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Sample records for activity varied significantly

  1. Active spectral sensor evaluation under varying conditions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plant stress has been estimated by spectral signature using both passive and active sensors. As optical sensors measure reflected light from a target, changes in illumination characteristics critically affect sensor response. Active sensors are of benefit in minimizing uncontrolled illumination effe...

  2. Finding Significant Stress Episodes in a Discontinuous Time Series of Rapidly Varying Mobile Sensor Data

    PubMed Central

    Sarker, Hillol; Tyburski, Matthew; Rahman, Md. Mahbubur; Hovsepian, Karen; Sharmin, Moushumi; Epstein, David H.; Preston, Kenzie L.; Furr-Holden, C. Debra; Milam, Adam; Nahum-Shani, Inbal; al’Absi, Mustafa; Kumar, Santosh

    2016-01-01

    Management of daily stress can be greatly improved by delivering sensor-triggered just-in-time interventions (JITIs) on mobile devices. The success of such JITIs critically depends on being able to mine the time series of noisy sensor data to find the most opportune moments. In this paper, we propose a time series pattern mining method to detect significant stress episodes in a time series of discontinuous and rapidly varying stress data. We apply our model to 4 weeks of physiological, GPS, and activity data collected from 38 users in their natural environment to discover patterns of stress in real-life. We find that the duration of a prior stress episode predicts the duration of the next stress episode and stress in mornings and evenings is lower than during the day. We then analyze the relationship between stress and objectively rated disorder in the surrounding neighborhood and develop a model to predict stressful episodes. PMID:28058409

  3. The Activity of Antimicrobial Surfaces Varies by Testing Protocol Utilized

    PubMed Central

    Campos, Matias D.; Zucchi, Paola C.; Phung, Ann; Leonard, Steven N.; Hirsch, Elizabeth B.

    2016-01-01

    Background Contaminated hospital surfaces are an important source of nosocomial infections. A major obstacle in marketing antimicrobial surfaces is a lack of efficacy data based on standardized testing protocols. Aim We compared the efficacy of multiple testing protocols against several “antimicrobial” film surfaces. Methods Four clinical isolates were used: one Escherichia coli, one Klebsiella pneumoniae, and two Staphylococcus aureus strains. Two industry methods (modified ISO 22196 and ASTM E2149), a “dried droplet”, and a “transfer” method were tested against two commercially available antimicrobial films, one film in development, an untreated control, and a positive (silver) control film. At 2 (only ISO) and 24 hours following inoculation, bacteria were collected from film surfaces and enumerated. Results Compared to untreated films in all protocols, there were no significant differences in recovery on either commercial brand at 2 or 24 hours after inoculation. The silver surface demonstrated significant microbicidal activity (mean loss 4.9 Log10 CFU/ml) in all methods and time points with the exception of 2 hours in the ISO protocol and the transfer method. Using our novel droplet method, no differences between placebo and active surfaces were detected. The surface in development demonstrated variable activity depending on method, organism, and time point. The ISO demonstrated minimal activity at 2 hours but significant activity at 24 hours (mean 4.5 Log10 CFU/ml difference versus placebo). The ASTEM protocol exhibited significant differences in recovery of staphylococci (mean 5 Log10 CFU/ml) but not Gram-negative isolates (10 fold decrease). Minimal activity was observed with this film in the transfer method. Conclusions Varying results between protocols suggested that efficacy of antimicrobial surfaces cannot be easily and reproducibly compared. Clinical use should be considered and further development of representative methods is needed. PMID

  4. Basic Business and Economics: Varied Activities Encourage Active Student Involvement.

    ERIC Educational Resources Information Center

    Baker, Robert Lee, Jr.

    1978-01-01

    Describes a variety of activities for the basic business classroom, such as having guest speakers, question-and-answer sessions, simulations, role playing, debates, small group work, field trips, games, and individualized instruction. Includes a report of business teachers' knowledge of and attitudes toward these activities. (MF)

  5. Evaluation of active appearance models in varying background conditions

    NASA Astrophysics Data System (ADS)

    Kowalski, Marek; Naruniec, Jacek

    2013-10-01

    In this paper we present an evaluation of the chosen versions of Active Appearance Models (AAM) in varying background conditions. Algorithms were tested on a subset of the CMU PIE database and chosen background im- ages. Our experiments prove, that the accuracy of those methods is strictly correlated with the used background, where the differences in the success rate differ even up to 50%.

  6. Constraints on global fire activity vary across a resource gradient.

    PubMed

    Krawchuk, Meg A; Moritz, Max A

    2011-01-01

    We provide an empirical, global test of the varying constraints hypothesis, which predicts systematic heterogeneity in the relative importance of biomass resources to burn and atmospheric conditions suitable to burning (weather/climate) across a spatial gradient of long-term resource availability. Analyses were based on relationships between monthly global wildfire activity, soil moisture, and mid-tropospheric circulation data from 2001 to 2007, synthesized across a gradient of long-term averages in resources (net primary productivity), annual temperature, and terrestrial biome. We demonstrate support for the varying constraints hypothesis, showing that, while key biophysical factors must coincide for wildfires to occur, the relative influence of resources to burn and moisture/weather conditions on fire activity shows predictable spatial patterns. In areas where resources are always available for burning during the fire season, such as subtropical/tropical biomes with mid-high annual long-term net primary productivity, fuel moisture conditions exert their strongest constraint on fire activity. In areas where resources are more limiting or variable, such as deserts, xeric shrublands, or grasslands/savannas, fuel moisture has a diminished constraint on wildfire, and metrics indicating availability of burnable fuels produced during the antecedent wet growing seasons reflect a more pronounced constraint on wildfire. This macro-scaled evidence for spatially varying constraints provides a synthesis with studies performed at local and regional scales, enhances our understanding of fire as a global process, and indicates how sensitivity to future changes in temperature and precipitation may differ across the world.

  7. Positive Selection or Free to Vary? Assessing the Functional Significance of Sequence Change Using Molecular Dynamics

    PubMed Central

    Allison, Jane R.; Lechner, Marcus; Hoeppner, Marc P.; Poole, Anthony M.

    2016-01-01

    Evolutionary arms races between pathogens and their hosts may be manifested as selection for rapid evolutionary change of key genes, and are sometimes detectable through sequence-level analyses. In the case of protein-coding genes, such analyses frequently predict that specific codons are under positive selection. However, detecting positive selection can be non-trivial, and false positive predictions are a common concern in such analyses. It is therefore helpful to place such predictions within a structural and functional context. Here, we focus on the p19 protein from tombusviruses. P19 is a homodimer that sequesters siRNAs, thereby preventing the host RNAi machinery from shutting down viral infection. Sequence analysis of the p19 gene is complicated by the fact that it is constrained at the sequence level by overprinting of a viral movement protein gene. Using homology modeling, in silico mutation and molecular dynamics simulations, we assess how non-synonymous changes to two residues involved in forming the dimer interface—one invariant, and one predicted to be under positive selection—impact molecular function. Interestingly, we find that both observed variation and potential variation (where a non-synonymous change to p19 would be synonymous for the overprinted movement protein) does not significantly impact protein structure or RNA binding. Consequently, while several methods identify residues at the dimer interface as being under positive selection, MD results suggest they are functionally indistinguishable from a site that is free to vary. Our analyses serve as a caveat to using sequence-level analyses in isolation to detect and assess positive selection, and emphasize the importance of also accounting for how non-synonymous changes impact structure and function. PMID:26871901

  8. Does Compound I Vary Significantly between Isoforms of Cytochrome P450?

    PubMed Central

    2011-01-01

    The cytochrome P450 (CYP) enzymes are important in many areas, including pharmaceutical development. Subtle changes in the electronic structure of the active species, Compound I, have been postulated previously to account partly for the experimentally observed differences in reactivity between isoforms. Current predictive models of CYP metabolism typically assume an identical Compound I in all isoforms. Here we present a method to calculate the electronic structure and to estimate the Fe–O bond enthalpy of Compound I, and apply it to several human and bacterial CYP isoforms. Conformational flexibility is accounted for by sampling large numbers of structures from molecular dynamics simulations, which are subsequently optimized with density functional theory (B3LYP) based quantum mechanics/molecular mechanics. The observed differences in Compound I between human isoforms are small: They are generally smaller than the spread of values obtained for the same isoform starting from different initial structures. Hence, it is unlikely that the variation in activity between human isoforms is due to differences in the electronic structure of Compound I. A larger difference in electronic structure is observed between the human isoforms and P450cam and may be explained by the slightly different hydrogen-bonding environment surrounding the cysteinyl sulfur. The presence of substrate in the active site of all isoforms studied appears to cause a slight decrease in the Fe–O bond enthalpy, apparently due to displacement of water out of the active site, suggesting that Compound I is less stable in the presence of substrate. PMID:21863858

  9. Innovation diffusion on time-varying activity driven networks

    NASA Astrophysics Data System (ADS)

    Rizzo, Alessandro; Porfiri, Maurizio

    2016-01-01

    Since its introduction in the 1960s, the theory of innovation diffusion has contributed to the advancement of several research fields, such as marketing management and consumer behavior. The 1969 seminal paper by Bass [F.M. Bass, Manag. Sci. 15, 215 (1969)] introduced a model of product growth for consumer durables, which has been extensively used to predict innovation diffusion across a range of applications. Here, we propose a novel approach to study innovation diffusion, where interactions among individuals are mediated by the dynamics of a time-varying network. Our approach is based on the Bass' model, and overcomes key limitations of previous studies, which assumed timescale separation between the individual dynamics and the evolution of the connectivity patterns. Thus, we do not hypothesize homogeneous mixing among individuals or the existence of a fixed interaction network. We formulate our approach in the framework of activity driven networks to enable the analysis of the concurrent evolution of the interaction and individual dynamics. Numerical simulations offer a systematic analysis of the model behavior and highlight the role of individual activity on market penetration when targeted advertisement campaigns are designed, or a competition between two different products takes place.

  10. Significance of IDH mutations varies with tumor histology, grade, and genetics in Japanese glioma patients.

    PubMed

    Mukasa, Akitake; Takayanagi, Shunsaku; Saito, Kuniaki; Shibahara, Junji; Tabei, Yusuke; Furuya, Kazuhide; Ide, Takafumi; Narita, Yoshitaka; Nishikawa, Ryo; Ueki, Keisuke; Saito, Nobuhito

    2012-03-01

    Mutations in isocitrate dehydrogenase 1 (IDH1) and IDH2 are found frequently in malignant gliomas and are likely involved in early gliomagenesis. To understand the prevalence of these mutations and their relationship to other genetic alterations and impact on prognosis for Japanese glioma patients, we analyzed 250 glioma cases. Mutations of IDH1 and IDH2 were found in 73 (29%) and 2 (1%) cases, respectively. All detected mutations were heterozygous, and most mutations were an Arg132His (G395A) substitution. IDH mutations were frequent in oligodendroglial tumors (37/52, 71%) and diffuse astrocytomas (17/29, 59%), and were less frequent in anaplastic astrocytomas (8/29, 28%) and glioblastomas (13/125, 10%). The pilocytic astrocytomas and gangliogliomas did not have either mutation. Notably, 28 of 30 oligodendroglial tumors harboring the 1p/19q co-deletion also had an IDH mutation, and these alterations were significantly correlated (P < 0.001). The association between TP53 and IDH mutation was significant in diffuse astrocytomas (P = 0.0018). MGMT promoter methylation was significantly associated with IDH mutation in grade 2 (P < 0.001) and grade 3 (P = 0.02) gliomas. IDH mutation and 1p/19q co-deletion were independent favorable prognostic factors for patients with grade 3 gliomas. For patients with grade 3 gliomas and without 1p/19q co-deletion, IDH mutation was strongly associated with increased progression-free survival (P < 0.0001) and overall survival (P < 0.0001), but no such marked correlation was observed with grade 2 gliomas or glioblastomas. Therefore, IDH mutation would be most useful when assessing prognosis of patients with grade 3 glioma with intact 1p/19q; anaplastic astrocytomas account for most of these grade 3 gliomas.

  11. Varying protein source and quantity does not significantly improve weight loss, fat loss, or satiety in reduced energy diets among midlife adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This pilot study tested whether varying protein source and quantity in a reduced energy diet would result in significant differences in weight, body composition, and renin angiotensin aldosterone system activity in midlife adults. Eighteen subjects enrolled in a 5 month weight reduction study, invol...

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

    PubMed

    Cai, Zuowei; Huang, Lihong; Zhang, Lingling

    2015-05-01

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

  13. Motoneuron and sensory neuron plasticity to varying neuromuscular activity levels

    NASA Technical Reports Server (NTRS)

    Ishihara, Akihiko; Roy, Roland R.; Ohira, Yoshinobu; Edgerton, V. Reggie

    2002-01-01

    The size and phenotypic properties of the neural and muscular elements of the neuromuscular unit are matched under normal conditions. When subjected to chronic decreases or increases in neuromuscular activity, however, the adaptations in these properties are much more limited in the neural compared with the muscular elements.

  14. Significant Quantum Effects in Hydrogen Activation

    SciTech Connect

    Kyriakou, Georgios; Davidson, Erlend R.; Peng, Guowen; Roling, Luke T.; Singh, Suyash; Boucher, Matthew B.; Marcinkowski, Matthew D.; Mavrikakis, Manos; Michaelides, Angelos; Sykes, E. Charles H.

    2014-03-31

    Dissociation of molecular hydrogen is an important step in a wide variety of chemical, biological, and physical processes. Due to the light mass of hydrogen, it is recognized that quantum effects are often important to its reactivity. However, understanding how quantum effects impact the reactivity of hydrogen is still in its infancy. Here, we examine this issue using a well-defined Pd/Cu(111) alloy that allows the activation of hydrogen and deuterium molecules to be examined at individual Pd atom surface sites over a wide range of temperatures. Experiments comparing the uptake of hydrogen and deuterium as a function of temperature reveal completely different behavior of the two species. The rate of hydrogen activation increases at lower sample temperature, whereas deuterium activation slows as the temperature is lowered. Density functional theory simulations in which quantum nuclear effects are accounted for reveal that tunneling through the dissociation barrier is prevalent for H2 up to 190 K and for D2 up to 140 K. Kinetic Monte Carlo simulations indicate that the effective barrier to H2 dissociation is so low that hydrogen uptake on the surface is limited merely by thermodynamics, whereas the D2 dissociation process is controlled by kinetics. These data illustrate the complexity and inherent quantum nature of this ubiquitous and seemingly simple chemical process. Examining these effects in other systems with a similar range of approaches may uncover temperature regimes where quantum effects can be harnessed, yielding greater control of bond-breaking processes at surfaces and uncovering useful chemistries such as selective bond activation or isotope separation.

  15. Significant Quantum Effects in Hydrogen Activation

    PubMed Central

    2014-01-01

    Dissociation of molecular hydrogen is an important step in a wide variety of chemical, biological, and physical processes. Due to the light mass of hydrogen, it is recognized that quantum effects are often important to its reactivity. However, understanding how quantum effects impact the reactivity of hydrogen is still in its infancy. Here, we examine this issue using a well-defined Pd/Cu(111) alloy that allows the activation of hydrogen and deuterium molecules to be examined at individual Pd atom surface sites over a wide range of temperatures. Experiments comparing the uptake of hydrogen and deuterium as a function of temperature reveal completely different behavior of the two species. The rate of hydrogen activation increases at lower sample temperature, whereas deuterium activation slows as the temperature is lowered. Density functional theory simulations in which quantum nuclear effects are accounted for reveal that tunneling through the dissociation barrier is prevalent for H2 up to ∼190 K and for D2 up to ∼140 K. Kinetic Monte Carlo simulations indicate that the effective barrier to H2 dissociation is so low that hydrogen uptake on the surface is limited merely by thermodynamics, whereas the D2 dissociation process is controlled by kinetics. These data illustrate the complexity and inherent quantum nature of this ubiquitous and seemingly simple chemical process. Examining these effects in other systems with a similar range of approaches may uncover temperature regimes where quantum effects can be harnessed, yielding greater control of bond-breaking processes at surfaces and uncovering useful chemistries such as selective bond activation or isotope separation. PMID:24684530

  16. Cytochrome bd Displays Significant Quinol Peroxidase Activity

    PubMed Central

    Al-Attar, Sinan; Yu, Yuanjie; Pinkse, Martijn; Hoeser, Jo; Friedrich, Thorsten; Bald, Dirk; de Vries, Simon

    2016-01-01

    Cytochrome bd is a prokaryotic terminal oxidase that catalyses the electrogenic reduction of oxygen to water using ubiquinol as electron donor. Cytochrome bd is a tri-haem integral membrane enzyme carrying a low-spin haem b558, and two high-spin haems: b595 and d. Here we show that besides its oxidase activity, cytochrome bd from Escherichia coli is a genuine quinol peroxidase (QPO) that reduces hydrogen peroxide to water. The highly active and pure enzyme preparation used in this study did not display the catalase activity recently reported for E. coli cytochrome bd. To our knowledge, cytochrome bd is the first membrane-bound quinol peroxidase detected in E. coli. The observation that cytochrome bd is a quinol peroxidase, can provide a biochemical basis for its role in detoxification of hydrogen peroxide and may explain the frequent findings reported in the literature that indicate increased sensitivity to hydrogen peroxide and decreased virulence in mutants that lack the enzyme. PMID:27279363

  17. Resting Brain Activity Varies with Dream Recall Frequency Between Subjects

    PubMed Central

    Eichenlaub, Jean-Baptiste; Nicolas, Alain; Daltrozzo, Jérôme; Redouté, Jérôme; Costes, Nicolas; Ruby, Perrine

    2014-01-01

    Dreaming is still poorly understood. Notably, its cerebral underpinning remains unclear. Neuropsychological studies have shown that lesions in the temporoparietal junction (TPJ) and/or the white matter of the medial prefrontal cortex (MPFC) lead to the global cessation of dream reports, suggesting that these regions of the default mode network have key roles in the dreaming process (forebrain ‘dream-on' hypothesis). To test this hypothesis, we measured regional cerebral blood flow (rCBF) using [15O]H2O positron emission tomography in healthy subjects with high and low dream recall frequencies (DRFs) during wakefulness (rest) and sleep (rapid eye movement (REM) sleep, N2, and N3). Compared with Low recallers (0.5±0.3 dream recall per week in average), High recallers (5.2±1.4) showed higher rCBF in the TPJ during REM sleep, N3, and wakefulness, and in the MPFC during REM sleep and wakefulness. We demonstrate that the resting states of High recallers and Low recallers differ during sleep and wakefulness. It coheres with previous ERP results and confirms that a high/low DRF is associated with a specific functional organization of the brain. These results support the forebrain ‘dream-on' hypothesis and suggest that TPJ and MPFC are not only involved in dream recall during wakefulness but also have a role in dreaming during sleep (production and/or encoding). Increased activity in the TPJ and MPFC might promote the mental imagery and/or memory encoding of dreams. Notably, increased activity in TPJ might facilitate attention orienting toward external stimuli and promote intrasleep wakefulness, facilitating the encoding of the dreams in memory. PMID:24549103

  18. Resting brain activity varies with dream recall frequency between subjects.

    PubMed

    Eichenlaub, Jean-Baptiste; Nicolas, Alain; Daltrozzo, Jérôme; Redouté, Jérôme; Costes, Nicolas; Ruby, Perrine

    2014-06-01

    Dreaming is still poorly understood. Notably, its cerebral underpinning remains unclear. Neuropsychological studies have shown that lesions in the temporoparietal junction (TPJ) and/or the white matter of the medial prefrontal cortex (MPFC) lead to the global cessation of dream reports, suggesting that these regions of the default mode network have key roles in the dreaming process (forebrain 'dream-on' hypothesis). To test this hypothesis, we measured regional cerebral blood flow (rCBF) using [(15)O]H2O positron emission tomography in healthy subjects with high and low dream recall frequencies (DRFs) during wakefulness (rest) and sleep (rapid eye movement (REM) sleep, N2, and N3). Compared with Low recallers (0.5 ± 0.3 dream recall per week in average), High recallers (5.2 ± 1.4) showed higher rCBF in the TPJ during REM sleep, N3, and wakefulness, and in the MPFC during REM sleep and wakefulness. We demonstrate that the resting states of High recallers and Low recallers differ during sleep and wakefulness. It coheres with previous ERP results and confirms that a high/low DRF is associated with a specific functional organization of the brain. These results support the forebrain 'dream-on' hypothesis and suggest that TPJ and MPFC are not only involved in dream recall during wakefulness but also have a role in dreaming during sleep (production and/or encoding). Increased activity in the TPJ and MPFC might promote the mental imagery and/or memory encoding of dreams. Notably, increased activity in TPJ might facilitate attention orienting toward external stimuli and promote intrasleep wakefulness, facilitating the encoding of the dreams in memory.

  19. Active Control of Liner Impedance by Varying Perforate Orifice Geometry

    NASA Technical Reports Server (NTRS)

    Ahuji, K. K.; Gaeta, R. J., Jr.

    2000-01-01

    The present work explored the feasibility of controlling the acoustic impedance of a resonant type acoustic liner. This was accomplished by translating one perforate over another of the same porosity creating a totally new perforate that had an intermediate porosity. This type of adjustable perforate created a variable orifice perforate whose orifices were non-circular. The key objective of the present study was to quantify, the degree of attenuation control that can be achieved by applying such a concept to the buried septum in a two-degree-of-freedom (2DOF) acoustic liner. An additional objective was to examine the adequacy of the existing impedance models to explain the behavior of the unique orifice shapes that result from the proposed silding perforate concept. Different orifice shapes with equivalent area were also examined to determine if highly non-circular orifices had a significant impact on the impedance.

  20. Reduced risk of breast cancer associated with recreational physical activity varies by HER2 status

    PubMed Central

    Ma, Huiyan; Xu, Xinxin; Ursin, Giske; Simon, Michael S; Marchbanks, Polly A; Malone, Kathleen E; Lu, Yani; McDonald, Jill A; Folger, Suzanne G; Weiss, Linda K; Sullivan-Halley, Jane; Deapen, Dennis M; Press, Michael F; Bernstein, Leslie

    2015-01-01

    Convincing epidemiologic evidence indicates that physical activity is inversely associated with breast cancer risk. Whether this association varies by the tumor protein expression status of the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), or p53 is unclear. We evaluated the effects of recreational physical activity on risk of invasive breast cancer classified by the four biomarkers, fitting multivariable unconditional logistic regression models to data from 1195 case and 2012 control participants in the population-based Women’s Contraceptive and Reproductive Experiences Study. Self-reported recreational physical activity at different life periods was measured as average annual metabolic equivalents of energy expenditure [MET]-hours per week. Our biomarker-specific analyses showed that lifetime recreational physical activity was negatively associated with the risks of ER-positive (ER+) and of HER2-negative (HER2−) subtypes (both Ptrend ≤ 0.04), but not with other subtypes (all Ptrend > 0.10). Analyses using combinations of biomarkers indicated that risk of invasive breast cancer varied only by HER2 status. Risk of HER2–breast cancer decreased with increasing number of MET-hours of recreational physical activity in each specific life period examined, although some trend tests were only marginally statistically significant (all Ptrend ≤ 0.06). The test for homogeneity of trends (HER2– vs. HER2+ ) reached statistical significance only when evaluating physical activity during the first 10 years after menarche (Phomogeneity = 0.03). Our data suggest that physical activity reduces risk of invasive breast cancers that lack HER2 overexpression, increasing our understanding of the biological mechanisms by which physical activity acts. PMID:25924995

  1. Reduced risk of breast cancer associated with recreational physical activity varies by HER2 status.

    PubMed

    Ma, Huiyan; Xu, Xinxin; Ursin, Giske; Simon, Michael S; Marchbanks, Polly A; Malone, Kathleen E; Lu, Yani; McDonald, Jill A; Folger, Suzanne G; Weiss, Linda K; Sullivan-Halley, Jane; Deapen, Dennis M; Press, Michael F; Bernstein, Leslie

    2015-07-01

    Convincing epidemiologic evidence indicates that physical activity is inversely associated with breast cancer risk. Whether this association varies by the tumor protein expression status of the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), or p53 is unclear. We evaluated the effects of recreational physical activity on risk of invasive breast cancer classified by the four biomarkers, fitting multivariable unconditional logistic regression models to data from 1195 case and 2012 control participants in the population-based Women's Contraceptive and Reproductive Experiences Study. Self-reported recreational physical activity at different life periods was measured as average annual metabolic equivalents of energy expenditure [MET]-hours per week. Our biomarker-specific analyses showed that lifetime recreational physical activity was negatively associated with the risks of ER-positive (ER+) and of HER2-negative (HER2-) subtypes (both Ptrend  ≤ 0.04), but not with other subtypes (all Ptrend  > 0.10). Analyses using combinations of biomarkers indicated that risk of invasive breast cancer varied only by HER2 status. Risk of HER2-breast cancer decreased with increasing number of MET-hours of recreational physical activity in each specific life period examined, although some trend tests were only marginally statistically significant (all Ptrend  ≤ 0.06). The test for homogeneity of trends (HER2- vs. HER2+ ) reached statistical significance only when evaluating physical activity during the first 10 years after menarche (Phomogeneity  = 0.03). Our data suggest that physical activity reduces risk of invasive breast cancers that lack HER2 overexpression, increasing our understanding of the biological mechanisms by which physical activity acts.

  2. The Prognostic Significance of Resting Regional Left Ventricular Function in Patients With Varying Degrees of Myocardial Ischemia

    PubMed Central

    Kilcullen, Niamh M.; Uthamalingam, Shanmugan; Gurm, Gagandeep S; Gregory, Shawn A.; Picard, Michael H.

    2013-01-01

    Background Our aim was to determine whether regional left ventricular (LV) function on a resting transthoracic echo (TTE) provides prognostic information in patients with varying degrees of ischemia on myocardial perfusion imaging. Methods Between 2004 - 2009, we identified 503 patients (mean age 69 (SD 11); 79% male) with reversible ischemia on a myocardial SPECT scan who had a TTE within 30 days. We evaluated the rate of subsequent revascularization and death for all patients. Results Following the SPECT scan and TTE, 246/503(49%) patients underwent revascularization, 64/503 (13%) patients died, 369 (73%) patients had a normal left ventricular ejection fraction (LVEF), 242 (48%) patients had a resting wall motion abnormality (WMA), 21/261 (8%) with no WMA died compared to 43/242 (18%) in patients with a WMA. In patients with a WMA (n = 242) there was no significant difference in mortality when comparing patients with small (< 6 segments) and large (> 6 segments) WMA (P = 0.44). In patients with moderate/severe ischemia, the presence of a resting WMA was associated with a higher mortality rate (18% v 7%; P = 0.005). In a multivariable model, LVEF (< 50%) was associated with a hazard ratio of 2.2 (P = 0.002, 95% CI 1.34 - 3.68) however, WMA and number of abnormal segments did not reach statistical significance. Conclusion A resting wall motion abnormality in patients with moderate/severe ischemia is associated with a higher mortality compared to patients with mild ischemia on myocardial perfusion imaging. Regional left ventricular dysfunction unlike LVEF was not an independent predictor of mortality.

  3. A new iterative linear integral isoconversional method for the determination of the activation energy varying with the conversion degree.

    PubMed

    Cai, Junmeng; Chen, Siyu

    2009-10-01

    The conventional linear integral isoconversional methods may lead to important errors in the determination of the activation energy when the significant variation of the activation energy with the conversion degree occurs. Vyazovkin proposed an advanced nonlinear isoconversional method, which allows the activation energy to be accurately determined [Vyazovkin, J Comput Chem 2001, 22, 178]. However, the use of the Vyazovkin method raises the problem of the time-consuming minimization without derivatives. A new iterative linear integral isoconversional method for the determination of the activation energy as a function of the conversion degree has been proposed, which is capable of providing valid values of the activation energy even if the latter strongly varies with the conversion degree. Also, the new method leads to the correct values of the activation energy in much less time than the Vyazovkin method. The application of the new method is illustrated by processing of theoretically simulated data of a strongly varying activation energy process.

  4. Significant niche overlap between native and exotic Sonneratia mangrove species along a continuum of varying inundation periods

    NASA Astrophysics Data System (ADS)

    Chen, Luzhen; Tam, Nora F. Y.; Wang, Wenqing; Zhang, Yihui; Lin, Guanghui

    2013-01-01

    Sonneratia apetala Buch.-Ham., an introduced mangrove species from Bangladesh, has been popularly used in mangrove afforestation in China for more than 20 years. Whether there is an overlap in niche between this exotic species and native mangrove species is still unknown. The purpose of this study is to evaluate differences in growth and physiological responses to tidal inundation between the exotic S. apetala and its congeneric species in China, Sonneratia caseolaris. A set of tidal tanks was used to simulate different tidal ranges by controlling different inundation periods (0, 2, 4, 6, 8, 10, 12 h). Both the inundation period and species showed significant effects on almost all morphological, growth and physiological parameters measured; however, there were no significant differences between the two species in the responses of these parameters to the inundation period, except for specific leaf area (SLA) and light compensation point (LCP). Significant increases in SLA under the long inundation periods (10, 12 h) for the exotic, but not for the native species, indicate that the exotic one tended to increase its leaf area for assimilation. Thus, the exotic S. apetala seedling exhibited phenotypic plasticity to tidal inundation similar that of the native, S. caseolaris, which suggests that the exotic and native Sonneratia species will occupy a similar niche along the entire tidal range.

  5. Levels of dendritic cell populations and regulatory T cells vary significantly between two commonly used mouse strains.

    PubMed

    Vogelsang, Petra; Hovden, Arnt-Ove; Jonsson, Roland; Appel, Silke

    2009-12-01

    Dendritic cells (DC) are a heterogeneous group of professional antigen-presenting cells (APC) involved in both initiating immune responses and maintaining tolerance. Roughly, DC can be divided into plasmacytoid DC (pDC) and conventional DC (cDC). By controlling regulatory T cells (Treg), DC can influence the outcome of both immunity and autoimmunity. Since the use of mice as in vivo models became a practical tool for researchers studying pathological events in all kind of human diseases, we decided to compare levels of cDC, pDC and Treg in both spleen and blood between two inbred mouse strains. Here we show that two commonly used mouse strains, BALB/c and C57BL/10J mice, have significantly different levels of distinct CD11c(+)/CD4(-)/CD8a(+), CD11c(+)/CD4(+)/CD8a(-) and CD11c(+)/CD4(-)/CD8a(-) cDC populations, pDC and Treg. Therefore, we emphasize the importance of considering the proper model when comparing data sets from different mouse strains.

  6. The Influence of Epoch Length on Physical Activity Patterns Varies by Child's Activity Level

    ERIC Educational Resources Information Center

    Nettlefold, Lindsay; Naylor, P. J.; Warburton, Darren E. R.; Bredin, Shannon S. D.; Race, Douglas; McKay, Heather A.

    2016-01-01

    Purpose: Patterns of physical activity (PA) and sedentary time, including volume of bouted activity, are important health indicators. However, the effect of accelerometer epoch length on measurement of these patterns and associations with health outcomes in children remain unknown. Method: We measured activity patterns in 308 children (52% girls,…

  7. Significantly different coagulation factor activities underlying the variability of 'normal' activated partial thromboplastin time.

    PubMed

    Park, Kyoung-Jin; Kwon, Eui-Hoon; Ma, Youngeun; Park, In-Ae; Kim, Seon-Woo; Kim, Sun-Hee; Kim, Hee-Jin

    2012-01-01

    The activated partial thromboplastin time (aPTT) is a widely used coagulation screening test in routine laboratories. The aPTT level in the control population varies and is reflected by the reference interval. However, there have been no studies to investigate the coagulation status determining the variability of the aPTT. The aim of this study was to investigate the coagulation factor activities underlying the variability of aPTT in the population. The study participants were reference individuals with prothrombin time and aPTT within reference intervals. The aPTT was determined using STA-PTT Automate (Diagnostica Stago, Asnieres, France; local reference interval, 29.1-41.9 s). Those with aPTT within the marginal ranges of reference interval were selected for factor assays. We defined the lower marginal group as the lowest 10 percentile of reference interval (29.1-30.9 s) and the upper marginal group as the highest 10 percentile (38.0-41.9 s). Activities of factor II, V, VIII, IX, X, XI, and XII were determined in both groups. The lower marginal and upper marginal groups consisted of 220 and 209 individuals, respectively. All coagulation factors were significantly higher in the lower marginal than in the upper marginal group (P = 0.0127 for factor II and P < 0.0001 for the others). Multiple logistic regression analyses revealed factor XII and VIII were two strongest contributors determining the aPTT level, whereas factor XI was not significantly different between the groups (P = 0.095). This study firstly demonstrated significantly different coagulation factor activities underlying the variability of aPTT in reference individuals. The results suggested the possibility of disease association or phenotypic contribution of variable coagulation activities in the population.

  8. Quantifying Time-Varying Multiunit Neural Activity Using Entropy-Based Measures

    PubMed Central

    Choi, Young-Seok; Koenig, Matthew A.; Jia, Xiaofeng

    2011-01-01

    Modern microelectrode arrays make it possible to simultaneously record population neural activity. However, methods to analyze multiunit activity (MUA), which reflects the aggregate spiking activity of a population of neurons, have remained underdeveloped in comparison to those used for studying single unit activity (SUA). In scenarios where SUA is hard to record and maintain or is not representative of brain’s response, MUA is informative in deciphering the brain’s complex time-varying response to stimuli or to clinical insults. Here, we present two quantitative methods of analysis of the time-varying dynamics of MUA without spike detection. These methods are based on the multiresolution discrete wavelet transform (DWT) of an envelope of MUA (eMUA) followed by information theoretic measures: multiresolution entropy (MRE) and the multiresolution Kullback–Leibler distance (MRKLD).We test the proposed quantifiers on both simulated and experimental MUA recorded from rodent cortex in an experimental model of global hypoxic–ischemic brain injury. First, our results validate the use of the eMUA as an alternative to detecting and analyzing transient and complex spike activity. Second, the MRE and MRKLD are shown to respond to dynamic changes due to the brain’s response to global injury and to identify the transient changes in the MUA. PMID:20460201

  9. AST: Activity-Security-Trust driven modeling of time varying networks

    PubMed Central

    Wang, Jian; Xu, Jiake; Liu, Yanheng; Deng, Weiwen

    2016-01-01

    Network modeling is a flexible mathematical structure that enables to identify statistical regularities and structural principles hidden in complex systems. The majority of recent driving forces in modeling complex networks are originated from activity, in which an activity potential of a time invariant function is introduced to identify agents’ interactions and to construct an activity-driven model. However, the new-emerging network evolutions are already deeply coupled with not only the explicit factors (e.g. activity) but also the implicit considerations (e.g. security and trust), so more intrinsic driving forces behind should be integrated into the modeling of time varying networks. The agents undoubtedly seek to build a time-dependent trade-off among activity, security, and trust in generating a new connection to another. Thus, we reasonably propose the Activity-Security-Trust (AST) driven model through synthetically considering the explicit and implicit driving forces (e.g. activity, security, and trust) underlying the decision process. AST-driven model facilitates to more accurately capture highly dynamical network behaviors and figure out the complex evolution process, allowing a profound understanding of the effects of security and trust in driving network evolution, and improving the biases induced by only involving activity representations in analyzing the dynamical processes. PMID:26888717

  10. AST: Activity-Security-Trust driven modeling of time varying networks.

    PubMed

    Wang, Jian; Xu, Jiake; Liu, Yanheng; Deng, Weiwen

    2016-02-18

    Network modeling is a flexible mathematical structure that enables to identify statistical regularities and structural principles hidden in complex systems. The majority of recent driving forces in modeling complex networks are originated from activity, in which an activity potential of a time invariant function is introduced to identify agents' interactions and to construct an activity-driven model. However, the new-emerging network evolutions are already deeply coupled with not only the explicit factors (e.g. activity) but also the implicit considerations (e.g. security and trust), so more intrinsic driving forces behind should be integrated into the modeling of time varying networks. The agents undoubtedly seek to build a time-dependent trade-off among activity, security, and trust in generating a new connection to another. Thus, we reasonably propose the Activity-Security-Trust (AST) driven model through synthetically considering the explicit and implicit driving forces (e.g. activity, security, and trust) underlying the decision process. AST-driven model facilitates to more accurately capture highly dynamical network behaviors and figure out the complex evolution process, allowing a profound understanding of the effects of security and trust in driving network evolution, and improving the biases induced by only involving activity representations in analyzing the dynamical processes.

  11. AST: Activity-Security-Trust driven modeling of time varying networks

    NASA Astrophysics Data System (ADS)

    Wang, Jian; Xu, Jiake; Liu, Yanheng; Deng, Weiwen

    2016-02-01

    Network modeling is a flexible mathematical structure that enables to identify statistical regularities and structural principles hidden in complex systems. The majority of recent driving forces in modeling complex networks are originated from activity, in which an activity potential of a time invariant function is introduced to identify agents’ interactions and to construct an activity-driven model. However, the new-emerging network evolutions are already deeply coupled with not only the explicit factors (e.g. activity) but also the implicit considerations (e.g. security and trust), so more intrinsic driving forces behind should be integrated into the modeling of time varying networks. The agents undoubtedly seek to build a time-dependent trade-off among activity, security, and trust in generating a new connection to another. Thus, we reasonably propose the Activity-Security-Trust (AST) driven model through synthetically considering the explicit and implicit driving forces (e.g. activity, security, and trust) underlying the decision process. AST-driven model facilitates to more accurately capture highly dynamical network behaviors and figure out the complex evolution process, allowing a profound understanding of the effects of security and trust in driving network evolution, and improving the biases induced by only involving activity representations in analyzing the dynamical processes.

  12. Physical activity, subjective sleep quality and time in bed do not vary by moon phase in German adolescents.

    PubMed

    Smith, Maia P; Standl, Marie; Schulz, Holger; Heinrich, Joachim

    2016-12-08

    Lunar periodicity in human biology and behaviour, particularly sleep, has been reported. However, estimated relationships vary in direction (more or less sleep with full moon) if they exist at all, and studies tend to be so small that there is potential for confounding by weekly or monthly cycles. Lunar variation in physical activity has been posited as a driver of this relationship, but is likewise not well studied. We explore the association between lunar cycle, sleep and physical activity in a population-based sample of 1411 Germans age 14-17 years (46% male). Physical activity (daily minutes moderate-to-vigorous activity) was objectively assessed by accelerometry for a total of 8832 days between 2011 and 2014. At the same time, time in bed (h) and subjective sleep quality (1-6) were diaried each morning. In models corrected for confounding, we found that lunar phase was not significantly associated with physical activity, subjective sleep quality or time in bed in either sex, regardless of season. Observed relationships varied randomly in direction between models, suggesting artefact. Thus, this large, objectively-measured and well-controlled population of adolescents displayed no lunar periodicity in objective physical activity, subjective sleep quality or time in bed.

  13. Nonlinearly Activated Neural Network for Solving Time-Varying Complex Sylvester Equation.

    PubMed

    Li, Shuai; Li, Yangming

    2013-10-28

    The Sylvester equation is often encountered in mathematics and control theory. For the general time-invariant Sylvester equation problem, which is defined in the domain of complex numbers, the Bartels-Stewart algorithm and its extensions are effective and widely used with an O(n³) time complexity. When applied to solving the time-varying Sylvester equation, the computation burden increases intensively with the decrease of sampling period and cannot satisfy continuous realtime calculation requirements. For the special case of the general Sylvester equation problem defined in the domain of real numbers, gradient-based recurrent neural networks are able to solve the time-varying Sylvester equation in real time, but there always exists an estimation error while a recently proposed recurrent neural network by Zhang et al [this type of neural network is called Zhang neural network (ZNN)] converges to the solution ideally. The advancements in complex-valued neural networks cast light to extend the existing real-valued ZNN for solving the time-varying real-valued Sylvester equation to its counterpart in the domain of complex numbers. In this paper, a complex-valued ZNN for solving the complex-valued Sylvester equation problem is investigated and the global convergence of the neural network is proven with the proposed nonlinear complex-valued activation functions. Moreover, a special type of activation function with a core function, called sign-bi-power function, is proven to enable the ZNN to converge in finite time, which further enhances its advantage in online processing. In this case, the upper bound of the convergence time is also derived analytically. Simulations are performed to evaluate and compare the performance of the neural network with different parameters and activation functions. Both theoretical analysis and numerical simulations validate the effectiveness of the proposed method.

  14. Nonlinear parametrically excited vibration and active control of gear pair system with time-varying characteristic

    NASA Astrophysics Data System (ADS)

    Liu, Shuang; Wang, Jin-Jin; Liu, Jin-Jie; Li, Ya-Qian

    2015-10-01

    In the present work, we investigate the nonlinear parametrically excited vibration and active control of a gear pair system involving backlash, time-varying meshing stiffness and static transmission error. Firstly, a gear pair model is established in a strongly nonlinear form, and its nonlinear vibration characteristics are systematically investigated through different approaches. Several complicated phenomena such as period doubling bifurcation, anti period doubling bifurcation and chaos can be observed under the internal parametric excitation. Then, an active compensation controller is designed to suppress the vibration, including the chaos. Finally, the effectiveness of the proposed controller is verified numerically. Project supported by the National Natural Science Foundation of China (Grant No. 61104040), the Natural Science Foundation of Hebei Province, China (Grant No. E2012203090), and the University Innovation Team of Hebei Province Leading Talent Cultivation Project, China (Grant No. LJRC013).

  15. Does the Effect of a Physical Activity Behavioral Intervention Vary by Characteristics of People with Multiple Sclerosis?

    PubMed Central

    Dlugonski, Deirdre; Pilutti, Lara A.; Klaren, Rachel E.

    2015-01-01

    Background: Behavioral interventions have significantly increased physical activity in people with multiple sclerosis (MS). Nevertheless, there has been interindividual variability in the pattern and magnitude of change. This study documented the efficacy and variability of a behavioral intervention for changing physical activity and examined the possibility that efficacy varied by the characteristics of individuals with MS. Methods: Eighty-two people with MS were randomly assigned to one of two conditions: behavioral intervention (n = 41) or waitlist control (n = 41). We collected information before the study on MS type, disability status, weight status based on body-mass index, and current medications. Furthermore, all participants completed the Godin Leisure Time Exercise Questionnaire and the abbreviated International Physical Activity Questionnaire and wore an accelerometer for 1 week to measure minutes of moderate-to-vigorous physical activity before and after the 6-month intervention period. Results: Analysis of covariance (ANCOVA) indicated that participants in the behavioral intervention had significantly higher levels of physical activity than control participants after the 6-month period (P < .001). There was substantial interindividual variability in the magnitude of change, and ANCOVA indicated that MS type (relapsing vs. progressive) (P < .01), disability status (mild vs. moderate) (P < .01), and weight status (normal weight vs. overweight/obese) (P < .05) moderated the efficacy of the behavioral intervention. Conclusions: The behavioral intervention was associated with improvements in physical activity, particularly for those with mild disability, relapsing-remitting MS, or normal weight status. PMID:25892976

  16. Beyond Statistical Significance: Implications of Network Structure on Neuronal Activity

    PubMed Central

    Vlachos, Ioannis; Aertsen, Ad; Kumar, Arvind

    2012-01-01

    It is a common and good practice in experimental sciences to assess the statistical significance of measured outcomes. For this, the probability of obtaining the actual results is estimated under the assumption of an appropriately chosen null-hypothesis. If this probability is smaller than some threshold, the results are deemed statistically significant and the researchers are content in having revealed, within their own experimental domain, a “surprising” anomaly, possibly indicative of a hitherto hidden fragment of the underlying “ground-truth”. What is often neglected, though, is the actual importance of these experimental outcomes for understanding the system under investigation. We illustrate this point by giving practical and intuitive examples from the field of systems neuroscience. Specifically, we use the notion of embeddedness to quantify the impact of a neuron's activity on its downstream neurons in the network. We show that the network response strongly depends on the embeddedness of stimulated neurons and that embeddedness is a key determinant of the importance of neuronal activity on local and downstream processing. We extrapolate these results to other fields in which networks are used as a theoretical framework. PMID:22291581

  17. Flatness-based active disturbance rejection control for linear systems with unknown time-varying coefficients

    NASA Astrophysics Data System (ADS)

    Huang, Congzhi; Sira-Ramírez, Hebertt

    2015-12-01

    A flatness-based active disturbance rejection control approach is proposed to deal with the linear systems with unknown time-varying coefficients and external disturbances. By selecting appropriate nominal values for the parameters of the system, all the deviation between the nominal and actual dynamics of the controlled process, as well as all the external disturbances can be viewed as a total disturbance. Based on the accurately estimated total disturbance with the aid of the proposed extended state observer, a linear proportional derivative feedback control law taking into account the derivatives of the desired output is designed to eliminate the effect of the total disturbance on the system performance. Finally, the load frequency control problem of a single-area power system with non-reheated unit is employed as an illustrative example to demonstrate the effectiveness of the proposed approach.

  18. Controlling the antibacterial activity of CuSn thin films by varying the contents of Sn

    NASA Astrophysics Data System (ADS)

    Kang, Yujin; Park, Juyun; Kim, Dong-Woo; Kim, Hakjun; Kang, Yong-Cheol

    2016-12-01

    We investigated antibacterial activity of CuSn thin films against Gram positive Staphylococcus aureus (S. aureus). CuSn thin films with different Cu to Sn ratios were deposited on Si(100) by radio frequency (RF) magnetron sputtering method using Cu and Sn metal anodes. The film thickness was fixed at 200 nm by varying the sputtering time and RF power on the metal targets. The antibacterial test was conducted in various conditions such as different contact times and Cu to Sn ratios in the CuSn films. The antibacterial activities of CuSn thin films increased as the ratio of Cu and the contact time between the film and bacteria suspension increased execpt in the case of CuSn-83. The oxidation states of Cu and Sn and the chemical composition of CuSn thin films before and after the antibacterial test were investigated by X-ray photoelectron spectroscopy (XPS). When the contact time was fixed, the Cu species was further oxidized as the RF power on Cu target increased. The intensity of Sn 3d decreased with increasing Cu ratio. When the sample was fixed, the peak intensity of Sn 3d decreased as the contact time increased due to the permeation of Sn into the cell.

  19. Effects of activated sludge on the degradation of chlorate in soils under varying environmental conditions.

    PubMed

    Jiang, Chunxiao; Li, Huashou; Lin, Chuxia

    2009-03-15

    Incubation experiments were conducted to examine the effects of activated sludge on degradation of chlorate in soils. The results show that application of activated sludge could significantly promote the decomposition of soil chlorate though the degradation rate of chlorate did not necessarily increase with increasing application rate of the sludge. The effectiveness of activated sludge on soil chlorate degradation was significantly affected by temperature, moisture content and pH. There is a tendency that the rate of chlorate decomposition increased with increasing temperature and moisture content until optimal values of temperature and moisture content were reached. This can be attributed to the enhanced activity of chlorate-reducing microorganisms in hot and more reducing soil conditions. Soil pH also had important controls on the decomposition of chlorate. The experimental results demonstrate that neutral pH more favoured the degradation of soil chlorate, compared to either acidic or alkaline pH. While soil organic matter content could affect chlorate decomposition, its impact on the effectiveness of activated sludge on chlorate degradation was minor. This study has implications for developing cost-effective techniques for remediating chlorate-contaminated soils, particularly in the longan-producing countries.

  20. PCB concentrations and activity of sea lamprey Petromyzon marinus vary by sex

    USGS Publications Warehouse

    Madenjian, Charles P.; Johnson, Nicholas S.; Binder, Thomas R.; Rediske, Richard R.; O'Keefe, James P.

    2013-01-01

    We determined the polychlorinated biphenyl (PCB) concentrations of 40 male and 40 female adult sea lampreys Petromyzon marinus captured in the Cheboygan River, a tributary to Lake Huron, during May 2011. In addition, we performed a laboratory experiment using passive integrated transponder tags to determine whether male adult sea lampreys were more active than female adult sea lampreys. Sex had a significant effect on PCB concentration, and PCB concentration at a given level of sea lamprey condition was approximately 25 % greater in males than in females. Adjusting for the difference in condition between the sexes, males averaged a 17 % greater PCB concentration compared with females. Results from the laboratory experiment indicated that males were significantly more active than females. The observed sex difference in PCB concentrations was not due to female sea lampreys releasing eggs at spawning because the sea lamprey is semelparous, and we caught the sea lampreys before spawning. Rather, we attributed the sex difference in PCB concentrations to a greater rate of energy expenditure in males compared with females. We proposed that this greater rate of energy expenditure was likely due to greater activity. Our laboratory experiment results supported this hypothesis. A greater resting metabolic rate may also have contributed to a greater rate of energy expenditure. Our findings should eventually be applicable toward improving control of sea lamprey, a pest responsible for considerable damage to fisheries in lakes where it is not native.

  1. Varying responses of vegetation activity to climate changes on the Tibetan Plateau grassland.

    PubMed

    Cong, Nan; Shen, Miaogen; Yang, Wei; Yang, Zhiyong; Zhang, Gengxin; Piao, Shilong

    2017-02-28

    Vegetation activity on the Tibetan Plateau grassland has been substantially enhanced as a result of climate change, as revealed by satellite observations of vegetation greenness (i.e., the normalized difference vegetation index, NDVI). However, little is known about the temporal variations in the relationships between NDVI and temperature and precipitation, and understanding this is essential for predicting how future climate change would affect vegetation activity. Using NDVI data and meteorological records from 1982 to 2011, we found that the inter-annual partial correlation coefficient between growing season (May-September) NDVI and temperature (RNDVI-T) in a 15-year moving window for alpine meadow showed little change, likely caused by the increasing RNDVI-T in spring (May-June) and autumn (September) and decreasing RNDVI-T in summer (July-August). Growing season RNDVI-T for alpine steppe increased slightly, mainly due to increasing RNDVI-T in spring and autumn. The partial correlation coefficient between growing season NDVI and precipitation (RNDVI-P) for alpine meadow increased slightly, mainly in spring and summer, and RNDVI-P for alpine steppe increased, mainly in spring. Moreover, RNDVI-T for the growing season was significantly higher in those 15-year windows with more precipitation for alpine steppe. RNDVI-P for the growing season was significantly higher in those 15-year windows with higher temperature, and this tendency was stronger for alpine meadow than for alpine steppe. These results indicate that the impact of warming on vegetation activity of Tibetan Plateau grassland is more positive (or less negative) during periods with more precipitation and that the impact of increasing precipitation is more positive (or less negative) during periods with higher temperature. Such positive effects of the interactions between temperature and precipitation indicate that the projected warmer and wetter future climate will enhance vegetation activity of Tibetan

  2. Varying responses of vegetation activity to climate changes on the Tibetan Plateau grassland

    NASA Astrophysics Data System (ADS)

    Cong, Nan; Shen, Miaogen; Yang, Wei; Yang, Zhiyong; Zhang, Gengxin; Piao, Shilong

    2017-02-01

    Vegetation activity on the Tibetan Plateau grassland has been substantially enhanced as a result of climate change, as revealed by satellite observations of vegetation greenness (i.e., the normalized difference vegetation index, NDVI). However, little is known about the temporal variations in the relationships between NDVI and temperature and precipitation, and understanding this is essential for predicting how future climate change would affect vegetation activity. Using NDVI data and meteorological records from 1982 to 2011, we found that the inter-annual partial correlation coefficient between growing season (May-September) NDVI and temperature (RNDVI-T) in a 15-year moving window for alpine meadow showed little change, likely caused by the increasing RNDVI-T in spring (May-June) and autumn (September) and decreasing RNDVI-T in summer (July-August). Growing season RNDVI-T for alpine steppe increased slightly, mainly due to increasing RNDVI-T in spring and autumn. The partial correlation coefficient between growing season NDVI and precipitation (RNDVI-P) for alpine meadow increased slightly, mainly in spring and summer, and RNDVI-P for alpine steppe increased, mainly in spring. Moreover, RNDVI-T for the growing season was significantly higher in those 15-year windows with more precipitation for alpine steppe. RNDVI-P for the growing season was significantly higher in those 15-year windows with higher temperature, and this tendency was stronger for alpine meadow than for alpine steppe. These results indicate that the impact of warming on vegetation activity of Tibetan Plateau grassland is more positive (or less negative) during periods with more precipitation and that the impact of increasing precipitation is more positive (or less negative) during periods with higher temperature. Such positive effects of the interactions between temperature and precipitation indicate that the projected warmer and wetter future climate will enhance vegetation activity of Tibetan

  3. The Significance of Ras Activity in Pancreatic Cancer Initiation

    PubMed Central

    Logsdon, Craig D.; Lu, Weiqin

    2016-01-01

    The genetic landscape of pancreatic cancer shows nearly ubiquitous mutations of K-RAS. However, oncogenic K-Rasmt alone is not sufficient to lead to pancreatic ductal adenocarcinoma (PDAC) in either human or in genetically modified adult mouse models. Many stimulants, such as high fat diet, CCK, LPS, PGE2 and others, have physiological effects at low concentrations that are mediated in part through modest increases in K-Ras activity. However, at high concentrations, they induce inflammation that, in the presence of oncogenic K-Ras expression, substantially accelerates PDAC formation. The mechanism involves increased activity of oncogenic K-Rasmt. Unlike what has been proposed in the standard paradigm for the role of Ras in oncogenesis, oncogenic K-Rasmt is now known to not be constitutively active. Rather, it can be activated by standard mechanisms similar to wild-type K-Ras, but its activity is sustained for a prolonged period. Furthermore, if the level of K-Ras activity exceeds a threshold at which it begins to generate its own activators, then a feed-forward loop is formed between K-Ras activity and inflammation and pathological processes including oncogenesis are initiated. Oncogenic K-Rasmt activation, a key event in PDAC initiation and development, is subject to complex regulatory mechanisms. Reagents which inhibit inflammation, such as the Cox2 inhibitor celecoxib, block the feed-forward loop and prevent induction of PDAC in models with endogenous oncogenic K-Rasmt. Increased understanding of the role of activating and inhibitory mechanisms on oncogenic K-Rasmt activity is of paramount importance for the development of preventive and therapeutic strategies to fight against this lethal disease. PMID:26929740

  4. Adaptive significance of right hemisphere activation in aphasic language comprehension

    PubMed Central

    Meltzer, Jed A.; Wagage, Suraji; Ryder, Jennifer; Solomon, Beth; Braun, Allen R.

    2013-01-01

    Aphasic patients often exhibit increased right hemisphere activity during language tasks. This may represent takeover of function by regions homologous to the left-hemisphere language networks, maladaptive interference, or adaptation of alternate compensatory strategies. To distinguish between these accounts, we tested language comprehension in 25 aphasic patients using an online sentence-picture matching paradigm while measuring brain activation with MEG. Linguistic conditions included semantically irreversible (“The boy is eating the apple”) and reversible (“The boy is pushing the girl”) sentences at three levels of syntactic complexity. As expected, patients performed well above chance on irreversible sentences, and at chance on reversible sentences of high complexity. Comprehension of reversible non-complex sentences ranged from nearly perfect to chance, and was highly correlated with offline measures of language comprehension. Lesion analysis revealed that comprehension deficits for reversible sentences were predicted by damage to the left temporal lobe. Although aphasic patients activated homologous areas in the right temporal lobe, such activation was not correlated with comprehension performance. Rather, patients with better comprehension exhibited increased activity in dorsal fronto-parietal regions. Correlations between performance and dorsal network activity occurred bilaterally during perception of sentences, and in the right hemisphere during a post-sentence memory delay. These results suggest that effortful reprocessing of perceived sentences in short-term memory can support improved comprehension in aphasia, and that strategic recruitment of alternative networks, rather than homologous takeover, may account for some findings of right hemisphere language activation in aphasia. PMID:23566891

  5. Adaptive significance of right hemisphere activation in aphasic language comprehension.

    PubMed

    Meltzer, Jed A; Wagage, Suraji; Ryder, Jennifer; Solomon, Beth; Braun, Allen R

    2013-06-01

    Aphasic patients often exhibit increased right hemisphere activity during language tasks. This may represent takeover of function by regions homologous to the left-hemisphere language networks, maladaptive interference, or adaptation of alternate compensatory strategies. To distinguish between these accounts, we tested language comprehension in 25 aphasic patients using an online sentence-picture matching paradigm while measuring brain activation with MEG. Linguistic conditions included semantically irreversible ("The boy is eating the apple") and reversible ("The boy is pushing the girl") sentences at three levels of syntactic complexity. As expected, patients performed well above chance on irreversible sentences, and at chance on reversible sentences of high complexity. Comprehension of reversible non-complex sentences ranged from nearly perfect to chance, and was highly correlated with offline measures of language comprehension. Lesion analysis revealed that comprehension deficits for reversible sentences were predicted by damage to the left temporal lobe. Although aphasic patients activated homologous areas in the right temporal lobe, such activation was not correlated with comprehension performance. Rather, patients with better comprehension exhibited increased activity in dorsal fronto-parietal regions. Correlations between performance and dorsal network activity occurred bilaterally during perception of sentences, and in the right hemisphere during a post-sentence memory delay. These results suggest that effortful reprocessing of perceived sentences in short-term memory can support improved comprehension in aphasia, and that strategic recruitment of alternative networks, rather than homologous takeover, may account for some findings of right hemisphere language activation in aphasia.

  6. Individual differences in oscillatory brain activity in response to varying attentional demands during a word recall and oculomotor dual task

    PubMed Central

    Kwon, Gusang; Lim, Sanghyun; Kim, Min-Young; Kwon, Hyukchan; Lee, Yong-Ho; Kim, Kiwoong; Lee, Eun-Ju; Suh, Minah

    2015-01-01

    Every day, we face situations that involve multi-tasking. How our brain utilizes cortical resources during multi-tasking is one of many interesting research topics. In this study, we tested whether a dual-task can be differentiated in the neural and behavioral responses of healthy subjects with varying degree of working memory capacity (WMC). We combined word recall and oculomotor tasks because they incorporate common neural networks including the fronto-parietal (FP) network. Three different types of oculomotor tasks (eye fixation, Fix-EM; predictive and random smooth pursuit eye movement, P-SPEM and R-SPEM) were combined with two memory load levels (low-load: five words, high-load: 10 words) for a word recall task. Each of those dual-task combinations was supposed to create varying cognitive loads on the FP network. We hypothesize that each dual-task requires different cognitive strategies for allocating the brain’s limited cortical resources and affects brain oscillation of the FP network. In addition, we hypothesized that groups with different WMC will show differential neural and behavioral responses. We measured oscillatory brain activity with simultaneous MEG and EEG recordings and behavioral performance by word recall. Prominent frontal midline (FM) theta (4–6 Hz) synchronization emerged in the EEG of the high-WMC group experiencing R-SPEM with high-load conditions during the early phase of the word maintenance period. Conversely, significant parietal upper alpha (10–12 Hz) desynchronization was observed in the EEG and MEG of the low-WMC group experiencing P-SPEM under high-load conditions during the same period. Different brain oscillatory patterns seem to depend on each individual’s WMC and varying attentional demands from different dual-task combinations. These findings suggest that specific brain oscillations may reflect different strategies for allocating cortical resources during combined word recall and oculomotor dual-tasks. PMID:26175681

  7. Rural Enterprises, Incorporated report of significant activities and accomplishments

    NASA Technical Reports Server (NTRS)

    1985-01-01

    The ongoing activities of Rural Enterprises, Inc. are presented. The function of Rural Enterprises is to bring innovation from its rudimentary conceptual stages to useful and productive ends by means of cooperation with government, business, and educational institutions.

  8. EMG Activity of Selected Trunk and Hip Muscles During a Squat Lift: Effect of Varying the Lumbar Posture

    DTIC Science & Technology

    1990-01-01

    DIXC hLE O.. 1990 Thesis/i " EMG Activity of Selected Trunk and Hip Muscles During a Squat Lift: Effect of Varying the Lumbar Posture N Jim Vakos...1990 01-1’ ABSTRACT OF THESIS EMG ACTIVITY OF SELECTED TRUNK AND HIP MUSCLES DURING A SQUAT LIFT: EFFECT OF VARYING THE LUMBAR POSTURE - The...electromyographic ( EMG ) activity of selected hip and trunk muscles was recorded during a squat lift and the effects of two different lumbar spine postures were

  9. Routine Activities and Victimization at School: The Significance of Gender

    ERIC Educational Resources Information Center

    Popp, Ann Marie; Peguero, Anthony A.

    2011-01-01

    Routine activities theory has not fully considered the role of gender in shaping victimization and yet, the research literature clearly demonstrates that gender is associated with an individual's risk of victimization. In addition to the pervasive effect of gender on victimization, gender shapes an individual's daily routines and thus may create a…

  10. On the validity versus utility of activity landscapes: are all activity cliffs statistically significant?

    PubMed Central

    2014-01-01

    Background Most work on the topic of activity landscapes has focused on their quantitative description and visual representation, with the aim of aiding navigation of SAR. Recent developments have addressed applications such as quantifying the proportion of activity cliffs, investigating the predictive abilities of activity landscape methods and so on. However, all these publications have worked under the assumption that the activity landscape models are “real” (i.e., statistically significant). Results The current study addresses for the first time, in a quantitative manner, the significance of a landscape or individual cliffs in the landscape. In particular, we question whether the activity landscape derived from observed (experimental) activity data is different from a randomly generated landscape. To address this we used the SALI measure with six different data sets tested against one or more molecular targets. We also assessed the significance of the landscapes for single and multiple representations. Conclusions We find that non-random landscapes are data set and molecular representation dependent. For the data sets and representations used in this work, our results suggest that not all representations lead to non-random landscapes. This indicates that not all molecular representations should be used to a) interpret the SAR and b) combined to generate consensus models. Our results suggest that significance testing of activity landscape models and in particular, activity cliffs, is key, prior to the use of such models. PMID:24694189

  11. Finding Significant Correlates of Conscious Activity in Rhythmic EEG

    NASA Astrophysics Data System (ADS)

    Durka, Piotr J.

    2005-12-01

    One of the important issues in designing an EEG-based brain-computer interface is an exact delineation of the rhythms, related to the intended or performed action. Traditionally, related bands were found by trial and error procedures seeking maximum reactivity. Even then, large values of ERD/ERS did not imply the statistical significance of the results. This paper presents complete methodology, allowing for a high-resolution presentation of the whole time-frequency picture of event-related changes in the energy density of signals, revealing the microstructure of rhythms, and determination of the time-frequency regions of energy changes, which are related to the intentions in a statistically significant way.

  12. Prognotic significance of pretreatment proliferative activity in adult acute leukemia.

    PubMed

    Hart, J S; George, S L; Frei, E; Bodey, G P; Nickerson, R C; Freireich, E J

    1977-04-01

    A statistical analysis of the prognostic significance of eight pretreatment variables was undertaken for 71 previously untreated adult patients with acute leukemia seen at M.D. Anderson Hospital over a 5 1/2-year period. None of the patients had received any prior therapy. Nearly all of the patients (68 of the 71) were treated with 4- or 5-day courses of arabinosyl-cytosine alone or in combination with cyclophosphamide, vincristine (oncovin) and prednisone (COAP). The pretreatment variables studied were age at diagnosis, the percent labeling index of the bone marrow leukemic cells, diagnosis, the highest temperature prior to start of treatment, the marrow clot section cellularity and smear differential percent of blasts, percent absolute marrow leukemic cell infiltrate and absolute number of blasts X 10(3)/mm3 in the peripheral blood. Fifty-one patients had acute myeloblastic leukemia (AML) and 20 patients had acute lymphoblastic leukemia (ALL). Using a statistical regression model approach, the only variables found to be of significant prognostic importance with respect to the probability of complete remission for AML patients were the pretreatment percent labeling index, the age of the patient and the highest temperature prior to start of treatment. Unlike AML, the initial percent labeling index did not appear to be of prognostic significance for ALL patients. AML patients with high labeling indices (larger than or equal to 9%) and young patients in general (especially those less than 40 years old) had the best remission rates. With respect to the length of complete remission and survival for all patients, the only important variables were the pretreatment percent labeling index and the age of the patient, respectively. Once in complete remission, an initially high labeling index was an unfavorable sign with respect to length of remission, regardless of the patient's diagnosis. The results of this study are supportive of studies in experimental systems

  13. Use of a lag differential reinforcement contingency to increase varied selections of classroom activities.

    PubMed

    Cammilleri, Anthony P; Hanley, Gregory P

    2005-01-01

    The present study evaluated the effects of a lag differential reinforcement contingency on 2 students' activity selections using reversal designs. Results showed that the lag contingency was responsible for promoting increased novel selections, engagement in diverse activities, and greater progress with respect to programmed academic activities.

  14. Use of a Lag Differential Reinforcement Contingency to Increase Varied Selections of Classroom Activities

    ERIC Educational Resources Information Center

    Cammilleri, Anthony P.; Hanley, Gregory P.

    2005-01-01

    The present study evaluated the effects of a lag differential reinforcement contingency on 2 students' activity selections using reversal designs. Results showed that the lag contingency was responsible for promoting increased novel selections, engagement in diverse activities, and greater progress with respect to programmed academic activities.

  15. A Comparison of Attitudes and Exercise Habits of Alumni from Colleges with Varying Degrees of Physical Education Activity Programs.

    ERIC Educational Resources Information Center

    Adams, Thomas M.; Brynteson, Paul

    1992-01-01

    Study compared the exercise attitudes and habits of alumni from four colleges with varying physical education activity (PEA) requirements. Survey results indicated the type of PEA programs offered influenced alumni attitudes toward fitness and exercise behaviors. Students from colleges with higher PEA requirements had more positive exercise…

  16. Biodegradation of an Organophosphate Chemical Warfare Agent Simulant by Activated Sludge with Varying Solid Retention Times

    DTIC Science & Technology

    2013-03-21

    coefficient close to that of VX, which may yield similar sorption kinetics between the two. Walters (2013) found that sorption of malathion to the activated...weapons in the activated sludge or under what conditions this removal is optimal. This study examined the fate of malathion , a surrogate compound for...activated sludge process in wastewater treatment facilities. Results show that a constant influent of malathion will be removed from the effluent

  17. Effect of varying accelerometry criteria on physical activity: the Look AHEAD Study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The importance of physical activity in weight management is widely documented. Although accelerometers offer an objective measure of activity that provide a valuable tool for intervention research, considerations for processing these data need further development. Objective: This study tests the eff...

  18. The magnitudes of hyperpolarization-activated and low-voltage-activated potassium currents co-vary in neurons of the ventral cochlear nucleus.

    PubMed

    Cao, Xiao-Jie; Oertel, Donata

    2011-08-01

    In the ventral cochlear nucleus (VCN), neurons have hyperpolarization-activated conductances, which in some cells are enormous, that contribute to the ability of neurons to convey acoustic information in the timing of their firing by decreasing the input resistance and speeding-up voltage changes. Comparisons of the electrophysiological properties of neurons in the VCN of mutant mice that lack the hyperpolarization-activated cyclic nucleotide-gated channel α subunit 1 (HCN1(-/-)) (Nolan et al. 2003) with wild-type controls (HCN1(+/+)) and with outbred ICR mice reveal that octopus, T stellate, and bushy cells maintain their electrophysiological distinctions in all strains. Hyperpolarization-activated (I(h)) currents were smaller and slower, input resistances were higher, and membrane time constants were longer in HCN1(-/-) than in HCN1(+/+) in octopus, bushy, and T stellate cells. There were significant differences in the average magnitudes of I(h), input resistances, and time constants between HCN1(+/+) and ICR mice, but the resting potentials did not differ between strains. I(h) is opposed by a low-voltage-activated potassium (I(KL)) current in bushy and octopus cells, whose magnitudes varied widely between neuronal types and between strains. The magnitudes of I(h) and I(KL) were correlated across neuronal types and across mouse strains. Furthermore, these currents balanced one another at the resting potential in individual cells. The magnitude of I(h) and I(KL) is linked in bushy and octopus cells and varies not only between HCN1(-/-) and HCN1(+/+) but also between "wild-type" strains of mice, raising the question to what extent the wild-type strains reflect normal mice.

  19. The magnitudes of hyperpolarization-activated and low-voltage-activated potassium currents co-vary in neurons of the ventral cochlear nucleus

    PubMed Central

    Cao, Xiao-Jie

    2011-01-01

    In the ventral cochlear nucleus (VCN), neurons have hyperpolarization-activated conductances, which in some cells are enormous, that contribute to the ability of neurons to convey acoustic information in the timing of their firing by decreasing the input resistance and speeding-up voltage changes. Comparisons of the electrophysiological properties of neurons in the VCN of mutant mice that lack the hyperpolarization-activated cyclic nucleotide-gated channel α subunit 1 (HCN1−/−) (Nolan et al. 2003) with wild-type controls (HCN1+/+) and with outbred ICR mice reveal that octopus, T stellate, and bushy cells maintain their electrophysiological distinctions in all strains. Hyperpolarization-activated (Ih) currents were smaller and slower, input resistances were higher, and membrane time constants were longer in HCN1−/− than in HCN1+/+ in octopus, bushy, and T stellate cells. There were significant differences in the average magnitudes of Ih, input resistances, and time constants between HCN1+/+ and ICR mice, but the resting potentials did not differ between strains. Ih is opposed by a low-voltage-activated potassium (IKL) current in bushy and octopus cells, whose magnitudes varied widely between neuronal types and between strains. The magnitudes of Ih and IKL were correlated across neuronal types and across mouse strains. Furthermore, these currents balanced one another at the resting potential in individual cells. The magnitude of Ih and IKL is linked in bushy and octopus cells and varies not only between HCN1−/− and HCN1+/+ but also between “wild-type” strains of mice, raising the question to what extent the wild-type strains reflect normal mice. PMID:21562186

  20. Effect of Varying Accelerometry Criteria on Physical Activity: The Look AHEAD Study

    PubMed Central

    Miller, G. D.; Jakicic, J. M.; Rejeski, W. J.; Whit-Glover, M.; Lang, W.; Walkup, M. P.; Hodges, M.

    2012-01-01

    The importance of physical activity in weight management is widely documented. Although accelerometers offer an objective measure of activity that provide a valuable tool for intervention research, considerations for processing these data need further development. This study tests the effects of using different criteria for accelerometry data reduction. Data were obtained from 2,240 overweight and obese individuals with type 2 diabetes mellitus (T2DM) from the Look AHEAD study, with 2,177 baseline accelerometer files used for analysis. Number, duration, and intensity of moderate (≥3 METS) and vigorous (≥6 METS) activity bouts were compared using various data reduction criteria. Daily wear time was identified as 1,440 minutes per day minus non-wear time. Comparisons of physical activity patterns for non-wear time (using either 20, 30 or 60 minutes of continuous zeros), minimal daily wear time (8, 10, and 12 hours), number of days with available data (4, 5, and 6 days), weekdays versus weekends, and one- or two-minute time interruptions in an activity bout were performed. In this mostly obese population with T2DM (BMI = 36.4 kg/m2; mean age = 59.0 y), there were minimal differences in physical activity patterns using the different methods of data reduction. Altering criteria led to differences in the number of available data (sample size) meeting specific criteria. Although our results are likely directly applicable only to obese individuals with T2DM, an understudied population with regards to physical activity, the systematic analysis for data reduction employed can be more generalizable and provide guidance in this area in the absence of standard procedures. PMID:23505166

  1. Enzymatic activity of a mine soil varies according to vegetation cover and level of compost applied.

    PubMed

    de Varennes, Amerilis; Abreu, Maria Manuela; Qu, Guiwei; Cunha-Queda, Cristina

    2010-01-01

    We applied three doses of compost from mixed municipal solid waste (0, 15, and 30 g kg(-1) of soil) to a soil developed on pyrite mine wastes. Part of the soil was planted with young Erica australis L. collected at the mine; part was fertilized with N-P-K-Mg and sown with Dactylis glomerata L .Bare soil without mineral fertilization was included in the experiment, as well. Compost application to bare soil increased pH, provided plant nutrients, and enhanced the activity of the six soil enzymes tested. Growth of D. glomerata, and E. australis was stimulated in compost-amended soil compared with unamended controls. The presence of D. glomerata led to the greatest activities of soil acid phosphatase, beta-glucosidase, and cellulase compared with bare soil or with soil with E. australis. The presence of E. australis increased the activities of protease and cellulase in amended soil, compared with control, but it impaired dehydrogenase, fl-glucosidase, and acid phosphatase activities. These negative impacts probably derived from phenolic compounds known to be released from roots of this species. The survival strategy of this species seems to include a small need for P in the shoots, and the release of exudates that impair microbial activity and P cycling.

  2. Music Activity Reports by Music Teachers with Varying Training in Orff Schulwerk

    ERIC Educational Resources Information Center

    Sogin, David W.; Wang, Cecilia Chu

    2008-01-01

    The purpose of this study was to examine music activities occurring in the music classroom of teachers who received different levels of training in Orff Schulwerk. The subjects (N = 49) were teachers participating in three training levels at a summer Orff Schulwerk certification program in a university in the USA. Teachers were asked to report the…

  3. The Engagement in Musical Activities of Young Children with Varied Hearing Abilities

    ERIC Educational Resources Information Center

    Chen-Hafteck, Lily; Schraer-Joiner, Lyn

    2011-01-01

    This multiple case study examined the musical experiences of five hard-of-hearing/deaf children (hearing loss ranging from 35-95 dB) and four typical-hearing children, ages 3-4. Their responses to various musical activities were observed and analysed using flow indicators. It was found that both groups of children: (1) were capable of engaging in…

  4. Effects of Varying Team Sizes on Physical Activity Levels of College Students

    ERIC Educational Resources Information Center

    Gaudreault, Karen Lux; Cluphf, David; Russell, Jared; Lecheminant, James

    2014-01-01

    The purpose of this exploratory study was to examine physical activity levels among various team sizes for basketball and soccer in a C/UIPAP setting. Twenty-eight university physical education majors participated in the study. Participants engaged in three-on-three and five-on-five basketball and five-on-five and 11-on-11 soccer games. All games…

  5. Cutaneous immune activity varies with physiological state in female house sparrows (Passer domesticus).

    PubMed

    Martin, L B; Han, P; Kwong, J; Hau, M

    2006-01-01

    Many vertebrates show seasonality in immune defenses, perhaps because of trade-offs with other physiological processes. Trade-offs between reproduction and immune function have been well studied, but how other life cycle events such as molt affect immune function remains unclear. Here, we hypothesize that one possible explanation is that accumulative dissociated processes (e.g., resource deficits generated over the long term by physiological processes) can have delayed effects on immune activity. To test this hypothesis, we compared cutaneous immune responses in groups of captive female house sparrows (Passer domesticus) photoperiodically induced into six different life cycle stages. We predicted that if delayed trade-offs occur, immune activity would be reduced after a mature life state was reached (e.g., postmolt) and not just compromised when other tissues were actively growing (instantaneous trade-off). We found evidence for both types of trade-offs: immune responses were weakest in sparrows that had just completed postnuptial molt, but they were also weak in birds growing reproductive tissues or feathers. Birds in mature reproductive states or light molt had strong immune responses comparable with birds in a nonbreeding/nonmolting state. Altogether, our results indicate that immune activity in female house sparrows can be influenced by both instantaneous and delayed trade-offs.

  6. Alzheimer's Disease Variants with the Genome-Wide Significance are Significantly Enriched in Immune Pathways and Active in Immune Cells.

    PubMed

    Jiang, Qinghua; Jin, Shuilin; Jiang, Yongshuai; Liao, Mingzhi; Feng, Rennan; Zhang, Liangcai; Liu, Guiyou; Hao, Junwei

    2017-01-01

    The existing large-scale genome-wide association studies (GWAS) datasets provide strong support for investigating the mechanisms of Alzheimer's disease (AD) by applying multiple methods of pathway analysis. Previous studies using selected single nucleotide polymorphisms (SNPs) with several thresholds of nominal significance for pathway analysis determined that the threshold chosen for SNPs can reflect the disease model. Presumably, then, pathway analysis with a stringent threshold to define "associated" SNPs would test the hypothesis that highly associated SNPs are enriched in one or more particular pathways. Here, we selected 599 AD variants (P < 5.00E-08) to investigate the pathways in which these variants are enriched and the cell types in which these variants are active. Our results showed that AD variants are significantly enriched in pathways of the immune system. Further analysis indicated that AD variants are significantly enriched for enhancers in a number of cell types, in particular the B-lymphocyte, which is the most substantially enriched cell type. This cell type maintains its dominance among the strongest enhancers. AD SNPs also display significant enrichment for DNase in 12 cell types, among which the top 6 significant signals are from immune cell types, including 4 B cells (top 4 significant signals) and CD14+ and CD34+ cells. In summary, our results show that these AD variants with P < 5.00E-08 are significantly enriched in pathways of the immune system and active in immune cells. To a certain degree, the genetic predisposition for development of AD is rooted in the immune system, rather than in neuronal cells.

