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Sample records for activation step occurs

  1. Two-step mechanism of photodamage to photosystem II: step 1 occurs at the oxygen-evolving complex and step 2 occurs at the photochemical reaction center.

    PubMed

    Ohnishi, Norikazu; Allakhverdiev, Suleyman I; Takahashi, Shunichi; Higashi, Shoichi; Watanabe, Masakatsu; Nishiyama, Yoshitaka; Murata, Norio

    2005-06-14

    Under strong light, photosystem II (PSII) of oxygenic photosynthetic organisms is inactivated, and this phenomenon is called photoinhibition. In a widely accepted model, photoinhibition is induced by excess light energy, which is absorbed by chlorophyll but not utilized in photosynthesis. Using monochromatic light from the Okazaki Large Spectrograph and thylakoid membranes from Thermosynechococcus elongatus, we observed that UV and blue light inactivated the oxygen-evolving complex much faster than the photochemical reaction center of PSII. These observations suggested that the light-induced damage was associated with a UV- and blue light-absorbing center in the oxygen-evolving complex of PSII. The action spectrum of the primary event in photodamage to PSII revealed the strong effects of UV and blue light and differed considerably from the absorption spectra of chlorophyll and thylakoid membranes. By contrast to the photoinduced inactivation of the oxygen-evolving complex in untreated thylakoid membranes, red light efficiently induced inactivation of the PSII reaction center in Tris-treated thylakoid membranes, and the action spectrum resembled the absorption spectrum of chlorophyll. Our observations suggest that photodamage to PSII occurs in two steps. Step 1 is the light-induced inactivation of the oxygen-evolving complex. Step 2, occurring after step 1 is complete, is the inactivation of the PSII reaction center by light absorbed by chlorophyll. We confirmed our model by illumination of untreated thylakoid membranes with blue and UV light, which inactivated the oxygen-evolving complex, and then with red light, which inactivated the photochemical reaction center.

  2. Persulfate activation by naturally occurring trace minerals.

    PubMed

    Teel, Amy L; Ahmad, Mushtaque; Watts, Richard J

    2011-11-30

    The potential for 13 naturally occurring minerals to mediate the decomposition of persulfate and generate a range of reactive oxygen species was investigated to provide fundamental information on activation mechanisms when persulfate is used for in situ chemical oxidation (ISCO). Only four of the minerals (cobaltite, ilmenite, pyrite, and siderite) promoted the decomposition of persulfate more rapidly than persulfate-deionized water control systems. The other nine minerals decomposed persulfate at the same rate or more slowly than the control systems. Mineral-mediated persulfate activation was conducted with the addition of one of three probe compounds to detect the generation of reactive oxygen species: anisole (sulfate+hydroxyl radical), nitrobenzene (hydroxyl radical), and hexachloroethane (reductants and nucleophiles). The reduced mineral pyrite promoted rapid generation of sulfate+hydroxyl radical. However, the remainder of the minerals provided minimal potential for the generation of reactive oxygen species. The results of this research demonstrate that the majority of naturally occurring trace minerals do not activate persulfate to generate reactive oxygen species, and other mechanisms of activation are necessary to promote contaminant destruction in the subsurface during persulfate ISCO.

  3. Commonly occurring plant flavonoids have estrogenic activity.

    PubMed

    Miksicek, R J

    1993-07-01

    A remarkable diversity of naturally occurring and synthetic compounds have been shown to mimic the biological effects of 17 beta-estradiol by virtue of their ability to bind to and activate the nuclear estrogen receptor. This report extends the family of nonsteroidal estrogens to include several multiply hydroxylated chalcones, flavanones, and flavones. The hormone-like activity of these natural plant products is indicated by their ability to stimulate an estrogen receptor-dependent transcriptional response and to promote growth of estrogen-dependent MCF7 cells in culture. The transcriptional response can be inhibited by the steroidal estrogen antagonist ICI-164,384 and is specific for the estrogen receptor. Evidence is presented to show that selected hydroxylated flavonoids interact directly with the estrogen receptor, based on their ability to compete for the binding of 17 beta-[3H]estradiol to the receptor in cell-free extracts. These compounds are less active, on a molar basis, than 17 beta-estradiol or the synthetic dihydroxystilbene estrogens, but they have potencies comparable to those of other known phytoestrogens. Together, these findings broaden our understanding of the structure-activity relationships for nonsteroidal estrogens and present a series of new chemical prototypes for the future development of potentially useful agonists and antagonists for this nuclear receptor. The wide distribution of weakly estrogenic flavonoid pigments in food crops and medicinal plants raises additional questions about the possible health risks and benefits of these compounds, meriting closer examination of their presence in the human diet.

  4. Tetrahydroberberine, a pharmacologically active naturally occurring alkaloid.

    PubMed

    Pingali, Subramanya; Donahue, James P; Payton-Stewart, Florastina

    2015-04-01

    Tetrahydroberberine (systematic name: 9,10-dimethoxy-5,8,13,13a-tetrahydro-6H-benzo[g][1,3]benzodioxolo[5,6-a]quinolizine), C20H21NO4, a widely distributed naturally occurring alkaloid, has been crystallized as a racemic mixture about an inversion center. A bent conformation of the molecule is observed, with an angle of 24.72 (5)° between the arene rings at the two ends of the reduced quinolizinium core. The intermolecular hydrogen bonds that play an apparent role in crystal packing are 1,3-benzodioxole -CH2···OCH3 and -OCH3···OCH3 interactions between neighboring molecules.

  5. Estrogenic activity of naturally occurring anthocyanidins.

    PubMed

    Schmitt, E; Stopper, H

    2001-01-01

    Anthocyanins, which are natural plant pigments from the flavonoid family, represent substantial constituents of the human diet. Because some other bioflavonoids are known to have estrogenic activity, the aim of this study was to determine the estrogenic activity of the anthocyanine aglycones. Binding affinity to the estrogen receptor-alpha was 10,000- to 20,000-fold lower than that of the endogenous estrogen estradiol. In the estrogen receptor-positive cell line MCF-7, the anthocyanidins induced expression of a reporter gene. The tested anthocyanidins showed estrogen-inducible cell proliferation in two cell lines (MCF-7 and BG-1), but not in the receptor-negative human breast cancer cell line MDA-MB-231. The phytoestrogen-induced cell proliferation could be blocked by addition of the receptor antagonist 4-hydroxytamoxifen. Combination treatments with the endogenous estrogen estradiol resulted in a reduction of estradiol-induced cell proliferation. Overall, the tested anthocyanidins exert estrogenic activity, which might play a role in altering the development of hormone-dependent adverse effects.

  6. Nuclear fusion during yeast mating occurs by a three-step pathway.

    PubMed

    Melloy, Patricia; Shen, Shu; White, Erin; McIntosh, J Richard; Rose, Mark D

    2007-11-19

    In Saccharomyces cerevisiae, mating culminates in nuclear fusion to produce a diploid zygote. Two models for nuclear fusion have been proposed: a one-step model in which the outer and inner nuclear membranes and the spindle pole bodies (SPBs) fuse simultaneously and a three-step model in which the three events occur separately. To differentiate between these models, we used electron tomography and time-lapse light microscopy of early stage wild-type zygotes. We observe two distinct SPBs in approximately 80% of zygotes that contain fused nuclei, whereas we only see fused or partially fused SPBs in zygotes in which the site of nuclear envelope (NE) fusion is already dilated. This demonstrates that SPB fusion occurs after NE fusion. Time-lapse microscopy of zygotes containing fluorescent protein tags that localize to either the NE lumen or the nucleoplasm demonstrates that outer membrane fusion precedes inner membrane fusion. We conclude that nuclear fusion occurs by a three-step pathway.

  7. NBS Steps Up Environmental Activities

    ERIC Educational Resources Information Center

    Chemical and Engineering News, 1974

    1974-01-01

    Discusses the increased environmental activities of the National Bureau of Standards which include the development of standard reference materials (each containing a known concentration of a pollutant or pollutants), accurate methods of measurement, and pollution monitoring instruments. (JR)

  8. 32 CFR 716.6 - Death occurring after active service.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 5 2011-07-01 2011-07-01 false Death occurring after active service. 716.6 Section 716.6 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY PERSONNEL DEATH GRATUITY Provisions Applicable to the Navy and the Marine Corps § 716.6 Death occurring after...

