongli; Jing, Benxin; Murray, Brian; Sorci, Mirco; Belfort, Georges; Zhu, Y.

2013-03-01

In vitro experiments have been widely used to characterize the misfolding/unfolding pathway characteristic of amylodogenic proteins. Conversion from natively folded amyloidogenic proteins to oligomers via nucleation is the accepted path to fibril formation upon heating over a certain lag time period. In this work, we investigate the effect of crowing environment and external electric fields on the pathway and kinetics of insulin, a well-established amyloid model protein by single fluorescence spectroscopy and imaging. With added co-solutes, such as glycerol and polyvinylpyrrolidone (PVP), to mimic the cellular crowding environments, we have observed that the lag time can be significantly prolonged. The lag time increases with increasing co-solute concentration, yet showing little dependence on solution viscosity. Conversely, applied ac-electric fields can considerably shorten the lag timewhen a critical ac-voltage is exceeded. The strong dependence of lag time on ac-frequency over a narrow range of 500 Hz-5 kHz indicates the effect of ac-electroosmosis on the diffusion controlled process of insulin nucleation. Yet, no conformational structure is detected with insulin under applied ac-fields, suggesting the equivalence of ac-polarization to the conventional thermal activation process for insulin aggregation. These finding suggest that at least the aggregation kinetics of insulin can be altered by local solution condition or external stimuli, which gives new insight to the treatment of amyloid related diseases.

The effects and measures of auricular acupressure and interactive multimedia for smoking cessation in college students.

PubMed

Yeh, Mei-Ling; Wang, Pei-Lan; Lin, Jaung-Geng; Chung, Mei-Ling

2014-01-01

The earlier one starts to smoke, the more likely it is that one's tobacco use will increase. Either auricular acupressure or multimedia education could improve physiological health status and reduce smoking for young smokers. This study aimed to evaluate the effects of a 10-week auricular acupressure (AA) and interactive multimedia (IM) on smoking cessation in college smokers. A pre- and posttest control research design with two experiments (AA and IM) and one control was used. Thirty-two participants were in each of three groups. A significant difference from pretest to posttest among three groups was exhibited on carbon monoxide (CO), cotinine, and nicotine dependence. Scheffe's post hoc test found significances on CO in the AA between the IM and the control and cotinine and nicotine dependence between the AA and the control. After controlling the covariates, the main effect of the group was no difference in all outcomes. The interventions, especially AA, may contribute to a decrease of CO, cotinine, and nicotine dependence along with the time change. An analysis without controlling influences may overestimate interventional effects.

The Effects and Measures of Auricular Acupressure and Interactive Multimedia for Smoking Cessation in College Students

PubMed Central

Yeh, Mei-Ling; Wang, Pei-Lan; Lin, Jaung-Geng; Chung, Mei-Ling

2014-01-01

The earlier one starts to smoke, the more likely it is that one's tobacco use will increase. Either auricular acupressure or multimedia education could improve physiological health status and reduce smoking for young smokers. This study aimed to evaluate the effects of a 10-week auricular acupressure (AA) and interactive multimedia (IM) on smoking cessation in college smokers. A pre- and posttest control research design with two experiments (AA and IM) and one control was used. Thirty-two participants were in each of three groups. A significant difference from pretest to posttest among three groups was exhibited on carbon monoxide (CO), cotinine, and nicotine dependence. Scheffe's post hoc test found significances on CO in the AA between the IM and the control and cotinine and nicotine dependence between the AA and the control. After controlling the covariates, the main effect of the group was no difference in all outcomes. The interventions, especially AA, may contribute to a decrease of CO, cotinine, and nicotine dependence along with the time change. An analysis without controlling influences may overestimate interventional effects. PMID:24987436

Increased nitrogen availability counteracts climatic change feedback from increased temperature on boreal forest soil organic matter degradation

NASA Astrophysics Data System (ADS)

Erhagen, Bjorn; Nilsson, Mats; Oquist, Mats; Ilstedt, Ulrik; Sparrman, Tobias; Schleucher, Jurgen

2014-05-01

Over the last century, the greenhouse gas concentrations in the atmosphere have increased dramatically, greatly exceeding pre-industrial levels that had prevailed for the preceding 420 000 years. At the same time the annual anthropogenic contribution to the global terrestrial nitrogen cycle has increased and currently exceeds natural inputs. Both temperature and nitrogen levels have profound effects on the global carbon cycle including the rate of organic matter decomposition, which is the most important biogeochemical process that returns CO2 to the atmosphere. Here we show for the first time that increasing the availability of nitrogen not only directly affects the rate of organic matter decomposition but also significantly affects its temperature dependence. We incubated litter and soil organic matter from a long-term (40 years) nitrogen fertilization experiment in a boreal Scots pine (Pinus silvestris L.) forest at different temperatures and determined the temperature dependence of the decomposition of the sample's organic matter in each case. Nitrogen fertilization did not affect the temperature sensitivity (Q10) of the decomposition of fresh plant litter but strongly reduced that for humus soil organic matter. The Q10 response of the 0-3 cm soil layer decreased from 2.5±0.35 to an average of 1.9±0.21 over all nitrogen treatments, and from 2.2±0.19 to 1.6±0.16 in response to the most intense nitrogen fertilization treatment in the 4-7 cm soil layer. Long-term nitrogen additions also significantly affected the organic chemical composition (as determined by 13C CP-MAS NMR spectroscopy) of the soil organic matter. These changes in chemical composition contributed significantly (p<0.05) to the reduced Q10 response. These new insights into the relationship between nitrogen availability and the temperature sensitivity of organic matter decomposition will be important for understanding and predicting how increases in global temperature and rising anthropogenic nitrogen inputs will affect the global carbon cycle and the associated climatic feedback processes.