  7. Clinical significance of plasminogen activator inhibitor activity in patients with exercise-induced ischemia

    SciTech Connect

    Sakata, K.; Kurata, C.; Taguchi, T.; Suzuki, S.; Kobayashi, A.; Yamazaki, N.; Rydzewski, A.; Takada, Y.; Takada, A. )

    1990-10-01

    To assess the fibrinolytic system in patients with exercise-induced ischemia and its relation to ischemia and severity of coronary artery disease (CAD), 47 patients with CAD confirmed by results of coronary angiography underwent symptom-limited multistage exercise thallium-201 emission computed tomography. All patients with CAD had exercise-induced ischemia as assessed from thallium-201 images. Pre- and peak exercise blood samples from each patient and preexercise blood samples from control subjects were assayed for several fibrinolytic components and were also assayed for plasma adrenaline. The extent of ischemia was defined as delta visual uptake score (total visual uptake score in delayed images minus total visual uptake score in initial images) and the severity of CAD as the number of diseased vessels. In the basal condition, plasminogen activator inhibitor (PAI) activity was significantly higher in patients with exercise-induced ischemia as compared to control subjects (p less than 0.01), although there were no significant differences in other fibrinolytic variables between the two groups. Moreover, PAI activity in the basal condition displayed a significantly positive correlation with the extent of ischemia (r = 0.47, p less than 0.01). Patients with exercise-induced ischemia were divided into two groups (24 with single-vessel disease and 23 with multivessel disease). There were no significant differences in coronary risk factors, hemodynamics, or plasma adrenaline levels during exercise between single-vessel and multivessel disease except that delta visual uptake score was significantly higher in multivessel disease (p less than 0.01).

  8. Alteration and modulation of protein activity by varying post-translational modification

    DOEpatents

    Thompson, David N; Reed, David W; Thompson, Vicki S; Lacey, Jeffrey A; Apel, William A

    2015-03-03

    Embodiments of the invention include methods of altering the enzymatic activity or solubility of an extremophilic enzyme or post-translationally modifying a protein of interest via using isolated or partially purified glycosyltransferases and/or post-translational modification proteins, extracts of cells comprising glycosyltransferases and/or post-translational modification proteins, and/or in cells comprising one or more glycosyltransferases and/or post-translational modification proteins.

  9. Alteration and modulation of protein activity by varying post-translational modification

    DOEpatents

    Thompson, David N.; Reed, David W.; Thompson, Vicki S.; Lacey, Jeffrey A.; Apel, William A.

    2016-07-12

    Embodiments of the invention include methods of altering the enzymatic activity or solubility of an extremophilic enzyme or post-translationally modifying a protein of interest via using isolated or partially purified glycosyltransferases and/or post-translational modification proteins, extracts of cells comprising glycosyltransferases and/or post-translational modification proteins, and/or in cells comprising one or more glycosyltransferases and/or post-translational modification proteins.

  10. An active principle of Nigella sativa L., thymoquinone, showing significant antimicrobial activity against anaerobic bacteria

    PubMed Central

    Randhawa, Mohammad Akram; Alenazy, Awwad Khalaf; Alrowaili, Majed Gorayan; Basha, Jamith

    2017-01-01

    Aim/Background: Thymoquinone (TQ) is the major active principle of Nigella sativa seed (black seed) and is known to control many fungi, bacteria, and some viruses. However, the activity of TQ against anaerobic bacteria is not well demonstrated. Anaerobic bacteria can cause severe infections, including diarrhea, aspiration pneumonia, and brain abscess, particularly in immunodeficient individuals. The present study aimed to investigate the in vitro antimicrobial activity of TQ against some anaerobic pathogens in comparison to metronidazole. Methods: Standard, ATCC, strains of four anaerobic bacteria (Clostridium difficile, Clostridium perfringens, Bacteroides fragilis, and Bacteroides thetaiotaomicron), were initially isolated on special Brucella agar base (with hemin and vitamin K). Then, minimum inhibitory concentrations (MICs) of TQ and metronidazole were determined against these anaerobes when grown in Brucella agar, using serial agar dilution method according to the recommended guidelines for anaerobic organisms instructed by the Clinical and Laboratory Standards Institute. Results: TQ showed a significant antimicrobial activity against anaerobic bacteria although much weaker than metronidazole. MICs of TQ and metronidazole against various anaerobic human pathogens tested were found to be between 10-160 mg/L and 0.19-6.25 mg/L, respectively. Conclusions: TQ controlled the anaerobic human pathogenic bacteria, which supports the use of N. sativa in the treatment of diarrhea in folk medicine. Further investigations are in need for determination of the synergistic effect of TQ in combination with metronidazole and the activity of derivatives of TQ against anaerobic infections. PMID:28163966

  11. Asymptotic theory of time-varying social networks with heterogeneous activity and tie allocation.

    PubMed

    Ubaldi, Enrico; Perra, Nicola; Karsai, Márton; Vezzani, Alessandro; Burioni, Raffaella; Vespignani, Alessandro

    2016-10-24

    The dynamic of social networks is driven by the interplay between diverse mechanisms that still challenge our theoretical and modelling efforts. Amongst them, two are known to play a central role in shaping the networks evolution, namely the heterogeneous propensity of individuals to i) be socially active and ii) establish a new social relationships with their alters. Here, we empirically characterise these two mechanisms in seven real networks describing temporal human interactions in three different settings: scientific collaborations, Twitter mentions, and mobile phone calls. We find that the individuals' social activity and their strategy in choosing ties where to allocate their social interactions can be quantitatively described and encoded in a simple stochastic network modelling framework. The Master Equation of the model can be solved in the asymptotic limit. The analytical solutions provide an explicit description of both the system dynamic and the dynamical scaling laws characterising crucial aspects about the evolution of the networks. The analytical predictions match with accuracy the empirical observations, thus validating the theoretical approach. Our results provide a rigorous dynamical system framework that can be extended to include other processes shaping social dynamics and to generate data driven predictions for the asymptotic behaviour of social networks.

  12. Asymptotic theory of time-varying social networks with heterogeneous activity and tie allocation

    NASA Astrophysics Data System (ADS)

    Ubaldi, Enrico; Perra, Nicola; Karsai, Márton; Vezzani, Alessandro; Burioni, Raffaella; Vespignani, Alessandro

    2016-10-01

    The dynamic of social networks is driven by the interplay between diverse mechanisms that still challenge our theoretical and modelling efforts. Amongst them, two are known to play a central role in shaping the networks evolution, namely the heterogeneous propensity of individuals to i) be socially active and ii) establish a new social relationships with their alters. Here, we empirically characterise these two mechanisms in seven real networks describing temporal human interactions in three different settings: scientific collaborations, Twitter mentions, and mobile phone calls. We find that the individuals’ social activity and their strategy in choosing ties where to allocate their social interactions can be quantitatively described and encoded in a simple stochastic network modelling framework. The Master Equation of the model can be solved in the asymptotic limit. The analytical solutions provide an explicit description of both the system dynamic and the dynamical scaling laws characterising crucial aspects about the evolution of the networks. The analytical predictions match with accuracy the empirical observations, thus validating the theoretical approach. Our results provide a rigorous dynamical system framework that can be extended to include other processes shaping social dynamics and to generate data driven predictions for the asymptotic behaviour of social networks.

  13. Brain regional networks active during the mismatch negativity vary with paradigm.

    PubMed

    MacLean, Shannon E; Blundon, Elizabeth G; Ward, Lawrence M

    2015-08-01

    We used independent component analysis (ICA) of high-density EEG recordings coupled with single dipole fitting to identify the dominant brain regions active during the MMN in two different versions of a passive oddball paradigm: a simple, monotic, frequency-deviant paradigm and a more complex, dichotic, frequency-deviant paradigm with deviants occurring in either ear alone or in both ears at the same time. In both paradigms we found brain regional sources in the temporal and frontal cortices active during the MMN period, consistent with some previous studies. In the simpler paradigm, the scalp-potential variance during the earlier (70-120 ms) MMN was mostly accounted for by a wide array of temporal, frontal, and parietal sources. In the more complex paradigm, however, a generator in the prefrontal cortex accounted for a substantial amount of the variance of the scalp potential during the somewhat later MMN period (120-200 ms). These findings are consistent with a more nuanced view of the MMN and its generators than has been held in the past.

  14. Asymptotic theory of time-varying social networks with heterogeneous activity and tie allocation

    PubMed Central

    Ubaldi, Enrico; Perra, Nicola; Karsai, Márton; Vezzani, Alessandro; Burioni, Raffaella; Vespignani, Alessandro

    2016-01-01

    The dynamic of social networks is driven by the interplay between diverse mechanisms that still challenge our theoretical and modelling efforts. Amongst them, two are known to play a central role in shaping the networks evolution, namely the heterogeneous propensity of individuals to i) be socially active and ii) establish a new social relationships with their alters. Here, we empirically characterise these two mechanisms in seven real networks describing temporal human interactions in three different settings: scientific collaborations, Twitter mentions, and mobile phone calls. We find that the individuals’ social activity and their strategy in choosing ties where to allocate their social interactions can be quantitatively described and encoded in a simple stochastic network modelling framework. The Master Equation of the model can be solved in the asymptotic limit. The analytical solutions provide an explicit description of both the system dynamic and the dynamical scaling laws characterising crucial aspects about the evolution of the networks. The analytical predictions match with accuracy the empirical observations, thus validating the theoretical approach. Our results provide a rigorous dynamical system framework that can be extended to include other processes shaping social dynamics and to generate data driven predictions for the asymptotic behaviour of social networks. PMID:27774998

  15. Cytoplasmic streaming in Drosophila oocytes varies with kinesin activity and correlates with the microtubule cytoskeleton architecture.

    PubMed

    Ganguly, Sujoy; Williams, Lucy S; Palacios, Isabel M; Goldstein, Raymond E

    2012-09-18

    Cells can localize molecules asymmetrically through the combined action of cytoplasmic streaming, which circulates their fluid contents, and specific anchoring mechanisms. Streaming also contributes to the distribution of nutrients and organelles such as chloroplasts in plants, the asymmetric position of the meiotic spindle in mammalian embryos, and the developmental potential of the zygote, yet little is known quantitatively about the relationship between streaming and the motor activity which drives it. Here we use Particle Image Velocimetry to quantify the statistical properties of Kinesin-dependent streaming during mid-oogenesis in Drosophila. We find that streaming can be used to detect subtle changes in Kinesin activity and that the flows reflect the architecture of the microtubule cytoskeleton. Furthermore, based on characterization of the rheology of the cytoplasm in vivo, we establish estimates of the number of Kinesins required to drive the observed streaming. Using this in vivo data as the basis of a model for transport, we suggest that the disordered character of transport at mid-oogenesis, as revealed by streaming, is an important component of the localization dynamics of the body plan determinant oskar mRNA.

  16. The varied functions of aluminium-activated malate transporters–much more than aluminium resistance

    PubMed Central

    Palmer, Antony J.; Baker, Alison; Muench, Stephen P.

    2016-01-01

    The ALMT (aluminium-activated malate transporter) family comprises a functionally diverse but structurally similar group of ion channels. They are found ubiquitously in plant species, expressed throughout different tissues, and located in either the plasma membrane or tonoplast. The first family member identified was TaALMT1, discovered in wheat root tips, which was found to be involved in aluminium resistance by means of malate exudation into the soil. However, since this discovery other family members have been shown to have many other functions such as roles in stomatal opening, general anionic homoeostasis, and in economically valuable traits such as fruit flavour. Recent evidence has also shown that ALMT proteins can act as key molecular actors in GABA (γ-aminobutyric acid) signalling, the first evidence that GABA can act as a signal transducer in plants. PMID:27284052

  17. Fate of malathion and a phosphonic acid in activated sludge with varying solids retention times.

    PubMed

    Janeczko, Allen K; Walters, Edward B; Schuldt, Steven J; Magnuson, Matthew L; Willison, Stuart A; Brown, Lisa M; Ruiz, Oscar N; Felker, Daniel L; Racz, LeeAnn

    2014-06-15

    This study examined the ability of activated sludge (AS) to sorb and biodegrade ethylmethylphosphonic acid (EMPA) and malathion, a degradation product and surrogate, respectively, for an organophosphate chemical warfare agent. Sorption equilibrium isotherm experiments indicate that sorption of EMPA and malathion to AS is negligible. EMPA at a concentration of 1 mg L(-1) degraded by approximately 30% with apparent first-order kinetics, possibly via co-metabolism from nitrification. Heterotrophic bacteria and abiotic mechanisms, however, are largely responsible for malathion degradation also with apparent first-order kinetics. EMPA did not inhibit chemical oxygen demand (COD) oxidation or nitrification activity, although malathion did appear to induce a stress response resulting in inhibition of COD oxidation. The study also included a 30-day experiment in which malathion, at a concentration of 5 mg L(-1), was repeatedly fed to AS in bench-scale sequencing batch reactors (SBRs) operating at different solids retention times (SRTs). Peak malathion concentrations occurred at day 4.5, with the longer SRTs yielding greater peak malathion concentrations. The AS reduced the malathion concentrations to nearly zero by day 10 for all SRTs, even when the malathion concentration in the influent increased to 20.8 mg L(-1). The data suggest a biodegradation pathway for malathion involving an oxygenase. Phylogenetic analyses revealed that all samples had an abundance of Zoogloea, though there was greater bacterial diversity in the SBR with the SRT of 50 days. The SBR with an SRT of 9.5 days had an apparent reduction in the diversity of the bacterial community.

  18. Gender Differences in Barriers to Physical Activity among College Students Reporting Varying Levels of Regular Physical Activity

    ERIC Educational Resources Information Center

    Munford, Shawn N.

    2011-01-01

    Researchers have studied the primary determinants of physical activity in an effort to enhance health promotion initiatives nationwide. These physical activity determinants have been observed to differ among various segments of the population, suggesting a further examination of physical activity barriers among differing populations. Little…

  19. Active dynamics of colloidal particles in time-varying laser speckle patterns

    PubMed Central

    Bianchi, Silvio; Pruner, Riccardo; Vizsnyiczai, Gaszton; Maggi, Claudio; Di Leonardo, Roberto

    2016-01-01

    Colloidal particles immersed in a dynamic speckle pattern experience an optical force that fluctuates both in space and time. The resulting dynamics presents many interesting analogies with a broad class of non-equilibrium systems like: active colloids, self propelled microorganisms, transport in dynamical intracellular environments. Here we show that the use of a spatial light modulator allows to generate light fields that fluctuate with controllable space and time correlations and a prescribed average intensity profile. In particular we generate ring-shaped random patterns that can confine a colloidal particle over a quasi one-dimensional random energy landscape. We find a mean square displacement that is diffusive at both short and long times, while a superdiffusive or subdiffusive behavior is observed at intermediate times depending on the value of the speckles correlation time. We propose two alternative models for the mean square displacement in the two limiting cases of a short or long speckles correlation time. A simple interpolation formula is shown to account for the full phenomenology observed in the mean square displacement across the entire range from fast to slow fluctuating speckles. PMID:27279540

  20. Progression to active tuberculosis, but not transmission, varies by M. tuberculosis lineage in The Gambia

    PubMed Central

    de Jong, Bouke C.; Hill, Philip C.; Aiken, Alex; Awine, Timothy; Antonio, Martin; Adetifa, Ifedayo M.; Jackson-Sillah, Dolly J.; Fox, Annette; DeRiemer, Kathryn; Gagneux, Sebastien; Borgdorff, Martien W.; McAdam, Keith P.W.J.; Corrah, Tumani; Small, Peter M.; Adegbola, Richard A.

    2008-01-01

    Considerable variability exists in the outcome of M. tuberculosis infection. We hypothesized that M. africanum was less likely than M. tuberculosis to transmit and progress to tuberculosis disease. In a cohort study of tuberculosis patients and their household contacts in the Gambia, we categorized 1,808 HIV negative tuberculosis contacts according to exposure to M. tuberculosis or to M. africanum. A positive skin test indicated transmission and development of tuberculosis during 2 years of follow-up indicated progression to disease. Transmission was similar, but progression to disease was significantly lower in contacts exposed to M. africanum than to M. tuberculosis (1.0% vs 2.9%; Hazard Ratio (HR) 3.1, 95% CI 1.1–8.7). Within M. tuberculosis sensu stricto, contacts exposed to a Beijing family strain were most likely to progress to disease (5.6%; HR 6.7 (2.0–22) relative to M. africanum). M. africanum and M. tuberculosis transmit equally well to household contacts, but contacts exposed to M. africanum are less likely to progress to tuberculosis disease than those exposed to M. tuberculosis. The variable rate of progression by lineage suggests that TB variability matters in clinical settings and should be taken into account in studies evaluating tuberculosis vaccines and treatment regimens for latent tuberculosis infection. PMID:18702608

  1. Repeated dose (28-day) administration of silver nanoparticles of varied size and coating does not significantly alter the indigenous murine gut microbiome.

    PubMed

    Wilding, Laura A; Bassis, Christine M; Walacavage, Kim; Hashway, Sara; Leroueil, Pascale R; Morishita, Masako; Maynard, Andrew D; Philbert, Martin A; Bergin, Ingrid L

    2016-01-01

    Silver nanoparticles (AgNPs) have been used as antimicrobials in a number of applications, including topical wound dressings and coatings for consumer products and biomedical devices. Ingestion is a relevant route of exposure for AgNPs, whether occurring unintentionally via Ag dissolution from consumer products, or intentionally from dietary supplements. AgNP have also been proposed as substitutes for antibiotics in animal feeds. While oral antibiotics are known to have significant effects on gut bacteria, the antimicrobial effects of ingested AgNPs on the indigenous microbiome or on gut pathogens are unknown. In addition, AgNP size and coating have been postulated as significantly influential towards their biochemical properties and the influence of these properties on antimicrobial efficacy is unknown. We evaluated murine gut microbial communities using culture-independent sequencing of 16S rRNA gene fragments following 28 days of repeated oral dosing of well-characterized AgNPs of two different sizes (20 and 110 nm) and coatings (PVP and Citrate). Irrespective of size or coating, oral administration of AgNPs at 10 mg/kg body weight/day did not alter the membership, structure or diversity of the murine gut microbiome. Thus, in contrast to effects of broad-spectrum antibiotics, repeat dosing of AgNP, at doses equivalent to 2000 times the oral reference dose and 100-400 times the effective in vitro anti-microbial concentration, does not affect the indigenous murine gut microbiome.

  2. DNA-directed alkylating agents. 3. Structure-activity relationships for acridine-linked aniline mustards: consequences of varying the length of the linker chain.

    PubMed

    Valu, K K; Gourdie, T A; Boritzki, T J; Gravatt, G L; Baguley, B C; Wilson, W R; Wakelin, L P; Woodgate, P D; Denny, W A

    1990-11-01

    Four series of acridine-linked aniline mustards have been prepared and evaluated for in vitro cytotoxicity, in vivo antitumor activity, and DNA cross-linking ability. The anilines were attached to the DNA-intercalating acridine chromophores by link groups (-O-, -CH2-, -S-, and -SO2-) of widely varying electronic properties, providing four series of widely differing mustard reactivity where the alkyl chain linking the acridine and mustard moieties was varied from two to five carbons. Relationships were sought between chain length and biological properties. Within each series, increasing the chain length did not alter the reactivity of the alkylating moiety but did appear to position it differently on the DNA, since cross-linking ability (measured by agarose gel assay) altered with chain length, being maximal with the C4 analogue. The in vivo antitumor activities of the compounds depended to some extent on the reactivity of the mustard, with the least reactive SO2 compounds being inactive. However, DNA-targeting did appear to allow the use of less reactive mustards, since the S-linked acridine mustards showed significant activity whereas the parent S-mustard did not. Within each active series, the most active compound was the C4 homologue, suggesting some relationship between activity and extent of DNA alkylation.

  3. Multistability of neural networks with discontinuous non-monotonic piecewise linear activation functions and time-varying delays.

    PubMed

    Nie, Xiaobing; Zheng, Wei Xing

    2015-05-01

    This paper is concerned with the problem of coexistence and dynamical behaviors of multiple equilibrium points for neural networks with discontinuous non-monotonic piecewise linear activation functions and time-varying delays. The fixed point theorem and other analytical tools are used to develop certain sufficient conditions that ensure that the n-dimensional discontinuous neural networks with time-varying delays can have at least 5(n) equilibrium points, 3(n) of which are locally stable and the others are unstable. The importance of the derived results is that it reveals that the discontinuous neural networks can have greater storage capacity than the continuous ones. Moreover, different from the existing results on multistability of neural networks with discontinuous activation functions, the 3(n) locally stable equilibrium points obtained in this paper are located in not only saturated regions, but also unsaturated regions, due to the non-monotonic structure of discontinuous activation functions. A numerical simulation study is conducted to illustrate and support the derived theoretical results.

  4. The Regulation of Skeletal Muscle Active Hyperemia: The Differential Role of Adenosine in Muscles of Varied Fiber Types

    DTIC Science & Technology

    1986-04-21

    0.2 Hz and three mnscles ~;timulated to contract at 0.4 Hz during BADA infuston. These m~tabolites were also mea~•1red in two muscles contractin ~ at...APR 1986 2. REPORT TYPE N/A 3. DATES COVERED - 4. TITLE AND SUBTITLE The Regulation of Skeletal Muscle Active Hyperemia: The Differential...Role of Adenosine in Muscles of Varied Fiber Types 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER

  5. Trends in space activities in 2014: The significance of the space activities of governments

    NASA Astrophysics Data System (ADS)

    Paikowsky, Deganit; Baram, Gil; Ben-Israel, Isaac

    2016-01-01

    This article addresses the principal events of 2014 in the field of space activities, and extrapolates from them the primary trends that can be identified in governmental space activities. In 2014, global space activities centered on two vectors. The first was geopolitical, and the second relates to the matrix between increasing commercial space activities and traditional governmental space activities. In light of these two vectors, the article outlines and analyzes trends of space exploration, human spaceflights, industry and technology, cooperation versus self-reliance, and space security and sustainability. It also reviews the space activities of the leading space-faring nations.

  6. Novel structurally varied N-alkyl 1,4-dihydropyridines as ABCB1 inhibitors: structure-activity relationships, biological activity and first bioanalytical evaluation.

    PubMed

    Hilgeroth, Andreas; Baumert, Christiane; Coburger, Claudius; Seifert, Marianne; Krawczyk, Sören; Hempel, Cornelius; Neubauer, Felix; Krug, Martin; Molnár, Josef; Lage, Hermann

    2013-06-01

    Series of structurally varied N-alkyl 1,4-dihydropyridines and novel benzo-annelated derivatives as 1,4- dihydroquinolines have been characterized as ABCB1 inhibitors. Structure-activity relationships (SARs) are discussed. Cytotoxic activities of selected compounds have been determined. A first bioanalysis of ABCB1 substrate properties has been carried out in a cell-based model. Compounds with highest ABCB1 inhibiting activities were no substrates of ABCB1 and not transported by the efflux pump, thus profiling the new ABCB1 inhibitors.

  7. Effect of using repurposed science-rich feature films with varying levels of student activity in middle grades science instruction

    NASA Astrophysics Data System (ADS)

    Cavanaugh, Terence William

    This study provided an initial investigation into the use of repurposed content-rich entertainment videos (versus traditional educational videos) presented in either an active or passive educational setting. Eight classes of seventh grade general science students (n = 361) were randomly assigned to one of four video treatment groups: (1) repurposed content-rich entertainment video in a passive setting, (2) repurposed content-rich entertainment video in an active setting, (3) traditional educational video in a passive setting, and (4) traditional educational video in an active setting. The subject matter of the videos focused on basic chemistry, scientific method, and the nature of life. The repurposed content-rich entertainment groups watched a StarTrek the Next Generation episode, and the traditional educational video groups watched videos from NASA and the Understanding Science Corporation. Students completed a knowledge-based pretest and an initial attitude survey prior to the treatment. During the treatment, all participants watched the videos, discussed the science content, and answered directed questions. Active setting groups discussed and answered questions during the video, while the passive setting groups discussed and answered questions after the video. The treatment period lasted approximately 135 minutes. Immediately following treatment, participants received a knowledge-based posttest and an attitude survey. Three weeks after treatment, retention tests and follow-up surveys were administered. Test and survey data were analyzed using single factor and repeated measures ANOVA followed by post hoc tests. Significant gains (p < 0.05) in test scores were found for repurposed content-rich entertainment video over traditional educational video groups. No significant differences were found in test scores between the active and passive setting groups. When the variables were combined, additional effects were noted. Specifically, significant differences were

  8. Biotite dissolution in brine at varied temperatures and CO2 pressures: its activation energy and potential CO2 intercalation.

    PubMed

    Hu, Yandi; Jun, Young-Shin

    2012-10-16

    For sustainable geologic CO(2) sequestration (GCS), it is important to understand the effects of temperature and CO(2) pressure on mica's dissolution and surface morphological changes under saline hydrothermal conditions. Batch experiments were conducted with biotite (Fe-end member mica) under conditions relevant to GCS sites (35-95 °C and 75-120 atm CO(2)), and 1 M NaCl solution was used to mimic the brine. With increasing temperature, a transition from incongruent to congruent dissolution of biotite was observed. The dissolution activation energy based on Si release was calculated to be 52 ± 5 kJ mol(-1). By comparison with N(2) experiments, we showed that CO(2) injection greatly enhanced biotite's dissolution and its surface morphology evolutions, such as crack formation and detachment of newly formed fibrous illite. For biotite's dissolution and morphological evolutions, the pH effects of CO(2) were differentiated from the effects of bicarbonate complexation and CO(2) intercalation. Bicarbonate complexation effects on ion release from biotite were found to be minor under our experimental conditions. On the other hand, the CO(2) molecules in brine could get into the biotite interlayer and cause enhanced swelling of the biotite interlayer and hence the observed promotion of biotite surface cracking. The cracking created more reactive surface area in contact with brine and thus enhanced the later ion release from biotite. These results provide new information for understanding CO(2)-brine-mica interactions in saline aquifers with varied temperatures and CO(2) pressures, which can be useful for GCS site selection and operations.

  9. Analysis of the locomotor activity of a nocturnal desert lizard (Reptilia: Gekkonidae: Teratoscincus scincus) under varying moonlight.

    PubMed

    Seligmann, Hervé; Anderson, Steven C; Autumn, Kellar; Bouskila, Amos; Saf, Rachel; Tuniyev, Boris S; Werner, Yehudah L

    2007-01-01

    1. This project seeks to identify determinants of the variation observed in the foraging behavior of predatory animals, especially in moonlight, using a lizard as a model. 2. Moonlight generally enhances the foraging efficiency of nocturnal visual predators and often depresses the locomotor activity of prey animals. Previous evidence has indicated for three different nocturnal species of smallish gecko lizards that they respond to moonlight by increasing their activity. 3. In this study some aspects of the foraging activity of the somewhat larger nocturnal psammophilous Teratoscincus scincus, observed near Repetek and Ashgabat, Turkmenistan, were significantly depressed by moonlight, while several confounding factors (sex, maturity, size, sand temperature, hour, prior handling and observer effect) were taken into account. 4. This behavioral difference may relate to the eye size of the various species. 5. Additionally, a novel method of analyzing foraging behavior shows that in this species the duration of moves increases the duration of subsequent stationary pauses. Measurement of locomotor speed, yielding an average speed of 220% of the maximum aerobic speed, indicates a need for these pauses. Secondarily, pause duration decreases the duration of subsequent moves, precluding escalation of move duration. 6. The results of this and related projects advocate the taking into account of physiological and environmental factors that may affect an animal's foraging behavior.

  10. Transcriptional activities of methanogens and methanotrophs vary with methane emission flux in rice soils under chronic nutrient constraints of phosphorus and potassium

    NASA Astrophysics Data System (ADS)

    Sheng, Rong; Chen, Anlei; Zhang, Miaomiao; Whiteley, Andrew S.; Kumaresan, Deepak; Wei, Wenxue

    2016-12-01

    Nutrient status in soil is crucial for the growth and development of plants which indirectly or directly affect the ecophysiological functions of resident soil microorganisms. Soil methanogens and methanotrophs can be affected by soil nutrient availabilities and plant growth, which in turn modulate methane (CH4) emissions. Here, we assessed whether deficits in soil-available phosphorus (P) and potassium (K) modulated the activities of methanogens and methanotrophs in a long-term (20 year) experimental system involving limitation in either one or both nutrients. Results showed that a large amount of CH4 was emitted from paddy soil at rice tillering stage (flooding) while CH4 flux was minimum at ripening stage (drying). Compared to soils amended with NPK fertiliser treatment, the soils without P input significantly reduced methane flux rates, whereas those without K input did not. Under P limitation, methanotroph transcript copy number significantly increased in tandem with a decrease in methanogen transcript abundance, suggesting that P-deficiency-induced changes in soil physio-chemical properties, in tandem with rice plant growth, might constrain the activity of methanogens, whereas the methanotrophs might be adaptive to this soil environment. In contrast, lower transcript abundance of both methanogen and methanotrophs were observed in K-deficient soils. Assessments of community structures based upon transcripts indicated that soils deficient in P induced greater shifts in the active methanotrophic community than K-deficient soils, while similar community structures of active methanogens were observed in both treatments. These results suggested that the population dynamics of methanogens and methanotrophs could vary along with the changes in plant growth states and soil properties induced by nutrient deficiency.

  11. An Acute Lateral Ankle Sprain Significantly Decreases Physical Activity across the Lifespan.

    PubMed

    Hubbard-Turner, Tricia; Wikstrom, Erik A; Guderian, Sophie; Turner, Michael J

    2015-09-01

    We do not know the impact an ankle sprain has on physical activity levels across the lifespan. With the negative consequences of physical inactivity well established, understanding the effect of an ankle sprain on this outcome is critical. The objective of this study was to measure physical activity across the lifespan after a single ankle sprain in an animal model. Thirty male mice (CBA/J) were randomly placed into one of three groups: the transected calcaneofibular ligament (CFL) group, the transected anterior talofibular ligament (ATFL)/CFL group, and a SHAM group. Three days after surgery, all of the mice were individually housed in a cage containing a solid surface running wheel. Physical activity levels were recorded and averaged every week across the mouse's lifespan. The SHAM mice ran significantly more distance each day compared to the remaining two running groups (post hoc p = 0.011). Daily duration was different between the three running groups (p = 0.048). The SHAM mice ran significantly more minutes each day compared to the remaining two running groups (post hoc p=0.046) while the ATFL/CFL mice ran significantly less minutes each day (post hoc p = 0.028) compared to both the SHAM and CFL only group. The SHAM mice ran at a faster daily speed versus the remaining two groups of mice (post hoc p = 0.019) and the ATFL/CFL mice ran significantly slower each day compared to the SHAM and CFL group (post hoc p = 0.005). The results of this study indicate that a single ankle sprain significantly decreases physical activity across the lifespan in mice. This decrease in physical activity can potentially lead to the development of numerous chronic diseases. An ankle sprain thus has the potential to lead to significant long term health risks if not treated appropriately. Key pointsA single ankle significantly decreased physical activity levels in mice across the lifespan.Decreased physical activity could significantly negatively impact overall health if not modified

  12. An Acute Lateral Ankle Sprain Significantly Decreases Physical Activity across the Lifespan

    PubMed Central

    Hubbard-Turner, Tricia; Wikstrom, Erik A.; Guderian, Sophie; Turner, Michael J.

    2015-01-01

    We do not know the impact an ankle sprain has on physical activity levels across the lifespan. With the negative consequences of physical inactivity well established, understanding the effect of an ankle sprain on this outcome is critical. The objective of this study was to measure physical activity across the lifespan after a single ankle sprain in an animal model. Thirty male mice (CBA/J) were randomly placed into one of three groups: the transected calcaneofibular ligament (CFL) group, the transected anterior talofibular ligament (ATFL)/CFL group, and a SHAM group. Three days after surgery, all of the mice were individually housed in a cage containing a solid surface running wheel. Physical activity levels were recorded and averaged every week across the mouse’s lifespan. The SHAM mice ran significantly more distance each day compared to the remaining two running groups (post hoc p = 0.011). Daily duration was different between the three running groups (p = 0.048). The SHAM mice ran significantly more minutes each day compared to the remaining two running groups (post hoc p=0.046) while the ATFL/CFL mice ran significantly less minutes each day (post hoc p = 0.028) compared to both the SHAM and CFL only group. The SHAM mice ran at a faster daily speed versus the remaining two groups of mice (post hoc p = 0.019) and the ATFL/CFL mice ran significantly slower each day compared to the SHAM and CFL group (post hoc p = 0.005). The results of this study indicate that a single ankle sprain significantly decreases physical activity across the lifespan in mice. This decrease in physical activity can potentially lead to the development of numerous chronic diseases. An ankle sprain thus has the potential to lead to significant long term health risks if not treated appropriately. Key points A single ankle significantly decreased physical activity levels in mice across the lifespan. Decreased physical activity could significantly negatively impact overall health if not

  13. Pathogenesis and significance of glomerular C4d deposition in lupus nephritis: activation of classical and lectin pathways

    PubMed Central

    Kim, Min-Kyung; Maeng, Young-In; Lee, Sun-Jae; Lee, In Hee; Bae, Jisuk; Kang, Yu-Na; Park, Byung-Tae; Park, Kwan-Kyu

    2013-01-01

    Immune complex-mediated complement activation through the classic pathway plays a key role in the pathogenesis of lupus nephritis (LN). C4d deposition in renal tissue reflects the prognosis of systemic lupus erythematosus (SLE). The aim of the current study is to investigate the pathogenesis and clinicopathologic significance of glomerular C4d deposition in LN. We retrospectively analyzed clinical and histopathological data of 20 SLE patients with renal biopsy-proven LN and 10 non-SLE renal biopsy samples as control. LN biopsies showed varying degrees of glomerular C4d staining associated with immune complex deposits, IgG (p = 0.015), C1q (p = 0.032) and C3 (p = 0.049). 7 LN biopsies had all of C4d, C1q and C3 deposits in their glomeruli, indicative of the activation of the classical pathway, whereas 2 LN biopsies had C4d and C3 deposits without accompanying C1q deposits, indicating the activation of the lectin pathway. Glomerular C4d deposition was correlated with the LN subtype (p < 0.001). In particular, a diffusely intense and coarsely granular pattern of C4d deposition in all glomeruli was detected in class V membranous LN. However, glomerular C4d deposition was correlated with neither disease activity of SLE nor histological activity and chronicity of LN. In conclusion, the activation of the lectin pathway as well as the classical pathway seems to play a crucial role in the pathogenesis of LN. Glomerular C4d staining could be helpful for diagnosing class V membranous LN, although glomerular C4d deposition does not reflect SLE disease activity and histological activity and chronicity. PMID:24133594

  14. Risk Factors for Clinically Significant Intimate Partner Violence among Active-Duty Members

    ERIC Educational Resources Information Center

    Smith Slep, Amy M.; Foran, Heather M.; Heyman, Richard E.; Snarr, Jeffery D.

    2011-01-01

    Hypothesized risk factors for men's and women's clinically significant intimate partner violence (CS-IPV) from four ecological levels (i.e., individual, family, workplace, community) were tested in a representative sample of active-duty U.S. Air Force members (N = 42,744). When considered together, we expected only individual and family factors to…

  15. Subjective Significance Shapes Arousal Effects on Modified Stroop Task Performance: A Duality of Activation Mechanisms Account

    PubMed Central

    Imbir, Kamil K.

    2016-01-01

    Activation mechanisms such as arousal are known to be responsible for slowdown observed in the Emotional Stroop and modified Stroop tasks. Using the duality of mind perspective, we may conclude that both ways of processing information (automatic or controlled) should have their own mechanisms of activation, namely, arousal for an experiential mind, and subjective significance for a rational mind. To investigate the consequences of both, factorial manipulation was prepared. Other factors that influence Stroop task processing such as valence, concreteness, frequency, and word length were controlled. Subjective significance was expected to influence arousal effects. In the first study, the task was to name the color of font for activation charged words. In the second study, activation charged words were, at the same time, combined with an incongruent condition of the classical Stroop task around a fixation point. The task was to indicate the font color for color-meaning words. In both studies, subjective significance was found to shape the arousal impact on performance in terms of the slowdown reduction for words charged with subjective significance. PMID:26869974

  16. Chicken embryo fibroblasts exposed to weak, time-varying magnetic fields share cell proliferation, adenosine deaminase activity, and membrane characteristics of transformed cells

    SciTech Connect

    Parola, A.H.; Porat, N.; Kiesow, L.A. )

    1993-01-01

    Chicken embryo fibroblasts (CEF) exposed to a sinusoidally varying magnetic field (SVMF) (100 Hz, 700 microT, for 24 h) showed a remarkable rise of segmental rotational relaxation rate of adenosine deaminase (ADA, EC 3.5.4.4) as determined by multifrequency phase fluorometry. Pyrene-labeled, small subunit ADA was applied to cultured (normal) CEF, which have available and abundant ADA complexing protein (ADCP) on their plasma membranes. Sine-wave-modulated fluorometry of the pyrene yielded a profile of phase angle vs. modulation frequency. In SVMF-treated cells and in Rous-sarcoma-virus (RSV) transformed cells the differential phase values at low modulation frequencies of the excitation are remarkably reduced. This effect is magnetic rather than thermal, because the temperature was carefully controlled and monitored; nevertheless to further check this matter we studied CEF, infected by the RSV-Ts68 temperature-sensitive mutant (36 degrees C transformed, 41 degrees C revertant). When grown at 36 degrees C in the SVMF, cells did not show the slightest trend towards reversion, as would be expected had there been local heating. Concomitant with the increased segmental rotational relaxation rate of ADA, there was a decrease in fluorescence lifetime and a slight, yet significant, increase in membrane lipid microfluidity. These biophysical observations prompted us to examine the effect of SVMF on cell proliferation and ADA activity (a malignancy marker): higher rates of cell proliferation and reduced specific activity of ADA were observed.

  17. Penicillium verruculosum SG: a source of polyketide and bioactive compounds with varying cytotoxic activities against normal and cancer lines.

    PubMed

    Shah, Salma Gul; Shier, W Thomas; Jamaluddin; Tahir, Nawaz; Hameed, Abdul; Ahmad, Safia; Ali, Naeem

    2014-04-01

    A newly isolated fungus Penicillium verruculosum SG was evaluated for the production and characterization of bioactive colored secondary metabolites using solid-state fermentation along with their cytotoxic activities against normal and cancer cell lines. Logical fragmentation pattern following column chromatography, thin layer chromatography and liquid chromatography and mass spectrometry of crude culture filtrate of fungus revealed the presence of different polyketide pigments and other bioactive compounds. Cytotoxicity of the selected colored fractions of fungal filtrate containing different compounds revealed IC50 (μg/ml) values ranging from 5 to 100. It was significantly higher in case of orevactaene (5 + 0.44) and monascorubrine followed by pyripyropene (8 + 0.63) against cancer cell line KA3IT. Overall, these compounds considerably showed less toxicity toward normal cell lines NIH3T3, HSCT6, HEK293 and MDCK. XRD of a yellow crystalline compound (224.21 m/z) confirmed its 3-dimensional structure as phenazine 1 carboxylic acid (C13H8N2O2) (broad spectrum antibiotic), and it is first time reported in fungi.

  18. The content of macro- and microelements and the phosphatase activity of soils under a varied plant cultivation technology

    NASA Astrophysics Data System (ADS)

    Bartkowiak, A.; Lemanowicz, J.; Kobierski, M.

    2015-12-01

    The paper presents the results of the analyses of selected physicochemical properties and the activity of alkaline and acid phosphatase in the soils which differed in terms of plant cultivation technology. Profile sI represented arable land in the crop rotation with cereals dominating (medium intensive technology), without irrigation, while profile sII—represented arable land with vegetable crops cultivation (intensive technology), intensively fertilized and irrigated. The content of available phosphorus in the two soil profiles investigated ranged from 6.6 to 69.1 mg/kg. The highest contents of phosphorus available to plants were reported in the plough horizon of both soils, while the abundance of potassium and magnesium was highest in the illuvial horizon of both soils. The soil profiles investigated showed a significant variation in terms of the cultivation technologies applied. The contents of plant-available Cu and Zn in soil were low and they resulted in the inhibition of neither alkaline nor acid phosphatase. The intensive vegetable crops cultivation technology decreased the content of organic matter and increased the content of the nutrients in soil. Using the Ward method, it was found that relatively similar physicochemical and chemical properties were reported for the genetic horizons of both soil profiles, especially Ap horizon of the soil representing arable land with intensive cultivation of vegetable crops.

  19. Are secular correlations between sunspots, geomagnetic activity, and global temperature significant?

    USGS Publications Warehouse

    Love, J.J.; Mursula, K.; Tsai, V.C.; Perkins, D.M.

    2011-01-01

    Recent studies have led to speculation that solar-terrestrial interaction, measured by sunspot number and geomagnetic activity, has played an important role in global temperature change over the past century or so. We treat this possibility as an hypothesis for testing. We examine the statistical significance of cross-correlations between sunspot number, geomagnetic activity, and global surface temperature for the years 1868-2008, solar cycles 11-23. The data contain substantial autocorrelation and nonstationarity, properties that are incompatible with standard measures of cross-correlational significance, but which can be largely removed by averaging over solar cycles and first-difference detrending. Treated data show an expected statistically- significant correlation between sunspot number and geomagnetic activity, Pearson p < 10-4, but correlations between global temperature and sunspot number (geomagnetic activity) are not significant, p = 0.9954, (p = 0.8171). In other words, straightforward analysis does not support widely-cited suggestions that these data record a prominent role for solar-terrestrial interaction in global climate change. With respect to the sunspot-number, geomagnetic-activity, and global-temperature data, three alternative hypotheses remain difficult to reject: (1) the role of solar-terrestrial interaction in recent climate change is contained wholly in long-term trends and not in any shorter-term secular variation, or, (2) an anthropogenic signal is hiding correlation between solar-terrestrial variables and global temperature, or, (3) the null hypothesis, recent climate change has not been influenced by solar-terrestrial interaction. ?? 2011 by the American Geophysical Union.

  20. Occurrence of neutral endopeptidase activity in the cat carotid body and its significance in chemoreception.

    PubMed

    Kumar, G K; Runold, M; Ghai, R D; Cherniack, N S; Prabhakar, N R

    1990-05-28

    The carotid body contains both tachykinins and enkephalins. Neutral endopeptidase (NEP, E.C. 3.4.24.11), has been suggested to involve in the metabolism of these neuropeptides in several organs. In the present study we determined neutral endopeptidase activity of the cat carotid body and assessed its significance in chemoreception. The cytosolic and membrane fractions of the carotid body contained NEP-like activity whereas it occurred only in the membrane fractions of the superior cervical and the nodose ganglia. Phosphoramidon, thiorphan and metal ion chelators inhibited NEP-like activity of all the 3 tissues studied; other protease inhibitors, however, were ineffective. Close carotid body administration of phosphoramidon significantly potentiated the carotid body response to low PO2 but not to hypercapnia. The enhanced response to hypoxia following phosphoramidon was further augmented by naloxone, an enkephalin antagonist. These results demonstrate that the glomus tissue contains detectable amounts of NEP-like activity and its inhibition selectively affects the hypoxic response of the carotid body.

  1. Surface modification of CoCr alloy using varying concentrations of phosphoric and phosphonoacetic acids: albumin and fibrinogen adsorption, platelet adhesion, activation, and aggregation studies.

    PubMed

    Thiruppathi, Eagappanath; Larson, Mark K; Mani, Gopinath

    2015-01-01

    CoCr alloy is commonly used in various cardiovascular medical devices for its excellent physical and mechanical properties. However, the formation of blood clots on the alloy surfaces is a serious concern. This research is focused on the surface modification of CoCr alloy using varying concentrations (1, 25, 50, 75, and 100 mM) of phosphoric acid (PA) and phosphonoacetic acid (PAA) to generate various surfaces with different wettability, chemistry, and roughness. Then, the adsorption of blood plasma proteins such as albumin and fibrinogen and the adhesion, activation, and aggregation of platelets with the various surfaces generated were investigated. Contact angle analysis showed PA and PAA coatings on CoCr provided a gradient of hydrophilic surfaces. FTIR showed PA and PAA were covalently bound to CoCr surface and formed different bonding configurations depending on the concentrations of coating solutions used. AFM showed the formation of homogeneous PA and PAA coatings on CoCr. The single and dual protein adsorption studies showed that the amount of albumin and fibrinogen adsorbed on the alloy surfaces strongly depend on the type of PA and PAA coatings prepared by different concentrations of coating solutions. All PA coated CoCr showed reduced platelet adhesion and activation when compared to control CoCr. Also, 75 and 100 mM PA-CoCr showed reduced platelet aggregation. For PAA coated CoCr, no significant difference in platelet adhesion and activation was observed between PAA coated CoCr and control CoCr. Thus, this study demonstrated that CoCr can be surface modified using PA for potentially reducing the formation of blood clots and improving the blood compatibility of the alloy.

  2. Varying behavior of different window sizes on the classification of static and dynamic physical activities from a single accelerometer.

    PubMed

    Fida, Benish; Bernabucci, Ivan; Bibbo, Daniele; Conforto, Silvia; Schmid, Maurizio

    2015-07-01

    Accuracy of systems able to recognize in real time daily living activities heavily depends on the processing step for signal segmentation. So far, windowing approaches are used to segment data and the window size is usually chosen based on previous studies. However, literature is vague on the investigation of its effect on the obtained activity recognition accuracy, if both short and long duration activities are considered. In this work, we present the impact of window size on the recognition of daily living activities, where transitions between different activities are also taken into account. The study was conducted on nine participants who wore a tri-axial accelerometer on their waist and performed some short (sitting, standing, and transitions between activities) and long (walking, stair descending and stair ascending) duration activities. Five different classifiers were tested, and among the different window sizes, it was found that 1.5 s window size represents the best trade-off in recognition among activities, with an obtained accuracy well above 90%. Differences in recognition accuracy for each activity highlight the utility of developing adaptive segmentation criteria, based on the duration of the activities.

  3. Functional significance of UDP-glucuronosyltransferase variants in the metabolism of active tamoxifen metabolites.

    PubMed

    Blevins-Primeau, Andrea S; Sun, Dongxiao; Chen, Gang; Sharma, Arun K; Gallagher, Carla J; Amin, Shantu; Lazarus, Philip

    2009-03-01

    Tamoxifen (TAM) is a selective estrogen receptor modulator widely used in the prevention and treatment of breast cancer. A major mode of metabolism of the major active metabolites of TAM, 4-OH-TAM and endoxifen, is by glucuronidation via the UDP-glucuronosyltransferase (UGT) family of enzymes. To examine whether polymorphisms in the UGT enzymes responsible for the glucuronidation of active TAM metabolites play an important role in interindividual differences in TAM metabolism, cell lines overexpressing wild-type or variant UGTs were examined for their activities against TAM metabolites in vitro. For variants of active extrahepatic UGTs, the UGT1A8(173Ala/277Tyr) variant exhibited no detectable glucuronidation activity against the trans isomers of either 4-OH-TAM or endoxifen. Little or no difference in TAM glucuronidating activity was observed for the UGT1A8(173Gly/277Cys) or UGT1A10(139Lys) variants compared with their wild-type counterparts. For active hepatic UGTs, the UGT2B7(268Tyr) variant exhibited significant (P < 0.01) 2- and 5-fold decreases in activity against the trans isomers of 4-OH-TAM and endoxifen, respectively, compared with wild-type UGT2B7(268His). In studies of 111 human liver microsomal specimens, the rate of O-glucuronidation against trans-4-OH-TAM and trans-endoxifen was 28% (P < 0.001) and 27% (P = 0.002) lower, respectively, in individuals homozygous for the UGT2B7 Tyr(268)Tyr genotype compared with subjects with the UGT2B7 His(268)His genotype, with a significant (P < 0.01) trend of decreasing activity against both substrates with increasing numbers of the UGT2B7(268His) allele. These results suggest that functional polymorphisms in TAM-metabolizing UGTs, including UGT2B7 and potentially UGT1A8, may be important in interindividual variability in TAM metabolism and response to TAM therapy.

  4. Biological significance of nuclear localization of mitogen-activated protein kinase Pmk1 in fission yeast.

    PubMed

    Sánchez-Mir, Laura; Franco, Alejandro; Madrid, Marisa; Vicente-Soler, Jero; Villar-Tajadura, M Antonia; Soto, Teresa; Pérez, Pilar; Gacto, Mariano; Cansado, José

    2012-07-27

    Mitogen-activated protein kinase (MAPK) signaling pathways play a fundamental role in the response of eukaryotic cells to environmental changes. Also, much evidence shows that the stimulus-dependent nuclear targeting of this class of regulatory kinases is crucial for adequate regulation of distinct cellular events. In the fission yeast Schizosaccharomyces pombe, the cell integrity MAPK pathway, whose central element is the MAPK Pmk1, regulates multiple processes such as cell wall integrity, vacuole fusion, cytokinesis, and ionic homeostasis. In non-stressed cells Pmk1 is constitutively localized in both cytoplasm and nucleus, and its localization pattern appears unaffected by its activation status or in response to stress, thus questioning the biological significance of the presence of this MAPK into the nucleus. We have addressed this issue by characterizing mutants expressing Pmk1 versions excluded from the cell nucleus and anchored to the plasma membrane in different genetic backgrounds. Although nuclear Pmk1 partially regulates cell wall integrity at a transcriptional level, membrane-tethered Pmk1 performs many of the biological functions assigned to wild type MAPK like regulation of chloride homeostasis, vacuole fusion, and cellular separation. However, we found that down-regulation of nuclear Pmk1 by MAPK phosphatases induced by the stress activated protein kinase pathway is important for the fine modulation of extranuclear Pmk1 activity. These results highlight the importance of the control of MAPK activity at subcellular level.

  5. Biological Significance of Nuclear Localization of Mitogen-activated Protein Kinase Pmk1 in Fission Yeast*

    PubMed Central

    Sánchez-Mir, Laura; Franco, Alejandro; Madrid, Marisa; Vicente-Soler, Jero; Villar-Tajadura, M. Antonia; Soto, Teresa; Pérez, Pilar; Gacto, Mariano; Cansado, José

    2012-01-01

    Mitogen-activated protein kinase (MAPK) signaling pathways play a fundamental role in the response of eukaryotic cells to environmental changes. Also, much evidence shows that the stimulus-dependent nuclear targeting of this class of regulatory kinases is crucial for adequate regulation of distinct cellular events. In the fission yeast Schizosaccharomyces pombe, the cell integrity MAPK pathway, whose central element is the MAPK Pmk1, regulates multiple processes such as cell wall integrity, vacuole fusion, cytokinesis, and ionic homeostasis. In non-stressed cells Pmk1 is constitutively localized in both cytoplasm and nucleus, and its localization pattern appears unaffected by its activation status or in response to stress, thus questioning the biological significance of the presence of this MAPK into the nucleus. We have addressed this issue by characterizing mutants expressing Pmk1 versions excluded from the cell nucleus and anchored to the plasma membrane in different genetic backgrounds. Although nuclear Pmk1 partially regulates cell wall integrity at a transcriptional level, membrane-tethered Pmk1 performs many of the biological functions assigned to wild type MAPK like regulation of chloride homeostasis, vacuole fusion, and cellular separation. However, we found that down-regulation of nuclear Pmk1 by MAPK phosphatases induced by the stress activated protein kinase pathway is important for the fine modulation of extranuclear Pmk1 activity. These results highlight the importance of the control of MAPK activity at subcellular level. PMID:22685296

  6. Biochemical changes in the liver and gill of Cathorops spixii collected seasonally in two Brazilian estuaries under varying influences of anthropogenic activities.

    PubMed

    Azevedo, J S; Braga, E S; Silva de Assis, H C; Oliveira Ribeiro, C A

    2013-10-01

    In order to understand environmental health by the use of a bioindicator species in estuaries, biochemical responses observed in the catfish Cathorops spixii such as catalase (CAT), glutathione-S-transferase (GST), lipid peroxidation (LPO) and acetylcholinesterase (AChE) were evaluated in liver and muscle. Furthermore, histological changes were also verified in liver and gills preparations. Fish were collected in three sites of the Santos-São Vicente estuary located at São Paulo (Brazil), subjected to varying levels of inputs of pollutants. For a reference site, specimens were sampled at Cananéia estuary at southern coast of São Paulo, a region with low anthropogenic influence. In general, no significant seasonal differences in antioxidant enzymes and lipid peroxidation responses were found in the organisms from the Cananéia estuary. However, in the polluted estuary (Santos-São Vicente), biochemical responses were observed by increases in GST hydroperoxides and decreases in AChE activities in the summer. Inhibition of AChE expression in fish from different areas of the Santos-São Vicente estuary in the summer was also found and can indicate neurotoxic effects in these organisms. Histopathological observation of gill and liver showed severe lesions, such as lamellar fusion and necrosis.

  7. Activation of Human Salivary Aldehyde Dehydrogenase by Sulforaphane: Mechanism and Significance

    PubMed Central

    Alam, Md. Fazle; Laskar, Amaj Ahmed; Maryam, Lubna

    2016-01-01

    Cruciferous vegetables contain the bio-active compound sulforaphane (SF) which has been reported to protect individuals against various diseases by a number of mechanisms, including activation of the phase II detoxification enzymes. In this study, we show that the extracts of five cruciferous vegetables that we commonly consume and SF activate human salivary aldehyde dehydrogenase (hsALDH), which is a very important detoxifying enzyme in the mouth. Maximum activation was observed at 1 μg/ml of cabbage extract with 2.6 fold increase in the activity. There was a ~1.9 fold increase in the activity of hsALDH at SF concentration of ≥ 100 nM. The concentration of SF at half the maximum response (EC50 value) was determined to be 52 ± 2 nM. There was an increase in the Vmax and a decrease in the Km of the enzyme in the presence of SF. Hence, SF interacts with the enzyme and increases its affinity for the substrate. UV absorbance, fluorescence and CD studies revealed that SF binds to hsALDH and does not disrupt its native structure. SF binds with the enzyme with a binding constant of 1.23 x 107 M-1. There is one binding site on hsALDH for SF, and the thermodynamic parameters indicate the formation of a spontaneous strong complex between the two. Molecular docking analysis depicted that SF fits into the active site of ALDH3A1, and facilitates the catalytic mechanism of the enzyme. SF being an antioxidant, is very likely to protect the catalytic Cys 243 residue from oxidation, which leads to the increase in the catalytic efficiency and hence the activation of the enzyme. Further, hsALDH which is virtually inactive towards acetaldehyde exhibited significant activity towards it in the presence of SF. It is therefore very likely that consumption of large quantities of cruciferous vegetables or SF supplements, through their activating effect on hsALDH can protect individuals who are alcohol intolerant against acetaldehyde toxicity and also lower the risk of oral cancer

  8. Volcanic activity before and after large tectonic earthquakes: Observations and statistical significance

    NASA Astrophysics Data System (ADS)

    Eggert, Silke; Walter, Thomas R.

    2009-06-01

    The study of volcanic triggering and interaction with the tectonic surroundings has received special attention in recent years, using both direct field observations and historical descriptions of eruptions and earthquake activity. Repeated reports of clustered eruptions and earthquakes may imply that interaction is important in some subregions. However, the subregions likely to suffer such clusters have not been systematically identified, and the processes responsible for the observed interaction remain unclear. We first review previous works about the clustered occurrence of eruptions and earthquakes, and describe selected events. We further elaborate available databases and confirm a statistically significant relationship between volcanic eruptions and earthquakes on the global scale. Moreover, our study implies that closed volcanic systems in particular tend to be activated in association with a tectonic earthquake trigger. We then perform a statistical study at the subregional level, showing that certain subregions are especially predisposed to concurrent eruption-earthquake sequences, whereas such clustering is statistically less significant in other subregions. Based on this study, we argue that individual and selected observations may bias the perceptible weight of coupling. The activity at volcanoes located in the predisposed subregions (e.g., Japan, Indonesia, Melanesia), however, often unexpectedly changes in association with either an imminent or a past earthquake.

  9. The temporal structures and functional significance of scale-free brain activity

    PubMed Central

    He, Biyu J.; Zempel, John M.; Snyder, Abraham Z.; Raichle, Marcus E.

    2010-01-01

    SUMMARY Scale-free dynamics, with a power spectrum following P ∝ f-β, are an intrinsic feature of many complex processes in nature. In neural systems, scale-free activity is often neglected in electrophysiological research. Here, we investigate scale-free dynamics in human brain and show that it contains extensive nested frequencies, with the phase of lower frequencies modulating the amplitude of higher frequencies in an upward progression across the frequency spectrum. The functional significance of scale-free brain activity is indicated by task performance modulation and regional variation, with β being larger in default network and visual cortex and smaller in hippocampus and cerebellum. The precise patterns of nested frequencies in the brain differ from other scale-free dynamics in nature, such as earth seismic waves and stock market fluctuations, suggesting system-specific generative mechanisms. Our findings reveal robust temporal structures and behavioral significance of scale-free brain activity and should motivate future study on its physiological mechanisms and cognitive implications. PMID:20471349

  10. The Crowded Sea: Incorporating Multiple Marine Activities in Conservation Plans Can Significantly Alter Spatial Priorities

    PubMed Central

    Mazor, Tessa; Possingham, Hugh P.; Edelist, Dori; Brokovich, Eran; Kark, Salit

    2014-01-01

    Successful implementation of marine conservation plans is largely inhibited by inadequate consideration of the broader social and economic context within which conservation operates. Marine waters and their biodiversity are shared by a host of stakeholders, such as commercial fishers, recreational users and offshore developers. Hence, to improve implementation success of conservation plans, we must incorporate other marine activities while explicitly examining trade-offs that may be required. In this study, we test how the inclusion of multiple marine activities can shape conservation plans. We used the entire Mediterranean territorial waters of Israel as a case study to compare four planning scenarios with increasing levels of complexity, where additional zones, threats and activities were added (e.g., commercial fisheries, hydrocarbon exploration interests, aquaculture, and shipping lanes). We applied the marine zoning decision support tool Marxan to each planning scenario and tested a) the ability of each scenario to reach biodiversity targets, b) the change in opportunity cost and c) the alteration of spatial conservation priorities. We found that by including increasing numbers of marine activities and zones in the planning process, greater compromises are required to reach conservation objectives. Complex plans with more activities incurred greater opportunity cost and did not reach biodiversity targets as easily as simplified plans with less marine activities. We discovered that including hydrocarbon data in the planning process significantly alters spatial priorities. For the territorial waters of Israel we found that in order to protect at least 10% of the range of 166 marine biodiversity features there would be a loss of ∼15% of annual commercial fishery revenue and ∼5% of prospective hydrocarbon revenue. This case study follows an illustrated framework for adopting a transparent systematic process to balance biodiversity goals and economic

  11. The DNA polymerase activity of Saccharomyces cerevisiae Rev1 is biologically significant.

    PubMed

    Wiltrout, Mary Ellen; Walker, Graham C

    2011-01-01

    A cell's ability to tolerate DNA damage is directly connected to the human development of diseases and cancer. To better understand the processes underlying mutagenesis, we studied the cell's reliance on the potentially error-prone translesion synthesis (TLS), and an error-free, template-switching pathway in Saccharomyces cerevisiae. The primary proteins mediating S. cerevisiae TLS are three DNA polymerases (Pols): Rev1, Pol ζ (Rev3/7), and Pol η (Rad30), all with human homologs. Rev1's noncatalytic role in recruiting other DNA polymerases is known to be important for TLS. However, the biological significance of Rev1's unusual conserved DNA polymerase activity, which inserts dC, is much less well understood. Here, we demonstrate that inactivating Rev1's DNA polymerase function sensitizes cells to both chronic and acute exposure to 4-nitroquinoline-1-oxide (4-NQO) but not to UV or cisplatin. Full Rev1-dependent resistance to 4-NQO, however, also requires the additional Rev1 functions. When error-free tolerance is disrupted through deletion of MMS2, Rev1's catalytic activity is more vital for 4-NQO resistance, possibly explaining why the biological significance of Rev1's catalytic activity has been elusive. In the presence or absence of Mms2-dependent error-free tolerance, the catalytic dead strain of Rev1 exhibits a lower 4-NQO-induced mutation frequency than wild type. Furthermore, Pol ζ, but not Pol η, also contributes to 4-NQO resistance. These results show that Rev1's catalytic activity is important in vivo when the cell has to cope with specific DNA lesions, such as N(2)-dG.

  12. Significant correlation between refractive index and activity of mitochondria: single mitochondrion study.

    PubMed

    Haseda, Keisuke; Kanematsu, Keita; Noguchi, Keiichi; Saito, Hiromu; Umeda, Norihiro; Ohta, Yoshihiro

    2015-03-01

    Measurements of refractive indices (RIs) of intracellular components can provide useful information on the structure and function of cells. The present study reports, for the first time, determination of the RI of an isolated mitochondrion in isotonic solution using retardation-modulated differential interference contrast microscopy. The value was 1.41 ± 0.01, indicating that mitochondria are densely packed with molecules having high RIs. Further, the RIs of each mitochondrion were significantly correlated with the mitochondrial membrane potential, an index of mitochondrial activity. These results will provide useful information on the structures and functions of cells based on the intracellular distribution of RIs.

  13. Relative activity of cerebral subcortical gray matter in varying states of attention and awareness in normal subjects and patient studies

    SciTech Connect

    Cooper, M.; Chen, C.T.; Levy, J.; Wagner, N.; Spire, J.P.; Jacobsen, J.; Meltzer, H.; Metz, J.; Beck, R.N.

    1985-05-01

    An important aspect of the study of brain function involves measurement of the relationships; between activities in the subcortical gray matter of the caudate and of the thalamus; and between these structures and functional cortical areas. The authors have studied these relationships in 22 subjects under different conditions of activation, sleep and sensory deprivation using a PET VI system and F-18-2DG to determine regional cerebral metabolism. Subject activating conditions were maintained throughout the period of equilibration of F-18-2DG and E.E.G.'s were monitored. Multiple tomographic slices of 1-2 million counts were obtained simultaneously with slice separation of 14mm and each plane parallel to the cantho-meatal line. In activated and non-activated awake conditions for normal subjects, left and right thalmus-to-caudate ratios were similar and greater than unity. This relationship was maintained in non-REM sleep, but was reversed and divergent in REM sleep and sensory deprivation; this was also evident in 3/4 narcoleptics awake and asleep in non-REM and REM and 2/3 schizophrenics and affective disorder, subjects. This approach appears to have potential for characterizating normal and disordered regional cerebral function.

  14. Fire Activity and Severity in the Western US Vary along Proxy Gradients Representing Fuel Amount and Fuel Moisture

    PubMed Central

    Parks, Sean A.; Parisien, Marc-André; Miller, Carol; Dobrowski, Solomon Z.

    2014-01-01

    Numerous theoretical and empirical studies have shown that wildfire activity (e.g., area burned) at regional to global scales may be limited at the extremes of environmental gradients such as productivity or moisture. Fire activity, however, represents only one component of the fire regime, and no studies to date have characterized fire severity along such gradients. Given the importance of fire severity in dictating ecological response to fire, this is a considerable knowledge gap. For the western US, we quantify relationships between climate and the fire regime by empirically describing both fire activity and severity along two climatic water balance gradients, actual evapotranspiration (AET) and water deficit (WD), that can be considered proxies for fuel amount and fuel moisture, respectively. We also concurrently summarize fire activity and severity among ecoregions, providing an empirically based description of the geographic distribution of fire regimes. Our results show that fire activity in the western US increases with fuel amount (represented by AET) but has a unimodal (i.e., humped) relationship with fuel moisture (represented by WD); fire severity increases with fuel amount and fuel moisture. The explicit links between fire regime components and physical environmental gradients suggest that multivariable statistical models can be generated to produce an empirically based fire regime map for the western US. Such models will potentially enable researchers to anticipate climate-mediated changes in fire recurrence and its impacts based on gridded spatial data representing future climate scenarios. PMID:24941290

  15. Fire activity and severity in the western US vary along proxy gradients representing fuel amount and fuel moisture.

    PubMed

    Parks, Sean A; Parisien, Marc-André; Miller, Carol; Dobrowski, Solomon Z

    2014-01-01

    Numerous theoretical and empirical studies have shown that wildfire activity (e.g., area burned) at regional to global scales may be limited at the extremes of environmental gradients such as productivity or moisture. Fire activity, however, represents only one component of the fire regime, and no studies to date have characterized fire severity along such gradients. Given the importance of fire severity in dictating ecological response to fire, this is a considerable knowledge gap. For the western US, we quantify relationships between climate and the fire regime by empirically describing both fire activity and severity along two climatic water balance gradients, actual evapotranspiration (AET) and water deficit (WD), that can be considered proxies for fuel amount and fuel moisture, respectively. We also concurrently summarize fire activity and severity among ecoregions, providing an empirically based description of the geographic distribution of fire regimes. Our results show that fire activity in the western US increases with fuel amount (represented by AET) but has a unimodal (i.e., humped) relationship with fuel moisture (represented by WD); fire severity increases with fuel amount and fuel moisture. The explicit links between fire regime components and physical environmental gradients suggest that multivariable statistical models can be generated to produce an empirically based fire regime map for the western US. Such models will potentially enable researchers to anticipate climate-mediated changes in fire recurrence and its impacts based on gridded spatial data representing future climate scenarios.

  16. Contextualized Approach to Language and Literacy (Project CALL): Capitalizing on Varied Activities and Contexts to Teach Early Literacy Skills

    ERIC Educational Resources Information Center

    Culatta, Barbara; Hall, Kendra; Kovarsky, Dana; Theadore, Geraldine

    2007-01-01

    In a federally funded early literacy project, various instructional activities were embedded into an array of classroom contexts to provide supplemental literacy instruction and to contrast children's engagement and participation in different contexts and participant structures. The study was conducted with English- and Spanish-speaking children…

  17. Leisure-Time Physical Activity, Sedentary Behavior, and Physical Fitness among Adolescents: Varying Definitions Yield Differing Results in Fitness Research

    ERIC Educational Resources Information Center

    Kerner, Matthew S.

    2005-01-01

    The aims of the study were (1) to assess the relationships among leisure-time physical activity, sedentary behaviors, and measures of health-related and performance-related physical fitness, and (2) to determine the primary predictors of performance-related physical fitness from the variables investigated. This study updates the literature with…

  18. Aspects of igneous activity significant to a repository at Yucca Mountain, Nevada

    SciTech Connect

    Krier, D. J.; Perry, F. V.

    2004-01-01

    Location, timing, volume, and eruptive style of post-Miocene volcanoes have defined the volcanic hazard significant to a proposed high-level radioactive waste (HLW) and spent nuclear fuel (SNF) repository at Yucca Mountain, Nevada, as a low-probability, high-consequence event. Examination of eruptive centers in the region that may be analogueues to possible future volcanic activity at Yucca Mountain have aided in defining and evaluating the consequence scenarios for intrusion into and eruption above a repository. The probability of a future event intersecting a repository at Yucca Mountain has a mean value of 1.7 x 10{sup -8} per year. This probability comes from the Probabilistic Volcanic Hazard Assessment (PVHA) completed in 1996 and updated to reflect change in repository layout. Since that time, magnetic anomalies representing potential buried volcanic centers have been identified fiom magnetic surveys; however these potential buried centers only slightly increase the probability of an event intersecting the repository. The proposed repository will be located in its central portion of Yucca Mountain at approximately 300m depth. The process for assessing performance of a repository at Yucca Mountain has identified two scenarios for igneous activity that, although having a very low probability of occurrence, could have a significant consequence should an igneous event occur. Either a dike swarm intersecting repository drifts containing waste packages, or a volcanic eruption through the repository could result in release of radioactive material to the accessible environment. Ongoing investigations are assessing the mechanisms and significance of the consequence scenarios. Lathrop Wells Cone ({approx}80,000 yrs), a key analogue for estimating potential future volcanic activity, is the youngest surface expression of apparent waning basaltic volcanism in the region. Cone internal structure, lavas, and ash-fall tephra have been examined to estimate eruptive volume

  19. Significant antitumor activity in vivo following treatment with the microtubule agent ENMD-1198.

    PubMed

    LaVallee, Theresa M; Burke, Patricia A; Swartz, Glenn M; Hamel, Ernest; Agoston, Gregory E; Shah, Jamshed; Suwandi, Lita; Hanson, Art D; Fogler, William E; Sidor, Carolyn F; Treston, Anthony M

    2008-06-01

    Clinical studies using the microtubule-targeting agent 2-methoxyestradiol (2ME2; Panzem) in cancer patients show that treatment is associated with clinical benefit, including prolonged stable disease, complete and partial responses, and an excellent safety profile. Studies have shown that 2ME2 is metabolized by conjugation at positions 3 and 17 and oxidation at position 17. To define structure-activity relationships for these positions of 2ME2 and to generate metabolically stable analogues with improved anti-tubulin properties, a series of analogues was generated and three lead analogues were selected, ENMD-1198, ENMD-1200, and ENMD-1237. These molecules showed improved metabolic stability with >65% remaining after 2-h incubation with hepatocytes. Pharmacokinetic studies showed that oral administration of the compounds resulted in increased plasma levels compared with 2ME2. All three analogues bind the colchicine binding site of tubulin, induce G(2)-M cell cycle arrest and apoptosis, and reduce hypoxia-inducible factor-1alpha levels. ENMD-1198 and ENMD-1200 showed improved in vitro antiproliferative activities. Significant reductions in tumor volumes compared with vehicle-treated mice were observed in an orthotopic breast carcinoma (MDA-MB-231) xenograft model following daily oral treatment with all compounds (ANOVA, P < 0.05). Significantly improved median survival time was observed with ENMD-1198 and ENMD-1237 (200 mg/kg/d) in a Lewis lung carcinoma metastatic model (P < 0.05). In both tumor models, the high-dose group of ENMD-1198 showed antitumor activity equivalent to that of cyclophosphamide. ENMD-1198 was selected as the lead molecule in this analogue series and is currently in a phase I clinical trial in patients with refractory solid tumors.

  20. Expression and biological significance of Ca2+-activated ion channels in human keratinocytes.

    PubMed

    Koegel, H; Alzheimer, C

    2001-01-01

    In whole-cell recordings from HaCaT keratinocytes, ATP, bradykinin, and histamine caused a biphasic change of the membrane potential consisting of an initial transient depolarization, followed by a pronounced and long-lasting hyperpolarization. Flash photolysis of caged IP3 mimicked the agonist-induced voltage response, suggesting that intracellular Ca2+ release and subsequent opening of Ca2+-activated ion channels serve as the common transduction mechanism. In contrast, cAMP- and PKC-dependent pathways were not involved in the electrophysiological effects of the extracellular signaling molecules. The depolarization was predominantly mediated by a DIDS- and niflumic acid-sensitive Cl- current, whereas a charybdotoxin- and clotrimazole-sensitive K+ current underlay the prominent hyperpolarization. Consistent with the electrophysiological data, RT-PCR showed that HaCaT keratinocytes express two types of Ca2+-activated Cl- channels, CaCC2 and CaCC3 (CLCA2), as well as the Ca2+-activated K+ channel hSK4. That the pronounced hSK4-mediated hyperpolarization bears significance on the growth and differentiation properties of keratinocytes is suggested by RNase protection assays showing that hSK4 mRNA expression is strongly down-regulated under conditions that allow keratinocyte differentiation. hSK4 might thus play a role in linking changes in membrane potential to the biological fate of keratinocytes.

  1. A Smartphone Application Significantly Improved Diabetes Self-Care Activities with High User Satisfaction

    PubMed Central

    Kim, Yu Jin; Byun, Jong Kyu; Park, So Young; Hong, Soo Min; Chin, Sang Ouk; Chon, Suk; Oh, Seungjoon; Woo, Jeong-taek; Kim, Sung Woon; Kim, Young Seol

    2015-01-01

    Background We developed for the first time a smartphone application designed for diabetes self-management in Korea and registered a patent for the relevant algorithm. We also investigated the user satisfaction with the application and the change in diabetes related self-care activities after using the application. Methods We conducted a questionnaire survey on volunteers with diabetes who were using the application. Ninety subjects responded to the questionnaire between June 2012 and March 2013. A modified version of the Summary of Diabetes Self-Care Activities (SDSCA) was used in this study. Results The survey results exhibited a mean subject age of 44.0 years old, and males accounted for 78.9% of the subjects. Fifty percent of the subjects had diabetes for less than 3 years. The majority of respondents experienced positive changes in their clinical course after using the application (83.1%) and were satisfied with the structure and completeness of the application (86.7%). Additionally, the respondents' answers indicated that the application was easy to use (96.7%) and recommendable to others (97.7%) and that they would continue using the application to manage their diabetes (96.7%). After using the Diabetes Notepad application, diabetes related self-care activities assessed by SDSCA displayed statistically significant improvements (P<0.05), except for the number of days of drinking. Conclusion This smartphone-based application can be a useful tool leading to positive changes in diabetes related self-care activities and increase user satisfaction. PMID:26124991

  2. Learning and memory in the forced swimming test: effects of antidepressants having varying degrees of anticholinergic activity.

    PubMed

    Enginar, Nurhan; Yamantürk-Çelik, Pınar; Nurten, Asiye; Güney, Dilvin Berrak

    2016-07-01

    The antidepressant-induced reduction in immobility time in the forced swimming test may depend on memory impairment due to the drug's anticholinergic efficacy. Therefore, the present study evaluated learning and memory of the immobility response in rats after the pretest and test administrations of antidepressants having potent, comparatively lower, and no anticholinergic activities. Immobility was measured in the test session performed 24 h after the pretest session. Scopolamine and MK-801, which are agents that have memory impairing effects, were used as reference drugs for a better evaluation of the memory processes in the test. The pretest administrations of imipramine (15 and 30 mg/kg), amitriptyline (7.5 and 15 mg/kg), trazodone (10 mg/kg), fluoxetine (10 and 20 mg/kg), and moclobemide (10 and 20 mg/kg) were ineffective, whereas the pretest administrations of scopolamine (0.5 mg/kg) and MK-801 (0.1 mg/kg) decreased immobility time suggesting impaired "learning to be immobile" in the animals. The test administrations of imipramine (30 mg/kg), amitriptyline (15 mg/kg), moclobemide (10 mg/kg), scopolamine (0.5 and 1 mg/kg), and MK-801 (0.1 mg/kg) decreased immobility time, which suggested that the drugs exerted antidepressant activity or the animals did not recall that attempting to escape was futile. The test administrations of trazodone (10 mg/kg) and fluoxetine (10 and 20 mg/kg) produced no effect on immobility time. Even though the false-negative and positive responses made it somewhat difficult to interpret the findings, this study demonstrated that when given before the pretest antidepressants with or without anticholinergic activity seemed to be devoid of impairing the learning process in the test.

  3. DNA-directed alkylating agents. 1. Structure-activity relationships for acridine-linked aniline mustards: consequences of varying the reactivity of the mustard.

    PubMed

    Gourdie, T A; Valu, K K; Gravatt, G L; Boritzki, T J; Baguley, B C; Wakelin, L P; Wilson, W R; Woodgate, P D; Denny, W A

    1990-04-01

    A series of DNA-targeted aniline mustards have been prepared, and their chemical reactivity and in vitro and in vivo cytotoxicity have been evaluated and compared with that of the corresponding simple aniline mustards. The alkylating groups were anchored to the DNA-intercalating 9-aminoacridine chromophore by an alkyl chain of fixed length attached at the mustard 4-position through a link group X, while the corresponding simple mustards possessed an electronically identical small group at this position. The link group was varied to provide a series of compounds of similar geometry but widely differing mustard reactivity. Variation in biological activity should then largely be a consequence of this varying reactivity. Rates of mustard hydrolysis in the two series related only to the electronic properties of the link group, with attachment of the intercalating chromophore having no effect. The cytotoxicities of the simple mustards correlated well with group electronic properties (with a 200-300-fold range in IC50S). The corresponding DNA-targeted mustards were much more potent (up to 100-fold), but their IC50 values varied much less with linker group electronic properties. Most of the DNA-targeted mustards showed in vivo antitumor activity, being both more active and more dose-potent than either the corresponding untargeted mustards and chlorambucil. These results show that targeting alkylating agents to DNA by attachment to DNA-affinic units may be a useful strategy.

  4. Breaking the Meyer-Overton rule: predicted effects of varying stiffness and interfacial activity on the intrinsic potency of anesthetics.

    PubMed Central

    Cantor, R S

    2001-01-01

    Exceptions to the Meyer-Overton rule are commonly cited as evidence against indirect, membrane-mediated mechanisms of general anesthesia. However, another interpretation is possible within the context of an indirect mechanism in which solubilization of an anesthetic in the membrane causes a redistribution of lateral pressures in the membrane, which in turn shifts the conformational equilibrium of membrane proteins such as ligand-gated ion channels. It is suggested that compounds of different stiffness and interfacial activity have different intrinsic potencies, i.e., they cause widely different redistributions of the pressure profile (and thus different effects on protein conformational equilibria) per unit concentration of the compound in the membrane. Calculations incorporating the greater stiffness of perfluoromethylenic chains and the large interfacial attraction of hydroxyl groups predict the higher intrinsic potency of short alkanols than alkanes, the cutoffs in potency of alkanes and alkanols and the much shorter cutoffs for their perfluorinated analogues. Both effects, increased stiffness and interfacial activity, are present in unsaturated hydrocarbon solutes, and the intrinsic potencies are predicted to depend on the magnitude of both effects and on the number and locations of multiple bonds within the molecule. Most importantly, the intrinsic potencies of polymeric alkanols with regularly spaced hydroxyl groups are predicted to rise with increasing chain length, without cutoff; such molecules should serve to distinguish unambiguously between indirect mechanisms and direct binding mechanisms of anesthesia. PMID:11325730

  5. [Lymphokine-activated killer cell adoptive immunotherapy for cancer treatment and its significance].