  9. 32 CFR 716.6 - Death occurring after active service.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 5 2012-07-01 2012-07-01 false Death occurring after active service. 716.6 Section 716.6 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY PERSONNEL DEATH GRATUITY Provisions Applicable to the Navy and the Marine Corps § 716.6 Death occurring after...

  10. 32 CFR 716.6 - Death occurring after active service.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 5 2014-07-01 2014-07-01 false Death occurring after active service. 716.6 Section 716.6 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY PERSONNEL DEATH GRATUITY Provisions Applicable to the Navy and the Marine Corps § 716.6 Death occurring after...

  11. 32 CFR 716.6 - Death occurring after active service.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 5 2013-07-01 2013-07-01 false Death occurring after active service. 716.6 Section 716.6 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY PERSONNEL DEATH GRATUITY Provisions Applicable to the Navy and the Marine Corps § 716.6 Death occurring after...

  12. 32 CFR 716.6 - Death occurring after active service.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 5 2010-07-01 2010-07-01 false Death occurring after active service. 716.6 Section 716.6 National Defense Department of Defense (Continued) DEPARTMENT OF THE NAVY PERSONNEL DEATH GRATUITY Provisions Applicable to the Navy and the Marine Corps § 716.6 Death occurring after...

  13. Temporal Sequencing of Brain Activations During Naturally Occurring Thermoregulatory Events

    PubMed Central

    Diwadkar, Vaibhav A.; Murphy, Eric R.; Freedman, Robert R.

    2014-01-01

    Thermoregulatory events are associated with activity in the constituents of the spinothalamic tract. Whereas studies have assessed activity within constituents of this pathway, in vivo functional magnetic resonance imaging (fMRI) studies have not determined if neuronal activity in the constituents of the tract is temporally ordered. Ordered activity would be expected in naturally occurring thermal events, such as menopausal hot flashes (HFs), which occur in physiological sequence. The origins of HFs may lie in brainstem structures where neuronal activity may occur earlier than in interoceptive centers, such as the insula and the prefrontal cortex. To study such time ordering, we conducted blood oxygen level-dependent-based fMRI in a group of postmenopausal women to measure neuronal activity in the brainstem, insula, and prefrontal cortex around the onset of an HF (detected using synchronously acquired skin conductance responses). Rise in brainstem activity occurred before the detectable onset of an HF. Activity in the insular and prefrontal trailed that in the brainstem, appearing following the onset of the HF. Additional activations associated with HF's were observed in the anterior cingulate cortex and the basal ganglia. Pre-HF brainstem responses may reflect the functional origins of internal thermoregulatory events. By comparison insular, prefrontal and striatal activity may be associated with the phenomenological correlates of HFs. PMID:23787950

  14. Final Step of Phosphatidic Acid Synthesis in Pea Chloroplasts Occurs in the Inner Envelope Membrane 1

    PubMed Central

    Andrews, Jaen; Ohlrogge, John B.; Keegstra, Kenneth

    1985-01-01

    The second enzyme of phosphatidic acid synthesis from glycerol-3-phosphate, 1-acylglycerophospate acyltransferase, was localized to the inner envelope membrane of pea chloroplasts. The activity of this enzyme was measured by both a coupled enzyme assay and a direct enzyme assay. Using the coupled enzyme assay, phosphatidic acid phosphatase was also localized to the inner envelope membrane, although this enzyme has very low activity in pea chloroplasts. The addition of UDP-galactose to unfractionated pea chloroplast envelope preparations did not result in significant conversion of newly synthesized diacylglycerol to monogalactosyldiacylglycerol. Thus, the envelope synthesized phosphatidic acid may not be involved in galactolipid synthesis in pea chloroplasts. PMID:16664266

  15. Proton permeation into single vesicles occurs via a sequential two-step mechanism and is heterogeneous.

    PubMed

    Kuyper, Christopher L; Kuo, Jason S; Mutch, Sarah A; Chiu, Daniel T

    2006-03-15

    This article describes the first single-vesicle study of proton permeability across the lipid membrane of small (approximately 100 nm) uni- and multilamellar vesicles, which were composed of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC). To follow proton permeation into the internal volume of each vesicle, we encapsulated carboxyfluorescein, a pH-sensitive dye whose fluorescence was quenched in the presence of excess protons. A microfluidic platform was used for easy exchange of high- and low-pH solutions, and fluorescence quenching of single vesicles was detected with single-molecule total internal reflection fluorescence (TIRF) microscopy. Upon solution exchange and acidification of the extravesicular solution (from pH 9 to 3.5), we observed for each vesicle a biphasic decay in fluorescence. Through single-vesicle analysis, we found that rate constants for the first decay followed a Poisson distribution, whereas rate constants for the second decay followed a normal distribution. We propose that proton permeation into each vesicle first arose from formation of transient pores and then transitioned into the second decay phase, which occurred by the solubility-diffusion mechanism. Furthermore, for the bulk population of vesicles, the decay rate constant and vesicle intensity (dependent on size) correlated to give an average permeability coefficient; however, for individual vesicles, we found little correlation, which suggested that proton permeability among single vesicles was heterogeneous in our experiments.

  16. Light-dependent magnetoreception in birds: the crucial step occurs in the dark

    PubMed Central

    Wiltschko, Roswitha; Ahmad, Margaret; Nießner, Christine; Gehring, Dennis; Wiltschko, Wolfgang

    2016-01-01

    The Radical Pair Model proposes that the avian magnetic compass is based on spin-chemical processes: since the ratio between the two spin states singlet and triplet of radical pairs depends on their alignment in the magnetic field, it can provide information on magnetic directions. Cryptochromes, blue light-absorbing flavoproteins, with flavin adenine dinucleotide as chromophore, are suggested as molecules forming the radical pairs underlying magnetoreception. When activated by light, cryptochromes undergo a redox cycle, in the course of which radical pairs are generated during photo-reduction as well as during light-independent re-oxidation. This raised the question as to which radical pair is crucial for mediating magnetic directions. Here, we present the results from behavioural experiments with intermittent light and magnetic field pulses that clearly show that magnetoreception is possible in the dark interval, pointing to the radical pair formed during flavin re-oxidation. This differs from the mechanism considered for cryptochrome signalling the presence of light and rules out most current models of an avian magnetic compass based on the radical pair generated during photo-reduction. Using the radical pair formed during re-oxidation may represent a specific adaptation of the avian magnetic compass. PMID:27146685

  17. Two primes priming: does feature integration occur before response activation?

    PubMed

    Grainger, Julianne E; Scharnowski, Frank; Schmidt, Thomas; Herzog, Michael H

    2013-07-17

    Responses to a target can be sped up or slowed down by a congruent or incongruent prime, respectively. Even though presentations are rapid, the prime and the target are thought to activate motor responses in strict sequence, with prime activation preceding target activation. In feature fusion, the opposite seems to be the case. For example, a vernier offset to the left is immediately followed by a vernier offset to the right at the same location. The two verniers are not perceived as two elements in sequence but as a single, aligned vernier. Here, we ask the question as to how features are integrated: before or after motor activation? We presented two vernier primes with opposite offset directions preceding a single vernier target. No priming effect occurred when the vernier primes were presented at the same location, indicating that verniers integrate before motor activation. There was also no priming effect when the primes were presented simultaneously at different locations, indicating that there is an integration stage different from the perceptual fusion stage. When the second prime is delayed, it determines priming, even for very long delays. To explain these long integration times, we argue that there is a buffer preceding motor activation.