Competing risks models and time-dependent covariates

PubMed Central

Barnett, Adrian; Graves, Nick

2008-01-01

New statistical models for analysing survival data in an intensive care unit context have recently been developed. Two models that offer significant advantages over standard survival analyses are competing risks models and multistate models. Wolkewitz and colleagues used a competing risks model to examine survival times for nosocomial pneumonia and mortality. Their model was able to incorporate time-dependent covariates and so examine how risk factors that changed with time affected the chances of infection or death. We briefly explain how an alternative modelling technique (using logistic regression) can more fully exploit time-dependent covariates for this type of data. PMID:18423067

Robot flow, clogging and jamming in confined spaces

NASA Astrophysics Data System (ADS)

Monaenkova, Daria; Linevich, Vadim; Goodisman, Michael A. D.; Goldman, Daniel I.

We hypothesized that when a collection of robots operate in confined space, maximization of individual effort could negatively affect the collective performance by impeding the mobility of the individuals. To test our hypothesis, we built and programmed groups of 1-4 autonomous robotic diggers to construct a tunnel in a model cohesive soil. The robots' mobility, defined in terms of the residence time (T) required for a robot to move one body-length within the tunnel, was compared between groups of maximally active robots (mode 1), groups with different levels of activity between individuals (mode 2), and maximally active robots with a ``giving up'' behavior (mode 3), in which the robot ceased the attempt to excavate in a crowded tunnel. In small groups of two robots, T was ~3 sec and did not depend on the mode of operation. However, an increase in the number of robots caused an increase in T which depended upon mode. The residence time in groups of four robots in mode 1 (~9 sec) significantly exceeded the residence time in mode 2 and 3 (~4 sec), indicating that crowding was causing slower movement of individuals, particularly under maximum effort (mode 1). We will use our robophysical studies to discover principles of collective construction in subterranean social animals.

Effects of adrenal sensitivity, stress- and cue-induced craving, and anxiety on subsequent alcohol relapse and treatment outcomes.

PubMed

Sinha, Rajita; Fox, Helen C; Hong, Kwang-Ik Adam; Hansen, Julie; Tuit, Keri; Kreek, Mary Jeanne

2011-09-01

Alcoholism is a chronic, relapsing illness in which stress and alcohol cues contribute significantly to relapse risk. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, increased anxiety, and high alcohol craving have been documented during early alcohol recovery, but their influence on relapse risk has not been well studied. To investigate these responses in treatment-engaged, 1-month-abstinent, recovering alcohol-dependent patients relative to matched controls (study 1) and to assess whether HPA axis function, anxiety, and craving responses are predictive of subsequent alcohol relapse and treatment outcome (study 2). Experimental exposure to stress, alcohol cues, and neutral, relaxing context to provoke alcohol craving, anxiety, and HPA axis responses (corticotropin and cortisol levels and cortisol to corticotropin ratio) and a prospective 90-day follow-up outcome design to assess alcohol relapse and aftercare treatment outcomes. Inpatient treatment in a community mental health center and hospital-based research unit. Treatment-engaged alcohol-dependent individuals and healthy controls. Time to alcohol relapse and to heavy drinking relapse. Significant HPA axis dysregulation, marked by higher basal corticotropin level and lack of stress- and cue-induced corticotropin and cortisol responses, higher anxiety, and greater stress- and cue-induced alcohol craving, was seen in the alcohol-dependent patients vs the control group. Stress- and cue-induced anxiety and stress-induced alcohol craving were associated with fewer days in aftercare alcohol treatment. High provoked alcohol craving to both stress and to cues and greater neutral, relaxed-state cortisol to corticotropin ratio (adrenal sensitivity) were each predictive of shorter time to alcohol relapse. These results identify a significant effect of high adrenal sensitivity, anxiety, and increased stress- and cue-induced alcohol craving on subsequent alcohol relapse and treatment outcomes. Findings suggest that new treatments that decrease adrenal sensitivity, stress- and cue-induced alcohol craving, and anxiety could be beneficial in improving alcohol relapse outcomes.

Temporal characteristics of gustatory responses in rat parabrachial neurons vary by stimulus and chemosensitive neuron type.

PubMed

Geran, Laura; Travers, Susan

2013-01-01

It has been demonstrated that temporal features of spike trains can increase the amount of information available for gustatory processing. However, the nature of these temporal characteristics and their relationship to different taste qualities and neuron types are not well-defined. The present study analyzed the time course of taste responses from parabrachial (PBN) neurons elicited by multiple applications of "sweet" (sucrose), "salty" (NaCl), "sour" (citric acid), and "bitter" (quinine and cycloheximide) stimuli in an acute preparation. Time course varied significantly by taste stimulus and best-stimulus classification. Across neurons, the ensemble code for the three electrolytes was similar initially but quinine diverged from NaCl and acid during the second 500 ms of stimulation and all four qualities became distinct just after 1s. This temporal evolution was reflected in significantly broader tuning during the initial response. Metric space analyses of quality discrimination by individual neurons showed that increases in information (H) afforded by temporal factors was usually explained by differences in rate envelope, which had a greater impact during the initial 2s (22.5% increase in H) compared to the later response (9.5%). Moreover, timing had a differential impact according to cell type, with between-quality discrimination in neurons activated maximally by NaCl or citric acid most affected. Timing was also found to dramatically improve within-quality discrimination (80% increase in H) in neurons that responded optimally to bitter stimuli (B-best). Spikes from B-best neurons were also more likely to occur in bursts. These findings suggest that among PBN taste neurons, time-dependent increases in mutual information can arise from stimulus- and neuron-specific differences in response envelope during the initial dynamic period. A stable rate code predominates in later epochs.