    PubMed

    Toge, T; Yamaguchi, Y

    1992-09-01

    New culture system, CDCS-T1, was developed for clinical conduction of lymphokine-activated killer (LAK) cell adoptive immunotherapy (AIT). Advanced or recurrent cancer patients of digestive tract were treated with AIT with LAK cells generated by CDCS-T1 in combination with plasma exchange. Partial responses were shown in 10 to 20% of patients treated. Long survival was found in some responders, indicating the significance of LAK therapy for cancer treatment. AIT with LAK cell transfer was also conducted in patients with esophageal cancer as postoperative adjuvant therapy. Better restoration of postoperative depression of immunological parameters was found in patients with postoperative LAK cell transfer. It is suggested that postoperative LAK cell transfer is a good candidate for adjuvant immunotherapy for cancer treatment.

  6. Nanosilver based anionic linear globular dendrimer with a special significant antiretroviral activity.

    PubMed

    Ardestani, Mehdi Shafiee; Fordoei, Alireza Salehi; Abdoli, Asghar; Ahangari Cohan, Reza; Bahramali, Golnaz; Sadat, Seyed Mehdi; Siadat, Seyed Davar; Moloudian, Hamid; Nassiri Koopaei, Nasser; Bolhasani, Azam; Rahimi, Pooneh; Hekmat, Soheila; Davari, Mehdi; Aghasadeghi, Mohammad Reza

    2015-05-01

    HIV is commonly caused to a very complicated disease which has not any recognized vaccine, so designing and development of novel antiretroviral agents with specific application of nanomedicine is a globally interested research subject worldwide. In the current study, a novel structure of silver complexes with anionic linear globular dendrimer was synthesized, characterized and then assessed against HIV replication pathway in vitro as well. The results showed a very good yield of synthesis (up to 70%) for the nano-complex as well as a very potent significant (P < 0.05) antiretroviral activity with non-severe toxic effects in comparison with the Nevirapine as standard drug in positive control group. According to the present data, silver anionic linear globular dendrimers complex may have a promising future to inhibit replication of HIV viruse in clinical practice.

  7. Significant foreshock activities of M>7.5 earthquakes in the Kuril subduction zone

    NASA Astrophysics Data System (ADS)

    Harada, T.; Yokoi, S.; Satake, K.

    2014-12-01

    In the Kuril subduction zone, some M>7.5 earthquakes are accompanied by significant foreshock activities, providing a good opportunity to understand the characteristics of foreshocks for large interplate events such as occur along the Japan Trench and Nankai Trough etc. Some preliminary results from our examination of the foreshock sequences are as follows. Relocated foreshocks tend to migrate with time toward the trench axis. Foreshock distributions of the interplate earthquakes do not overlap with the large coseismic slips (asperities) of the mainshocks. Foreshocks of the 2007 northern Kuril outer-rise event, however, were distributed on the entire rupture area. Foreshock sequences seem to be limited in the regions where the background seismicity rates are relatively high. The foreshock activities were found in the examination of the space-time pattern of M>7 events along the northern Japan to Kuril trench since 1913 (e.g. Harada, Satake, and Ishibashi, 2011:AGU, 2012:AOGS). The large earthquakes preceded by active foreshock sequences are: the 2006 (M8.3), 2007 (M8.1) offshore Simushir earthquakes, the 1963 (M8.5), 1991 (M7.6), 1995 (M7.9) offshore Urup events, the 1978 (M7.8) offshore Iturup events, the 1969 (M8.2) offshore Shikotan event. In contrast, M>7.5 interplate earthquakes offshore Hokkaido (1952 (M8.1), 1973 (M7.8), 2003 (M8.1)) and intraslab earthquakes (1958 (M8.3), 1978 (M7.8), 1993 (M7.6), 1994 (M8.3)) had few or no foreshocks. In the examination of the active foreshocks, we relocated foreshocks by the Modified JHD method (Hurukawa, 1995), compared relocated foreshock areas with mainshock coseismic slip distributions estimated by the teleseismic body-wave inversion (Kikuchi and Kanamori, 2003), and examined the relation between active foreshock sequences and regional background seismicity. This study was supported by the MEXT's "New disaster mitigation research project on Mega thrust earthquakes around Nankai/Ryukyu subduction zones".

  8. Chronic methamphetamine exposure significantly decreases microglia activation in the arcuate nucleus.

    PubMed

    Lloyd, Steven A; Corkill, Beau; Bruster, Matthew C; Roberts, Rick L; Shanks, Ryan A

    2017-03-18

    Methamphetamine is a powerful psychostimulant drug and its use and abuse necessitates a better understanding of its neurobiobehavioral effects. The acute effects of binge dosing of methamphetamine on the neurons in the CNS are well studied. However, the long-term effects of chronic, low-dose methamphetamine are less well characterized, especially in other cell types and areas outside of the major dopamine pathways. Mice were administered 5mg/kg/day methamphetamine for ten days and brain tissue was analyzed using histochemistry and image analysis. Increased microglia activity in the striatum confirmed toxic effects of methamphetamine in this brain region using this dosing paradigm. A significant decrease in microglia activity in the arcuate nucleus of the hypothalamus was observed with no effect noted on dopamine neurons in the arcuate nucleus. Given the importance of this area in homeostatic and neuroendocrine regulation, the current study highlights the need to more fully understand the systemic effects of chronic, low-dose methamphetamine use. The novel finding of microglia downregulation after chronic methamphetamine could lead to advances in understanding neuroinflammatory responses towards addiction treatment and protection from psychostimulant-induced neurotoxicity.

  9. Risperidone significantly inhibits interferon-gamma-induced microglial activation in vitro.

    PubMed

    Kato, Takahiro; Monji, Akira; Hashioka, Sadayuki; Kanba, Shigenobu

    2007-05-01

    Microglia has recently been regarded to be a mediator of neuroinflammation via the release of proinflammatory cytokines, nitric oxide (NO) and reactive oxygen species (ROS) in the central nervous system (CNS). Microglia has thus been reported to play an important role in the pathology of neurodegenerative disease, such as Alzheimer's disease (AD) and Parkinson's disease (PD). The pathological mechanisms of schizophrenia remain unclear while some recent neuroimaging studies suggest even schizophrenia may be a kind of neurodegenerative disease. Risperidone has been reported to decrease the reduction of MRI volume during the clinical course of schizophrenia. Many recent studies have demonstrated that immunological mechanisms via such as interferon (IFN)-gamma and cytokines might be relevant to the pathophysiology of schizophrenia. In the present study, we thus investigated the effects of risperidone on the generation of nitric oxide, inducible NO synthase (iNOS) expression and inflammatory cytokines: interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha by IFN-gamma-activated microglia by using Griess assay, Western blotting and ELISA, respectively. In comparison with haloperidol, risperidone significantly inhibited the production of NO and proinflammatory cytokines by activated microglia. The iNOS levels of risperidone-treated cells were much lower than those of the haloperidol-treated cells. Antipsychotics, especially risperidone may have an anti-inflammatory effect via the inhibition of microglial activation, which is not only directly toxic to neurons but also has an inhibitory effect on neurogenesis and oligodendrogenesis, both of which have been reported to play a crucial role in the pathology of schizophrenia.

  10. Volcanic activity before and after large tectonic earthquakes: Observations and statistical significance

    NASA Astrophysics Data System (ADS)

    Eggert, S.; Walter, T. R.

    2009-04-01

    The study of volcanic triggering and coupling to the tectonic surroundings has received special attention in recent years, using both direct field observations and historical descriptions of eruptions and earthquake activity. Repeated reports of volcano-earthquake interactions in, e.g., Europe and Japan, may imply that clustered occurrence is important in some regions. However, the regions likely to suffer clustered eruption-earthquake activity have not been systematically identified, and the processes responsible for the observed interaction are debated. We first review previous works about the correlation of volcanic eruptions and earthquakes, and describe selected local clustered events. Following an overview of previous statistical studies, we further elaborate the databases of correlated eruptions and earthquakes from a global perspective. Since we can confirm a relationship between volcanic eruptions and earthquakes on the global scale, we then perform a statistical study on the regional level, showing that time and distance between events follow a linear relationship. In the time before an earthquake, a period of volcanic silence often occurs, whereas in the time after, an increase in volcanic activity is evident. Our statistical tests imply that certain regions are especially predisposed to concurrent eruption-earthquake pairs, e.g., Japan, whereas such pairing is statistically less significant in other regions, such as Europe. Based on this study, we argue that individual and selected observations may bias the perceptible weight of coupling. Volcanoes located in the predisposed regions (e.g., Japan, Indonesia, Melanesia), however, indeed often have unexpectedly changed in association with either an imminent or a past earthquake.

  11. Significance of Neuronal Cytochrome P450 Activity in Opioid-Mediated Stress-Induced Analgesia

    PubMed Central

    Hough, Lindsay B.; Nalwalk, Julia W.; Yang, Weizhu; Ding, Xinxin

    2014-01-01

    Stressful environmental changes can suppress nociceptive transmission, a phenomenon known as “stress-induced analgesia”. Depending on the stressor and the subject, opioid or non-opioid mechanisms are activated. Brain μ opioid receptors mediate analgesia evoked either by exogenous agents (e.g. morphine), or by the release of endogenous opioids following stressful procedures. Recent work with morphine and neuronal cytochrome P450 (P450)-deficient mice proposed a signal transduction role for P450 enzymes in μ analgesia. Since μ opioid receptors also mediate some forms of stress-induced analgesia, the present studies assessed the significance of brain P450 activity in opioid-mediated stress-induced analgesia. Two widely-used models of opioid stress-induced analgesia (restraint and warm water swim) were studied in both sexes of wild-type control and P450-deficient (Null) mice. In control mice, both stressors evoked moderate analgesic responses which were blocked by pretreatment with the opioid antagonist naltrexone, confirming the opioid nature of these responses. Consistent with literature, sex differences (control female > control male) were seen in swim-induced, but not restraint-induced, analgesia. Null mice showed differential responses to the two stress paradigms. As compared with control subjects, Null mice showed highly attenuated restraint-induced analgesia, showing a critical role for neuronal P450s in this response. However, warm water swim-induced analgesia was unchanged in Null vs. control mice. Additional control experiments confirmed the absence of morphine analgesia in Null mice. These results are the first to show that some forms of opioid-mediated stress-induced analgesia require brain neuronal P450 activity. PMID:25020125

  12. Regional and total body active heating and cooling of a resting diver in water of varied temperatures

    NASA Astrophysics Data System (ADS)

    Bardy, Erik; Mollendorf, Joseph; Pendergast, David

    2008-02-01

    Passive insulations alone are not sufficient for maintaining underwater divers in thermal balance or comfort. The purpose of this study was to experimentally determine the active heating and cooling requirements to keep a diver at rest in thermal balance and comfort in water temperatures between 10 and 40 °C. A diver wearing a prototype tubesuit and a wetsuit (3 or 6.5 mm foam neoprene) was fully submersed (0.6 m) in water at a specified temperature (10, 20, 30 and 40 °C). During immersion, the tubesuit was perfused with 30 °C water at a flow rate of 0.5 L min-1 to six individual body regions. An attempt was made to keep skin temperatures below 42 °C in hot water (>30 °C) and elevated but below 32 °C in cold water (<20 °C). A skin temperature of 32 °C is the threshold for maximal body thermal resistance due to vasoconstriction. Skin temperatures and core temperature were monitored during immersion to ensure they remained within set thermal limits. In addition skin heat flux, oxygen consumption and the thermal exchange of the tubesuit were measured. In both wetsuit thicknesses there was a linear correlation between the thermal exchange of the tubesuit and ambient water temperature. In the 6.5 mm wetsuit -214 W to 242 W of heating (-) and cooling (+) was necessary in 10 °C to 40 °C water, respectively. In the 3 mm wetsuit -462 to 342 W was necessary in 10 °C to 40 °C water, respectively. It was therefore concluded that a diver at rest can be kept in thermal balance in 10-40 °C water with active heating and cooling.

  13. Active fault detection and isolation of discrete-time linear time-varying systems: a set-membership approach

    NASA Astrophysics Data System (ADS)

    Mojtaba Tabatabaeipour, Seyed

    2015-08-01

    Active fault detection and isolation (AFDI) is used for detection and isolation of faults that are hidden in the normal operation because of a low excitation signal or due to the regulatory actions of the controller. In this paper, a new AFDI method based on set-membership approaches is proposed. In set-membership approaches, instead of a point-wise estimation of the states, a set-valued estimation of them is computed. If this set becomes empty the given model of the system is not consistent with the measurements. Therefore, the model is falsified. When more than one model of the system remains un-falsified, the AFDI method is used to generate an auxiliary signal that is injected into the system for detection and isolation of faults that remain otherwise hidden or non-isolated using passive FDI (PFDI) methods. Having the set-valued estimation of the states for each model, the proposed AFDI method finds an optimal input signal that guarantees FDI in a finite time horizon. The input signal is updated at each iteration in a decreasing receding horizon manner based on the set-valued estimation of the current states and un-falsified models at the current sample time. The problem is solved by a number of linear and quadratic programming problems, which result in a computationally efficient algorithm. The method is tested on a numerical example as well as on the pitch actuator of a benchmark wind turbine.

  14. Modeling and classifying human activities from trajectories using a class of space-varying parametric motion fields.

    PubMed

    Nascimento, Jacinto C; Marques, Jorge S; Lemos, João M

    2013-05-01

    Many approaches to trajectory analysis, such as clustering or classification, use probabilistic generative models, thus not requiring trajectory alignment/registration. Switched linear dynamical models (e.g., HMMs) have been used in this context, due to their ability to describe different motion regimes. However, these models are not suitable for handling space-dependent dynamics that are more naturally captured by nonlinear models. As is well known, these are more difficult to identify. In this paper, we propose a new way of modeling trajectories, based on a mixture of parametric motion vector fields that depend on a small number of parameters. Switching among these fields follows a probabilistic mechanism, characterized by a field of stochastic matrices. This approach allows representing a wide variety of trajectories and modeling space-dependent behaviors without using global nonlinear dynamical models. Experimental evaluation is conducted in both synthetic and real scenarios. The latter concerning with human trajectory modeling for activity classification, a central task in video surveillance.

  15. Multistability of memristive Cohen-Grossberg neural networks with non-monotonic piecewise linear activation functions and time-varying delays.

    PubMed

    Nie, Xiaobing; Zheng, Wei Xing; Cao, Jinde

    2015-11-01

    The problem of coexistence and dynamical behaviors of multiple equilibrium points is addressed for a class of memristive Cohen-Grossberg neural networks with non-monotonic piecewise linear activation functions and time-varying delays. By virtue of the fixed point theorem, nonsmooth analysis theory and other analytical tools, some sufficient conditions are established to guarantee that such n-dimensional memristive Cohen-Grossberg neural networks can have 5(n) equilibrium points, among which 3(n) equilibrium points are locally exponentially stable. It is shown that greater storage capacity can be achieved by neural networks with the non-monotonic activation functions introduced herein than the ones with Mexican-hat-type activation function. In addition, unlike most existing multistability results of neural networks with monotonic activation functions, those obtained 3(n) locally stable equilibrium points are located both in saturated regions and unsaturated regions. The theoretical findings are verified by an illustrative example with computer simulations.

  16. Significant bone microarchitecture impairment in premenopausal women with active celiac disease.

    PubMed

    Zanchetta, María Belén; Costa, Florencia; Longobardi, Vanesa; Longarini, Gabriela; Mazure, Roberto Martín; Moreno, María Laura; Vázquez, Horacio; Silveira, Fernando; Niveloni, Sonia; Smecuol, Edgardo; Temprano, María de la Paz; Hwang, Hui Jer; González, Andrea; Mauriño, Eduardo César; Bogado, Cesar; Zanchetta, Jose R; Bai, Julio César

    2015-07-01

    Patients with active celiac disease (CD) are more likely to have osteoporosis and increased risk of fractures. High-resolution peripheral quantitative computed tomography (HR-pQCT) permits three-dimensional exploration of bone microarchitectural characteristics measuring separately cortical and trabecular compartments, and giving a more profound insight into bone disease pathophysiology and fracture. We aimed to determine the volumetric and microarchitectural characteristics of peripheral bones-distal radius and tibia-in an adult premenopausal cohort with active CD assessed at diagnosis. We prospectively enrolled 31 consecutive premenopausal women with newly diagnosed CD (median age 29 years, range: 18-49) and 22 healthy women of similar age (median age 30 years, range 21-41) and body mass index. Compared with controls, peripheral bones of CD patients were significantly lower in terms of total volumetric density mg/cm(3) (mean ± SD: 274.7 ± 51.7 vs. 324.7 ± 45.8, p 0.0006 at the radius; 264.4 ± 48.7 vs. 307 ± 40.7, p 0.002 at the tibia), trabecular density mg/cm(3) (118.6 ± 31.5 vs. 161.9 ± 33.6, p<0.0001 at the radius; 127.9 ± 28.7 vs. 157.6 ± 15.6, p < 0.0001 at the tibia); bone volume/trabecular volume ratio % (9.9 ± 2.6 vs. 13.5 ± 2.8, p<0.0001 at the radius; 10.6 ± 2.4 vs. 13.1 ± 1.3, p < 0.0001 at the tibia); number of trabeculae 1/mm (1.69 ± 0.27 vs. 1.89 ± 0.26, p 0.009 at the radius; 1.53 ± 0.32 vs. 1.80 ± 0.26, p 0.002 at the tibia); and trabecular thickness mm (0.058 ± 0.010 vs. 0.071 ± 0.008, p < 0.0001 at the radius with no significant difference at the tibia). Cortical density was significantly lower in both regions (D comp mg/cm(3) 860 ± 57.2 vs. 893.9 ± 43, p 0.02; 902.7 ± 48.7 vs. 932.6 ± 32.6, p 0.01 in radius and tibia respectively). Although cortical thickness was lower in CD patients, it failed to show any significant inter-group difference (a-8% decay with p 0.11 in both bones). Patients with symptomatic CD (n = 22) had

  17. Significantly Enhanced Visible Light Photoelectrochemical Activity in TiO₂ Nanowire Arrays by Nitrogen Implantation.

    PubMed

    Wang, Gongming; Xiao, Xiangheng; Li, Wenqing; Lin, Zhaoyang; Zhao, Zipeng; Chen, Chi; Wang, Chen; Li, Yongjia; Huang, Xiaoqing; Miao, Ling; Jiang, Changzhong; Huang, Yu; Duan, Xiangfeng

    2015-07-08

    Titanium oxide (TiO2) represents one of most widely studied materials for photoelectrochemical (PEC) water splitting but is severely limited by its poor efficiency in the visible light range. Here, we report a significant enhancement of visible light photoactivity in nitrogen-implanted TiO2 (N-TiO2) nanowire arrays. Our systematic studies show that a post-implantation thermal annealing treatment can selectively enrich the substitutional nitrogen dopants, which is essential for activating the nitrogen implanted TiO2 to achieve greatly enhanced visible light photoactivity. An incident photon to electron conversion efficiency (IPCE) of ∼10% is achieved at 450 nm in N-TiO2 without any other cocatalyst, far exceeding that in pristine TiO2 nanowires (∼0.2%). The integration of oxygen evolution reaction (OER) cocatalyst with N-TiO2 can further increase the IPCE at 450 nm to ∼17% and deliver an unprecedented overall photocurrent density of 1.9 mA/cm(2), by integrating the IPCE spectrum with standard AM 1.5G solar spectrum. Systematic photoelectrochemical and electrochemical studies demonstrated that the enhanced PEC performance can be attributed to the significantly improved visible light absorption and more efficient charge separation. Our studies demonstrate the implantation approach can be used to reliably dope TiO2 to achieve the best performed N-TiO2 photoelectrodes to date and may be extended to fundamentally modify other semiconductor materials for PEC water splitting.

  18. Non-conductive and miniature fiber-optic imaging system for real-time detection of neuronal activity in time-varying electromagnetic fields.

    PubMed

    Saito, Atsushi; Takahashi, Masayuki; Jimbo, Yasuhiko; Nakasono, Satoshi

    2017-01-15

    Establishing an appropriate threshold value for neuronal modulation by time-varying electromagnetic field (EMF) exposure is important for developing international guidelines to protect against the potential health effects, and to design a variety of medical devices. However, it is technically difficult to achieve real-time detection of neuronal activity under repetitive and long-term exposure to EMF. For this purpose, we developed a non-conductive, miniature, and flexible fiber-optic imaging system that does not affect the electromagnetic noise, induction heating, or vibration in a high-intensity and repetitive time-varying EMF exposure. Using the proposed system, we succeeded at real-time detection of spontaneous Ca(2+) oscillations in single neuronal and glial cells, as well as synchronized bursting activities of multiple neuronal networks at a micrometer-scale and millisecond-order spatiotemporal resolution during long-term EMF exposure (sinusoidal wave, 20kHz, 8.6mT, >30min). The results indicated that short-term (<5min) exposure-related neuronal modulation was not detectable; however, long-term (15-30min) exposure was observed to depress neuronal activities. In addition, the simultaneous and real-time recording of neuronal activity and the environmental temperature revealed that the neuronal modulation was accompanied by a 0.5-1°C rise in the temperature of the culture medium induced by the heat generation of exposure coils. These findings suggest that our real-time imaging system can be used for precise evaluation of the threshold values and clarification of the mechanisms of neuronal modulation induced by time-varying EMF exposure.

  19. Cationic Polymethacrylate-Modified Liposomes Significantly Enhanced Doxorubicin Delivery and Antitumor Activity

    PubMed Central

    Wang, Wenxi; Shao, Anna; Zhang, Nan; Fang, Jinzhang; Ruan, Jennifer Jin; Ruan, Benfang Helen

    2017-01-01

    Liposome (LP) encapsulation of doxorubicin (DOX) is a clinically validated method for cancer drug delivery, but its cellular uptake is actually lower than the free DOX. Therefore, we modified DOX-LP with a cationic polymer (Eudragit RL100; ER) to improve its cellular uptake and antitumor activity. The resulting DOX-ERLP was a 190 nm nanoparticle that was absorbed efficiently and caused cancer cell death in 5 hrs. Growth as measured by the MTT assay or microscopic imaging demonstrated that DOX-ERLP has at least a two-fold greater potency than the free DOX in inhibiting the growth of a DOX resistant (MCF7/adr) cell and an aggressive liver cancer H22 cell. Further, its in vivo efficacy was tested in H22-bearing mice, where four injections of DOX-ERLP reduced the tumor growth by more than 60% and caused an average of 60% tumor necrosis, which was significantly better than the DOX and DOX-LP treated groups. Our work represents the first use of polymethacrylate derivatives for DOX liposomal delivery, demonstrating the great potential of cationic polymethacrylate modified liposomes for improving cancer drug delivery. PMID:28225062

  20. Seasonal activity of millipedes (Diplopoda)--their economic and medical significance.

    PubMed

    Kania, Grzegorz; Kłapeć, Teresa

    2012-01-01

    The millipede Brachydesmus superus Latzel, Polydesmus inconstans Latzel (Diplopoda: Polydesmida) and Kryphioiulus occultus C. L. Koch (Diplopoda: Julida) were collected from compost in gardens in Lublin, eastern Poland. Collections were made by using pitfall traps between April - September 2009 and 2010. Brachydesmus superus, Polydesmus inconstans and Kryphioiulus occultus play a significant role in composting of plant residues. Cylindroiulus caeruleocinctus Wood and Ommatoiulus sabulosus Linnaeus (Diplopoda: Julida) were collected manually in 2009-2011 in fallows and ruderals of Lublin and Kraków. C. caeruleocinctus and O. sabulosus caused considerable nuisance during mass occurrence and migration in human residences. The sex ratio has been determined for populations of C. caeruleocinctus, total sex ratio average 1:1.46. The number of females prevailed. Millipedes of the temperate climate have two peaks in the spring and autumn pattern of activity of the year. Both common species C. caeruleocinctus and O. sabulosus were analysed bacteriologically. The millipede Cylindroiulus caeruleocinctus transmits Citrobacter freundii, Pantoea agglomerans, Serratia marcescens, Raoultella planticola, Salmonella arizonae. The millipede Ommatoiulus sabulosus transmits Citrobacter freundii, Pantoea agglomerans, Raoultella planticola and Xanthomonas maltophila.

  1. Novel pyrazole derivatives as neutral CB₁ antagonists with significant activity towards food intake.

    PubMed

    Manca, Ilaria; Mastinu, Andrea; Olimpieri, Francesca; Falzoi, Matteo; Sani, Monica; Ruiu, Stefania; Loriga, Giovanni; Volonterio, Alessandro; Tambaro, Simone; Bottazzi, Mirko Emilio Heiner; Zanda, Matteo; Pinna, Gérard Aimè; Lazzari, Paolo

    2013-04-01

    In spite of rimonabant's withdrawal from the European market due to its adverse effects, interest in the development of drugs based on CB1 antagonists is revamping on the basis of the peculiar properties of this class of compounds. In particular, new strategies have been proposed for the treatment of obesity and/or related risk factors through CB1 antagonists, i.e. by the development of selectively peripherally acting agents or by the identification of neutral CB1 antagonists. New compounds based on the lead CB1 antagonist/inverse agonist rimonabant have been synthesized with focus on obtaining neutral CB1 antagonists. Amongst the new derivatives described in this paper, the mixture of the two enantiomers (±)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-3-(2-cyclohexyl-1-hydroxyethyl)-4-methyl-1H-pyrazole ((±)-5), and compound 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-3-[(Z)-2-cyclohexyl-1-fluorovinyl]-4-methyl-1H-pyrazole ((Z)-6), showed interesting pharmacological profiles. According to the preliminary pharmacological evaluation, these novel pyrazole derivatives showed in fact both neutral CB1 antagonism behaviour and significant in vivo activity towards food intake.

  2. Coexistence and local μ-stability of multiple equilibrium points for memristive neural networks with nonmonotonic piecewise linear activation functions and unbounded time-varying delays.

    PubMed

    Nie, Xiaobing; Zheng, Wei Xing; Cao, Jinde

    2016-12-01

    In this paper, the coexistence and dynamical behaviors of multiple equilibrium points are discussed for a class of memristive neural networks (MNNs) with unbounded time-varying delays and nonmonotonic piecewise linear activation functions. By means of the fixed point theorem, nonsmooth analysis theory and rigorous mathematical analysis, it is proven that under some conditions, such n-neuron MNNs can have 5(n) equilibrium points located in ℜ(n), and 3(n) of them are locally μ-stable. As a direct application, some criteria are also obtained on the multiple exponential stability, multiple power stability, multiple log-stability and multiple log-log-stability. All these results reveal that the addressed neural networks with activation functions introduced in this paper can generate greater storage capacity than the ones with Mexican-hat-type activation function. Numerical simulations are presented to substantiate the theoretical results.

  3. Efflux pumps of Mycobacterium tuberculosis play a significant role in antituberculosis activity of potential drug candidates.

    PubMed

    Balganesh, Meenakshi; Dinesh, Neela; Sharma, Sreevalli; Kuruppath, Sanjana; Nair, Anju V; Sharma, Umender

    2012-05-01

    Active efflux of drugs mediated by efflux pumps that confer drug resistance is one of the mechanisms developed by bacteria to counter the adverse effects of antibiotics and chemicals. To understand these efflux mechanisms in Mycobacterium tuberculosis, we generated knockout (KO) mutants of four efflux pumps of the pathogen belonging to different classes. We measured the MICs and kill values of two different compound classes on the wild type (WT) and the efflux pump (EP) KO mutants in the presence and absence of the efflux inhibitors verapamil and l-phenylalanyl-l-arginyl-β-naphthylamide (PAβN). Among the pumps studied, the efflux pumps belonging to the ABC (ATP-binding cassette) class, encoded by Rv1218c, and the SMR (small multidrug resistance) class, encoded by Rv3065, appear to play important roles in mediating the efflux of different chemical classes and antibiotics. Efflux pumps encoded by Rv0849 and Rv1258c also mediate the efflux of these compounds, but to a lesser extent. Increased killing is observed in WT M. tuberculosis cells by these compounds in the presence of either verapamil or PAβN. The efflux pump KO mutants were more susceptible to these compounds in the presence of efflux inhibitors. We have shown that these four efflux pumps of M. tuberculosis play a vital role in mediating efflux of different chemical scaffolds. Inhibitors of one or several of these efflux pumps could have a significant impact in the treatment of tuberculosis. The identification and characterization of Rv0849, a new efflux pump belonging to the MFS (major facilitator superfamily) class, are reported.

  4. Breadth and Intensity: Salient, Separable, and Developmentally Significant Dimensions of Structured Youth Activity Involvement

    ERIC Educational Resources Information Center

    Busseri, Michael A.; Rose-Krasnor, Linda

    2009-01-01

    In recent years, an impressive volume of evidence has accumulated demonstrating that youth involvement in structured, organized activities (e.g. school sports, community clubs) may facilitate positive youth development. We present a theory-based framework for studying structured activity involvement (SAI) as a context for positive youth…

  5. Batch and column adsorption of herbicide fluroxypyr on different types of activated carbons from water with varied degrees of hardness and alkalinity.

    PubMed

    Pastrana-Martínez, L M; López-Ramón, M V; Fontecha-Cámara, M A; Moreno-Castilla, C

    2010-02-01

    There has been little research into the effects of the water hardness and alkalinity of surface waters on the adsorption of herbicides on activated carbons. The aim of this study was to determine the influence of these water characteristics on fluroxypyr adsorption on different activated carbons. At low fluroxypyr surface concentrations, the amount adsorbed from distilled water was related to the surface hydrophobicity. Surface area of carbons covered by fluroxypyr molecules ranged from 60 to 65%. Variations in fluroxypyr solubility with water hardness and alkalinity showed a salting-in effect. Calcium, magnesium and bicarbonate ions were adsorbed to a varied extent on the activated carbons. The presence of fluroxypyr in solution decreased their adsorption due to a competition effect. K(F) from the Freundlich equation linearly increased with water hardness due to salt-screened electrostatic repulsions between charged fluroxypyr molecules. The amount adsorbed from distilled water was largest at high fluroxypyr solution concentrations, because there was no competition between inorganic ions and fluroxypyr molecules. The column breakthrough volume and the amount adsorbed at breakthrough were smaller in tap versus distilled water. Carbon consumption was lower with activated carbon cloth than with the use of granular activated carbon.

  6. The Significance of Turning Passive Into Active in Control Mastery Theory

    PubMed Central

    FOREMAN, STEVEN A.

    1996-01-01

    Turning passive into active was first described by Freud but was later given expanded importance by Weiss. This new conceptualization of turning passive into active as an interpersonal communication and test has made a major contribution to the clinical treatment of difficult patients. This article reviews "control mastery" theory and puts its notion of passive-into-active testing into perspective with regard to Freud’s original conception as well as other conceptions, such as identification with the aggressor and projective identification. Formulation and the treatment of patients are illustrated with clinical examples. PMID:22700271

  7. Varying DNA base-pair size in subangstrom increments: evidence for a loose, not large, active site in low-fidelity Dpo4 polymerase.

    PubMed

    Mizukami, Shin; Kim, Tae Woo; Helquist, Sandra A; Kool, Eric T

    2006-03-07

    We describe the first systematic test of steric effects in the active site of a Y-family DNA polymerase, Dpo4. It has been hypothesized that low-fidelity repair polymerases in this family more readily accept damaged or mismatched base pairs because of a sterically more open active site, which might place lower geometric constraints on the incipient pair. We have tested the origin of low fidelity by use of five nonpolar thymidine analogues that vary in size by a total of 1.0 A over the series. The efficiency and fidelity of base-pair synthesis was measured by steady-state kinetics for single-nucleotide insertions. Analogues were examined both as incoming deoxynucleoside triphosphate (dNTP) derivatives and as template bases. The results showed that Dpo4 preferred to pair the thymidine shape mimics with adenine and, surprisingly, the preferred size was at the center of the range, the same optimum size as recently found for the high-fidelity Klenow fragment (Kf) of Escherichia coli DNA Pol I. However, the size preference with Dpo4 was quite small, varying by a factor of only 30-35 from most to least efficient thymidine analogue. This is in marked contrast to Kf, which showed a rigid size preference, varying by 1100-fold from best to worst. The fidelity for the non-hydrogen-bonding analogues in pairing with A over T, C, or G was much lower in Dpo4 than in the previous high-fidelity enzyme. The data establish that, unlike Kf, Dpo4 has very low steric selectivity and that steric effects alone cannot explain the fidelity (albeit low) that Dpo4 has for a correct base pair; the findings suggest that hydrogen bonds may be important in determining the fidelity of this enzyme. The results suggest that the low steric selectivity of this enzyme is the result of a conformationally flexible or loose active site that adapts with small energetic cost to different base-pair sizes (as measured by the glycosidic C1'-C1' distance), rather than a spatially large active site.

  8. Significance of peroxisome proliferator-activated receptors in the cardiovascular system in health and disease.

    PubMed

    Robinson, Emma; Grieve, David J

    2009-06-01

    Peroxisome proliferator-activated receptors (PPARs) are ligand-activated nuclear transcription factors that belong to the nuclear receptor superfamily. Three isoforms of PPAR have been identified, alpha, delta and gamma, which play distinct roles in the regulation of key metabolic processes, such as glucose and lipid redistribution. PPARalpha is expressed predominantly in the liver, kidney and heart, and is primarily involved in fatty acid oxidation. PPARgamma is mainly associated with adipose tissue, where it controls adipocyte differentiation and insulin sensitivity. PPARdelta is abundantly and ubiquitously expressed, but as yet its function has not been clearly defined. Activators of PPARalpha (fibrates) and gamma (thiazolidinediones) have been used clinically for a number of years in the treatment of hyperlipidaemia and to improve insulin sensitivity in diabetes. More recently, PPAR activation has been found to confer additional benefits on endothelial function, inflammation and thrombosis, suggesting that PPAR agonists may be good candidates for the treatment of cardiovascular disease. In this regard, it has been demonstrated that PPAR activators are capable of reducing blood pressure and attenuating the development of atherosclerosis and cardiac hypertrophy. This review will provide a detailed discussion of the current understanding of basic PPAR physiology, with particular reference to the cardiovascular system. It will also examine the evidence supporting the involvement of the different PPAR isoforms in cardiovascular disease and discuss the current and potential future clinical applications of PPAR activators.

  9. Binding of nickel and copper to fish gills predicts toxicity when water hardness varies, but free-ion activity does not

    SciTech Connect

    Meyer, J.S.; Bobbitt, J.P.; Debrey, L.D.; Boese, C.J.; Bergman, H.L.; Santore, R.C.; Paquin, P.R.; Ditoro, D.M.; Allen, H.E.

    1999-03-15

    Based on a biotic-ligand model (BLM), the authors hypothesized that the concentration of a transition metal bound to fish gills ([M{sub gill}]) will be a constant predictor of mortality, whereas a free-ion activity model is generally interpreted to imply that the chemical activity of the aquo (free) ion of the metal will be a constant predictor of mortality. In laboratory tests, measured [Ni{sub gill}] and calculated [Cu{sub gill}] were constant predictors of acute toxicity of Ni and Cu to fathead minnows (Pimephales promelas) when water hardness varied up to 10-fold, whereas total aqueous concentrations and free-ion activities of Ni and Cu were not. Thus, the BLM, which simultaneously accounts for (a) metal speciation in the exposure water and (b) competitive binding of transition-metal ions and other cations to biotic ligands predicts acute toxicity better than does free-ion activity of Ni or Cu. Adopting a biotic-ligand modeling approach could help establish a more defensible, mechanistic basis for regulating aqueous discharges of metals.

  10. Significant role of climatic trends on hydrothermal activity Coso Hot Springs, California

    SciTech Connect

    Lofgren, B.E. )

    1990-05-01

    The hydrothermal features of Coso Hot Springs have attracted visitors for 130 yr and scientific investigators for two decades. In 1978, anticipating effects of major geothermal developments nearby, the Naval Weapons Center (NWC) initiated a comprehensive monitoring program at a dozen hydrothermal sites in the Coso Hot Springs area. Nine years of monitoring preceded power production in the nearby Coso geothermal field in July 1987. During this period, steam was rising from numerous vents and gently boiling mud pots. Local rainfall caused increased boiling activity in several mud pots, with some overflowing during wet periods. Then in August 1988, a year after geothermal power production began major changes in hot spring activity commenced. Small mud pots and steamers started to grow and coalesce. In March 1989, mud-pot activity became more violent. Many buried wells failed causing surface activity in other areas to diminish. During ensuing months, large mud cones developed and much of the steam and boiling water occurred in a few major pots. Because the abrupt changes in hydrothermal activity followed so closely after nearby geothermal production began, the obvious cause has been attributed to geothermal developments. Studies of NWC baseline monitoring data indicate, however, that no effects of geothermal developments have been felt in the hot springs area. Rainfall and barometric effects account for most of the fluctuations in records of the past decade. Early accounts and field evidence suggest similar changes have occurred in the past.

  11. Newly identified active faults in the Pollino seismic gap, southern Italy, and their seismotectonic significance

    NASA Astrophysics Data System (ADS)

    Brozzetti, Francesco; Cirillo, Daniele; de Nardis, Rita; Cardinali, Mauro; Lavecchia, Giusy; Orecchio, Barbara; Presti, Debora; Totaro, Cristina

    2017-01-01

    The following is a geological study of a Quaternary and active normal fault-system, which crops out in the Pollino area, a seismogenic sector of the Southern Apennines, Italy. From 2010 to 2014, this area was affected by long lasting seismic activity characterized by three major events which occurred in May 2012 (Mw 4.3), in October 2012 (Mw 5.2) and in June 2014 (Mw 4.0). The integration of structural-geological data with morpho-structural and remote sensing analyses, led to define the geometry, the kinematics, the cross-cutting relationships and the slip rates of the inferred active fault segments within and near the epicentral area. We reconstructed an asymmetric extensional pattern characterized by low-angle, E and NNE-dipping faults, and by antithetic, high-angle, SW- to WSW-dipping faults. The geometry of the faults at depth was constrained using high-resolution hypocenter distributions. The overall system fits well with the deformation field obtained from focal mechanisms and geodetic data. Comparing the fault pattern with the time-space evolution of the Pollino seismic activity, we identified the seismogenic sources in two, near-parallel, WSW-dipping faults, whose seismogenic potential were assessed. The peculiar perpendicular-to-fault-strike evolution of the seismic activity, is discussed in the frame of the reconstructed seismotectonic model.

  12. The evolution of magnetic activity on V711 Tauri and evidence for a significant facular contribution

    NASA Technical Reports Server (NTRS)

    Dorren, J. D.; Guinan, E. F.

    1990-01-01

    The nature of the long-term evolution of magnetic activity in the RS CVn binary V711 Tauri is investigated using the complete set of available archival IUE SWP low-dispersion spectra of V711 Tau for the period covering August 1978 - December 1984. An analysis of the spectra confirmed the pattern of a long-term smooth variation of chromospheric and transition region emission found previosly by Dorren et al. (1986). An explanation of the relationship between the different facets of the magnetic activity on V711 Tau is presented.

  13. The Measurement of Brain Electrical Activity and Its Significance to the Educator.

    ERIC Educational Resources Information Center

    Torello, Michael W.

    The article discusses the measurement of brain electrical activity and, in particular, the examination of electroencephalographic (EEG) data, as providing useful information in the diagnosis of dyslexia and other learning disabilities. Topographic imaging of EEG (TIE) is described as a procedure which provides functional data at comparatively low…

  14. Significant Centers of Tectonic Activity as Identified by Wrinkle Ridges for the Western Hemisphere of Mars

    NASA Technical Reports Server (NTRS)

    Anderson, R.C.; Haldemann, A. F. C.; Golombek, M. P.; Franklin, B. J.; Dohm, J. M.; Lias, J.

    2000-01-01

    The western hemisphere region of Mars has been the site of numerous scientific investigations regarding its tectonic evolution. For this region of Mars, the dominant tectonic region is the Tharsis province. Tharsis is characterized by an enormous system of radiating grabens and a circumferential system of wrinkle ridges. Past investigations of grabens associated with Tharsis have identified specific centers of tectonic activity. A recent structural analysis of the western hemisphere region of Mars which includes the Tharsis region, utilized 25,000 structures to determine the history of local and regional centers of tectonic activity based primarily on the spatial and temporal relationships of extensional features. This investigation revealed that Tharsis is more structurally complex (heterogeneous) than has been previously identified: it consists of numerous regional and local centers of tectonic activity (some are more dominant and/or more long lived than others). Here we use the same approach as Anderson et al. to determine whether the centers of tectonic activity that formed the extensional features also contributed to wrinkle ridge (compressional) formation.

  15. The Social and Economic Significance of Recreation Activities in the Marine Environment.

    ERIC Educational Resources Information Center

    Ditton, Robert B.

    Although the data obtained by an Outdoor Recreation Resources Review Commission in 1960 indicated that 44 percent of participants in outdoor recreation prefer water-based activities, the potential demand for recreation within the coastal zone is much greater than that study indicates, because the unfulfilled recreational demands of the urban…

  16. Using the Significant Learning Taxonomy and Active Learning to Improve Accounting Education

    ERIC Educational Resources Information Center

    Killian, Larita J.; Brandon, Christopher D.

    2009-01-01

    Like other members of the academy, accounting professors are challenged to improve student learning. We must help students move beyond the "bean counter" role and develop higher-level skills such as analysis, synthesis, and problem-solving. The Significant Learning Taxonomy was used as a template to improve learning in an introductory accounting…

  17. Culture, Leadership, and Activism: Translating Fink's Taxonomy of Significant Learning into Pedagogical Practice

    ERIC Educational Resources Information Center

    Jenkins, Toby S.

    2016-01-01

    Through the article, I share the theoretical foundations, structure, knowledge acquisition, and outcomes of a cultural leadership course. The process for course development integrates several theories and research methods into practice: L. Dee Fink's Taxonomy of Significant Learning, Feminist Theory, Critical Race Theory, and…

  18. Constitutive nitric oxide synthase activation is a significant route for nitroglycerin-mediated vasodilation

    PubMed Central

    Bonini, Marcelo G.; Stadler, Krisztian; de Oliveira Silva, Sueli; Corbett, Jean; Dore, Michael; Petranka, John; Fernandes, Denise C.; Tanaka, Leonardo Y.; Duma, Danielle; Laurindo, Francisco R. M.; Mason, Ronald P.

    2008-01-01

    The physiological effects of nitroglycerin as a potent vasodilator have long been documented. However, the molecular mechanisms by which nitroglycerin exerts its biological functions are still a matter of intense debate. Enzymatic pathways converting nitroglycerin to vasoactive compounds have been identified, but none of them seems to fully account for the reported clinical observations. Here, we demonstrate that nitroglycerin triggers constitutive nitric oxide synthase (NOS) activation, which is a major source of NO responsible for low-dose (1–10 nM) nitroglycerin-induced vasorelaxation. Our studies in cell cultures, isolated vessels, and whole animals identified endothelial NOS activation as a fundamental requirement for nitroglycerin action at pharmacologically relevant concentrations in WT animals. PMID:18562300

  19. Population Pharmacokinetic Model for Docetaxel in Patients with Varying Degrees of Liver Function: Incorporating Cytochrome P450 3A Activity Measurements

    PubMed Central

    Hooker, AC; ten Tije, AJ; Carducci, MA; Weber, J; Garrett-Mayer, E; Gelderblom, H; McGuire, WP; Verweij, J; Karlsson, MO; Baker, SD

    2011-01-01

    The relationship between cytochrome P4503A4 (CYP3A4) activity and docetaxel clearance in patients with varying degrees of liver function (LF) was evaluated. Docetaxel 40, 50, or 75 mg/m2 was administered to 85 patients with advanced cancer; 23 of 77 evaluable patients had abnormalities in liver function tests. Baseline CYP3A activity was assessed using the erythromycin breath test (ERMBT). Pharmacokinetic studies and toxicity assessments were performed during cycle 1 of therapy and population modeling was performed using NONMEM. Docetaxel unbound clearance was lower (317 vs. 470 L/h) and more variable in patients with liver function abnormalities compared to patients with normal LF. Covariates evaluated accounted for 83% of variability on clearance in patients with liver dysfunction, with CYP3A4 activity accounting for 47% of variation; covariates accounted for only 23% of variability in patients with normal LF. The clinical utility of the ERMBT may be in identifying safe docetaxel doses for patients with LF abnormalities. PMID:18183036

  20. Molecular and functional significance of Ca2+-activated Cl− channels in pulmonary arterial smooth muscle

    PubMed Central

    Forrest, Abigail S.; Ayon, Ramon J.; Wiwchar, Michael; Angermann, Jeff E.; Pritchard, Harry A. T.; Singer, Cherie A.; Valencik, Maria L.; Britton, Fiona; Greenwood, Iain A.

    2015-01-01

    Abstract Increased peripheral resistance of small distal pulmonary arteries is a hallmark signature of pulmonary hypertension (PH) and is believed to be the consequence of enhanced vasoconstriction to agonists, thickening of the arterial wall due to remodeling, and increased thrombosis. The elevation in arterial tone in PH is attributable, at least in part, to smooth muscle cells of PH patients being more depolarized and displaying higher intracellular Ca2+ levels than cells from normal subjects. It is now clear that downregulation of voltage-dependent K+ channels (e.g., Kv1.5) and increased expression and activity of voltage-dependent (Cav1.2) and voltage-independent (e.g., canonical and vanilloid transient receptor potential [TRPC and TRPV]) Ca2+ channels play an important role in the functional remodeling of pulmonary arteries in PH. This review focuses on an anion-permeable channel that is now considered a novel excitatory mechanism in the systemic and pulmonary circulations. It is permeable to Cl− and is activated by a rise in intracellular Ca2+ concentration (Ca2+-activated Cl− channel, or CaCC). The first section outlines the biophysical and pharmacological properties of the channel and ends with a description of the molecular candidate genes postulated to encode for CaCCs, with particular emphasis on the bestrophin and the newly discovered TMEM16 and anoctamin families of genes. The second section provides a review of the various sources of Ca2+ activating CaCCs, which include stimulation by mobilization from intracellular Ca2+ stores and Ca2+ entry through voltage-dependent and voltage-independent Ca2+ channels. The third and final section summarizes recent findings that suggest a potentially important role for CaCCs and the gene TMEM16A in PH. PMID:26064450

  1. Significant Modules and Biological Processes between Active Components of Salvia miltiorrhiza Depside Salt and Aspirin.

    PubMed

    Li, Yuan; Xie, Yanming; Wang, Lianxin; Zhang, Yingying; Gu, Hao; Chai, Yan

    2016-01-01

    The aim of this study is to examine and compare the similarities and differences between active components of S. miltiorrhiza depside salt and aspirin using perspective of pharmacological molecular networks. Active components of S. miltiorrhiza depside salt and aspirin's related genes were identified via the STITCH4.0 and GeneCards Database. A text search engine (Agilent Literature Search 2.71) and MCODE software were applied to construct network and divide modules, respectively. Finally, 32, 2, and 28 overlapping genes, modules, and pathways were identified between active components of S. miltiorrhiza depside salt and aspirin. A multidimensional framework of drug network showed that two networks reflected commonly in human aortic endothelial cells and atherosclerosis process. Aspirin plays a more important role in metabolism, such as the well-known AA metabolism pathway and other lipid or carbohydrate metabolism pathways. S. miltiorrhiza depside salt still plays a regulatory role in type II diabetes mellitus, insulin resistance, and adipocytokine signaling pathway. Therefore, this study suggests that aspirin combined with S. miltiorrhiza depside salt may be more efficient in treatment of CHD patients, especially those with diabetes mellitus or hyperlipidemia. Further clinical trials to confirm this hypothesis are still needed.

  2. Therapeutic significance and pharmacological activities of antidiarrheal medicinal plants mention in Ayurveda: A review

    PubMed Central

    Mishra, Ashish; Seth, Ankit; Maurya, Santosh Kumar

    2016-01-01

    Diarrhea is a serious problem affecting 3-5 billion people per year around the world, especially children of below 5 years. 70% of the world population uses traditional and indigenous medicine for their primary health care. The facts of these indigenous remedies are passed verbally and sometimes as documents. Since ancient time, Ayurveda is the main system of healing in South East Asian countries. Indian literature from ayurvedic texts and other books claim the potency of several plants in the treatment of diarrhea. As the global prospective of ayurvedic medicine is increasing, interest regarding the scientific basis of their action is parallely increasing. Researchers are doing experiments to establish the relation between the claimed action and observed pharmacological activities. In the present article, an attempt was made to compile the scientific basis of medicinal plants used to cure diarrhea in Ayurveda. Literature was collected via electronic search (PubMed, ScienceDirect, Medline, and Google Scholar) from published articles that reports antidiarrheal activity of plants that were mentioned in Ayurveda classics. A total of 109 plant species belonging to 58 families were reported for their antidiarrheal activity. Several Indian medicinal plants have demonstrated promising antidiarrheal effects, but the studies on the antidiarrheal potentials of these plants are not taken beyond proof of concept stage. It is hoped that the article would stimulate future clinical studies because of the paucity of knowledge in this area. PMID:27366356

  3. Significant Modules and Biological Processes between Active Components of Salvia miltiorrhiza Depside Salt and Aspirin

    PubMed Central

    Xie, Yanming; Wang, Lianxin; Zhang, Yingying; Gu, Hao; Chai, Yan

    2016-01-01

    The aim of this study is to examine and compare the similarities and differences between active components of S. miltiorrhiza depside salt and aspirin using perspective of pharmacological molecular networks. Active components of S. miltiorrhiza depside salt and aspirin's related genes were identified via the STITCH4.0 and GeneCards Database. A text search engine (Agilent Literature Search 2.71) and MCODE software were applied to construct network and divide modules, respectively. Finally, 32, 2, and 28 overlapping genes, modules, and pathways were identified between active components of S. miltiorrhiza depside salt and aspirin. A multidimensional framework of drug network showed that two networks reflected commonly in human aortic endothelial cells and atherosclerosis process. Aspirin plays a more important role in metabolism, such as the well-known AA metabolism pathway and other lipid or carbohydrate metabolism pathways. S. miltiorrhiza depside salt still plays a regulatory role in type II diabetes mellitus, insulin resistance, and adipocytokine signaling pathway. Therefore, this study suggests that aspirin combined with S. miltiorrhiza depside salt may be more efficient in treatment of CHD patients, especially those with diabetes mellitus or hyperlipidemia. Further clinical trials to confirm this hypothesis are still needed. PMID:27069488

  4. Therapeutic significance and pharmacological activities of antidiarrheal medicinal plants mention in Ayurveda: A review.

    PubMed

    Mishra, Ashish; Seth, Ankit; Maurya, Santosh Kumar

    2016-01-01

    Diarrhea is a serious problem affecting 3-5 billion people per year around the world, especially children of below 5 years. 70% of the world population uses traditional and indigenous medicine for their primary health care. The facts of these indigenous remedies are passed verbally and sometimes as documents. Since ancient time, Ayurveda is the main system of healing in South East Asian countries. Indian literature from ayurvedic texts and other books claim the potency of several plants in the treatment of diarrhea. As the global prospective of ayurvedic medicine is increasing, interest regarding the scientific basis of their action is parallely increasing. Researchers are doing experiments to establish the relation between the claimed action and observed pharmacological activities. In the present article, an attempt was made to compile the scientific basis of medicinal plants used to cure diarrhea in Ayurveda. Literature was collected via electronic search (PubMed, ScienceDirect, Medline, and Google Scholar) from published articles that reports antidiarrheal activity of plants that were mentioned in Ayurveda classics. A total of 109 plant species belonging to 58 families were reported for their antidiarrheal activity. Several Indian medicinal plants have demonstrated promising antidiarrheal effects, but the studies on the antidiarrheal potentials of these plants are not taken beyond proof of concept stage. It is hoped that the article would stimulate future clinical studies because of the paucity of knowledge in this area.

  5. Serotonin2c receptor constitutive activity: in vivo direct and indirect evidence and functional significance.

    PubMed

    Navailles, Sylvia; Lagière, Mélanie; Guthrie, Martin; De Deurwaerdère, Philippe

    2013-06-01

    Serotonin2c (5-HT2c) receptors are widely expressed in the central nervous system where they play a pivotal role in the regulation of neuronal network excitability. Along with this fundamental physiological function, 5-HT2c receptors are thought to be implicated in the pathophysiology of several neuropsychiatric disorders and have become a major pharmacological target for the development of improved treatments of these disorders. In the past decade, many studies have focused on the constitutive activity of 5-HT2c receptors and the therapeutic potential of drugs acting as inverse agonists. Although the constitutive activity of the 5-HT2c receptor has been clearly described in vitro, the transposition of this concept to living animals is often difficult to ascertain. Nevertheless, cumulating evidence has demonstrated the functional relevance of such property in regulating physiological systems in vivo both at the level of the central and peripheral nervous systems. The present review provides an update of the growing number of studies that show, by means of pharmacological tools, the participation of the constitutive activity of 5-HT2c receptors in the control of various biochemical and behavioural functions in vivo and emphasizes the functional organization of this constitutive control together with the phasic and tonic (involving the spontaneous release of 5-HT) modalities of the 5-HT2c receptor in the brain.

  6. Temporal relationships between ceramide production, caspase activation and mitochondrial dysfunction in cell lines with varying sensitivity to anti-Fas-induced apoptosis.

    PubMed Central

    Rodriguez-Lafrasse, C; Alphonse, G; Broquet, P; Aloy, M T; Louisot, P; Rousson, R

    2001-01-01

    To clarify the chronology of events leading to anti-Fas-induced apoptosis, and the mechanisms of resistance to this death effector, we compared the response kinetics of three tumour cell lines that display varying sensitivity to anti-Fas (based on levels of apoptosis), in terms of ceramide release, mitochondrial function and the caspase-activation pathway. In the highly sensitive Jurkat cell line, early caspase-8 activation, observed from 2 h after treatment, was chronologically associated with an acute depletion of glutathione and the cleavage of caspase-3 and poly-ADP ribosyl polymerase (PARP), followed by a progressive fall in the mitochondrial transmembrane potential (Delta(psi)m), between 4 and 48 h after treatment. Ceramide levels began to increase 2 h after the addition of anti-Fas (with no increase during the first hour), and increased continuously to 640% of control cells at 48 h. In the moderately sensitive SCC61 adherent cells, comparable results were observed, though with lower levels of ceramide and a delay in the response kinetics, with apoptotic cells becoming flotant. Finally, despite early cleavage of caspase-8 at 2 h, and a sustained level of activation until 48 h, no apoptotic response was observed in anti-Fas-resistant SQ20B cells. This was confirmed by a lack of ceramide generation and mitochondrial changes, and by the absence of any detectable cleavage of caspase-3 or PARP. Inhibition of caspase processing, and amplification of endogenous ceramide signalling by pharmacological agents, allowed us to establish the order of cellular events, locating ceramide release after caspase-8 activation and before caspase-3 activation, and demonstrating a direct involvement for ceramide release in mitochondrial dysfunction. Furthermore, these experiments provide strong arguments for the role of endogenous ceramide as a key executor of apoptosis, rather than as a consequence of membrane alterations. PMID:11439090

  7. Adsorption capacities of activated carbons for geosmin and 2-methylisoborneol vary with activated carbon particle size: Effects of adsorbent and adsorbate characteristics.

    PubMed

    Matsui, Yoshihiko; Nakao, Soichi; Sakamoto, Asuka; Taniguchi, Takuma; Pan, Long; Matsushita, Taku; Shirasaki, Nobutaka

    2015-11-15

    The adsorption capacities of nine activated carbons for geosmin and 2-methylisoborneol (MIB) were evaluated. For some carbons, adsorption capacity substantially increased when carbon particle diameter was decreased from a few tens of micrometers to a few micrometers, whereas for other carbons, the increase of adsorption capacity was small for MIB and moderate for geosmin. An increase of adsorption capacity was observed for other hydrophobic adsorbates besides geosmin and MIB, but not for hydrophilic adsorbates. The parameter values of a shell adsorption model describing the increase of adsorption capacity were negatively correlated with the oxygen content of the carbon among other characteristics. Low oxygen content indicated low hydrophilicity. The increase of adsorption capacity was related to the hydrophobic properties of both adsorbates and activated carbons. For adsorptive removal of hydrophobic micropollutants such as geosmin, it is therefore recommended that less-hydrophilic activated carbons, such as coconut-shell-based carbons, be microground to a particle diameter of a few micrometers to enhance their equilibrium adsorption capacity. In contrast, adsorption by hydrophilic carbons or adsorption of hydrophilic adsorbates occur in the inner pores, and therefore adsorption capacity is unchanged by particle size reduction.

  8. Dissociated functional significance of decision-related activity in the primate dorsal stream

    PubMed Central

    Katz, Leor N.; Yates, Jacob L.; Pillow, Jonathan W.; Huk, Alexander C.

    2016-01-01

    During decision-making, neurons in multiple brain regions exhibit responses that are correlated with decisions1-6. However, it remains uncertain whether or not various forms of decision-related activity are causally related to decision-making7-9. Here we address this question by recording and reversibly inactivating the lateral intraparietal (LIP) and middle temporal (MT) areas of rhesus macaques performing a motion direction discrimination task. Neurons in area LIP exhibited firing rate patterns that directly resembled the evidence accumulation process posited to govern decision making2,10, with strong correlations between their response fluctuations and the animal's choices. Neurons in area MT, in contrast, exhibited weak correlations between their response fluctuations and animal choices, and had firing rate patterns consistent with their sensory role in motion encoding1. The behavioral impact of pharmacological inactivation of each area was inversely related to their degree of decision-related activity: while inactivation of neurons in MT profoundly impaired psychophysical performance, inactivation in LIP had no measurable impact on decision-making performance, despite having silenced the very clusters that exhibited strong decision-related activity. Although LIP inactivation did not impair psychophysical behavior, it did influence spatial selection and oculomotor metrics in a free-choice control task. The absence of an effect on perceptual decision-making was stable over trials and sessions, arguing against several forms of compensation, and was robust to changes in stimulus type and task geometry. Thus, decision-related signals in LIP do not appear to be necessary for computing perceptual decisions. Our findings highlight a dissociation between decision correlation and causation, showing that strong neuron-decision correlations may reflect secondary or epiphenomenal signals, and do not necessarily offer direct access to the neural computations underlying

  9. Caffeine-activated large-conductance plasma membrane cation channels in cardiac myocytes: characteristics and significance.

    PubMed

    Zhang, Yu-An; Tuft, Richard A; Lifshitz, Lawrence M; Fogarty, Kevin E; Singer, Joshua J; Zou, Hui

    2007-10-01

    Caffeine-activated, large-conductance, nonselective cation channels (LCCs) have been found in the plasma membrane of isolated cardiac myocytes in several species. However, little is known about the effects of opening these channels. To examine such effects and to further understand the caffeine-activation mechanism, we carried out studies using whole-cell patch-clamp techniques with freshly isolated cardiac myocytes from rats and mice. Unlike previous studies, thapsigargin was used so that both the effect of opening LCCs and the action of caffeine were independent of Ca(2+) release from intracellular stores. These Ca(2+)-permeable LCCs were found in a majority of the cells from atria and ventricles, with a conductance of approximately 370 pS in rat atria. Caffeine and all its direct metabolic products (theophylline, theobromine, and paraxanthine) activated the channel, while isocaffeine did not. Although they share some similarities with ryanodine receptors (RyRs, the openings of which give rise to Ca(2+) sparks), LCCs also showed some different characteristics. With simultaneous Ca(2+) imaging and current recording, the localized fluorescence increase due to Ca(2+) entry through a single opening of an LCC (SCCaFT) was detected. When membrane potential, instead of current, was recorded, SCCaFT-like fluorescence transients (indicating single LCC openings) were found to accompany membrane depolarizations. To our knowledge, this is the first report directly linking membrane potential changes to a single opening of an ion channel. Moreover, these events in cardiac cells suggest a possible additional mechanism by which caffeine and theophylline contribute to the generation of cardiac arrhythmias.

  10. Dissociated functional significance of decision-related activity in the primate dorsal stream.

    PubMed

    Katz, Leor N; Yates, Jacob L; Pillow, Jonathan W; Huk, Alexander C

    2016-07-14

    During decision making, neurons in multiple brain regions exhibit responses that are correlated with decisions. However, it remains uncertain whether or not various forms of decision-related activity are causally related to decision making. Here we address this question by recording and reversibly inactivating the lateral intraparietal (LIP) and middle temporal (MT) areas of rhesus macaques performing a motion direction discrimination task. Neurons in area LIP exhibited firing rate patterns that directly resembled the evidence accumulation process posited to govern decision making, with strong correlations between their response fluctuations and the animal's choices. Neurons in area MT, in contrast, exhibited weak correlations between their response fluctuations and choices, and had firing rate patterns consistent with their sensory role in motion encoding. The behavioural impact of pharmacological inactivation of each area was inversely related to their degree of decision-related activity: while inactivation of neurons in MT profoundly impaired psychophysical performance, inactivation in LIP had no measurable impact on decision-making performance, despite having silenced the very clusters that exhibited strong decision-related activity. Although LIP inactivation did not impair psychophysical behaviour, it did influence spatial selection and oculomotor metrics in a free-choice control task. The absence of an effect on perceptual decision making was stable over trials and sessions and was robust to changes in stimulus type and task geometry, arguing against several forms of compensation. Thus, decision-related signals in LIP do not appear to be critical for computing perceptual decisions, and may instead reflect secondary processes. Our findings highlight a dissociation between decision correlation and causation, showing that strong neuron-decision correlations do not necessarily offer direct access to the neural computations underlying decisions.

  11. UNESCO active learning approach in optics and photonics leads to significant change in Morocco

    NASA Astrophysics Data System (ADS)

    Berrada, K.; Channa, R.; Outzourhit, A.; Azizan, M.; Oueriagli, A.

    2014-07-01

    There are many difficulties in teaching science and technology in developing countries. Several different teaching strategies have to be applied in these cases. More specifically, for developing countries competencies in teaching science in the introductory classroom has attracted much attention. As a specific example we will consider the Moroccan system. In most developing countries everything is moving so slowly that the progress stays static for development. Also, any change needs time, effort and engagement. In our case we discovered that many teachers feel uncomfortable when introducing new teaching methods and evaluation in classes at introductory physics. However, the introduction of an Active Learning in our curricula showed difficulties that students have in understanding physics and especially concepts. Students were interested in having Active Learning courses much more than passive and traditional ones. Changing believes on physical phenomena and reality of the world students become more attractive and their way of thinking Science changed. The main philosophy of fostering modern hands-on learning techniques -adapted to local needs and availability of teaching resources- is elaborated. The Active Learning program provides the teachers with a conceptual evaluation instrument, drawn from relevant physics education research, giving teachers an important tool to measure student learning. We will try to describe the UNESCO Chair project in physics created in 2010 at Cadi Ayyad University since our first experience with UNESCO ALOP program. Many efforts have been done so far and the project helps now to develop more national and international collaborations between universities and Regional Academies of Education and Training. As a new result of these actions and according to our local needs, the translation of the ALOP program into Arabic is now available under the auspice of UNESCO and encouragement of international partners SPIE, ICTP, ICO and OSA.

  12. Significance of conservative asparagine residues in the thermal hysteresis activity of carrot antifreeze protein.

    PubMed Central

    Zhang, Dang-Quan; Liu, Bing; Feng, Dong-Ru; He, Yan-Ming; Wang, Shu-Qi; Wang, Hong-Bin; Wang, Jin-Fa

    2004-01-01

    The approximately 24-amino-acid leucine-rich tandem repeat motif (PXXXXXLXXLXXLXLSXNXLXGXI) of carrot antifreeze protein comprises most of the processed protein and should contribute at least partly to the ice-binding site. Structural predictions using publicly available online sources indicated that the theoretical three-dimensional model of this plant protein includes a 10-loop beta-helix containing the approximately 24-amino-acid tandem repeat. This theoretical model indicated that conservative asparagine residues create putative ice-binding sites with surface complementarity to the 1010 prism plane of ice. We used site-specific mutagenesis to test the importance of these residues, and observed a distinct loss of thermal hysteresis activity when conservative asparagines were replaced with valine or glutamine, whereas a large increase in thermal hysteresis was observed when phenylalanine or threonine residues were replaced with asparagine, putatively resulting in the formation of an ice-binding site. These results confirmed that the ice-binding site of carrot antifreeze protein consists of conservative asparagine residues in each beta-loop. We also found that its thermal hysteresis activity is directly correlated with the length of its asparagine-rich binding site, and hence with the size of its ice-binding face. PMID:14531728

  13. 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.

  14. Novel activities of CYP11A1 and their potential physiological significance

    PubMed Central

    Slominski, Andrzej T.; Li, Wei; Kim, Tae-Kang; Semak, Igor; Wang, Jin; Zjawiony, Jordan K.; Tuckey, Robert C.

    2014-01-01

    CYP11A1, found only in vertebrates, catalyzes the first step of steroidogenesis where cholesterol is converted to pregnenolone. The purified enzyme, also converts desmosterol and plant sterols including campesterol and β-sitosterol, to pregnenolone. Studies, initially with purified enzyme, reveal that 7-dehydrocholesterol (7DHC), ergosterol, lumisterol 3, and vitamins D3 and D2 also serve as substrates for CYP11A1, with 7DHC being better and vitamins D3 and D2 being poorer substrates than cholesterol. Adrenal glands, placenta, and epidermal keratinocytes can also carry out these conversions and 7-dehydropregnenolone has been detected in the epidermis, adrenal glands, and serum, and 20-hydroxyvitamin D3 was detected in human serum and the epidermis. Thus, this metabolism does appear to occur in vivo, although its quantitative importance and physiological role remain to be established. CYP11A1 action on 7DHC in vivo is further supported by detection of Δ7steroids in Smith-Lemli-Opitz syndrome patients. The activity of CYP11A1 is affected by the structure of the substrate with sterols having steroidal or Δ7-steroidal structures undergoing side chain cleavage following hydroxylations at C22 and C20. In contrast, metabolism of vitamin D involves sequential hydroxylations that start at C20 but do not lead to cleavage. Molecular modeling using the crystal structure of CYP11A1 predicts that other intermediates of cholesterol synthesis could also serve as substrates for CYP11A1. Finally, CYP11A1-derived secosteroidal hydroxy-derivatives and Δ7steroids are biologically active when administered in vitro in a manner dependent on the structure of the compound and the lineage of the target cells, suggesting physiological roles for these metabolites. This article is part of a special issue entitled ‘SI: Steroid/Sterol signaling’. PMID:25448732

  15. Novel activities of CYP11A1 and their potential physiological significance.

    PubMed

    Slominski, Andrzej T; Li, Wei; Kim, Tae-Kang; Semak, Igor; Wang, Jin; Zjawiony, Jordan K; Tuckey, Robert C

    2015-07-01

    CYP11A1, found only in vertebrates, catalyzes the first step of steroidogenesis where cholesterol is converted to pregnenolone. The purified enzyme, also converts desmosterol and plant sterols including campesterol and β-sitosterol, to pregnenolone. Studies, initially with purified enzyme, reveal that 7-dehydrocholesterol (7DHC), ergosterol, lumisterol 3, and vitamins D3 and D2 also serve as substrates for CYP11A1, with 7DHC being better and vitamins D3 and D2 being poorer substrates than cholesterol. Adrenal glands, placenta, and epidermal keratinocytes can also carry out these conversions and 7-dehydropregnenolone has been detected in the epidermis, adrenal glands, and serum, and 20-hydroxyvitamin D3 was detected in human serum and the epidermis. Thus, this metabolism does appear to occur in vivo, although its quantitative importance and physiological role remain to be established. CYP11A1 action on 7DHC in vivo is further supported by detection of Δ(7)steroids in Smith-Lemli-Opitz syndrome patients. The activity of CYP11A1 is affected by the structure of the substrate with sterols having steroidal or Δ(7)-steroidal structures undergoing side chain cleavage following hydroxylations at C22 and C20. In contrast, metabolism of vitamin D involves sequential hydroxylations that start at C20 but do not lead to cleavage. Molecular modeling using the crystal structure of CYP11A1 predicts that other intermediates of cholesterol synthesis could also serve as substrates for CYP11A1. Finally, CYP11A1-derived secosteroidal hydroxy-derivatives and Δ(7)steroids are biologically active when administered in vitro in a manner dependent on the structure of the compound and the lineage of the target cells, suggesting physiological roles for these metabolites. This article is part of a special issue entitled 'SI: Steroid/Sterol signaling'.

  16. Single-trial estimation of stimulus and spike-history effects on time-varying ensemble spiking activity of multiple neurons: a simulation study

    NASA Astrophysics Data System (ADS)

    Shimazaki, Hideaki

    2013-12-01

    Neurons in cortical circuits exhibit coordinated spiking activity, and can produce correlated synchronous spikes during behavior and cognition. We recently developed a method for estimating the dynamics of correlated ensemble activity by combining a model of simultaneous neuronal interactions (e.g., a spin-glass model) with a state-space method (Shimazaki et al. 2012 PLoS Comput Biol 8 e1002385). This method allows us to estimate stimulus-evoked dynamics of neuronal interactions which is reproducible in repeated trials under identical experimental conditions. However, the method may not be suitable for detecting stimulus responses if the neuronal dynamics exhibits significant variability across trials. In addition, the previous model does not include effects of past spiking activity of the neurons on the current state of ensemble activity. In this study, we develop a parametric method for simultaneously estimating the stimulus and spike-history effects on the ensemble activity from single-trial data even if the neurons exhibit dynamics that is largely unrelated to these effects. For this goal, we model ensemble neuronal activity as a latent process and include the stimulus and spike-history effects as exogenous inputs to the latent process. We develop an expectation-maximization algorithm that simultaneously achieves estimation of the latent process, stimulus responses, and spike-history effects. The proposed method is useful to analyze an interaction of internal cortical states and sensory evoked activity.

  17. A Novel Time-Varying Spectral Filtering Algorithm for Reconstruction of Motion Artifact Corrupted Heart Rate Signals During Intense Physical Activities Using a Wearable Photoplethysmogram Sensor

    PubMed Central

    Salehizadeh, Seyed M. A.; Dao, Duy; Bolkhovsky, Jeffrey; Cho, Chae; Mendelson, Yitzhak; Chon, Ki H.

    2015-01-01

    Accurate estimation of heart rates from photoplethysmogram (PPG) signals during intense physical activity is a very challenging problem. This is because strenuous and high intensity exercise can result in severe motion artifacts in PPG signals, making accurate heart rate (HR) estimation difficult. In this study we investigated a novel technique to accurately reconstruct motion-corrupted PPG signals and HR based on time-varying spectral analysis. The algorithm is called Spectral filter algorithm for Motion Artifacts and heart rate reconstruction (SpaMA). The idea is to calculate the power spectral density of both PPG and accelerometer signals for each time shift of a windowed data segment. By comparing time-varying spectra of PPG and accelerometer data, those frequency peaks resulting from motion artifacts can be distinguished from the PPG spectrum. The SpaMA approach was applied to three different datasets and four types of activities: (1) training datasets from the 2015 IEEE Signal Process. Cup Database recorded from 12 subjects while performing treadmill exercise from 1 km/h to 15 km/h; (2) test datasets from the 2015 IEEE Signal Process. Cup Database recorded from 11 subjects while performing forearm and upper arm exercise. (3) Chon Lab dataset including 10 min recordings from 10 subjects during treadmill exercise. The ECG signals from all three datasets provided the reference HRs which were used to determine the accuracy of our SpaMA algorithm. The performance of the SpaMA approach was calculated by computing the mean absolute error between the estimated HR from the PPG and the reference HR from the ECG. The average estimation errors using our method on the first, second and third datasets are 0.89, 1.93 and 1.38 beats/min respectively, while the overall error on all 33 subjects is 1.86 beats/min and the performance on only treadmill experiment datasets (22 subjects) is 1.11 beats/min. Moreover, it was found that dynamics of heart rate variability can be

  18. A Novel Time-Varying Spectral Filtering Algorithm for Reconstruction of Motion Artifact Corrupted Heart Rate Signals During Intense Physical Activities Using a Wearable Photoplethysmogram Sensor.

    PubMed

    Salehizadeh, Seyed M A; Dao, Duy; Bolkhovsky, Jeffrey; Cho, Chae; Mendelson, Yitzhak; Chon, Ki H

    2015-12-23

    Accurate estimation of heart rates from photoplethysmogram (PPG) signals during intense physical activity is a very challenging problem. This is because strenuous and high intensity exercise can result in severe motion artifacts in PPG signals, making accurate heart rate (HR) estimation difficult. In this study we investigated a novel technique to accurately reconstruct motion-corrupted PPG signals and HR based on time-varying spectral analysis. The algorithm is called Spectral filter algorithm for Motion Artifacts and heart rate reconstruction (SpaMA). The idea is to calculate the power spectral density of both PPG and accelerometer signals for each time shift of a windowed data segment. By comparing time-varying spectra of PPG and accelerometer data, those frequency peaks resulting from motion artifacts can be distinguished from the PPG spectrum. The SpaMA approach was applied to three different datasets and four types of activities: (1) training datasets from the 2015 IEEE Signal Process. Cup Database recorded from 12 subjects while performing treadmill exercise from 1 km/h to 15 km/h; (2) test datasets from the 2015 IEEE Signal Process. Cup Database recorded from 11 subjects while performing forearm and upper arm exercise. (3) Chon Lab dataset including 10 min recordings from 10 subjects during treadmill exercise. The ECG signals from all three datasets provided the reference HRs which were used to determine the accuracy of our SpaMA algorithm. The performance of the SpaMA approach was calculated by computing the mean absolute error between the estimated HR from the PPG and the reference HR from the ECG. The average estimation errors using our method on the first, second and third datasets are 0.89, 1.93 and 1.38 beats/min respectively, while the overall error on all 33 subjects is 1.86 beats/min and the performance on only treadmill experiment datasets (22 subjects) is 1.11 beats/min. Moreover, it was found that dynamics of heart rate variability can be

  19. Activation of muscarinic receptors by ACh release in hippocampal CA1 depolarizes VIP but has varying effects on parvalbumin-expressing basket cells

    PubMed Central

    Bell, L Andrew; Bell, Karen A; McQuiston, A Rory

    2015-01-01

    We investigated the effect of acetylcholine release on mouse hippocampal CA1 perisomatically projecting interneurons. Acetylcholine was optogenetically released in hippocampal slices by expressing the excitatory optogenetic protein oChIEF-tdTomato in medial septum/diagonal band of Broca cholinergic neurons using Cre recombinase-dependent adeno-associated virally mediated transfection. The effect of optogenetically released acetylcholine was assessed on interneurons expressing Cre recombinase in vasoactive intestinal peptide (VIP) or parvalbumin (PV) interneurons using whole cell patch clamp methods. Acetylcholine released onto VIP interneurons that innervate pyramidal neuron perisomatic regions (basket cells, BCs) were depolarized by muscarinic receptors. Although PV BCs were also excited by muscarinic receptor activation, they more frequently responded with hyperpolarizing or biphasic responses. Muscarinic receptor activation resulting from ACh release increased the frequency of spontaneous inhibitory postsynaptic currents (sIPSCs) in downstream hippocampal CA1 pyramidal neurons with peak instantaneous frequencies occurring in both the gamma and theta bandwidths. Both PV and VIP BCs contributed to the increased sIPSC frequency in pyramidal neurons and optogenetic suppression of PV or VIP BCs inhibited sIPSCs occurring in the gamma range. Therefore, we propose acetylcholine release in CA1 has a complex effect on CA1 pyramidal neuron output through varying effects on perisomatically projecting interneurons. PMID:25556796

  20. The cross-sectional area of the gluteus maximus muscle varies according to habitual exercise loading: Implications for activity-related and evolutionary studies.

    PubMed

    Niinimäki, Sirpa; Härkönen, Laura; Nikander, Riku; Abe, Shinya; Knüsel, Christopher; Sievänen, Harri

    2016-04-01

    Greater size of the gluteus maximus muscle in humans compared to non-human primates has been considered an indication of its function in bipedal posture and gait, especially running capabilities. Our aim was to find out how the size of the gluteus maximus muscle varies according to sports while controlling for variation in muscle strength and body weight. Data on gluteus maximus muscle cross-sectional area (MCA) were acquired from magnetic resonance images of the hip region of female athletes (N=91), and physically active controls (N=20). Dynamic muscle force was measured as counter movement jump and isometric knee extension force as leg press. Five exercise loading groups were created: high impact (triple-jumpers and high-jumpers), odd impact (soccer and squash players), high magnitude (power-lifters), repetitive impact (endurance runners) and repetitive non-impact (swimmers) loadings. Individuals in high impact, odd impact or high-magnitude loading groups had greater MCA compared to those of controls, requiring powerful hip extension, trunk stabilization in rapid directional change and high explosive muscle force. Larger body size and greater muscle strength were associated with larger MCA. An increase in dynamic force was associated with larger MCA, but the strength of this relationship varied with body weight. Thus, gluteal adaptation in humans promotes powerful lower limb movements required in sprinting and rapid changes in direction, as well as maintenance and stabilization of an erect trunk which also provides a platform for powerful motions of the upper limbs. These movements have likely evolved to facilitate food acquisition, including hunting.