  18. An Update on Antitumor Activity of Naturally Occurring Chalcones

    PubMed Central

    Zhang, En-Hui; Wang, Ru-Feng; Guo, Shu-Zhen; Liu, Bin

    2013-01-01

    Chalcones, which have characteristic 1,3-diaryl-2-propen-1-one skeleton, are mainly produced in roots, rhizomes, heartwood, leaves, and seeds of genera Angelica, Sophora, Glycyrrhiza, Humulus, Scutellaria, Parartocarpus, Ficus, Dorstenia, Morus, Artocarpus, and so forth. They have become of interest in the research and development of natural antitumor agents over the past decades due to their broad range of mechanisms including anti-initiation, induction of apoptosis, antiproliferation, antimetastasis, antiangiogenesis, and so forth. This review summarizes the studies on the antitumor activity of naturally occurring chalcones and their underlying mechanisms in detail during the past decades. PMID:23690855

  19. Synthetic muscle promoters: activities exceeding naturally occurring regulatory sequences

    NASA Technical Reports Server (NTRS)

    Li, X.; Eastman, E. M.; Schwartz, R. J.; Draghia-Akli, R.

    1999-01-01

    Relatively low levels of expression from naturally occurring promoters have limited the use of muscle as a gene therapy target. Myogenic restricted gene promoters display complex organization usually involving combinations of several myogenic regulatory elements. By random assembly of E-box, MEF-2, TEF-1, and SRE sites into synthetic promoter recombinant libraries, and screening of hundreds of individual clones for transcriptional activity in vitro and in vivo, several artificial promoters were isolated whose transcriptional potencies greatly exceed those of natural myogenic and viral gene promoters.

  20. Antituberculosis Activity of a Naturally Occurring Flavonoid, Isorhamnetin.

    PubMed

    Jnawali, Hum Nath; Jeon, Dasom; Jeong, Min-Cheol; Lee, Eunjung; Jin, Bongwhan; Ryoo, Sungweon; Yoo, Jungheon; Jung, In Duk; Lee, Seung Jun; Park, Yeong-Min; Kim, Yangmee

    2016-04-22

    Isorhamnetin (1) is a naturally occurring flavonoid having anticancer and anti-inflammatory properties. The present study demonstrated that 1 had antimycobacterial effects on Mycobacterium tuberculosis H37Rv, multi-drug- and extensively drug-resistant clinical isolates with minimum inhibitory concentrations of 158 and 316 μM, respectively. Mycobacteria mainly affect the lungs, causing an intense local inflammatory response that is critical to the pathogenesis of tuberculosis. We investigated the effects of 1 on interferon (IFN)-γ-stimulated human lung fibroblast MRC-5 cells. Isorhamnetin suppressed the release of tumor necrosis factor (TNF)-α and interleukin (IL)-12. A nontoxic dose of 1 reduced mRNA expression of TNF-α, IL-1β, IL-6, IL-12, and matrix metalloproteinase-1 in IFN-γ-stimulated cells. Isorhamnetin inhibited IFN-γ-mediated stimulation of extracellular signal-regulated kinase and p38 mitogen-activated protein kinase and showed high-affinity binding to these kinases (binding constants: 4.46 × 10(6) M(-1) and 7.6 × 10(6) M(-1), respectively). The 4'-hydroxy group and the 3'-methoxy group of the B-ring and the 5-hydroxy group of the A-ring of 1 play key roles in these binding interactions. A mouse in vivo study of lipopolysaccharide-induced lung inflammation revealed that a nontoxic dose of 1 reduced the levels of IL-1β, IL-6, IL-12, and INF-γ in lung tissue. These data provide the first evidence that 1 could be developed as a potent antituberculosis drug.

  1. Brain activation associated with active and passive lower limb stepping

    PubMed Central

    Jaeger, Lukas; Marchal-Crespo, Laura; Wolf, Peter; Riener, Robert; Michels, Lars; Kollias, Spyros

    2014-01-01

    Reports about standardized and repeatable experimental procedures investigating supraspinal activation in patients with gait disorders are scarce in current neuro-imaging literature. Well-designed and executed tasks are important to gain insight into the effects of gait-rehabilitation on sensorimotor centers of the brain. The present study aims to demonstrate the feasibility of a novel imaging paradigm, combining the magnetic resonance (MR)-compatible stepping robot (MARCOS) with sparse sampling functional magnetic resonance imaging (fMRI) to measure task-related BOLD signal changes and to delineate the supraspinal contribution specific to active and passive stepping. Twenty-four healthy participants underwent fMRI during active and passive, periodic, bilateral, multi-joint, lower limb flexion and extension akin to human gait. Active and passive stepping engaged several cortical and subcortical areas of the sensorimotor network, with higher relative activation of those areas during active movement. Our results indicate that the combination of MARCOS and sparse sampling fMRI is feasible for the detection of lower limb motor related supraspinal activation. Activation of the anterior cingulate and medial frontal areas suggests motor response inhibition during passive movement in healthy participants. Our results are of relevance for understanding the neural mechanisms underlying gait in the healthy. PMID:25389396

  2. When a Step Is Not a Step! Specificity Analysis of Five Physical Activity Monitors

    PubMed Central

    O’Connell, Sandra; ÓLaighin, Gearóid

    2017-01-01

    Introduction Physical activity is an essential aspect of a healthy lifestyle for both physical and mental health states. As step count is one of the most utilized measures for quantifying physical activity it is important that activity-monitoring devices be both sensitive and specific in recording actual steps taken and disregard non-stepping body movements. The objective of this study was to assess the specificity of five activity monitors during a variety of prescribed non-stepping activities. Methods Participants wore five activity monitors simultaneously for a variety of prescribed activities including deskwork, taking an elevator, taking a bus journey, automobile driving, washing and drying dishes; functional reaching task; indoor cycling; outdoor cycling; and indoor rowing. Each task was carried out for either a specific duration of time or over a specific distance. Activity monitors tested were the ActivPAL micro™, NL-2000™ pedometer, Withings Smart Activity Monitor Tracker (Pulse O2)™, Fitbit One™ and Jawbone UP™. Participants were video-recorded while carrying out the prescribed activities and the false positive step count registered on each activity monitor was obtained and compared to the video. Results All activity monitors registered a significant number of false positive steps per minute during one or more of the prescribed activities. The Withings™ activity performed best, registering a significant number of false positive steps per minute during the outdoor cycling activity only (P = 0.025). The Jawbone™ registered a significant number of false positive steps during the functional reaching task and while washing and drying dishes, which involved arm and hand movement (P < 0.01 for both). The ActivPAL™ registered a significant number of false positive steps during the cycling exercises (P < 0.001 for both). Conclusion As a number of false positive steps were registered on the activity monitors during the non-stepping activities, the

  3. Epigenetic silencing of the c-fms locus during B-lymphopoiesis occurs in discrete steps and is reversible

    PubMed Central

    Tagoh, Hiromi; Schebesta, Alexandra; Lefevre, Pascal; Wilson, Nicola; Hume, David; Busslinger, Meinrad; Bonifer, Constanze

    2004-01-01

    The murine c-fms (Csf1r) gene encodes the macrophage colony-stimulating factor receptor, which is essential for macrophage development. It is expressed at a low level in haematopoietic stem cells and is switched off in all non-macrophage cell types. To examine the role of chromatin structure in this process we studied epigenetic silencing of c-fms during B-lymphopoiesis. c-fms chromatin in stem cells and multipotent progenitors is in the active conformation and bound by transcription factors. A similar result was obtained with specified common myeloid and lymphoid progenitor cells. In developing B cells, c-fms chromatin is silenced in distinct steps, whereby first the binding of transcription factors and RNA expression is lost, followed by a loss of nuclease accessibility. Interestingly, regions of de novo DNA methylation in B cells overlap with an intronic antisense transcription unit that is differently regulated during lymphopoiesis. However, even at mature B cell stages, c-fms chromatin is still in a poised conformation and c-fms expression can be re-activated by conditional deletion of the transcription factor Pax5. PMID:15483629

  4. Recurrent Jets Occurred Nearby Active Region NOAA 11931

    NASA Astrophysics Data System (ADS)

    Yu-kun, Hu; Zhi, Xu; Zhi-ke, Xue; Xiao-li, Yan; Yuan-deng, Shen; Ning, Wu; Jun, Lin