Temporal Characteristics of Gustatory Responses in Rat Parabrachial Neurons Vary by Stimulus and Chemosensitive Neuron Type

PubMed Central

Geran, Laura; Travers, Susan

2013-01-01

It has been demonstrated that temporal features of spike trains can increase the amount of information available for gustatory processing. However, the nature of these temporal characteristics and their relationship to different taste qualities and neuron types are not well-defined. The present study analyzed the time course of taste responses from parabrachial (PBN) neurons elicited by multiple applications of “sweet” (sucrose), “salty” (NaCl), “sour” (citric acid), and “bitter” (quinine and cycloheximide) stimuli in an acute preparation. Time course varied significantly by taste stimulus and best-stimulus classification. Across neurons, the ensemble code for the three electrolytes was similar initially but quinine diverged from NaCl and acid during the second 500ms of stimulation and all four qualities became distinct just after 1s. This temporal evolution was reflected in significantly broader tuning during the initial response. Metric space analyses of quality discrimination by individual neurons showed that increases in information (H) afforded by temporal factors was usually explained by differences in rate envelope, which had a greater impact during the initial 2s (22.5% increase in H) compared to the later response (9.5%). Moreover, timing had a differential impact according to cell type, with between-quality discrimination in neurons activated maximally by NaCl or citric acid most affected. Timing was also found to dramatically improve within-quality discrimination (80% increase in H) in neurons that responded optimally to bitter stimuli (B-best). Spikes from B-best neurons were also more likely to occur in bursts. These findings suggest that among PBN taste neurons, time-dependent increases in mutual information can arise from stimulus- and neuron-specific differences in response envelope during the initial dynamic period. A stable rate code predominates in later epochs. PMID:24124597

Cisplatin radiosensitizes radioresistant human mesenchymal stem cells.

PubMed

Rühle, Alexander; Perez, Ramon Lopez; Glowa, Christin; Weber, Klaus-Josef; Ho, Anthony D; Debus, Jürgen; Saffrich, Rainer; Huber, Peter E; Nicolay, Nils H

2017-10-20

Cisplatin-based chemo-radiotherapy is widely used to treat cancers with often severe therapy-associated late toxicities. While mesenchymal stem cells (MSCs) were shown to aid regeneration of cisplatin- or radiation-induced tissue lesions, the effect of the combined treatment on the stem cells remains unknown. Here we demonstrate that cisplatin treatment radiosensitized human bone marrow-derived MSCs in a dose-dependent manner and increased levels of radiation-induced apoptosis. However, the defining stem cell properties of MSCs remained largely intact after cisplatin-based chemo-radiation, and stem cell motility, adhesion, surface marker expression and the characteristic differentiation potential were not significantly influenced. The increased cisplatin-mediated radiosensitivity was associated with a cell cycle shift of MSCs towards the radiosensitive G2/M phase and increased residual DNA double-strand breaks. These data demonstrate for the first time a dose-dependent radiosensitization effect of MSCs by cisplatin. Clinically, the observed increase in radiation sensitivity and subsequent loss of regenerative MSCs may contribute to the often severe late toxicities observed after cisplatin-based chemo-radiotherapy in cancer patients.

Pain Volatility and Prescription Opioid Addiction Treatment Outcomes in Patients with Chronic Pain

PubMed Central

Worley, Matthew J.; Heinzerling, Keith G.; Shoptaw, Steven; Ling, Walter

2015-01-01

The combination of prescription opioid dependence and chronic pain is increasingly prevalent and hazardous to public health. Variability in pain may explain poor prescription opioid addiction treatment outcomes in persons with chronic pain. This study examined pain trajectories and pain volatility in patients with chronic pain receiving treatment for prescription opioid addiction. We conducted secondary analyses of adults with chronic pain (N = 149) who received buprenorphine-naloxone (BUP-NLX) and counseling for 12 weeks in an outpatient, multi-site clinical trial. Good treatment outcome was defined as urine-verified abstinence from opioids at treatment endpoint (Week 12) and during at least two of the previous three weeks. Pain severity significantly declined over time during treatment (b = − 0.36, p < .001). Patients with greater pain volatility were less likely to have a good treatment outcome (OR = 0.55, p < .05), controlling for baseline pain severity and rate of change in pain over time. A one standard deviation increase in pain volatility was associated with a 44% reduction in the probability of endpoint abstinence. The significant reduction in subjective pain during treatment provides observational support for the analgesic effects of BUP-NLX in patients with chronic pain and opioid dependence. Patients with greater volatility in subjective pain during treatment have increased risk for returning to opioid use by the conclusion of an intensive treatment with BUP-NLX and counseling. Future research should examine underlying mechanisms of pain volatility and identify related therapeutic targets to optimize interventions for prescription opioid addiction and co-occurring chronic pain. PMID:26302337

Pain volatility and prescription opioid addiction treatment outcomes in patients with chronic pain.

PubMed

Worley, Matthew J; Heinzerling, Keith G; Shoptaw, Steven; Ling, Walter

2015-12-01

The combination of prescription opioid dependence and chronic pain is increasingly prevalent and hazardous to public health. Variability in pain may explain poor prescription opioid addiction treatment outcomes in persons with chronic pain. This study examined pain trajectories and pain volatility in patients with chronic pain receiving treatment for prescription opioid addiction. We conducted secondary analyses of adults with chronic pain (n = 149) who received buprenorphine/naloxone (BUP/NLX) and counseling for 12 weeks in an outpatient, multisite clinical trial. Good treatment outcome was defined as urine-verified abstinence from opioids at treatment endpoint (Week 12) and during at least 2 of the previous 3 weeks. Pain severity significantly declined over time during treatment (b = -0.36, p < .001). Patients with greater pain volatility were less likely to have a good treatment outcome (odds ratio = 0.55, p < .05), controlling for baseline pain severity and rate of change in pain over time. A 1 standard deviation increase in pain volatility was associated with a 44% reduction in the probability of endpoint abstinence. The significant reduction in subjective pain during treatment provides observational support for the analgesic effects of BUP/NLX in patients with chronic pain and opioid dependence. Patients with greater volatility in subjective pain during treatment have increased risk of returning to opioid use by the conclusion of an intensive treatment with BUP/NLX and counseling. Future research should examine underlying mechanisms of pain volatility and identify related therapeutic targets to optimize interventions for prescription opioid addiction and co-occurring chronic pain. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

Effect of DHA supplementation on oxylipin levels in plasma and immune cell stimulated blood.