  1. Activation of Big Grain1 significantly improves grain size by regulating auxin transport in rice.

    PubMed

    Liu, Linchuan; Tong, Hongning; Xiao, Yunhua; Che, Ronghui; Xu, Fan; Hu, Bin; Liang, Chengzhen; Chu, Jinfang; Li, Jiayang; Chu, Chengcai

    2015-09-01

    Grain size is one of the key factors determining grain yield. However, it remains largely unknown how grain size is regulated by developmental signals. Here, we report the identification and characterization of a dominant mutant big grain1 (Bg1-D) that shows an extra-large grain phenotype from our rice T-DNA insertion population. Overexpression of BG1 leads to significantly increased grain size, and the severe lines exhibit obviously perturbed gravitropism. In addition, the mutant has increased sensitivities to both auxin and N-1-naphthylphthalamic acid, an auxin transport inhibitor, whereas knockdown of BG1 results in decreased sensitivities and smaller grains. Moreover, BG1 is specifically induced by auxin treatment, preferentially expresses in the vascular tissue of culms and young panicles, and encodes a novel membrane-localized protein, strongly suggesting its role in regulating auxin transport. Consistent with this finding, the mutant has increased auxin basipetal transport and altered auxin distribution, whereas the knockdown plants have decreased auxin transport. Manipulation of BG1 in both rice and Arabidopsis can enhance plant biomass, seed weight, and yield. Taking these data together, we identify a novel positive regulator of auxin response and transport in a crop plant and demonstrate its role in regulating grain size, thus illuminating a new strategy to improve plant productivity.

  2. Acute response of hypophysiotropic thyrotropin releasing hormone neurons and thyrotropin release to behavioral paradigms producing varying intensities of stress and physical activity.

    PubMed

    Gutiérrez-Mariscal, Mariana; Sánchez, Edith; García-Vázquez, Arlene; Rebolledo-Solleiro, Daniela; Charli, Jean-Louis; Joseph-Bravo, Patricia

    2012-11-10

    The activity of the hypothalamus-pituitary-thyroid (HPT) axis is essential for energy homeostasis and is differentially modulated by physical and by psychological stress. Contradictory effects of stressful behavioral paradigms on TSH or thyroid hormone release are due to type, length and controllability of the stressor. We hypothesized that an additional determinant of the activity of the HPT axis is the energy demand due to physical activity. We thus evaluated the response of thyrotropin releasing hormone (TRH) neurons of the hypothalamic paraventricular nucleus (PVN) in Wistar male rats submitted to the elevated plus maze (EPM), the open field test (OFT), or restraint, and sacrificed within 1h after test completion; the response to OFT was compared during light (L) or dark (D) phases. Locomotion and anxiety behaviors were similar if animals were tested in L or D phases but their relation to the biochemical parameters differed. All paradigms increased serum corticosterone concentration; the levels of corticotropin releasing hormone receptor 1 and of glucocorticoid receptor (GR) mRNAs in the PVN were enhanced after restraint or OFT-L. Levels of proTRH mRNA increased in the PVN after exposure to EPM-L or OFT-D; serum levels of thyrotropin (TSH) and T(4) only after OFT-D. In contrast, restraint decreased TRH mRNA and serum TSH levels, while it increased TRH content in the mediobasal hypothalamus, implying reduced release. Expression of proTRH in the PVN varied proportionally to the degree of locomotion in OFT-D, while inversely to anxiety in the EPM-L, and to corticosterone in EPM-L and OFT-D. TRH mRNA levels were analyzed by in situ hybridization in the rostral, middle and caudal zones of the PVN in response to OFT-D; they increased in the middle PVN, where most TRH hypophysiotropic neurons reside; levels correlated positively with the velocity attained in the periphery of the OF and negatively, with anxiety. Variations of serum TSH levels correlated positively with

  3. The Lipid Portion of Activated Platelet-Rich Plasma Significantly Contributes to Its Wound Healing Properties

    PubMed Central

    Hoeferlin, Lauren Alexis; Huynh, Quoc K.; Mietla, Jennifer A.; Sell, Scott A.; Tucker, Jason; Chalfant, Charles Edward; Wijesinghe, Dayanjan Shanaka

    2015-01-01

    Objective: Platelet-rich plasma (PRP) is a popular choice for the treatment of chronic wounds. Current dogma attributes these healing properties to the peptide growth factors of PRP. However, PRP is also rich in bioactive lipids whose contribution to healing has not been characterized and warrants investigation due to the protease-rich environment of chronic wounds. Approach: The lipid fraction of PRP was tested with respect to proliferation and migration of primary adult human dermal fibroblasts (HDFa)±exposure to chronic wound fluid (CWF). This fraction was also characterized via LC-MS/MS for bioactive lipids. A synthetic formulation of the bioactive lipid composition was developed and tested for the ability to overcome proliferative growth arrest induced by CWF. Results: The data demonstrate the ability of the lipid fraction of PRP to significantly enhance the migration and proliferation of HDFa, and to overcome the proliferative growth arrest induced by CWF. Furthermore, the synthetic lipid formulation generated following characterization of the PRP lipidome demonstrated a similar ability to overcome proliferative arrest of HDFa in the presence of CWF. Innovation: For the first time, we demonstrate the relevance of the lipid fraction of PRP toward the biology of wound healing. These studies open the possibility of altering the lipid profile of PRP via diet or exogenous pathway manipulation to obtain a better healing outcome. Conclusion: The lipid fraction of PRP is under investigated and yet relevant component in wound healing. The current study demonstrates the relevance of this fraction in wound healing by PRP. PMID:25713752

  4. The effect of varying dietary starch and fat content on serum creatine kinase activity and substrate availability in equine polysaccharide storage myopathy.

    PubMed

    Ribeiro, W P; Valberg, S J; Pagan, J D; Gustavsson, B Essen

    2004-01-01

    The effect of dietary starch and fat content on serum creatine kinase (CK) activity and substrate availability was evaluated in 4 mares of Quarter Horse-related breeds with polysaccharide storage myopathy (PSSM). Four isocaloric diets ranging in digestible energy (DE) from 21.2% (diet A), 14.8% (B), 8.4% (C), to 3.9% (D) for starch, and 7.2% DE (diet A), 9.9% (B), to 12.7% DE (diet C and D) for fat were fed for 6-week periods (4 weeks with exercise) using a 4 X 4 Latin square design. Postprandial glucose and insulin responses were measured, and 4 hours postexercise, serum CK activity, glucose, insulin, free fatty acids (FFA), and beta-hydroxybutyrate (beta-HBA) were analyzed. Glycogen, glucose-6-phosphate, citrate synthase, 3-hydroxy-acyl-CoA dehydrogenase, lactate dehydrogenase as well as abnormal polysaccharide and lipid content were measured in middle gluteal muscle samples. Postprandial insulin and glucose response was higher for diet A versus D. Log CK activity was higher with diets A, B, and C versus D. Daily insulin was higher and FFA lower on diet A versus B, C, and D, whereas glucose varied only slightly with diet. Muscle oxidative capacity and lipid stores were low in PSSM horses and muscle glycogen and abnormal polysaccharide content high on both diets A and D. Individual variation occurred in the response of PSSM horses to diets differing in starch and fat content. However, for those horses with clinical manifestations of PSSM, a diet with <5% DE starch and >12% DE fat can reduce exertional rhabdomyolysis, potentially by increasing availability of FFA for muscle metabolism.

  5. Significance of an Active Volcanic Front in the Far Western Aleutian Arc

    NASA Astrophysics Data System (ADS)

    Yogodzinski, G. M.; Kelemen, P. B.; Hoernle, K.

    2015-12-01

    Discovery of a volcanic front west of Buldir Volcano, the western-most emergent Aleutian volcano, demonstrates that the surface expression of Aleutian volcanism falls below sea level just west of 175.9° E longitude, but is otherwise continuous from mainland Alaska to Kamchatka. The newly discovered sites of western Aleutian seafloor volcanism are the Ingenstrem Depression, a 60 km-long structural depression just west of Buldir, and an unnamed area 300 km further west, referred to as the Western Cones. These locations fall along a volcanic front that stretches from Buldir to Piip Seamount near the Komandorsky Islands. Western Aleutian seafloor volcanic rocks include large quantities of high-silica andesite and dacite, which define a highly calc-alkaline igneous series and carry trace element signatures that are unmistakably subduction-related. This indicates that subducting oceanic lithosphere is present beneath the westernmost Aleutian arc. The rarity of earthquakes below depths of 200 km indicates that the subducting plate is unusually hot. Some seafloor volcanoes are 6-8 km wide at the base, and so are as large as many emergent Aleutian volcanoes. The seafloor volcanoes are submerged in water depths >3000 m because they sit on oceanic lithosphere of the Bering Sea. The volcanic front is thus displaced to the north of the ridge of arc crust that underlies the western Aleutian Islands. This displacement, which developed since approximately 6 Ma when volcanism was last active on the islands, must be a consequence of oblique convergence in a system where the subducting plate and large blocks of arc crust are both moving primarily in an arc-parallel sense. The result is a hot-slab system where low subduction rates probably limit advection of hot mantle to the subarc, and produce a relatively cool and perhaps stagnant mantle wedge. The oceanic setting and highly oblique subduction geometry also severely limit rates of sediment subduction, so the volcanic rocks, which

  6. Concentrations and δ²H values of cuticular n-alkanes vary significantly among plant organs, species and habitats in grasses from an alpine and a temperate European grassland.

    PubMed

    Gamarra, Bruno; Kahmen, Ansgar

    2015-08-01

    n-Alkanes are long-chained hydrocarbons contained in the cuticle of terrestrial plants. Their hydrogen isotope ratios (δ(2)H) have been used as a proxy for environmental and plant ecophysiological processes. Calibration studies designed to resolve the mechanisms that determine the δ(2)H values of n-alkanes have exclusively focused on n-alkanes derived from leaves. It is, however, unclear in which quantities n-alkanes are also produced by other plant organs such as roots or inflorescences, or whether different plant organs produce distinct n-alkane δ(2)H values. To resolve these open questions, we sampled leaves, sheaths, stems, inflorescences and roots from a total of 15 species of European C3 grasses in an alpine and a temperate grassland in Switzerland. Our data show slightly increased n-alkane concentrations and n-alkane δ(2)H values in the alpine compared to the temperate grassland. More importantly, inflorescences had typically much higher n-alkane concentrations than other organs while roots had very low n-alkane concentrations. Most interestingly, the δ(2)H values of the carbon autonomous plant organs leaves, sheaths and stems were in general depleted compared to the overall mean δ(2)H value of a species, while non-carbon autonomous organs such as roots and inflorescences show δ(2)H values that are higher compared to the overall mean δ(2)H value of a species. We attribute organ-specific δ(2)H values to differences in the H-NADPH biosynthetic origin in different plant organs as a function of their carbon relationships. Finally, we employed simple mass balance calculations to show that leaves are in fact the main source of n-alkanes in the sediment. As such, studies assessing the environmental and physiological drivers of n-alkanes that focus on leaves produce relationships that can be employed to interpret the δ(2)H values of n-alkanes derived from sediments. This is despite the significant differences that we found among the δ(2)H values in the

  7. The clinical significance of K-Cl cotransport activity in red cells of patients with HbSC disease.

    PubMed

    Rees, David C; Thein, Swee Lay; Osei, Anna; Drasar, Emma; Tewari, Sanjay; Hannemann, Anke; Gibson, John S

    2015-05-01

    HbSC disease is the second commonest form of sickle cell disease, with poorly understood pathophysiology and few treatments. We studied the role of K-Cl cotransport activity in determining clinical and laboratory features, and investigated its potential role as a biomarker. Samples were collected from 110 patients with HbSC disease and 41 with sickle cell anemia (HbSS). K-Cl cotransport activity was measured in the oxygenated (K-Cl cotransport(100)) and deoxygenated (K-Cl cotransport(0)) states, using radioactive tracer studies. K-Cl cotransport activity was high in HbSC and decreased significantly on deoxygenation. K-Cl cotransport activity correlated significantly and positively with the formation of sickle cells. On multiple regression analysis, K-Cl cotransport increased significantly and independently with increasing reticulocyte count and age. K-Cl cotransport activity was increased in patients who attended hospital with acute pain in 2011 compared to those who did not (K-Cl cotransport(100): mean 3.87 versus 3.20, P=0.009, independent samples T-test; K-Cl cotransport(0): mean 0.96 versus 0.68, P=0.037). On logistic regression only K-Cl cotransport was associated with hospital attendance. Increased K-Cl cotransport activity was associated with the presence of retinopathy, but this effect was confounded by age. This study links variability in a fundamental aspect of cellular pathology with a clinical outcome, suggesting that K-Cl cotransport is central to the pathology of HbSC disease. Increased K-Cl cotransport activity is associated with increasing age, which may be of pathophysiological significance. Effective inhibition of K-Cl cotransport activity is likely to be of therapeutic benefit.

  8. Altered erythrocyte C3b receptor expression, immune complexes, and complement activation in homosexual men in varying risk groups for acquired immune deficiency syndrome.

    PubMed Central

    Tausk, F A; McCutchan, A; Spechko, P; Schreiber, R D; Gigli, I

    1986-01-01

    We studied levels of erythrocyte C3b receptors (E-CR1) and correlated them to the level of circulating immune complexes (CIC) and complement activation in patients with or at risk for acquired immunodeficiency syndrome (AIDS). A significant reduction was found in patients with AIDS (185 +/- 93 CR1/cell), AIDS-related complex, and generalized lymphadenopathy, whereas healthy male homosexuals or normal controls had 434 +/- 193 and 509 +/- 140 CR1/cell, respectively (P less than 0.001). Family studies indicate that this defect is acquired. Reduction in E-CR1 was associated with increased levels of CIC when assayed by binding to Raji cells, but not when tested by C1q binding. Complement activation was assessed by levels of C3bi/C3d-g in plasma, measured with a monoclonal antibody specific for a neoantigen in C3d. AIDS patients had increased C3 activation (2.68 +/- 1.67%) when compared with normal controls (0.9 +/- 0.22%) (P less than 0.01). The decreased E-CR1, the presence of CIC, and C3 activation suggest that complement activation by immune complexes may play a role in the clinical expression of the disease. PMID:2944915

  9. 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.

  10. Rat long-chain acyl-CoA synthetase mRNA, protein, and activity vary in tissue distribution and in response to diet.

    PubMed

    Mashek, Douglas G; Li, Lei O; Coleman, Rosalind A

    2006-09-01

    Distinct isoforms of long-chain acyl-CoA synthetases (ACSLs) may partition fatty acids toward specific metabolic cellular pathways. For each of the five members of the rat ACSL family, we analyzed tissue mRNA distributions, and we correlated the mRNA, protein, and activity of ACSL1 and ACSL4 after fasting and refeeding a 69% sucrose diet. Not only did quantitative real-time PCR analyses reveal unique tissue expression patterns for each ACSL isoform, but expression varied markedly in different adipose depots. Fasting increased ACSL4 mRNA abundance in liver, muscle, and gonadal and inguinal adipose tissues, and refeeding decreased ACSL4 mRNA. A similar pattern was observed for ACSL1, but both fasting and refeeding decreased ACSL1 mRNA in gonadal adipose. Fasting also decreased ACSL3 and ACSL5 mRNAs in liver and ACSL6 mRNA in muscle. Surprisingly, in nearly every tissue measured, the effects of fasting and refeeding on the mRNA abundance of ACSL1 and ACSL4 were discordant with changes in protein abundance. These data suggest that the individual ACSL isoforms are distinctly regulated across tissues and show that mRNA expression may not provide useful information about isoform function. They further suggest that translational or posttranslational modifications are likely to contribute to the regulation of ACSL isoforms.

  11. Brain activations evoked by tactile stimulation varies with the intensity and not with number of receptive fields stimulated: An fMRI study

    NASA Astrophysics Data System (ADS)

    Ramirez Garzón, Y. T.; Pasaye, E. H.; Barrios, F. A.

    2014-11-01

    Using functional Magnetic Resonance Imaging (fMRI) it is possible to study the functional anatomy of primary cortices. Cortical representations in the primary somatosensory cortex have shown discrepancies between activations related to the same body region in some studies; these differences have been more pronounced for lower limb representations. The aim of this study was to observe the influence of the tactile stimulus intensity in somatosensory cortical responses using fMRI. Based in the sensitivity and pain threshold of each subject, we used Von Frey filaments for stimulate 12 control subject in three receptive fields on the right thigh. One filament near to sensitivity threshold (VFS), other close to pain threshold (VFP) and one intermediate filament between the two previous thresholds (VFI). The tactile stimulation with VFS produced no activation on SI, while that the contralateral SI was activated by stimulation with VFI in 5 subjects and with the stimulation of VFP in all subjects. Second level statistical analysis showed significant differences between SI activations related to the stimulation with VFP and VFI (VFP > VFI), in the comparison between the applied different intensities, a small cluster of activation was observed on SI for the unique possible contrast (VFP > VFI). The time course per trial for each subject was extracted and averaged to extract the activation in the contralateral SI and compared across the stimulus modalities, between the sites of field receptive stimulated and the intensities used. The time course of tactile stimulus responses revealed a consistent single peak of activity per cycle (30 s), approximately 12 s after the onset of the stimulus, with exception of the VFI stimulation,_which showed the peak at 10 s. Thus, our results indicate that the cortical representation of a tactile stimulus with fMRI is modulated for the intensity of the stimulus applied.

  12. Pomalidomide shows significant therapeutic activity against CNS lymphoma with a major impact on the tumor microenvironment in murine models.

    PubMed

    Li, Zhimin; Qiu, Yushi; Personett, David; Huang, Peng; Edenfield, Brandy; Katz, Jason; Babusis, Darius; Tang, Yang; Shirely, Michael A; Moghaddam, Mehran F; Copland, John A; Tun, Han W

    2013-01-01

    Primary CNS lymphoma carries a poor prognosis. Novel therapeutic agents are urgently needed. Pomalidomide (POM) is a novel immunomodulatory drug with anti-lymphoma activity. CNS pharmacokinetic analysis was performed in rats to assess the CNS penetration of POM. Preclinical evaluation of POM was performed in two murine models to assess its therapeutic activity against CNS lymphoma. The impact of POM on the CNS lymphoma immune microenvironment was evaluated by immunohistochemistry and immunofluorescence. In vitro cell culture experiments were carried out to further investigate the impact of POM on the biology of macrophages. POM crosses the blood brain barrier with CNS penetration of ~ 39%. Preclinical evaluations showed that it had significant therapeutic activity against CNS lymphoma with significant reduction in tumor growth rate and prolongation of survival, that it had a major impact on the tumor microenvironment with an increase in macrophages and natural killer cells, and that it decreased M2-polarized tumor-associated macrophages and increased M1-polarized macrophages when macrophages were evaluated based on polarization status. In vitro studies using various macrophage models showed that POM converted the polarization status of IL4-stimulated macrophages from M2 to M1, that M2 to M1 conversion by POM in the polarization status of lymphoma-associated macrophages is dependent on the presence of NK cells, that POM induced M2 to M1 conversion in the polarization of macrophages by inactivating STAT6 signaling and activating STAT1 signaling, and that POM functionally increased the phagocytic activity of macrophages. Based on our findings, POM is a promising therapeutic agent for CNS lymphoma with excellent CNS penetration, significant preclinical therapeutic activity, and a major impact on the tumor microenvironment. It can induce significant biological changes in tumor-associated macrophages, which likely play a major role in its therapeutic activity against CNS

  13. Changes in the flavonoid and phenolic acid contents and antioxidant activity of red leaf lettuce (Lollo Rosso) due to cultivation under plastic films varying in ultraviolet transparency.

    PubMed

    García-Macías, Paulina; Ordidge, Matthew; Vysini, Eleni; Waroonphan, Saran; Battey, Nicholas H; Gordon, Michael H; Hadley, Paul; John, Philip; Lovegrove, Julie A; Wagstaffe, Alexandra

    2007-12-12

    Red leaf lettuce (Lollo Rosso) was grown under three types of plastic films that varied in transparency to UV radiation (designated as UV block, UV low, and UV window). Flavonoid composition was determined by high-performance liquid chromatography (HPLC), total phenolics by the Folin-Ciocalteu assay, and antioxidant capacity by the oxygen radical absorbance capacity (ORAC) assay. Exposure to increased levels of UV radiation during cultivation caused the leaves to redden and increased concentrations of total phenols and the main flavonoids, quercetin and cyanidin glycosides, as well as luteolin conjugates and phenolic acids. The total phenol content increased from 1.6 mg of gallic acid equivalents (GAE)/g of fresh weight (FW) for lettuce grown under UV block film to 2.9 and 3.5 mg of GAE/g of FW for lettuce grown under the UV low and UV window films. The antioxidant activity was also higher in lettuce exposed to higher levels of UV radiation with ORAC values of 25.4 and 55.1 micromol of Trolox equivalents/g of FW for lettuce grown under the UV block and UV window films, respectively. The content of phenolic acids, quantified as caffeic acid, was also different, ranging from 6.2 to 11.1 micromol/g of FW for lettuce cultivated under the lowest and highest UV exposure plastic films, respectively. Higher concentrations of the flavonoid glycosides were observed with increased exposure to UV radiation, as demonstrated by the concentrations of aglycones after hydrolysis, which were cyanidin (ranging from 165 to 793 microg/g), quercetin (ranging from 196 to 880 microg/g), and luteolin (ranging from 19 to 152 microg/g). The results demonstrate the potential of the use of UV-transparent plastic as a means of increasing beneficial flavonoid content of red leaf lettuce when the crop is grown in polytunnels.

  14. Work activity in food service: The significance of customer relations, tipping practices and gender for preventing musculoskeletal disorders.

    PubMed

    Laperrière, Ève; Messing, Karen; Bourbonnais, Renée

    2017-01-01

    Some evidence shows that food servers are exposed to an elevated risk of musculoskeletal disorders and injuries, and that their work activity varies by gender. Interviews of servers and observations of food service in Québec, Canada, were carried out in three restaurants and a questionnaire was administered to 64 workers from 44 other restaurants. The relationship with the customer has specific effects on work activity and transforms the physical, emotional and cognitive work. Strategies intended to speed service or otherwise related to the customer relationship can involve health risks. Women reported more direct food service (p < 0.01), a tendency to do more "housekeeping" tasks (p < 0.07) and fewer hours of work per week (p < 0.01). Women workers reported experiencing more sites of pain (p < 0.003). This exploratory study suggests that managing the server-customer relationship could be important in preventing musculoskeletal disorders in this population and that women are at particular risk.

  15. Coadministration of Pinellia ternata Can Significantly Reduce Aconitum carmichaelii to Inhibit CYP3A Activity in Rats

    PubMed Central

    Wu, Jinjun; Cheng, Zaixing; Zhu, Lijun; Lu, Linlin; Zhang, Guiyu; Wang, Ying; Xu, Ying; Lin, Na; Liu, Zhongqiu

    2014-01-01

    Chuanwu (CW), the mother root of Aconitum carmichaelii Debx., is a traditional Chinese medicine (TCM) for treating traumatic injuries, rheumatoid arthritis, and tumors. CW coadministered with banxia (BX), the root of Pinellia ternata, is also widely prescribed in clinical practice. However, the mechanism of this combination is yet deciphered. Current study aimed to investigate the effects of CW, including raw chuanwu (RCW) and processed chuanwu (PCW) alone, as well as CW coadministered with BX on CYP3A activity. Buspirone (BP) and testosterone (Tes) were used as specific probe substrates in vivo and ex vivo, respectively. CYP3A activity was determined by the metabolites formation ratios from the substrates. Compared with those in the control group, the metabolites formation ratios significantly decreased in the RCW and PCW alone groups, accompanied by a marked decrease in CYP3A protein and mRNA levels. However, there was a significant increase in those ratios in the RCW-BX and PCW-BX groups compared to the RCW and PCW alone groups. The results indicated that both RCW and PCW can inhibit CYP3A activity in rats because of downregulation of CYP3A protein and mRNA levels. Decreases in CYP3A activity can be reversed by coadministration with BX. PMID:25371696

  16. HIV-1 Structural Proteins Serve as PAMPs for TLR2 Heterodimers Significantly Increasing Infection and Innate Immune Activation

    PubMed Central

    Henrick, Bethany M.; Yao, Xiao-Dan; Rosenthal, Kenneth Lee

    2015-01-01

    Immune activation is critical to HIV infection and pathogenesis; however, our understanding of HIV innate immune activation remains incomplete. Recently we demonstrated that soluble TLR2 (sTLR2) physically inhibited HIV-induced NFκB activation and inflammation, as well as HIV-1 infection. In light of these findings, we hypothesized that HIV-1 structural proteins may serve as pathogen-associated molecular patterns (PAMPs) for cellular TLR2 heterodimers. These studies made use of primary human T cells and TZMbl cells stably transformed to express TLR2 (TZMbl-2). Our results demonstrated that cells expressing TLR2 showed significantly increased proviral DNA compared to cells lacking TLR2, and mechanistically this may be due to a TLR2-mediated increased CCR5 expression. Importantly, we show that HIV-1 structural proteins, p17, p24, and gp41, act as viral PAMPs signaling through TLR2 and its heterodimers leading to significantly increased immune activation via the NFκB signaling pathway. Using co-immunoprecipitation and a dot blot method, we demonstrated direct protein interactions between these viral PAMPs and TLR2, while only p17 and gp41 bound to TLR1. Specifically, TLR2/1 heterodimer recognized p17 and gp41, while p24 lead to immune activation through TLR2/6. These results were confirmed using TLR2/1 siRNA knock down assays which ablated p17 and gp41-induced cellular activation and through studies of HEK293 cells expressing selected TLRs. Interestingly, our results show in the absence of TLR6, p24 bound to TLR2 and blocked p17 and gp41-induced activation, thus providing a novel mechanism by which HIV-1 can manipulate innate sensing. Taken together, our results identified, for the first time, novel HIV-1 PAMPs that play a role in TLR2-mediated cellular activation and increased proviral DNA. These findings have important implications for our fundamental understanding of HIV-1 immune activation and pathogenesis, as well as HIV-1 vaccine development. PMID:26347747

  17. Quercetin phospholipid complex significantly protects against oxidative injury in ARPE-19 cells associated with activation of Nrf2 pathway.

    PubMed

    Xu, Xin-Rong; Yu, Hai-Tao; Yang, Yan; Hang, Li; Yang, Xue-Wen; Ding, Shu-Hua

    2016-01-05

    Age-related macular degeneration (AMD) is a major cause of blindness worldwide. Oxidative stress plays a crucial role in the pathogenesis of dry AMD. Quercetin has potent anti-oxidative activities, but poor bioavailability limits its therapeutic application. Herein, we prepared the phospholipid complex of quercetin (quercetin-PC), characterized its structure by differential scanning calorimetry, infrared spectrum and x-ray diffraction. Quercetin-PC had equilibrium solubility of 38.36 and 1351.27μg/ml in water and chloroform, respectively, which was remarkably higher than those of quercetin alone. Then we established hydrogen peroxide (H2O2)-induced oxidative injury model in human ARPE-19 cells to examine the effects of quercetin-PC. Quercetin-PC, stronger than quercetin, promoted cell proliferation, and the proliferation rate was increased to be 78.89% when treated with Quercetin-PC at 400μM. Moreover, quercetin-PC effectively prevented ARPE-19 cells from apoptosis, and the apoptotic rate was reduced to be 3.1% when treated with Quercetin-PC at 200μM. In addition, quercetin-PC at 200μM significantly increased the activities of SOD, CAT and GSH-PX, and reduced the levels of reactive oxygen species and MDA in H2O2-treated ARPE-19 cells, but quercetin at 200μM failed to do so. Molecular examinations revealed that quercetin-PC at 200μM significantly activated Nrf2 nuclear translocation and significantly enhanced the expression of target genes HO-1, NQO-1 and GCL by different folds at both mRNA and protein levels. Our current data collectively indicated that quercetin-PC had stronger protective effects against oxidative-induced damages in ARPE-19 cells, which was associated with activation of Nrf2 pathway and its target genes implicated in antioxidant defense.

  18. Early-Onset Hypertrophic Cardiomyopathy Mutations Significantly Increase the Velocity, Force, and Actin-Activated ATPase Activity of Human β-Cardiac Myosin.

    PubMed

    Adhikari, Arjun S; Kooiker, Kristina B; Sarkar, Saswata S; Liu, Chao; Bernstein, Daniel; Spudich, James A; Ruppel, Kathleen M

    2016-12-13

    Hypertrophic cardiomyopathy (HCM) is a heritable cardiovascular disorder that affects 1 in 500 people. A significant percentage of HCM is attributed to mutations in β-cardiac myosin, the motor protein that powers ventricular contraction. This study reports how two early-onset HCM mutations, D239N and H251N, affect the molecular biomechanics of human β-cardiac myosin. We observed significant increases (20%-90%) in actin gliding velocity, intrinsic force, and ATPase activity in comparison to wild-type myosin. Moreover, for H251N, we found significantly lower binding affinity between the S1 and S2 domains of myosin, suggesting that this mutation may further increase hyper-contractility by releasing active motors. Unlike previous HCM mutations studied at the molecular level using human β-cardiac myosin, early-onset HCM mutations lead to significantly larger changes in the fundamental biomechanical parameters and show clear hyper-contractility.

  19. Activating killer-cell immunoglobulin-like receptors (KIR) and their cognate HLA ligands are significantly increased in autism

    PubMed Central

    Torres, Anthony R.; Westover, Jonna B.; Gibbons, Cole; Johnson, Randall C.; Ward, David C.

    2012-01-01

    Killer-cell immunoglobulin-like receptor (KIR) proteins are expressed on natural killer (NK) cells and appear important in innate and adaptive immunity. There are about 14 KIR genes on chromosome 19q13.4, composed of those that inhibit and those that activate NK cell killing. Haplotypes have different combinations of these genes meaning that not all genes are present in a subject. There are two main classes of cognate human leukocyte antigen (HLA) ligands (HLA-Bw4 and HLA-C1/C2) that bind to the inhibitory/activating receptors. As a general rule, the inhibitory state is maintained except when virally infected or tumor cells are encountered; however, both increased activation and inhibition states have been associated with susceptibility and protection against numerous disease states including cancer, arthritis, and psoriasis. Utilizing DNA from 158 Caucasian subjects with autism and 176 KIR control subjects we show for the first time a highly significant increase in four activating KIR genes (2DS5, 3DS1, 2DS1 and 2DS4) as measured by chi square values and odds ratios. In addition, our data suggests a highly significant increase in the activating KIR gene 2DS1 and its cognate HLA-C2 ligand (2DS1+C2; p=0.00003 [Odds Ratio=2.87]). This information ties together two major immune gene complexes, the Human Leukocyte Complex and the Leukocyte Receptor Complex, and may partially explain immune abnormalities observed in many subjects with autism. PMID:22884899

  20. Presence of diadenosine 5',5''' -P1, P4-tetraphosphate (Ap4A) in mamalian cells in levels varying widely with proliferative activity of the tissue: a possible positive "pleiotypic activator".

    PubMed Central

    Rapaport, E; Zamecnik, P C

    1976-01-01

    An accurate assay of diadenosine 5',5'''- P1,P4-tetraphosphate [A(5') pppp(5')A], which was shown to be formed in vitro in the backreaction of the amino acid activation step, has been developed in various cell lines in culture and in normal mouse liver or hepatoma in vivo. Use of radioactive labeling of acid-soluble nucleotides to high specific activity followed by chromatographic separation techniques yielded levels of Ap4A varying from 5 to 0.05 muM (from 30 pmol/mg of protein to 0.15 pmol), depending on the doubling time of the cell line or the proliferative state of the cells. The levels of Ap4A incells is inversely related to their doubling time, varying from 0.1 X 10(-4) of the cellular ATP levels in slowly growing cells to 20 X 10(-4) of the ATP levels of cells with rapid doubling times. The steady-state levels of ATP of different cell lines, although showing some fluctuations, are not related to the doubling time of the cells. Arrest of cellular proliferation by serum deprivation or amino acid starvation, which does not alter the cellular ATP levels more than 2-fold, does nevertheless cause a decrease of 30 to 50-fold in the Ap4A levels. Inhibition of protein synthesis by pactamycin or puromycin, or inhibition of DNA synthesis by hydroxyurea, leads to a more dramatic decrease of 50 to 100-fold in intracellular Ap4A levels. The metabolic lability of Ap4A is also demonstrated by its rapid depletion after decreases in the ATP/ADP ratio. The possibility of Ap4A being a metabolic "signal nucleotide" that is formed at the onset of protein synthesis and is active in positive growth regulation (positive pleiotypic activation) is discussed. PMID:1069282

  1. An Antimicrobial Metabolite from Bacillus sp.: Significant Activity Against Pathogenic Bacteria Including Multidrug-Resistant Clinical Strains

    PubMed Central

    Chalasani, Ajay G.; Dhanarajan, Gunaseelan; Nema, Sushma; Sen, Ramkrishna; Roy, Utpal

    2015-01-01

    In this study, the cell free modified tryptone soya broth (pH 7.4 ± 0.2) of Bacillus subtilis URID 12.1 showed significant antimicrobial activity against multidrug-resistant strains of Staphylococcus aureus, S. epidermidis, Streptococcus pyogenes and Enterococcus faecalis. The partially purified antimicrobial molecule was found to be resistant to extremes of pH and temperatures and also to higher concentrations of trypsin and proteinase K. The antimicrobial molecule was purified by a three-step method that included reversed-phase high performance liquid chromatography (RP-HPLC). The minimum inhibitory concentration (MIC) values were determined for 14 species of bacteria using a microbroth dilution technique. The HPLC-purified fraction showed the MICs ranging from 0.5 to 16 μg/ml for methicillin and vancomycin-resistant Staphylococcus aureus (MVRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE) strains. The molecular mass of the antimicrobial compound was determined to be 842.37 Da. The same antimicrobial fraction showed negligible haemolytic activity against human red blood cells even at a concentration as high as 100 μg/ml. Because of its significant antimicrobial activity at low MIC values coupled with its non-haemolytic property, it may prove to be a novel antimicrobial lead molecule. PMID:26696963

  2. Spaceflight and simulated microgravity cause a significant reduction of key gene expression in early T-cell activation.

    PubMed

    Martinez, Emily M; Yoshida, Miya C; Candelario, Tara Lynne T; Hughes-Fulford, Millie

    2015-03-15

    Healthy immune function depends on precise regulation of lymphocyte activation. During the National Aeronautics and Space Administration (NASA) Apollo and Shuttle eras, multiple spaceflight studies showed depressed lymphocyte activity under microgravity (μg) conditions. Scientists on the ground use two models of simulated μg (sμg): 1) the rotating wall vessel (RWV) and 2) the random positioning machine (RPM), to study the effects of altered gravity on cell function before advancing research to the true μg when spaceflight opportunities become available on the International Space Station (ISS). The objective of this study is to compare the effects of true μg and sμg on the expression of key early T-cell activation genes in mouse splenocytes from spaceflight and ground animals. For the first time, we compared all three conditions of microgravity spaceflight, RPM, and RWV during immune gene activation of Il2, Il2rα, Ifnγ, and Tagap; moreover, we confirm two new early T-cell activation genes, Iigp1 and Slamf1. Gene expression for all samples was analyzed using quantitative real-time PCR (qRT-PCR). Our results demonstrate significantly increased gene expression in activated ground samples with suppression of mouse immune function in spaceflight, RPM, and RWV samples. These findings indicate that sμg models provide an excellent test bed for scientists to develop baseline studies and augment true μg in spaceflight experiments. Ultimately, sμg and spaceflight studies in lymphocytes may provide insight into novel regulatory pathways, benefiting both future astronauts and those here on earth suffering from immune disorders.

  3. Spaceflight and simulated microgravity cause a significant reduction of key gene expression in early T-cell activation

    PubMed Central

    Martinez, Emily M.; Yoshida, Miya C.; Candelario, Tara Lynne T.

    2015-01-01

    Healthy immune function depends on precise regulation of lymphocyte activation. During the National Aeronautics and Space Administration (NASA) Apollo and Shuttle eras, multiple spaceflight studies showed depressed lymphocyte activity under microgravity (μg) conditions. Scientists on the ground use two models of simulated μg (sμg): 1) the rotating wall vessel (RWV) and 2) the random positioning machine (RPM), to study the effects of altered gravity on cell function before advancing research to the true μg when spaceflight opportunities become available on the International Space Station (ISS). The objective of this study is to compare the effects of true μg and sμg on the expression of key early T-cell activation genes in mouse splenocytes from spaceflight and ground animals. For the first time, we compared all three conditions of microgravity spaceflight, RPM, and RWV during immune gene activation of Il2, Il2rα, Ifnγ, and Tagap; moreover, we confirm two new early T-cell activation genes, Iigp1 and Slamf1. Gene expression for all samples was analyzed using quantitative real-time PCR (qRT-PCR). Our results demonstrate significantly increased gene expression in activated ground samples with suppression of mouse immune function in spaceflight, RPM, and RWV samples. These findings indicate that sμg models provide an excellent test bed for scientists to develop baseline studies and augment true μg in spaceflight experiments. Ultimately, sμg and spaceflight studies in lymphocytes may provide insight into novel regulatory pathways, benefiting both future astronauts and those here on earth suffering from immune disorders. PMID:25568077

  4. [Changes of ADAMTS13 activity and vWF antigen level in patients with acute myelogenous leukemia and their significance].

    PubMed

    Zhang, Wen-Juan; Han, Yue; Ma, Zhen-Ni; Wang, Qian; Tang, Ya-Qiong; Wang, Jie; Su, Jian; Sun, Ai-Ning; Wang, Zhao-Yue; Ruan, Chang-Geng; Wu, De-Pei

    2014-12-01

    This study was purposed to investigate the changes of von Willebrand factor cleaving protease (ADAMTS13) activity and vWF antigen level in patients with acute myelogenous leukemia (AML) before and after treatment and evaluate their clinical significance. Seventy-three AML patients were enrolled in this study, the sodium citrate anticoagulated plasma was collected before and after their induction chemotherapy. Fluorescence resonance energy transfer substrate vWF73 (FRETS-vWF73) assay was established to detect the plasma ADAMTS13 activity while vWF antigen level was measured by ELISA. The results showed that the ADAMTS13 activity in newly diagnosed patients with AML before induction therapy was obviously lower than that in normal controls (63.3 ± 25.5)% vs (105.1 ± 37.7)(P < 0.01), while the vWF antigen level was higher than that in normal controls (226.6 ± 127.0)% vs (111.4 ± 39.7)% (P < 0.01). After standard induction chemotherapy, the ADAMTS13 activity of AML patients in complete remission period was higher than that in AML patients before therapy (P < 0.01), and was not significant difference with that in normal controls; the vWF antigen was significantly lower than that in AML patients before therapy (P < 0.01), but it still was higher than that in controls (P < 0.05). The ADAMTS13 activity in newly diagnosed AML patients complicated with infection before therapy was obviously lower than that in AML patients without infection (52.2 ± 20.6)% vs (73.9 ± 24.7)% (P < 0.01), while the vWF antigen level was significantly higher than that in AML patients without infection (262.2 ± 135.7)% vs (193.8 ± 110.2)% (P < 0.05). The ADAMTS13 activity in AML patients with disseminated intravascular coagulation (DIC) was significantly lower than that in AML patients without DIC (42.0 ± 14.5)% vs (73.4 ± 22.7)% (P < 0.01), while the vWF antigen level was obviously higher that in AML patients without DIC (274.2 ± 140.0)% vs (204.7 ± 115.5)% (P < 0.01). It is concluded

  5. Marine organism sulfated polysaccharides exhibiting significant antimalarial activity and inhibition of red blood cell invasion by Plasmodium

    PubMed Central

    Marques, Joana; Vilanova, Eduardo; Mourão, Paulo A. S.; Fernàndez-Busquets, Xavier

    2016-01-01

    The antimalarial activity of heparin, against which there are no resistances known, has not been therapeutically exploited due to its potent anticoagulating activity. Here, we have explored the antiplasmodial capacity of heparin-like sulfated polysaccharides from the sea cucumbers Ludwigothurea grisea and Isostichopus badionotus, from the red alga Botryocladia occidentalis, and from the marine sponge Desmapsamma anchorata. In vitro experiments demonstrated for most compounds significant inhibition of Plasmodium falciparum growth at low-anticoagulant concentrations. This activity was found to operate through inhibition of erythrocyte invasion by Plasmodium, likely mediated by a coating of the parasite similar to that observed for heparin. In vivo four-day suppressive tests showed that several of the sulfated polysaccharides improved the survival of Plasmodium yoelii-infected mice. In one animal treated with I. badionotus fucan parasitemia was reduced from 10.4% to undetectable levels, and Western blot analysis revealed the presence of antibodies against P. yoelii antigens in its plasma. The retarded invasion mediated by sulfated polysaccharides, and the ensuing prolonged exposure of Plasmodium to the immune system, can be explored for the design of new therapeutic approaches against malaria where heparin-related polysaccharides of low anticoagulating activity could play a dual role as drugs and as potentiators of immune responses. PMID:27071342

  6. Significant alterations in anisotropic ice growth rate induced by the ice nucleation-active bacteria Xanthomonas campestris

    NASA Astrophysics Data System (ADS)

    Nada, Hiroki; Zepeda, Salvador; Miura, Hitoshi; Furukawa, Yoshinori

    2010-09-01

    In the present study, we found that the ice nucleation-active bacteria Xanthomonas campestris significantly altered anisotropic ice growth rate. Results of ice growth experiments in the presence of X. campestris showed that this bacterium decreased the ice crystal growth rate in the c-axis, whereas it increased growth rates in directions normal to the c-axis. These results indicate that these alterations in anisotropic growth rate are the result of selective binding of bacterial ice-nucleating proteins along the {0 0 0 1} basal plane.

  7. Plasma Thrombin Generation and Sensitivity to Activated Protein C Among Patients With Myeloma and Monoclonal Gammopathy of Undetermined Significance.

    PubMed

    Crowley, Maeve P; Kevane, Barry; O'Shea, Susan I; Quinn, Shane; Egan, Karl; Gilligan, Oonagh M; Ní Áinle, Fionnuala

    2016-09-01

    The etiology of the prothrombotic state in myeloma has yet to be definitively characterized. Similarly, while recent evidence suggests that patients with monoclonal gammopathy of undetermined significance (MGUS) may also be at increased risk of thrombosis, the magnitude and the etiology of this risk have also yet to be defined. The present study aims to characterize patterns of plasma thrombin generation and sensitivity to the anticoagulant activity of activated protein C (APC) at the time of initial diagnosis of myeloma and in response to therapy in comparison to that observed among patients with MGUS and matched, healthy volunteers. Patients presenting with newly diagnosed/newly relapsed myeloma (n = 8), MGUS (n = 8), and matched healthy volunteers (n = 8) were recruited. Plasma thrombin generation was determined by calibrated automated thrombography. Peak thrombin generation was significantly higher in patients with myeloma (383.4 ± 33.4 nmol/L) and MGUS (353.4 ± 16.5 nmol/L) compared to healthy volunteers (276.7 ± 20.8 nmol/L; P < .05). In the presence of APC, endogenous thrombin potential was significantly lower in control plasma (228.6 ± 44.5 nmol/L × min) than in either myeloma (866.2 ± 241.3 nmol/L × min, P = .01) or MGUS plasma (627 ± 91.5 nmol/L × min, P = .003). Within the myeloma cohort, peak thrombin generation was significantly higher at diagnosis (353.2 ± 15.9 nmol/L) than following completion of the third cycle of therapy (282.1 ± 15.2 nmol/L; P < .005). Moreover, sensitivity to APC increased progressively with each cycle of chemotherapy. Further study of the etiology and evolving patterns of hypercoagulability among patients with these conditions is warranted and may have future implications for thromboprophylaxis strategies.

  8. Discovery of a Potent HIV Integrase Inhibitor That Leads to a Prodrug with Significant anti-HIV Activity

    PubMed Central

    2011-01-01

    Worldwide research efforts in drug discovery involving HIV integrase have produced only one compound, raltegravir, that has been approved for clinical use in HIV/AIDS. As resistance, toxicity, and drug–drug interactions are recurring issues with all classes of anti-HIV drugs, the discovery of novel integrase inhibitors remains a significant scientific challenge. We have designed a lead HIV-1 strand transfer (ST) inhibitor (IC50 70 nM), strategically assembled on a pyridinone scaffold. A focused structure–activity investigation of this parent compound led to a significantly more potent ST inhibitor, 2 (IC50 6 ± 3 nM). Compound 2 exhibits good stability in pooled human liver microsomes. It also displays a notably favorable profile with respect to key human cytochrome P450 (CYP) isozymes and human UDP glucuronosyl transferases (UGTs). The prodrug of inhibitor 2, i.e., compound 10, was found to possess remarkable anti-HIV-1 activity in cell culture (EC50 9 ± 4 nM, CC50 135 ± 7 μM, therapeutic index = 15 000). PMID:22328963

  9. Enhanced activity of the free radical producing enzyme xanthine oxidase in hypoxic rat liver. Regulation and pathophysiologic significance.

    PubMed Central

    Brass, C A; Narciso, J; Gollan, J L

    1991-01-01

    It has been widely proposed that conversion of xanthine dehydrogenase (XDH) to its free radical-producing form, xanthine oxidase (XOD), underlies ischemic/reperfusion injury, although the relationship of this conversion to hypoxia and its physiologic control have not been defined. This study details the time course and control of this enzymatic interconversion. In a functionally intact, isolated perfused rat liver model, mean % XOD activity increased as a function of both the duration (25 to 45% in 3 h) and degree (r = 0.97) of hypoxia. This process was markedly accelerated in ischemic liver by an overnight fast (45 vs. 30% at 2 h), and by imposing a short period of in vivo ischemia (cardiopulmonary arrest 72%). Moreover, only under these conditions was there a significant rise in the XOD activity due to the conformationally altered XDH molecule (XODc, 18%), as well as concomitant morphologic injury. Neither circulating white blood cells nor thrombosis appeared to contribute to the effects of in vivo ischemia on enzyme conversion. Thus, it is apparent that conversion to the free radical-producing state, with high levels of XOD activity and concurrent cellular injury, can be achieved during a relatively short period of hypoxia under certain well-defined physiologic conditions, in a time course consistent with its purported role in modulating reperfusion injury. These data also suggest that the premorbid condition of organ donors (e.g., nutritional status and relative state of hypoxia) is important in achieving optimal organ preservation. Images PMID:1991828

  10. Alterations in activities of acid phosphatase, alkaline phosphatase, ATPase and ATP content in response to seasonally varying Pi status in okra (Abelmoschus esculentus).

    PubMed

    Sen, Supatra; Mukherji, S

    2004-04-01

    Phosphorus (P) is the second most important macronutrient for plant growth. Plants exhibit numerous physiological and metabolic adaptations in response to seasonal variations in phosphorus content. Activities of acid and alkaline phosphatases, ATPase and ATP content were studied in summer, rainy and winter seasons at two different developmental stages (28 and 58 days after sowing) in Okra. Activities of both acid and alkaline phosphatases increased manifold in winter to cope up with low phosphorus content. ATP content and ATPase activity were high in summer signifying an active metabolic period. Phosphorus deficiency is characterized by low ATP content and ATPase activity (which are in turn partly responsible for a drastic reduction in growth and yield) and enhanced activities of acid and alkaline phosphatases which increase the availability of P in P-deficient seasons.

  11. Functional significance of parasitism-induced suppression of juvenile hormone esterase activity in developmentally delayed Choristoneura fumiferana larvae.

    PubMed

    Cusson, M; Laforge, M; Miller, D; Cloutier, C; Stoltz, D

    2000-03-01

    The parasitic wasp Tranosema rostrale transmits a polydnavirus (PDV) to its host, Choristoneura fumiferana, during oviposition. Last-instar C. fumiferana larvae parasitized by T. rostrale early in the stadium fail to undergo metamorphosis, and injection of the wasp's calyx fluid (CxF; contains PDV) into healthy caterpillars induces a dose-dependent delay in initiation of metamorphosis (D. Doucet and M. Cusson, 1996, Entomol. Exp. Appl. 81, 21-30). In the present work, parasitization and injection of CxF (0.5 female equivalent) on the first day of the last stadium both prevented the rise in hemolymph 20-hydroxyecdysone (20HE) titer observed between day 4 and day 7 in control and saline-injected larvae. Similarly, juvenile hormone esterase (JHE) activity was depressed following parasitization or CxF injection, whereas control larvae displayed a peak on day 4. However, neither parasitism nor injection of CxF on day 1 prevented the JH-producing glands from turning off during the first half of the last stadium. Likewise, low but clearly detectable JH titers were observed in the first hours following the molt but very low titers, at or near the detection limit of our radioimmunoassay, were seen in both control and parasitized larvae on day 4. Prothoracic glands showed no apparent sign of degeneration 4 days after injection of CxF but had significantly smaller cells than saline-injected larvae 7 days postinjection. It is not clear whether this was a direct effect of T. rostrale PDV. Thus, disruption of spruce budworm metamorphosis by T. rostrale CxF involves depression of 20HE titers but is not associated with a measurable increase in the level of JH, as shown for some other host-parasitoid systems. In view of the latter observation, we put forward three hypotheses regarding the functional significance of the observed suppression of JHE activity in developmentally arrested C. fumiferana larvae.

  12. Fluorosis varied treatment options

    PubMed Central

    Sherwood, I Anand

    2010-01-01

    Fluorosis has been reported way back in 1901. The treatment options for fluorosis are varied depending upon individual cases. This article comes from Madurai in India where its surrounding towns are fluorosis-prone zones. The purpose of this article is to report various treatment options available for dental fluorosis; this is the first time that complete full mouth rehabilitation for dental fluorosis is being reported. This article also dwells on the need for the dentists to be aware of their local indigenous pathologies to treat it in a better manner. PMID:20582220

  13. Sulfur Use Efficiency Is a Significant Determinant of Drought Stress Tolerance in Relation to Photosynthetic Activity in Brassica napus Cultivars

    PubMed Central

    Lee, Bok-Rye; Zaman, Rashed; Avice, Jean-Christophe; Ourry, Alain; Kim, Tae-Hwan

    2016-01-01

    To investigate the varietal difference in sulfur use efficiency (SUE) and drought stress tolerance, Brassica napus ‘Mosa’ and ‘Saturnin’ were exposed to polyethylene glycol (PEG)-induced drought stress for 72 h. Direct quantification of S uptake, de novo synthesis of amino acids and proteins was performed by tracing 34S. The responses of photosynthetic activity in relation to SUE were also examined. The total amount of newly absorbed S decreased with drought stress in both cultivars but the decrease rate was significantly higher in Mosa (-64%) than in Saturnin (-41%). Drought stress also decreased the amount of S assimilated into amino acids (34S-amino acids) and proteins (34S-proteins). The total amount of S incorporated into amino acids and proteins was generally higher in Saturnin (663.7 μg S per plant) than in Mosa (337.3 μg S per plant). The estimation of SUE based on S uptake (SUpE) and S assimilation (SUaE) showed that SUE was much higher in Saturnin than in Mosa. The inhibition of photosynthetic activity including Rubisco protein degradation caused by drought stress was much lower in the cultivar with higher SUE (Saturnin). The present study clearly indicates that the genotype with higher SUE is more tolerant to PEG-induced drought stress. PMID:27092167

  14. Sulfur Use Efficiency Is a Significant Determinant of Drought Stress Tolerance in Relation to Photosynthetic Activity in Brassica napus Cultivars.

    PubMed

    Lee, Bok-Rye; Zaman, Rashed; Avice, Jean-Christophe; Ourry, Alain; Kim, Tae-Hwan

    2016-01-01

    To investigate the varietal difference in sulfur use efficiency (SUE) and drought stress tolerance, Brassica napus 'Mosa' and 'Saturnin' were exposed to polyethylene glycol (PEG)-induced drought stress for 72 h. Direct quantification of S uptake, de novo synthesis of amino acids and proteins was performed by tracing (34)S. The responses of photosynthetic activity in relation to SUE were also examined. The total amount of newly absorbed S decreased with drought stress in both cultivars but the decrease rate was significantly higher in Mosa (-64%) than in Saturnin (-41%). Drought stress also decreased the amount of S assimilated into amino acids ((34)S-amino acids) and proteins ((34)S-proteins). The total amount of S incorporated into amino acids and proteins was generally higher in Saturnin (663.7 μg S per plant) than in Mosa (337.3 μg S per plant). The estimation of SUE based on S uptake (SUpE) and S assimilation (SUaE) showed that SUE was much higher in Saturnin than in Mosa. The inhibition of photosynthetic activity including Rubisco protein degradation caused by drought stress was much lower in the cultivar with higher SUE (Saturnin). The present study clearly indicates that the genotype with higher SUE is more tolerant to PEG-induced drought stress.

  15. Gas-Phase Ambient Air Contaminants Exhibit Significant Dioxin-like and Estrogen-like Activity in Vitro

    PubMed Central

    Klein, Gail P.; Hodge, Erin M.; Diamond, Miriam L.; Yip, Amelia; Dann, Tom; Stern, Gary; Denison, Michael S.; Harper, Patricia A.

    2006-01-01

    Several adverse health effects, such as respiratory and cardiovascular morbidity, have been linked to exposure to particulate matter in ambient air; however, the biologic activity of gas-phase ambient organic air contaminants has not been examined as thoroughly. Using aryl hydrocarbon receptor (AHR)–based and estrogen receptor (ER)–based cell bioassay systems, we assessed the dioxin-like and estrogenic activities of gas-phase organic ambient air contaminants compared with those of particulate-phase contaminants using samples collected between seasons over 2 years from an urban and a rural location in the Greater Toronto Area, Canada. The concentration of the sum (∑) of polycyclic aromatic hydrocarbons, which was highest in the gas phase, was 10–100 times more abundant than that of ∑polychlorinated biphenyls, ∑nitro-polycyclic aromatic hydrocarbons, and ∑organochlorine pesticides, and 103 to 104 times more abundant than ∑polychlorinated dibenzo-p-dioxins/dibenzofurans. Gas-phase samples induced significant AHR- and ER-dependent gene expression. The activity of the gas-phase samples was greater than that of the particulate-phase samples in the estrogen assay and, in one case, in the AHR assay. We found no strong associations between either summer or winter seasons or urban or rural locations in the relative efficacy of the extracts in either the ER or AHR assay despite differences in chemical composition, concentrations, and abundance. Our results suggest that mechanistic studies of the health effects of ambient air must consider gas and particulate phases because chemicals present in both phases can affect AHR and ER signaling pathways. PMID:16675423

  16. Antioxidant Activity and Phenolic Content of Defatted Buckwheat (Fagopyrum esculentum Moench) Flour in Water or Ethanol Heated using Microwave Irradiation at Varying Temperatures

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Buckwheat (Fagopyrum esculentum) has potential to be a nutritionally beneficial crop due to its high phenolic content and antioxidant activity. We explored new technologies to enhance buckwheat phenolic content and antioxidant activity. Buckwheat achenes were ground and flour was extracted for 15 ...

  17. Chk1 inhibition significantly potentiates activity of nucleoside analogs in TP53-mutated B-lymphoid cells

    PubMed Central

    Zemanova, Jana; Hylse, Ondrej; Collakova, Jana; Vesely, Pavel; Oltova, Alexandra; Borsky, Marek; Zaprazna, Kristina; Kasparkova, Marie; Janovska, Pavlina; Verner, Jan; Kohoutek, Jiri; Dzimkova, Marta; Bryja, Vitezslav; Jaskova, Zuzana; Brychtova, Yvona; Paruch, Kamil; Trbusek, Martin

    2016-01-01

    Treatment options for TP53-mutated lymphoid tumors are very limited. In experimental models, TP53-mutated lymphomas were sensitive to direct inhibition of checkpoint kinase 1 (Chk1), a pivotal regulator of replication. We initially tested the potential of the highly specific Chk1 inhibitor SCH900776 to synergize with nucleoside analogs (NAs) fludarabine, cytarabine and gemcitabine in cell lines derived from B-cell malignancies. In p53-proficient NALM-6 cells, SCH900776 added to NAs enhanced signaling towards Chk1 (pSer317/pSer345), effectively blocked Chk1 activation (Ser296 autophosphorylation), increased replication stress (p53 and γ-H2AX accumulation) and temporarily potentiated apoptosis. In p53-defective MEC-1 cell line representing adverse chronic lymphocytic leukemia (CLL), Chk1 inhibition together with NAs led to enhanced and sustained replication stress and significantly potentiated apoptosis. Altogether, among 17 tested cell lines SCH900776 sensitized four of them to all three NAs. Focusing further on MEC-1 and co-treatment of SCH900776 with fludarabine, we disclosed chromosome pulverization in cells undergoing aberrant mitoses. SCH900776 also increased the effect of fludarabine in a proportion of primary CLL samples treated with pro-proliferative stimuli, including those with TP53 disruption. Finally, we observed a fludarabine potentiation by SCH900776 in a T-cell leukemia 1 (TCL1)-driven mouse model of CLL. Collectively, we have substantiated the significant potential of Chk1 inhibition in B-lymphoid cells. PMID:27556692

  18. Efficacious gene silencing in serum and significant apoptotic activity induction by survivin downregulation mediated by new cationic gemini tocopheryl lipids.

    PubMed

    Kumar, Krishan; Maiti, Bappa; Kondaiah, Paturu; Bhattacharya, Santanu

    2015-02-02

    Nonviral gene delivery offers cationic liposomes as promising instruments for the delivery of double-stranded RNA (ds RNA) molecules for successful sequence-specific gene silencing (RNA interference). The efficient delivery of siRNA (small interfering RNA) to cells while avoiding unexpected side effects is an important prerequisite for the exploitation of the power of this excellent tool. We present here six new tocopherol based cationic gemini lipids, which induce substantial gene knockdown without any obvious cytotoxicity. All the efficient coliposomal formulations derived from each of these geminis and a helper lipid, dioleoylphosphatidylethanolamine (DOPE), were well characterized using physical methods such as atomic force microscopy (AFM) and dynamic light scattering (DLS). Zeta potential measurements were conducted to estimate the surface charge of these formulations. Flow cytometric analysis showed that the optimized coliposomal formulations could transfect anti-GFP siRNA efficiently in three different GFP expressing cell lines, viz., HEK 293T, HeLa, and Caco-2, significantly better than a potent commercial standard Lipofectamine 2000 (L2K) both in the absence and in the presence of serum (FBS). Notably, the knockdown activity of coliposomes of gemini lipids was not affected even in the presence of serum (10% and 50% FBS) while it dropped down for L2K significantly. Observations under a fluorescence microscope, RT-PCR, and Western blot analysis substantiated the flow cytometry results. The efficient cellular entry of labeled siRNA in GFP expressing cells as evidenced from confocal microscopy put forward these gemini lipids among the potent lipidic carriers for siRNA. The efficient transfection capabilities were also profiled in a more relevant fashion while performing siRNA transfections against survivin (an anti-apoptotic protein) which induced substantial apoptosis. Furthermore, the survivin downregulation improved the therapeutic efficacy levels of an

  19. Telomerase activity is more significant for predicting the outcome of IVF treatment than telomere length in granulosa cells.

    PubMed

    Wang, Wenjun; Chen, Hong; Li, Ruiqi; Ouyang, Nengyong; Chen, Jinghua; Huang, Lili; Mai, Meiqi; Zhang, Ningfeng; Zhang, Qingxue; Yang, Dongzi

    2014-05-01

    Our previous study has demonstrated that luteinized granulosa cells (GCs) have the potential to proliferate and that the telomerase activity (TA) of luteinized GCs may predict the clinical outcomes of IVF treatment. However, in the field of telomere research, there have always been different opinions regarding the significance of TA and telomere length (TL). Thus, in the present study, we compared the effects of these two parameters on IVF treatment outcomes in the same individuals. TL did not differ significantly between the pregnant group and the non-pregnant group. The TA, number of retrieved oocytes and rate of blastocyst transfer were significantly higher in the pregnant group than in the non-pregnant group (0.8825 OD×mm, 12.75±2.20 and 34.48%, respectively, in the pregnant group vs 0.513 OD×mm, 11.60±0.93 and 14.89%, respectively, in the non-pregnant group (P<0.05)), while basal FSH level was lower in the pregnant group than in the non-pregnant group. The subjects did not differ with regard to ovarian stimulation or other clinical characteristics. A TA increase of 1 OD×mm increased the chance of becoming pregnant 4.769-fold (odds ratio: 5.769, 95% CI: 1.434-23.212, P<0.014). The areas under the receiver operating characteristic curves were 0.576 for TL and 0.674 for TA (P=0.271 and P<0. 012 respectively). The corresponding cut-off points were 4.470 for TL and 0.650 OD×mm for TA. These results demonstrate that TA is a better predictor of pregnancy outcomes following IVF treatment than TL. No other clinical parameters, including age, baseline FSH level or peak oestradiol level, distinguished between the pregnant group and the non-pregnant group as effectively as TA.

  20. Time Varying Feature Data

    NASA Astrophysics Data System (ADS)

    Echterhoff, J.; Simonis, I.; Atkinson, R.

    2012-04-01

    The infrastructure to gather, store and access information about our environment is improving and growing rapidly. The increasing amount of information allows us to get a better understanding of the current state of our environment, historical processes and to simulate and predict the future state of the environment. Finer grained spatial and temporal data and more reliable communications make it easier to model dynamic states and ephemeral features. The exchange of information within and across geospatial domains is facilitated through the use of harmonized information models. The Observations & Measurements (O&M) developed through OGC and standardised by ISO is an example of such a cross-domain information model. It is used in many domains, including meteorology, hydrology as well as the emergency management. O&M enables harmonized representation of common metadata that belong to the act of determining the state of a feature property, whether by sensors, simulations or humans. In addition to the resulting feature property value, information such as the result quality but especially the time that the result applies to the feature property can be represented. Temporal metadata is critical to modelling past and future states of a feature. The features, and the semantics of each property, are defined in domain specific Application Schema using the General Feature Model (GFM) from ISO 19109 and usually encoded following ISO 19136. However, at the moment these standards provide only limited support for the representation and handling of time varying feature data. Features like rivers, wildfires or gas plumes have a defined state - for example geographic extent - at any given point in time. To keep track of changes, a more complex model for example using time-series coverages is required. Furthermore, the representation and management of feature property value changes via the service interfaces defined by OGC and ISO - namely: WFS and WCS - would be rather complex

  1. Significant difference in active metabolite levels of ginseng in humans consuming Asian or Western diet: The link with enteric microbiota.

    PubMed

    Wan, Jin-Yi; Wang, Chong-Zhi; Zhang, Qi-Hui; Liu, Zhi; Musch, Mark W; Bissonnette, Marc; Chang, Eugene B; Li, Ping; Qi, Lian-Wen; Yuan, Chun-Su

    2017-04-01

    After ingestion of ginseng, the bioavailability of its parent compounds is low and enteric microbiota plays an important role in parent compound biotransformation to their metabolites. Diet type can influence the enteric microbiota profile. When human subjects on different diets ingest ginseng, their different gut microbiota profiles may influence the metabolism of ginseng parent compounds. In this study, the effects of different diet type on gut microbiota metabolism of American ginseng saponins were investigated. We recruited six healthy adults who regularly consumed different diet types. These subjects received 7 days' oral American ginseng, and their biological samples were collected for LC-Q-TOF-MS analysis. We observed significant ginsenoside Rb1 (a major parent compound) and compound K (a major active metabolite) level differences in the samples from the subjects consuming different diets. Subjects on an Asian diet had much higher Rb1 levels but much lower compound K levels compared with those on a Western diet. Since compound K possesses much better cancer chemoprevention potential, our data suggested that consumers on a Western diet should obtain better cancer prevention effects with American ginseng intake compared with those on an Asian diet. Ginseng compound levels could be enhanced or reduced via gut microbiota manipulation for clinical utility.

  2. Significant change of local atomic configurations at surface of reduced activation Eurofer steels induced by hydrogenation treatments

    NASA Astrophysics Data System (ADS)

    Greculeasa, S. G.; Palade, P.; Schinteie, G.; Kuncser, A.; Stanciu, A.; Lungu, G. A.; Porosnicu, C.; Lungu, C. P.; Kuncser, V.

    2017-04-01

    Reduced-activation steels such as Eurofer alloys are candidates for supporting plasma facing components in tokamak-like nuclear fusion reactors. In order to investigate the impact of hydrogen/deuterium insertion in their crystalline lattice, annealing treatments in hydrogen atmosphere have been applied on Eurofer slabs. The resulting samples have been analyzed with respect to local structure and atomic configuration both before and after successive annealing treatments, by X-ray diffractometry (XRD), scanning electron microscopy and energy dispersive spectroscopy (SEM-EDS), X-ray photoelectron spectroscopy (XPS) and conversion electron Mössbauer spectroscopy (CEMS). The corroborated data point out for a bcc type structure of the non-hydrogenated alloy, with an average alloy composition approaching Fe0.9Cr0.1 along a depth of about 100 nm. EDS elemental maps do not indicate surface inhomogeneities in concentration whereas the Mössbauer spectra prove significant deviations from a homogeneous alloying. The hydrogenation increases the expulsion of the Cr atoms toward the surface layer and decreases their oxidation, with considerable influence on the surface properties of the steel. The hydrogenation treatment is therefore proposed as a potential alternative for a convenient engineering of the surface of different Fe-Cr based alloys.

  3. Zero Valent Iron Significantly Enhances Methane Production from Waste Activated Sludge by Improving Biochemical Methane Potential Rather Than Hydrolysis Rate

    NASA Astrophysics Data System (ADS)

    Liu, Yiwen; Wang, Qilin; Zhang, Yaobin; Ni, Bing-Jie

    2015-02-01

    Anaerobic digestion has been widely applied for waste activated sludge (WAS) treatment. However, methane production from anaerobic digestion of WAS is usually limited by the slow hydrolysis rate and/or poor biochemical methane potential of WAS. This work systematically studied the effects of three different types of zero valent iron (i.e., iron powder, clean scrap and rusty scrap) on methane production from WAS in anaerobic digestion, by using both experimental and mathematical approaches. The results demonstrated that both the clean and the rusty iron scrap were more effective than the iron powder for improving methane production from WAS. Model-based analysis showed that ZVI addition significantly enhanced methane production from WAS through improving the biochemical methane potential of WAS rather than its hydrolysis rate. Economic analysis indicated that the ZVI-based technology for enhancing methane production from WAS is economically attractive, particularly considering that iron scrap can be freely acquired from industrial waste. Based on these results, the ZVI-based anaerobic digestion process of this work could be easily integrated with the conventional chemical phosphorus removal process in wastewater treatment plant to form a cost-effective and environment-friendly approach, enabling maximum resource recovery/reuse while achieving enhanced methane production in wastewater treatment system.

  4. Appropriate Fe (II) Addition Significantly Enhances Anaerobic Ammonium Oxidation (Anammox) Activity through Improving the Bacterial Growth Rate

    PubMed Central

    Liu, Yiwen; Ni, Bing-Jie

    2015-01-01

    The application of anaerobic ammonium oxidation (Anammox) process is often limited by the slow growth rate of Anammox bacteria. As the essential substrate element that required for culturing Anammox sludge, Fe (II) is expected to affect Anammox bacterial growth. This work systematically studied the effects of Fe (II) addition on Anammox activity based on the kinetic analysis of specific growth rate using data from batch tests with an enriched Anammox sludge at different dosing levels. Results clearly demonstrated that appropriate Fe (II) dosing (i.e., 0.09 mM) significantly enhanced the specific Anammox growth rate up to 0.172 d−1 compared to 0.118 d−1 at regular Fe (II) level (0.03 mM). The relationship between Fe (II) concentration and specific Anammox growth rate was found to be well described by typical substrate inhibition kinetics, which was integrated into currently well-established Anammox model to describe the enhanced Anammox growth with Fe (II) addition. The validity of the integrated Anammox model was verified using long-term experimental data from three independent Anammox reactors with different Fe (II) dosing levels. This Fe (II)-based approach could be potentially implemented to enhance the process rate for possible mainstream application of Anammox technology, in order for an energy autarchic wastewater treatment. PMID:25644239

  5. Zero Valent Iron Significantly Enhances Methane Production from Waste Activated Sludge by Improving Biochemical Methane Potential Rather Than Hydrolysis Rate

    PubMed Central

    Liu, Yiwen; Wang, Qilin; Zhang, Yaobin; Ni, Bing-Jie

    2015-01-01

    Anaerobic digestion has been widely applied for waste activated sludge (WAS) treatment. However, methane production from anaerobic digestion of WAS is usually limited by the slow hydrolysis rate and/or poor biochemical methane potential of WAS. This work systematically studied the effects of three different types of zero valent iron (i.e., iron powder, clean scrap and rusty scrap) on methane production from WAS in anaerobic digestion, by using both experimental and mathematical approaches. The results demonstrated that both the clean and the rusty iron scrap were more effective than the iron powder for improving methane production from WAS. Model-based analysis showed that ZVI addition significantly enhanced methane production from WAS through improving the biochemical methane potential of WAS rather than its hydrolysis rate. Economic analysis indicated that the ZVI-based technology for enhancing methane production from WAS is economically attractive, particularly considering that iron scrap can be freely acquired from industrial waste. Based on these results, the ZVI-based anaerobic digestion process of this work could be easily integrated with the conventional chemical phosphorus removal process in wastewater treatment plant to form a cost-effective and environment-friendly approach, enabling maximum resource recovery/reuse while achieving enhanced methane production in wastewater treatment system. PMID:25652244

  6. Zero valent iron significantly enhances methane production from waste activated sludge by improving biochemical methane potential rather than hydrolysis rate.

    PubMed

    Liu, Yiwen; Wang, Qilin; Zhang, Yaobin; Ni, Bing-Jie

    2015-02-05

    Anaerobic digestion has been widely applied for waste activated sludge (WAS) treatment. However, methane production from anaerobic digestion of WAS is usually limited by the slow hydrolysis rate and/or poor biochemical methane potential of WAS. This work systematically studied the effects of three different types of zero valent iron (i.e., iron powder, clean scrap and rusty scrap) on methane production from WAS in anaerobic digestion, by using both experimental and mathematical approaches. The results demonstrated that both the clean and the rusty iron scrap were more effective than the iron powder for improving methane production from WAS. Model-based analysis showed that ZVI addition significantly enhanced methane production from WAS through improving the biochemical methane potential of WAS rather than its hydrolysis rate. Economic analysis indicated that the ZVI-based technology for enhancing methane production from WAS is economically attractive, particularly considering that iron scrap can be freely acquired from industrial waste. Based on these results, the ZVI-based anaerobic digestion process of this work could be easily integrated with the conventional chemical phosphorus removal process in wastewater treatment plant to form a cost-effective and environment-friendly approach, enabling maximum resource recovery/reuse while achieving enhanced methane production in wastewater treatment system.

  7. Electropositive charge in alpha-defensin bactericidal activity: functional effects of Lys-for-Arg substitutions vary with the peptide primary structure.

    PubMed

    Llenado, R Alan; Weeks, Colby S; Cocco, Melanie J; Ouellette, André J

    2009-11-01

    Cationic amino acids contribute to alpha-defensin bactericidal activity. Curiously, although Arg and Lys have equivalent electropositive charges at neutral pH, alpha-defensins contain an average of nine Arg residues per Lys residue. To investigate the role of high alpha-defensin Arg content, all Arg residues in mouse Paneth cell alpha-defensin cryptdin 4 (Crp4) and rhesus myeloid alpha-defensin 4 (RMAD-4) were replaced with Lys to prepare (R/K)-Crp4 and (R/K)-RMAD-4, respectively. Lys-for-Arg replacements in Crp4 attenuated bactericidal activity and slowed the kinetics of Escherichia coli ML35 cell permeabilization, and (R/K)-Crp4 required longer exposure times to reduce E. coli cell survival. In marked contrast, Lys substitutions in RMAD-4 improved microbicidal activity against certain bacteria and permeabilized E. coli more effectively. Therefore, Arg-->Lys substitutions attenuated activity in Crp4 but not in RMAD-4, and the functional consequences of Arg-->Lys replacements in alpha-defensins are dependent on the peptide primary structure. In addition, the bactericidal effects of (R/K)-Crp4 and (R/K)-RMAD-4 were more sensitive to inhibition by NaCl than those of the native peptides, suggesting that the high Arg content of alpha-defensins may be under selection to confer superior microbicidal function under physiologic conditions.

  8. PHENOLIC CONTENT AND ANTIOXIDANT ACTIVITY OF SUPERCRITICAL CARBON DIOXIDE TREATED AND AIR-CLASSIFIED OAT BRAN CONCENTRATE MICROWAVE-IRRADIATED IN SOLVENTS AT VARYING TEMPERATURES

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In addition to health-beneficial beta-glucans, oats contain phenolic compounds (PC) and other antioxidant activity (AA). We investigated processing technologies to produce oat ingredients with concentrated levels of PC and AA. Oat bran concentrate (OBC) had lipids removed by supercritical carbon d...

  9. Local treatment of vaginal infections of varying etiology with dequalinium chloride or povidone iodine. A randomised, double-blind, active-controlled, multicentric clinical study.

    PubMed

    Petersen, Eiko E; Weissenbacher, Ernst R; Hengst, Peter; Spitzbart, Heinz; Weise, Wolfgang; Wolff, Friedrich; Dreher, Ekkehard; Ernst, Uwe; Della Casa, Vera; Pohlig, Gabriele; Graf, Federico; Kaiser, R Renato

    2002-01-01

    This randomised, double-blind, multicentric clinical study compared the efficacy and tolerability of the two vaginal antiseptics, 10 mg dequalinium chloride (CAS 522-51-0, Fluomycin N) and 200 mg povidone iodine (CAS 25655-41-8), in a parallel-group design. A total of 180 patients with vaginal infections of varying etiology participated in this study (bacterial vaginosis, fluor vaginalis, vulvo-vaginal candidiasis, trichomoniasis). Patients were randomly allocated to one of the two treatment groups and were treated once per day for 6 days. Control examinations took place 5 to 7 days after the end of treatment, and 3 to 4 weeks after the first control examination. The total symptoms score, a summary score for the clinical symptoms, discharge, burning, pruritus, redness of vulva/vagina, was defined as primary efficacy parameter. The treatments at the first control examination were compared in the full analysis set using the Wilcoxon-Mann-Whitney U-test, 2-sided, thereby proving equivalence of both treatments at the 5% level. Both treatments strongly improved the symptoms of vaginal infections both on short-term and long-term follow-up. Descriptive analysis of the secondary parameters, vaginal pH, degree of purity of the vaginal flora, and number of lactobacilli in the wet mounts, supported the comparable efficacy of both therapies to restore the vaginal milieu. Analysis of the diagnostic subgroups indicated that irrespective of the diagnosis, both treatments improved the efficacy criteria as observed for the entire population. The global assessment of the therapeutic efficacy by investigators and patients supported the results of the efficacy analysis with good to very good ratings in 70-90% of the cases. A good tolerability of both preparations was observed in this study with a low number of adverse events in the test group (5.8%).

  10. Deciphering the mechanism behind the varied binding activities of COXIBs through Molecular Dynamic Simulations, MM-PBSA binding energy calculations and per-residue energy decomposition studies.

    PubMed

    Chaudhary, Neha; Aparoy, Polamarasetty

    2017-03-01

    COX-2 is a well-known drug target in inflammatory disorders. COX-1/COX-2 selectivity of NSAIDs is crucial in assessing the gastrointestinal side effects associated with COX-1 inhibition. Celecoxib, rofecoxib, and valdecoxib are well-known specific COX-2 inhibiting drugs. Recently, polmacoxib, a COX-2/CA-II dual inhibitor has been approved by the Korean FDA. These COXIBs have similar structure with diverse activity range. Present study focuses on unraveling the mechanism behind the 10-fold difference in the activities of these sulfonamide-containing COXIBs. In order to obtain insights into their binding with COX-2 at molecular level, molecular dynamics simulations studies, and MM-PBSA approaches were employed. Further, per-residue decomposition of these energies led to the identification of crucial amino acids and interactions contributing to the differential binding of COXIBs. The results clearly indicated that Leu338, Ser339, Arg499, Ile503, Phe504, Val509, and Ser516 (Leu352, Ser353, Arg513, Ile517, Phe518, Val523, and Ser530 in PGHS-1 numbering) were imperative in determining the activity of these COXIBs. The binding energies and energy contribution of various residues were similar in all the three simulations. The results suggest that hydrogen bond interaction between the hydroxyl group of Ser516 and five-membered ring of diarylheterocycles augments the affinity in COXIBs. The SAR of the inhibitors studied and the per-residue energy decomposition values suggested the importance of Ser516. Additionally, the positive binding energy obtained with Arg106 explains the binding of COXIBs in hydrophobic channel deep in the COX-2 active site. The findings of the present work would aid in the development of potent COX-2 inhibitors.

  11. Prognostic Significance of Active and Modified forms of Endothelin 1 in Patients with Heart Failure with Reduced Ejection Fraction

    PubMed Central

    Gottlieb, Stephen S.; Harris, Kristie; Todd, John; Estis, Joel; Christenson, Robert H.; Torres, Victoria; Whittaker, Kerry; Rebuck, Heather; Wawrzyniak, Andrew; Krantz, David S.