    2016-10-01

    According to the 171 Å observation of Solar Dynamics Observatory/Atmospheric Imaging Assembly (SDO/AIA) in 2013 December 25∼26, a series of homologous jets were continuously found in the southwestern area of the active region NOAA 11931, from which 12 typical jets were selected and studied in this paper. The magnetic field structures in most jets had an obviously untwisting motion in the ejection process, though a few of them didn't have. The process of some jets was divided into two phases: the slow ejection without untwisting, and the rapid untwisting ejection. Before some jets started, a bright point grew along the bottom of magnetic arcade, and extended from the end remote from the jet to the end proximate to the jet, and there were two parts of magnetic structures near the bottom of magnetic arcade untwisted simultaneously in the ejection process. During the final one jet, two magnetic arcades appeared successively in the southeastern end of the magnetic structure on the jet bottom, while a small magnetic loop emerged in the northwestern end. Compared with the line-of-sight magnetogram of SDO/Helioseismic and Magnetic Imager (SDO/HMI), in about 4 h before the first jet appeared, a pair of magnetic dipoles emerged from the bottom of magnetic structure, and continuously lifted during the whole jet event. Although overall the bottom magnetic field emerged before and after the 12 jets, but for each individual jet, the variation of the bottom magnetic field was different from one another: in some jets, the magnetic field near the magnetic arcade on the jet bottom exhibited both magnetic emergence and cancellation; but in other jets, the magnetic field near the jet bottom exhibited only an obvious emergence or cancellation.

  5. Targeting physical activity interventions for adults: When should intervention occur?

    PubMed

    Holliday, Katelyn M; Lin, Dan Yu; Chakladar, Sujatro; Castañeda, Sheila F; Daviglus, Martha L; Evenson, Kelly R; Marquez, David X; Qi, Qibin; Shay, Christina M; Sotres-Alvarez, Daniela; Vidot, Denise C; Zeng, Donglin; Avery, Christy L

    2016-12-23

    Understanding demographic differences in transitions across physical activity (PA) levels is important for informing PA-promoting interventions, yet few studies have examined these transitions in contemporary multi-ethnic adult populations. We estimated age-, race/ethnicity-, and sex-specific 1-year net transition probabilities (NTPs) for National Health and Nutrition Examination Survey (2007-2012, n=11,556) and Hispanic Community Health Study/Study of Latinos (2008-2011, n=15,585) adult participants using novel Markov-type state transition models developed for cross-sectional data. Among populations with ideal PA (≥150min/week; ranging from 56% (non-Hispanic black females) to 88% (non-Hispanic white males) at age 20), NTPs to intermediate PA (>0-<149min/week) generally increased with age, particularly for non-Hispanic black females for whom a net 0.0% (95% confidence interval (CI): 0.0, 0.2) transitioned from ideal to intermediate PA at age 20; by age 70, the NTP rose to 3.6% (95% CI: 2.3, 4.8). Heterogeneity in intermediate to poor (0min/week) PA NTPs also was observed, with NTPs peaking at age 20 for Hispanic/Latino males and females [age 20 NTP=3.7% (95% CI: 2.0, 5.5) for females and 5.0% (1.2, 8.7) for males], but increasing throughout adulthood for non-Hispanic blacks and whites [e.g. age 70 NTP=7.8% (95% CI: 6.1, 9.6%) for black females and 8.1% (4.7, 11.6) for black males]. Demographic differences in PA net transitions across adulthood justify further development of tailored interventions. However, innovative efforts may be required for populations in which large proportions have already transitioned from ideal PA by early adulthood.

  6. Nigeria to step up tar sands activity

    SciTech Connect

    Not Available

    1987-03-01

    The Nigerian government has directed its Ministry of Mines, Power and Steel to assume responsibility for the exploration and exploitation of tar sands deposits in Bendel, Ondo and Oyo States. The directive resulted from a survey report by the University of Ife's geological consultancy unit on bituminous sand deposits in the area. The statement said the government was satisfied that there were large commercial quantities of the sands in the three states. The survey had reported that Nigeria could recover between 31 and 40 billion barrels of heavy crude from the tar sand deposits. Exploration for hydrocarbons is currently going on in Anambra and Lake Chad basins as well as the Benue Trough. Apart from the Nigerian National Petroleum Corporation, Shell Petroleum and Gulf Oil have begun exploration activities in the Ondo area. Meanwhile, Nigeria has had to import heavy crude from Venezuela, for processing at the Kaduna refinery.

  7. Stochastic steps in secondary active sugar transport.

    PubMed

    Adelman, Joshua L; Ghezzi, Chiara; Bisignano, Paola; Loo, Donald D F; Choe, Seungho; Abramson, Jeff; Rosenberg, John M; Wright, Ernest M; Grabe, Michael

    2016-07-05

    Secondary active transporters, such as those that adopt the leucine-transporter fold, are found in all domains of life, and they have the unique capability of harnessing the energy stored in ion gradients to accumulate small molecules essential for life as well as expel toxic and harmful compounds. How these proteins couple ion binding and transport to the concomitant flow of substrates is a fundamental structural and biophysical question that is beginning to be answered at the atomistic level with the advent of high-resolution structures of transporters in different structural states. Nonetheless, the dynamic character of the transporters, such as ion/substrate binding order and how binding triggers conformational change, is not revealed from static structures, yet it is critical to understanding their function. Here, we report a series of molecular simulations carried out on the sugar transporter vSGLT that lend insight into how substrate and ions are released from the inward-facing state of the transporter. Our simulations reveal that the order of release is stochastic. Functional experiments were designed to test this prediction on the human homolog, hSGLT1, and we also found that cytoplasmic release is not ordered, but we confirmed that substrate and ion binding from the extracellular space is ordered. Our findings unify conflicting published results concerning cytoplasmic release of ions and substrate and hint at the possibility that other transporters in the superfamily may lack coordination between ions and substrate in the inward-facing state.

  8. Stochastic steps in secondary active sugar transport

    PubMed Central

    Adelman, Joshua L.; Ghezzi, Chiara; Bisignano, Paola; Loo, Donald D. F.; Choe, Seungho; Abramson, Jeff; Rosenberg, John M.; Wright, Ernest M.; Grabe, Michael

    2016-01-01

    Secondary active transporters, such as those that adopt the leucine-transporter fold, are found in all domains of life, and they have the unique capability of harnessing the energy stored in ion gradients to accumulate small molecules essential for life as well as expel toxic and harmful compounds. How these proteins couple ion binding and transport to the concomitant flow of substrates is a fundamental structural and biophysical question that is beginning to be answered at the atomistic level with the advent of high-resolution structures of transporters in different structural states. Nonetheless, the dynamic character of the transporters, such as ion/substrate binding order and how binding triggers conformational change, is not revealed from static structures, yet it is critical to understanding their function. Here, we report a series of molecular simulations carried out on the sugar transporter vSGLT that lend insight into how substrate and ions are released from the inward-facing state of the transporter. Our simulations reveal that the order of release is stochastic. Functional experiments were designed to test this prediction on the human homolog, hSGLT1, and we also found that cytoplasmic release is not ordered, but we confirmed that substrate and ion binding from the extracellular space is ordered. Our findings unify conflicting published results concerning cytoplasmic release of ions and substrate and hint at the possibility that other transporters in the superfamily may lack coordination between ions and substrate in the inward-facing state. PMID:27325773

  9. How valid are wearable physical activity trackers for measuring steps?

    PubMed

    An, Hyun-Sung; Jones, Gregory C; Kang, Seoung-Ki; Welk, Gregory J; Lee, Jung-Min

    2017-04-01

    Wearable activity trackers have become popular for tracking individual's daily physical activity, but little information is available to substantiate the validity of these devices in step counts. Thirty-five healthy individuals completed three conditions of activity tracker measurement: walking/jogging on a treadmill, walking over-ground on an indoor track, and a 24-hour free-living condition. Participants wore 10 activity trackers at the same time for both treadmill and over-ground protocol. Of these 10 activity trackers three were randomly given for 24-hour free-living condition. Correlations of steps measured to steps observed were r = 0.84 and r = 0.67 on a treadmill and over-ground protocol, respectively. The mean MAPE (mean absolute percentage error) score for all devices and speeds on a treadmill was 8.2% against manually counted steps. The MAPE value was higher for over-ground walking (9.9%) and even higher for the 24-hour free-living period (18.48%) on step counts. Equivalence testing for step count measurement resulted in a significant level within ±5% for the Fitbit Zip, Withings Pulse, and Jawbone UP24 and within ±10% for the Basis B1 band, Garmin VivoFit, and SenseWear Armband Mini. The results show that the Fitbit Zip and Withings Pulse provided the most accurate measures of step count under all three different conditions (i.e. treadmill, over-ground, and 24-hour condition), and considerable variability in accuracy across monitors and also by speeds and conditions.