PubMed

Schuchardt, Jan Philipp; Ostermann, Annika I; Stork, Lisa; Fritzsch, Sabrina; Kohrs, Heike; Greupner, Theresa; Hahn, Andreas; Schebb, Nils Helge

2017-06-01

EPA and DHA cause different physiological effects, which are in many cases mediated via their oxidative metabolites (oxylipins). However, metabolism studies investigating the effect of either EPA or DHA on comprehensive oxylipin patterns are lacking. The short and long term (1, 3, 6, and 12 week) effect of 1076mg/d DHA (free of EPA) on free (unesterified) oxylipin concentrations in plasma and lipopolysacharid (LPS) stimulated blood of 12 healthy men (mean age 25.1 ± 1.5 years) was investigated. After DHA supplementation, plasma levels of all DHA-oxylipins (HDHAs, EpDPEs, DiHDPEs) significantly increased (up to 600%) in a time-dependent fashion. Oxylipins of EPA and arachidonic acid (AA) were also affected. Whereas a slight increase in several EPA-derived hydroxy-FAs (including the RvE1 precursor 18-HEPE) and dihydroxy-FAs was observed after DHA supplementation, a trend to a slight decline in AA-derived oxylipin levels was found. In LPS stimulated blood, it is shown that DHA supplementation significantly reduces the ability of immune cells to form AA-derived COX (TXB2 and PGB2) and 12-LOX (12-HETE) eicosanoids. While no increase in EPA COX metabolites was found, n-3 PUFA 12-LOX metabolites of EPA (12-HEPE) and DHA (14-HDHA) were highly induced. We demonstrated that DHA supplementation causes a time-dependent shift in the entire oxylipin profile suggesting a cross-linked metabolism of PUFAs and subsequent formation of oxygenated lipid mediators. Copyright © 2017 Elsevier Ltd. All rights reserved.

Circadian clocks govern calorie restriction-mediated life span extension through BMAL1- and IGF-1-dependent mechanisms.

PubMed

Patel, Sonal A; Chaudhari, Amol; Gupta, Richa; Velingkaar, Nikkhil; Kondratov, Roman V

2016-04-01

Calorie restriction (CR) increases longevity in many species by unknown mechanisms. The circadian clock was proposed as a potential mediator of CR. Deficiency of the core component of the circadian clock-transcriptional factor BMAL1 (brain and muscle ARNT [aryl hydrocarbon receptor nuclear translocator]-like protein 1)-results in accelerated aging. Here we investigated the role of BMAL1 in mechanisms of CR. The 30% CR diet increased the life span of wild-type (WT) mice by 20% compared to mice on anad libitum(AL) diet but failed to increase life span ofBmal1(-/-)mice. BMAL1 deficiency impaired CR-mediated changes in the plasma levels of IGF-1 and insulin. We detected a statistically significantly reduction of IGF-1 in CRvs.AL by 50 to 70% in WT mice at several daily time points tested, while inBmal1(-/-)the reduction was not significant. Insulin levels in WT were reduced by 5 to 9%, whileBmal1(-/-)induced it by 10 to 35% at all time points tested. CR up-regulated the daily average expression ofBmal1(by 150%) and its downstream target genesPeriods(by 470% forPer1and by 130% forPer2). We propose that BMAL1 is an important mediator of CR, and activation of BMAL1 might link CR mechanisms with biologic clocks.-Patel, S. A., Chaudhari, A., Gupta, R., Velingkaar, N., Kondratov, R. V. Circadian clocks govern calorie restriction-mediated life span extension through BMAL1- and IGF-1-dependent mechanisms. © FASEB.

Proton-coupled organic cation antiporter-mediated uptake of apomorphine enantiomers in human brain capillary endothelial cell line hCMEC/D3.

PubMed

Okura, Takashi; Higuchi, Kei; Kitamura, Atsushi; Deguchi, Yoshiharu

2014-01-01

R(-)-Apomorphine is a dopamine agonist used for rescue management of motor function impairment associated with levodopa therapy in Parkinson's disease patients. The aim of this study was to examine the role of proton-coupled organic cation antiporter in uptake of R(-)-apomorphine and its S-enantiomer in human brain, using human endothelial cell line hCMEC/D3 as a model. Uptake of R(-)- or S(+)-apomorphine into hCMEC/D3 cells was measured under various conditions to evaluate its time-, concentration-, energy- and ion-dependency. Inhibition by selected organic cations was also examined. Uptakes of both R(-)- and S(+)-apomorphine increased with time. The initial uptake velocities of R(-)- and S(+)-apomorphine were concentration-dependent, with similar Km and Vmax values. The cell-to-medium (C/M) ratio of R(-)-apomorphine was significantly reduced by pretreatment with sodium azide, but was not affected by replacement of extracellular sodium ion with N-methylglucamine or potassium. Intracellular alkalization markedly reduced the uptake, while intracellular acidification increased it, suggesting that the uptake is driven by an oppositely directed proton gradient. The C/M ratio was significantly decreased by amantadine, verapamil, pyrilamine and diphenhydramine (substrates or inhibitors of proton-coupled organic cation antiporter), while tetraethylammonium (substrate of organic cation transporters (OCTs)) and carnitine (substrate of carnitine/organic cation transporter 2; (OCTN2)) had no effect. R(-)-Apomorphine uptake was competitively inhibited by diphenhydramine. Our results indicate that R(-)-apomorphine transport in human blood-brain barrier (BBB) model cells is similar to S(+)-apomorphine uptake. The transport was dependent on an oppositely directed proton gradient, but was sodium- or membrane potential-independent. The transport characteristics were consistent with involvement of the previously reported proton-coupled organic cation antiporter.