    2015-01-01

    Objectives Concentrations of endothelin I (ET1) are elevated in CHF patients, and, like other biomarkers that reflect hemodynamic status and cardiac pathophysiology, are prognostic. The Singulex assay (Sgx-ET1) measures the active form of ET1, with a short in-vivo half-life and C-terminal endothelin-1 (CT-ET1) is measured by the Brahms assay and is a modified (degraded) product with longer half-life. We aimed to determine the prognostic importance of active and modified forms of endothelin 1 (Singulex and Brahms assays) in comparison with other commonly measured biomarkers of inflammation, hemodynamic status and cardiac physiology in CHF. Design & Methods Plasma biomarkers (Sgx-ET1, CT-ET1, NTproBNP, IL-6, TNFα, cTnI, VEGF, hs-CRP, Galectin-3, ST2) were measured in 134 NYHA class II and III CHF patients with systolic dysfunction. Prognostic importance of biomarkers for hospitalization or death were calculated by both logistic regression and Kaplan-Meier survival analyses. Results CT-ET1 (OR 5.2, 95% CI 1.7–15.7) and Sgx-ET1 (OR 2.9, CI 1.1–7.7) were independent predictors of hospitalization and death and additively predicted events after adjusting for age, sex and other significant biomarkers. Other biomarkers did not improve the model. Similarly, in Cox regression analysis, only CT-ET1 (HR 3.4, 95% CI 1.4–8.4), VEGF (2.7, 95% CI 1.3–5.4) and Sgx-ET1 (HR 2.6, 95% CI 1.2–5.6) were independently prognostic. Conclusions Elevated concentrations of endothelin 1 predict mortality and hospitalizations in HF patients. Endothelin 1 was more prognostic than commonly obtained hemodynamic, inflammatory and fibrotic biomarkers. Two different assays of endothelin 1 independently and synergistically were prognostic, suggesting either complementary information or extreme prognostic importance. PMID:25541019

  12. Requirements for intercistronic distance and level of eukaryotic initiation factor 2 activity in reinitiation on GCN4 mRNA vary with the downstream cistron.

    PubMed Central

    Grant, C M; Miller, P F; Hinnebusch, A G

    1994-01-01

    Translational control of the GCN4 gene in response to amino acid availability is mediated by four short open reading frames in the GCN4 mRNA leader (uORFs) and by phosphorylation of eukaryotic initiation factor 2 (eIF-2). We have proposed that reducing eIF-2 activity by phosphorylation of its alpha subunit or by a mutation in the eIF-2 recycling factor eIF-2B allows ribosomes which have translated the 5'-proximal uORF1 to bypass uORF2 to uORF4 and reinitiate at GCN4 instead. In this report, we present two lines of evidence that all ribosomes which synthesize GCN4 have previously translated uORF1, resumed scanning, and reinitiated at the GCN4 start site. First, GCN4 expression was abolished when uORF1 was elongated to make it overlap the beginning of the GCN4 coding region. Second, GCN4 expression was reduced as uORF1 was moved progressively closer to GCN4, decreasing to only 5% of the level seen in the absence of all uORFs when only 32 nucleotides separated uORF1 from GCN4. We additionally found that inserting small synthetic uORFs between uORF4 and GCN4 inhibited GCN4 expression under derepressing conditions, confirming the idea that reinitiation at GCN4 under conditions of diminished eIF-2 activity is proportional to the distance of the reinitiation site downstream from uORF1. While uORF4 and GCN4 appear to be equally effective at capturing ribosomes scanning downstream from the 5' cap of mRNA, these two ORFs differ greatly in their ability to capture reinitiating ribosomes scanning from uORF1. When the active form of eIF-2 is present at high levels, reinitiation appears to be much more efficient at uORF4 than at GCN4 when each is located very close to uORF1. Under conditions of reduced recycling of eIF-2, reinitiation at uORF4 is substantially suppressed, which allows ribosomes to reach the GCN4 start site; in contrast, reinitiation at GCN4 in constructs lacking uORF4 is unaffected by decreasing the level of eIF-2 activity. This last finding raises the

  13. Ovarian cycle activity varies with respect to age and social status in free-ranging elephants in Addo Elephant National Park, South Africa.

    PubMed

    Freeman, Elizabeth W; Meyer, Jordana M; Putman, Sarah B; Schulte, Bruce A; Brown, Janine L

    2013-01-01

    Free-ranging African elephants live in a fission-fusion society, at the centre of which is the matriarch. Matriarchs are generally older females that guide their families to resources and co-ordinate group defense. While much is known about elephant society, knowledge is generally lacking about how age affects the physiology of wild elephants. Investigation of the ovarian activity of free-ranging elephants could provide insight into the reproductive ageing process, with implications for population management. Faecal samples were collected from 46 individuals ranging in age from 14 to 60 years for a 2-year period, and progestagen metabolite analyses were used to examine relationships between social status, age, season, and ovarian activity in female elephants in Addo Elephant National Park, South Africa. Social status was the strongest predictor of faecal progestagen metabolite concentrations in non-pregnant elephants, with grand matriarchs (n = 6) having the lowest values compared with matriarchs (n = 21) and non-matriarch females (n = 19). Likewise, social status and age were the strongest predictors of faecal progestagen metabolite concentrations in pregnant elephants (n = 27). The number of years since a non-pregnant female gave birth to her last calf (post-partum duration) was longer for older females with a higher social status, as well as during the dry season. Our results indicate that social standing and age of elephants are related to reproductive function, and that older females exhibit reductions in ovarian capacity. These results expand our understanding of reproduction and fertility throughout an elephant's lifespan, and the factors that impact gonadal function in free-ranging females. Given that possible over-abundance of elephants in areas such as Addo Elephant National Park is fuelling the debate over how best to manage these populations, knowledge about the reproductive potential of high-ranking females can provide managers with

  14. Fathoms Below: Propagation of Deep Water-driven Fractures and Implications for Surface Expression and Temporally-varying Activity at Europa

    NASA Astrophysics Data System (ADS)

    Walker, C. C.; Craft, K.; Schmidt, B. E.

    2015-12-01

    The fracture and failure of Europa's icy shell are not only observable scars of variable stress and activity throughout its evolution, they also serve key as mechanisms in the interaction of surface and subsurface material, and thus crucial aspects of the study of crustal overturn and ice shell habitability. Galileo images, our best and only reasonable-resolution views of Europa until the Europa Multiple Flyby Mission arrives in the coming decades, illustrates a single snapshot in time in Europa's history from which we deduce many temporally-based hypotheses. One of those hypotheses, which we investigate here, is that sub-surface water-both in the form of Great Lake-sized perched water pockets in the near-surface and the larger global ocean below-drives the deformation, fracture, and failure of the surface. Using Galileo's snapshot in time, we use a 2D/3D hydraulic fracturing model to investigate the propagation of vertical fractures upward into the ice shell, motion of water within and between fractures, and the subsequent break-up of ice over shallow water, forming the chaos regions and other smaller surface features. We will present results from a cohesive fragmentation model to determine the time over which chaos formation occurs, and use a fracking model to determine the time interval required to allow water to escape from basal fractures in the ice shell. In determining the style, energy, and timescale of these processes, we constrain temporal variability in observable activity and topography at the surface. Finally, we compare these results to similar settings on Earth-Antarctica-where we have much higher resolution imagery and observations to better understand how sub-surface water can affect ice surface morphology, which most certainly have implications for future flyby and surface lander exploration.

  15. Antimicrobial activity of oregano oil against antibiotic-resistant Salmonella enterica on organic leafy greens at varying exposure times and storage temperatures.

    PubMed

    Moore-Neibel, Katherine; Gerber, Colin; Patel, Jitendra; Friedman, Mendel; Jaroni, Divya; Ravishankar, Sadhana

    2013-05-01

    The objective of this study was to evaluate the effectiveness of oregano oil on four organic leafy greens (Iceberg and Romaine lettuces and mature and baby spinaches) inoculated with Salmonella Newport as a function of treatment exposure times as well as storage temperatures. Leaf samples were washed, dip inoculated with S. Newport (6-log CFU/ml) and dried. Oregano oil was prepared at 0.1, 0.3, and 0.5% concentrations in sterile phosphate buffered saline (PBS). Inoculated leaves were immersed in the treatment solution for 1 or 2 min, and individually incubated at 4 or 8 °C. Samples were taken at day 0, 1, and 3 for enumeration of survivors. The results showed that oregano oil was effective against S. Newport at all concentrations. S. Newport showed reductions from the PBS control of 0.7-4.8 log CFU/g (Romaine lettuce), 0.8-4.8 log CFU/g (Iceberg lettuce), 0.8-4.9 log CFU/g (mature spinach), and 0.5-4.7 log CFU/g (baby spinach), respectively. The antibacterial activity also increased with exposure time. Leaf samples treated for 2 min generally showed greater reductions (by 1.4-3.2 log CFU/g), than those samples treated for 1 min; however, there was minimal difference in antimicrobial activity among samples stored under refrigeration and abuse temperatures. This study demonstrates the potential of oregano oil to inactivate S. Newport on organic leafy greens.

  16. Cosmology with varying constants.

    PubMed

    Martins, Carlos J A P

    2002-12-15

    The idea of possible time or space variations of the 'fundamental' constants of nature, although not new, is only now beginning to be actively considered by large numbers of researchers in the particle physics, cosmology and astrophysics communities. This revival is mostly due to the claims of possible detection of such variations, in various different contexts and by several groups. I present the current theoretical motivations and expectations for such variations, review the current observational status and discuss the impact of a possible confirmation of these results in our views of cosmology and physics as a whole.

  17. Double-stranded RNA-activated protein kinase PKR of fishes and amphibians: Varying the number of double-stranded RNA binding domains and lineage-specific duplications

    PubMed Central

    Rothenburg, Stefan; Deigendesch, Nikolaus; Dey, Madhusudan; Dever, Thomas E; Tazi, Loubna

    2008-01-01

    Background Double-stranded (ds) RNA, generated during viral infection, binds and activates the mammalian anti-viral protein kinase PKR, which phosphorylates the translation initiation factor eIF2α leading to the general inhibition of protein synthesis. Although PKR-like activity has been described in fish cells, the responsible enzymes eluded molecular characterization until the recent discovery of goldfish and zebrafish PKZ, which contain Z-DNA-binding domains instead of dsRNA-binding domains (dsRBDs). Fish and amphibian PKR genes have not been described so far. Results Here we report the cloning and identification of 13 PKR genes from 8 teleost fish and amphibian species, including zebrafish, demonstrating the coexistence of PKR and PKZ in this latter species. Analyses of their genomic organization revealed up to three tandemly arrayed PKR genes, which are arranged in head-to-tail orientation. At least five duplications occurred independently in fish and amphibian lineages. Phylogenetic analyses reveal that the kinase domains of fish PKR genes are more closely related to those of fish PKZ than to the PKR kinase domains of other vertebrate species. The duplication leading to fish PKR and PKZ genes occurred early during teleost fish evolution after the divergence of the tetrapod lineage. While two dsRBDs are found in mammalian and amphibian PKR, one, two or three dsRBDs are present in fish PKR. In zebrafish, both PKR and PKZ were strongly upregulated after immunostimulation with some tissue-specific expression differences. Using genetic and biochemical assays we demonstrate that both zebrafish PKR and PKZ can phosphorylate eIF2α in yeast. Conclusion Considering the important role for PKR in host defense against viruses, the independent duplication and fixation of PKR genes in different lineages probably provided selective advantages by leading to the recognition of an extended spectrum of viral nucleic acid structures, including both dsRNA and Z-DNA/RNA, and

  18. Factors that Influence Physical Activity in Long-Term Care: Perspectives of Residents, Staff, and Significant Others

    ERIC Educational Resources Information Center

    Benjamin, Kathleen; Edwards, Nancy; Guitard, Paulette; Murray, Mary Ann; Caswell, Wenda; Perrier, Marie Josee

    2011-01-01

    Physical activity has been linked to positive health outcomes for frail seniors. However, our understanding of factors that influence the physical activity of residents in the long-term care (LTC) setting is limited. This article describes our work with focus groups, one component of a multi-component study that examined factors influencing the…

  19. Agreement Between pQCT- and DXA-Derived Indices of Bone Geometry, Density, and Theoretical Strength in Females of Varying Age, Maturity, and Physical Activity

    PubMed Central

    Dowthwaite, Jodi Noelle; Flowers, Portia PE; Scerpella, Tamara Ann

    2011-01-01

    Measurement of bone mass, geometry, density, and strength are critical in bone research and clinical studies. For peripheral quantitative computed tomography (pQCT), single and repeated measurements are particularly adversely affected by movement and positional variation. Dual-energy X-ray absorptiometry (DXA)–derived indices may alleviate these problems and provide useful alternative assessments. To evaluate this hypothesis, distal radius DXA and pQCT indices were compared in 101 healthy females aged 8.0 to 22.8 years (prepuberty to adulthood), reflecting a broad range of body sizes, physical maturity, and activity exposures. At the diaphysis, correlations were ρ =+0.74 to +0.98, with strong intermethod agreement for most indices. At the metaphysis, correlations were ρ =+0.64 to +0.97; intermethod agreement improved with modifications to the simplified geometric formulas more closely reflecting metaphyseal bone geometry. Further improvements may be possible because skeletal size and maturity-related biases in agreement were detected. Overall, DXA-derived indices may provide a useful assessment of bone geometry, density, and theoretical strength contingent on appropriate consideration of their limitations. PMID:21611973

  20. EVIDENCE OF A WARM ABSORBER THAT VARIES WITH QUASI-PERIODIC OSCILLATION PHASE IN THE ACTIVE GALACTIC NUCLEUS RE J1034+396

    SciTech Connect

    Maitra, Dipankar; Miller, Jon M. E-mail: jonmm@umich.ed

    2010-07-20

    A recent observation of the nearby (z = 0.042) narrow-line Seyfert 1 galaxy RE J1034+396 on 2007 May 31 showed strong quasi-periodic oscillations (QPOs) in the 0.3-10 keV X-ray flux. We present phase-resolved spectroscopy of this observation, using data obtained by the EPIC PN detector on board XMM-Newton. The 'low' phase spectrum, associated with the troughs in the light curve, shows (at >4{sigma} confidence level) an absorption edge at 0.86 {+-} 0.05 keV with an absorption depth of 0.3 {+-} 0.1. Ionized oxygen edges are hallmarks of X-ray warm absorbers in Seyfert active galactic nuclei; the observed edge is consistent with H-like O VIII and implies a column density of N{sub OVIII} {approx} 3 x 10{sup 18} cm{sup -2}. The edge is not seen in the 'high' phase spectrum associated with the crests in the light curve, suggesting the presence of a warm absorber in the immediate vicinity of the supermassive black hole that periodically obscures the continuum emission. If the QPO arises due to Keplerian orbital motion around the central black hole, the periodic appearance of the O VIII edge would imply a radius of {approx}9.4(M/[4x10{sup 6}M{sub sun}]){sup -2/3}(P/[1 hr]){sup 2/3} r{sub g} for the size of the warm absorber.

  1. Actin polymerization plays a significant role in asbestos-induced inflammasome activation in mesothelial cells in vitro.

    PubMed

    MacPherson, Maximilian; Westbom, Catherine; Kogan, Helen; Shukla, Arti

    2016-12-24

    Asbestos exposure leads to malignant mesothelioma (MM), a deadly neoplasm of mesothelial cells of various locations. Although there is no doubt about the role of asbestos in MM tumorigenesis, mechanisms are still not well explored. Recently, our group demonstrated that asbestos causes inflammasome priming and activation in mesothelial cells, which in part is dependent on oxidative stress. Our current study sheds light on yet another mechanism of inflammasome activation by asbestos. Here we show the role of actin polymerization in asbestos-induced activation of the nod-like receptor pyrin domain-containing protein 3 (NLRP3) inflammasome. Using human mesothelial cells, we first demonstrate that asbestos and carbon nanotubes induced caspase-1 activation and high-mobility group box 1, interleukin 1 beta and interleukin 18 secretion was blocked by Cytochalasin D (Cyto D) an actin polymerization inhibitor. Next, to understand the mechanism, we assessed whether phagocytosis of fibers by mesothelial cells is affected by actin polymerization inhibition. Transmission electron microscopy showed the inhibition of fiber uptake by mesothelial cells in the presence of Cyto D. Furthermore, localization of components of the inflammasome, apoptotic speck-like protein containing a CARD domain (ASC) and NLRP3, to the perinuclear space in mitochondria or endoplasmic reticulum in response to fiber exposure was also interrupted in the presence of Cyto D. Taken together, our studies suggest that actin polymerization plays important roles in inflammasome activation by fibers via regulation of phagocytosis and/or spatial localization of inflammasome components.

  2. Significant differences in the activities of alpha-amylases in the absence and presence of polyethylene glycol assayed on eight starches solubilized by two methods.

    PubMed

    Mukerjea, Rupendra; Slocum, Giles; Mukerjea, Romila; Robyt, John F

    2006-09-04

    Starch is a reserve chemical source of the energy of the sun found in plants as a water-insoluble granule that differs in their chemical and physical properties, depending on the source. The granules can be solubilized by heating in water or by treatment with various reagents, such as 1M NaOH. alpha-Amylases are widely distributed enzymes that initiate the hydrolysis of starch into low molecular weight maltodextrins. We recently found that the activities of a single alpha-amylase on two different starches were significantly different. We then determined the activities of Bacillus amyloliquefaciens and porcine pancreas alpha-amylases, using eight different starches, solubilized by two methods: autoclaving at 121 degrees C and 1M NaOH at 20 degrees C. There were significant differences in the activities of both of the amylases on all eight of the starches. Previously, it had been found that polyethylene glycol (PEG) stabilized and activated the activities of both enzymes, using a soluble amylose as the substrate. Addition of PEG to the enzymes greatly increased the activities on the eight starches, but the activities still differed significantly. The different activities with the starches were hypothesized as differences in the amounts of secondary and tertiary structures that are partially retained when the different starches are solubilized; the activities on addition of PEG is hypothesized as the formation of highly active species from a series of less active forms.

  3. Development of an activity-directed selection system enabled significant improvement of the carboxylation efficiency of Rubisco.

    PubMed

    Cai, Zhen; Liu, Guoxia; Zhang, Junli; Li, Yin

    2014-07-01

    Photosynthetic CO(2) fixation is the ultimate source of organic carbon on earth and thus is essential for crop production and carbon sequestration. Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) catalyzes the first step of photosynthetic CO(2) fixation. However, the extreme low carboxylation efficiency of Rubisco makes it the most attractive target for improving photosynthetic efficiency. Extensive studies have focused on re-engineering a more efficient enzyme, but the effort has been impeded by the limited understanding of its structure-function relationships and the lack of an efficient selection system towards its activity. To address the unsuccessful molecular engineering of Rubisco, we developed an Escherichia coli-based activity-directed selection system which links the growth of host cell solely to the Rubisco activity therein. A Synechococcus sp. PCC7002 Rubisco mutant with E49V and D82G substitutions in the small subunit was selected from a total of 15,000 mutants by one round of evolution. This mutant showed an 85% increase in specific carboxylation activity and a 45% improvement in catalytic efficiency towards CO(2). The small-subunit E49V mutation was speculated to influence holoenzyme catalysis through interaction with the large-subunit Q225. This interaction is conserved among various Rubisco from higher plants and Chlamydomonas reinhardtii. Knowledge of these might provide clues for engineering Rubisco from higher plants, with the potential of increasing the crop yield.

  4. Cloud condensation nucleus activity comparison of dry- and wet-generated mineral dust aerosol: the significance of soluble material

    NASA Astrophysics Data System (ADS)

    Garimella, S.; Huang, Y.-w.; Seewald, J. S.; Cziczo, D. J.

    2013-11-01

    This study examines the interaction of clay mineral particles and water vapor to determine the conditions required for cloud droplet formation. Droplet formation conditions are investigated for three clay minerals: illite, sodium-rich montmorillonite, and Arizona Test Dust. Using wet and dry particle generation coupled to a differential mobility analyzer (DMA) and cloud condensation nuclei counter, the critical activation of the clay mineral particles as cloud condensation nuclei is characterized. Electron microscopy (EM) is used to determine non-sphericity in particle shape. EM is also used to determine particle surface area and account for transmission of multiply charged particles by the DMA. Single particle mass spectrometry and ion chromatography are used to investigate soluble material in wet-generated samples and demonstrate that wet and dry generation yield compositionally different particles. Activation results are analyzed in the context of both κ-Köhler theory and Frenkel, Halsey, and Hill (FHH) adsorption activation theory. This study has two main results: (1) κ-Köhler is a suitable framework, less complex than FHH theory, to describe clay mineral nucleation activity despite apparent differences in κ with respect to size. For dry-generated particles the size dependence is likely an artifact of the shape of the size distribution: there is a sharp drop-off in particle concentration at ~300 nm, and a large fraction of particles classified with a mobility diameter less than ~300 nm are actually multiply charged, resulting in a much lower critical supersaturation for droplet activation than expected. For wet-generated particles, deviation from κ-Köhler theory is likely a result of the dissolution and redistribution of soluble material. (2) Wet-generation is found to be unsuitable for simulating the lofting of fresh dry dust because it changes the size-dependent critical supersaturations by fractionating and re-partitioning soluble material.

  5. Dermatophyte susceptibility varies towards antimicrobial textiles.

    PubMed

    Hammer, Timo R; Mucha, Helmut; Hoefer, Dirk

    2012-07-01

    Dermatophytoses are a widespread problem worldwide. Textiles in contact with infected skin can serve as a carrier for fungus propagation. Hitherto, it is unknown, whether antifungal textiles could contribute in controlling dermatophytes e.g. by disrupting the chain of infection. Testing of antimicrobial fabrics for their antifungal activities therefore is a fundamental prerequisite to assess the putative clinical relevance of textiles for dermatophyte prevention. Fabrics finished with either didecyldimethylammonium chloride (DDAC), poly-hexamethylenbiguanide, copper and two silver chloride concentrations were tested for their antifungal activity against Trichophyton rubrum, Trichophyton mentagrophytes and Candida albicans. To prove dermatophyte susceptibility towards the textiles, swatches were subjected to DIN EN 14199 (Trichophyton sp.) or DIN EN ISO 20743 (C. albicans) respectively. In addition, samples were embedded, and semi-thin sections were analysed microscopically. While all samples showed a clear inhibition of C. albicans, activity against Trichophyton sp. varied significantly: For example, DDAC completely inhibited T. rubrum growth, whereas T. mentagrophytes growth remained unaffected even in direct contact to the fibres. The results favour to add T. mentagrophytes as a test organism in textile dermatophyte efficacy tests. Microscopic analysis of swatches allowed detailed evaluation of additional parameters like mycelium thickness, density and hyphae penetration depth into the fabric.

  6. Middle School Teams Increasing Access to General Education for Students with Significant Disabilities: Issues Encountered and Activities Observed across Contexts

    ERIC Educational Resources Information Center

    Matzen, Katherine; Ryndak, Diane; Nakao, Taketo

    2010-01-01

    The experiences of three students with significant disabilities and their educational teams were studied during these students' first year of receiving general education services. Interviews were conducted with general educators, special educators, and parents to identify issues encountered during the year. Also, classroom observations were…

  7. Selective modification of the 3''-amino group of kanamycin prevents significant loss of activity in resistant bacterial strains.

    PubMed

    Santana, Andrés G; Zárate, Sandra G; Asensio, Juan Luis; Revuelta, Julia; Bastida, Agatha

    2016-01-14

    Aminoglycosides are highly potent, wide-spectrum bactericidals. N-1 modification of aminoglycosides has thus far been the best approach to regain bactericidal efficiency of this class of antibiotics against resistant bacterial strains. In the present study we have evaluated the effect that both, the number of modifications and their distribution on the aminoglycoside amino groups (N-1, N-3, N-6' and N-3''), have on the antibiotic activity. The modification of N-3'' in the antibiotic kanamycin A is the key towards the design of new aminoglycoside antibiotics. This derivative maintains the antibiotic activity against aminoglycoside acetyl-transferase- and nucleotidyl-transferase-expressing strains, which are two of the most prevalent modifying enzymes found in aminoglycoside resistant bacteria.

  8. Adaptive Cellular Interactions in the Immune System: The Tunable Activation Threshold and the Significance of Subthreshold Responses

    NASA Astrophysics Data System (ADS)

    Grossman, Zvi; Paul, William E.

    1992-11-01

    A major challenge for immunologists is to explain how the immune system adjusts its responses to the microenvironmental context in which antigens are recognized. We propose that lymphocytes achieve this by tuning and updating their responsiveness to recurrent signals. In particular, cellular anergy in vivo is a dynamic state in which the threshold for a stereotypic mode of activation has been elevated. Anergy is associated with other forms of cellular activity, not paralysis. Cells engaged in such subthreshold interactions mediate functions such as maintenance of immunological memory and control of infections. In such interactions, patterns of signals are recognized and classified and evoke selective responses. The robust mechanism proposed for segregation of suprathreshold and subthreshold immune responses allows lymphocytes to use recognition of self-antigens in executing physiological functions. Autoreactivity is allowed where it is dissociated from uncontrolled aggression.

  9. Electrogastrography in Adults and Children: The Strength, Pitfalls, and Clinical Significance of the Cutaneous Recording of the Gastric Electrical Activity

    PubMed Central

    Indrio, Flavia

    2013-01-01

    Cutaneous electrogastrography (EGG) is a non-invasive technique to record gastric myoelectrical activity from the abdominal surface. Although the recent rapid increase in the development of electrocardiography, EGG still suffers from several limitations. Currently, computer analysis of EGG provides few reliable parameters, such as frequency and the percentage of normal and altered slow wave activity (bradygastria and tachygastria). New EGG hardware and software, along with an appropriate arrangement of abdominal electrodes, could detect the coupling of the gastric slow wave from the EGG. At present, EGG does not diagnose a specific disease, but it puts in evidence stomach motor dysfunctions in different pathological conditions as gastroparesis and functional dyspepsia. Despite the current pitfalls of EGG, a multitasking diagnostic protocol could involve the EGG and the 13C-breath testing for the evaluation of the gastric emptying time—along with validated gastrointestinal questionnaires and biochemical evaluations of the main gastrointestinal peptides—to identify dyspeptic subgroups. The present review tries to report the state of the art about the pathophysiological background of the gastric electrical activity, the recording and processing methodology of the EGG with particular attention to multichannel recording, and the possible clinical application of the EGG in adult and children. PMID:23762836

  10. A nanotherapy strategy significantly enhances anticryptosporidial activity of an inhibitor of bifunctional thymidylate synthase-dihydrofolate reductase from Cryptosporidium.

    PubMed

    Mukerjee, Anindita; Iyidogan, Pinar; Castellanos-Gonzalez, Alejandro; Cisneros, José A; Czyzyk, Daniel; Ranjan, Amalendu Prakash; Jorgensen, William L; White, A Clinton; Vishwanatha, Jamboor K; Anderson, Karen S

    2015-01-01

    Cryptosporidiosis, a gastrointestinal disease caused by protozoans of the genus Cryptosporidium, is a common cause of diarrheal diseases and often fatal in immunocompromised individuals. Bifunctional thymidylate synthase-dihydrofolate reductase (TS-DHFR) from Cryptosporidium hominis (C. hominis) has been a molecular target for inhibitor design. C. hominis TS-DHFR inhibitors with nM potency at a biochemical level have been developed however drug delivery to achieve comparable antiparasitic activity in Cryptosporidium infected cell culture has been a major hurdle for designing effective therapies. Previous mechanistic and structural studies have identified compound 906 as a nM C. hominis TS-DHFR inhibitor in vitro, having μM antiparasitic activity in cell culture. In this work, proof of concept studies are presented using a nanotherapy approach to improve drug delivery and the antiparasitic activity of 906 in cell culture. We utilized PLGA nanoparticles that were loaded with 906 (NP-906) and conjugated with antibodies to the Cryptosporidium specific protein, CP2, on the nanoparticle surface in order to specifically target the parasite. Our results indicate that CP2 labeled NP-906 (CP2-NP-906) reduces the level of parasites by 200-fold in cell culture, while NP-906 resulted in 4.4-fold decrease. Moreover, the anticryptosporidial potency of 906 improved 15 to 78-fold confirming the utility of the antibody conjugated nanoparticles as an effective drug delivery strategy.

  11. Cloud condensation nucleus activity comparison of dry- and wet-generated mineral dust aerosol: the significance of soluble material

    NASA Astrophysics Data System (ADS)

    Garimella, S.; Huang, Y.-W.; Seewald, J. S.; Cziczo, D. J.

    2014-06-01

    This study examines the interaction of clay mineral particles and water vapor for determining the conditions required for cloud droplet formation. Droplet formation conditions are investigated for two common clay minerals, illite and sodium-rich montmorillonite, and an industrially derived sample, Arizona Test Dust. Using wet and dry particle generation coupled to a differential mobility analyzer (DMA) and cloud condensation nuclei counter, the critical activation of the clay mineral particles as cloud condensation nuclei is characterized. Electron microscopy (EM) is used in order to determine non-sphericity in particle shape. It is also used in order to determine particle surface area and account for transmission of multiply charged particles by the DMA. Single particle mass spectrometry and ion chromatography are used to investigate soluble material in wet-generated samples and demonstrate that wet and dry generation yield compositionally different particles. Activation results are analyzed in the context of both κ-Köhler theory (κ-KT) and Frenkel-Halsey-Hill (FHH) adsorption activation theory. This study has two main results: (1) κ-KT is the suitable framework to describe clay mineral nucleation activity. Apparent differences in κ with respect to size arise from an artifact introduced by improper size-selection methodology. For dust particles with mobility sizes larger than ~300 nm, i.e., ones that are within an atmospherically relevant size range, both κ-KT and FHH theory yield similar critical supersaturations. However, the former requires a single hygroscopicity parameter instead of the two adjustable parameters required by the latter. For dry-generated particles, the size dependence of κ is likely an artifact of the shape of the size distribution: there is a sharp drop-off in particle concentration at ~300 nm, and a large fraction of particles classified with a mobility diameter less than ~300 nm are actually multiply charged, resulting in a much

  12. Magnetic-activated cell sorting (MACS) significantly decreases the hybridization efficiency of fluorescence in situ hybridization (FISH).

    PubMed

    Kuo, P L; Guo, H R

    2001-05-01

    Fetal cells were enriched from maternal blood using density gradient centrifugation of Histopaque followed by magnetic-activated cell sorting (MACS) to select CD71-positive cells. For each specimen, cells partially purified by Histopaque were split into equal portions, and each portion was subjected to purification by MACS in parallel. Cells before and after MACS were subjected to dual-color fluorescence in situ hybridization (FISH) analysis with X- and Y-chromosome-specific probes. We found that the hybridization rates were decreased by approximately 10% after MACS based on duplicated analysis for each sample.

  13. The opportunity for and significance of alteration of ribulose 1,5-bisphosphate carboxylase activities in crop production.

    PubMed

    Hardy, R W; Havelka, U D; Quebedeaux, B

    1978-01-01

    Increased population and the dietary changes accompanying increased affluence are creating a need for a suggested doubling of world cereal grain production (a 3% per year compounding rate) and quadrupling of grain legume production (a 6% per year compounding rate) during this quarter century (1). CO2 enrichment of field-grown crops has demonstrated the possibility of enhancing RuBP carboxylase activity to achieve improved crop production; it increases the production of grain legumes by 50 to 100% and that of cereal grains, for which the studies are less complete, by perhaps 10 to 50%. Results of O2 alteration of growth-room legumes and cereal grains are consistent with the results of CO2 enrichment except for a second role of O2 in assimilate partitioning. It may be necessary to include other components of the system, e.g., additional soil fertility, especially for non-N2-fixing plants, to enable an improved RuBP carboxylase to increase production. No practical method--chemical, genetic, or physical--of improving RuBP carboxylase activity has been reported.

  14. Significant antibacterial activity and synergistic effects of camel lactoferrin with antibiotics against methicillin-resistant Staphylococcus aureus (MRSA).

    PubMed

    Redwan, Elrashdy M; El-Baky, Nawal Abd; Al-Hejin, Ahmed M; Baeshen, Mohammed N; Almehdar, Hussein A; Elsaway, Abdulrahman; Gomaa, Abu-Bakr M; Al-Masaudi, Saad Berki; Al-Fassi, Fahad A; AbuZeid, Isam Eldin; Uversky, Vladimir N

    2016-01-01

    Methicillin-resistant Staphylococcus aureus (MRSA) causes major healthcare problems in many countries, as it is present as several hospital- and community-associated strains. Hospital-associated MRSA is one of the most prevalent nosocomial pathogens throughout the world and infections caused by community-acquired MRSA are rising. This emphasizes the need for new and efficient anti-MRSA agents. We evaluated the antibacterial effects of camel lactoferrin (cLf) and human lactoferrin (hLf) alone and in combination with several antibiotics against MRSA. Antimicrobials were tested against MRSA and an S. aureus control strain by the agar disc diffusion method. The minimum inhibitory concentration (MIC) was determined for antimicrobials by the broth microdilution method. Synergy between cLf or hLf and antibiotics was examined by checkerboard and time-kill assays. The agar disc diffusion assay showed that MRSA growth was inhibited by cLf at 0.25-3 mg/ml and hLf at 1-3 mg/ml. cLf demonstrated 3 times higher inhibitory activity against MRSA than hLf in terms of MIC values (250 vs. 750 μg/ml, respectively). Biotinylated cLf was recognized by two membrane proteins of MRSA, 66-67 KDa. Combinations of cLf or hLf and oxacillin or vancomycin at sub-MIC levels enhanced in vitro antibacterial activity against MRSA compared with each agent alone.

  15. Synergistic activity of rifampicin and ethambutol against slow-growing nontuberculous mycobacteria is currently of questionable clinical significance.

    PubMed

    van Ingen, Jakko; Hoefsloot, Wouter; Mouton, Johan W; Boeree, Martin J; van Soolingen, Dick

    2013-07-01

    A key issue in the treatment of disease caused by slow-growing nontuberculous mycobacteria is the limited association between in vitro minimum inhibitory concentrations (MICs) of rifampicin and ethambutol alone and the in vivo outcome of treatment with these drugs. Combined susceptibility testing to rifampicin and ethambutol could provide a more realistic view of the efficacy of these drugs. In this study, Mycobacterium avium (n = 5), Mycobacterium chimaera (n = 6), Mycobacterium intracellulare (n = 4), Mycobacterium xenopi (n = 4), Mycobacterium malmoense (n = 3) and Mycobacterium simiae (n = 2) clinical isolates were selected and the MICs of rifampicin and ethambutol alone and in combination were measured using the Middlebrook 7H10 agar dilution method. Synergy was defined as a fractional inhibitory concentration index ≤ 0.5. Rifampicin and ethambutol showed synergistic activity against the majority of M. avium (4/5), M. chimaera (5/6) and M. intracellulare (3/4) isolates and 1 of 2 eligible M. malmoense isolates. No synergistic activity was measured against M. xenopi and M. simiae. Synergy was neither universal for all species nor for all isolates of one species; it thus needs to be tested for rather than assumed. Even if this synergy exists in vivo, it is questionable whether the MICs to the combined drugs can be overcome by the drug exposure attained by current regimens at the recommended dosages. New dosing strategies for rifampicin and ethambutol should be studied to increase the exposure to these drugs and thus maximise their impact.

  16. Dactyloditerpenol acetate, a new prenylbisabolane-type diterpene from Aplysia dactylomela with significant in vitro anti-neuroinflammatory activity.

    PubMed

    Jiménez-Romero, Carlos; Mayer, Alejandro M S; Rodríguez, Abimael D

    2014-01-01

    A new regular diterpene possessing an unusual 1,6-anti-3-methylcyclohex-2-en-1-ol ring system, dactyloditerpenol acetate (1), has been extracted from the tropical sea hare Aplysia dactylomela and its stereostructure elucidated by spectroscopic methods. The absolute configuration of 1 was determined as 1S, 6S, 7R, 10S, and 11R by application of Kishi's method for the assignment of absolute configuration of alcohols. The new diterpene potently inhibited in vitro thromboxane B2 (TXB2) (IC50 0.4μM) and superoxide anion (O2(-)) (IC50 1μM) generation from Escherichia coli lipopolysaccharide (LPS)-activated rat neonatal microglia, with concomitant low short-term toxicity.

  17. Phylogenetic and experimental characterization of an acyl-ACP thioesterase family reveals significant diversity in enzymatic specificity and activity

    PubMed Central

    2011-01-01

    Background Acyl-acyl carrier protein thioesterases (acyl-ACP TEs) catalyze the hydrolysis of the thioester bond that links the acyl chain to the sulfhydryl group of the phosphopantetheine prosthetic group of ACP. This reaction terminates acyl chain elongation of fatty acid biosynthesis, and in plant seeds it is the biochemical determinant of the fatty acid compositions of storage lipids. Results To explore acyl-ACP TE diversity and to identify novel acyl ACP-TEs, 31 acyl-ACP TEs from wide-ranging phylogenetic sources were characterized to ascertain their in vivo activities and substrate specificities. These acyl-ACP TEs were chosen by two different approaches: 1) 24 TEs were selected from public databases on the basis of phylogenetic analysis and fatty acid profile knowledge of their source organisms; and 2) seven TEs were molecularly cloned from oil palm (Elaeis guineensis), coconut (Cocos nucifera) and Cuphea viscosissima, organisms that produce medium-chain and short-chain fatty acids in their seeds. The in vivo substrate specificities of the acyl-ACP TEs were determined in E. coli. Based on their specificities, these enzymes were clustered into three classes: 1) Class I acyl-ACP TEs act primarily on 14- and 16-carbon acyl-ACP substrates; 2) Class II acyl-ACP TEs have broad substrate specificities, with major activities toward 8- and 14-carbon acyl-ACP substrates; and 3) Class III acyl-ACP TEs act predominantly on 8-carbon acyl-ACPs. Several novel acyl-ACP TEs act on short-chain and unsaturated acyl-ACP or 3-ketoacyl-ACP substrates, indicating the diversity of enzymatic specificity in this enzyme family. Conclusion These acyl-ACP TEs can potentially be used to diversify the fatty acid biosynthesis pathway to produce novel fatty acids. PMID:21831316

  18. Plasma renin activity and serum aldosterone during prolonged physical strain. The significance of sleep and energy deprivation.

    PubMed

    Opstad, P K; Oktedalen, O; Aakvaag, A; Fonnum, F; Lund, P K

    1985-01-01

    Plasma renin activity (PRA), serum aldosterone and the serum and urinary levels of sodium and potassium have been investigated in 24 young men participating in a 5-day military training course with heavy continuous physical exercise, energy and sleep deprivation. The subjects were divided into three groups. Group 1 did not get any extra sleep or food, group 2 were compensated for the energy deficiency, and group 3 slept 3 h each night. The basic diet given to all the subjects was about 5,000 kJ and 2 g NaCl X 24 h-1 X cadet-1. The high calorie diet contained approximately 25,000-35,000 kJ and 20 g of NaCl X 24 h-1 X cadet-1. The study showed that serum aldosterone and PRA were extremely activated during such prolonged physical strain combined with lack of food and salt, whereas sleep deprivation did not seem to have any large influence. Only small variations were found in the serum levels of sodium and potassium and the urinary level of potassium during the course, whereas a decrease was seen in urinary sodium concentration. The fairly good correlations between the decrease in urinary sodium levels and the increase in PRA (r = 0.7) and further between PRA and serum aldosterone (r = 0.8) during the course indicate that there is a causal connection between the decrease in urinary sodium excretion and the increase in PRA and serum aldosterone.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. [Hepatitis non-A, non-B: epidemiological significance in acute viral hepatitis and chronic active hepatitis of hepatological consultation].

    PubMed

    Jmelnitzky, A C; Basualdo, J A; Belloni, P O; Ponce de León, H H; García, C; Curciarello, J

    1987-01-01

    157 acute viral hepatitis and 60 chronic active ones have been analyzed focusing on NANB etiology. HAV was implicated in 36.3% of the hole acute viral hepatitis sample, HBV in 29.3%, and HNANBV was presumed as etiology in 31.2%, 5 patients (3.2%) had acute infection by HAV, on previous one by HBV, except for Epstein-Barr virus, no other test for viruses were determined (CMV, HSV, etc.). Male/female ratio was 1.4:1, 1.9:1, and 1.4:1 for HAV, HBV and HNANBV acute hepatitis respectively; HAV was the main etiology in the 0-9 age group (72.2%) although it only represents 11.5% of the sample; small occurrence of HAV hepatitis were found in patients over 40 (8.8%); HBV was clearly prevalent in patients over 50 (65.2%); the highest concentration of NANB etiology was found between 20-39 years old, but it was represented in all age-groups. Out of 49 NANB acute hepatitis, 12.2% had related transfusional antecedents, 12.2% belonged to health care worker group, and 4.1% had a close family NANB hepatitis contact; 71.5% had no reported antecedent. Viral source was presumably implicated in 75.0% of chronic active hepatitis, 25.0% attributable to HNANBV. Results seem not feasible to transfer to general population due to the facts that most patients were of specialized consult, and pediatric assistance is unusual to the authors practice.

  20. Sag-ponding and its Significance in determining Paleo-seismic events along the active strike- slip fault

    NASA Astrophysics Data System (ADS)

    Li, C.; Zhang, P.; Yuan, D.

    2007-12-01

    During the development of one active fault, we really want to know how it behaves and what it will do next. This mostly depends on the record and preservation of the information showing the action of the fault. Sparse young sediments or sediments with coarse grain along most of big strike-slip faults make it hard record and preserve the vestige of the paleo-seismic events. This extremely restricts the development of the Paleo-seismic research. Sag-ponding as well as the deposits in ponds, which are formed by the movement of the fault, can help settling the difficulty. Periodic sag-ponding is a feature to which should be paid more attention along the strike-slip fault, it can develop a pond to capture plenty fine sediments which well record the action of the faults. Sag-ponding can easily be found on the main active strike-slip faults in northern and eastern Tibet. By disclosing the sag-ponding depositions with 3-D excavations, sediment distribution and characters of relevant sag-ponds, and the relation between the sag-ponding and faulting were discussed. 1. Mechanism of the formation of the sag-pond When the valleys and ridges intersecting with the fault are displaced, the fault scarps will block the flow of the streams cut by the fault, or make the gullies develop ancon-like bend. This would form a space for water-storage, and thus a sag-pond comes into being. If the fault behaves like this many times, multi-sag-ponding will occur. 2. Rhythmic sag-ponding deposition features and stratigraphic sequence (1) Vertical characteristics. Observed from the stratigraphic profiles disclosed by the excavation, stratigraphic sequence shows good rhythms. There are several rhythms in each pond, and one rhythm is composed of the lower coarse layers and the upper fine layers. That is, the grains are coarser below and finer upward. (2) Transverse variation. In the direction parallel to the fault, the deposition center of each sag-pond appears regular movement, or migration

  1. Total body calcium by neutron activation analysis in normals and osteoporotic populations: a discriminator of significant bone mass loss

    SciTech Connect

    Ott, S.M.; Murano, R.; Lewellen, T.K.; Nelp, W.B.; Chesnut, C.M.

    1983-10-01

    Measurements of total body calcium by neutron activation (TBC) in 94 normal individuals and 86 osteoporotic patients are reported. The ability of TBC to discriminate normal from osteoporotic females was evaluated with decision analysis. Bone mineral content (BMC) by single-photon absorptiometry was also measured. TBC was higher in males (range 826 to 1363 gm vs 537 to 1054 in females) and correlated with height in all normals. In females over age 55 there was a negative correlation with age. Thus, for normals an algorithm was derived to allow comparison between measured TBC and that predicted by sex, age, and height (TBCp). In the 28 normal females over age 55, the TBC was 764 +/- 115 gm vs. 616 +/- 90 in the osteoporotics. In 63 of the osteoporotic females an estimated height, from tibial length, was used to predict TBC. In normals the TBC/TBCp ratio was 1.00 +/- 0.12, whereas in osteoporotic females it was 0.80 +/- 0.12. A receiver operating characteristic curve showed better discrimination of osteoporosis with TBC/TBCp than with wrist BMC. By using Bayes' theorem, with a 25% prevalence of osteoporosis (estimate for postmenopausal women), the posttest probability of disease was 90% when the TBC/TBCp ratio was less than 0.84. The authors conclude that a low TBC/TBCp ratio is very helpful in determining osteoporosis.

  2. Structures, chemotaxonomic significance, cytotoxic and Na(+),K(+)-ATPase inhibitory activities of new cardenolides from Asclepias curassavica.

    PubMed

    Zhang, Rong-Rong; Tian, Hai-Yan; Tan, Ya-Fang; Chung, Tse-Yu; Sun, Xiao-Hui; Xia, Xue; Ye, Wen-Cai; Middleton, David A; Fedosova, Natalya; Esmann, Mikael; Tzen, Jason T C; Jiang, Ren-Wang

    2014-11-28

    Five new cardenolide lactates (1–5) and one new dioxane double linked cardenolide glycoside (17) along with 15 known compounds (6–16 and 18–21) were isolated from the ornamental milkweed Asclepias curassavica. Their structures were elucidated by extensive spectroscopic methods (IR, UV, MS, 1D- and 2D-NMR). The molecular structures and absolute configurations of 1–3 and 17 were further confirmed by single-crystal X-ray diffraction analysis. Simultaneous isolation of dioxane double linked cardenolide glycosides (17–21) and cardenolide lactates (1–5) provided unique chemotaxonomic markers for this genus. Compounds 1–21 were evaluated for the inhibitory activities against DU145 prostate cancer cells. The dioxane double linked cardenolide glycosides showed the most potent cytotoxic effect followed by normal cardenolides and cardenolide lactates, while the C21 steroids were non-cytotoxic. Enzymatic assay established a correlation between the cytotoxic effects in DU145 cancer cells and the Ki for the inhibition of Na(+),K(+)-ATPase. Molecular docking analysis revealed relatively strong H-bond interactions between the bottom of the binding cavity and compounds 18 or 20, and explained why the dioxane double linked cardenolide glycosides possessed higher inhibitory potency on Na(+),K(+)-ATPase than the cardenolide lactate.

  3. Lipid droplets in activated mast cells - a significant source of triglyceride-derived arachidonic acid for eicosanoid production.

    PubMed

    Dichlberger, Andrea; Schlager, Stefanie; Kovanen, Petri T; Schneider, Wolfgang J

    2016-08-15

    Mast cells are potent effectors of immune reactions and key players in various inflammatory diseases such as atherosclerosis, asthma, and rheumatoid arthritis. The cellular defense response of mast cells represents a unique and powerful system, where external signals can trigger cell activation resulting in a stimulus-specific and highly coordinated release of a plethora of bioactive mediators. The arsenal of mediators encompasses preformed molecules stored in cytoplasmic secretory granules, as well as newly synthesized proteinaceous and lipid mediators. The release of mediators occurs in strict chronological order and requires proper coordination between the endomembrane system and various enzymatic machineries. For the generation of lipid mediators, cytoplasmic lipid droplets have been shown to function as a major intracellular pool of arachidonic acid, the precursor for eicosanoid biosynthesis. Recent studies have revealed that not only phospholipids in mast cell membranes, but also triglycerides in mast cell lipid droplets are a substrate source for eicosanoid formation. The present review summarizes current knowledge about mast cell lipid droplet biology, and discusses expansions and challenges of traditional mechanistic models for eicosanoid production.

  4. Purification and properties of a beta-galactosidase from carambola fruit with significant activity towards cell wall polysaccharides.

    PubMed

    Balasubramaniam, Sumathi; Lee, Heng Chin; Lazan, Hamid; Othman, Roohaida; Ali, Zainon Mohd

    2005-01-01

    beta-Galactosidase (EC. 3.2.1.23) from ripe carambola (Averrhoa carambola L. cv. B10) fruit was fractionated through a combination of ion exchange and gel filtration chromatography into four isoforms, viz. beta-galactosidase I, II, III and IV. This beta-galactosidases had apparent native molecular masses of 84, 77, 58 and 130 kDa, respectively. beta-Galactosidase I, the predominant isoform, was purified to electrophoretic homogeneity; analysis of the protein by SDS-PAGE revealed two subunits with molecular masses of 48 and 36 kDa. N-terminal amino acid sequence of the respective polypeptides shared high similarities albeit at different domains, with the deduced amino acid sequence of certain plant beta-galactosidases, thus, explaining the observed low similarity between the two subunits. beta-Galactosidase I was probably a heterodimer that have glycoprotein properties and a pI value of 7.2, with one of the potential glycosylation sites appeared to reside within the 48-kDa-polypeptide. The purified beta-galactosidase I was substantially active in hydrolyzing (1-->4)beta-linked spruce and a mixture of (1-->3)beta- and (1-->6)beta-linked gum arabic galactans. This isoform also had the capability to solubilize and depolymerize structurally intact pectins as well as to modify alkaline-soluble hemicelluloses, reflecting in part changes that occur during ripening.

  5. Parents' dietary patterns are significantly correlated: findings from the Melbourne Infant Feeding Activity and Nutrition Trial Program.

    PubMed

    Lioret, Sandrine; McNaughton, Sarah A; Crawford, David; Spence, Alison C; Hesketh, Kylie; Campbell, Karen J

    2012-08-01

    The objectives of the present study were to identify dietary patterns independently in first-time mothers and fathers, and to examine whether these patterns were correlated within families. Dietary intakes were collected at baseline in the Melbourne Infant Feeding Activity and Nutrition Trial Program using a validated FFQ in 454 pairs of first-time mothers and fathers. Education level was reported in associated questionnaires. Principal components analyses included frequencies of fifty-five food groups and were performed independently in mothers and fathers. Spearman's correlation coefficients were used to assess associations between dietary pattern scores. A total of four dietary patterns were identified in mothers and fathers. Of these, three dietary patterns had similar characteristics between these two populations, namely 'Fruits and vegetables', 'High-energy snack and processed foods', 'High-fat foods' in mothers; and 'Fruits', 'High-energy snack and processed foods', 'High-fat foods' in fathers. The following two additional patterns were identified: 'Cereals and sweet foods' in mothers and 'Potatoes and vegetables' in fathers. Patterns incorporating healthier food items were found to be positively associated with parent education. An inverse association with education was found for the 'High-fat foods' and 'High-energy snack and processed foods' dietary patterns. Qualitatively similar patterns between corresponding mothers and fathers were the most strongly correlated (ρ = 0·34-0·45, P < 0·001). There were some differences in dietary patterns between mothers and fathers, suggesting that it is worth deriving patterns separately when considering couples, and more generally between men and women. Exploring how these various patterns correlate within households provides important insights to guide the development and implementation of family-based interventions.

  6. Analysis and Design of Time-Varying Filter Banks

    NASA Astrophysics Data System (ADS)

    Sodagar, Iraj

    Analysis-synthesis filter banks have been studied extensively and a wide range of theoretical problems have been subsequently addressed. However, almost all the research activity has been concentrated on time-invariant filter banks whose components are fixed and do not change in time. The objective of this thesis is to develop analysis and design techniques for time-varying FIR analysis-synthesis filter banks that are perfect reconstructing (PR). In such systems, the analysis and/or synthesis filters, the down-up sampling rates, or even the number of bands can change in time. The underlying idea is that by adapting the basis functions of the filter bank transform to the signal properties, one can represent the relevant information of the signal more efficiently. For analysis purposes, we derive the time-varying impulse response of the filter bank in terms of the analysis and synthesis filter coefficients. We are able to represent this impulse response in terms of the product of the analysis and synthesis matrix transforms. Our approach to the PR time-varying filter bank design is to change the analysis -synthesis filter bank among a set of time-invariant filter banks. The analysis filter banks are switched instantaneously. To eliminate the distortion during switching, a new time-varying synthesis section is designed for each transition. Three design techniques are developed for the time-varying filter bank design. The first technique uses the least squares synthesis filters. This method improves the reconstruction quality significantly, but does not usually achieve the perfect reconstruction. Using the second technique, one can design PR time-varying systems by redesigning the analysis filters. The drawback is that this method requires numerical optimizations. The third technique introduces a new structure for exactly reconstructing time-varying filter banks. This structure consists of the conventional filter bank followed by a time-varying post filter. The post

  7. Cell response to silica gels with varying mechanical properties

    NASA Astrophysics Data System (ADS)

    Lefebvre, Molly Ann

    Sol-gel encapsulation has a variety of applications in biotechnology and medicine: creating biosensors, biocatalysts, and bioartificial organs. However, encapsulated cell viability is a major challenge. Consequently, interactions between cells and their 3D microenvironment were studied through rheological, metabolic activity, and extraction studies to aid in the development of new gel protocols. The cells were encapsulated in variations of three silica sol-gels with varying stiffness. It was hypothesized that the cell viability and the amount of extracted cells would depend on gel stiffness. For two gels, there was no apparent correlation between the gel stiffness and the cell viability and extracted cell quantity. These gels did strongly depend on the varying gel ingredient, polyethylene glycol. The third gel appeared to follow the hypothesized correlation, but it was not statistically significant. Finally, one gel had a significantly longer period of cell viability and higher quantity of extracted cells than the other gels.

  8. Genetic and biochemical characterization of OXA-405, an OXA-48-type extended-spectrum β-lactamase without significant carbapenemase activity.

    PubMed

    Dortet, Laurent; Oueslati, Saoussen; Jeannot, Katy; Tandé, Didier; Naas, Thierry; Nordmann, Patrice

    2015-07-01

    The epidemiology of carbapenemases worldwide is showing that OXA-48 variants are becoming the predominant carbapenemase type in Enterobacteriaceae in many countries. However, not all OXA-48 variants possess significant activity toward carbapenems (e.g., OXA-163). Two Serratia marcescens isolates with resistance either to carbapenems or to extended-spectrum cephalosporins were successively recovered from the same patient. A genomic comparison using pulsed-field gel electrophoresis and automated Rep-PCR typing identified a 97.8% similarity between the two isolates. Both strains were resistant to penicillins and first-generation cephalosporins. The first isolate was susceptible to expanded-spectrum cephalosporins, was resistant to carbapenems, and had a significant carbapenemase activity (positive Carba NP test) related to the expression of OXA-48. The second isolate was resistant to expanded-spectrum cephalosporins, was susceptible to carbapenems, and did not express a significant imipenemase activity, (negative for the Carba NP test) despite possessing a blaOXA-48-type gene. Sequencing identified a novel OXA-48-type β-lactamase, OXA-405, with a four-amino-acid deletion compared to OXA-48. The blaOXA-405 gene was located on a ca. 46-kb plasmid identical to the prototype IncL/M blaOXA-48-carrying plasmid except for a ca. 16.4-kb deletion in the tra operon, leading to the suppression of self-conjugation properties. Biochemical analysis showed that OXA-405 has clavulanic acid-inhibited activity toward expanded-spectrum activity without significant imipenemase activity. This is the first identification of a successive switch of catalytic activity in OXA-48-like β-lactamases, suggesting their plasticity. Therefore, this report suggests that the first-line screening of carbapenemase producers in Enterobacteriaceae may be based on the biochemical detection of carbapenemase activity in clinical settings.

  9. LY3009120, a panRAF inhibitor, has significant anti-tumor activity in BRAF and KRAS mutant preclinical models of colorectal cancer.

    PubMed

    Vakana, Eliza; Pratt, Susan; Blosser, Wayne; Dowless, Michele; Simpson, Nicholas; Yuan, Xiu-Juan; Jaken, Susan; Manro, Jason; Stephens, Jennifer; Zhang, Youyan; Huber, Lysiane; Peng, Sheng-Bin; Stancato, Louis F

    2017-02-07

    Activating mutations in the KRAS and BRAF genes, leading to hyperactivation of the RAS/RAF/MAPK oncogenic signaling cascade, are common in patients with colorectal cancer (CRC). While selective BRAF inhibitors are efficacious in BRAFmut melanoma, they have limited efficacy in BRAFmut CRC patients. In a RASmut background, selective BRAF inhibitors are contraindicated due to paradoxical activation of the MAPK pathway through potentiation of CRAF kinase activity. A way to overcome such paradoxical activation is through concurrent inhibition of the kinase activity of both RAF isoforms. Here, we further examined the effects of LY3009120, a panRAF and RAF dimer inhibitor, in human models of CRC with various mutational backgrounds. We demonstrate that LY3009120 induced anti-proliferative effects in BRAFmut and KRASmut CRC cell lines through G1-cell cycle arrest. The anti-proliferative effects of LY3009120 in KRASmut CRC cell lines phenocopied molecular inhibition of RAF isoforms by simultaneous siRNA-mediated knockdown of ARAF, BRAF and CRAF. Additionally, LY3009120 displayed significant activity in in vivo BRAFmut and KRASmut CRC xenograft models. Examination of potential resistance to LY3009120 demonstrated RAF-independent ERK and AKT activation in the KRASmut CRC cell line HCT 116. These findings describe the preclinical activity of a panRAF inhibitor in a BRAFmut and KRASmut CRC setting.

  10. Significant Correlation between TLR2 Agonist Activity and TNF-α Induction in J774.A1 Macrophage Cells by Different Medicinal Mushroom Products.

    PubMed

    Coy, Catherine; Standish, Leanna J; Bender, Geoff; Lu, Hailing

    2015-01-01

    In the US market, there is a variety of mushroom preparations available, even within the same species of mushroom. Nonetheless, little is known about whether species or the various extraction methods affect biological activity and potency of the immune modulatory activity of mushroom extracts. After discovering that protein-bound polysaccharide-K, a hot water extract from Trametes versicolor, was a potent Toll-like receptor (TLR)-2 agonist that stimulates both innate and adaptive immunity, this study was initiated to evaluate whether other medicinal mushroom products also have TLR2 agonist activity and immune-enhancing potential as measured by the induction of tumor necrosis factor (TNF)-α in J774.A1 murine macrophage cells. Furthermore, the products were divided by extraction method and species to determine whether these factors affect their immunomodulatory activity. The results showed that the majority (75%) of mushroom products tested had TLR2 agonist activity and that there was a significant correlation between TLR2 agonist activity and TNF-α induction potential in the mushroom products analyzed. In addition, the data demonstrated that hot water mushroom extracts are more potent than ground mushroom products in activating TLR2 and inducing TNF-α. These data provide evidence that extraction methods may affect the biological activity of mushroom products; thus, further studies are warranted to investigate the structural differences between various mushroom products.

  11. Recombinant interleukin-2 significantly augments activity of rituximab in human tumor xenograft models of B-cell non-Hodgkin lymphoma.

    PubMed

    Lopes de Menezes, Daniel E; Denis-Mize, Kimberly; Tang, Yan; Ye, Helen; Kunich, John C; Garrett, Evelyn N; Peng, Jing; Cousens, Lawrence S; Gelb, Arnold B; Heise, Carla; Wilson, Susan E; Jallal, Bahija; Aukerman, Sharon L

    2007-01-01

    Recombinant interleukin-2 (rIL-2) is a pleiotropic cytokine that activates select immune effector cell responses associated with antitumor activity, including antibody-dependent cellular cytotoxicity (ADCC). Rituximab is an anti-CD20 monoclonal antibody that activates ADCC in non-Hodgkin lymphoma (NHL). The ability of rIL-2 to augment rituximab-dependent tumor responses was investigated. The efficacy of rIL-2 in combination with rituximab was evaluated in 2 NHL tumor xenograft models: the CD20hi, rituximab-sensitive, low-grade Daudi model and the CD20lo, aggressive, rituximab-resistant Namalwa model. Combination of rIL-2 plus rituximab was synergistic in a rituximab-sensitive Daudi tumor model, as evidenced by significant tumor regressions and increased time to tumor progression, compared with rIL-2 and rituximab single agents. In contrast, rituximab-resistant Namalwa tumors were responsive to single-agent rIL-2 and showed an increased response when combined with rituximab. Using in vitro killing assays, rIL-2 was shown to enhance activity of rituximab by activating ADCC and lymphokine-activated killer activity. Additionally, the activity of rIL-2 plus rituximab F(ab')2 was similar to that of rIL-2 alone, indicating a critical role for immunoglobulin G1 Fc-FcgammaR-effector responses in mediating ADCC. Antiproliferative and apoptotic tumor responses, along with an influx of immune effector cells, were observed by immunohistochemistry. Collectively, the data suggest that rIL-2 mediates potent tumoricidal activity against NHL tumors, in part, through activation and trafficking of monocytes and natural killer cells to tumors. These data support the mechanistic and therapeutic rationale for combination of rIL-2 with rituximab in NHL clinical trials and for single-agent rIL-2 in rituximab-resistant NHL patients.

  12. [Long-term effect of a cognitive intervention on learning and participation in a significant leisure activity in early dementia of Alzheimer type: a case study].

    PubMed

    Provencher, Véronique; Bier, Nathalie; Audet, Thérèse; Gagnon, Lise

    2009-06-01

    Decreased ability to accomplish significant leisure activities often occurs in early stages of dementia of Alzheimer type (DAT). As a long term effect, it may eventually affect the quality of life of the patient as well as that of the caregiver's. In a previous study, a woman with early DAT (77 years old, MMSE: 24/30) improved her participation in 2 leisure activities (listening to music and praying in a group) following the learning of a few tasks (e.g. using a radio cassette, remembering the significance of an pre-programmed ring) as a result of a cognitive intervention. The present study presents the long term effect of this intervention on the retention of the learned tasks and on spontaneous participation in both leisure activities of her daily living. Measures of tasks' learning and spontaneous participation in activities have been obtained through direct observation (ex: ability to use the tasks learned without assistance) and telephone conversations with the caregiver. The measures were taken 9 to 15 months post-intervention. Nine months after the end of the intervention, the participant could no longer use the radio cassette, but was able to remember the significance of the pre-programmed ring. Similarly, she stopped listening to music, but still attended her prayer group. The intervention appears to maintain participation in a leisure activity for several months in a patient with early DAT, in spite of expected functional decline. This functional impact can be achieved through retention of specific learned tasks as well as by strong external cues (daily pre-programmed ring), and can increase the quality of life for patients with DAT.

  13. Significant enhancement in the photocatalytic activity of N, W co-doped TiO2 nanomaterials for promising environmental applications.

    PubMed

    Thind, Sapanbir S; Wu, Guosheng; Tian, Min; Chen, Aicheng

    2012-11-30

    In this work, a mesoporous N, W co-doped TiO(2) photocatalyst was synthesized via a one-step solution combustion method, which utilized urea as the nitrogen source and sodium tungstate as the tungsten source. The photocatalytic activity of the N, W co-doped TiO(2) photocatalyst was significantly enhanced by a facile UV pretreatment approach and was evaluated by measuring the rate of photodegradation of Rhodamine B under both UV and visible (λ > 420) light. Following the UV pretreatment, the UV photocatalytic activity of the N, W co-doped TiO(2) was doubled. In terms of visible light activity, the UV pretreatment resulted in an extraordinary >12 fold improvement. In order to gain insight into this substantial enhancement, the N, W co-doped TiO(2) photocatalysts were studied using x-ray diffraction, transmission electron microscopy, N(2) physisorption, UV-vis absorbance spectroscopy and x-ray photoelectron spectroscopy prior to and following the UV pretreatment. Our experimental results have revealed that this significant augmentation of photocatalytic activity may be attributed to several synergetic factors, including increase of the specific surface area, reduction of the band gap energy and the removal of carbon impurities.

  14. Integrating the public in mosquito management: active education by community peers can lead to significant reduction in peridomestic container mosquito habitats.

    PubMed

    Healy, Kristen; Hamilton, George; Crepeau, Taryn; Healy, Sean; Unlu, Isik; Farajollahi, Ary; Fonseca, Dina M

    2014-01-01

    Mosquito species that utilize peridomestic containers for immature development are commonly aggressive human biters, and because they often reach high abundance, create significant nuisance. One of these species, the Asian tiger mosquito Aedes albopictus, is an important vector of emerging infectious diseases, such as dengue, chikungunya, and Zika fevers. Integrated mosquito management (IMM) of Ae. albopictus is particularly difficult because it requires access to private yards in urban and suburban residences. It has become apparent that in the event of a public health concern due to this species, homeowners will have to be active participants in the control process by reducing mosquito habitats in their properties, an activity known as source reduction. However, limited attempts at quantifying the effect of source reduction by homeowners have had mixed results. Of note, many mosquito control programs in the US have some form of education outreach, however the primary approach is often passive focusing on the distribution of education materials as flyers. In 2010, we evaluated the use of active community peer education in a source reduction program, using AmeriCorps volunteers. The volunteers were mobilized over a 4-week period, in two areas with approximately 1,000 residences each in urban Mercer and suburban Monmouth counties in New Jersey, USA. The volunteers were first provided training on peridomestic mosquitoes and on basic approaches to reducing the number of container habitats for mosquito larvae in backyards. Within the two treatment areas the volunteers successfully engaged 758 separate homes. Repeated measures analysis of variance showed a significant reduction in container habitats in the sites where the volunteers actively engaged the community compared to untreated control areas in both counties. Our results suggest that active education using community peer educators can be an effective means of source reduction, and a critical tool in the arsenal

  15. Integrating the Public in Mosquito Management: Active Education by Community Peers Can Lead to Significant Reduction in Peridomestic Container Mosquito Habitats

    PubMed Central

    Healy, Kristen; Hamilton, George; Crepeau, Taryn; Healy, Sean; Unlu, Isik; Farajollahi, Ary; Fonseca, Dina M.

    2014-01-01

    Mosquito species that utilize peridomestic containers for immature development are commonly aggressive human biters, and because they often reach high abundance, create significant nuisance. One of these species, the Asian tiger mosquito Aedes albopictus, is an important vector of emerging infectious diseases, such as dengue, chikungunya, and Zika fevers. Integrated mosquito management (IMM) of Ae. albopictus is particularly difficult because it requires access to private yards in urban and suburban residences. It has become apparent that in the event of a public health concern due to this species, homeowners will have to be active participants in the control process by reducing mosquito habitats in their properties, an activity known as source reduction. However, limited attempts at quantifying the effect of source reduction by homeowners have had mixed results. Of note, many mosquito control programs in the US have some form of education outreach, however the primary approach is often passive focusing on the distribution of education materials as flyers. In 2010, we evaluated the use of active community peer education in a source reduction program, using AmeriCorps volunteers. The volunteers were mobilized over a 4-week period, in two areas with approximately 1,000 residences each in urban Mercer and suburban Monmouth counties in New Jersey, USA. The volunteers were first provided training on peridomestic mosquitoes and on basic approaches to reducing the number of container habitats for mosquito larvae in backyards. Within the two treatment areas the volunteers successfully engaged 758 separate homes. Repeated measures analysis of variance showed a significant reduction in container habitats in the sites where the volunteers actively engaged the community compared to untreated control areas in both counties. Our results suggest that active education using community peer educators can be an effective means of source reduction, and a critical tool in the arsenal

  16. Cry1Ac Transgenic Sugarcane Does Not Affect the Diversity of Microbial Communities and Has No Significant Effect on Enzyme Activities in Rhizosphere Soil within One Crop Season.

    PubMed

    Zhou, Dinggang; Xu, Liping; Gao, Shiwu; Guo, Jinlong; Luo, Jun; You, Qian; Que, Youxiong

    2016-01-01

    Cry1Ac transgenic sugarcane provides a promising way to control stem-borer pests. Biosafety assessment of soil ecosystem for cry1Ac transgenic sugarcane is urgently needed because of the important role of soil microorganisms in nutrient transformations and element cycling, however little is known. This study aimed to explore the potential impact of cry1Ac transgenic sugarcane on rhizosphere soil enzyme activities and microbial community diversity, and also to investigate whether the gene flow occurs through horizontal gene transfer. We found no horizontal gene flow from cry1Ac sugarcane to soil. No significant difference in the population of culturable microorganisms between the non-GM and cry1Ac transgenic sugarcane was observed, and there were no significant interactions between the sugarcane lines and the growth stages. A relatively consistent trend at community-level, represented by the functional diversity index, was found between the cry1Ac sugarcane and the non-transgenic lines. Most soil samples showed no significant difference in the activities of four soil enzymes: urease, protease, sucrose, and acid phosphate monoester between the non-transgenic and cry1Ac sugarcane lines. We conclude, based on one crop season, that the cry1Ac sugarcane lines may not affect the microbial community structure and functional diversity of the rhizosphere soil and have few negative effects on soil enzymes.

  17. Novel sulfated glucomannan-barium-alginate microcapsules in islet transplantation: significantly decreased the secretion of monocyte chemotactic protein 1 and improved the activity of islet in rats.

    PubMed

    Chen, X; Zhang, L; Qi, Z; Guo, B; Zhong, L; Shen, B; Yan, Z; Zhang, J

    2009-12-01

    The sulfated glucomannan can be used to filter the heparin-binding properties of cytokines. In this study, novel sulfated glucomannan-barium-alginate (SGA) microcapsules were prepared to encapsulate islets with barium-alginate (ABa) and calcium alginate-poly-l-lysine (APA) microcapsules as controls. SD rat islets were purified as donor cells to Lewis rats that had been treated with streptozotocin. Intraperitoneal transplantation was performed with about 3000 islet equivalent (IEQ) rat. At week three after transplantation, the concentrations of monocyte chemotactic protein-1 (MCP-1), interleukin (IL)-1 beta, interferon (IFN)-gamma, and tumor necrosis factor (TNF)-alpha in intraperitoneal fluid were determined using ELISA. At week 8, the islet cell mass in the abdominal microcapsules was excised to test insulin release. The EB-FDA fluorescence staining method was used to observe the functional activity of the islet cells. Compared with ABa and APA microcapsules, SGA microcapsules showed significantly decreased MCP-1 secretion by beta-cells. Also, the concentrations of cytokines IL-1beta, IFN-gamma, and TNF-alpha were decreased significantly. The activity of the transplanted islets was significantly improved in SGA microcapsules, which shielded against cytokines better than ABa or APA microcapsules and may serve as novel method.

  18. Cry1Ac Transgenic Sugarcane Does Not Affect the Diversity of Microbial Communities and Has No Significant Effect on Enzyme Activities in Rhizosphere Soil within One Crop Season

    PubMed Central

    Zhou, Dinggang; Xu, Liping; Gao, Shiwu; Guo, Jinlong; Luo, Jun; You, Qian; Que, Youxiong

    2016-01-01

    Cry1Ac transgenic sugarcane provides a promising way to control stem-borer pests. Biosafety assessment of soil ecosystem for cry1Ac transgenic sugarcane is urgently needed because of the important role of soil microorganisms in nutrient transformations and element cycling, however little is known. This study aimed to explore the potential impact of cry1Ac transgenic sugarcane on rhizosphere soil enzyme activities and microbial community diversity, and also to investigate whether the gene flow occurs through horizontal gene transfer. We found no horizontal gene flow from cry1Ac sugarcane to soil. No significant difference in the population of culturable microorganisms between the non-GM and cry1Ac transgenic sugarcane was observed, and there were no significant interactions between the sugarcane lines and the growth stages. A relatively consistent trend at community-level, represented by the functional diversity index, was found between the cry1Ac sugarcane and the non-transgenic lines. Most soil samples showed no significant difference in the activities of four soil enzymes: urease, protease, sucrose, and acid phosphate monoester between the non-transgenic and cry1Ac sugarcane lines. We conclude, based on one crop season, that the cry1Ac sugarcane lines may not affect the microbial community structure and functional diversity of the rhizosphere soil and have few negative effects on soil enzymes. PMID:27014291

  19. Leucine aminopeptidase, beta-glucosidase and alkaline phosphatase activity rates and their significance in nutrient cycles in some coastal Mediterranean sites.

    PubMed

    Caruso, Gabriella

    2010-03-29

    In aquatic microbial ecology, knowledge of the processes involved in the turnover of organic matter is of utmost importance to understand ecosystem functioning. Microorganisms are major players in the cycling of nutrients (nitrogen, phosphorus) and carbon, thanks to their enzymatic activities (leucine aminopeptidase, LAP, alkaline phosphatase, AP, and beta-glucosidase, beta-GLU) on organic polymers (proteins, organic phosphates and polysaccharides, respectively). Estimates of the decomposition rates of organic polymers are performed using fluorogenic compounds, whose hydrolysis rate allow us to obtain information on the "potential" metabolic activity of the prokaryotic community. This paper refers the enzyme patterns measured during recent oceanographic cruises performed in some coastal Mediterranean sites, not yet fully investigated in terms of microbial biogeochemical processes. Mean enzyme activity rates ranged from 5.24 to 5558.1 nM/h, from 12.68 to 244.73 nM/h and from 0.006 to 9.51 nM/h for LAP, AP and beta-GLU, respectively. The highest LAP and AP activity rates were measured in the Gulf of Milazzo (Tyrrhenian Sea) and in the Straits of Messina, in association with the lowest bacterioplankton abundance; in contrast, the lowest ones were found in the northern Adriatic Sea. beta-GLU was more active in the Straits of Messina. Activity rates were analysed in relation to the main environmental variables. Along the northern Adriatic coastal side affected by the Po river, significant inverse relationships linked LAP and AP with salinity, pointing out that fluvial inputs provided organic substrates for microbial metabolism. Both in the Gulf of Manfredonia and in the Straits of Messina, LAP and AP levels were inversely related with the concentration of nitrate and inorganic phosphorus, respectively. In the Gulf of Milazzo, high cell-specific AP measured in spite of phosphorus availability suggested the role of this enzyme not only in phosphorus, but also in carbon

  20. Zephycandidine A, the First Naturally Occurring Imidazo[1,2-f]phenanthridine Alkaloid from Zephyranthes candida, Exhibits Significant Anti-tumor and Anti-acetylcholinesterase Activities

    NASA Astrophysics Data System (ADS)

    Zhan, Guanqun; Qu, Xiaolan; Liu, Junjun; Tong, Qingyi; Zhou, Junfei; Sun, Bin; Yao, Guangmin

    2016-09-01

    Zephycandidine A (1), the first naturally occurring imidazo[1,2-f]phenanthridine alkaloid, was isolated from Zephyranthes candida (Amaryllidaceae). The structure of 1 was elucidated by spectroscopic analyses and NMR calculation, and a plausible biogenetic pathway for zephycandidine A (1) was proposed. Zephycandidine A (1) exhibited significant cytotoxicity against five cancer cell lines with IC50 values ranging from 1.98 to 7.03 μM with selectivity indices as high as 10 when compared to the normal Beas-2B cell. Further studies suggested that zephycandidine A (1) induces apoptosis in leukemia cells by the activation of caspase-3, upregulation of Bax, downregulation of Bcl-2, and degradation of PARP expression. In addition, zephycandidine A (1) showed acetylcholinesterase (AChE) inhibitory activity, and the docking studies of zephycandidine A (1) and galanthamine (2) with AChE revealed that interactions with W286 and Y337 are necessary.

  1. Zephycandidine A, the First Naturally Occurring Imidazo[1,2-f]phenanthridine Alkaloid from Zephyranthes candida, Exhibits Significant Anti-tumor and Anti-acetylcholinesterase Activities

    PubMed Central

    Zhan, Guanqun; Qu, Xiaolan; Liu, Junjun; Tong, Qingyi; Zhou, Junfei; Sun, Bin; Yao, Guangmin

    2016-01-01

    Zephycandidine A (1), the first naturally occurring imidazo[1,2-f]phenanthridine alkaloid, was isolated from Zephyranthes candida (Amaryllidaceae). The structure of 1 was elucidated by spectroscopic analyses and NMR calculation, and a plausible biogenetic pathway for zephycandidine A (1) was proposed. Zephycandidine A (1) exhibited significant cytotoxicity against five cancer cell lines with IC50 values ranging from 1.98 to 7.03 μM with selectivity indices as high as 10 when compared to the normal Beas-2B cell. Further studies suggested that zephycandidine A (1) induces apoptosis in leukemia cells by the activation of caspase-3, upregulation of Bax, downregulation of Bcl-2, and degradation of PARP expression. In addition, zephycandidine A (1) showed acetylcholinesterase (AChE) inhibitory activity, and the docking studies of zephycandidine A (1) and galanthamine (2) with AChE revealed that interactions with W286 and Y337 are necessary. PMID:27658482

  2. Environmental Assessment and Finding of No Significant Impact: Waste Remediation Activities at Elk Hills (Former Naval petroleum Reserve No. 1), Kern County, California

    SciTech Connect

    N /A

    1999-12-17

    DOE proposes to conduct a variety of post-sale site remediation activities, such as characterization, assessment, clean-up, and formal closure, at a number of inactive waste sites located at Elk Hills. The proposed post-sale site remediation activities, which would be conducted primarily in developed portions of the oil field, currently are expected to include clean-up of three basic categories of waste sites: (1) nonhazardous solid waste surface trash scatters, (2) produced wastewater sumps, and (3) small solid waste landfills. Additionally, a limited number of other inactive waste sites, which cannot be typified under any of these three categories, have been identified as requiring remediation. Table 2.1-1 presents a summary, organized by waste site category, of the inactive waste sites that require remediation per the PSA, the ASA, and/or the UPCTA. The majority of these sites are known to contain no hazardous waste. However, one of the surface scatter sites (2G) contains an area of burn ash with hazardous levels of lead and zinc, another surface scatter site (25S) contains an area with hazardous levels of lead, a produced wastewater sump site (23S) and a landfill (42-36S) are known to contain hazardous levels of arsenic, and some sites have not yet been characterized. Furthermore, additional types of sites could be discovered. For example, given the nature of oil field operations, sites resulting from either spills or leaks of hazardous materials could be discovered. Given the nature of the agreements entered into by DOE regarding the required post-sale clean-up of the inactive waste sites at Elk Hills, the Proposed Action is the primary course of action considered in this EA. The obligatory remediation activities included in the Proposed Action are standard procedures such that possible variations of the Proposed Action would not vary substantially enough to require designation as a separate, reasonable alternative. Thus, the No Action Alternative is the only

  3. Conjugation of 10 kDa Linear PEG onto Trastuzumab Fab' Is Sufficient to Significantly Enhance Lymphatic Exposure while Preserving in Vitro Biological Activity.