  10. Stepping Up” Activity Poststroke: Ankle-Positioned Accelerometer Can Accurately Record Steps During Slow Walking

    PubMed Central

    Klassen, Tara D.; Simpson, Lisa A.; Lim, Shannon B.; Louie, Dennis R.; Parappilly, Beena; Sakakibara, Brodie M.; Zbogar, Dominik

    2016-01-01

    Background As physical activity in people poststroke is low, devices that monitor and provide feedback of walking activity provide motivation to engage in exercise and may assist rehabilitation professionals in auditing walking activity. However, most feedback devices are not accurate at slow walking speeds. Objective This study assessed the accuracy of one accelerometer to measure walking steps of community-dwelling individuals poststroke. Design This was a cross-sectional study. Methods Two accelerometers were positioned on the nonparetic waist and ankle of participants (N=43), and walking steps from these devices were recorded at 7 speeds (0.3–0.9 m/s) and compared with video recordings (gold standard). Results When positioned at the waist, the accelerometer had more than 10% error at all speeds, except 0.8 and 0.9 m/s, and numerous participants recorded zero steps at 0.3 to 0.5 m/s. The device had 10% or less error when positioned at the ankle for all speeds between 0.4 and 0.9 m/s. Limitations Some participants were unable to complete the faster walking speeds due to their walking impairments and inability to maintain the requested walking speed. Conclusions Although not recommended by the manufacturer, positioning the accelerometer at the ankle (compared with the waist) may fill a long-standing need for a readily available device that provides accurate feedback for the altered and slow walking patterns that occur with stroke. PMID:26251478

  11. Scalable wavelet-based active network detection of stepping stones

    NASA Astrophysics Data System (ADS)

    Gilbert, Joseph I.; Robinson, David J.; Butts, Jonathan W.; Lacey, Timothy H.

    2012-06-01

    Network intrusions leverage vulnerable hosts as stepping stones to penetrate deeper into a network and mask malicious actions from detection. Identifying stepping stones presents a significant challenge because network sessions appear as legitimate traffic. This research focuses on a novel active watermark technique using discrete wavelet transformations to mark and detect interactive network sessions. This technique is scalable, resilient to network noise, and difficult for attackers to discern that it is in use. Previously captured timestamps from the CAIDA 2009 dataset are sent using live stepping stones in the Amazon Elastic Compute Cloud service. The client system sends watermarked and unmarked packets from California to Virginia using stepping stones in Tokyo, Ireland and Oregon. Five trials are conducted in which the system sends simultaneous watermarked samples and unmarked samples to each target. The live experiment results demonstrate approximately 5% False Positive and 5% False Negative detection rates. Additionally, watermark extraction rates of approximately 92% are identified for a single stepping stone. The live experiment results demonstrate the effectiveness of discerning watermark traffic as applied to identifying stepping stones.

  12. Intrinsic activity and poisoning rate for HCOOH oxidation on platinum stepped surfaces.

    PubMed

    Grozovski, Vitali; Climent, Víctor; Herrero, Enrique; Feliu, Juan M

    2010-08-21

    Pulsed voltammetry has been used to study formic acid oxidation on platinum stepped surfaces to determine the kinetics of the reaction and the role of the surface structure in the reactivity. From the current transients at different potentials, the intrinsic activity of the electrode through the active intermediate reaction path (j(theta = 0)), as well as the rate constant for the CO formation (k(ads)) have been calculated. The kinetics for formic acid oxidation through the active intermediate reaction path is strongly dependent on the surface structure of the electrode, with the highest activity found for the Pt(100) surface. The presence of steps, both on (100) and (111) terraces, does not increase the activity of these surfaces. CO formation only takes place in a narrow potential window very close to the local potential of zero total charge. The extrapolation of the results obtained with stepped surfaces with (111) terraces to zero step density indicates that CO formation should not occur on an ideal Pt(111) electrode. Additionally, the analysis of the Tafel slopes obtained for the different electrodes suggests that the oxidation of formic acid is strongly affected by the presence of adsorbed anions, hydrogen and water.

  13. High endocytotic activity occurs periodically in the endplate region of denervated mouse striated muscle fibers.

    PubMed

    Lawoko, G; Tågerud, S

    1995-08-01

    High endocytotic activity after denervation of skeletal muscle occurs in a proportion of muscle fibers (both slow and fast fiber types) in the endplate region. The present study was performed in order to examine if a periodicity in the endocytotic activity could explain why the process is not observed in all fibers at a given time. Three markers, horseradish peroxidase (HRP), rhodamine B isothiocyanate-labeled dextran, and fluorescein isothiocyanate-labeled dextran were used to demonstrate endocytotic activity of muscle fibers of the denervated mouse hemidiaphragm in vivo. Acetylcholine esterase staining was used in conjunction with HRP uptake to determine the proportion of denervated muscle fibers with endocytotic activity in the endplate region at any one time. The results show that 25-50% of the muscle fibers display high endocytotic activity in the endplate region at a given time 10 days after denervation. The existence of a periodicity in this endocytotic activity is suggested by results obtained using two different endocytotic markers administered at time intervals of 0-7 days. We conclude that loss of contact with the innervating motorneuron induces a high endocytotic activity which occurs periodically in the perisynaptic region of skeletal muscle fibers.

  14. Synaptic activation of ribosomal protein S6 phosphorylation occurs locally in activated dendritic domains.

    PubMed

    Pirbhoy, Patricia Salgado; Farris, Shannon; Steward, Oswald

    2016-06-01

    Previous studies have shown that induction of long-term potentiation (LTP) induces phosphorylation of ribosomal protein S6 (rpS6) in postsynaptic neurons, but the functional significance of rpS6 phosphorylation is poorly understood. Here, we show that synaptic stimulation that induces perforant path LTP triggers phosphorylation of rpS6 (p-rpS6) locally near active synapses. Using antibodies specific for phosphorylation at different sites (ser235/236 versus ser240/244), we show that strong synaptic activation led to dramatic increases in immunostaining throughout postsynaptic neurons with selectively higher staining for p-ser235/236 in the activated dendritic lamina. Following LTP induction, phosphorylation at ser235/236 was detectable by 5 min, peaked at 30 min, and was maintained for hours. Phosphorylation at both sites was completely blocked by local infusion of the NMDA receptor antagonist, APV. Despite robust induction of p-rpS6 following high frequency stimulation, assessment of protein synthesis by autoradiography revealed no detectable increases. Exploration of a novel environment led to increases in the number of p-rpS6-positive neurons throughout the forebrain in a pattern reminiscent of immediate early gene induction and many individual neurons that were p-rpS6-positive coexpressed Arc protein. Our results constrain hypotheses about the possible role of rpS6 phosphorylation in regulating postsynaptic protein synthesis during induction of synaptic plasticity.