Re-offending in forensic patients released from secure care: the role of antisocial/borderline personality disorder co-morbidity, substance dependence and severe childhood conduct disorder.

PubMed

Howard, Rick; McCarthy, Lucy; Huband, Nick; Duggan, Conor

2013-07-01

Research suggests that a particular externalising phenotype, manifested in a developmental trajectory from severe childhood conduct disorder through early-onset substance abuse to adult antisocial/borderline personality disorder co-morbidity, may increase risk of antisocial behaviour in general and criminal recidivism in particular. This study aims to test the hypothesis that antisocial/borderline co-morbidity together with the triad of substance dependence, severe conduct disorder and borderline pathology would result in an increased risk of criminal recidivism. Fifty-three men who had been assessed and treated in a secure hospital unit were followed up after they had returned to the community. They were assessed for severity of the following: (i) antisocial personality disorder; (ii) borderline personality disorder; (iii) drug/alcohol dependence; and (iv) high Psychopathy Checklist Revised scores (factors 1 and 2). Patients with antisocial/borderline co-morbidity took significantly less time to re-offend compared with those without such co-morbidity. Both Psychopathy Checklist Revised factor 2 and the tripartite risk measure significantly predicted time to re-offence; the former largely accounted for the predictive accuracy of the latter. Risk of criminal recidivism can be adequately assessed without recourse to the pejorative term 'psychopath'. It is sufficient to assess the presence of the three elements of our risk measure: borderline and antisocial personality disorders in the context of drug/alcohol dependence and severe childhood conduct disorder. Practical implications of the study are as follows. (i) Sound assessment of personality, inclusive of a detailed history of childhood conduct disorder as well as adolescent and adult substance misuse, yields good enough information about risk of recidivism without recourse to the pejorative concept of 'psychopathy'. (ii) Given the high risk of alcohol-related violence in individuals with antisocial/borderline co-morbidity, there is a need for specific alcohol-directed interventions to help such men retain control of their substance use. Copyright © 2013 John Wiley & Sons, Ltd.

Effect of butorphanol on thermal nociceptive threshold in healthy pony foals.

PubMed

McGowan, K T; Elfenbein, J R; Robertson, S A; Sanchez, L C

2013-07-01

Pain management is an important component of foal nursing care, and no objective data currently exist regarding the analgesic efficacy of opioids in foals. To evaluate the somatic antinociceptive effects of 2 commonly used doses of intravenous (i.v.) butorphanol in healthy foals. Our hypothesis was that thermal nociceptive threshold would increase following i.v. butorphanol in a dose-dependent manner in both neonatal and older pony foals. Seven healthy neonatal pony foals (age 1-2 weeks), and 11 healthy older pony foals (age 4-8 weeks). Five foals were used during both age periods. Treatments, which included saline (0.5 ml), butorphanol (0.05 mg/kg bwt) and butorphanol (0.1 mg/kg bwt), were administered i.v. in a randomised crossover design with at least 2 days between treatments. Response variables included thermal nociceptive threshold, skin temperature and behaviour score. Data within each age period were analysed using a 2-way repeated measures ANOVA, followed by a Holm-Sidak multiple comparison procedure if warranted. There was a significant (P<0.05) increase in thermal threshold, relative to Time 0, following butorphanol (0.1 mg/kg bwt) administration in both age groups. No significant time or treatment effects were apparent for skin temperature. Significant time, but not treatment, effects were evident for behaviour score in both age groups. Butorphanol (0.1 mg/kg bwt, but not 0.05 mg/kg bwt) significantly increased thermal nociceptive threshold in neonatal and older foals without apparent adverse behavioural effects. Butorphanol shows analgesic potential in foals for management of somatic painful conditions. © 2012 EVJ Ltd.

Climate change and dissolved organic carbon export to the Gulf of Maine

USGS Publications Warehouse

Huntington, Thomas G.; Balch, William M.; Aiken, George R.; Sheffield, Justin; Luo, Lifeng; Roesler, Collin S.; Camill, Philip

2016-01-01

Ongoing climate change is affecting the concentration, export (flux), and timing of dissolved organic carbon (DOC) exported to the Gulf of Maine (GoM) through changes in hydrologic regime. DOC export was calculated for water years 1950 through 2013 for 20 rivers and for water years 1930 through 2013 for 14 rivers draining to the GoM. DOC export was also estimated for the 21st century based on climate and hydrologic modeling in a previously published study. DOC export was calculated by using the regression model LOADEST to fit seasonally adjusted concentration discharge (C-Q) relations. Our results are an analysis of the sensitivity of DOC export to changes in hydrologic conditions over time since land cover and vegetation were held constant over time. Despite large interannual variability, all rivers had increasing DOC export during winter and these trends were significant (p < 0.05) in 10 out of 20 rivers for 1950 to 2013 and in 13 out of 14 rivers for 1930 to 2013. All rivers also had increasing annual export of DOC although fewer trends were statistically significant than for winter export. Projections for DOC export during the 21st century were variable depending on the climate model and greenhouse gas emission scenario that affected future river discharge through effects on precipitation and evapotranspiration. The most consistent result was a significant increase in DOC export in winter in all model-by-emission scenarios. DOC export was projected to decrease during the summer in all model-by-emission scenarios, with statistically significant decreases in half of the scenarios.