    PubMed

    Chan, Linda J; Ascher, David B; Yadav, Rajbharan; Bulitta, Jürgen B; Williams, Charlotte C; Porter, Christopher J H; Landersdorfer, Cornelia B; Kaminskas, Lisa M

    2016-04-04

    The lymphatic system is a major conduit by which many diseases spread and proliferate. There is therefore increasing interest in promoting better lymphatic drug targeting. Further, antibody fragments such as Fabs have several advantages over full length monoclonal antibodies but are subject to rapid plasma clearance, which can limit the lymphatic exposure and activity of Fabs against lymph-resident diseases. This study therefore explored ideal PEGylation strategies to maximize biological activity and lymphatic exposure using trastuzumab Fab' as a model. Specifically, the Fab' was conjugated with single linear 10 or 40 kDa PEG chains at the hinge region. PEGylation led to a 3-4-fold reduction in binding affinity to HER2, but antiproliferative activity against HER2-expressing BT474 cells was preserved. Lymphatic pharmacokinetics were then examined in thoracic lymph duct cannulated rats after intravenous and subcutaneous dosing at 2 mg/kg, and the data were evaluated via population pharmacokinetic modeling. The Fab' displayed limited lymphatic exposure, but conjugation of 10 kDa PEG improved exposure by approximately 11- and 5-fold after intravenous (15% dose collected in thoracic lymph over 30 h) and subcutaneous (9%) administration, respectively. Increasing the molecular weight of the PEG to 40 kDa, however, had no significant impact on lymphatic exposure after intravenous (14%) administration and only doubled lymphatic exposure after subcutaneous administration (18%) when compared to 10 kDa PEG-Fab'. The data therefore suggests that minimal PEGylation has the potential to enhance the exposure and activity of Fab's against lymph-resident diseases, while no significant benefit is achieved with very large PEGs.

  4. Peroxisome proliferator-activated receptor gamma and spermidine/spermine N1-acetyltransferase gene expressions are significantly correlated in human colorectal cancer

    PubMed Central

    Linsalata, Michele; Giannini, Romina; Notarnicola, Maria; Cavallini, Aldo

    2006-01-01

    Background The peroxisome proliferator-activated receptor γ (PPARγ) is a transcription factor that regulates adipogenic differentiation and glucose homeostasis. Spermidine/spermine N1-acetyltransferase (SSAT) and ornithine decarboxylase (ODC) are key enzymes involved in the metabolism of polyamines, compounds that play an important role in cell proliferation. While the PPARγ role in tumour growth has not been clearly defined, the involvement of the altered polyamine metabolism in colorectal carcinogenesis has been established. In this direction, we have evaluated the PPARγ expression and its relationship with polyamine metabolism in tissue samples from 40 patients operated because of colorectal carcinoma. Since it is known that the functional role of K-ras mutation in colorectal tumorigenesis is associated with cell growth and differentiation, polyamine metabolism and the PPARγ expression were also investigated in terms of K-ras mutation. Methods PPARγ, ODC and SSAT mRNA levels were evaluated by reverse transcriptase and real-time PCR. Polyamines were quantified by high performance liquid chromatography (HPLC). ODC and SSAT activity were measured by a radiometric technique. Results PPARγ expression, as well as SSAT and ODC mRNA levels were significantly higher in cancer as compared to normal mucosa. Tumour samples also showed significantly higher polyamine levels and ODC and SSAT activities in comparison to normal samples. A significant and positive correlation between PPARγ and the SSAT gene expression was observed in both normal and neoplastic tissue (r = 0.73, p < 0.0001; r = 0.65, p < 0.0001, respectively). Moreover, gene expression, polyamine levels and enzymatic activities were increased in colorectal carcinoma samples expressing K-ras mutation as compared to non mutated K-ras samples. Conclusion In conclusion, our data demonstrated a close relationship between PPARγ and SSAT in human colorectal cancer and this could represent an attempt to decrease

  5. Significant decrease of ADP release rate underlies the potent activity of dimethylenastron to inhibit mitotic kinesin Eg5 and cancer cell proliferation

    SciTech Connect

    Sun, Linlin; Sun, Xiaodong; Xie, Songbo; Yu, Haiyang; Zhong, Diansheng

    2014-05-09

    Highlights: • DIMEN displays higher anti-proliferative activity than enastron. • DIMEN induced mitotic arrest and apoptosis more significantly than enastron. • DIMEN blocked the conformational change of ADP-binding pocket more effectively. • DIMEN hindered ADP release more potently than enastron. - Abstract: Eg5 is a mitotic kinesin that plays a crucial role in the formation of bipolar mitotic spindles, by hydrolyzing ATP to push apart anti-parallel microtubules. Dimethylenastron is potent specific small molecule inhibitor of Eg5. The mechanism by which dimethylenastron inhibits Eg5 function remains unclear. By comparing with enastron, here we report that dimethylenastron prevents the growth of pancreatic and lung cancer cells more effectively, by halting mitotic progression and triggering apoptosis. We analyze their interactions with ADP-bound Eg5 crystal structure, and find that dimethylenastron binds Eg5 motor domain with higher affinity. In addition, dimethylenastron allosterically blocks the conformational change of the “sandwich”-like ADP-binding pocket more effectively. We subsequently use biochemical approach to reveal that dimethylenastron slows ADP release more significantly than enastron. These data thus provide biological, structural and mechanistic insights into the potent inhibitory activity of dimethylenastron.

  6. Silvestrol exhibits significant in vivo and in vitro antileukemic activities and inhibits FLT3 and miR-155 expressions in acute myeloid leukemia

    PubMed Central

    2013-01-01

    Background Activating mutations [internal tandem duplication (ITD)] or overexpression of the FMS-like tyrosine kinase receptor-3 (FLT3) gene are associated with poor outcome in acute myeloid leukemia (AML) patients, underscoring the need for novel therapeutic approaches. The natural product silvestrol has potent antitumor activity in several malignancies, but its therapeutic impact on distinct molecular high-risk AML subsets remains to be fully investigated. We examined here the preclinical activity of silvestrol in FLT3-ITD and FLT3 wild-type (wt) AML. Methods Silvestrol in vitro anti-leukemic activity was examined by colorimetric cell viability assay, colony-forming and flow cytometry assays assessing growth inhibition and apoptosis, respectively. Pharmacological activity of silvestrol on FLT3 mRNA translation, mRNA and protein expression was determined by RNA-immunoprecipitation, qRT-PCR and immunoblot analyses, respectively. Silvestrol in vivo efficacy was investigated using MV4-11 leukemia-engrafted mice. Results Silvestrol shows antileukemia activity at nanomolar concentrations both in FLT3-wt overexpressing (THP-1) and FLT3-ITD (MV4-11) expressing AML cell lines (IC50 = 3.8 and 2.7 nM, respectively) and patients’ primary blasts [IC50 = ~12 nM (FLT3-wt) and ~5 nM (FLT3-ITD)]. Silvestrol increased apoptosis (~4fold, P = 0.0001), and inhibited colony-formation (100%, P < 0.0001) in primary blasts. Silvestrol efficiently inhibited FLT3 translation reducing FLT3 protein expression by 80–90% and decreased miR-155 levels (~60%), a frequently co-regulated onco-miR in FLT3-ITD-positive AML. The median survival of silvestrol-treated vs vehicle-treated mice was 63 vs 29 days post-engraftment, respectively (P < 0.0001). Conclusions Silvestrol exhibits significant in vivo and in vitro antileukemic activities in AML through a novel mechanism resulting in inhibition of FLT3 and miR-155 expression. These encouraging results warrant a rapid

  7. In vitro exposure to the herbicide atrazine inhibits T cell activation, proliferation, and cytokine production and significantly increases the frequency of Foxp3+ regulatory T cells.

    PubMed

    Thueson, Lindsay E; Emmons, Tiffany R; Browning, Dianna L; Kreitinger, Joanna M; Shepherd, David M; Wetzel, Scott A

    2015-02-01

    The herbicide atrazine (2-chloro-4-[ethylamino]-6-[isopropylamino]-s-triazine) is the most common water contaminant in the United States. Atrazine is a phosphodiesterase inhibitor and is classified as an estrogen disrupting compound because it elevates estrogen levels via induction of the enzyme aromatase. Previous studies have shown that atrazine exposure alters the function of innate immune cells such as NK cells, DC, mast cells, and macrophages. In this study we have examined the impact of in vitro atrazine exposure on the activation, proliferation, and effector cytokine production by primary murine CD4(+) T lymphocytes. We found that atrazine exposure significantly inhibited CD4(+) T cell proliferation and accumulation as well as the expression of the activation markers CD25 and CD69 in a dose-dependent manner. Interestingly, the effects were more pronounced in cells from male animals. These effects were partially mimicked by pharmacological reagents that elevate intracellular cAMP levels and addition of exogenous rmIL-2 further inhibited proliferation and CD25 expression. Consistent with these findings, atrazine exposure during T cell activation resulted in a 2- to 5-fold increase in the frequency of Foxp3(+) CD4(+) T cells.

  8. Immunization of teenagers with a fifth dose of reduced DTaP-IPV induces high levels of pertussis antibodies with a significant increase in opsonophagocytic activity.

    PubMed

    Aase, Audun; Herstad, Tove Karin; Merino, Samuel; Bolstad, Merete; Sandbu, Synne; Bakke, Hilde; Aaberge, Ingeborg S

    2011-08-01

    Waning vaccine-induced immunity against Bordetella pertussis is observed among adolescents and adults. A high incidence of pertussis has been reported in this population, which serves as a reservoir for B. pertussis. A fifth dose of reduced antigen of diphtheria-tetanus-acellular-pertussis and inactivated polio vaccine was given as a booster dose to healthy teenagers. The antibody activity against B. pertussis antigens was measured prior to and 4 to 8 weeks after the booster by different assays: enzyme-linked immunosorbent assays (ELISAs) of IgG and IgA against pertussis toxin (PT) and filamentous hemagglutinin (FHA), IgG against pertactin (PRN), opsonophagocytic activity (OPA), and IgG binding to live B. pertussis. There was a significant increase in the IgG activity against PT, FHA, and PRN following the booster immunization (P < 0.001). The prebooster sera showed a geometric mean OPA titer of 65.1 and IgG binding to live bacteria at a geometric mean concentration of 164.9 arbitrary units (AU)/ml. Following the fifth dose, the OPA increased to a titer of 360.4, and the IgG concentration against live bacteria increased to 833.4 AU/ml (P < 0.001 for both). The correlation analyses between the different assays suggest that antibodies against FHA and PRN contribute the most to the OPA and IgG binding.

  9. Trichoderma harzianum IOC-4038: A promising strain for the production of a cellulolytic complex with significant β-glucosidase activity from sugarcane bagasse cellulignin.

    PubMed

    de Castro, Aline Machado; Pedro, Kelly Cristina Nascimento Rodrigues; da Cruz, Juliana Cunha; Ferreira, Marcela Costa; Leite, Selma Gomes Ferreira; Pereira, Nei

    2010-11-01

    Sugarcane bagasse is an agroindustrial residue generated in large amounts in Brazil. This biomass can be used for the production of cellulases, aiming at their use in second-generation processes for bioethanol production. Therefore, this work reports the ability of a fungal strain, Trichoderma harzianum IOC-4038, to produce cellulases on a novel material, xylan free and cellulose rich, generated from sugarcane bagasse, named partially delignified cellulignin. The extract produced by T. harzianum under submerged conditions reached 745, 97, and 559 U L(-1) of β-glucosidase, FPase, and endoglucanase activities, respectively. The partial characterization of this enzyme complex indicated, using a dual analysis, that the optimal pH values for the biocatalysis ranged from 4.9 to 5.2 and optimal temperatures were between 47 and 54 °C, depending on the activity studied. Thermal stability analyses revealed no significant decrease in activity at 37 °C during 23 h of incubation. When compared to model strains, Aspergillus niger ATCC-16404 and Trichoderma reesei RutC30, T. harzianum fermentation was faster and its extract showed a better balanced enzyme complex, with adequate characteristics for its application in simultaneous saccharification and fermentation processes.

  10. The significance of matrix effects on the measurement of lactate dehydrogenase (LD) activity using Kodak dry slide technology in the Ontario Laboratory Proficiency Testing Program.

    PubMed

    Hill, S A; Heathcote, J C; McQueen, M J

    1990-04-01

    A recent lactate dehydrogenase (LD) survey of the Laboratory Proficiency Testing Program (LPTP) of Ontario showed interlaboratory coefficients of variation ranging from 6.5% to 40% for five lyophilized vials on the 12 Kodak analyzers. All the LPTP survey samples had similar protein and LD isoenzyme electrophoretic patterns which remained unchanged after reconstitution and storage for 5 days at 4 degrees C, although the total LD activities fell. Four Ektachem 700 analyzers were subsequently tested using LPTP material and no difference in LD activity between instruments or between two LD slide lot numbers was shown. Generation 9 slides gave higher LD activities than generation 10 on all the reconstituted lyophilized proficiency testing samples. There was no significant difference between slide generations when 19 liquid human sera were analyzed, indicating that the variability on LPTP samples was due to a matrix effect. Definition of the matrix effect of lyophilized proficiency testing material is essential before any proficiency testing program can use such material to reflect analytical performance on patient specimens.

  11. Varying Constants, Gravitation and Cosmology.

    PubMed

    Uzan, Jean-Philippe

    2011-01-01

    Fundamental constants are a cornerstone of our physical laws. Any constant varying in space and/or time would reflect the existence of an almost massless field that couples to matter. This will induce a violation of the universality of free fall. Thus, it is of utmost importance for our understanding of gravity and of the domain of validity of general relativity to test for their constancy. We detail the relations between the constants, the tests of the local position invariance and of the universality of free fall. We then review the main experimental and observational constraints that have been obtained from atomic clocks, the Oklo phenomenon, solar system observations, meteorite dating, quasar absorption spectra, stellar physics, pulsar timing, the cosmic microwave background and big bang nucleosynthesis. At each step we describe the basics of each system, its dependence with respect to the constants, the known systematic effects and the most recent constraints that have been obtained. We then describe the main theoretical frameworks in which the low-energy constants may actually be varying and we focus on the unification mechanisms and the relations between the variation of different constants. To finish, we discuss the more speculative possibility of understanding their numerical values and the apparent fine-tuning that they confront us with.

  12. Learning Time-Varying Coverage Functions

    PubMed Central

    Du, Nan; Liang, Yingyu; Balcan, Maria-Florina; Song, Le

    2015-01-01

    Coverage functions are an important class of discrete functions that capture the law of diminishing returns arising naturally from applications in social network analysis, machine learning, and algorithmic game theory. In this paper, we propose a new problem of learning time-varying coverage functions, and develop a novel parametrization of these functions using random features. Based on the connection between time-varying coverage functions and counting processes, we also propose an efficient parameter learning algorithm based on likelihood maximization, and provide a sample complexity analysis. We applied our algorithm to the influence function estimation problem in information diffusion in social networks, and show that with few assumptions about the diffusion processes, our algorithm is able to estimate influence significantly more accurately than existing approaches on both synthetic and real world data. PMID:25960624

  13. Interactions outside the proteinase-binding loop contribute significantly to the inhibition of activated coagulation factor XII by its canonical inhibitor from corn.

    PubMed

    Korneeva, Vera A; Trubetskov, Mikhail M; Korshunova, Alena V; Lushchekina, Sofya V; Kolyadko, Vladimir N; Sergienko, Olga V; Lunin, Vladimir G; Panteleev, Mikhail A; Ataullakhanov, Fazoil I

    2014-05-16

    Activated factor XII (FXIIa) is selectively inhibited by corn Hageman factor inhibitor (CHFI) among other plasma proteases. CHFI is considered a canonical serine protease inhibitor that interacts with FXIIa through its protease-binding loop. Here we examined whether the protease-binding loop alone is sufficient for the selective inhibition of serine proteases or whether other regions of a canonical inhibitor are involved. Six CHFI mutants lacking different N- and C-terminal portions were generated. CHFI-234, which lacks the first and fifth disulfide bonds and 11 and 19 amino acid residues at the N and C termini, respectively, exhibited no significant changes in FXIIa inhibition (Ki = 3.2 ± 0.4 nm). CHFI-123, which lacks 34 amino acid residues at the C terminus and the fourth and fifth disulfide bridges, inhibited FXIIa with a Ki of 116 ± 16 nm. To exclude interactions outside the FXIIa active site, a synthetic cyclic peptide was tested. The peptide contained residues 20-45 (Protein Data Bank code 1BEA), and a C29D substitution was included to avoid unwanted disulfide bond formation between unpaired cysteines. Surprisingly, the isolated protease-binding loop failed to inhibit FXIIa but retained partial inhibition of trypsin (Ki = 11.7 ± 1.2 μm) and activated factor XI (Ki = 94 ± 11 μm). Full-length CHFI inhibited trypsin with a Ki of 1.3 ± 0.2 nm and activated factor XI with a Ki of 5.4 ± 0.2 μm. Our results suggest that the protease-binding loop is not sufficient for the interaction between FXIIa and CHFI; other regions of the inhibitor also contribute to specific inhibition.

  14. Field studies of beach cones as coastal erosion control/reversal devices for areas with significant oil and gas activities. Final report, February 24, 1992--September 18, 1995

    SciTech Connect

    Law, V.J.

    1995-09-18

    The primary objective of this project was to evaluate the utility of a device called the {open_quotes}beach cone{close_quotes} in combating coastal erosion. Seven initial sites were selected for testing beach cones in a variety of geometric configurations. Permits were obtained from the State of Louisiana and the U.S. Army Corps of Engineers to perform the work associated with this study. Six hundred beach cones were actually installed at six of the sites in late July and early August, 1992. Findings indicate that beach cones accreted significant amounts of materials along the beach of a barrier island, and they might have been instrumental in repairing an approximately 200 meter gap in the island. At the eighth installation the amount of accreted material was measured by surveys to be 2200 cubic meters (2900 cubic yards) in February of 1993, when the cones were found to have been completely covered by the material. At other test sites, accretion rates have been less dramatic but importantly, no significant additional erosion has occurred, which is a positive result. The cost of sediment accretion using beach cones was found to be about $13.72 per cubic yard, which would be much lower if the cones were mass produced (on the order of $3.00 per cubic yard). The survival of the cones through the fringes of Hurricane Andrew indicates that they can be anchored sufficiently to survive significant storms. The measurements of the cones settling rates indicate that this effect is not significant enough to hinder their effectiveness. A subcontract to Xavier University to assess the ecological quality of the experimental sites involved the study of the biogeochemical cycle of trace metals. The highest concentration of heavy metals were near a fishing camp while the lowest levels were in the beach sand of a barrier island. This suggests that the metals do not occur naturally in these areas, but have been placed in the sediments by man`s activities.

  15. Powerful Complex Immunoadjuvant Based on Synergistic Effect of Combined TLR4 and NOD2 Activation Significantly Enhances Magnitude of Humoral and Cellular Adaptive Immune Responses

    PubMed Central

    Dzharullaeva, Alina S.; Tukhvatulina, Natalia M.; Shcheblyakov, Dmitry V.; Shmarov, Maxim M.; Dolzhikova, Inna V.; Stanhope-Baker, Patricia; Naroditsky, Boris S.; Gudkov, Andrei V.; Logunov, Denis Y.; Gintsburg, Alexander L.

    2016-01-01

    Binding of pattern recognition receptors (PRRs) by pathogen-associated molecular patterns (PAMPs) activates innate immune responses and contributes to development of adaptive immunity. Simultaneous stimulation of different types of PRRs can have synergistic immunostimulatory effects resulting in enhanced production of molecules that mediate innate immunity such as inflammatory cytokines, antimicrobial peptides, etc. Here, we evaluated the impact of combined stimulation of PRRs from different families on adaptive immunity by generating alum-based vaccine formulations with ovalbumin as a model antigen and the Toll-like receptor 4 (TLR4) agonist MPLA and the Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) agonist MDP adsorbed individually or together on the alum-ovalbumin particles. Multiple in vitro and in vivo readouts of immune system activation all showed that while individual PRR agonists increased the immunogenicity of vaccines compared to alum alone, the combination of both PRR agonists was significantly more effective. Combined stimulation of TLR4 and NOD2 results in a stronger and broader transcriptional response in THP-1 cells compared to individual PRR stimulation. Immunostimulatory composition containing both PRR agonists (MPLA and MDP) in the context of the alum-based ovalbumin vaccine also enhanced uptake of vaccine particles by bone marrow derived dendritic cells (BMDCs) and promoted maturation (up-regulation of expression of CD80, CD86, MHCII) and activation (production of cytokines) of BMDCs. Finally, immunization of mice with vaccine particles containing both PRR agonists resulted in enhanced cellular immunity as indicated by increased proliferation and activation (IFN-γ production) of splenic CD4+ and CD8+ T cells following in vitro restimulation with ovalbumin and enhanced humoral immunity as indicated by higher titers of ovalbumin-specific IgG antibodies. These results indicate that combined stimulation of TLR4 and NOD2

  16. Powerful Complex Immunoadjuvant Based on Synergistic Effect of Combined TLR4 and NOD2 Activation Significantly Enhances Magnitude of Humoral and Cellular Adaptive Immune Responses.

    PubMed

    Tukhvatulin, Amir I; Dzharullaeva, Alina S; Tukhvatulina, Natalia M; Shcheblyakov, Dmitry V; Shmarov, Maxim M; Dolzhikova, Inna V; Stanhope-Baker, Patricia; Naroditsky, Boris S; Gudkov, Andrei V; Logunov, Denis Y; Gintsburg, Alexander L

    2016-01-01

    Binding of pattern recognition receptors (PRRs) by pathogen-associated molecular patterns (PAMPs) activates innate immune responses and contributes to development of adaptive immunity. Simultaneous stimulation of different types of PRRs can have synergistic immunostimulatory effects resulting in enhanced production of molecules that mediate innate immunity such as inflammatory cytokines, antimicrobial peptides, etc. Here, we evaluated the impact of combined stimulation of PRRs from different families on adaptive immunity by generating alum-based vaccine formulations with ovalbumin as a model antigen and the Toll-like receptor 4 (TLR4) agonist MPLA and the Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) agonist MDP adsorbed individually or together on the alum-ovalbumin particles. Multiple in vitro and in vivo readouts of immune system activation all showed that while individual PRR agonists increased the immunogenicity of vaccines compared to alum alone, the combination of both PRR agonists was significantly more effective. Combined stimulation of TLR4 and NOD2 results in a stronger and broader transcriptional response in THP-1 cells compared to individual PRR stimulation. Immunostimulatory composition containing both PRR agonists (MPLA and MDP) in the context of the alum-based ovalbumin vaccine also enhanced uptake of vaccine particles by bone marrow derived dendritic cells (BMDCs) and promoted maturation (up-regulation of expression of CD80, CD86, MHCII) and activation (production of cytokines) of BMDCs. Finally, immunization of mice with vaccine particles containing both PRR agonists resulted in enhanced cellular immunity as indicated by increased proliferation and activation (IFN-γ production) of splenic CD4+ and CD8+ T cells following in vitro restimulation with ovalbumin and enhanced humoral immunity as indicated by higher titers of ovalbumin-specific IgG antibodies. These results indicate that combined stimulation of TLR4 and NOD2

  17. Delaying discharge after the stimulus significantly decreases muscle activation thresholds with small impact on the selectivity: an in vivo study using TIME.

    PubMed

    Maciejasz, Paweł; Badia, Jordi; Boretius, Tim; Andreu, David; Stieglitz, Thomas; Jensen, Winnie; Navarro, Xavier; Guiraud, David

    2015-04-01

    The number of devices for electrical stimulation of nerve fibres implanted worldwide for medical applications is constantly increasing. Stimulation charge is one of the most important parameters of stimulation. High stimulation charge may cause tissue and electrode damage and also compromise the battery life of the electrical stimulators. Therefore, the objective of minimizing stimulation charge is an important issue. Delaying the second phase of biphasic stimulation waveform may decrease the charge required for fibre activation, but its impact on stimulation selectivity is not known. This information is particularly relevant when transverse intrafascicular multichannel electrode (TIME) is used, since it has been designed to provide for high selectivity. In this in vivo study, the rat sciatic nerve was electrically stimulated using monopolar and bipolar configurations with TIME. The results demonstrated that the inclusion of a 100-μs delay between the cathodic and the anodic phase of the stimulus allows to reduce charge requirements by around 30 %, while only slightly affecting stimulation selectivity. This study shows that adding a delay to the typical stimulation waveform significantly ([Formula: see text]) reduces the charge required for nerve fibres activation. Therefore, waveforms with the delayed discharge phase are more suitable for electrical stimulation of nerve fibres.

  18. The Activating NKG2C Receptor Is Significantly Reduced in NK Cells after Allogeneic Stem Cell Transplantation in Patients with Severe Graft-versus-Host Disease.

    PubMed

    Kordelas, Lambros; Steckel, Nina-Kristin; Horn, Peter A; Beelen, Dietrich W; Rebmann, Vera

    2016-10-27

    Natural killer (NK) cells play a central role in the innate immune system. In allogeneic stem cell transplantation (alloSCT), alloreactive NK cells derived by the graft are discussed to mediate the elimination of leukemic cells and dendritic cells in the patient and thereby to reduce the risk for leukemic relapses and graft-versus-host reactions. The alloreactivity of NK cells is determined by various receptors including the activating CD94/NKG2C and the inhibitory CD94/NKG2A receptors, which both recognize the non-classical human leukocyte antigen E (HLA-E). Here we analyze the contribution of these receptors to NK cell alloreactivity in 26 patients over the course of the first year after alloSCT due to acute myeloid leukemia, myelodysplastic syndrome and T cell Non-Hodgkin-Lymphoma. Our results show that NK cells expressing the activating CD94/NKG2C receptor are significantly reduced in patients after alloSCT with severe acute and chronic graft-versus-host disease (GvHD). Moreover, the ratio of CD94/NKG2C to CD94/NKG2A was reduced in patients with severe acute and chronic GvHD after receiving an HLA-mismatched graft. Collectively, these results provide evidence for the first time that CD94/NKG2C is involved in GvHD prevention.

  19. Very low amount of TiO2 on N-doped carbon nanotubes significantly improves oxygen reduction activity and stability of supported Pt nanoparticles.

    PubMed

    Zhao, Anqi; Masa, Justus; Xia, Wei

    2015-04-28

    Electrochemical corrosion is a major problem for carbon materials used in electrocatalysis. Highly dispersed TiO2 was deposited on O-functionalized and N-doped carbon nanotubes by chemical vapour deposition to tackle the carbon corrosion problem. Very low Ti loadings of about 1 wt% were applied to minimize the negative influence of TiO2 as a semiconductor on the high conductivity of carbon materials. Both N doping and TiO2 coating facilitate strong metal-support interactions and favour the formation of small Pt particles. N doping improved the intrinsic catalytic activity of the carbon support and enhanced the conductivity due to the removal of surface oxygen groups, while the negative effect of TiO2 on conductivity is counterbalanced by its promoting effect on metal-support interactions leading to enhanced overall catalytic performance. Pt/TiO2/NCNTs showed the highest ORR activity, and significantly outperformed Pt/NCNTs in electrochemical stability tests.

  20. Significant In Vivo Anti-Inflammatory Activity of Pytren4Q-Mn a Superoxide Dismutase 2 (SOD2) Mimetic Scorpiand-Like Mn (II) Complex

    PubMed Central

    Serena, Carolina; Calvo, Enrique; Clares, Mari Paz; Diaz, María Luisa; Chicote, Javier U.; Beltrán-Debon, Raúl; Fontova, Ramón; Rodriguez, Alejandro; García-España, Enrique; García-España, Antonio

    2015-01-01

    Background The clinical use of purified SOD enzymes has strong limitations due to their large molecular size, high production cost and immunogenicity. These limitations could be compensated by using instead synthetic SOD mimetic compounds of low molecular weight. Background/Methodology We have recently reported that two SOD mimetic compounds, the MnII complexes of the polyamines Pytren2Q and Pytren4Q, displayed high antioxidant activity in bacteria and yeast. Since frequently molecules with antioxidant properties or free-radical scavengers also have anti-inflammatory properties we have assessed the anti-inflammatory potential of Pytren2Q and Pytren4Q MnII complexes, in cultured macrophages and in a murine model of inflammation, by measuring the degree of protection they could provide against the cellular injury produced by lipopolisacharide, a bacterial endotoxin. Principal Findings In this report we show that the MnII complex of Pytren4Q but not that of Pytren2Q effectively protected human cultured THP-1 macrophages and whole mice from the inflammatory effects produced by LPS. These results obtained with two molecules that are isomers highlight the importance of gathering experimental data from animal models of disease in assessing the potential of candidate molecules. Conclusion/Significance The effective anti-inflammatory activity of the MnII complex of Pytren4Q in addition to its low toxicity, water solubility and ease of production would suggest it is worth taking into consideration for future pharmacological studies. PMID:25742129

  1. Tectonic activity as a significant source of crustal tetrafluoromethane emissions to the atmosphere: Observations in groundwaters along the San Andreas Fault

    NASA Astrophysics Data System (ADS)

    Deeds, Daniel A.; Kulongoski, Justin T.; Mühle, Jens; Weiss, Ray F.

    2015-02-01

    Tetrafluoromethane (CF4) concentrations were measured in 14 groundwater samples from the Cuyama Valley, Mil Potrero and Cuddy Valley aquifers along the Big Bend section of the San Andreas Fault System (SAFS) in California to assess whether tectonic activity in this region is a significant source of crustal CF4 to the atmosphere. Dissolved CF4 concentrations in all groundwater samples but one were elevated with respect to estimated recharge concentrations including entrainment of excess air during recharge (Cre; ∼30 fmol kg-1 H2O), indicating subsurface addition of CF4 to these groundwaters. Groundwaters in the Cuyama Valley contain small CF4 excesses (0.1-9 times Cre), which may be attributed to an in situ release from weathering and a minor addition of deep crustal CF4 introduced to the shallow groundwater through nearby faults. CF4 excesses in groundwaters within 200 m of the SAFS are larger (10-980 times Cre) and indicate the presence of a deep crustal flux of CF4 that is likely associated with the physical alteration of silicate minerals in the shear zone of the SAFS. Extrapolating CF4 flux rates observed in this study to the full extent of the SAFS (1300 km × 20-100 km) suggests that the SAFS potentially emits (0.3- 1) ×10-1 kg CF4 yr-1 to the Earth's surface. For comparison, the chemical weathering of ∼ 7.5 ×104km2 of granitic rock in California is estimated to release (0.019- 3.2) ×10-1 kg CF4 yr-1. Tectonic activity is likely an important, and potentially the dominant, driver of natural emissions of CF4 to the atmosphere. Variations in preindustrial atmospheric CF4 as observed in paleo-archives such as ice cores may therefore represent changes in both continental weathering and tectonic activity, including changes driven by variations in continental ice cover during glacial-interglacial transitions.

  2. Synchronization in time-varying networks

    NASA Astrophysics Data System (ADS)

    Kohar, Vivek; Ji, Peng; Choudhary, Anshul; Sinha, Sudeshna; Kurths, Jüergen

    2014-08-01

    We study the stability of the synchronized state in time-varying complex networks using the concept of basin stability, which is a nonlocal and nonlinear measure of stability that can be easily applied to high-dimensional systems [P. J. Menck, J. Heitzig, N. Marwan, and J. Kurths, Nature Phys. 9, 89 (2013), 10.1038/nphys2516]. The time-varying character is included by stochastically rewiring each link with the average frequency f. We find that the time taken to reach synchronization is lowered and the stability range of the synchronized state increases considerably in dynamic networks. Further we uncover that small-world networks are much more sensitive to link changes than random ones, with the time-varying character of the network having a significant effect at much lower rewiring frequencies. At very high rewiring frequencies, random networks perform better than small-world networks and the synchronized state is stable over a much wider window of coupling strengths. Lastly we show that the stability range of the synchronized state may be quite different for small and large perturbations, and so the linear stability analysis and the basin stability criterion provide complementary indicators of stability.

  3. Synchronization in time-varying networks.

    PubMed

    Kohar, Vivek; Ji, Peng; Choudhary, Anshul; Sinha, Sudeshna; Kurths, Jüergen

    2014-08-01

    We study the stability of the synchronized state in time-varying complex networks using the concept of basin stability, which is a nonlocal and nonlinear measure of stability that can be easily applied to high-dimensional systems [P. J. Menck, J. Heitzig, N. Marwan, and J. Kurths, Nature Phys. 9, 89 (2013)]. The time-varying character is included by stochastically rewiring each link with the average frequency f. We find that the time taken to reach synchronization is lowered and the stability range of the synchronized state increases considerably in dynamic networks. Further we uncover that small-world networks are much more sensitive to link changes than random ones, with the time-varying character of the network having a significant effect at much lower rewiring frequencies. At very high rewiring frequencies, random networks perform better than small-world networks and the synchronized state is stable over a much wider window of coupling strengths. Lastly we show that the stability range of the synchronized state may be quite different for small and large perturbations, and so the linear stability analysis and the basin stability criterion provide complementary indicators of stability.

  4. Dynamic Factor Analysis Models with Time-Varying Parameters

    ERIC Educational Resources Information Center

    Chow, Sy-Miin; Zu, Jiyun; Shifren, Kim; Zhang, Guangjian

    2011-01-01

    Dynamic factor analysis models with time-varying parameters offer a valuable tool for evaluating multivariate time series data with time-varying dynamics and/or measurement properties. We use the Dynamic Model of Activation proposed by Zautra and colleagues (Zautra, Potter, & Reich, 1997) as a motivating example to construct a dynamic factor…

  5. Significant and Sustained Antitumor Activity in Post-Docetaxel, Castration-Resistant Prostate Cancer With the CYP17 Inhibitor Abiraterone Acetate

    PubMed Central

    Reid, Alison H.M.; Attard, Gerhardt; Danila, Daniel C.; Oommen, Nikhil Babu; Olmos, David; Fong, Peter C.; Molife, L. Rhoda; Hunt, Joanne; Messiou, Christina; Parker, Christopher; Dearnaley, David; Swennenhuis, Joost F.; Terstappen, Leon W.M.M.; Lee, Gloria; Kheoh, Thian; Molina, Arturo; Ryan, Charles J.; Small, Eric; Scher, Howard I.; de Bono, Johann S.

    2010-01-01

    Purpose The principal objective of this trial was to evaluate the antitumor activity of abiraterone acetate, an oral, specific, irreversible inhibitor of CYP17 in docetaxel-treated patients with castration-resistant prostate cancer (CRPC). Patients and Methods In this multicenter, two-stage, phase II study, abiraterone acetate 1,000 mg was administered once daily continuously. The primary end point was achievement of a prostate-specific antigen (PSA) decline of ≥ 50% in at least seven of 35 patients. Per an attained phase II design, more than 35 patients could be enrolled if the primary end point was met. Secondary objectives included: PSA declines of ≥ 30% and ≥ 90%; rate of RECIST (Response Evaluation Criteria in Solid Tumors) responses and duration on study; time to PSA progression; safety and tolerability; and circulating tumor cell (CTC) enumeration. Results Docetaxel-treated patients with CRPC (N = 47) were enrolled. PSA declines of ≥ 30%, ≥ 50% and ≥ 90% were seen in 68% (32 of 47), 51% (24 of 47), and 15% (seven of 47) of patients, respectively. Partial responses (by RECIST) were reported in eight (27%) of 30 patients with measurable disease. Median time to PSA progression was 169 days (95% CI, 113 to 281 days). The median number of weeks on study was 24, and 12 (25.5%) of 47 patients remained on study ≥ 48 weeks. CTCs were enumerated in 34 patients; 27 (79%) of 34 patients had at least five CTCs at baseline. Eleven (41%) of 27 patients had a decline from at least five to less than 5 CTCs, and 18 (67%) of 27 had a ≥ 30% decline in CTCs after starting treatment with abiraterone acetate. Abiraterone acetate was well tolerated. Conclusion Abiraterone acetate has significant antitumor activity in post-docetaxel patients with CRPC. Randomized, phase III trials of abiraterone acetate are underway to define the future role of this agent. PMID:20159823

  6. Tectonic activity as a significant source of crustal tetrafluoromethane emissions to the atmosphere: observations in groundwaters along the San Andreas Fault

    USGS Publications Warehouse

    Deeds, Daniel A.; Kulongoski, Justin T.; Muhle, Jens; Weiss, Ray F.

    2015-01-01

    Tetrafluoromethane (CF4) concentrations were measured in 14 groundwater samples from the Cuyama Valley, Mil Potrero and Cuddy Valley aquifers along the Big Bend section of the San Andreas Fault System (SAFS) in California to assess whether tectonic activity in this region is a significant source of crustal CF4 to the atmosphere. Dissolved CF4 concentrations in all groundwater samples but one were elevated with respect to estimated recharge concentrations including entrainment of excess air during recharge (CreCre; ∼30 fmol kg−1 H2O), indicating subsurface addition of CF4 to these groundwaters. Groundwaters in the Cuyama Valley contain small CF4 excesses (0.1–9 times CreCre), which may be attributed to an in situ release from weathering and a minor addition of deep crustal CF4 introduced to the shallow groundwater through nearby faults. CF4 excesses in groundwaters within 200 m of the SAFS are larger (10–980 times CreCre) and indicate the presence of a deep crustal flux of CF4 that is likely associated with the physical alteration of silicate minerals in the shear zone of the SAFS. Extrapolating CF4 flux rates observed in this study to the full extent of the SAFS (1300 km × 20–100 km) suggests that the SAFS potentially emits (0.3–1)×10−1 kg(0.3–1)×10−1 kg CF4 yr−1 to the Earth's surface. For comparison, the chemical weathering of ∼7.5×104 km2∼7.5×104 km2 of granitic rock in California is estimated to release (0.019–3.2)×10−1 kg(0.019–3.2)×10−1 kg CF4 yr−1. Tectonic activity is likely an important, and potentially the dominant, driver of natural emissions of CF4 to the atmosphere. Variations in preindustrial atmospheric CF4 as observed in paleo-archives such as ice cores may therefore represent changes in both continental weathering and tectonic activity, including changes driven by variations in continental ice cover during glacial–interglacial transitions.

  7. Stable Inversion for Nonlinear Nonminimum-Phase Time Varying Systems

    NASA Technical Reports Server (NTRS)

    Devasia, S.; Paden, B.

    1998-01-01

    In this paper, we extend stable inversion to nonlinear time-varying systems and study computational issues; the technique is applicable to minimum-phase as well as nonminimum-phase systems. The inversion technique is new, even in the linear time-varying case, and relies on partitioning (the dichotomic split of) the linearized system dynamics into time-varying, stable, and unstable, submanifolds. This dichotomic split is used to build time-varying filters which are, in turn, the basis of a contraction used to find a bounded inverse input-state trajectory. Finding the inverse input-state trajectory allows the development or exact-output tracking controllers. The method is local to the time-varying trajectory and requires that the internal dynamics vary slowly; however, the method represents a significant advance relative to presently available tracking controllers. Present techniques are restricted to time-invariant nonlinear systems and, in the general case, track only asymptotically.

  8. The prognostic significance of the Birmingham Vasculitis Activity Score (BVAS) with systemic vasculitis patients transferred to the intensive care unit (ICU)

    PubMed Central

    Biscetti, Federico; Carbonella, Angela; Parisi, Federico; Bosello, Silvia Laura; Schiavon, Franco; Padoan, Roberto; Gremese, Elisa; Ferraccioli, Gianfranco

    2016-01-01

    Abstract Systemic vasculitides represent a heterogeneous group of diseases that share clinical features including respiratory distress, renal dysfunction, and neurologic disorders. These diseases may often cause life-threatening complications requiring admission to an intensive care unit (ICU). The aim of the study was to evaluate the validity and responsiveness of Birmingham Vasculitis Activity Score (BVAS) score to predict survival in patients with systemic vasculitides admitted to ICU. A retrospective study was carried out from 2004 to 2014 in 18 patients with systemic vasculitis admitted to 2 different Rheumatology divisions and transferred to ICU due to clinical worsening, with a length of stay beyond 24 hours. We found that ICU mortality was significantly associated with higher BVAS scores performed in the ward (P = 0.01) and at the admission in ICU (P = 0.01), regardless of the value of Acute Physiology And Chronic Health Evaluation (APACHE II) scores (P = 0.50). We used receiver-operator characteristic (ROC) curve analysis to evaluate the possible cutoff value for the BVAS in the ward and in ICU and we found that a BVAS > 8 in the ward and that a BVAS > 10 in ICU might be a useful tool to predict in-ICU mortality. BVAS appears to be an excellent tool for assessing ICU mortality risk of systemic vasculitides patients admitted to specialty departments. Our experience has shown that performing the assessment at admission to the ward is more important than determining the evaluation before the clinical aggravation causing the transfer to ICU. PMID:27902615

  9. The crystal structure of rice (Oryza sativa L.) Os4BGlu12, an oligosaccharide and tuberonic acid glucoside-hydrolyzing β-glucosidase with significant thioglucohydrolase activity.

    PubMed

    Sansenya, Sompong; Opassiri, Rodjana; Kuaprasert, Buabarn; Chen, Chun-Jung; Cairns, James R Ketudat

    2011-06-01

    Rice Os4BGlu12, a glycoside hydrolase family 1 (GH1) β-glucosidase, hydrolyzes β-(1,4)-linked oligosaccharides of 3-6 glucosyl residues and the β-(1,3)-linked disaccharide laminaribiose, as well as certain glycosides. The crystal structures of apo Os4BGlu12, and its complexes with 2,4-dinitrophenyl-2-deoxyl-2-fluoroglucoside (DNP2FG) and 2-deoxy-2-fluoroglucose (G2F) were solved at 2.50, 2.45 and 2.40Å resolution, respectively. The overall structure of rice Os4BGlu12 is typical of GH1 enzymes, but it contains an extra disulfide bridge in the loop B region. The glucose ring of the G2F in the covalent intermediate was found in a (4)C(1) chair conformation, while that of the noncovalently bound DNP2FG had a (1)S(3) skew boat, consistent with hydrolysis via a (4)H(3) half-chair transition state. The position of the catalytic nucleophile (Glu393) in the G2F structure was more similar to that of the Sinapsis alba myrosinase G2F complex than to that in covalent intermediates of other O-glucosidases, such as rice Os3BGlu6 and Os3BGlu7 β-glucosidases. This correlated with a significant thioglucosidase activity for Os4BGlu12, although with 200- to 1200-fold lower k(cat)/K(m) values for S-glucosides than the comparable O-glucosides, while hydrolysis of S-glucosides was undetectable for Os3BGlu6 and Os3BGlu7.

  10. Transient, spatially varied groundwater recharge modeling

    NASA Astrophysics Data System (ADS)

    Assefa, Kibreab Amare; Woodbury, Allan D.

    2013-08-01

    The objective of this work is to integrate field data and modeling tools in producing temporally and spatially varying groundwater recharge in a pilot watershed in North Okanagan, Canada. The recharge modeling is undertaken by using the Richards equation based finite element code (HYDRUS-1D), ArcGIS™, ROSETTA, in situ observations of soil temperature and soil moisture, and a long-term gridded climate data. The public version of HYDUS-1D and another version with detailed freezing and thawing module are first used to simulate soil temperature, snow pack, and soil moisture over a one year experimental period. Statistical analysis of the results show both versions of HYDRUS-1D reproduce observed variables to the same degree. After evaluating model performance using field data and ROSETTA derived soil hydraulic parameters, the HYDRUS-1D code is coupled with ArcGIS™ to produce spatially and temporally varying recharge maps throughout the Deep Creek watershed. Temporal and spatial analysis of 25 years daily recharge results at various representative points across the study watershed reveal significant temporal and spatial variations; average recharge estimated at 77.8 ± 50.8 mm/year. Previous studies in the Okanagan Basin used Hydrologic Evaluation of Landfill Performance without any attempt of model performance evaluation, notwithstanding its inherent limitations. Thus, climate change impact results from this previous study and similar others, such as Jyrkama and Sykes (2007), need to be interpreted with caution.

  11. Lycorine, the Main Phenanthridine Amaryllidaceae Alkaloid, Exhibits Significant Anti-Tumor Activity in Cancer Cells that Display Resistance to Proapoptotic Stimuli: an Investigation of Structure-Activity Relationship and Mechanistic Insight

    PubMed Central

    Lamoral-Theys, Delphine; Andolfi, Anna; Van Goietsenoven, Gwendoline; Cimmino, Alessio; Le Calvé, Benjamin; Wauthoz, Nathalie; Mégalizzi, Véronique; Gras, Thierry; Bruyère, Céline; Dubois, Jacques; Mathieu, Véronique; Kornienko, Alexander; Kiss, Robert; Evidente, Antonio

    2011-01-01

    Twenty-two lycorine-related compounds were investigated for in vitro anti-tumor activity using four cancer cell lines displaying different levels of resistance to pro-apoptotic stimuli and two cancer cell lines sensitive to pro-apoptotic stimuli. Lycorine and six of its congeners exhibited potency in the single-digit micromolar range, while no compound appeared more active than lycorine. Lycorine also displayed the highest potential (in vitro) therapeutic ratio, being at least 15 times more active against cancer than normal cells. Our studies also showed that lycorine exerts its in vitro anti-tumor activity through cytostatic rather than cytotoxic effects. Furthermore, lycorine provided significant therapeutic benefit in mice bearing brain grafts of the B16F10 melanoma model at non-toxic doses. Thus, the results of the current study make lycorine an excellent lead for the generation of compounds able to combat cancers, which are naturally resistant to pro-apoptotic stimuli, such as glioblastoma, melanoma, non-small-cell-lung cancers, metastatic cancers, among others. PMID:19788245

  12. Lycorine, the main phenanthridine Amaryllidaceae alkaloid, exhibits significant antitumor activity in cancer cells that display resistance to proapoptotic stimuli: an investigation of structure-activity relationship and mechanistic insight.

    PubMed

    Lamoral-Theys, Delphine; Andolfi, Anna; Van Goietsenoven, Gwendoline; Cimmino, Alessio; Le Calvé, Benjamin; Wauthoz, Nathalie; Mégalizzi, Véronique; Gras, Thierry; Bruyère, Céline; Dubois, Jacques; Mathieu, Véronique; Kornienko, Alexander; Kiss, Robert; Evidente, Antonio

    2009-10-22

    Twenty-two lycorine-related compounds were investigated for in vitro antitumor activity using four cancer cell lines displaying different levels of resistance to proapoptotic stimuli and two cancer cell lines sensitive to proapoptotic stimuli. Lycorine and six of its congeners exhibited potency in the single-digit micromolar range, while no compound appeared more active than lycorine. Lycorine also displayed the highest potential (in vitro) therapeutic ratio, being at least 15 times more active against cancer than normal cells. Our studies also showed that lycorine exerts its in vitro antitumor activity through cytostatic rather than cytotoxic effects. Furthermore, lycorine provided significant therapeutic benefit in mice bearing brain grafts of the B16F10 melanoma model at nontoxic doses. Thus, the results of the current study make lycorine an excellent lead for the generation of compounds able to combat cancers, which are naturally resistant to proapoptotic stimuli, such as glioblastoma, melanoma, non-small-cell-lung cancers, and metastatic cancers, among others.

  13. Experimentally-induced immune activation in natural hosts of SIV induces significant increases in viral replication and CD4+ T cell depletion

    SciTech Connect

    Ribeiro, Ruy M

    2008-01-01

    Chronically SIVagm-infected African green monkeys (AGMs) have a remarkably stable non-pathogenic disease course, with levels of immune activation in chronic SIVagm infection similar to those observed in uninfected monkeys and stable viral loads (VLs) for long periods of time. In vivo administration of lipopolysaccharide (LPS) or an IL-2/diphtheria toxin fusion protein (Ontak) to chronically SIVagm-infected AGMs triggered increases in immune activation and subsequently of viral replication and depletion of intestinal CD4{sup +} T cells. Our study indicates that circulating microbial products can increase viral replication by inducing immune activation and increasing the number of viral target cells, thus demonstrating that immune activation and T cell prolifeation are key factors in AIDS pathogenesis.

  14. Inverse agonism and its therapeutic significance

    PubMed Central

    Khilnani, Gurudas; Khilnani, Ajeet Kumar

    2011-01-01

    A large number of G-protein-coupled receptors (GPCRs) show varying degrees of basal or constitutive activity. This constitutive activity is usually minimal in natural receptors but is markedly observed in wild type and mutated (naturally or induced) receptors. According to conventional two-state drug receptor interaction model, binding of a ligand may initiate activity (agonist with varying degrees of positive intrinsic activity) or prevent the effect of an agonist (antagonist with zero intrinsic activity). Inverse agonists bind with the constitutively active receptors, stabilize them, and thus reduce the activity (negative intrinsic activity). Receptors of many classes (α-and β-adrenergic, histaminergic, GABAergic, serotoninergic, opiate, and angiotensin receptors) have shown basal activity in suitable in vitro models. Several drugs that have been conventionally classified as antagonists (β-blockers, antihistaminics) have shown inverse agonist effects on corresponding constitutively active receptors. Nearly all H1 and H2 antihistaminics (antagonists) have been shown to be inverse agonists. Among the β-blockers, carvedilol and bucindolol demonstrate low level of inverse agonism as compared to propranolol and nadolol. Several antipsychotic drugs (D2 receptors antagonist), antihypertensive (AT1 receptor antagonists), antiserotoninergic drugs and opioid antagonists have significant inverse agonistic activity that contributes partly or wholly to their therapeutic value. Inverse agonism may also help explain the underlying mechanism of beneficial effects of carvedilol in congestive failure, naloxone-induced withdrawal syndrome in opioid dependence, clozapine in psychosis, and candesartan in cardiac hypertrophy. Understanding inverse agonisms has paved a way for newer drug development. It is now possible to develop agents, which have only desired therapeutic value and are devoid of unwanted adverse effect. Pimavanserin (ACP-103), a highly selective 5-HT2A inverse

  15. A bis-malonic acid fullerene derivative significantly suppressed IL-33-induced IL-6 expression by inhibiting NF-κB activation.

    PubMed

    Funakoshi-Tago, Megumi; Miyagawa, Yurika; Ueda, Fumihito; Mashino, Tadahiko; Moriwaki, Yasuhiro; Tago, Kenji; Kasahara, Tadashi; Tamura, Hiroomi

    2016-11-01

    IL-33 functions as a ligand for ST2L, which is mainly expressed in immune cells, including mast cells. IL-33 is a potent inducer of pro-inflammatory cytokines, such as IL-6, and has been implicated in the pathogenesis of allergic inflammatory diseases. Therefore, IL-33 has recently been attracting attention as a new target for the treatment of inflammatory diseases. In the present study, we demonstrated that a water-soluble bis-malonic acid fullerene derivative (C60-dicyclopropane-1,1,1',1'-tetracarboxylic acid) markedly diminished the IL-33-induced expression of IL-6 in bone marrow-derived mast cells (BMMC). The bis-malonic acid fullerene derivative suppressed the canonical signaling steps required for NF-κB activation such as the degradation of IκBα and nuclear translocation of NF-κB by directly inhibiting the IL-33-induced IKK activation. Although p38 and JNK also contributed to IL-33-induced expression of IL-6, the bis-malonic acid fullerene derivative did not affect their activation. Furthermore, the bis-malonic acid fullerene derivative had no effect on the NF-κB activation pathway induced by TNFα and IL-1. These results suggest that the bis-malonic fullerene derivative has potential as a specific drug for the treatment of IL-33-induced inflammatory diseases by specifically inhibiting the NF-κB activation pathway.

  16. The Ratio of a Urinary Tobacco-Specific Lung Carcinogen Metabolite to Cotinine is Significantly Higher in Passive than in Active Smokers

    PubMed Central

    Vogel, Rachel Isaksson; Carmella, Steven G.; Stepanov, Irina; Hatsukami, Dorothy K.; Hecht, Stephen S.

    2011-01-01

    4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol plus its glucuronides (total NNAL), metabolites of the lung carcinogen NNK, and total cotinine, metabolites of nicotine, are biomarkers of active and passive cigarette smoking. We calculated the total NNAL: total cotinine (× 103) ratio in 408 passive (infants, children, adults) and 1088 active smokers. The weighted averages were 0.73 (95% CI 0.71, 0.76) for passive smokers and 0.07 (0.06, 0.08) for active smokers (p<0.0001). These results demonstrate that cotinine measurements may underestimate exposure of passive smokers to the lung carcinogen NNK in secondhand cigarette smoke. The total NNAL:total cotinine (× 103) ratio may provide an improved biomarker for evaluating the health effects of passive smoking. PMID:21812592

  17. Targeting CXCR1/2 Significantly Reduces Breast Cancer Stem Cell Activity and Increases the Efficacy of Inhibiting HER2 via HER2-dependent and -independent Mechanisms

    PubMed Central

    Singh, Jagdeep K.; Farnie, Gillian; Bundred, Nigel J.; Simões, Bruno M; Shergill, Amrita; Landberg, Göran; Howell, Sacha; Clarke, Robert B.

    2012-01-01

    Purpose Breast cancer stem-like cells (CSCs) are an important therapeutic target as they are predicted to be responsible for tumour initiation, maintenance and metastases. Interleukin-8 (IL-8) is upregulated in breast cancer and associated with poor prognosis. Breast cancer cell line studies indicate that IL-8 via its cognate receptors, CXCR1 and CXCR2, is important in regulating breast CSC activity. We investigated the role of IL-8 in the regulation of CSC activity using patient-derived breast cancers and determined the potential benefit of combining CXCR1/2 inhibition with HER2-targeted therapy. Experimental design CSC activity of metastatic and invasive human breast cancers (n=19) was assessed ex vivo using the mammosphere colony forming assay. Results Metastatic fluid IL-8 level correlated directly with mammosphere formation (r=0.652; P<0.05; n=10). Recombinant IL-8 directly increased mammosphere formation/self-renewal in metastatic and invasive breast cancers (n=17). IL-8 induced activation of EGFR/HER2 and downstream signalling pathways and effects were abrogated by inhibition of SRC, EGFR/HER2, PI3K or MEK. Furthermore, lapatinib inhibited the mammosphere-promoting effect of IL-8 in both HER2-positive and negative patient-derived cancers. CXCR1/2 inhibition also blocked the effect of IL-8 on mammosphere formation and added to the efficacy of lapatinib in HER2-positive cancers. Conclusions These studies establish a role for IL-8 in the regulation of patient-derived breast CSC activity and demonstrate that IL-8/CXCR1/2 signalling is partly mediated via a novel SRC and EGFR/HER2-dependent pathway. Combining CXCR1/2 inhibitors with current HER2-targeted therapies has potential as an effective therapeutic strategy to reduce CSC activity in breast cancer and improve the survival of HER2-positive patients. PMID:23149820

  18. Overexpression of an exotic thermotolerant β-glucosidase in trichoderma reesei and its significant increase in cellulolytic activity and saccharification of barley straw

    PubMed Central

    2012-01-01

    Background Trichoderma reesei is a widely used industrial strain for cellulase production, but its low yield of β-glucosidase has prevented its industrial value. In the hydrolysis process of cellulolytic residues by T. reesei, a disaccharide known as cellobiose is produced and accumulates, which inhibits further cellulases production. This problem can be solved by adding β-glucosidase, which hydrolyzes cellobiose to glucose for fermentation. It is, therefore, of high vvalue to construct T. reesei strains which can produce sufficient β-glucosidase and other hydrolytic enzymes, especially when those enzymes are capable of tolerating extreme conditions such as high temperature and acidic or alkali pH. Results We successfully engineered a thermostable β-glucosidase gene from the fungus Periconia sp. into the genome of T. reesei QM9414 strain. The engineered T. reesei strain showed about 10.5-fold (23.9 IU/mg) higher β-glucosidase activity compared to the parent strain (2.2 IU/mg) after 24 h of incubation. The transformants also showed very high total cellulase activity (about 39.0 FPU/mg) at 24 h of incubation whereas the parent strain almost did not show any total cellulase activity at 24 h of incubation. The recombinant β-glucosidase showed to be thermotolerant and remains fully active after two-hour incubation at temperatures as high as 60°C. Additionally, it showed to be active at a wide pH range and maintains about 88% of its maximal activity after four-hour incubation at 25°C in a pH range from 3.0 to 9.0. Enzymatic hydrolysis assay using untreated, NaOH, or Organosolv pretreated barley straw as well as microcrystalline cellulose showed that the transformed T. reesei strains released more reducing sugars compared to the parental strain. Conclusions The recombinant T. reesei overexpressing Periconia sp. β-glucosidase in this study showed higher β-glucosidase and total cellulase activities within a shorter incubation time (24 h) as well as

  19. Addition of an N-terminal epitope tag significantly increases the activity of plant fatty acid desaturases expressed in yeast cells

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Saccharomyces cerevisiae shows great potential for development of bioreactor systems geared towards the production of high-value lipids such as polyunsaturated omega-3 fatty acids, the yields of which are largely dependent on the activity of ectopically-expressed enzymes. Here we show that the addit...

  20. [The significance of activities in the Imperial Orthodox Palestine Society for progression of medicine in the Middle East (to the 130th anniversary of foundation)].

    PubMed

    Gorelova, L Ye; Afanasiyeva, Ye A

    2012-01-01

    The article deals with the history of foundation of the Imperial Orthodox Palestine Society in Jerusalem and its input into progression of medicine in the Middle east. The medical activity of Russian physicians in medical institutions of the Society is reflected too.

  1. Partial construction of apoptotic pathway in PBMC obtained from active SLE patients and the significance of plasma TNF-alpha on this pathway.

    PubMed

    Pitidhammabhorn, Dhanesh; Kantachuvesiri, Surasak; Totemchokchyakarn, Kitti; Kitiyanant, Yindee; Ubol, Sukathida

    2006-09-01

    Systemic lupus erythematosus (SLE) is a complex autoimmune disorder that affects various organs and systems. Increased apoptosis, together with defects in the uptake of apoptotic bodies, are thought to have a pathogenic role in SLE. By detection of chromatin condensation, 30% of apoptosis was detected in peripheral blood mononuclear cells (PBMC) from Thai patients with active SLE. Therefore, understanding of the molecular processes in PBMC apoptosis may allow us to gain insight into pathophysiology of SLE. Thus, genes involved in the apoptosis of PBMC from these patients were investigated ex vivo by cDNA array analysis. Seventeen apoptosis-related genes were stimulated in active SLE, more than twofold higher than in inactive SLE. These genes are classified into six groups, namely death receptors, death ligands, caspases, bcl-family, and neutral proteases and genes involved in endoplasmic reticulum stress-mediated apoptosis, such as caspase-4 and GADD153. Among those stimulated genes, tumor necrosis factor (TNF) and the TNF-receptor family were drastically up-regulated 60- and 19-fold higher than in healthy controls, respectively. Moreover, the degree of apoptosis correlated with the level of TNF-alpha in plasma, suggesting that the TNF family plays a role in the induction of apoptosis in SLE. To verify this hypothesis, PBMC from healthy individuals were treated with plasma from active SLE patients in the presence or absence of etanercept, a TNF inhibitor. In the presence of etanercept, active SLE plasma reduced the level of apoptosis to 26.43%. In conclusion, massive apoptotic death of PBMC occurred during the active stage of SLE. The molecular pathway of SLE-PBMC apoptosis was mediated at least via TNF/TNFR signaling pathway, which was confirmed by functional test of TNF-alpha in SLE patients' plasma.

  2. Varying electric charge in multiscale spacetimes

    NASA Astrophysics Data System (ADS)

    Calcagni, Gianluca; Magueijo, João; Fernández, David Rodríguez

    2014-01-01

    We derive the covariant equations of motion for Maxwell field theory and electrodynamics in multiscale spacetimes with weighted Laplacian. An effective spacetime-dependent electric charge of geometric origin naturally emerges from the theory, thus giving rise to a varying fine-structure constant. The theory is compared with other varying-coupling models, such as those with a varying electric charge or varying speed of light. The theory is also confronted with cosmological observations, which can place constraints on the characteristic scales in the multifractional measure. We note that the model considered here is fundamentally different from those previously proposed in the literature, either of the varying-e or varying-c persuasion.

  3. Variation in cellular glutathione peroxidase activity in lens epithelial cells, transgenics and knockouts does not significantly change the response to H2O2 stress.

    PubMed

    Spector, A; Yang, Y; Ho, Y S; Magnenat, J L; Wang, R R; Ma, W; Li, W C

    1996-05-01

    This investigation examines the contribution of glutathione peroxidase (GSHPx-1) in degrading H2O2 in lens preparations. Rabbit (N/N1003A) and normal and GSHPx-1 transfected mouse (alpha TN4-1) lens epithelial cell lines and normal and GSHPx-1 transgenic and knockout mouse lenses were utilized. GSHPx-1 activity in the cell lines was increased from two-fold to about four-fold, in the lenses from transgenics more than four-fold and the lenses from knockouts had less than 3% of normal GSHPx-1 activity. The transgenic and knockout mice as well as their lenses appeared normal for up to 3 to 4 months, the longest period of observation. The preparations were subjected to oxidative stress by placing them either in a medium containing 120 or 300 microM H2O2 or utilizing photochemical stress where the H2O2 levels normally rise to about 100 microM over a few hours in the presence of a normal lens. With all preparations, it was found that either markedly increasing or eliminating GSHPx-1 activity had only a small effect on the system's ability to metabolize H2O2, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), an inhibitor of GSSG reductase (GSSG Red) and 3-aminotriazole (3-AT), an inhibitor of catalase, also had little effect. However, the addition of both inhibitors caused a marked decrease in H2O2 degradation. Examination of the distribution of GSHPx-1 in the lens indicated that the activity per milligram of protein was evenly distributed between the epithelium and the remainder of the lens in the normal lens and was about 1.7-fold greater in the epithelium of transgenic lenses than in the remainder of the lens. Surprisingly, the distribution of GSSG Red was quite different with eight- to ten-fold more activity in the epithelium. Catalase was also found to be concentrated in the epithelium. With H2O2 exposure, a rapid loss of non-protein thiol (NP-thiol) was found in cell cultures and in the epithelia of cultured lenses. However, the remainder of the lens showed little change

  4. Evolutionary Significance of an Algal Gene Encoding an [FeFe]-Hydrogenase with F-Domain Homology and Hydrogenase Activity in Chlorella Variabilis NC64A

    SciTech Connect

    Meuser, J. E.; Boyd, E. S.; Ananyev, G.; Karns, D.; Radakovits, R.; Murthy, U. M. N.; Ghirardi, M. L.; Dismukes, G. C.; Peters, J. W.; Posewitz, M. C.

    2011-10-01

    [FeFe]-hydrogenases (HYDA) link the production of molecular H{sub 2} to anaerobic metabolism in many green algae. Similar to Chlamydomonas reinhardtii, Chlorella variabilis NC64A (Trebouxiophyceae, Chlorophyta) exhibits [FeFe]-hydrogenase (HYDA) activity during anoxia. In contrast to C. reinhardtii and other chlorophycean algae, which contain hydrogenases with only the HYDA active site (H-cluster), C. variabilis NC64A is the only known green alga containing HYDA genes encoding accessory FeS cluster-binding domains (F-cluster). cDNA sequencing confirmed the presence of F-cluster HYDA1 mRNA transcripts, and identified deviations from the in silico splicing models. We show that HYDA activity in C. variabilis NC64A is coupled to anoxic photosynthetic electron transport (PSII linked, as well as PSII-independent) and dark fermentation. We also show that the in vivo H{sub 2}-photoproduction activity observed is as O2 sensitive as in C. reinhardtii. The two C. variabilis NC64A HYDA sequences are similar to homologs found in more deeply branching bacteria (Thermotogales), diatoms, and heterotrophic flagellates, suggesting that an F-cluster HYDA is the ancestral enzyme in algae. Phylogenetic analysis indicates that the algal HYDA H-cluster domains are monophyletic, suggesting that they share a common origin, and evolved from a single ancestral F-cluster HYDA. Furthermore, phylogenetic reconstruction indicates that the multiple algal HYDA paralogs are the result of gene duplication events that occurred independently within each algal lineage. Collectively, comparative genomic, physiological, and phylogenetic analyses of the C. variabilis NC64A hydrogenase has provided new insights into the molecular evolution and diversity of algal [FeFe]-hydrogenases.

  5. MAPK-ERK activation in kidney of male rats chronically fed ochratoxin A at a dose causing a significant incidence of renal carcinoma

    SciTech Connect

    Marin-Kuan, M. Nestler, S.; Verguet, C.; Bezencon, C.; Piguet, D.; Delatour, T.; Mantle, P.; Cavin, C.; Schilter, B.

    2007-10-15

    Kidney samples of male Fischer 344 (F-344) rats fed a carcinogenic dose of OTA over 7 days, 21 days and 12 months were analysed for various cell signalling proteins known to be potentially involved in chemical carcinogenicity. OTA was found to increase the phosphorylation of atypical-PKC. This was correlated with a selective downstream activation of the MAP-kinase extracellular regulated kinases isoforms 1 and 2 (ERK1/2) and of their substrates ELK1/2 and p90RSK. Moreover, analysis of effectors acting upstream of PKC indicated a possible mobilisation of the insulin-like growth factor-1 receptor (lGFr) and phosphoinositide-dependent kinase-1 (PDK1) system. An increased histone deacetylase (HDAC) enzymatic activity associated with enhanced HDAC3 protein expression was also observed. These findings are potentially relevant with respect to the understanding of OTA nephrocarcinogenicity. HDAC-induced gene silencing has previously been shown to play a role in tumour development. Furthermore, PKC and the MEK-ERK MAP-kinase pathways are known to play important roles in cell proliferation, cell survival, anti-apoptotic activity and renal cancer development.

  6. [16S rDNA diversity analysis of 30 Streptomycetes isolates displaying significant cytotoxic activity against B16 cell from near-shore sediments of Hainan Island].

    PubMed

    Yan, Li-Ping; Hong, Kui; Hu, Shen-cai; Liu, Li-hua

    2005-04-01

    A total of 354 isolates of actinomycetes, of which 76 were detected cytotoxic activity was isolated from near-shore marine samples collected at Wenchang mangrove, DanZhou harbor and YanPu harbor. Four isolation methods were employed, which are SDS pretreatment, phenol pretreatment, heating pretreatment and potassium dichromate selection culture, and media such as'Yeast extract-Malt extract (YE), Glucose-Asprine (GA), Starch-Casin (SC), Starch-KNO3 (Gause) were used. It was showed that heating pretreatment and potassium dichromate selection culture were more considerable methods for extensive isolation of actinomycetes. Medium YE and Gause showed best results in both the total number of actinomycetes and the number of active isolates against tumor cell B16. The genotypic diversity of 30 strains of Streptomycetes possessing strong cytotoxic activity against B16 cell (ID50 > or =200) was analyzed by 16S ARDRA, which resulted in 17 RFLP types, and indicated relatively rich genotypic diversity among these Streptomycetes. 16S rDNA sequence analysis of three strains, 050642, 060386 and 060524 (ID50 > or = 1200) further confirmed that they all belong to Streptomyces genus and strain 050642 was suggested a novel Streptomyces. Spp with the highest similarity of 95% to Streptomyces cattleya.

  7. The time-course of hindbrain neuronal activity varies according to location during either intraperitoneal or subcutaneous tumor growth in rats: single Fos and dual Fos/dopamine β-hydroxylase immunohistochemistry.

    PubMed

    Lackovicova, Lubica; Gaykema, Ronald P; Banovska, Lucia; Kiss, Alexander; Goehler, Lisa E; Mravec, Boris

    2013-07-15

    Neuronal activity in the nucleus of the solitary tract, ventrolateral medulla, area postrema, and parabrachial nucleus was studied in rats with intraperitoneal or subcutaneous tumors on the 7th, 14th, 21st, and 28th day after injection of fibrosarcoma tumor cells. We found that the number of Fos and dopamine β-hydroxylase immunopositive neurons differs between animals with intraperitoneal and subcutaneous tumors and also between tumor-bearing rats at different times following injection. Our data indicate that responses of the brainstem structures to peripheral tumor growth depend on the localization as well as the stage of the tumor growth.

  8. Significance of postgrowth processing of ZnO nanostructures on antibacterial activity against gram-positive and gram-negative bacteria

    PubMed Central

    Mehmood, Shahid; Rehman, Malik A; Ismail, Hammad; Mirza, Bushra; Bhatti, Arshad S

    2015-01-01

    In this work, we highlighted the effect of surface modifications of one-dimensional (1D) ZnO nanostructures (NSs) grown by the vapor–solid mechanism on their antibacterial activity. Two sets of ZnO NSs were modified separately – one set was modified by annealing in an Ar environment, and the second set was modified in O2 plasma. Annealing in Ar below 800°C resulted in a compressed lattice, which was due to removal of Zn interstitials and increased O vacancies. Annealing above 1,000°C caused the formation of a new prominent phase, Zn2SiO4. Plasma oxidation of the ZnO NSs caused an expansion in the lattice due to the removal of O vacancies and incorporation of excess O. Photoluminescence (PL) spectroscopy was employed for the quantification of defects associated with Zn and O in the as-grown and processed ZnO NS. Two distinct bands were observed, one in the ultraviolet (UV) region, due to interband transitions, and other in the visible region, due to defects associated with Zn and O. PL confirmed the surface modification of ZnO NS, as substantial decrease in intensities of visible band was observed. Antibacterial activity of the modified ZnO NSs demonstrated that the surface modifications by Ar annealing limited the antibacterial characteristics of ZnO NS against Staphylococcus aureus. However, ZnO NSs annealed at 1,000°C or higher showed a remarkable antibacterial activity against Escherichia coli. O2 plasma–treated NS showed appreciable antibacterial activity against both E. coli and S. aureus. The minimum inhibition concentration was determined to be 0.5 mg/mL and 1 mg/mL for Ar-annealed and plasma-oxidized ZnO NS, respectively. It was thus proved that the O content at the surface of the ZnO NS was crucial to tune the antibacterial activity against both selected gram-negative (E. coli) and gram-positive (S. aureus) bacterial species. PMID:26213466

  9. Increased levels of IL-6 in the cerebrospinal fluid of patients with chronic schizophrenia — significance for activation of the kynurenine pathway

    PubMed Central

    Schwieler, Lilly; Larsson, Markus K.; Skogh, Elisabeth; Kegel, Magdalena E.; Orhan, Funda; Abdelmoaty, Sally; Finn, Anja; Bhat, Maria; Samuelsson, Martin; Lundberg, Kristina; Dahl, Marja-Liisa; Sellgren, Carl; Schuppe-Koistinen, Ina; Svensson, Camilla I.; Erhardt, Sophie; Engberg, Göran

    2015-01-01

    Background Accumulating evidence indicates that schizophrenia is associated with brain immune activation. While a number of reports suggest increased cytokine levels in patients with schizophrenia, many of these studies have been limited by their focus on peripheral cytokines or confounded by various antipsychotic treatments. Here, well-characterized patients with schizophrenia, all receiving olanzapine treatment, and healthy volunteers were analyzed with regard to cerebrospinal fluid (CSF) levels of cytokines. We correlated the CSF cytokine levels to previously analyzed metabolites of the kynurenine (KYN) pathway. Methods We analyzed the CSF from patients and controls using electrochemiluminescence detection with regard to cytokines. Cell culture media from human cortical astrocytes were analyzed for KYN and kynurenic acid (KYNA) using high-pressure liquid chromatography or liquid chromatography/mass spectrometry. Results We included 23 patients and 37 controls in our study. Patients with schizophrenia had increased CSF levels of interleukin (IL)-6 compared with healthy volunteers. In patients, we also observed a positive correlation between IL-6 and the tryptophan:KYNA ratio, indicating that IL-6 activates the KYN pathway. In line with this, application of IL-6 to cultured human astrocytes increased cell medium concentration of KYNA. Limitations The CSF samples had been frozen and thawed twice before analysis of cytokines. Median age differed between patients and controls. When appropriate, all present analyses were adjusted for age. Conclusion We have shown that IL-6, KYN and KYNA are elevated in patients with chronic schizophrenia, strengthening the idea of brain immune activation in patients with this disease. Our concurrent cell culture and clinical findings suggest that IL-6 induces the KYN pathway, leading to increased production of the N-methyl-d-aspartate receptor antagonist KYNA in patients with schizophrenia. PMID:25455350

  10. Magmatic Trigger for Extensional Collapse? Character and Significance of Pre-Extensional Volcanic Activity in the Whipple Mountains Region, Lower Colorado River Extensional Corridor

    NASA Astrophysics Data System (ADS)

    Fidler, M. K.; Gans, P. B.

    2014-12-01

    The character and timing of voluminous Miocene volcanic activity associated with regional crustal extension in the lower Colorado River Extensional Corridor (CREC) shed light on the interplay between tectonic and magmatic processes in the area. New 40Ar/39Ar ages from holocrystaline groundmass separates of mafic lava flows and phenocrystic plagioclase, biotite, hornblende, and sanidine from silicic extrusive rocks, combined with LA-ICPMS U-Pb ages of zircon from the more altered intermediate to silicic rocks provide important new constraints on the ages of pre-, syn-, and post-extensional volcanic sequences in the vicinity of the Whipple Mountains metamorphic core complex. Local eruptive activity began ~20.5 Ma and persisted for 1.5 million years prior to the inception of major extensional faulting and tilting at ~19 Ma, as recorded by upper plate tilt blocks. The pre-extensional sequences are homoclinal, steeply tilted, and disconformably overlie older arkosic sedimentary rocks. There is no compelling evidence for angular unconformities or growth faulting during this earliest pre-extensional volcanic activity. These early erupted units are dominantly mafic, forming ≥1 km thick sections of olivine-basalt and olv-cpx-plag basaltic andesite lava flows punctuated by rare aphyric to crystal poor dacite ignimbrites. Plag±pyx±bio±hbl dacite lava flows and domes with associated pyroclastic deposits appear late in the pre-extensional sequence, immediately prior to and during the onset of major extensional faulting. These crystal-poor to aphyric silicic rocks show abundant evidence of magma mingling and may represent hybridized partial melts generated by the influx of basaltic magma into the crust. The pre-extensional sequence is locally overlain by ~18.5 to 18.8 Ma syn- and post-extensional volcanic and sedimentary rocks along a pronounced 30-60° angular unconformity, indicating very rapid extension during the early stages of the CREC's development. This overall

  11. Development and Application of a Physiological-based Framework for Assessing the Biological Significance of Military Activities on Threatened and Endangered Animal Species

    DTIC Science & Technology

    2009-03-17

    from rather large shallow water ponds such as Bull pond (5-10 acres) on the B-70 range and a series of reference ponds (2-3 acres) south of the B-70...and K. Aida. 1999. Effects of steroids on the antibody producing activity of lymphocytes in rainbow trout . Fisheries Sci. 65:850-855. Hurley, J...J.C. and B. Dorr. 2004. Habitat associations of gopher tortoise burrows on industrial timberlands. Wildl. Soc. Bull . 32:456-464. Kelly, J.R. and

  12. Significant applications of ERTS-1 data to resource management activities at the state level in Ohio. [strip mining and land use mapping

    NASA Technical Reports Server (NTRS)

    Sweet, D. C.; Pincura, P. G.; Meier, C. J.; Garrett, G. B.; Herd, L.; Wukelic, G. E.; Stephan, J. G.; Smail, H. E.

    1974-01-01

    Described are techniques utilized and the progress made in applying ERTS-1 data to (1) detecting, inventorying, and monitoring surface mining activities, particularly in relation to recently passed strip mine legislation in Ohio; (2) updating current land use maps at various scales for multiagency usage, and (3) solving other real-time problems existing throughout the various Ohio governmental agencies. General conclusions regarding current user views as to the opportunities and limitations of operationally using ERTS-1 data at the state level are also noted.