  15. Activity, specificity, and titer of naturally occurring canine anti-DEA 7 antibodies.

    PubMed

    Spada, Eva; Proverbio, Daniela; Baggiani, Luciana; Canzi, Ilaria; Perego, Roberta

    2016-11-01

    The reported prevalence of naturally occurring anti-dog erythrocyte antigen (DEA) 7 antibodies in DEA 7-negative dogs is as high as 50%. Characterization of these antibodies may better define their importance in canine transfusion medicine. We determined in vitro activity, specificity, and titer of anti-DEA 7 antibodies in DEA 7-negative dogs. Plasma samples from 317 DEA 7-negative dogs were cross-matched with DEA 7-positive red blood cells (RBCs) using gel column technology. Agglutination occurred with DEA 7-positive RBCs but not with DEA 7-negative RBCs in 73 samples (23%), which were hence classified as containing anti-DEA 7 antibodies. These samples were evaluated for hemolytic and agglutinating activity, strength of agglutination, and antibody specificity and titers. All samples showed agglutination but none showed hemolysis. Gel agglutination was graded as 1+ for 20 samples (27%), 2+ for 49 samples (67%), 3+ for 4 samples (6%); no samples were graded 4+. The agglutination titer was <1:2 for 51 samples (73%), 1:2 for 13 samples (19%), 1:4 for 4 samples (5%), and 1:8 for 2 samples (3%). Of 16 samples treated with 2-mercaptoethanol, 11 samples (69%) contained only IgM, 4 samples (25%) exhibited only IgG activity, and 1 sample (6%) had both IgG and IgM activity. Low titers of warm, weakly agglutinating, mostly naturally occurring IgM anti-DEA 7 antibodies were found in 23% of DEA 7-negative dogs. The presence of naturally occurring anti-DEA 7 antibodies suggests that cross-matching of canine blood recipients is advisable, even at first transfusion, to minimize delayed transfusion reactions.

  16. Recruiting Older Adults into a Physical Activity Promotion Program: "Active Living Every Day" Offered in a Naturally Occurring Retirement Community

    ERIC Educational Resources Information Center

    Hildebrand, Mary; Neufeld, Peggy

    2009-01-01

    Purpose: This article explores recruitment strategies based on the transtheoretical model (TTM) with older adults living in a naturally occurring retirement community (NORC) to encourage enrollment in a physical activity promotion program, "Active Living Every Day" (ALED). Reasons for participation or nonparticipation are identified. Design and…

  17. Naturally Occurring Nrf2 Activators: Potential in Treatment of Liver Injury

    PubMed Central

    2016-01-01

    Oxidative stress plays a major role in acute and chronic liver injury. In hepatocytes, oxidative stress frequently triggers antioxidant response by activating nuclear erythroid 2-related factor 2 (Nrf2), a transcription factor, which upregulates various cytoprotective genes. Thus, Nrf2 is considered a potential therapeutic target to halt liver injury. Several studies indicate that activation of Nrf2 signaling pathway ameliorates liver injury. The hepatoprotective potential of naturally occurring compounds has been investigated in various models of liver injuries. In this review, we comprehensively appraise various phytochemicals that have been assessed for their potential to halt acute and chronic liver injury by enhancing the activation of Nrf2 and have the potential for use in humans. PMID:28101296

  18. Poly(anhydride-esters) Comprised Exclusively of Naturally Occurring Antimicrobials and EDTA: Antioxidant and Antibacterial Activities

    PubMed Central

    2015-01-01

    Carvacrol, thymol, and eugenol are naturally occurring phenolic compounds known to possess antimicrobial activity against a range of bacteria, as well as antioxidant activity. Biodegradable poly(anhydride-esters) composed of an ethylenediaminetetraacetic acid (EDTA) backbone and antimicrobial pendant groups (i.e., carvacrol, thymol, or eugenol) were synthesized via solution polymerization. The resulting polymers were characterized to confirm their chemical composition and understand their thermal properties and molecular weight. In vitro release studies demonstrated that polymer hydrolytic degradation was complete after 16 days, resulting in the release of free antimicrobials and EDTA. Antioxidant and antibacterial assays determined that polymer release media exhibited bioactivity similar to that of free compound, demonstrating that polymer incorporation and subsequent release had no effect on activity. These polymers completely degrade into components that are biologically relevant and have the capability to promote preservation of consumer products in the food and personal care industries via antimicrobial and antioxidant pathways. PMID:24702678

  19. Poly(anhydride-esters) comprised exclusively of naturally occurring antimicrobials and EDTA: antioxidant and antibacterial activities.

    PubMed

    Carbone-Howell, Ashley L; Stebbins, Nicholas D; Uhrich, Kathryn E

    2014-05-12

    Carvacrol, thymol, and eugenol are naturally occurring phenolic compounds known to possess antimicrobial activity against a range of bacteria, as well as antioxidant activity. Biodegradable poly(anhydride-esters) composed of an ethylenediaminetetraacetic acid (EDTA) backbone and antimicrobial pendant groups (i.e., carvacrol, thymol, or eugenol) were synthesized via solution polymerization. The resulting polymers were characterized to confirm their chemical composition and understand their thermal properties and molecular weight. In vitro release studies demonstrated that polymer hydrolytic degradation was complete after 16 days, resulting in the release of free antimicrobials and EDTA. Antioxidant and antibacterial assays determined that polymer release media exhibited bioactivity similar to that of free compound, demonstrating that polymer incorporation and subsequent release had no effect on activity. These polymers completely degrade into components that are biologically relevant and have the capability to promote preservation of consumer products in the food and personal care industries via antimicrobial and antioxidant pathways.

  20. Biological activity of some naturally occurring resins, gums and pigments against in vitro LDL oxidation.

    PubMed

    Andrikopoulos, Nikolaos K; Kaliora, Andriana C; Assimopoulou, Andreana N; Papapeorgiou, Vassilios P

    2003-05-01

    Naturally occurring gums and resins with beneficial pharmaceutical and nutraceutical properties were tested for their possible protective effect against copper-induced LDL oxidation in vitro. Chiosmastic gum (CMG) (Pistacia lentiscus var. Chia resin) was the most effective in protecting human LDL from oxidation. The minimum and maximum doses for the saturation phenomena of inhibition of LDL oxidation were 2.5 mg and 50 mg CMG (75.3% and 99.9%, respectively). The methanol/water extract of CMG was the most effective compared with other solvent combinations. CMG when fractionated in order to determine a structure-activity relationship showed that the total mastic essential oil, collofonium-like residue and acidic fractions of CMG exhibited a high protective activity ranging from 65.0% to 77.8%. The other natural gums and resins (CMG resin 'liquid collection', P. terebinthus var. Chia resin, dammar resin, acacia gum, tragacanth gum, storax gum) also tested as above, showed 27.0%-78.8% of the maximum LDL protection. The other naturally occurring substances, i.e. triterpenes (amyrin, oleanolic acid, ursolic acid, lupeol, 18-a-glycyrrhetinic acid) and hydroxynaphthoquinones (naphthazarin, shikonin and alkannin) showed 53.5%-78.8% and 27.0%-64.1% LDL protective activity, respectively. The combination effects (68.7%-76.2% LDL protection) of ursolic-, oleanolic- and ursodeoxycholic- acids were almost equal to the effect (75.3%) of the CMG extract in comparable doses.

  1. Leishmanicidal and cytotoxic activities of extracts and naturally-occurring compounds from two Lauraceae species.

    PubMed

    Sánchez-Suárez, Jeysson; Coy-Barrera, Ericsson; Cuca, Luis Enrique; Delgado, Gabriela

    2011-02-01

    The in vitro leishmanicidal effects of ethanolic extracts and fifteen naturally-occurring compounds (five lignans, eight neolignans, a diterpene and a dihydrochalcone), obtained from Pleurothyrium cinereum and Ocotea macrophylla, were evaluated on promastigotes of Leishmania panamensis and L. braziliensis. In addition, in order to determine the selective action on Leishmania species as a safety principle, in vitro cytotoxicity on J774 cells was also evaluated for test compounds and extracts. One extract and seven compounds showed activity against Leishmania parasites at different levels. Dihydroflavokawin B (8) was found to be the most potent antileishmanial compound on both parasites, whilst (+)-otobaphenol (14), was found to be the most selective compound on L. panamensis.