Time-dependent strains and stresses in a pumpkin balloon

NASA Technical Reports Server (NTRS)

Gerngross, T.; Xu, Y.; Pellegrino, S.

2006-01-01

This paper presents a study of pumpkin-shaped superpressure balloons, consisting of gores made from a thin polymeric film attached to high stiffness, meridional tendons. This type of design is being used for the NASA ULDB balloons. The gore film shows considerable time-dependent stress relaxation, whereas the behaviour of the tendons is essentially time-independent. Upon inflation and pressurization, the "instantaneous", i.e. linear-elastic strain and stress distribution in the film show significantly higher values in the meridional direction. However, over time, and due to the biaxial visco-elastic stress relaxation of the the material, the hoop strains increase and the meridional stresses decrease, whereas the remaining strain and stress components remain substantially unchanged. These results are important for a correct assessment of the structural integrity of a pumpkin balloon in a long-duration mission, both in terms of the material performance and the overall stability of the shape of the balloon. An experimental investigation of the time dependence of the biaxial strain distribution in the film of a 4 m diameter, 48 gore pumpkin balloon is presented. The inflated shape of selected gores has been measured using photogrammetry and the time variation in strain components at some particular points of these gores has been measured under constant pressure and temperature. The results show good correlation with a numerical study, using the ABAQUS finite-element package, that includes a widely used model of the visco-elastic response of the gore material:

Estimating economic gains for landowners due to time-dependent changes in biotechnology

Treesearch

John E. Wagner; Thomas P. Holmes

1998-01-01

This paper presents a model for examining the economic value of biotechnological research given time-dependent changes in biotechnology. Previous papers examined this issue assuming a time-neutral change in biotechnology. However, when analyzing the genetic improvements of increasing a tree's resistance to a pathogen, this assumption is untenable. The authors...

Maturation of Sensori-Motor Functional Responses in the Preterm Brain.

PubMed

Allievi, Alessandro G; Arichi, Tomoki; Tusor, Nora; Kimpton, Jessica; Arulkumaran, Sophie; Counsell, Serena J; Edwards, A David; Burdet, Etienne

2016-01-01

Preterm birth engenders an increased risk of conditions like cerebral palsy and therefore this time may be crucial for the brain's developing sensori-motor system. However, little is known about how cortical sensori-motor function matures at this time, whether development is influenced by experience, and about its role in spontaneous motor behavior. We aimed to systematically characterize spatial and temporal maturation of sensori-motor functional brain activity across this period using functional MRI and a custom-made robotic stimulation device. We studied 57 infants aged from 30 + 2 to 43 + 2 weeks postmenstrual age. Following both induced and spontaneous right wrist movements, we saw consistent positive blood oxygen level-dependent functional responses in the contralateral (left) primary somatosensory and motor cortices. In addition, we saw a maturational trend toward faster, higher amplitude, and more spatially dispersed functional responses; and increasing integration of the ipsilateral hemisphere and sensori-motor associative areas. We also found that interhemispheric functional connectivity was significantly related to ex-utero exposure, suggesting the influence of experience-dependent mechanisms. At term equivalent age, we saw a decrease in both response amplitude and interhemispheric functional connectivity, and an increase in spatial specificity, culminating in the establishment of a sensori-motor functional response similar to that seen in adults. © The Author 2015. Published by Oxford University Press.

[Role of caveolin-1 in pulmonary microvascular endothelial cells injury induced by lipopolysaccharide in rat].

PubMed

You, Qing-hai; Zhang, Dan; Sun, Geng-yun; Yue, Yang; Xu, Xiu-juan

2013-12-01

To investigate the role of caveolin-1 (Cav-1) in the modulation of rat pulmonary microvascular endothelial cells (RPMVEC) injury induced by lipopolysaccharide (LPS). Cultured RPMVEC were randomly divided into time-dependent injury group induced by LPS and intervention group in which cells were pretreated by protein kinase A inhibitor (PKI). In the time-dependent injury group, monolayers of cells were constructed to determine permeability changes after 10 μg/mL LPS challenge for 0, 1, 3, 6, 12 and 24 hours with the method of Evans blue-labeled albumin flux across the monolayer (Pd). Western blotting was used to determine the Cav-1 expression after LPS stimulation and the phosphorylation-Cav-1 (p-Cav-1) expression after LPS challenge for 0, 10, 30, 60, 90, 120 minutes. In the intervention group, after pre-treatment with 10 μmol/L PKI for 30 minutes, RPMVECs were challenged with 10 μg/mL LPS, and the expression of p-Cav-1 was determined 30 minutes after LPS challenge, the permeability and the Cav-1 protein expression were assessed by Pd and Western blotting, respectively. Non-stimulation group and single PKI simulation group served as controls. Western blotting revealed that the expression of Cav-1 protein was elevated at 1 hour (2.97 ± 0.07), peaking at 3 hours (3.77 ± 0.37), then it lowered gradually, but it was still higher at 24 hours (1.45 ± 0.18) when compared with 0 hour group (1.12±0.08) with significant differences (F=178.047, P=0.000). After RPMVEC monolayers were challenged by LPS for different periods (0, 1, 3, 6, 12 and 24 hours), there were significant increases in a time-dependent manner in Cav-1 expression in the permeability as measured by Pd [(99.67 ± 4.32)%, (118.17 ± 2.32)%, (159.00 ± 2.61)%, (141.17 ± 2.64)%, (120.17 ± 2.79)% and (108.83 ± 2.04)%, F=345.869, P=0.000] which was similar to the changes in Cav-1 expression. LPS also increased Cav-1 phosphorylation in a time-dependent manner occurring at 10 minutes (2.41 ± 0.11), peaking at 30 minutes (2.83 ± 0.10), and then it decreased gradually, finally returned to basal levels (1.03±0.04) at 120 minutes (1.04 ± 0.04) after LPS treatment with significant difference (F=519.417, P=0.000). When PKI was pre-treated with RPMVEC the expression of Cav-1 was significantly increased (5.07 ± 0.22 vs. 3.81 ± 0.23, P<0.01), and p-Cav-1 (3.93 ± 0.23 vs. 2.77±0.10, P<0.01), and RPMVEC monolayers permeability was enhanced [(184.17 ± 5.49)% vs. (151.50 ± 3.08)%, P<0.01] after being challenged. Up-regulated expression of Cav-1 and phosphorylation-Cav-1 that may be modulated by protein kinase A signal pathway plays an important role in RPMVEC permeability injury as induced by LPS.