  13. Nonlinear Varying Coefficient Models with Applications to Studying Photosynthesis

    PubMed Central

    Kürüm, Esra; Li, Runze; Wang, Yang; ŞEntürk, Damla

    2014-01-01

    Motivated by a study on factors affecting the level of photosynthetic activity in a natural ecosystem, we propose nonlinear varying coefficient models, in which the relationship between the predictors and the response variable is allowed to be nonlinear. One-step local linear estimators are developed for the nonlinear varying coefficient models and their asymptotic normality is established leading to point-wise asymptotic confidence bands for the coefficient functions. Two-step local linear estimators are also proposed for cases where the varying coefficient functions admit different degrees of smoothness; bootstrap confidence intervals are utilized for inference based on the two-step estimators. We further propose a generalized F test to study whether the coefficient functions vary over a covariate. We illustrate the proposed methodology via an application to an ecology data set and study the finite sample performance by Monte Carlo simulation studies. PMID:24976756

  14. Nonlinear Varying Coefficient Models with Applications to Studying Photosynthesis.

    PubMed

    Kürüm, Esra; Li, Runze; Wang, Yang; SEntürk, Damla

    2014-03-01

    Motivated by a study on factors affecting the level of photosynthetic activity in a natural ecosystem, we propose nonlinear varying coefficient models, in which the relationship between the predictors and the response variable is allowed to be nonlinear. One-step local linear estimators are developed for the nonlinear varying coefficient models and their asymptotic normality is established leading to point-wise asymptotic confidence bands for the coefficient functions. Two-step local linear estimators are also proposed for cases where the varying coefficient functions admit different degrees of smoothness; bootstrap confidence intervals are utilized for inference based on the two-step estimators. We further propose a generalized F test to study whether the coefficient functions vary over a covariate. We illustrate the proposed methodology via an application to an ecology data set and study the finite sample performance by Monte Carlo simulation studies.

  15. Site-specific replacement of the thymine methyl group by fluorine in thrombin binding aptamer significantly improves structural stability and anticoagulant activity

    PubMed Central

    Virgilio, Antonella; Petraccone, Luigi; Vellecco, Valentina; Bucci, Mariarosaria; Varra, Michela; Irace, Carlo; Santamaria, Rita; Pepe, Antonietta; Mayol, Luciano; Esposito, Veronica; Galeone, Aldo

    2015-01-01

    Here we report investigations, based on circular dichroism, nuclear magnetic resonance spectroscopy, molecular modelling, differential scanning calorimetry and prothrombin time assay, on analogues of the thrombin binding aptamer (TBA) in which individual thymidines were replaced by 5-fluoro-2′-deoxyuridine residues. The whole of the data clearly indicate that all derivatives are able to fold in a G-quadruplex structure very similar to the ‘chair-like’ conformation typical of the TBA. However, only ODNs TBA-F4 and TBA-F13 have shown a remarkable improvement both in the melting temperature (ΔTm ≈ +10) and in the anticoagulant activity in comparison with the original TBA. These findings are unusual, particularly considering previously reported studies in which modifications of T4 and T13 residues in TBA sequence have clearly proven to be always detrimental for the structural stability and biological activity of the aptamer. Our results strongly suggest the possibility to enhance TBA properties through tiny straightforward modifications. PMID:26582916

  16. Field studies of beach cones as coastal erosion control/reversal devices for areas with significant oil and gas activities. Annual report, February 24, 1993--February 23, 1994

    SciTech Connect

    Law, V.J.

    1994-07-07

    The primary objective of this project was to evaluate the utility of a device called the ``beach cone`` in combating coastal erosion. Seven initial sites were selected for testing beach cones in a variety of geometric configurations, and six sites were actually used. Six hundred beach cones were installed at the six sites in late July and early August, 1992. An additional 109 cones were installed at an eighth site in December of 1992. Findings indicate that beach cones accreted significant amounts of materials along the beach of a barrier island. At the eighth installation the amount of accreted material was measured by surveys to be 2200 cubic meters (2900 cubic yards) in February of 1993, when the cones were found to have been completely covered by the material. The average increase in elevation was about 7 inches (0. 18 in) with a maximum buildup of 3 ft. (I in). At other test sites, accretion rates have been less dramatic but importantly, no significant additional erosion has occurred, which is a positive result. The cost of sediment accretion using beach cones was found to be about $13.72 per cubic yard of sand or approximately $500,000 per mile of beach, which would be much lower if the cones were mass produced. The survival of the cones through the fringes of Hurricane Andrew indicates that they can be anchored sufficiently to survive significant storms. The measurements of the cones settling rates indicate that this effect is negligible, does not hinder their effectiveness. We do not yet have sufficient data to state the categorical success of the beach cones, but results to date are encouraging.

  17. Varying Inundation Regimes Differentially Affect Natural and ...

    EPA Pesticide Factsheets

    Climate change is altering sea-level rise rates and precipitation patterns worldwide. Coastal wetlands are vulnerable to these changes. System responses to stressors are important for resource managers and environmental stewards to understand in order to best manage them. Thin layer sand or sediment application to drowning and eroding marshes is one approach to build elevation and resilience. The above- and below-ground structure, soil carbon dioxide emissions, and pore water constituents in vegetated natural marsh sediments and sand-amended sediments were examined at varying inundation regimes between mean sea level and mean high water (0.82 m NAVD88 to 1.49 m NAVD88) in a field experiment at Laws Point, part of the Plum Island Sound Estuary (MA). Significantly lower salinities, pH, sulfides, phosphates, and ammonium were measured in the sand-amended sediments than in the natural sediments. In natural sediments there was a pattern of increasing salinity with increasing elevation while in the sand-amended sediments the trend was reversed, showing decreasing salinity with increasing elevation. Sulfide concentrations generally increased from low to high inundation with highest concentrations at the highest inundation (i.e., at the lowest elevations). High pore water phosphate concentrations were measured at low elevations in the natural sediments, but the sand-amended treatments had mostly low concentrations of phosphate and no consistent pattern with elevation. A

  18. Fractal analysis of time varying data

    DOEpatents

    Vo-Dinh, Tuan; Sadana, Ajit

    2002-01-01

    Characteristics of time varying data, such as an electrical signal, are analyzed by converting the data from a temporal domain into a spatial domain pattern. Fractal analysis is performed on the spatial domain pattern, thereby producing a fractal dimension D.sub.F. The fractal dimension indicates the regularity of the time varying data.

  19. Novel shock absorber features varying yield strengths

    NASA Technical Reports Server (NTRS)

    Geier, D. J.

    1964-01-01

    A shock absorbent webbing of partially drawn synthetic strands is arranged in sections of varying density related to the varying mass of the human body. This is contoured to protect the body at points of contact, when subjected to large acceleration or deceleration forces.

  20. Field studies of beach cones as coastal erosion control/reversal devices for areas with significant oil and gas activities. [Annual report], February 24, 1992--February 23, 1993

    SciTech Connect

    Law, V.J.

    1993-03-15

    The primary objective of this project is to evaluate the utility of a device called the ``beach cone`` in combating coastal erosion. Seven initial sites were selected for testing beach cones in a variety of geometric configurations. Permits were obtained from the State of Louisiana and the US Army Corps of Engineers to perform the work associated with this study. Six hundred beach cones were actually installed at six of the sites in late July and early August, 1992. One of the initial sites was abandoned because it was found to be unsuitable for beach cone placement. The test sites have been observed for six months and preliminary findings indicate that beach cones accreted significant amounts of materials along the beach of a barrier island. At other test sites, accretion rates have been less dramatic but importantly, no significant additional erosion has occurred, which is a positive result. It is too soon to state the categorical success of the beach cones, but results to date are encouraging.

  1. How specific halide adsorption varies hydrophobic interactions.

    PubMed

    Stock, Philipp; Müller, Melanie; Utzig, Thomas; Valtiner, Markus

    2016-03-11

    Hydrophobic interactions (HI) are driven by the water structure around hydrophobes in aqueous electrolytes. How water structures at hydrophobic interfaces and how this influences the HI was subject to numerous studies. However, the effect of specific ion adsorption on HI and hydrophobic interfaces remains largely unexplored or controversial. Here, the authors utilized atomic force microscopy force spectroscopy at well-defined nanoscopic hydrophobic interfaces to experimentally address how specific ion adsorption of halide ions as well as NH4 (+), Cs(+), and Na(+) cations alters interaction forces across hydrophobic interfaces. Our data demonstrate that iodide adsorption at hydrophobic interfaces profoundly varies the hydrophobic interaction potential. A long-range and strong hydration repulsion at distances D > 3 nm, is followed by an instability which could be explained by a subsequent rapid ejection of adsorbed iodides from approaching hydrophobic interfaces. In addition, the authors find only a weakly pronounced influence of bromide, and as expected no influence of chloride. Also, all tested cations do not have any significant influence on HI. Complementary, x-ray photoelectron spectroscopy and quartz-crystal-microbalance with dissipation monitoring showed a clear adsorption of large halide ions (Br(-)/I(-)) onto hydrophobic self-assembled monolayers (SAMs). Interestingly, iodide can even lead to a full disintegration of SAMs due to specific and strong interactions of iodide with gold. Our data suggest that hydrophobic surfaces are not intrinsically charged negatively by hydroxide adsorption, as it was generally believed. Hydrophobic surfaces rather interact strongly with negatively charged large halide ions, leading to a surface charging and significant variation of interaction forces.

  2. Mono- and disaccharides enhance the activity and enantioselectivity of Burkholderia cepacia lipase in organic solvent but do not significantly affect its conformation.

    PubMed

    Secundo, Francesco; Carrea, Giacomo

    2005-11-20

    Sucrose, trehalose, and mannitol were colyophilized with lipase from Burkholderia cepacia and their effects on the activity and enantioselectitivity of the enzyme evaluated using as model reactions the transesterification between n-octanol or 6-methyl-5-hepten-2-ol with vinyl acetate. The lipase co-lyophilized with sugars showed an activity which was up to 4.7-fold higher (at a sugar/lipase ratio >or= 20) than that observed without sugar. Analogously, lipase enantioselectivity, expressed as the enantiomeric ratio, increased up to 2.8-fold in the presence of sugars. The conformation of the lipase was investigated by means of Fourier transform infrared spectroscopy (FT/IR) in water and as lyophilized powder. The infrared spectra of lyophilized lipase in the presence and, even more so, in the absence of sugars were different from that of the enzyme in water. In particular, the band at around 1,654/cm, typically assigned to alpha-helix, was less intense in the lyophilized samples. Nevertheless, the enzyme in the presence of sugars showed a decrease of the bands at 1,614-1,620/cm and at 1,680-1,695/cm that indicates a lower content of intermolecular beta-sheets (typical of protein aggregates). Additionally the increase of the component at 1,546/cm in the amide II region is consistent with a hydrogen bond pattern of the enzyme more similar to that shown in water. These results suggest that although sugars are not able to fully preserve the native secondary structure, they might contribute to reduce the conformational changes caused by protein/protein interactions. These factors in combinations with others (e.g., ability to reduce deleterious interactions between the enzyme and inert supports) make sugars (both mono- and disaccharides) an interesting class of additives for improving the performance of biocatalysts in organic solvents.

  3. Evaluation of metal and radionuclide data from neutron activation and acid-digestion-based spectrometry analyses of background soils: Significance in environmental restoration

    SciTech Connect

    Lee, S.Y.; Watkins, D.R.; Jackson, B.L.; Schmoyer, R.L.; Lietzke, D.A.; Burgoa, B.B.; Branson, J.T.; Ammons, J.T.

    1995-12-31

    A faster, more cost-effective, and higher-quality data acquisition procedure for natural background-level metals and radionuclides in soils is needed for remedial investigations of contaminated sites. In this project, a total of 120 soil samples were collected from uncontaminated areas on and near the Oak Ridge Reservation. The samples were taken at three different depths and from three different geologic groups to establish background concentrations of metals and radionuclides. The objective of this presentation is to discuss the advantages and disadvantages of neutron activation analysis (NAA) compared with those of acid-digestion-based spectrometry (ADS) methods; the advantages and disadvantages were evaluated from Al, Sb, As, Cr, Co, Fe, Mg, Mn, Hg, K, Ag, {sup 232}Th, {sup 235}U, {sup 238}U, V, and Zn data. The ADS methods used for this project were inductively coupled plasma (ICP), ICP-mass spectrometry (ICP-MS), and alpha spectrometry. The scatter plots showed that the NAA results for As, Co, Fe, Mn, {sup 232}Th, and {sup 238}U are reasonably correlated with the results from the other analytical methods. Compared to NAA, however, the ADS methods underestimated Al, Cr, Mg, K, V, and Zn. The skew distributions were caused by incomplete dissolution of the analytes during acid digestion of the soil samples. Because of the high detection limits of the spectrometric methods, the NAA results and the ADS results for some elements, including Sb, Hg, and Ag, did not show a definite relationship. The NAA results were highly correlated with the alpha spectrometry results for {sup 232}Th and {sup 238}U but poorly correlated for {sup 235}U, probably because of a larger counting error associated with the lower activity of the isotope. The NAA methods, including the delayed neutron counting method, were far superior techniques for quantifying background levels of radionuclides ({sup 232}Th, {sup 235}U, and {sup 238}U) and metals (Al, Cr, Mg, K, V, and Zn) in soils.

  4. Gene Expression and Activity Profiling Reveal a Significant Contribution of Exo-Phosphotransferases to the Extracellular Nucleotides Metabolism in HUVEC Endothelial Cells.

    PubMed

    Wujak, Magdalena; Hetmann, Anna; Porowińska, Dorota; Roszek, Katarzyna

    2016-11-11

    Purinergic signaling maintains local tissue homeostasis in blood vessels via the regulation of vascular tone, blood platelet aggregation, cell proliferation, and differentiation as well as inflammatory responses. Extracellular purines are important signaling molecules in the vasculature, and both purine-hydrolysing as well as -phosphorylating enzymes are considered to selectively govern extracellular nucleotide/nucleoside metabolism. Recent studies have provided some evidence for the existence of these enzymes in a soluble form in human blood and their secretion into the extracellular space under physiological and pathological conditions. However, the comprehensive analysis of endothelium-derived enzymes involved in purine metabolic pathways has received no attention so far. In the presented study, in vitro cultured human umbilical vein endothelial cells (HUVEC) are shown to be an abundant source of exo-nucleotidases comprising 5'-nucleotidase (exo-5'-NT), and nucleoside triphosphate diphosphohydrolases (exo-NTPDase) as well as phosphotransferases, represented by nucleoside diphosphate kinase (exo-NDPK) and adenylate kinase (exo-AK). An attempt is also made to demonstrate that, in contrast to the metabolic pattern determined on the endothelial cell surface, exo-phosphorylating activities markedly predominate over exo-hydrolytic ones. We present for the first time the expression profiles of genes encoding isoenzymes belonging to distinct nucleotide kinase and nucleotidase families. The genes encoding NDPK1, NDPK2, AK1, and AK2 phosphotransferases have been shown to be expressed at the highest level in HUVEC cells. The data indicate the coexistence of secreted and cell-associated factors of endothelial origin mediating ATP-consuming and ATP-generating pathways with the predominance of exo-phosphotransferases activity. The described enzymes contribute to the regulation of purinergic signal duration and extent in the venous vasculature. J. Cell. Biochem. 9999: 1

  5. Brief Report: Secukinumab Provides Significant and Sustained Inhibition of Joint Structural Damage in a Phase III Study of Active Psoriatic Arthritis

    PubMed Central

    Landewé, Robert B.; Mease, Philip J.; McInnes, Iain B.; Conaghan, Philip G.; Pricop, Luminita; Ligozio, Greg; Richards, Hanno B.; Mpofu, Shephard

    2016-01-01

    Objective To assess whether secukinumab treatment in patients with active psoriatic arthritis (PsA) is associated with sustained inhibition of radiographic progression. Methods In this phase III, double‐blind, placebo‐controlled study, 606 patients with PsA were randomized to receive intravenous (IV) secukinumab at a dose of 10 mg/kg (weeks 0, 2, 4) followed by subcutaneous secukinumab at a dose of 150 mg or 75 mg (the IV→150 mg and IV→75 mg groups, respectively) or placebo. Patients were stratified according to prior anti–tumor necrosis factor (anti‐TNF) exposure (71% were anti‐TNF naive). At week 16, placebo‐treated patients who had at least a 20% reduction in the tender and swollen joint counts (responders) continued to receive placebo until week 24; nonresponders were re‐randomized to receive secukinumab at a dose of 150 mg or 75 mg. The modified total Sharp/van der Heijde score (SHS) was determined at baseline, week 16 or 24, and week 52. Results In the overall population, radiographic progression was inhibited through 52 weeks; efficacy was demonstrated for both erosion and joint space narrowing scores and in patients who switched from placebo to secukinumab at week 24. Subgroup analyses showed that secukinumab reduced radiographic progression at week 24, regardless of previous anti‐TNF treatment. Among anti‐TNF–naive patients, the mean changes from baseline to week 24 in the modified total SHS were 0.05 in the pooled secukinumab group and 0.57 in the placebo group; among patients with an inadequate response or intolerance to anti‐TNF treatment, the mean changes were 0.16 and 0.58, respectively. Anti‐TNF–naive patients showed negligible progression through week 52. Inhibition of structural damage was observed through week 52 irrespective of concomitant methotrexate use. A high proportion of patients receiving secukinumab showed no progression (change in SHS of ≤ 0.5) from baseline to week 24 (82.3% of the IV→150 mg group

  6. Optical Measurement Technologies for High Temperature, Radiation Exposure, and Corrosive Environments—Significant Activities and Findings: In-vessel Optical Measurements for Advanced SMRs

    SciTech Connect

    Anheier, Norman C.; Cannon, Bret D.; Qiao, Hong; Suter, Jonathan D.

    2012-09-01

    Development of advanced Small Modular Reactors (aSMRs) is key to providing the United States with a sustainable, economically viable, and carbon-neutral energy source. The aSMR designs have attractive economic factors that should compensate for the economies of scale that have driven development of large commercial nuclear power plants to date. For example, aSMRs can be manufactured at reduced capital costs in a factory and potentially shorter lead times and then be shipped to a site to provide power away from large grid systems. The integral, self-contained nature of aSMR designs is fundamentally different than conventional reactor designs. Future aSMR deployment will require new instrumentation and control (I&C) architectures to accommodate the integral design and withstand the extreme in-vessel environmental conditions. Operators will depend on sophisticated sensing and machine vision technologies that provide efficient human-machine interface for in-vessel telepresence, telerobotic control, and remote process operations. The future viability of aSMRs is dependent on understanding and overcoming the significant technical challenges involving in-vessel reactor sensing and monitoring under extreme temperatures, pressures, corrosive environments, and radiation fluxes

  7. Identification of a locality in snake venom alpha-neurotoxins with a significant compositional similarity to marine snail alpha-conotoxins: implications for evolution and structure/activity.

    PubMed

    Dufton, M J; Bladon, P; Harvey, A L

    1989-10-01

    alpha-neurotoxins from elapid snake venoms and alpha-conotoxins from marine snails bind specifically and with high affinity to nicotinic cholinoceptors. Although both types of toxin are polypeptides, there is more than a fourfold difference in size between the two and no clear sequence homology is evident. A systematic computer search of the three-dimensional structure of erabutoxin b (an alpha-neurotoxin from the false sea snake Laticauda semifasciata) was performed to identify the locality that most closely matched the amino acid compositions of the smaller alpha-conotoxins (from the marine snails Conus magus and Conus geographus). The area of greatest similarity centered on residue position 25 of erabutoxin b, a locale that is conserved throughout the snake alpha-neurotoxins and their homologues. Six proteins unrelated to erabutoxin b were compared to the alpha-conotoxins to show that the extent of the erabutoxin b/alpha-conotoxin match was too high to be coincidental. Homologues of erabutoxin b, namely alpha-cobratoxin from Naja naja siamensis and cytotoxin VII4 from Naja mossambica mossambica, were also analyzed. The extent of the matching with the alpha-conotoxins decreased in the series erabutoxin b greater than alpha-cobratoxin greater than cytotoxin VII4, and this also relates the order of similarity to the pharmacological properties of the alpha-conotoxins. The alpha-conotoxin-like area of the snake alpha-neurotoxins is peripheral to the site previously considered important for binding to the cholinoceptor, even though it seems to represent the focus of evolutionary convergence between the two types of neurotoxin. The area of resemblance does, however, have strong associations with the conformational behavior of the snake toxins. Hence, the outcome of this study has important consequences for the current ideas on snake alpha-neurotoxin structure/activity relationships and the evolutionary origins of neurotoxicity.

  8. Similar mitochondrial activation kinetics in wild-type and creatine kinase-deficient fast-twitch muscle indicate significant Pi control of respiration.

    PubMed

    Jeneson, Jeroen A L; ter Veld, Frank; Schmitz, Joep P J; Meyer, Ronald A; Hilbers, Peter A J; Nicolay, Klaas

    2011-06-01

    Past simulations of oxidative ATP metabolism in skeletal muscle have predicted that elimination of the creatine kinase (CK) reaction should result in dramatically faster oxygen consumption dynamics during transitions in ATP turnover rate. This hypothesis was investigated. Oxygen consumption of fast-twitch (FT) muscle isolated from wild-type (WT) and transgenic mice deficient in the myoplasmic (M) and mitochondrial (Mi) CK isoforms (MiM CK(-/-)) were measured at 20°C at rest and during electrical stimulation. MiM CK(-/-) muscle oxygen consumption activation kinetics during a step change in contraction rate were 30% faster than WT (time constant 53 ± 3 vs. 69 ± 4 s, respectively; mean ± SE, n = 8 and 6, respectively). MiM CK(-/-) muscle oxygen consumption deactivation kinetics were 380% faster than WT (time constant 74 ± 4 s vs. 264 ± 4 s, respectively). Next, the experiments were simulated using a computational model of the oxidative ATP metabolic network in FT muscle featuring ADP and Pi feedback control of mitochondrial respiration (J. A. L. Jeneson, J. P. Schmitz, N. A. van den Broek, N. A. van Riel, P. A. Hilbers, K. Nicolay, J. J. Prompers. Am J Physiol Endocrinol Metab 297: E774-E784, 2009) that was reparameterized for 20°C. Elimination of Pi control via clamping of the mitochondrial Pi concentration at 10 mM reproduced past simulation results of dramatically faster kinetics in CK(-/-) muscle, while inclusion of Pi control qualitatively explained the experimental observations. On this basis, it was concluded that previous studies of the CK-deficient FT muscle phenotype underestimated the contribution of Pi to mitochondrial respiratory control.

  9. Organic particulate matter formation at varying relative humidity using surrogate secondary and primary organic compounds with activity corrections in the condensed phase obtained using a method based on the Wilson equation

    NASA Astrophysics Data System (ADS)

    Chang, E. I.; Pankow, J. F.

    2010-06-01

    Secondary organic aerosol (SOA) formation in the atmosphere is currently often modeled using a multiple lumped "two-product" (N·2p) approach. The N·2p approach neglects: 1) variation of activity coefficient (ζi) values and mean molecular weight MW in the particulate matter (PM) phase; 2) water uptake into the PM; and 3) the possibility of phase separation in the PM. This study considers these effects by adopting an (N·2p)ζpMW,ζ approach (θ is a phase index). Specific chemical structures are assigned to 25 lumped SOA compounds and to 15 representative primary organic aerosol (POA) compounds to allow calculation of ζi and MW values. The SOA structure assignments are based on chamber-derived 2p gas/particle partition coefficient values coupled with known effects of structure on vapor pressure pL,io (atm). To facilitate adoption of the (N·2p)ζpMW,θ approach in large-scale models, this study also develops CP-Wilson.1 (Chang-Pankow-Wilson.1), a group-contribution ζi-prediction method that is more computationally economical than the UNIFAC model of Fredenslund et al. (1975). Group parameter values required by CP-Wilson.1 are obtained by fitting ζi values to predictions from UNIFAC. The (N·2p)ζpMW,θ approach is applied (using CP-Wilson.1) to several real α-pinene/O3 chamber cases for high reacted hydrocarbon levels (ΔHC≈400 to 1000 μg m-3) when relative humidity (RH) ≍50%. Good agreement between the chamber and predicted results is obtained using both the (N·2p)ζpMW,θ and N·2p approaches, indicating relatively small water effects under these conditions. However, for a hypothetical α-pinene/O3 case at ΔHC=30 μg m-3 and

  10. Kinetics and mechanism of exogenous anion exchange in FeFbpA-NTA: significance of periplasmic anion lability and anion binding activity of ferric binding protein A.

    PubMed

    Heymann, Jared J; Gabricević, Mario; Mietzner, Timothy A; Crumbliss, Alvin L

    2010-02-01

    The bacterial transferrin ferric binding protein A (FbpA) requires an exogenous anion to facilitate iron sequestration, and subsequently to shuttle the metal across the periplasm to the cytoplasmic membrane. In the diverse conditions of the periplasm, numerous anions are known to be present. Prior in vitro experiments have demonstrated the ability of multiple anions to fulfill the synergistic iron-binding requirement, and the identity of the bound anion has been shown to modulate important physicochemical properties of iron-bound FbpA (FeFbpA). Here we address the kinetics and mechanism of anion exchange for the FeFbpA-nitrilotriacetate (NTA) assembly with several biologically relevant anions (citrate, oxalate, phosphate, and pyrophosphate), with nonphysiologic NTA serving as a representative synergistic anion/chelator. The kinetic data are consistent with an anion-exchange process that occurs in multiple steps, dependent on the identity of both the entering anion and the leaving anion. The exchange mechanism may proceed either as a direct substitution or through an intermediate FeFbpA-X* assembly based on anion (X) identity. Our kinetic results further develop an understanding of exogenous anion lability in the periplasm, as well as address the final step of the iron-free FbpA (apo-FbpA)/Fe(3+) sequestration mechanism. Our results highlight the kinetic significance of the FbpA anion binding site, demonstrating a correlation between apo-FbpA/anion affinity and the FeFbpA rate of anion exchange, further supporting the requirement of an exogenous anion to complete tight sequestration of iron by FbpA, and developing a mechanism for anion exchange within FeFbpA that is dependent on the identity of both the entering anion and the leaving anion.

  11. Reducing Human-Tsetse Contact Significantly Enhances the Efficacy of Sleeping Sickness Active Screening Campaigns: A Promising Result in the Context of Elimination

    PubMed Central

    Courtin, Fabrice; Camara, Mamadou; Rayaisse, Jean-Baptiste; Kagbadouno, Moise; Dama, Emilie; Camara, Oumou; Traoré, Ibrahima S.; Rouamba, Jérémi; Peylhard, Moana; Somda, Martin B.; Leno, Mamadou; Lehane, Mike J.; Torr, Steve J.; Solano, Philippe; Jamonneau, Vincent; Bucheton, Bruno

    2015-01-01

    Background Control of gambiense sleeping sickness, a neglected tropical disease targeted for elimination by 2020, relies mainly on mass screening of populations at risk and treatment of cases. This strategy is however challenged by the existence of undetected reservoirs of parasites that contribute to the maintenance of transmission. In this study, performed in the Boffa disease focus of Guinea, we evaluated the value of adding vector control to medical surveys and measured its impact on disease burden. Methods The focus was divided into two parts (screen and treat in the western part; screen and treat plus vector control in the eastern part) separated by the Rio Pongo river. Population census and baseline entomological data were collected from the entire focus at the beginning of the study and insecticide impregnated targets were deployed on the eastern bank only. Medical surveys were performed in both areas in 2012 and 2013. Findings In the vector control area, there was an 80% decrease in tsetse density, resulting in a significant decrease of human tsetse contacts, and a decrease of disease prevalence (from 0.3% to 0.1%; p=0.01), and an almost nil incidence of new infections (<0.1%). In contrast, incidence was 10 times higher in the area without vector control (>1%, p<0.0001) with a disease prevalence increasing slightly (from 0.5 to 0.7%, p=0.34). Interpretation Combining medical and vector control was decisive in reducing T. b. gambiense transmission and in speeding up progress towards elimination. Similar strategies could be applied in other foci. PMID:26267667

  12. Dynamic Factor Analysis Models With Time-Varying Parameters.

    PubMed

    Chow, Sy-Miin; Zu, Jiyun; Shifren, Kim; Zhang, Guangjian

    2011-04-11

    Dynamic factor analysis models with time-varying parameters offer a valuable tool for evaluating multivariate time series data with time-varying dynamics and/or measurement properties. We use the Dynamic Model of Activation proposed by Zautra and colleagues (Zautra, Potter, & Reich, 1997) as a motivating example to construct a dynamic factor model with vector autoregressive relations and time-varying cross-regression parameters at the factor level. Using techniques drawn from the state-space literature, the model was fitted to a set of daily affect data (over 71 days) from 10 participants who had been diagnosed with Parkinson's disease. Our empirical results lend partial support and some potential refinement to the Dynamic Model of Activation with regard to how the time dependencies between positive and negative affects change over time. A simulation study is conducted to examine the performance of the proposed techniques when (a) changes in the time-varying parameters are represented using the true model of change, (b) supposedly time-invariant parameters are represented as time-varying, and

  13. Risk behaviors for varying categories of disability in NELS:88.

    PubMed

    Hollar, David

    2005-11-01

    A large body of research shows that youth with disabilities, who comprise about 13% of the country's school-aged population, report comparable to higher incidence rates of alcohol, tobacco, and other drug (ATOD) use than their peers. Furthermore, youth with disabilities who reported ATOD use or who engaged in binge drinking had significantly more negative educational outcomes and engaged in sexual activity at a younger age than nonusers. This study describes risk factors for substance use, personal characteristics, aspects of the attitudinal environment, and educational, employment, and social outcomes among youth across 6 categories of disability. Data came from the National Center for Education Statistics' National Education Longitudinal Study of 1988-2000 (NELS:88). The findings indicate that (a) youth with varying types of disabilities are relatively homogenous with respect to risk behaviors, personal characteristics, and outcomes; (b) youth with emotional, learning, or multiple disabilities may be at heightened risk for binge drinking and marijuana use; and (c) youth with emotional and multiple disabilities may be less likely to graduate from high school or its equivalent 8 years beyond the 12th grade. Based on these results and limitations of the NELS sampling strategy, appropriate interventions are discussed as well as the need for more definitive operational definitions for disabilities, specifically the biopsychosocial approach used by the International Classification of Functioning, Disability, and Health.

  14. Time varying networks and the weakness of strong ties

    NASA Astrophysics Data System (ADS)

    Karsai, Márton; Perra, Nicola; Vespignani, Alessandro

    2014-02-01

    In most social and information systems the activity of agents generates rapidly evolving time-varying networks. The temporal variation in networks' connectivity patterns and the ongoing dynamic processes are usually coupled in ways that still challenge our mathematical or computational modelling. Here we analyse a mobile call dataset and find a simple statistical law that characterize the temporal evolution of users' egocentric networks. We encode this observation in a reinforcement process defining a time-varying network model that exhibits the emergence of strong and weak ties. We study the effect of time-varying and heterogeneous interactions on the classic rumour spreading model in both synthetic, and real-world networks. We observe that strong ties severely inhibit information diffusion by confining the spreading process among agents with recurrent communication patterns. This provides the counterintuitive evidence that strong ties may have a negative role in the spreading of information across networks.

  15. Song trait similarity in great tits varies with social structure.

    PubMed

    Snijders, Lysanne; van der Eijk, Jerine; van Rooij, Erica P; de Goede, Piet; van Oers, Kees; Naguib, Marc

    2015-01-01

    For many animals, long-range signalling is essential to maintain contact with conspecifics. In territorial species, individuals often have to balance signalling towards unfamiliar potential competitors (to solely broadcast territory ownership) with signalling towards familiar immediate neighbours (to also maintain so-called "dear enemy" relations). Hence, to understand how signals evolve due to these multilevel relationships, it is important to understand how general signal traits vary in relation to the overall social environment. For many territorial songbirds dawn is a key signalling period, with several neighbouring individuals singing simultaneously without immediate conflict. In this study we tested whether sharing a territory boundary, rather than spatial proximity, is related to similarity in dawn song traits between territorial great tits (Parus major) in a wild personality-typed population. We collected a large dataset of automatized dawn song recordings from 72 unique male great tits, during the fertile period of their mate, and compared specific song traits between neighbours and non-neighbours. We show here that both song rate and start time of dawn song were repeatable song traits. Moreover, neighbours were significantly more dissimilar in song rate compared to non-neighbours, while there was no effect of proximity on song rate similarity. Additionally, similarity in start time of dawn song was unrelated to sharing a territory boundary, but birds were significantly more similar in start time of dawn song when they were breeding in close proximity of each other. We suggest that the dissimilarity in dawn song rate between neighbours is either the result of neighbouring great tits actively avoiding similar song rates to possibly prevent interference, or a passive consequence of territory settlement preferences relative to the types of neighbours. Neighbourhood structuring is therefore likely to be a relevant selection pressure shaping variation in

  16. Mobile Robot Positioning with 433-MHz Wireless Motes with Varying Transmission Powers and a Particle Filter

    PubMed Central

    Canedo-Rodriguez, Adrian; Rodriguez, Jose Manuel; Alvarez-Santos, Victor; Iglesias, Roberto; Regueiro, Carlos V.

    2015-01-01

    In wireless positioning systems, the transmitter's power is usually fixed. In this paper, we explore the use of varying transmission powers to increase the performance of a wireless localization system. To this extent, we have designed a robot positioning system based on wireless motes. Our motes use an inexpensive, low-power sub-1-GHz system-on-chip (CC1110) working in the 433-MHz ISM band. Our localization algorithm is based on a particle filter and infers the robot position by: (1) comparing the power received with the expected one; and (2) integrating the robot displacement. We demonstrate that the use of transmitters that vary their transmission power over time improves the performance of the wireless positioning system significantly, with respect to a system that uses fixed power transmitters. This opens the door for applications where the robot can localize itself actively by requesting the transmitters to change their power in real time. PMID:25942641

  17. Varying G. [in Einstein gravitation theory

    NASA Technical Reports Server (NTRS)

    Canuto, V.; Hsieh, S.-H.; Owen, J. R.

    1979-01-01

    The problem of the variation of the gravitational constant with cosmological time is critically analyzed. Since Einstein's equation does not allow G to vary on any time scale, no observational data can be analyzed within the context of the standard theory. The recently proposed scale covariant theory, which allows (but does not demand) G to vary, and which has been shown to have passed several standard cosmological tests, is employed to discuss some recent nonnull observational results which indicate a time variation of G.

  18. Relaxation Assessment with Varied Structured Milieu (RELAX).

    ERIC Educational Resources Information Center

    Cassel, Russell N.; Cassel, Susie L.

    1983-01-01

    Describes Relaxation Assessment with Varied Structured Milieu (RELAX), a clinical program designed to assess the degree to which an individual is able to demonstrate self-control for overall general relaxation. The program is designed for use with the Cassel Biosensors biofeedback equipment. (JAC)

  19. Regularizing cosmological singularities by varying physical constants

    SciTech Connect

    Dąbrowski, Mariusz P.; Marosek, Konrad E-mail: k.marosek@wmf.univ.szczecin.pl

    2013-02-01

    Varying physical constant cosmologies were claimed to solve standard cosmological problems such as the horizon, the flatness and the Λ-problem. In this paper, we suggest yet another possible application of these theories: solving the singularity problem. By specifying some examples we show that various cosmological singularities may be regularized provided the physical constants evolve in time in an appropriate way.

  20. The Varied Uses of Readability Measurement.

    ERIC Educational Resources Information Center

    Fry, Edward

    Readability formulas have varied uses. In education they are used to match children's reading ability to the difficulty level of material, select stories and books for classroom use and for individual students' particular needs, select textbooks and other reading materials, aid educational research, and check reading materials of newly literate…

  1. Varying potential silicon carbide gas sensor

    NASA Technical Reports Server (NTRS)

    Shields, Virgil B. (Inventor); Ryan, Margaret A. (Inventor); Williams, Roger M. (Inventor)

    1997-01-01

    A hydrocarbon gas detection device operates by dissociating or electro-chemically oxidizing hydrocarbons adsorbed to a silicon carbide detection layer. Dissociation or oxidation are driven by a varying potential applied to the detection layer. Different hydrocarbon species undergo reaction at different applied potentials so that the device is able to discriminate among various hydrocarbon species. The device can operate at temperatures between 100.degree. C. and at least 650.degree. C., allowing hydrocarbon detection in hot exhaust gases. The dissociation reaction is detected either as a change in a capacitor or, preferably, as a change of current flow through an FET which incorporates the silicon carbide detection layers. The silicon carbide detection layer can be augmented with a pad of catalytic material which provides a signal without an applied potential. Comparisons between the catalytically produced signal and the varying potential produced signal may further help identify the hydrocarbon present.

  2. Continuously Varying Critical Exponents Beyond Weak Universality

    PubMed Central

    Khan, N.; Sarkar, P.; Midya, A.; Mandal, P.; Mohanty, P. K.

    2017-01-01

    Renormalization group theory does not restrict the form of continuous variation of critical exponents which occurs in presence of a marginal operator. However, the continuous variation of critical exponents, observed in different contexts, usually follows a weak universality scenario where some of the exponents (e.g., β, γ, ν) vary keeping others (e.g., δ, η) fixed. Here we report ferromagnetic phase transition in (Sm1−yNdy)0.52Sr0.48MnO3 (0.5 ≤ y ≤ 1) single crystals where all three exponents β, γ, δ vary with Nd concentration y. Such a variation clearly violates both universality and weak universality hypothesis. We propose a new scaling theory that explains the present experimental results, reduces to the weak universality as a special case, and provides a generic route leading to continuous variation of critical exponents and multi-criticality. PMID:28327622

  3. The Thermal Collector With Varied Glass Covers

    NASA Astrophysics Data System (ADS)

    Luminosu, I.; Pop, N.

    2010-08-01

    The thermal collector with varied glass covers represents an innovation realized in order to build a collector able to reach the desired temperature by collecting the solar radiation from the smallest surface, with the highest efficiency. In the case of the thermal collector with variable cover glasses, the number of the glass plates covering the absorber increases together with the length of the circulation pipe for the working fluid. The thermal collector with varied glass covers compared to the conventional collector better meet user requirements because: for the same temperature increase, has the collecting area smaller; for the same collection area, realizes the highest temperature increase and has the highest efficiency. This works is addressed to researchers in the solar energy and to engineers responsible with air-conditioning systems design or industrial and agricultural products drying.

  4. Continuously Varying Critical Exponents Beyond Weak Universality

    NASA Astrophysics Data System (ADS)

    Khan, N.; Sarkar, P.; Midya, A.; Mandal, P.; Mohanty, P. K.

    2017-03-01

    Renormalization group theory does not restrict the form of continuous variation of critical exponents which occurs in presence of a marginal operator. However, the continuous variation of critical exponents, observed in different contexts, usually follows a weak universality scenario where some of the exponents (e.g., β, γ, ν) vary keeping others (e.g., δ, η) fixed. Here we report ferromagnetic phase transition in (Sm1‑yNdy)0.52Sr0.48MnO3 (0.5 ≤ y ≤ 1) single crystals where all three exponents β, γ, δ vary with Nd concentration y. Such a variation clearly violates both universality and weak universality hypothesis. We propose a new scaling theory that explains the present experimental results, reduces to the weak universality as a special case, and provides a generic route leading to continuous variation of critical exponents and multi-criticality.

  5. Varied line-space gratings and applications

    SciTech Connect

    McKinney, W.R.

    1991-07-15

    This paper presents a straightforward analytical and numerical method for the design of a specific type of varied line-space grating system. The mathematical development will assume plane or nearly-plane spherical gratings which are illuminated by convergent light, which covers many interesting cases for synchrotron radiation. The gratings discussed will have straight grooves whose spacing varies across the principal plane of the grating. Focal relationships and formulae for the optical grating-pole-to-exist-slit distance and grating radius previously presented by other authors will be derived with a symbolic algebra system. It is intended to provide the optical designer with the tools necessary to design such a system properly. Finally, some possible advantages and disadvantages for application to synchrotron to synchrotron radiation beamlines will be discussed.

  6. Significance of periodogram peaks

    NASA Astrophysics Data System (ADS)

    Süveges, Maria; Guy, Leanne; Zucker, Shay

    2016-10-01

    Three versions of significance measures or False Alarm Probabilities (FAPs) for periodogram peaks are presented and compared for sinusoidal and box-like signals, with specific application on large-scale surveys in mind.

  7. Time varying market efficiency of the GCC stock markets

    NASA Astrophysics Data System (ADS)

    Charfeddine, Lanouar; Khediri, Karim Ben

    2016-02-01

    This paper investigates the time-varying levels of weak-form market efficiency for the GCC stock markets over the period spanning from May 2005 to September 2013. We use two empirical approaches: (1) the generalized autoregressive conditional heteroscedasticity in mean (GARCH-M) model with state space time varying parameter (Kalman filter), and (2) a rolling technique sample test of the fractional long memory parameter d. As long memory estimation methods, we use the detrended fluctuation analysis (DFA) technique, the modified R/S statistic, the exact local whittle (ELW) and the feasible Exact Local Whittle (FELW) methods. Moreover, we use the Bai and Perron (1998, 2003) multiple structural breaks technique to test and date the time varying behavior of stock market efficiency. Empirical results show that GCC markets have different degrees of time-varying efficiency, and also have experiencing periods of efficiency improvement. Results also show evidence of structural breaks in all GCC markets. Moreover, we observe that the recent financial shocks such as Arab spring and subprime crises have a significant impact on the time path evolution of market efficiency.

  8. A varying polytropic gas universe and phase space analysis

    NASA Astrophysics Data System (ADS)

    Khurshudyan, M.

    2016-05-01

    In this paper, we will consider a phenomenological model of a dark fluid that is able to explain an accelerated expansion of our low redshift universe and the phase transition to this accelerated expanding universe. Recent developments in modern cosmology towards understanding of the accelerated expansion of the large scale universe involve various scenarios and approaches. Among these approaches, one of well-known and accepted practice is modeling of the content of our universe via dark fluid. There are various models of dark energy fluid actively studied in recent literature and polytropic gas is among them. In this work, we will consider a varying polytropic gas which is a phenomenological modification of polytropic gas. Our model of varying polytropic dark fluid has been constructed to analogue to a varying Chaplygin gas actively discussed in the literature. We will consider interacting models, where dark matter is a pressureless fluid, to have a comprehensive picture. Phase space analysis is an elegant mathematical tool to earn general understanding of large scale universe and easily see an existence of a solution to cosmological coincidence problem. Imposing some constraints on parameters of the models, we found late time attractors for each case analytically. Cosmological consequences for the obtained late time attractors are discussed.

  9. Linear Parameter Varying Control for Actuator Failure

    NASA Technical Reports Server (NTRS)

    Shin, Jong-Yeob; Wu, N. Eva; Belcastro, Christine; Bushnell, Dennis M. (Technical Monitor)

    2002-01-01

    A robust linear parameter varying (LPV) control synthesis is carried out for an HiMAT vehicle subject to loss of control effectiveness. The scheduling parameter is selected to be a function of the estimates of the control effectiveness factors. The estimates are provided on-line by a two-stage Kalman estimator. The inherent conservatism of the LPV design is reducing through the use of a scaling factor on the uncertainty block that represents the estimation errors of the effectiveness factors. Simulations of the controlled system with the on-line estimator show that a superior fault-tolerance can be achieved.

  10. 3D-printing spatially varying BRDFs.

    PubMed

    Rouiller, Olivier; Bickel, Bernd; Kautz, Jan; Matusik, Wojciech; Alexa, Marc

    2013-01-01

    A new method fabricates custom surface reflectance and spatially varying bidirectional reflectance distribution functions (svBRDFs). Researchers optimize a microgeometry for a range of normal distribution functions and simulate the resulting surface's effective reflectance. Using the simulation's results, they reproduce an input svBRDF's appearance by distributing the microgeometry on the printed material's surface. This method lets people print svBRDFs on planar samples with current 3D printing technology, even with a limited set of printing materials. It extends naturally to printing svBRDFs on arbitrary shapes.

  11. A time-varying magnetic flux concentrator

    NASA Astrophysics Data System (ADS)

    Kibret, B.; Premaratne, M.; Lewis, P. M.; Thomson, R.; Fitzgerald, P. B.

    2016-08-01

    It is known that diverse technological applications require the use of focused magnetic fields. This has driven the quest for controlling the magnetic field. Recently, the principles in transformation optics and metamaterials have allowed the realization of practical static magnetic flux concentrators. Extending such progress, here, we propose a time-varying magnetic flux concentrator cylindrical shell that uses electric conductors and ferromagnetic materials to guide magnetic flux to its center. Its performance is discussed based on finite-element simulation results. Our proposed design has potential applications in magnetic sensors, medical devices, wireless power transfer, and near-field wireless communications.

  12. Statistical Significance Testing.

    ERIC Educational Resources Information Center

    McLean, James E., Ed.; Kaufman, Alan S., Ed.

    1998-01-01

    The controversy about the use or misuse of statistical significance testing has become the major methodological issue in educational research. This special issue contains three articles that explore the controversy, three commentaries on these articles, an overall response, and three rejoinders by the first three authors. They are: (1)…

  13. Significance of brown dwarfs

    NASA Technical Reports Server (NTRS)

    Black, D. C.

    1986-01-01

    The significance of brown dwarfs for resolving some major problems in astronomy is discussed. The importance of brown dwarfs for models of star formation by fragmentation of molecular clouds and for obtaining independent measurements of the ages of stars in binary systems is addressed. The relationship of brown dwarfs to planets is considered.

  14. Brown Dwarf Variability: What's Varying and Why?

    NASA Technical Reports Server (NTRS)

    Marley, Mark Scott

    2014-01-01

    Surveys by ground based telescopes, HST, and Spitzer have revealed that brown dwarfs of most spectral classes exhibit variability. The spectral and temporal signatures of the variability are complex and apparently defy simplistic classification which complicates efforts to model the changes. Important questions include understanding if clearings are forming in an otherwise uniform cloud deck or if thermal perturbations, perhaps associated with breaking gravity waves, are responsible. If clouds are responsible how long does it take for the atmospheric thermal profile to relax from a hot cloudy to a cooler cloudless state? If thermal perturbations are responsible then what atmospheric layers are varying? How do the observed variability timescales compare to atmospheric radiative, chemical, and dynamical timescales? I will address such questions by presenting modeling results for time-varying partly cloudy atmospheres and explore the importance of various atmospheric processes over the relevant timescales for brown dwarfs of a range of effective temperatures. Regardless of the origin of the observed variability, the complexity seen in the atmospheres of the field dwarfs hints at the variability that we may encounter in the next few years in directly imaged young Jupiters. Thus understanding the nature of variability in the field dwarfs, including sensitivity to gravity and metallicity, is of particular importance for exoplanet characterization.

  15. Spatially varying relationships between land-cover change and driving factors at multiple sampling scales.

    PubMed

    Du, Shihong; Wang, Qiao; Guo, Luo

    2014-05-01

    Modeling the relationships between environment, human activity, and natural conditions is very important for understanding human-environment interactions. This study aims at examining how these relationships vary over spatial sampling scales and investigating the spatially varying relationships between land-cover changes and driving factors, as well as the variations in the relationships at different sampling scales in the Tibetan Autonomous Prefecture of Qinghai Province, P.R. China. Regular sampling methods are used first to generate eight sets of data points at different scales, and then the values for land-cover changes and the factors are extracted for these data points. Geographically weighted regression (GWR) model is applied to analyze the relationships between land-cover changes and the factors at different sampling scales. The results indicate that the influences of the factors (e.g. the signs, significances, and values of coefficients) change greatly over different sampling scales; similarly, for different types of land-cover changes, the contributions of the factors also vary. Generally, roads, rivers, and lakes contribute greatly to land-cover changes, while villages, temples, and elevations contribute less. A possible reason is that the densities of roads, rivers, and lakes is much greater than those of villages and temples, and the populations in temples and villages are too small to have much effect on land-cover changes. The results demonstrate that the sampling scales have an important influence on the relationships between land-cover change and the factors.

  16. AGN-2979, an inhibitor of tryptophan hydroxylase activation, does not affect serotonin synthesis in Flinders Sensitive Line rats, a rat model of depression, but produces a significant effect in Flinders Resistant Line rats

    PubMed Central

    Kanemaru, Kazuya; Nishi, Kyoko; Diksic, Mirko

    2009-01-01

    The neurotransmitter, serotonin, is involved in several brain functions, including both normal, physiological functions, and pathophysiological functions. Alterations in any of the normal parameters of serotonergic neurotransmission can produce several different psychiatric disorders, including major depression. In many instances, brain neurochemical variables are not able to be studied properly in humans, thus making the use of good animal models extremely valuable. One of these animal models is the Flinders Sensitive Line (FSL) of rats, which has face, predictive and constructive validities in relation to human depression. The objective of this study was to quantify the effect of the tryptophan hydroxylase (TPH) activation inhibitor, AGN-2979, on the FSL rats (rats with depression-like behaviour), and compare it to the effect on the Flinders Resistant Line (FRL) of rats used as the control rats. The effect was evaluated by measuring changes in regional serotonin synthesis in the vehicle treated rats (FSL-VEH and FRL-VEH) relative to those measured in the AGN-2979 treated rats (FSL-AGN and FRL-AGN). Regional serotonin synthesis was measured autoradiographically in more than thirty brain regions. The measurements were performed using α-[14C]methyl-L-tryptophan as the tracer. The results indicate that AGN-2979 did not produce a significant reduction of TPH activity in the AGN-2979 group relative to the vehicle group (a reduction would have been observed if there had been an activation of TPH by the experimental set up) in the FSL rats. On the other hand, there was a highly significant reduction of synthesis in the FRL rats treated by AGN-2979, relative to the vehicle group. Together, the results demonstrate that in the FSL rats, AGN-2979 does not affect serotonin synthesis. This suggests that there was no activation of TPH in the FSL rats during the experimental procedure, but such activation did occur in the FRL rats. Because of this finding, it could be

  17. Hemolymph drop impact outcomes on surfaces with varying wettability

    NASA Astrophysics Data System (ADS)

    Milionis, Athanasios; Ghokulla Krishnan, K.; Loth, Eric

    2015-08-01

    Insect fouling from coagulated hemolymph and exoskeleton parts is a major challenge in the aerospace industry for the next generation of aerodynamic surfaces, which will employ laminar flow that requires extremely smooth surfaces. However, the wetting physics and dynamics of hemolymph (insect blood) on surfaces are not well understood. The present study seeks to gain a fundamental insight on the effect of surface wetting characteristics and dynamics resulting from a hemolymph drop impact, the first such study. In particular, hemolymph drops extracted from Acheta domesticus were dispensed from a range of heights to vary the kinetic impact on surfaces, which had widely varying water wetting behavior (from superhydrophilic to superhydrophobic). The impact dynamics were investigated with high-speed imaging while the dried residues were studied with optical microscopy. It was found that a superhydrophobic surface (based on thermoplastic with silica nano-particles) was able to significantly reduce hemolymph drop spreading, and even provide complete rebound when impacting on inclined surfaces.

  18. Composite Defect Significance.

    DTIC Science & Technology

    1982-07-13

    A12i 299 COMPOSITE DEFECT SIGNIFICANCE(U) MATERIALS SCIENCES 1/1 \\ CORP SPRING HOUSE PA S N CHATTERJEE ET AL. 13 JUL 82 MSC/TFR/1288/il87 NADC-80848...Directorate 30 Sensors & Avionics Technology Directorate 40 Communication & Navigation Technology Directorate 50 Software Computer Directorate 60 Aircraft ...instructions concerning commercial products herein do not constitute an endorsement by the Government nor do they convey or imply the license or right to use

  19. Significant Tsunami Events

    NASA Astrophysics Data System (ADS)

    Dunbar, P. K.; Furtney, M.; McLean, S. J.; Sweeney, A. D.

    2014-12-01

    Tsunamis have inflicted death and destruction on the coastlines of the world throughout history. The occurrence of tsunamis and the resulting effects have been collected and studied as far back as the second millennium B.C. The knowledge gained from cataloging and examining these events has led to significant changes in our understanding of tsunamis, tsunami sources, and methods to mitigate the effects of tsunamis. The most significant, not surprisingly, are often the most devastating, such as the 2011 Tohoku, Japan earthquake and tsunami. The goal of this poster is to give a brief overview of the occurrence of tsunamis and then focus specifically on several significant tsunamis. There are various criteria to determine the most significant tsunamis: the number of deaths, amount of damage, maximum runup height, had a major impact on tsunami science or policy, etc. As a result, descriptions will include some of the most costly (2011 Tohoku, Japan), the most deadly (2004 Sumatra, 1883 Krakatau), and the highest runup ever observed (1958 Lituya Bay, Alaska). The discovery of the Cascadia subduction zone as the source of the 1700 Japanese "Orphan" tsunami and a future tsunami threat to the U.S. northwest coast, contributed to the decision to form the U.S. National Tsunami Hazard Mitigation Program. The great Lisbon earthquake of 1755 marked the beginning of the modern era of seismology. Knowledge gained from the 1964 Alaska earthquake and tsunami helped confirm the theory of plate tectonics. The 1946 Alaska, 1952 Kuril Islands, 1960 Chile, 1964 Alaska, and the 2004 Banda Aceh, tsunamis all resulted in warning centers or systems being established.The data descriptions on this poster were extracted from NOAA's National Geophysical Data Center (NGDC) global historical tsunami database. Additional information about these tsunamis, as well as water level data can be found by accessing the NGDC website www.ngdc.noaa.gov/hazard/

  20. Human osteoblasts express functional CXC chemokine receptors 3 and 5: activation by their ligands, CXCL10 and CXCL13, significantly induces alkaline phosphatase and beta-N-acetylhexosaminidase release.

    PubMed

    Lisignoli, Gina; Toneguzzi, Stefania; Piacentini, Anna; Cattini, Luca; Lenti, Anna; Tschon, Matilde; Cristino, Sandra; Grassi, Francesco; Facchini, Andrea

    2003-01-01

    Osteoblasts (OBs) contribute to the maintenance of bone homeostasis and their activity can be influenced by immune cells localized in bone lacunae. We investigated the expression of the chemokine receptors in isolated human OBs by reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry, and report a novel finding, namely, that OBs express high levels of CXC chemokine receptor 3 (CXCR3) and 5 (CXCR5). Functional assays to evaluate CXCR3 and CXCR5 demonstrated that their ligands-CXCL10 and CXCL13, respectively-significantly induce the release of beta-N-acetylhexosaminidase, an enzyme involved in endochondral ossification and bone remodeling able to degrade important extracellular matrix components. Alkaline phosphatase activity, a useful index of matrix formation was also up-regulated by CXCL10 and CXCL13. However, OB activation by these ligands does not affect OB proliferation. Both Bordetella pertussis toxin and neutralizing anti-CXCR3/anti-CXCR5 monoclonal antibodies block CXCL10 and CXCL13 induction, respectively. We also demonstrated the expression of CXCL10 and CXCL13 in human bone tissue biopsies. These results indicate that both CXCR3/CXCL10 and CXCR5/CXCL13 receptor-ligand pairs may play an important role in OB activity through the specific up-regulation of two enzymes, which are involved in the bone remodeling process. Moreover, our data suggest that OBs may play a role in the modulation of bone formation through the combined action of these two enzymes.

  1. Quantification of sound instability in embouchure tremor based on the time-varying fundamental frequency.

    PubMed

    Lee, André; Voget, Jakob; Furuya, Shinichi; Morise, Masanori; Altenmüller, Eckart

    2016-05-01

    Task-specific tremor in musicians is an involuntary oscillating muscular activity mostly of the hand or the embouchure, which predominantly occurs while playing the instrument. In contrast to arm or hand tremors, which have been examined and objectified based on movement kinematics and muscular activity, embouchure tremor has not yet been investigated. To quantify and describe embouchure tremor we analysed sound production and investigated the fluctuation of the time-varying fundamental frequency of sustained notes. A comparison between patients with embouchure tremor and healthy controls showed a significantly higher fluctuation of the fundamental frequency for the patients in the high pitch with a tremor frequency range between 3 and 8 Hz. The present findings firstly provide further information about a scarcely described movement disorder and secondly further evaluate a new quantification method for embouchure tremor, which has recently been established for embouchure dystonia.

  2. Public health significance of neuroticism.

    PubMed

    Lahey, Benjamin B

    2009-01-01

    The personality trait of neuroticism refers to relatively stable tendencies to respond with negative emotions to threat, frustration, or loss. Individuals in the population vary markedly on this trait, ranging from frequent and intense emotional reactions to minor challenges to little emotional reaction even in the face of significant difficulties. Although not widely appreciated, there is growing evidence that neuroticism is a psychological trait of profound public health significance. Neuroticism is a robust correlate and predictor of many different mental and physical disorders, comorbidity among them, and the frequency of mental and general health service use. Indeed, neuroticism apparently is a predictor of the quality and longevity of our lives. Achieving a full understanding of the nature and origins of neuroticism, and the mechanisms through which neuroticism is linked to mental and physical disorders, should be a top priority for research. Knowing why neuroticism predicts such a wide variety of seemingly diverse outcomes should lead to improved understanding of commonalities among those outcomes and improved strategies for preventing them.

  3. An ETAS model with varying productivity rates

    NASA Astrophysics Data System (ADS)

    Harte, D. S.

    2014-07-01

    We present an epidemic type aftershock sequenc (ETAS) model where the offspring rates vary both spatially and temporally. This is achieved by distinguishing between those space-time volumes where the interpoint space and time distances are small, and those where they are considerably larger. We also question the nature of the background component in the ETAS model. Is it simply a temporal boundary correction (t = 0) or does it represent an additional tectonic process not described by the aftershock component? The form of these stochastic models should not be considered to be fixed. As we accumulate larger and better earthquake catalogues, GPS data, strain rates, etc., we have the ability to ask more complex questions about the nature of the process. By fitting modified models consistent with such questions, we should gain a better insight into the earthquake process. Hence, we consider a sequence of incrementally modified ETAS type models rather than `the' ETAS model.

  4. Tuning ferromagnetism by varying ion beam profiles

    NASA Astrophysics Data System (ADS)

    Hariwal, Rajesh V.; Malik, Hitendra K.; Asokan, K.

    2017-02-01

    Present study demonstrates a novel technique to tune the ferromagnetism at room temperature by varying the ion beam profiles from 3 to 7 mm during Carbon ion implantation in ZnO matrix and keeping other beam parameters constant. The interaction of implanted C ions with host ZnO matrix at different profiles result in variable ferromagnetism from 0.75 to 3.0  ×  10‑4 emu gm‑1 due to difference in the induced radiation pressure. Similar variation is also observed in the optical bandgap from 3.35 to 3.24 eV for different beam profiles. This study shows that the material properties can be tuned and controlled by the variation of beam profiles during the ion implantation.

  5. Time varying arctic climate change amplification

    SciTech Connect

    Chylek, Petr; Dubey, Manvendra K; Lesins, Glen; Wang, Muyin

    2009-01-01

    During the past 130 years the global mean surface air temperature has risen by about 0.75 K. Due to feedbacks -- including the snow/ice albedo feedback -- the warming in the Arctic is expected to proceed at a faster rate than the global average. Climate model simulations suggest that this Arctic amplification produces warming that is two to three times larger than the global mean. Understanding the Arctic amplification is essential for projections of future Arctic climate including sea ice extent and melting of the Greenland ice sheet. We use the temperature records from the Arctic stations to show that (a) the Arctic amplification is larger at latitudes above 700 N compared to those within 64-70oN belt, and that, surprisingly; (b) the ratio of the Arctic to global rate of temperature change is not constant but varies on the decadal timescale. This time dependence will affect future projections of climate changes in the Arctic.

  6. Varying ghost dark energy and particle creation

    NASA Astrophysics Data System (ADS)

    Khurshudyan, M.

    2016-02-01

    One of the models of dark energy is the ghost dark energy, which has a geometrical origin. Recently, a certain type of phenomenological modification of ghost dark energy has been suggested which motivated us for this work. The goal of this paper is twofold. First, we would like to study the cosmological scenario involving interacting varying ghost dark energy. A cosmographic analysis of a non-interacting model is also performed. Then, we study the particle creation following the straight analogy between quantization in Minkowski background and canonical quantization of a scalar field in curved dynamical backgrounds. Particular attention will be paid to massless-particle production from a radiation-dominated universe (according to our toy model) which evolves to our large-scale universe. Constraints on the parameters of the models obtained during the cosmographic analysis did allow to demonstrate the possibility of a massless-particle creation in a radiation-dominated universe.

  7. Photon Propagation in Slowly Varying Electromagnetic Fields

    NASA Astrophysics Data System (ADS)

    Karbstein, F.

    2017-03-01

    Effective theory of soft photons in slowly varying electromagnetic background fields is studied at one-loop order in QED. This is of relevance for the study of all-optical signatures of quantum vacuum nonlinearity in realistic electromagnetic background fields as provided by high-intensity lasers. The central result derived in this article is a new analytical expression for the photon polarization tensor in two linearly polarized counterpropagating pulsed Gaussian laser beams. Treating the peak field strengths of both laser beams as free parameters, this field configuration can be considered as interpolating between the limiting cases of a purely right- or left-moving laser beam (if one of the peak field strengths is set equal to zero) and the standing-wave type scenario with two counter-propagating beams of equal strength.

  8. [Comparative toxicity of photosensitizers in varying destruction].

    PubMed

    Sinitsina, O O; Zholdakova, Z I; Poliakova, E E; Golovach, E N; Sycheva, L P; Beliaeva, N N; Kuznetsova, N A

    2007-01-01

    The toxicity of the photosensitizers proflavine acetate (PA) versus methylene blue (MB) was evaluated during their varying destruction. Under the influence of visible light, a partial (25%) transformation of the photosensitizers was shown to be attended by their enhanced toxicity and 100% destruction of the parent substances caused a reduction in their hazard. PA and its phototransformation products mainly affect the antiperoxide protection system and the structural and functional states of the liver, kidney, and duodenum. The maximum noneffective dose is 0.002 mg/kg. The possibility of using PA for water disinfection depends on the ratio of safe and effective concentrations. A partial (25%) MB destruction products cause mutagenic effects; the permissible dose of the mutagen is 0.00025 mg/kg. MB is not recommended for disinfection of all types of waters.

  9. Application of Hamilton's law of varying action

    NASA Technical Reports Server (NTRS)

    Bailey, C. D.

    1975-01-01

    The law of varying action enunciated by Hamilton in 1834-1835 permits the direct analytical solution of the problems of mechanics, both stationary and nonstationary, without consideration of force equilibrium and the theory of differential equations associated therewith. It has not been possible to obtain direct analytical solutions to nonstationary systems through the use of energy theory, which has been limited for 140 years to the principle of least action and to Hamilton's principle. It is shown here that Hamilton's law permits the direct analytical solution to nonstationary, initial value systems in the mechanics of solids without any knowledge or use of the theory of differential equations. Solutions are demonstrated for nonconservative, nonstationary particle motion, both linear and nonlinear.

  10. Significance of research.

    PubMed

    Kanpolat, Y

    2002-01-01

    The development of the central nervous system (CNS) in humans is the most important factor differentiating the human being from other species. Intelligence is the most important result of evolution of the CNS in humans. However, human intelligence is not a static factor, having evolved during the historical progression of cultural factors and educational systems. Since the Middle Ages, universities have been the most dominant open-society institutions to regulate intellectual influences, share scientific knowledge and values, and promote research in natural sciences. Research is particularly important in contemporary neurosurgery and neurological sciences with regard to the development of new techniques and testing of the acquired knowledge of the CNS. Research activities in neuroscience and neurosurgery have especially involved anatomical and functional aspects. However, advances in molecular biology and genetics have been remarkably effective in research activities in neurosciences. Such progress will help us to understand nature, environment and humans. Of course, research is now a domain of method, organisation and financial gain. The dedication, heroism and creativity which used to be the driving forces behind scientific research are now diminishing in value and are a source of controversy.

  11. Time varying, multivariate volume data reduction

    SciTech Connect

    Ahrens, James P; Fout, Nathaniel; Ma, Kwan - Liu

    2010-01-01

    Large-scale supercomputing is revolutionizing the way science is conducted. A growing challenge, however, is understanding the massive quantities of data produced by large-scale simulations. The data, typically time-varying, multivariate, and volumetric, can occupy from hundreds of gigabytes to several terabytes of storage space. Transferring and processing volume data of such sizes is prohibitively expensive and resource intensive. Although it may not be possible to entirely alleviate these problems, data compression should be considered as part of a viable solution, especially when the primary means of data analysis is volume rendering. In this paper we present our study of multivariate compression, which exploits correlations among related variables, for volume rendering. Two configurations for multidimensional compression based on vector quantization are examined. We emphasize quality reconstruction and interactive rendering, which leads us to a solution using graphics hardware to perform on-the-fly decompression during rendering. In this paper we present a solution which addresses the need for data reduction in large supercomputing environments where data resulting from simulations occupies tremendous amounts of storage. Our solution employs a lossy encoding scheme to acrueve data reduction with several options in terms of rate-distortion behavior. We focus on encoding of multiple variables together, with optional compression in space and time. The compressed volumes can be rendered directly with commodity graphics cards at interactive frame rates and rendering quality similar to that of static volume renderers. Compression results using a multivariate time-varying data set indicate that encoding multiple variables results in acceptable performance in the case of spatial and temporal encoding as compared to independent compression of variables. The relative performance of spatial vs. temporal compression is data dependent, although temporal compression has the

  12. 40 CFR 1508.27 - Significantly.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... species or its habitat that has been determined to be critical under the Endangered Species Act of 1973... (human, national), the affected region, the affected interests, and the locality. Significance varies... areas. (4) The degree to which the effects on the quality of the human environment are likely to...

  13. Optimal transport in time-varying small-world networks

    NASA Astrophysics Data System (ADS)

    Chen, Qu; Qian, Jiang-Hai; Zhu, Liang; Han, Ding-Ding

    2016-03-01

    The time-order of interactions, which is regulated by some intrinsic activity, surely plays a crucial role regarding the transport efficiency of transportation systems. Here we study the optimal transport structure by measure of the length of time-respecting paths. Our network is built from a two-dimensional regular lattice, and long-range connections are allocated with probability Pi j˜rij -α , where ri j is the Manhattan distance. By assigning each shortcut an activity rate subjected to its geometric distance τi j˜rij -C , long-range links become active intermittently, leading to the time-varying dynamics. We show that for 0 varying transportation networks. Empirical studies on British Airways and Austrian Airlines provide consistent evidence with our conclusion.

  14. Lamb Wave Propagation in Varying Thermal Environments

    DTIC Science & Technology

    2007-03-01

    recent years. Typical Nondestructive Evaluation ( NDE ) techniques include ultrasonic technology, acoustic emission, magnetic field analysis, penetrant...sensor. Therefore, they have been combined with other NDE techniques to identify the location of damage in larger structures. The pitch-catch method...Piezoelectric Wafer Active Sensor Ultrasonics One new method implemented in the NDE of structures is the use of the Piezoelectric Wafer Active Sensor

  15. Delivery of continuously-varying stimuli using channelrhodopsin-2

    PubMed Central

    Tchumatchenko, Tatjana; Newman, Jonathan P.; Fong, Ming-fai; Potter, Steve M.

    2013-01-01

    To study sensory processing, stimuli are delivered to the sensory organs of animals and evoked neural activity is recorded downstream. However, noise and uncontrolled modulatory input can interfere with repeatable delivery of sensory stimuli to higher brain regions. Here we show how channelrhodopsin-2 (ChR2) can be used to deliver continuous, subthreshold, time-varying currents to neurons at any point along the sensory-motor pathway. To do this, we first deduce the frequency response function of ChR2 using a Markov model of channel kinetics. We then confirm ChR2's frequency response characteristics using continuously-varying optical stimulation of neurons that express one of three ChR2 variants. We find that wild-type ChR2 and the E123T/H134R mutant (“ChETA”) can pass continuously-varying subthreshold stimuli with frequencies up to ~70 Hz. Additionally, we find that wild-type ChR2 exhibits a strong resonance at ~6–10 Hz. Together, these results indicate that ChR2-derived optogenetic tools are useful for delivering highly repeatable artificial stimuli that mimic in vivo synaptic bombardment. PMID:24367294

  16. On Varying-coefficient Independence Screening for High-dimensional Varying-coefficient Models.

    PubMed

    Song, Rui; Yi, Feng; Zou, Hui

    2014-01-01

    Varying coefficient models have been widely used in longitudinal data analysis, nonlinear time series, survival analysis, and so on. They are natural non-parametric extensions of the classical linear models in many contexts, keeping good interpretability and allowing us to explore the dynamic nature of the model. Recently, penalized estimators have been used for fitting varying-coefficient models for high-dimensional data. In this paper, we propose a new computationally attractive algorithm called IVIS for fitting varying-coefficient models in ultra-high dimensions. The algorithm first fits a gSCAD penalized varying-coefficient model using a subset of covariates selected by a new varying-coefficient independence screening (VIS) technique. The sure screening property is established for VIS. The proposed algorithm then iterates between a greedy conditional VIS step and a gSCAD penalized fitting step. Simulation and a real data analysis demonstrate that IVIS has very competitive performance for moderate sample size and high dimension.

  17. On Varying-coefficient Independence Screening for High-dimensional Varying-coefficient Models

    PubMed Central

    Song, Rui; Yi, Feng; Zou, Hui

    2014-01-01

    Varying coefficient models have been widely used in longitudinal data analysis, nonlinear time series, survival analysis, and so on. They are natural non-parametric extensions of the classical linear models in many contexts, keeping good interpretability and allowing us to explore the dynamic nature of the model. Recently, penalized estimators have been used for fitting varying-coefficient models for high-dimensional data. In this paper, we propose a new computationally attractive algorithm called IVIS for fitting varying-coefficient models in ultra-high dimensions. The algorithm first fits a gSCAD penalized varying-coefficient model using a subset of covariates selected by a new varying-coefficient independence screening (VIS) technique. The sure screening property is established for VIS. The proposed algorithm then iterates between a greedy conditional VIS step and a gSCAD penalized fitting step. Simulation and a real data analysis demonstrate that IVIS has very competitive performance for moderate sample size and high dimension. PMID:25484548

  18. High and varying prices for privately insured patients underscore hospital market power.

    PubMed

    White, Chapin; Bond, Amelia M; Reschovsky, James D

    2013-09-01

    Across 13 selected U.S. metropolitan areas, hospital prices for privately insured patients are much higher than Medicare payment rates and vary widely across and within markets, according to a study by the Center for Studying Health System Change (HSC) based on claims data for about 590,000 active and retired nonelderly autoworkers and their dependents. Across the 13 communities, aver­age hospital prices for privately insured patients are about one-and-a-half times Medicare rates for inpatient care and two times what Medicare pays for outpa­tient care. Within individual communities, prices vary widely, with the highest-priced hospital typically paid 60 percent more for inpatient services than the lowest-priced hospital. The price gap within markets is even greater for hospital outpatient care, with the highest-priced hospital typically paid nearly double the lowest-priced hospital. In contrast to the wide variation in hospital prices for pri­vately insured patients across and within markets, prices for primary care physi­cian services generally are close to Medicare rates and vary little within markets. Prices for specialist physician services, however, are higher relative to Medicare and vary more across and within markets. Of the 13 markets, five are in Michigan, which has an unusually concentrated private insurance market, with one insurer commanding a 70-percent market share. Despite the presence of a dominant insurer, almost all Michigan hospi­tals command prices that are higher than Medicare, and some hospitals com­mand prices that are twice what Medicare pays. In the eight markets outside of Michigan, private insurers generally pay even higher hospital prices, with even wider gaps between high- and low-priced hospitals. The variation in hospital and specialist physician prices within communities underscores that some hospitals and physicians have significant market power to command high prices, even in markets with a dominant insurer.

  19. Does the Newtonian Gravity "Constant" G Vary?

    NASA Astrophysics Data System (ADS)

    Noerdlinger, Peter D.

    2015-08-01

    A series of measurements of Newton's gravity constant, G, dating back as far as 1893, yielded widely varying values, the variation greatly exceeding the stated error estimates (Gillies, 1997; Quinn, 2000, Mohr et al 2008). The value of G is usually said to be unrelated to other physics, but we point out that the 8B Solar Neutrino Rate ought to be very sensitive. Improved pulsar timing could also help settle the issue as to whether G really varies. We claim that the variation in measured values over time (1893-2014 C.E.) is a more serious problem than the failure of the error bars to overlap; it appears that challenging or adjusting the error bars hardly masks the underlying disagreement in central values. We have assessed whether variations in the gravitational potential due to (for example) local dark matter (DM) could explain the variations. We find that the required potential fluctuations could transiently accelerate the Solar System and nearby stars to speeds in excess of the Galactic escape speed. Previous theories for the variation in G generally deal with supposed secular variation on a cosmological timescale, or very rapid oscillations whose envelope changes on that scale (Steinhardt and Will 1995). Therefore, these analyses fail to support variations on the timescale of years or spatial scales of order parsecs, which would be required by the data for G. We note that true variations in G would be associated with variations in clock rates (Derevianko and Pospelov 2014; Loeb and Maoz 2015), which could mask changes in orbital dynamics. Geringer-Sameth et al (2014) studied γ-ray emission from the nearby Reticulum dwarf galaxy, which is expected to be free of "ordinary" (stellar, black hole) γ-ray sources and found evidence for DM decay. Bernabei et al (2003) also found evidence for DM penetrating deep underground at Gran Sasso. If, indeed, variations in G can be tied to variations in gravitational potential, we have a new tool to assess the DM density.

  20. Efficient Encoding and Rendering of Time-Varying Volume Data

    NASA Technical Reports Server (NTRS)

    Ma, Kwan-Liu; Smith, Diann; Shih, Ming-Yun; Shen, Han-Wei

    1998-01-01

    Visualization of time-varying volumetric data sets, which may be obtained from numerical simulations or sensing instruments, provides scientists insights into the detailed dynamics of the phenomenon under study. This paper describes a coherent solution based on quantization, coupled with octree and difference encoding for visualizing time-varying volumetric data. Quantization is used to attain voxel-level compression and may have a significant influence on the performance of the subsequent encoding and visualization steps. Octree encoding is used for spatial domain compression, and difference encoding for temporal domain compression. In essence, neighboring voxels may be fused into macro voxels if they have similar values, and subtrees at consecutive time steps may be merged if they are identical. The software rendering process is tailored according to the tree structures and the volume visualization process. With the tree representation, selective rendering may be performed very efficiently. Additionally, the I/O costs are reduced. With these combined savings, a higher level of user interactivity is achieved. We have studied a variety of time-varying volume datasets, performed encoding based on data statistics, and optimized the rendering calculations wherever possible. Preliminary tests on workstations have shown in many cases tremendous reduction by as high as 90% in both storage space and inter-frame delay.

  1. A finite crack with arbitrarily varied surface piezoelectricity

    NASA Astrophysics Data System (ADS)

    Xu, Yang; Wang, Xu

    2017-01-01

    We study the contribution of arbitrarily varied surface piezoelectricity to the anti-plane deformation and in-plane electric fields of a hexagonal piezoelectric material containing a finite crack. The varied surface piezoelectricity is incorporated by using an extended version of the continuum-based surface/interface model of Gurtin and Murdoch. In our discussion, the surface properties, including the surface elastic stiffness, the surface piezoelectric modulus and the surface dielectric permittivity, are assumed to be varied arbitrarily along the crack surfaces. By using the Green’s function method, the original boundary value problem is reduced to a system of two coupled first-order Cauchy singular integro-differential equations. Through a diagonalization strategy, the coupled system is transformed into two independent singular integro-differential equations, each of which can be numerically solved by using the collocation method. Our results indicate that the variation of the surface electroelastic moduli exerts a significant influence on the crack opening displacement, the electric potential jump across the crack faces and on the strengths of the logarithmic singularity in stresses and electric displacements at the crack tips.

  2. Serotonin release varies with brain tryptophan levels

    NASA Technical Reports Server (NTRS)

    Schaechter, Judith D.; Wurtman, Richard J.

    1990-01-01

    This study examines directly the effects on serotonin release of varying brain tryptophan levels within the physiologic range. It also addresses possible interactions between tryptophan availability and the frequency of membrane depolarization in controlling serotonin release. We demonstrate that reducing tryptophan levels in rat hypothalamic slices (by superfusing them with medium supplemented with 100 microM leucine) decreases tissue serotonin levels as well as both the spontaneous and the electrically-evoked serotonin release. Conversely, elevating tissue tryptophan levels (by superfusing slices with medium supplemented with 2 microM tryptophan) increases both the tissue serotonin levels and the serotonin release. Serotonin release was found to be affected independently by the tryptophan availability and the frequency of electrical field-stimulation (1-5 Hz), since increasing both variables produced nearly additive increases in release. These observations demonstrate for the first time that both precursor-dependent elevations and reductions in brain serotonin levels produce proportionate changes in serotonin release, and that the magnitude of the tryptophan effect is unrelated to neuronal firing frequency. The data support the hypothesis that serotonin release is proportionate to intracellular serotonin levels.

  3. Rumor Detection over Varying Time Windows.

    PubMed

    Kwon, Sejeong; Cha, Meeyoung; Jung, Kyomin

    2017-01-01

    This study determines the major difference between rumors and non-rumors and explores rumor classification performance levels over varying time windows-from the first three days to nearly two months. A comprehensive set of user, structural, linguistic, and temporal features was examined and their relative strength was compared from near-complete date of Twitter. Our contribution is at providing deep insight into the cumulative spreading patterns of rumors over time as well as at tracking the precise changes in predictive powers across rumor features. Statistical analysis finds that structural and temporal features distinguish rumors from non-rumors over a long-term window, yet they are not available during the initial propagation phase. In contrast, user and linguistic features are readily available and act as a good indicator during the initial propagation phase. Based on these findings, we suggest a new rumor classification algorithm that achieves competitive accuracy over both short and long time windows. These findings provide new insights for explaining rumor mechanism theories and for identifying features of early rumor detection.