  2. A Novel Two-Step Hierarchial Quantitative Structure-Activity ...

    EPA Pesticide Factsheets

    Background: Accurate prediction of in vivo toxicity from in vitro testing is a challenging problem. Large public–private consortia have been formed with the goal of improving chemical safety assessment by the means of high-throughput screening. Methods and results: A database containing experimental cytotoxicity values for in vitro half-maximal inhibitory concentration (IC50) and in vivo rodent median lethal dose (LD50) for more than 300 chemicals was compiled by Zentralstelle zur Erfassung und Bewertung von Ersatz- und Ergaenzungsmethoden zum Tierversuch (ZEBET ; National Center for Documentation and Evaluation of Alternative Methods to Animal Experiments) . The application of conventional quantitative structure–activity relationship (QSAR) modeling approaches to predict mouse or rat acute LD50 values from chemical descriptors of ZEBET compounds yielded no statistically significant models. The analysis of these data showed no significant correlation between IC50 and LD50. However, a linear IC50 versus LD50 correlation could be established for a fraction of compounds. To capitalize on this observation, we developed a novel two-step modeling approach as follows. First, all chemicals are partitioned into two groups based on the relationship between IC50 and LD50 values: One group comprises compounds with linear IC50 versus LD50 relationships, and another group comprises the remaining compounds. Second, we built conventional binary classification QSAR models t

  3. Measurement of activity in older adults: reliability and validity of the Step Activity Monitor.

    PubMed

    Resnick, B; Nahm, E S; Orwig, D; Zimmerman, S S; Magaziner, J

    2001-01-01

    The purpose of this study was to test the reliability and validity of the Step Activity Monitor (SAM) when used with older adults. A total of 30 subjects with a mean age of 86 +/- 6.1 participated in the study. Sixty one-minute walks were measured with the SAM, and two observers visually counted steps. Four participants wore the SAM for 6 to 48 hours and maintained activity diaries. The intraclass correlation for the SAM recordings was R = .84. There was an overall step counting accuracy of 96%. The diaries supported the SAM data for those who wore the SAM for extended periods. The SAM is an easy to use, comfortable, valid, and reliable measure of activity in older adults and particularly may be useful to triangulate measurement of activity in these individuals.

  4. Catalytic, oxidative condensation of CH4 to CH3COOH in one step via CH activation.

    PubMed

    Periana, Roy A; Mironov, Oleg; Taube, Doug; Bhalla, Gaurav; Jones, C J

    2003-08-08

    Acetic acid is an important petrochemical that is currently produced from methane (or coal) in a three-step process based on carbonylation of methanol. We report a direct, selective, oxidative condensation of two methane molecules to acetic acid at 180 degrees C in liquid sulfuric acid. Carbon-13 isotopic labeling studies show that both carbons of acetic acid originate from methane. The reaction is catalyzed by palladium, and the results are consistent with the reaction occurring by tandem catalysis, involving methane C-H activation to generate Pd-CH3 species, followed by efficient oxidative carbonylation with methanol, generated in situ from methane, to produce acetic acid.

  5. Antioxidant activity, ascorbic acid and total phenol of exotic fruits occurring in Brazil.

    PubMed

    de Assis, Sandra Aparecida; Vellosa, José Carlos Rebuglio; Brunetti, Iguatemy Lourenço; Khalil, Najeh Maissar; Leite, Kátia Maria da Silva Cerqueira; Martins, Antonio Baldo Geraldo; Oliveira, Olga Maria Mascarenhas de Faria

    2009-08-01

    The antioxidant activity, ascorbic acid and phenolic content were studied in 10 exotic fruits from Brazil: abiu, acerola, wax jambu, cashew, mamey sapote, carambola or star fruit, Surinam cherry, longan, sapodilla and jaboticaba. The ascorbic acid was determined by 2,6-dichloroindophenol titrimetic methods and total phenols were measured colorimetrically using the Folin-Ciocalteu reagent. The antioxidant activity was investigated with three different methods: hypochlorous acid scavenging activity, 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) radical cation decolorization assay, and 2,2-diphenyl-1-picrylhydrazyl radical scavenging method. The highest content of vitamin C (1,525.00 mg/100 g pulp) occurred in acerola. The total phenol content was higher in abiu, acerola, Surinam cherry and sapodilla. In relation to antioxidant activity, acerola has showed the great values in all three different methods tested. It was found that the fruits have a significant antioxidant effect when tested by each method, respectively, and these antioxidant capacities are promising. The sample concentration also influenced its antioxidant power.

  6. Step detection and activity recognition accuracy of seven physical activity monitors.

    PubMed

    Storm, Fabio A; Heller, Ben W; Mazzà, Claudia

    2015-01-01

    The aim of this study was to compare the seven following commercially available activity monitors in terms of step count detection accuracy: Movemonitor (Mc Roberts), Up (Jawbone), One (Fitbit), ActivPAL (PAL Technologies Ltd.), Nike+ Fuelband (Nike Inc.), Tractivity (Kineteks Corp.) and Sensewear Armband Mini (Bodymedia). Sixteen healthy adults consented to take part in the study. The experimental protocol included walking along an indoor straight walkway, descending and ascending 24 steps, free outdoor walking and free indoor walking. These tasks were repeated at three self-selected walking speeds. Angular velocity signals collected at both shanks using two wireless inertial measurement units (OPAL, ADPM Inc) were used as a reference for the step count, computed using previously validated algorithms. Step detection accuracy was assessed using the mean absolute percentage error computed for each sensor. The Movemonitor and the ActivPAL were also tested within a nine-minute activity recognition protocol, during which the participants performed a set of complex tasks. Posture classifications were obtained from the two monitors and expressed as a percentage of the total task duration. The Movemonitor, One, ActivPAL, Nike+ Fuelband and Sensewear Armband Mini underestimated the number of steps in all the observed walking speeds, whereas the Tractivity significantly overestimated step count. The Movemonitor was the best performing sensor, with an error lower than 2% at all speeds and the smallest error obtained in the outdoor walking. The activity recognition protocol showed that the Movemonitor performed best in the walking recognition, but had difficulty in discriminating between standing and sitting. Results of this study can be used to inform choice of a monitor for specific applications.

  7. Step Detection and Activity Recognition Accuracy of Seven Physical Activity Monitors

    PubMed Central

    Storm, Fabio A.; Heller, Ben W.; Mazzà, Claudia

    2015-01-01

    The aim of this study was to compare the seven following commercially available activity monitors in terms of step count detection accuracy: Movemonitor (Mc Roberts), Up (Jawbone), One (Fitbit), ActivPAL (PAL Technologies Ltd.), Nike+ Fuelband (Nike Inc.), Tractivity (Kineteks Corp.) and Sensewear Armband Mini (Bodymedia). Sixteen healthy adults consented to take part in the study. The experimental protocol included walking along an indoor straight walkway, descending and ascending 24 steps, free outdoor walking and free indoor walking. These tasks were repeated at three self-selected walking speeds. Angular velocity signals collected at both shanks using two wireless inertial measurement units (OPAL, ADPM Inc) were used as a reference for the step count, computed using previously validated algorithms. Step detection accuracy was assessed using the mean absolute percentage error computed for each sensor. The Movemonitor and the ActivPAL were also tested within a nine-minute activity recognition protocol, during which the participants performed a set of complex tasks. Posture classifications were obtained from the two monitors and expressed as a percentage of the total task duration. The Movemonitor, One, ActivPAL, Nike+ Fuelband and Sensewear Armband Mini underestimated the number of steps in all the observed walking speeds, whereas the Tractivity significantly overestimated step count. The Movemonitor was the best performing sensor, with an error lower than 2% at all speeds and the smallest error obtained in the outdoor walking. The activity recognition protocol showed that the Movemonitor performed best in the walking recognition, but had difficulty in discriminating between standing and sitting. Results of this study can be used to inform choice of a monitor for specific applications. PMID:25789630

  8. Monitoring Natural Occurring Asbestos in ophiolite sequences and derived soils: implication with human activities

    NASA Astrophysics Data System (ADS)