Excited-state dynamics of size-dependent colloidal TiO2-Au nanocomposites

NASA Astrophysics Data System (ADS)

Karam, Tony E.; Khoury, Rami A.; Haber, Louis H.

2016-03-01

The ultrafast excited-state dynamics of size-dependent TiO2-Au nanocomposites synthesized by reducing gold nanoclusters to the surface of colloidal TiO2 nanoparticles are studied using pump-probe transient absorption spectroscopy with 400 nm excitation pulses. The results show that the relaxation processes of the plasmon depletion band, which are described by electron-phonon and phonon-phonon scattering lifetimes, are independent of the gold nanocluster shell size surrounding the TiO2 nanoparticle core. The dynamics corresponding to interfacial electron transfer between the gold nanoclusters and the TiO2 bandgap are observed to spectrally overlap with the gold interband transition signal, and the electron transfer lifetimes are shown to significantly decrease as the nanocluster shell size increases. Additionally, size-dependent periodic oscillations are observed and are attributed to acoustic phonons of a porous shell composed of aggregated gold nanoclusters around the TiO2 core, with frequencies that decrease and damping times that remain constant as the nanocluster shell size increases. These results are important for the development of improved catalytic nanomaterial applications.

Evaluation of Augmented Reality Feedback in Surgical Training Environment.

PubMed

Zahiri, Mohsen; Nelson, Carl A; Oleynikov, Dmitry; Siu, Ka-Chun

2018-02-01

Providing computer-based laparoscopic surgical training has several advantages that enhance the training process. Self-evaluation and real-time performance feedback are 2 of these advantages, which avoid dependency of trainees on expert feedback. The goal of this study was to investigate the use of a visual time indicator as real-time feedback correlated with the laparoscopic surgical training. Twenty novices participated in this study working with (and without) different presentations of time indicators. They performed a standard peg transfer task, and their completion times and muscle activity were recorded and compared. Also of interest was whether the use of this type of feedback induced any side effect in terms of motivation or muscle fatigue. Of the 20 participants, 15 (75%) preferred using a time indicator in the training process rather than having no feedback. However, time to task completion showed no significant difference in performance with the time indicator; furthermore, no significant differences in muscle activity or muscle fatigue were detected with/without time feedback. The absence of significant difference between task performance with/without time feedback shows that using visual real-time feedback can be included in surgical training based on user preference. Trainees may benefit from this type of feedback in the form of increased motivation. The extent to which this can influence training frequency leading to performance improvement is a question for further study.

The influence of corticosteroid treatment on the outcome of influenza A(H1N1pdm09)-related critical illness.

PubMed

Delaney, Jesse W; Pinto, Ruxandra; Long, Jennifer; Lamontagne, François; Adhikari, Neill K; Kumar, Anand; Marshall, John C; Cook, Deborah J; Jouvet, Philippe; Ferguson, Niall D; Griesdale, Donald; Burry, Lisa D; Burns, Karen E A; Hutchison, Jamie; Mehta, Sangeeta; Menon, Kusum; Fowler, Robert A

2016-03-30

Patients with 2009 pandemic influenza A(H1N1pdm09)-related critical illness were frequently treated with systemic corticosteroids. While observational studies have reported significant corticosteroid-associated mortality after adjusting for baseline differences in patients treated with corticosteroids or not, corticosteroids have remained a common treatment in subsequent influenza outbreaks, including avian influenza A(H7N9). Our objective was to describe the use of corticosteroids in these patients and investigate predictors of steroid prescription and clinical outcomes, adjusting for both baseline and time-dependent factors. In an observational cohort study of adults with H1N1pdm09-related critical illness from 51 Canadian ICUs, we investigated predictors of steroid administration and outcomes of patients who received and those who did not receive corticosteroids. We adjusted for potential baseline confounding using multivariate logistic regression and propensity score analysis and adjusted for potential time-dependent confounding using marginal structural models. Among 607 patients, corticosteroids were administered to 280 patients (46.1%) at a median daily dose of 227 (interquartile range, 154-443) mg of hydrocortisone equivalents for a median of 7.0 (4.0-13.0) days. Compared with patients who did not receive corticosteroids, patients who received corticosteroids had higher hospital crude mortality (25.5% vs 16.4%, p = 0.007) and fewer ventilator-free days at 28 days (12.5 ± 10.7 vs 15.7 ± 10.1, p < 0.001). The odds ratio association between corticosteroid use and hospital mortality decreased from 1.85 (95% confidence interval 1.12-3.04, p = 0.02) with multivariate logistic regression, to 1.71 (1.05-2.78, p = 0.03) after adjustment for propensity score to receive corticosteroids, to 1.52 (0.90-2.58, p = 0.12) after case-matching on propensity score, and to 0.96 (0.28-3.28, p = 0.95) using marginal structural modeling to adjust for time-dependent between-group differences. Corticosteroids were commonly prescribed for H1N1pdm09-related critical illness. Adjusting for only baseline between-group differences suggested a significant increased risk of death associated with corticosteroids. However, after adjusting for time-dependent differences, we found no significant association between corticosteroids and mortality. These findings highlight the challenges and importance in adjusting for baseline and time-dependent confounders when estimating clinical effects of treatments using observational studies.