  4. TIME-VARYING DYNAMICAL STAR FORMATION RATE

    SciTech Connect

    Lee, Eve J.; Chang, Philip; Murray, Norman

    2015-02-10

    We present numerical evidence of dynamic star formation in which the accreted stellar mass grows superlinearly with time, roughly as t {sup 2}. We perform simulations of star formation in self-gravitating hydrodynamic and magnetohydrodynamic turbulence that is continuously driven. By turning the self-gravity of the gas in the simulations on or off, we demonstrate that self-gravity is the dominant physical effect setting the mass accretion rate at early times before feedback effects take over, contrary to theories of turbulence-regulated star formation. We find that gravitational collapse steepens the density profile around stars, generating the power-law tail on what is otherwise a lognormal density probability distribution function. Furthermore, we find turbulent velocity profiles to flatten inside collapsing regions, altering the size-line width relation. This local flattening reflects enhancements of turbulent velocity on small scales, as verified by changes to the velocity power spectra. Our results indicate that gas self-gravity dynamically alters both density and velocity structures in clouds, giving rise to a time-varying star formation rate. We find that a substantial fraction of the gas that forms stars arrives via low-density flows, as opposed to accreting through high-density filaments.

  5. Proactive inhibitory control varies with task context.

    PubMed

    Wardak, Claire; Ramanoël, Stephen; Guipponi, Olivier; Boulinguez, Philippe; Ben Hamed, Suliann

    2012-12-01

    The goal of executive control is to adjust our behaviour to the environment. It involves not only the continuous planning and adaptation of actions but also the inhibition of inappropriate movements. Recently, a proactive form of inhibitory control has been shown, demonstrating that actions can be withheld, in an uncertain environment, thanks to the proactive locking of the mechanism by which motor commands are triggered (e.g. while waiting at traffic lights in a dense pedestrian zone, one will refrain in anticipation of a brisk acceleration when the green light comes on). However, little is known about this executive function and it remains unclear whether the overall amount of inhibitory control can be modulated as a function of the context. Here, we show that the level of this control varies parametrically as a function of the exogenous and endogenous factors setting the task context. We also show that the level of implemented proactive inhibitory control is dynamically readjusted to match the implicit temporal structure of the environment. These observations are discussed in relation to possible underlying functional substrates and related neurological and psychiatric pathologies.

  6. Rumor Detection over Varying Time Windows

    PubMed Central

    Kwon, Sejeong; Jung, Kyomin

    2017-01-01

    This study determines the major difference between rumors and non-rumors and explores rumor classification performance levels over varying time windows—from the first three days to nearly two months. A comprehensive set of user, structural, linguistic, and temporal features was examined and their relative strength was compared from near-complete date of Twitter. Our contribution is at providing deep insight into the cumulative spreading patterns of rumors over time as well as at tracking the precise changes in predictive powers across rumor features. Statistical analysis finds that structural and temporal features distinguish rumors from non-rumors over a long-term window, yet they are not available during the initial propagation phase. In contrast, user and linguistic features are readily available and act as a good indicator during the initial propagation phase. Based on these findings, we suggest a new rumor classification algorithm that achieves competitive accuracy over both short and long time windows. These findings provide new insights for explaining rumor mechanism theories and for identifying features of early rumor detection. PMID:28081135

  7. Device for varying engine valve timing

    SciTech Connect

    Hampton, K.

    1988-07-05

    A device is described for angularly displacing a camshaft relative to the crankshaft of an IC engine to vary the engine valve timing, comprising; a hub member; means to attach the hub member to the engine crankshaft; a drive member rotatably mounted on the hub member, and means connecting the drive member in driving relationship with the engine crankshaft; an advancing member; a first means interconnecting the advancing member with the hub member affecting limited axial movement of the advancing member relative to the hub member; a second means interconnecting the advancing member with the drive member which upon axial movement of the advancing member causes limited rotation of the drive member relative to the hub member; an annular means mounted on the hub member, the advancing member mounted on the annular means; coacting meshing means formed in part on the annular means for moving the advancing member axially relative to the hub upon limited rotation of the annular means relative to the hub; and a non-rotational retarder means which when actuated applies a retarding torque to the annular means causing limited rotation of the annular means relative to the hub and thus cause the advancing member to move axially of the hub whereby the drive member is moved a limited angular distance relative to the hub member.

  8. Vector curvaton with varying kinetic function

    SciTech Connect

    Dimopoulos, Konstantinos; Karciauskas, Mindaugas; Wagstaff, Jacques M.

    2010-01-15

    A new model realization of the vector curvaton paradigm is presented and analyzed. The model consists of a single massive Abelian vector field, with a Maxwell-type kinetic term. By assuming that the kinetic function and the mass of the vector field are appropriately varying during inflation, it is shown that a scale-invariant spectrum of superhorizon perturbations can be generated. These perturbations can contribute to the curvature perturbation of the Universe. If the vector field remains light at the end of inflation it is found that it can generate substantial statistical anisotropy in the spectrum and bispectrum of the curvature perturbation. In this case the non-Gaussianity in the curvature perturbation is predominantly anisotropic, which will be a testable prediction in the near future. If, on the other hand, the vector field is heavy at the end of inflation then it is demonstrated that particle production is approximately isotropic and the vector field alone can give rise to the curvature perturbation, without directly involving any fundamental scalar field. The parameter space for both possibilities is shown to be substantial. Finally, toy models are presented which show that the desired variation of the mass and kinetic function of the vector field can be realistically obtained, without unnatural tunings, in the context of supergravity or superstrings.

  9. Scrotal abscess: Varied etiology, associations, and management

    PubMed Central

    Ramareddy, Raghu S.; Alladi, Anand

    2016-01-01

    Aim: To report a series of scrotal abscess, a rare problem, their etiology, and management. Materials and Methods: A retrospective study of children who presented with scrotal abscess between January 2010 and March 2015, analyzed with respect to clinical features, pathophysiology of spread and management. Results: Eight infants and a 3-year-old phenotypically male child presented with scrotal abscess as a result of abdominal pathologies which included mixed gonadal dysgenesis (MGD) [1]; three anorectal malformations with ectopic ureter [1], urethral stricture [1], and neurogenic bladder [1]; meconium peritonitis with meconium periorchitis [2], ileal atresia [1], and intra-abdominal abscess [1]; posturethroplasty for Y urethral duplication with metal stenosis [1] and idiopathic pyocele [1]. Transmission of the organism had varied routes include fallopian tube [1], urethra ejaculatory reflux [4], hematogenous [2], and the patent process of vaginalis [2]. Two of the nine required extensive evaluation for further management. Treating the predisposing pathology resolved scrotal abscesses in eight of nine patients, one of whom, required vasectomy additionally. Idiopathic pyocele responded to needle aspiration and antibiotics. Conclusion: Scrotal abscess needs a high index of suspicion for predisposing pathology, especially in infants. Laparoscopy is safe and effective in the management of the MGD and ectopic ureter. PMID:27695207

  10. Stratospheric Impact of Varying Sea Surface Temperatures

    NASA Technical Reports Server (NTRS)

    Newman, Paul A.; Nash, Eric R.; Nielsen, Jon E.; Waugh, Darryn; Pawson, Steven

    2004-01-01

    The Finite-Volume General Circulation Model (FVGCM) has been run in 50 year simulations with the: 1) 1949-1999 Hadley Centre sea surface temperatures (SST), and 2) a fixed annual cycle of SSTs. In this presentation we first show that the 1949-1999 FVGCM simulation produces a very credible stratosphere in comparison to an NCEP/NCAR reanalysis climatology. In particular, the northern hemisphere has numerous major and minor stratospheric warming, while the southern hemisphere has only a few over the 50-year simulation. During the northern hemisphere winter, temperatures are both warmer in the lower stratosphere and the polar vortex is weaker than is found in the mid-winter southern hemisphere. Mean temperature differences in the lower stratosphere are shown to be small (less than 2 K), and planetary wave forcing is found to be very consistent with the climatology. We then will show the differences between our varying SST simulation and the fixed SST simulation in both the dynamics and in two parameterized trace gases (ozone and methane). In general, differences are found to be small, with subtle changes in planetary wave forcing that lead to reduced temperatures in the SH and increased temperatures in the NH.

  11. Tectonic significance of serpentinites

    NASA Astrophysics Data System (ADS)

    Guillot, Stéphane; Schwartz, Stéphane; Reynard, Bruno; Agard, Philippe; Prigent, Cécile

    2015-04-01

    At plate boundaries, where deformation is localized along centimetre- to kilometre-scale shear zones, the influence of serpentinite on tectonic processes is linked to its unique rheological properties. In this paper we review the physical properties of serpentinites and their role in tectonic processes. At the ocean-continent transition, serpentinization weakens the upper mantle layer, promoting strain localization and allowing the normal faults in the distal margin to root at low angle. Similarly, at slow to ultra-slow spreading ridges, serpentinite is potentially very abundant at the seafloor and locally associated with domal structures. Extensional deformation is localized in a ~ 100 m thick shear zone at the footwall of detachment zones dominated by serpentine derived minerals. Within subduction zone, the depth of decoupling between the mantle wedge and the subducting slab corresponds to the stability depth of serpentine weak mineral. Dehydration of serpentine has also been hypothesized to play an important role in the origin of double seismic zones, however the exact mechanism through which dehydration promotes seismicity remains a matter of debate. During exhumation of high-pressure or ultrahigh-pressure rocks, the opposite trajectories of exhumation and subduction require a decoupling zone within the subducting slab. A serpentinized layer has the potential to become a decoupling zone between the oceanic crust and underlying lithosphere. The buoyancy of serpentinite also likely contributes to eclogite exhumation. Finally, along major strike-slip faults, serpentinites have been associated with fault creep, as well as low fault strength. The presence of serpentinite blocks along creeping segments of active faults worldwide is therefore likely to originate from fluids deriving from the progressive dehydration of the mantle wedge that move such bodies upward.

  12. Morphable Word Clouds for Time-Varying Text Data Visualization.

    PubMed

    Chi, Ming-Te; Lin, Shih-Syun; Chen, Shiang-Yi; Lin, Chao-Hung; Lee, Tong-Yee

    2015-12-01

    A word cloud is a visual representation of a collection of text documents that uses various font sizes, colors, and spaces to arrange and depict significant words. The majority of previous studies on time-varying word clouds focuses on layout optimization and temporal trend visualization. However, they do not fully consider the spatial shapes and temporal motions of word clouds, which are important factors for attracting people's attention and are also important cues for human visual systems in capturing information from time-varying text data. This paper presents a novel method that uses rigid body dynamics to arrange multi-temporal word-tags in a specific shape sequence under various constraints. Each word-tag is regarded as a rigid body in dynamics. With the aid of geometric, aesthetic, and temporal coherence constraints, the proposed method can generate a temporally morphable word cloud that not only arranges word-tags in their corresponding shapes but also smoothly transforms the shapes of word clouds over time, thus yielding a pleasing time-varying visualization. Using the proposed frame-by-frame and morphable word clouds, people can observe the overall story of a time-varying text data from the shape transition, and people can also observe the details from the word clouds in frames. Experimental results on various data demonstrate the feasibility and flexibility of the proposed method in morphable word cloud generation. In addition, an application that uses the proposed word clouds in a simulated exhibition demonstrates the usefulness of the proposed method.

  13. Dynamic Modulation of Innate Immune Response by Varying Dosages of Lipopolysaccharide (LPS) in Human Monocytic Cells*

    PubMed Central

    Morris, Matthew C.; Gilliam, Elizabeth A.; Button, Julia; Li, Liwu

    2014-01-01

    Innate monocytes and macrophages can be dynamically programmed into distinct states depending upon the strength of external stimuli. Innate programming may bear significant relevance to the pathogenesis and resolution of human inflammatory diseases. However, systems analyses with regard to the dynamic programming of innate leukocytes are lacking. In this study, we focused on the dynamic responses of human promonocytic THP-1 cells to lipopolysaccharide (LPS). We observed that varying dosages of LPS differentially modulate the expression of selected pro- and anti- inflammatory mediators such as IL-6 and IL-33. Super-low dosages of LPS preferentially induced the pro-inflammatory mediator IL-6, while higher dosages of LPS induced both IL-6 and IL-33. Mechanistically, we demonstrated that super-low and high doses of LPS cause differential activation of GSK3 and Akt, as well as the transcription factors FoxO1 and CREB. Inhibition of GSK3 enabled THP-1 cells to express IL-33 when challenged with super-low dose LPS. On the other hand, activation of CREB with adenosine suppressed IL-6 expression. Taken together, our study reveals a dynamic modulation of monocytic cells in response to varying dosages of endotoxin, and may shed light on our understanding of the dynamic balance that controls pathogenesis and resolution of inflammatory diseases. PMID:24970893

  14. Significant inhibitory impact of dibenzyl trisulfide and extracts of Petiveria alliacea on the activities of major drug-metabolizing enzymes in vitro: An assessment of the potential for medicinal plant-drug interactions.

    PubMed

    Murray, J; Picking, D; Lamm, A; McKenzie, J; Hartley, S; Watson, C; Williams, L; Lowe, H; Delgoda, R

    2016-06-01

    Dibenzyl trisulfide (DTS) is the major active ingredient expressed in Petiveria alliacea L., a shrub widely used for a range of conditions, such as, arthritis, asthma and cancer. Given its use alone and concomitantly with prescription medicines, we undertook to investigate its impact on the activities of important drug metabolizing enzymes, the cytochromes P450 (CYP), a key family of enzymes involved in many adverse drug reactions. DTS and seven standardized extracts from the plant were assessed for their impact on the activities of CYPs 1A2, 2C19, 2C9, 2D6 and 3A4 on a fluorometric assay. DTS revealed significant impact against the activities of CYPs 1A2, 2C19 and 3A4 with IC50 values of 1.9, 4.0 and 3.2μM, respectively, which are equivalent to known standard inhibitors of these enzymes (furafylline, and tranylcypromine), and the most potent interaction with CYP1A2 displayed irreversible enzyme kinetics. The root extract, drawn with 96% ethanol (containing 2.4% DTS), displayed IC50 values of 5.6, 3.9 and 4.2μg/mL respectively, against the same isoforms, CYPs 1A2, 2C19 and 3A4. These investigations identify DTS as a valuable CYP inhibitor and P. alliacea as a candidate plant worthy of clinical trials to confirm the conclusions that extracts yielding high DTS may lead to clinically relevant drug interactions, whilst extracts yielding low levels of DTS, such as aqueous extracts, are unlikely to cause adverse herb-drug interactions.

  15. Fungi producing significant mycotoxins.

    PubMed

    2012-01-01

    Mycotoxins are secondary metabolites of microfungi that are known to cause sickness or death in humans or animals. Although many such toxic metabolites are known, it is generally agreed that only a few are significant in causing disease: aflatoxins, fumonisins, ochratoxin A, deoxynivalenol, zearalenone, and ergot alkaloids. These toxins are produced by just a few species from the common genera Aspergillus, Penicillium, Fusarium, and Claviceps. All Aspergillus and Penicillium species either are commensals, growing in crops without obvious signs of pathogenicity, or invade crops after harvest and produce toxins during drying and storage. In contrast, the important Fusarium and Claviceps species infect crops before harvest. The most important Aspergillus species, occurring in warmer climates, are A. flavus and A. parasiticus, which produce aflatoxins in maize, groundnuts, tree nuts, and, less frequently, other commodities. The main ochratoxin A producers, A. ochraceus and A. carbonarius, commonly occur in grapes, dried vine fruits, wine, and coffee. Penicillium verrucosum also produces ochratoxin A but occurs only in cool temperate climates, where it infects small grains. F. verticillioides is ubiquitous in maize, with an endophytic nature, and produces fumonisins, which are generally more prevalent when crops are under drought stress or suffer excessive insect damage. It has recently been shown that Aspergillus niger also produces fumonisins, and several commodities may be affected. F. graminearum, which is the major producer of deoxynivalenol and zearalenone, is pathogenic on maize, wheat, and barley and produces these toxins whenever it infects these grains before harvest. Also included is a short section on Claviceps purpurea, which produces sclerotia among the seeds in grasses, including wheat, barley, and triticale. The main thrust of the chapter contains information on the identification of these fungi and their morphological characteristics, as well as factors

  16. A melanocortin 1 receptor allele suggests varying pigmentation among Neanderthals.

    PubMed

    Lalueza-Fox, Carles; Römpler, Holger; Caramelli, David; Stäubert, Claudia; Catalano, Giulio; Hughes, David; Rohland, Nadin; Pilli, Elena; Longo, Laura; Condemi, Silvana; de la Rasilla, Marco; Fortea, Javier; Rosas, Antonio; Stoneking, Mark; Schöneberg, Torsten; Bertranpetit, Jaume; Hofreiter, Michael

    2007-11-30

    The melanocortin 1 receptor (MC1R) regulates pigmentation in humans and other vertebrates. Variants of MC1R with reduced function are associated with pale skin color and red hair in humans of primarily European origin. We amplified and sequenced a fragment of the MC1R gene (mc1r) from two Neanderthal remains. Both specimens have a mutation that was not found in approximately 3700 modern humans analyzed. Functional analyses show that this variant reduces MC1R activity to a level that alters hair and/or skin pigmentation in humans. The impaired activity of this variant suggests that Neanderthals varied in pigmentation levels, potentially on the scale observed in modern humans. Our data suggest that inactive MC1R variants evolved independently in both modern humans and Neanderthals.

  17. Attitudes as Object-Evaluation Associations of Varying Strength

    PubMed Central

    Fazio, Russell H.

    2009-01-01

    Historical developments regarding the attitude concept are reviewed, and set the stage for consideration of a theoretical perspective that views attitude, not as a hypothetical construct, but as evaluative knowledge. A model of attitudes as object-evaluation associations of varying strength is summarized, along with research supporting the model’s contention that at least some attitudes are represented in memory and activated automatically upon the individual’s encountering the attitude object. The implications of the theoretical perspective for a number of recent discussions related to the attitude concept are elaborated. Among these issues are the notion of attitudes as “constructions,” the presumed malleability of automatically-activated attitudes, correspondence between implicit and explicit measures of attitude, and postulated dual or multiple attitudes. PMID:19424447

  18. Audibility of time-varying signals in time-varying backgrounds: Model and data

    NASA Astrophysics Data System (ADS)

    Moore, Brian C. J.; Glasberg, Brian R.

    2004-05-01

    We have described a model for calculating the partial loudness of a steady signal in the presence of a steady background sound [Moore et al., J. Audio Eng. Soc. 45, 224-240 (1997)]. We have also described a model for calculating the loudness of time-varying signals [B. R. Glasberg and B. C. J. Moore, J. Audio Eng. Soc. 50, 331-342 (2002)]. These two models have been combined to allow calculation of the partial loudness of a time-varying signal in the presence of a time-varying background. To evaluate the model, psychometric functions for the detection of a variety of time-varying signals (e.g., telephone ring tones) have been measured in a variety of background sounds sampled from everyday listening situations, using a two-alternative forced-choice task. The different signals and backgrounds were interleaved, to create stimulus uncertainty, as would occur in everyday life. The data are used to relate the detectability index, d', to the calculated partial loudness. In this way, the model can be used to predict the detectability of any signal, based on its calculated partial loudness. [Work supported by MRC (UK) and by Nokia.

  19. Governors Take Varied Routes in Boosting Aid

    ERIC Educational Resources Information Center

    Ujifusa, Andrew

    2013-01-01

    As states consider increases to K-12 spending amid better economic conditions, governors on opposite sides of the partisan divide are proposing significantly different plans and arguments for the best ways to use new education aid. Two prime examples: Minnesota and Ohio, a pair of Midwestern states with chief executives intent on pumping more…

  20. Linear-parameter-varying gain-scheduled control of aerospace systems

    NASA Astrophysics Data System (ADS)

    Barker, Jeffrey Michael

    The dynamics of many aerospace systems vary significantly as a function of flight condition. Robust control provides methods of guaranteeing performance and stability goals across flight conditions. In mu-syntthesis, changes to the dynamical system are primarily treated as uncertainty. This method has been successfully applied to many control problems, and here is applied to flutter control. More recently, two techniques for generating robust gain-scheduled controller have been developed. Linear fractional transformation (LFT) gain-scheduled control is an extension of mu-synthesis in which the plant and controller are explicit functions of parameters measurable in real-time. This LFT gain-scheduled control technique is applied to the Benchmark Active Control Technology (BACT) wing, and compared with mu-synthesis control. Linear parameter-varying (LPV) gain-scheduled control is an extension of Hinfinity control to parameter varying systems. LPV gain-scheduled control directly incorporates bounds on the rate of change of the scheduling parameters, and often reduces conservatism inherent in LFT gain-scheduled control. Gain-scheduled LPV control of the BACT wing compares very favorably with the LFT controller. Gain-scheduled LPV controllers are generated for the lateral-directional and longitudinal axes of the Innovative Control Effectors (ICE) aircraft and implemented in nonlinear simulations and real-time piloted nonlinear simulations. Cooper-Harper and pilot-induced oscillation ratings were obtained for an initial design, a reference aircraft and a redesign. Piloted simulation results for the initial LPV gain-scheduled control of the ICE aircraft are compared with results for a conventional fighter aircraft in discrete pitch and roll angle tracking tasks. The results for the redesigned controller are significantly better than both the previous LPV controller and the conventional aircraft.

  1. [EEG background activity in patients with dementia of the Alzheimer type--with special reference to analysis by t-statistic significance probability mapping (SPM) in Alzheimer's disease and senile dementia].

    PubMed

    Miyauchi, T; Hagimoto, H; Saito, T; Endo, K; Ishii, M; Yamaguchi, T; Kajiwara, A; Matsushita, M

    1989-01-01

    EEG power amplitude and power ratio data obtained from 15 (3 men and 12 women) patients with Alzheimer's disease (AD) and 8 (2 men and 6 women) with senile dementia of Alzheimer type (SDAT) were compared with similar data from 40 age- and sex-matched normal controls. Compared with the healthy controls, both patient groups demonstrated increased EEG background slowing, and it indicated more slower in AD than in SDAT. Moreover, both groups showed characteristic findings respectively on EEG topography and t-statistic significance probability mapping (SPM). The differences between AD and their controls indicated high slowing with reductions in alpha 2, beta 1 and beta 2 activity. The SPMs of power ratio in theta and alpha 2 bands showed most prominent significance in the right posterior-temporal region and delta and beta bands did in the frontal region. Severe AD indicated only frontal delta slowing compared to mild AD. The differences between SDAT and their controls indicated only mild slowing in delta and theta bands. The SPM of power amplitude showed occipital slowing, whereas the SPM of power ratio showed the slowing in the frontal region. Judging from both topographic findings, these were considered to denote diffuse slow tendency. In summary, these results presumed that in AD, cortical damages followed by EEG slowing with reductions of alpha 2 and beta bands originated rapidly and thereafter developed subcortical (non-specific area in thalamus) changes with frontal delta activity on SPM. On the other hand, in SDAT, diffuse cortico-subcortical damages with diffuse slowing on EEG topography were caused gradually.

  2. Significantly higher activity of a cytoplasmic hammerhead ribozyme than a corresponding nuclear counterpart: engineered tRNAs with an extended 3′ end can be exported efficiently and specifically to the cytoplasm in mammalian cells

    PubMed Central

    Kuwabara, Tomoko; Warashina, Masaki; Koseki, Shiori; Sano, Masayuki; Ohkawa, Jun; Nakayama, Kazuhisa; Taira, Kazunari

    2001-01-01

    Hammerhead ribozymes were expressed under the control of similar tRNA promoters, localizing transcripts either in the cytoplasm or the nucleus. The tRNAVal-driven ribozyme (tRNA-Rz; tRNA with extra sequences at the 3′ end) that has been used in our ribozyme studies was exported efficiently into the cytoplasm and ribozyme activity was detected only in the cytoplasmic fraction. Both ends of the transported tRNA-Rz were characterized comprehensively and the results confirmed that tRNA-Rz had unprocessed 5′ and 3′ ends. Furthermore, it was also demonstrated that the activity of the exported ribozyme was significantly higher than that of the ribozyme which remained in the nucleus. We suggest that it is possible to engineer tRNA-Rz, which can be exported to the cytoplasm based on an understanding of secondary structures, and then tRNA-driven ribozymes may be co-localized with their target mRNAs in the cytoplasm of mammalian cells. PMID:11433023

  3. Pre-clinical development as microbicide of zinc tetra-ascorbo-camphorate, a novel terpenoid derivative: Potent in vitro inhibitory activity against both R5- and X4-tropic HIV-1 strains without significant in vivo mucosal toxicity

    PubMed Central

    Saïdi, Héla; Jenabian, Mohammad-Ali; Gombert, Bernard; Charpentier, Charlotte; Mannarini, Aurèle; Bélec, Laurent

    2008-01-01

    Background Terpenoid derivatives originating from many plants species, are interesting compounds with numerous biological effects, such as anti-HIV-1 activity. The zinc tetra-ascorbo-camphorate complex (or "C14"), a new monoterpenoid derivative was evaluated in vitro for its anti-HIV-1 activity on both R5- and X4-HIV-1 infection of primary target cells (macrophages, dendritic cells and T cells) and on HIV-1 transfer from dendritic cells to T cells. Results The toxicity study was carried out in vitro and also with the New Zealand White rabbit vaginal irritation model. C14 was found to be no cytotoxic at high concentrations (CC50 > 10 μM) and showed to be a potential HIV-1 inhibitor of infection of all the primary cells tested (EC50 = 1 μM). No significant changes could be observed in cervicovaginal tissue of rabbit exposed during 10 consecutive days to formulations containing up to 20 μM of C14. Conclusion Overall, these preclinical studies suggest that zinc tetra-ascorbo-camphorate derivative is suitable for further testing as a candidate microbicide to prevent male-to-female heterosexual acquisition of HIV-1. PMID:18522743

  4. Acetic acid treatment in S. cerevisiae creates significant energy deficiency and nutrient starvation that is dependent on the activity of the mitochondrial transcriptional complex Hap2-3-4-5

    PubMed Central

    Kitanovic, Ana; Bonowski, Felix; Heigwer, Florian; Ruoff, Peter; Kitanovic, Igor; Ungewiss, Christin; Wölfl, Stefan

    2012-01-01

    Metabolic pathways play an indispensable role in supplying cellular systems with energy and molecular building blocks for growth, maintenance and repair and are tightly linked with lifespan and systems stability of cells. For optimal growth and survival cells rapidly adopt to environmental changes. Accumulation of acetic acid in stationary phase budding yeast cultures is considered to be a primary mechanism of chronological aging and induction of apoptosis in yeast, which has prompted us to investigate the dependence of acetic acid toxicity on extracellular conditions in a systematic manner. Using an automated computer controlled assay system, we investigated and model the dynamic interconnection of biomass yield- and growth rate-dependence on extracellular glucose concentration, pH conditions and acetic acid concentration. Our results show that toxic concentrations of acetic acid inhibit glucose consumption and reduce ethanol production. In absence of carbohydrates uptake, cells initiate synthesis of storage carbohydrates, trehalose and glycogen, and upregulate gluconeogenesis. Accumulation of trehalose and glycogen, and induction of gluconeogenesis depends on mitochondrial activity, investigated by depletion of the Hap2-3-4-5 complex. Analyzing the activity of glycolytic enzymes, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase (PYK), and glucose-6-phosphate dehydrogenase (G6PDH) we found that while high acetic acid concentration increased their activity, lower acetic acids concentrations significantly inhibited these enzymes. With this study we determined growth and functional adjustment of metabolism to acetic acid accumulation in a complex range of extracellular conditions. Our results show that substantial acidification of the intracellular environment, resulting from accumulation of dissociated acetic acid in the cytosol, is required for acetic acid toxicity, which creates a state of energy deficiency and nutrient starvation. PMID:23050242

  5. Chlorophyllin significantly reduces benzo[a]pyrene [BP]-DNA adduct formation and alters Cytochrome P450 1A1 and 1B1 expression and EROD activity in normal human mammary epithelial cells (NHMECs)

    PubMed Central

    Keshava, Channa; Divi, Rao L.; Einem, Tracey L.; Richardson, Diana L.; Leonard, Sarah L.; Keshava, Nagalakshmi; Poirier, Miriam C.; Weston, Ainsley

    2008-01-01

    We hypothesized that chlorophyllin (CHLN) would reduce BP-DNA adduct levels. Using NHMECs exposed to 4 μM BP for 24 hr in the presence or absence of 5 μM CHLN, we measured BP-DNA adducts by chemiluminescence immunoassay (CIA). The protocol included the following experimental groups: BP alone, BP given simultaneously with CHLN (BP+CHLN) for 24 hr, CHLN given for 24 hr followed by BP for 24 hr (preCHLN, postBP), and CHLN given for 48 hr with BP added for the last 24 hr (preCHLN, postBP+CHLN). Incubation with CHLN decreased BPdG levels in all groups, with 87 % inhibition in the preCHLN, postBP+CHLN group. To examine metabolic mechanisms, we monitored expression by Affymetrix microarray (U133A), and found BP-induced up-regulation of CYP1A1 and CYP1B1 expression, as well as up-regulation of groups of interferon-inducible, inflammation and signal transduction genes. Incubation of cells with CHLN and BP in any combination decreased expression of many of these genes. Using real time PCR (RT-PCR) the maximal inhibition of BP-induced gene expression, >85% for CYP1A1 and >70% for CYP1B1, was observed in the preCHLN, postBP+CHLN group. To explore the relationship between transcription and enzyme activity, the ethoxyresorufin-O-deethylase (EROD) assay was used to measure the combined CYP1A1 and CYP1B1 activities. BP exposure caused the EROD levels to double, compared to the unexposed controls. The CHLN-exposed groups all showed EROD levels similar to the unexposed controls. Therefore, the addition of CHLN to BP-exposed cells reduced BPdG formation and CYP1A1 and CYP1B1 expression, but EROD activity was not significantly reduced. PMID:19152381

  6. Acetic acid treatment in S. cerevisiae creates significant energy deficiency and nutrient starvation that is dependent on the activity of the mitochondrial transcriptional complex Hap2-3-4-5.

    PubMed

    Kitanovic, Ana; Bonowski, Felix; Heigwer, Florian; Ruoff, Peter; Kitanovic, Igor; Ungewiss, Christin; Wölfl, Stefan

    2012-01-01

    Metabolic pathways play an indispensable role in supplying cellular systems with energy and molecular building blocks for growth, maintenance and repair and are tightly linked with lifespan and systems stability of cells. For optimal growth and survival cells rapidly adopt to environmental changes. Accumulation of acetic acid in stationary phase budding yeast cultures is considered to be a primary mechanism of chronological aging and induction of apoptosis in yeast, which has prompted us to investigate the dependence of acetic acid toxicity on extracellular conditions in a systematic manner. Using an automated computer controlled assay system, we investigated and model the dynamic interconnection of biomass yield- and growth rate-dependence on extracellular glucose concentration, pH conditions and acetic acid concentration. Our results show that toxic concentrations of acetic acid inhibit glucose consumption and reduce ethanol production. In absence of carbohydrates uptake, cells initiate synthesis of storage carbohydrates, trehalose and glycogen, and upregulate gluconeogenesis. Accumulation of trehalose and glycogen, and induction of gluconeogenesis depends on mitochondrial activity, investigated by depletion of the Hap2-3-4-5 complex. Analyzing the activity of glycolytic enzymes, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), pyruvate kinase (PYK), and glucose-6-phosphate dehydrogenase (G6PDH) we found that while high acetic acid concentration increased their activity, lower acetic acids concentrations significantly inhibited these enzymes. With this study we determined growth and functional adjustment of metabolism to acetic acid accumulation in a complex range of extracellular conditions. Our results show that substantial acidification of the intracellular environment, resulting from accumulation of dissociated acetic acid in the cytosol, is required for acetic acid toxicity, which creates a state of energy deficiency and nutrient starvation.

  7. How Does the Sun's Spectrum Vary?

    NASA Technical Reports Server (NTRS)

    Lean, Judith L.; DeLand, Matthew T.

    2011-01-01

    Recent observations made by the Spectral Irradiance Monitor (SIM) on the Solar Radiation and Climate Experiment (SORCE) spacecraft suggest that the Sun's visible and infrared spectral irradiance increased from 2004 to 2008, even as the total solar irradiance measured simultaneously by SORCE's Total Irradiance Monitor (TIM) decreased. As well, solar ultraviolet (UV) irradiance decreased 3 to 10 times more than expected from prior observations and model calculations of the known effects of sunspot and facular solar features. Analysis of the SIM spectral irradiance observations during the solar minimum epoch of 2008, when solar activity was essentially invariant, exposes trends in the SIM observations relative to both total solar irradiance and solar activity that are unlikely solar in origin. We suggest that the SIM's radically different solar variability characterization is a consequence of undetected instrument sensitivity drifts, not true solar spectrum changes. It is thus doubtful that simulations of climate and atmospheric change using SIM measurements are indicative of real behavior in the Earth's climate and atmosphere.

  8. CNX-012-570, a direct AMPK activator provides strong glycemic and lipid control along with significant reduction in body weight; studies from both diet-induced obese mice and db/db mice models

    PubMed Central

    2014-01-01

    Objectives AMP activated protein kinase (AMPK) regulates the coordination of anabolic and catabolic processes and is an attractive therapeutic target for T2DM, obesity and metabolic syndrome. We report the anti-hyperglycemic and anti-hyperlipidemic effects of CNX-012-570 is an orally bioavailable small molecule (molecular weight of 530 Daltons) that directly activates AMPK in DIO and db/db animal models of diabetes. Methods Activity and efficacy of the compound was tested in cell based as well as cell free systems in vitro. Male C57BL/6 mice fed with high fat diet (HFD) were assigned to either vehicle or CNX-012-570 (3 mg/kg, orally once a day) for 8 weeks (n = 8). Genetically diabetic db/db mice on chow diet were dosed with vehicle control or CNX-012-570 (2.5 mg/kg, orally once a day) for 6 weeks (n = 8). Results CNX-012-570 is a highly potent and orally bioavailable compound activating AMPK in both cell and cell free systems. It inhibits lipolysis (33%) and gluconeogenesis (28%) in 3T3L1 cells and rat primary hepatocytes respectively. The efficacy of the molecule was translated to both DIO and db/db animal models of diabetes. CNX-012-570 has reduced fasting blood glucose levels by 14%, body weight by 24% and fasting serum triglycerides (TG) by 24%. CNX-012-570 showed a 22% reduction in fed serum cholesterol levels and 19% increase in HDL levels. In db/db mice model, CNX-012-570 has shown 18% decrease in fed glucose and 32% decrease in fasting glucose with a 2.57% reduction in absolute HbA1c. Decrease in serum insulin and glucose AUC indicates the increased insulin sensitivity. Body weight was reduced by 13% with increased browning of adipose tissue and decreased inguinal and mesenteric fat mass. There was significant reduction in liver TG and liver total cholesterol. Conclusions CNX-012-570 has the potential to control hyperglycemia and hyperlipidemia. It also reduces body weight gain with an additional benefit of minimizing cardiovascular risks in

  9. Ice Accretion with Varying Surface Tension

    NASA Technical Reports Server (NTRS)

    Bilanin, Alan J.; Anderson, David N.

    1995-01-01

    During an icing encounter of an aircraft in flight, super-cooled water droplets impinging on an airfoil may splash before freezing. This paper reports tests performed to determine if this effect is significant and uses the results to develop an improved scaling method for use in icing test facilities. Simple laboratory tests showed that drops splash on impact at the Reynolds and Weber numbers typical of icing encounters. Further confirmation of droplet splash came from icing tests performed in the NaSA Lewis Icing Research Tunnel (IRT) with a surfactant added to the spray water to reduce the surface tension. The resulting ice shapes were significantly different from those formed when no surfactant was added to the water. These results suggested that the droplet Weber number must be kept constant to properly scale icing test conditions. Finally, the paper presents a Weber-number-based scaling method and reports results from scaling tests in the IRT in which model size was reduced up to a factor of 3. Scale and reference ice shapes are shown which confirm the effectiveness of this new scaling method.

  10. Psycho-Physical Effects of Varied Rest Intervals Following Warm-Up

    ERIC Educational Resources Information Center

    Aronchick, Joel; Burke, Edmund J.

    1977-01-01

    An assessment of the effects of rest intervals of varying lengths following a five minute warm-up revealed no significant differeence among them for perceived exertion, heart rate, and state anxiety. (MB)

  11. Hydroquinone–pyrrole dyads with varied linkers

    PubMed Central

    Huang, Hao; Karlsson, Christoffer; Strømme, Maria; Sjödin, Martin

    2016-01-01

    Summary A series of pyrroles functionalized in the 3-position with p-dimethoxybenzene via various linkers (CH2, CH2CH2, CH=CH, C≡C) has been synthesized. Their electronic properties have been deduced from 1H NMR, 13C NMR, and UV–vis spectra to detect possible interactions between the two aromatic subunits. The extent of conjugation between the subunits is largely controlled by the nature of the linker, with the largest conjugation found with the trans-ethene linker and the weakest with the aliphatic linkers. DFT calculations revealed substantial changes in the HOMO–LUMO gap that correlated with the extent of conjugation found experimentally. The results of this work are expected to open up for use of the investigated compounds as components of redox-active materials in sustainable, organic electrical energy storage devices. PMID:26877811

  12. Environmental determinants of participation in tourism and recreation of people with varying degrees of disability.

    PubMed

    Bergier, Barbara; Bergier, Józef; Kubińska, Zofia

    2010-01-01

    Environmental determinants for participation of disabled subjects in tourism and recreation comprise an important social problem. The amount and use of free time for individuals with disabilities in daily life, holidays, and vacation leave and the location for tourism and recreation were examined. Seven hundred and fifty individuals, aged 16-75 yr, with varying degrees of disability, from three eastern provinces of Poland: Podlaskie, Lubelskie and Podkarpackie were investigated. In these studies, a diagnostic survey method with the use of questionnaire, interviews, and analysis of data was carried out. It was found that individuals with disabilities have a significant amount of free time, which is usually spent with family and friends. Among the specific benefits of participation in physical activities are well-being, health improvement, and making new acquaintances. The main factors determining participation in tourism and recreation were price, a friendly group, and doctor recommendations.

  13. Correlation-based characterisation of time-varying dynamical complexity in the Earth's magnetosphere

    NASA Astrophysics Data System (ADS)

    Donner, Reik V.; Balasis, George; Kurths, Jürgen

    2014-05-01

    The dynamical behaviour of the magnetosphere is known to be a sensitive indicator for the response of the system to solar wind coupling. Since the solar activity commonly displays very interesting non-stationary and multi-scale dynamics, the magnetospheric response also exhibits a high degree of dynamical complexity associated with fundamentally different characteristics during periods of quiescence and magnetic storms. The resulting temporal complexity profile has been explored regarding several approaches from applied statistics, dynamical systems theory and statistical mechanics. Here, we propose an alternative way of looking at time-varying dynamical complexity of nonlinear geophysical time series utilising subtle but significant changes in the linear auto-correlation structure of the recorded data. Our approach is demonstrated to sensitively trace the dynamic signatures associated with intense magnetic storms, and to display reasonable skills in distinguishing between quiescence and storm periods. The potentials and methodological limitations of this new viewpoint are discussed in some detail.

  14. Correlation-based characterisation of time-varying dynamical complexity in the Earth's magnetosphere

    NASA Astrophysics Data System (ADS)

    Donner, R. V.; Balasis, G.

    2013-11-01

    The dynamical behaviour of the magnetosphere is known to be a sensitive indicator for the response of the system to solar wind coupling. Since the solar activity commonly displays very interesting non-stationary and multi-scale dynamics, the magnetospheric response also exhibits a high degree of dynamical complexity associated with fundamentally different characteristics during periods of quiescence and magnetic storms. The resulting temporal complexity profile has been explored using several approaches from applied statistics, dynamical systems theory and statistical mechanics. Here, we propose an alternative way of looking at time-varying dynamical complexity of nonlinear geophysical time series utilising subtle but significant changes in the linear autocorrelation structure of the recorded data. Our approach is demonstrated to sensitively trace the dynamic signatures associated with intense magnetic storms, and to display reasonable skills in distinguishing between quiescence and storm periods. The potentials and methodological limitations of this new viewpoint are discussed in some detail.

  15. Gene expression profiling in response to ultraviolet radiation in maize genotypes with varying flavonoid content.

    PubMed

    Casati, Paula; Walbot, Virginia

    2003-08-01

    Microarray hybridization was used to assess acclimation responses to four UV regimes by near isogenic maize (Zea mays) lines varying in flavonoid content. We found that 355 of the 2,500 cDNAs tested were regulated by UV radiation in at least one genotype. Among these, 232 transcripts are assigned putative functions, whereas 123 encode unknown proteins. UV-B increased expression of stress response and ribosomal protein genes, whereas photosynthesis-associated genes were down-regulated; lines lacking UV-absorbing pigments had more dramatic responses than did lines with these pigments, confirming the shielding role of these compounds. Sunlight filtered to remove UV-B or UV-B plus UV-A resulted in significant expression changes in many genes not previously associated with UV responses. Some pathways regulated by UV radiation are shared with defense, salt, and oxidative stresses; however, UV-B radiation can activate additional pathways not shared with other stresses.

  16. Product Binding Varies Dramatically between Processive and Nonprocessive Cellulase Enzymes

    SciTech Connect

    Bu, L.; Nimlos, M. R.; Shirts, M. R.; Stahlberg, J.; Himmel, M. E.; Crowley, M. F.; Beckham, G. T.

    2012-07-13

    Cellulases hydrolyze {beta}-1,4 glycosidic linkages in cellulose, which are among the most prevalent and stable bonds in Nature. Cellulases comprise many glycoside hydrolase families and exist as processive or nonprocessive enzymes. Product inhibition negatively impacts cellulase action, but experimental measurements of product-binding constants vary significantly, and there is little consensus on the importance of this phenomenon. To provide molecular level insights into cellulase product inhibition, we examine the impact of product binding on processive and nonprocessive cellulases by calculating the binding free energy of cellobiose to the product sites of catalytic domains of processive and nonprocessive enzymes from glycoside hydrolase families 6 and 7. The results suggest that cellobiose binds to processive cellulases much more strongly than nonprocessive cellulases. We also predict that the presence of a cellodextrin bound in the reactant site of the catalytic domain, which is present during enzymatic catalysis, has no effect on product binding in nonprocessive cellulases, whereas it significantly increases product binding to processive cellulases. This difference in product binding correlates with hydrogen bonding between the substrate-side ligand and the cellobiose product in processive cellulase tunnels and the additional stabilization from the longer tunnel-forming loops. The hydrogen bonds between the substrate- and product-side ligands are disrupted by water in nonprocessive cellulase clefts, and the lack of long tunnel-forming loops results in lower affinity of the product ligand. These findings provide new insights into the large discrepancies reported for binding constants for cellulases and suggest that product inhibition will vary significantly based on the amount of productive binding for processive cellulases on cellulose.

  17. Chlorophyllin significantly reduces benzo[a]pyrene-DNA adduct formation and alters cytochrome P450 1A1 and 1B1 expression and EROD activity in normal human mammary epithelial cells.

    PubMed

    Keshava, Channa; Divi, Rao L; Einem, Tracey L; Richardson, Diana L; Leonard, Sarah L; Keshava, Nagalakshmi; Poirier, Miriam C; Weston, Ainsley

    2009-03-01

    We hypothesized that chlorophyllin (CHLN) would reduce benzo[a]pyrene-DNA (BP-DNA) adduct levels. Using normal human mammary epithelial cells (NHMECs) exposed to 4 microM BP for 24 hr in the presence or absence of 5 microM CHLN, we measured BP-DNA adducts by chemiluminescence immunoassay (CIA). The protocol included the following experimental groups: BP alone, BP given simultaneously with CHLN (BP+CHLN) for 24 hr, CHLN given for 24 hr followed by BP for 24 hr (preCHLN, postBP), and CHLN given for 48 hr with BP added for the last 24 hr (preCHLN, postBP+CHLN). Incubation with CHLN decreased BPdG levels in all groups, with 87% inhibition in the preCHLN, postBP+CHLN group. To examine metabolic mechanisms, we monitored expression by Affymetrix microarray (U133A), and found BP-induced up-regulation of CYP1A1 and CYP1B1 expression, as well as up-regulation of groups of interferon-inducible, inflammation and signal transduction genes. Incubation of cells with CHLN and BP in any combination decreased expression of many of these genes. Using reverse transcription real time PCR (RT-PCR) the maximal inhibition of BP-induced gene expression, >85% for CYP1A1 and >70% for CYP1B1, was observed in the preCHLN, postBP+CHLN group. To explore the relationship between transcription and enzyme activity, the ethoxyresorufin-O-deethylase (EROD) assay was used to measure the combined CYP1A1 and CYP1B1 activities. BP exposure caused the EROD levels to double, when compared with the unexposed controls. The CHLN-exposed groups all showed EROD levels similar to the unexposed controls. Therefore, the addition of CHLN to BP-exposed cells reduced BPdG formation and CYP1A1 and CYP1B1 expression, but EROD activity was not significantly reduced.

  18. Glucomannan and glucomannan plus spirulina added to pork significantly block dietary cholesterol effects on lipoproteinemia, arylesterase activity, and CYP7A1 expression in Zucker fa/fa rats.

    PubMed

    González-Torres, Laura; Vázquez-Velasco, Miguel; Olivero-David, Raúl; Bastida, Sara; Benedí, Juana; González, Rafaela Raposo; González-Muñoz, Ma José; Sánchez-Muniz, Francisco J

    2015-12-01

    Zucker fa/fa rats easily develop dyslipidemia and obesity. Restructured pork (RP) is a suitable matrix for including functional ingredients. The effects of glucomannan- RP or glucomannan plus spirulina-enriched RP on plasma lipid/lipoprotein levels, cytochrome P450 7A1 (CYP7A1) expression, and arylesterase activity in growing fa/fa rats fed high-energy, high-fat cholesterol-enriched diets were tested. Groups of six rats each received diet containing 15% control-RP (C), 15% glucomannan-RP diet (G), 15% glucomannan + spirulina-RP diet (GS), and same diets enriched with 2.4% cholesterol and 0.49% cholic acid (cholesterol-enriched control (HC), cholesterol-enriched glucomannan (HG), and cholesterol-enriched glucomannan + spirulina (HGS) diets) over a 7-week period. C diet induced obesity, severe hyperglycemia, moderate hypercholesterolemia, and hypertriglyceridemia. Those facts were not significantly modified by G or GS diets. G diet increased CYP7A1 expression but decreased the total cholesterol/high density lipoproteins (HDL)-cholesterol ratio (p < 0.05) vs. C diet. GS vs. G diet increased (p < 0.05) CYP7A1 expression. HC vs. C diet reduced food intake, body weight gain, and plasma glucose (p < 0.01) but increased cholesterolemia (p < 0.01), lipidemia (plasma cholesterol plus triglycerides) (p < 0.001), cholesterol/triglyceride ratio in very low density lipoproteins (VLDL), and HDL (p < 0.05), cholesterol transported by VLDL and intermediate density lipoproteins (IDL) + low density lipoproteins (LDL), total cholesterol/HDL-cholesterol ratio and CYP7A1 expression (at least p < 0.05). HG and HGS diets vs. HC noticeably reduced lipidemia (p < 0.001), normalized VLDL and IDL + LDL lipid composition, and increased CYP7A1 expression (p < 0.01) but did not modify the cholesterol/HDL-cholesterol ratio. HGS vs. HG decreased triglyceridemia, the triglyceride-glucose (TyG) index and increased arylesterase/HDL-cholesterol activity (p < 0

  19. Genome-wide DNA polymorphism analyses using VariScan

    PubMed Central

    Hutter, Stephan; Vilella, Albert J; Rozas, Julio

    2006-01-01

    Background DNA sequence polymorphisms analysis can provide valuable information on the evolutionary forces shaping nucleotide variation, and provides an insight into the functional significance of genomic regions. The recent ongoing genome projects will radically improve our capabilities to detect specific genomic regions shaped by natural selection. Current available methods and software, however, are unsatisfactory for such genome-wide analysis. Results We have developed methods for the analysis of DNA sequence polymorphisms at the genome-wide scale. These methods, which have been tested on a coalescent-simulated and actual data files from mouse and human, have been implemented in the VariScan software package version 2.0. Additionally, we have also incorporated a graphical-user interface. The main features of this software are: i) exhaustive population-genetic analyses including those based on the coalescent theory; ii) analysis adapted to the shallow data generated by the high-throughput genome projects; iii) use of genome annotations to conduct a comprehensive analyses separately for different functional regions; iv) identification of relevant genomic regions by the sliding-window and wavelet-multiresolution approaches; v) visualization of the results integrated with current genome annotations in commonly available genome browsers. Conclusion VariScan is a powerful and flexible suite of software for the analysis of DNA polymorphisms. The current version implements new algorithms, methods, and capabilities, providing an important tool for an exhaustive exploratory analysis of genome-wide DNA polymorphism data. PMID:16968531

  20. Optical waveguide device with an adiabatically-varying width

    DOEpatents

    Watts; Michael R. , Nielson; Gregory N.

    2011-05-10

    Optical waveguide devices are disclosed which utilize an optical waveguide having a waveguide bend therein with a width that varies adiabatically between a minimum value and a maximum value of the width. One or more connecting members can be attached to the waveguide bend near the maximum value of the width thereof to support the waveguide bend or to supply electrical power to an impurity-doped region located within the waveguide bend near the maximum value of the width. The impurity-doped region can form an electrical heater or a semiconductor junction which can be activated with a voltage to provide a variable optical path length in the optical waveguide. The optical waveguide devices can be used to form a tunable interferometer (e.g. a Mach-Zehnder interferometer) which can be used for optical modulation or switching. The optical waveguide devices can also be used to form an optical delay line.

  1. Molecular Genetic Response to Varied Wavelengths of Light in Xiphophorus maculatus Skin

    PubMed Central

    Chang, Jordan; Lu, Yuan; Boswell, William T.; Boswell, Mikki; Caballero, Kaela L.; Walter, Ronald B.

    2015-01-01

    Xiphophorus fishes represent a model often utilized to study UVB induced tumorigenesis. Recently, varied genetic responses to UVB exposure has been documented in the skin of female and male Xiphophorus, as have differences in UVB response in the skin of different parental species and for interspecies hybrids produced from crossing them. Additionally, it has been shown that exposure to “cool white” fluorescent light induces a shift in the genetic profiles of Xiphophorus skin that is nearly as robust as the UVB response, but involves a fundamentally different set of genes. Given these results and the use of Xiphophorus interspecies hybrids as an experimental model for UVB inducible melanoma, it is of interest to characterize genes that may be transcriptionally modulated in a wavelength specific manner. The global molecular genetic response of skin upon exposure of the intact animal to specific wavelengths of light has not been investigated. Herein, we report results of RNA-Seq experiments from the skin of male Xiphophorus maculatus Jp 163 B following exposure to varied 50 nm wavelengths of light ranging from 300–600 nm. We identify two specific wavelength regions, 350–400 nm (88 genes) and 500–550 nm (276 genes) that exhibit transcriptional modulation of a significantly greater number of transcripts than any of the other 50 nm regions in the 300–600 nm range. Observed functional sets of genes modulated within these two transcriptionally active light regions suggest different mechanisms of gene modulation. PMID:26460196

  2. Molecular genetic response to varied wavelengths of light in Xiphophorus maculatus skin.

    PubMed

    Chang, Jordan; Lu, Yuan; Boswell, William T; Boswell, Mikki; Caballero, Kaela L; Walter, Ronald B

    2015-12-01

    Xiphophorus fishes represent a model often utilized to study UVB induced tumorigenesis. Recently, varied genetic responses to UVB exposure have been documented in the skin of female and male Xiphophorus, as have differences in UVB response in the skin of different parental species and for interspecies hybrids produced from crossing them. Additionally, it has been shown that exposure to "cool white" fluorescent light induces a shift in the genetic profiles of Xiphophorus skin that is nearly as robust as the UVB response, but involves a fundamentally different set of genes. Given these results and the use of Xiphophorus interspecies hybrids as an experimental model for UVB inducible melanoma, it is of interest to characterize genes that may be transcriptionally modulated in a wavelength specific manner. The global molecular genetic response of skin upon exposure of the intact animal to specific wavelengths of light has not been investigated. Herein, we report results of RNA-Seq experiments from the skin of male Xiphophorus maculatus Jp 163 B following exposure to varied 50nm wavelengths of light ranging from 300-600nm. We identify two specific wavelength regions, 350-400nm (88 genes) and 500-550nm (276 genes), that exhibit transcriptional modulation of a significantly greater number of transcripts than any of the other 50nm regions in the 300-600nm range. Observed functional sets of genes modulated within these two transcriptionally active light regions suggest different mechanisms of gene modulation.

  3. The plasminogen activator inhibitor-1 (PAI-1) gene -844 A/G and -675 4G/5G promoter polymorphism significantly influences plasma PAI-1 levels in women with polycystic ovary syndrome.

    PubMed

    Lin, Sun; Huiya, Zhang; Bo, Liu; Wei, Wei; Yongmei, Guan

    2009-12-01

    Mutations in the plasminogen activator inhibitor-1 (PAI-1) gene, along with increased PAI-1 levels, have been implicated in the pathogenesis of polycystic ovarian syndrome (PCOS). We investigated a possible influence of the promoter polymorphism (-844 A/G and -675 4G/5G) in the PAI-1 gene on plasma PAI-1 levels in 126 PCOS patients and 97 healthy controls. Levels of total testosterone, luteinizing hormone (LH), follicle stimulating hormone (FSH), fasting plasma glucose (FPG), fasting insulin, and PAI-1 were measured, and body mass index (BMI), waist-to-hip ratio (WHR), LH/FSH ratio, and homeostasis model assessment for insulin resistance (HOMA-IR) were calculated. PAI-1 -675 4G/5G and -844 A/G gene polymorphisms were also performed. Total testosterone, fasting insulin, and PAI-1 levels; BMI, LH/FSH, and HOMA-IR were significantly higher in PCOS patients than controls (P < 0.05). The odds ratio of 4G/4G genotype, 4G allele, and the combination genotype of 4G/4G and -844 A/A were 2.49 (95% confidence interval (CI), 1.4-4.44), 2.1 (95% CI, 1.43-3.08), and 2.9 (95% CI, 1.41-5.98), respectively, (P < 0.001). In the PCOS group, the PAI-1 level of the A/A was significantly higher than that of the A/G or G/G genotype, similarly was 4G/4G genotype compared with 4G/5G or 5G/5G genotype. The plasma PAI-1 levels of the combination of the PAI-1 -844 A/A and -675 4G/4G or 4G/5G genotypes, or the coadunation of 4G/4G and -844 non-G/G (A/A + A/G) genotypes were significantly high in PCOS women compared with controls. A trend to a positive interaction between PAI-1 -675 4G/5G and -844 A/G gene polymorphism may elevate plasma PAI-1 levels and hypofibrinolysis, which is probably an important hereditary risk factor in PCOS.

  4. Crops Models for Varying Environmental Conditions

    NASA Technical Reports Server (NTRS)

    Jones, Harry; Cavazzoni, James; Keas, Paul

    2001-01-01

    New variable environment Modified Energy Cascade (MEC) crop models were developed for all the Advanced Life Support (ALS) candidate crops and implemented in SIMULINK. The MEC models are based on the Volk, Bugbee, and Wheeler Energy Cascade (EC) model and are derived from more recent Top-Level Energy Cascade (TLEC) models. The MEC models simulate crop plant responses to day-to-day changes in photosynthetic photon flux, photoperiod, carbon dioxide level, temperature, and relative humidity. The original EC model allows changes in light energy but uses a less accurate linear approximation. The simulation outputs of the new MEC models for constant nominal environmental conditions are very similar to those of earlier EC models that use parameters produced by the TLEC models. There are a few differences. The new MEC models allow setting the time for seed emergence, have realistic exponential canopy growth, and have corrected harvest dates for potato and tomato. The new MEC models indicate that the maximum edible biomass per meter squared per day is produced at the maximum allowed carbon dioxide level, the nominal temperatures, and the maximum light input. Reducing the carbon dioxide level from the maximum to the minimum allowed in the model reduces crop production significantly. Increasing temperature decreases production more than it decreases the time to harvest, so productivity in edible biomass per meter squared per day is greater at nominal than maximum temperatures, The productivity in edible biomass per meter squared per day is greatest at the maximum light energy input allowed in the model, but the edible biomass produced per light energy input unit is lower than at nominal light levels. Reducing light levels increases light and power use efficiency. The MEC models suggest we can adjust the light energy day-to- day to accommodate power shortages or Lise excess power while monitoring and controlling edible biomass production.

  5. Development of a Passively Varying Pitch Propeller

    NASA Astrophysics Data System (ADS)

    Heinzen, Stearns Beamon

    compared to the fixed pitch propellers currently used on most light aircraft and small unmanned systems, making significant improvements in aircraft performance possible. These improvements may yield aircraft with reduced takeoff distances, improved climb rates, increased range and endurance, and higher top speeds, without sacrificing on-design performance.

  6. Identification of Time-Varying Pilot Control Behavior in Multi-Axis Control Tasks

    NASA Technical Reports Server (NTRS)

    Zaal, Peter M. T.; Sweet, Barbara T.

    2012-01-01

    Recent developments in fly-by-wire control architectures for rotorcraft have introduced new interest in the identification of time-varying pilot control behavior in multi-axis control tasks. In this paper a maximum likelihood estimation method is used to estimate the parameters of a pilot model with time-dependent sigmoid functions to characterize time-varying human control behavior. An experiment was performed by 9 general aviation pilots who had to perform a simultaneous roll and pitch control task with time-varying aircraft dynamics. In 8 different conditions, the axis containing the time-varying dynamics and the growth factor of the dynamics were varied, allowing for an analysis of the performance of the estimation method when estimating time-dependent parameter functions. In addition, a detailed analysis of pilots adaptation to the time-varying aircraft dynamics in both the roll and pitch axes could be performed. Pilot control behavior in both axes was significantly affected by the time-varying aircraft dynamics in roll and pitch, and by the growth factor. The main effect was found in the axis that contained the time-varying dynamics. However, pilot control behavior also changed over time in the axis not containing the time-varying aircraft dynamics. This indicates that some cross coupling exists in the perception and control processes between the roll and pitch axes.

  7. Premorbid IQ varies across different definitions of schizophrenia

    PubMed Central

    URFER PARNAS, ANNICK; JANSSON, LENNART; HANDEST, PETER; NIELSEN, JAN; SÆBYE, DITTE; PARNAS, JOSEF

    2007-01-01

    The nature of the association between IQ and schizophrenia is still unclear. So far no study addressed this issue in relation to the breadth or scope of the very concept of schizophrenia. We examined the premorbid IQ in a polydiagnostic study with four classifications of schizophrenia: ICD-8/9, ICD-10, St. Louis and Flexible System-Wide. Only the ICD-10 schizophrenia patients exhibited a significantly lower premorbid IQ. There were suggestive differences between the four examined systems as well as between the ICD-10 paranoid and non-paranoid subtypes. Exploration of crucial diagnostic features of schizophrenia in relation to IQ revealed associations between low premorbid IQ and hallucinations as well as negative symptoms. It is concluded that premorbid IQ varies across different definitions of schizophrenia. PMID:17342225

  8. Pathological Significance of Mitochondrial Glycation

    PubMed Central

    Pun, Pamela Boon Li; Murphy, Michael P.

    2012-01-01

    Glycation, the nonenzymatic glycosylation of biomolecules, is commonly observed in diabetes and ageing. Reactive dicarbonyl species such as methylglyoxal and glyoxal are thought to be major physiological precursors of glycation. Because these dicarbonyls tend to be formed intracellularly, the levels of advanced glycation end products on cellular proteins are higher than on extracellular ones. The formation of glycation adducts within cells can have severe functional consequences such as inhibition of protein activity and promotion of DNA mutations. Although several lines of evidence suggest that there are specific mitochondrial targets of glycation, and mitochondrial dysfunction itself has been implicated in disease and ageing, it is unclear if glycation of biomolecules specifically within mitochondria induces dysfunction and contributes to disease pathology. We discuss here the possibility that mitochondrial glycation contributes to disease, focussing on diabetes, ageing, cancer, and neurodegeneration, and highlight the current limitations in our understanding of the pathological significance of mitochondrial glycation. PMID:22778743

  9. Oxidants and anti-oxidants status in acne vulgaris patients with varying severity.

    PubMed

    Al-Shobaili, Hani A

    2014-01-01

    Acne vulgaris is a common dermatological disorder with a multifactorial pathogenesis. Oxidative status has been implicated in the pathogenesis of several skin diseases, including acne. This study was aimed to investigate the levels of oxidative stress biomarkers in acne vulgaris patients with varying severities. The study involved 156 patients with acne and 46 healthy human controls. Based on clinical examination, patients were grouped into 3 subgroups as follows: mild, moderate, and severe acne. Oxidative stress was examined by measuring plasma levels of catalase (CAT), superoxide dismutase (SOD), total antioxidant capacity (TAC), and malondialdehyde (MDA). Plasma levels of MDA in acne patients were significantly higher as compared with that of the controls, whereas activities of the antioxidant enzymes SOD and CAT were lower. Moreover, TAC was also low in acne patients as compared with that of the controls. Higher MDA levels in the severe acne subgroup as compared with that of the mild and moderate subgroups were also observed. Furthermore, in the severe acne subgroup, a significant negative correlation was observed between MDA and CAT levels. The data suggests that oxidative stress plays a key role in acne progress and may be employed as a biomarker index to assess the disease's activity and to monitor its treatment.

  10. Prostate Cancer Treatments Have Varying Side Effects, Study Shows

    MedlinePlus

    ... page: https://medlineplus.gov/news/fullstory_164200.html Prostate Cancer Treatments Have Varying Side Effects, Study Shows Even ' ... News) -- The long-term side effects of different prostate cancer treatments vary -- and knowing that may help men ...

  11. The significance of methane ebullition

    NASA Astrophysics Data System (ADS)

    Walter, K.; Draluk, D. A.; Zimov, S. A.; Chapin, T.

    2003-12-01

    Ebullition is often the dominant pathway of methane release from aquatic ecosystems, yet it has seldom been carefully measured, due to heterogeneity in the spatial distribution and episodic release of gas bubbles. This likely results in an underestimation of total methane emission. We took advantage of ice formation over lake surfaces in NE Siberia to map patterns of ebullition. As ice forms in autumn, bubbles released from lake sediments are continually trapped under the ice at the water surface resulting in stacks of bubbles separated by thin films of ice called `koshkas'. Mapping the distribution of koshkas enabled us to identify `background' patterns of ebullition. In addition, we located `hot-spot' ebullition sites that remain permanently open throughout winter due to exceptionally high rates of methane bubbling. We used random and selective placement of underwater/ under-ice chambers to measure `background' and `hot-spot' fluxes annually. The combination of mapping and chamber measurements among different types of lakes and along lake margins varying in intensity of thermokarst erosion or aquatic plant growth enabled us to 1) improve estimates of total methane emissions from NE Siberian lakes, and to 2) identify landscape processes (thermokarst erosion vs. wetland mat formation) that enhance methane production and emission. Ignoring the contribution from hotspots, background ebullition comprised more than 75% of total methane emissions from lakes. From hotspot sites we measured up to 10-L m-2 of methane per day in early summer. Although hotspots comprised roughly 0.05% of the area along thermokarst margins, where they were most common, ebullition from hotspots contributed approximately 69% of the total ebullition flux. Including the flux from hotspots could increase estimates of CH4 ebullition from thermokarst margins 300%! Thermokarst lakes in Russia comprise a large proportion of the world's high latitude lakes; yet they are understudied. North Siberian

  12. Comparison of Linear Microinstability Calculations of Varying Input Realism

    SciTech Connect

    G. Rewoldt

    2003-09-08

    The effect of varying ''input realism'' or varying completeness of the input data for linear microinstability calculations, in particular on the critical value of the ion temperature gradient for the ion temperature gradient mode, is investigated using gyrokinetic and gyrofluid approaches. The calculations show that varying input realism can have a substantial quantitative effect on the results.

  13. Ekman Spiral in Horizontally Inhomogeneous Ocean with Varying Eddy Viscosity

    DTIC Science & Technology

    2015-01-01

    1 Ekman Spiral in Horizontally Inhomogeneous Ocean with Varying Eddy Viscosity ...in Horizontally Inhomogeneous Ocean with Varying Eddy Viscosity 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d...generated by surface wind stress with constant eddy viscosity in homogeneous ocean. In real oceans, the eddy viscosity varies due to turbulent mixing

  14. Identification of significant amino acids in multiple transmembrane domains of human transient receptor potential ankyrin 1 (TRPA1) for activation by eudesmol, an oxygenized sesquiterpene in hop essential oil.

    PubMed

    Ohara, Kazuaki; Fukuda, Takafumi; Okada, Hiroyuki; Kitao, Sayoko; Ishida, Yuko; Kato, Kyoko; Takahashi, Chika; Katayama, Mikio; Uchida, Kunitoshi; Tominaga, Makoto

    2015-01-30

    Transient receptor potential ankyrin 1 (TRPA1) is a calcium-permeable non-selective cation channel that is activated by various noxious or irritant substances in nature, including spicy compounds. Many TRPA1 chemical activators have been reported; however, only limited information is available regarding the amino acid residues that contribute to the activation by non-electrophilic activators, whereas activation mechanisms by electrophilic ligands have been well characterized. We used intracellular Ca(2+) measurements and whole-cell patch clamp recordings to show that eudesmol, an oxygenated sesquiterpene present at high concentrations in the essential oil of hop cultivar Hallertau Hersbrucker, could activate human TRPA1. Gradual activation of inward currents with outward rectification by eudesmol was observed in human embryonic kidney-derived 293 cells expressing human TRPA1. This activation was completely blocked by a TRPA1-specific inhibitor, HC03-0031. We identified three critical amino acid residues in human TRPA1 in putative transmembrane domains 3, 4, and 5, namely threonine at 813, tyrosine at 840, and serine at 873, for activation by β-eudesmol in a systematic mutational study. Our results revealed a new TRPA1 activator in hop essential oil and provide a novel insight into mechanisms of human TRPA1 activation by non-electrophilic chemicals.

  15. Identification of Significant Amino Acids in Multiple Transmembrane Domains of Human Transient Receptor Potential Ankyrin 1 (TRPA1) for Activation by Eudesmol, an Oxygenized Sesquiterpene in Hop Essential Oil

    PubMed Central

    Ohara, Kazuaki; Fukuda, Takafumi; Okada, Hiroyuki; Kitao, Sayoko; Ishida, Yuko; Kato, Kyoko; Takahashi, Chika; Katayama, Mikio; Uchida, Kunitoshi; Tominaga, Makoto

    2015-01-01

    Transient receptor potential ankyrin 1 (TRPA1) is a calcium-permeable non-selective cation channel that is activated by various noxious or irritant substances in nature, including spicy compounds. Many TRPA1 chemical activators have been reported; however, only limited information is available regarding the amino acid residues that contribute to the activation by non-electrophilic activators, whereas activation mechanisms by electrophilic ligands have been well characterized. We used intracellular Ca2+ measurements and whole-cell patch clamp recordings to show that eudesmol, an oxygenated sesquiterpene present at high concentrations in the essential oil of hop cultivar Hallertau Hersbrucker, could activate human TRPA1. Gradual activation of inward currents with outward rectification by eudesmol was observed in human embryonic kidney-derived 293 cells expressing human TRPA1. This activation was completely blocked by a TRPA1-specific inhibitor, HC03–0031. We identified three critical amino acid residues in human TRPA1 in putative transmembrane domains 3, 4, and 5, namely threonine at 813, tyrosine at 840, and serine at 873, for activation by β-eudesmol in a systematic mutational study. Our results revealed a new TRPA1 activator in hop essential oil and provide a novel insight into mechanisms of human TRPA1 activation by non-electrophilic chemicals. PMID:25525269

  16. The adaptive response of jaw muscles to varying functional demands.

    PubMed

    Grünheid, Thorsten; Langenbach, Geerling E J; Korfage, Joannes A M; Zentner, Andrej; van Eijden, Theo M G J

    2009-12-01

    Jaw muscles are versatile entities that are able to adapt their anatomical characteristics, such as size, cross-sectional area, and fibre properties, to altered functional demands. The dynamic nature of muscle fibres allows them to change their phenotype to optimize the required contractile function while minimizing energy use. Changes in these anatomical parameters are associated with changes in neuromuscular activity as the pattern of muscle activation by the central nervous system plays an important role in the modulation of muscle properties. This review summarizes the adaptive response of jaw muscles to various stimuli or perturbations in the orofacial system and addresses general changes in muscles as they adapt, specific adaptive changes in jaw muscles under various physiologic and pathologic conditions, and their adaptive response to non-surgical and surgical therapeutic interventions. Although the jaw muscles are used concertedly in the masticatory system, their adaptive changes are not always uniform and vary with the nature, intensity, and duration of the stimulus. In general, stretch, increases neuromuscular activity, and resistance training result in hypertrophy, elicits increases in mitochondrial content and cross-sectional area of the fibres, and may change the fibre-type composition of the muscle towards a larger percentage of slow-type fibres. In contrast, changes in the opposite direction occur when neuromuscular activity is reduced, the muscle is immobilized in a shortened position, or paralysed. The broad range of stimuli that affect the properties of jaw muscles might help explain the large variability in the anatomical and physiological characteristics found among individuals, muscles, and muscle portions.

  17. Significance and Biological Importance of Pyrimidine in the Microbial World

    PubMed Central

    Sharma, Vinita; Agarwal, Ajay Kumar

    2014-01-01

    Microbes are unique creatures that adapt to varying lifestyles and environment resistance in extreme or adverse conditions. The genetic architecture of microbe may bear a significant signature not only in the sequences position, but also in the lifestyle to which it is adapted. It becomes a challenge for the society to find new chemical entities which can treat microbial infections. The present review aims to focus on account of important chemical moiety, that is, pyrimidine and its various derivatives as antimicrobial agents. In the current studies we represent more than 200 pyrimidines as antimicrobial agents with different mono-, di-, tri-, and tetrasubstituted classes along with in vitro antimicrobial activities of pyrimidines derivatives which can facilitate the development of more potent and effective antimicrobial agents. PMID:25383216

  18. Public Health Significance of Neuroticism

    ERIC Educational Resources Information Center

    Lahey, Benjamin B.

    2009-01-01

    The personality trait of neuroticism refers to relatively stable tendencies to respond with negative emotions to threat, frustration, or loss. Individuals in the population vary markedly on this trait, ranging from frequent and intense emotional reactions to minor challenges to little emotional reaction even in the face of significant…

  19. Holographic cinematography of time-varying reflecting and time-varying phase objects using a Nd:YAG laser

    NASA Technical Reports Server (NTRS)

    Decker, A. J.

    1982-01-01

    The use of a Nd:YAG laser to record holographic motion pictures of time-varying reflecting objects and time-varying phase objects is discussed. Sample frames from both types of holographic motion pictures are presented. The holographic system discussed is intended for three-dimensional flow visualization of the time-varying flows that occur in jet-engine components.

  20. Significant Impairment in Immune Recovery Following Cancer Treatment

    PubMed Central

    Kang, Duck-Hee; Weaver, Michael T.; Park, Na-Jin; Smith, Barbara; McArdle, Traci; Carpenter, John

    2009-01-01

    Background Although immunosuppression from cancer adjuvant therapy has been documented, how these suppressed immune responses recover to baseline values after completion of cancer adjuvant therapy has not been studied systematically. Objectives To examine the probability of immune recovery following cancer adjuvant therapy and the potential impact of cancer adjuvant therapy type and cancer stage on immune recovery in newly diagnosed breast cancer patients. Method In a repeated-measures design, immune responses were measured 4 times in 80 early stage breast cancer patients: prior to, and at 2, 6, and 12 months from the beginning of cancer adjuvant therapy. Natural killer cell activity (NKCA), lymphokine-activated killer cell activity, lymphocyte proliferation, CD subsets (CD4, CD8, and CD56), and cytokines (IFN-γ, IL-2, IL-4, IL-6, and IL-1α) were selected for their relevance to breast cancer. Immune recovery was defined by the level of immune response reaching to and above baseline levels. Data were analyzed using a multivariate generalized linear mixed model approach. Results Delayed immune recovery to pretreatment baseline levels continued to the 12-month time point in all parameters. The percentages of immune recovery ranged from 6% to 76% of the patients, varying among immune parameters. Overall, immune recovery was poorer for IFN-γ, IL-2, IL-4, lymphocyte proliferation and NKCA than for CD subsets and IL-6. The type of cancer adjuvant therapy, not cancer stage, showed selective influence on immune recovery. Chemotherapy or chemo- and radiotherapy combination significantly delayed IL-2 recovery, whereas radiotherapy significantly delayed IL-4 recovery. Discussion Immune recovery following breast cancer adjuvant therapy is delayed significantly for an extended time period in numerous immune parameters. The type of cancer adjuvant therapy has selective influence on immune recovery. Future investigations are warranted to elucidate the time course of immune

  1. Adaptive conductance filtering for spatially varying noise in PET images

    NASA Astrophysics Data System (ADS)

    Padfield, Dirk R.; Manjeshwar, Ravindra

    2006-03-01

    PET images that have been reconstructed with unregularized algorithms are commonly smoothed with linear Gaussian filters to control noise. Since these filters are spatially invariant, they degrade feature contrast in the image, compromising lesion detectability. Edge-preserving smoothing filters can differentially preserve edges and features while smoothing noise. These filters assume spatially uniform noise models. However, the noise in PET images is spatially variant, approximately following a Poisson behavior. Therefore, different regions of a PET image need smoothing by different amounts. In this work, we introduce an adaptive filter, based on anisotropic diffusion, designed specifically to overcome this problem. In this algorithm, the diffusion is varied according to a local estimate of the noise using either the local median or the grayscale image opening to weight the conductance parameter. The algorithm is thus tailored to the task of smoothing PET images, or any image with Poisson-like noise characteristics, by adapting itself to varying noise while preserving significant features in the image. This filter was compared with Gaussian smoothing and a representative anisotropic diffusion method using three quantitative task-relevant metrics calculated on simulated PET images with lesions in the lung and liver. The contrast gain and noise ratio metrics were used to measure the ability to do accurate quantitation; the Channelized Hotelling Observer lesion detectability index was used to quantify lesion detectability. The adaptive filter improved the signal-to-noise ratio by more than 45% and lesion detectability by more than 55% over the Gaussian filter while producing "natural" looking images and consistent image quality across different anatomical regions.

  2. Impact of varying transmission bandwidth on image quality.

    PubMed

    Broderick, T J; Harnett, B M; Merriam, N R; Kapoor, V; Doarn, C R; Merrell, R C

    2001-01-01

    The objective of this paper is to determine the effect of varying transmission bandwidth on image quality in laparoscopic surgery. Surgeons located in remote operating rooms connected through a telemedicine link must be able to transmit medical images for interaction. Image clarity and color fidelity are of critical importance in telementoring laparoscopic procedures. The clarity of laparoscopic images was measured by assessing visual acuity using a video image of a Snellen eye chart obtained with standard diameter laparoscopes (2, 5, and 10 mm). The clarity of the local image was then compared to that of remote images transmitted using various bandwidths and connection protocols [33.6 Kbps POTS (IP), 128 Kbps ISDN, 384 Kbps ISDN, 10 Mbps LAN (IP)]. The laparoscopes were subsequently used to view standard color placards. These color images were sent via similar transmission bandwidths and connection protocols. The local and remote images of the color placards were compared to determine the effect of the transmission protocols on color fidelity. Use of laparoscopes of different diameter does not significantly affect image clarity or color fidelity as long as the laparoscopes are positioned at their optimal working distance. Decreasing transmission bandwidth does not significantly affect image clarity or color fidelity when sufficient time is allowed for the algorithms to redraw the remote image. Remote telementoring of laparoscopic procedures is feasible. However, low bandwidth connections require slow and/or temporarily stopped camera movements for the quality of the remote video image to approximate that of the local video image.

  3. Activity.

    ERIC Educational Resources Information Center

    Clearing: Nature and Learning in the Pacific Northwest, 1984

    1984-01-01

    Presents three activities: (1) investigating succession in a schoolground; (2) investigating oak galls; and (3) making sun prints (photographs made without camera or darkroom). Each activity includes a list of materials needed and procedures used. (JN)

  4. The Impact of Varying Statutory Arrangements on Spatial Data Sharing and Access in Regional NRM Bodies

    NASA Astrophysics Data System (ADS)

    Paudyal, D. R.; McDougall, K.; Apan, A.

    2014-12-01

    Spatial information plays an important role in many social, environmental and economic decisions and increasingly acknowledged as a national resource essential for wider societal and environmental benefits. Natural Resource Management is one area where spatial information can be used for improved planning and decision making processes. In Australia, state government organisations are the custodians of spatial information necessary for natural resource management and regional NRM bodies are responsible to regional delivery of NRM activities. The access and sharing of spatial information between government agencies and regional NRM bodies is therefore as an importan