Effect of basic physical parameters to control plasma meniscus and beam halo formation in negative ion sources

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

Miyamoto, K.; Okuda, S.; Nishioka, S.

2013-09-14

Our previous study shows that the curvature of the plasma meniscus causes the beam halo in the negative ion sources: the negative ions extracted from the periphery of the meniscus are over-focused in the extractor due to the electrostatic lens effect, and consequently become the beam halo. In this article, the detail physics of the plasma meniscus and beam halo formation is investigated with two-dimensional particle-in-cell simulation. It is shown that the basic physical parameters such as the H{sup −} extraction voltage and the effective electron confinement time significantly affect the formation of the plasma meniscus and the resultant beammore » halo since the penetration of electric field for negative ion extraction depends on these physical parameters. Especially, the electron confinement time depends on the characteristic time of electron escape along the magnetic field as well as the characteristic time of electron diffusion across the magnetic field. The plasma meniscus penetrates deeply into the source plasma region when the effective electron confinement time is short. In this case, the curvature of the plasma meniscus becomes large, and consequently the fraction of the beam halo increases.« less

Dose-dependency of dexamethasone on the analgesic effect of interscalene block for arthroscopic shoulder surgery using ropivacaine 0.5%: A randomised controlled trial.

PubMed

Woo, Jae Hee; Kim, Youn Jin; Kim, Dong Yeon; Cho, Sooyoung

2015-09-01

Dexamethasone prolongs the duration of single-shot interscalene brachial plexus block (SISB). However, dose-dependency of dexamethasone as an adjuvant for SISB remains insufficiently understood. The objective of this study is to evaluate the effect of different doses of dexamethasone on the duration of SISB using ropivacaine 0.5%. A randomised, double-blind controlled trial. Single university tertiary care centre. One hundred and forty-four patients scheduled for elective arthroscopic shoulder surgery were allocated randomly to one of four groups. Patients received 12 ml of ropivacaine 0.5% in 0.9% saline (control group), or containing dexamethasone 2.5, 5.0 or 7.5 mg for SISB. The primary endpoint was the time to the first analgesic request. Pain scores and adverse effects were also assessed up to 48 h postoperatively. Inclusion of dexamethasone 2.5, 5.0 and 7.5 mg resulted in significant (P < 0.001) increases in time to the first analgesic request by factors of 1.6, 2.2 and 1.8, respectively. The percentages of patients not requiring analgesics in the first 48 h postoperatively with dexamethasone 0.0, 2.5, 5.0 and 7.5 mg were 3, 22, 39 and 33%, respectively (P < 0.001). There were no significant effects on pain scores or incidences of adverse effects. Dexamethasone demonstrated significant beneficial dose-dependent effects on duration to the first analgesic request, the number of patients not requiring analgesics and analgesic use in the first 48 h after SISB for arthroscopic shoulder surgery. There were no significant effects on pain scores or incidences of adverse effects. the trial was registered with the Clinical Trial Registry of Korea: https://cris.nih.go.kr/cris/index.jsp. Identifier: KCT0001078.

A solar cycle dependence of nonlinearity in magnetospheric activity

NASA Astrophysics Data System (ADS)

Johnson, Jay R.; Wing, Simon

2005-04-01

The nonlinear dependencies inherent to the historical Kp data stream (1932-2003) are examined using mutual information and cumulant-based cost as discriminating statistics. The discriminating statistics are compared with surrogate data streams that are constructed using the corrected amplitude adjustment Fourier transform (CAAFT) method and capture the linear properties of the original Kp data. Differences are regularly seen in the discriminating statistics a few years prior to solar minima, while no differences are apparent at the time of solar maxima. These results suggest that the dynamics of the magnetosphere tend to be more linear at solar maximum than at solar minimum. The strong nonlinear dependencies tend to peak on a timescale around 40-50 hours and are statistically significant up to 1 week. Because the solar wind driver variables, VBs, and dynamical pressure exhibit a much shorter decorrelation time for nonlinearities, the results seem to indicate that the nonlinearity is related to internal magnetospheric dynamics. Moreover, the timescales for the nonlinearity seem to be on the same order as that for storm/ring current relaxation. We suggest that the strong solar wind driving that occurs around solar maximum dominates the magnetospheric dynamics, suppressing the internal magnetospheric nonlinearity. On the other hand, in the descending phase of the solar cycle just prior to solar minimum, when magnetospheric activity is weaker, the dynamics exhibit a significant nonlinear internal magnetospheric response that may be related to increased solar wind speed.

I get so lonely, baby: The effects of loneliness and social isolation on romantic dependency.

PubMed

Hasan, Michelle; Clark, Eddie M

2017-01-01

Individuals lacking fulfilling interpersonal interactions may experience feelings of loneliness. Consequently, these individuals may over-rely on their romantic partners to fulfill the need to belong. This study examined the effects of loneliness and social isolation on dependency on a romantic partner in a sample of college students (N = 104). Participants who were in a romantic relationship completed measures of loneliness, social isolation, and romantic dependency near the beginning of the semester (Time 1) and approximately 6 weeks later toward the end of the semester (Time 2). Toward the beginning of the semester, there were no significant predictors of dependency. Toward the end of the semester, individuals who reported higher social isolation reported higher levels of dependency. Time 1 dependency also predicted Time 2 dependency. Future methodological directions and suggestions regarding the examination of perceptions of loneliness and relationship expectations are discussed.