    Punturo, Rosalda; Bloise, Andrea; Cirrincione, Rosolino

    2016-04-01

    The present contribution focuses on soils that developed on serpentinite-metabasite bedrocks, which could potentially be rich in asbestos minerals and, as a consequence, have a negative impact on agricultural activity and on environmental quality. In order to investigate the natural occurrences of asbestos (NOA) on the surface of the soil formed from serpentinites and metabasite, we selected a study area located in Sila Piccola (Calabrian Peloritani Orogen, southern Italy), where previous studies highlighted the presence of asbestiform minerals within the large ophiolitic sequences that crop out (Punturo et al., 2015; Bloise et al., 2015). Agricultural soil samples have been collected mainly close to urban centres and characterized by using different analytical techniques such as X-ray powder diffraction (XRPD), transmission electron microscopy combined with energy dispersive spectrometry (TEM-EDS), thermogravimetry (TG) and differential scanning calorimetry (DSC) Results pointed out as all the collected soil samples contain serpentine minerals (e.g., chrysotile), asbestos amphiboles, clays, chlorite, muscovite, plagioclase and iron oxides in various amounts. Electron microscope images of the soils show that their contain a variety of aggregating agents such as organic matter and clay in which individual fibres of chrysotile and tremolite-actinolite are trapped. The investigation showed that both serpentinite and metabasite rocks act as a perennial source of contamination for the agriculture lands because of the high amount of tremolite-actinolite found in the studied soil samples developed on such lithotypes. Even if asbestiform minerals usually occur in aggregates which cannot be suspended in the air, agricultural activities such as plowing can destroy these soil aggregates with the creation of dust containing inhalable asbestos fibres that evolve into airborne increasing the exposure of population to them. Since the dispersion of fibres could be associated with

  9. Activation of respiratory muscles does not occur during cold-submergence in bullfrogs, Lithobates catesbeianus.

    PubMed

    Santin, Joseph M; Hartzler, Lynn K

    2017-01-17

    Semiaquatic frogs may not breathe air for several months because they overwinter in ice-covered ponds. In contrast to many vertebrates that experience decreased motor performance after inactivity, respiratory motor function in bullfrogs, Lithobates catesbeianus, remains functional following cold-submergence. Unlike mammalian hibernators with unloaded limb muscles and inactive locomotor systems, respiratory mechanics of frogs counterintuitively allow for ventilatory maneuvers when submerged. Thus we hypothesized that bullfrogs generate respiratory motor patterns during cold-submergence to avoid disuse and preserve motor performance. Accordingly, we measured activity of respiratory muscles (buccal floor compressor and glottal dilator) via electromyography in freely behaving bullfrogs at 20°C and 2°C. Although we confirm that ventilation cycles occur underwater at 20°C, bullfrogs did not activate either respiratory muscle when submerged acutely or chronically at 2°C. We conclude that cold-submerged bullfrogs endure respiratory motor inactivity, implying that other mechanisms, excluding underwater muscle activation, maintain a functional respiratory motor system throughout overwintering.

  10. Investigation of the activity level and radiological impacts of naturally occurring radionuclides in blast furnace slag.

    PubMed

    Uğur, F A; Turhan, S; Sahan, H; Sahan, M; Gören, E; Gezer, F; Yeğingil, Z

    2013-01-01

    The activity level and possible radiological impacts of naturally occurring radionuclides on the health of workers and members of the public, as a result of utilisation of blast furnace slag (BFS) samples as a substitute for aggregate in road construction were investigated by using a gamma-ray spectrometer and potential exposure scenarios given in Radiation Protection 122. The mean activity concentrations of the (226)Ra, (232)Th and (40)K in BFS samples were found to be 152.4, 54.9 and 183.1 Bq kg(-1), respectively. These values are compared with typical values measured in BFS samples from the European Union countries, which are 270, 70 and 240 Bq kg(-1) for (226)Ra, (232)Th and (40)K, respectively. The values of radium equivalent activity index calculated for BFS samples were within the recommended safety limits. The highest total annual effective doses evaluated as 0.9 and 0.4 mSv y(-1) for members of the public and workers, respectively, were lower than the annual limit of 1 mSv y(-1).

  11. T-cell activation is accompanied by an ubiquitination process occurring at the immunological synapse.

    PubMed

    Wiedemann, Aurelie; Müller, Sabina; Favier, Benoit; Penna, Doris; Guiraud, Martine; Delmas, Christelle; Champagne, Eric; Valitutti, Salvatore

    2005-04-15

    The immunological synapse (IS) is a specialized signaling area formed at the contact site between T-cells and antigen-presenting cells (APC), where sustained engagement and signaling of TCR and accessory molecules occur. A key feature of T-cell antigen recognition is that the process of TCR/peptide-MHC interaction is self-limited by the internalization and degradation of triggered TCR and recruited signaling components. The mechanism of signaling component degradation involves their ubiquitination and targeting for degradation. Yet, the relationship between the ubiquitination process and TCR signaling as well as the cellular localization of TCR-induced ubiquitination are still elusive. In the present work, we visualize for the first time ubiquitination at the TCR signaling area. We show an enrichment of ubiquitin staining in TCR/CD3 caps in T-lymphocytes stimulated by anti-CD3 antibodies. Remarkably, we also show the recruitment of the ubiquitin ligase Cbl-b and a significant ubiquitination at the immunological synapse in antigen-stimulated T-cells. Our results identify the immunological synapse as the cellular area where TCR-induced protein ubiquitination occurs. They imply that the synapse is a specialized site where the activation process is not only triggered, but also controlled via ubiquitination of signaling actors.

  12. Seizure activity occurring in two dogs after S-ketamine-induction.

    PubMed

    Adami, C; Spadavecchia, C; Casoni, D

    2013-10-01

    Two healthy dogs were anaesthetized to undergo elective orthopaedic procedures. After premedication with methadone and acepromazine, general anaesthesia was induced with midazolam and S-ketamine. Immediately after anaesthetic induction, seizures occurred in both dogs. In the first dog the syndrome was characterized by tonic and clonic motor activity, muscular hypertone, hypersalivation, urination, defecation and hyperthermia. In the second dog muscular twitches of the temporal and masseter regions were observed, followed by increased skeletal muscles tone, hypersalivation, spontaneous urination and increase in body temperature. Recoveries from anaesthesia were uneventful and no seizures were observed. Considering the temporal association between anaesthetic induction and occurrence of seizures, and the fact that other causative factors could not be identified, it is hypothesized that S-ketamine played a role in determining the convulsive phenomena observed in these patients. S-ketamine might carry the potential for inducing seizures in otherwise healthy dogs, despite the concomitant use of GABA-ergic drugs.

  13. Interleukin-37 Enhances the Suppressive Activity of Naturally Occurring CD4+CD25+ Regulatory T Cells

    PubMed Central

    Wang, Da-Wei; Dong, Ning; Wu, Yao; Zhu, Xiao-Mei; Wang, Chun-Ting; Yao, Yong-Ming

    2016-01-01

    Naturally occurring CD4+CD25+ regulatory T cells (Tregs) are essential for the suppression of autoimmunity and can control the immune-mediated pathology during the early phase of sepsis. Our previous data showed that silencing interleukin-37 (IL-37) in human CD4+CD25+ Tregs obviously reduced the suppressive activity of CD4+CD25+ Tregs. Here, we found that rhIL-37 stimulation markedly enhanced the suppressive activity of CD4+CD25+ Tregs isolated from naive C57BL/6 J mice in the absence or presence of lipopolysaccharide (LPS). Treatment with rhIL-37 could significantly upregulate the expression of cytotoxic T-lymphocyte-associated antigen (CTLA)-4 and forkhead/winged helix transcription factor p3 (Foxp3) on CD4+CD25+ Tregs. Also, rhIL-37 stimulation promoted the production of transforming growth factor-β1 (TGF-β1) but not IL-10 in the supernatants of cultured CD4+CD25+ Tregs. Pretreated CD4+CD25+ Tregs with rhIL-37 in the presence or absence of LPS were cocultured with CD4+CD25− T cells, ratio of IL-4/interferon-γ in the supernatants obviously increased in IL-37-stimulated groups. In addition, early administration of IL-37 significantly improved the survival rate of septic mice induced by cecal ligation and puncture. Taken together, we concluded that rhIL-37 enhances the suppressive activity of CD4+CD25+ Tregs and might be a potential immunomodulator for the treatment of septic complications. PMID:27941849

  14. Atomistic Characterization of the First Step of Calcium Pump Activation Associated with Proton Countertransport.

    PubMed

    Ramírez-Salinas, G Lizbeth; Espinoza-Fonseca, L Michel

    2015-08-25

    The calcium pump [sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA)] transports Ca(2+) from the cytosol to the SR lumen at the expense of ATP hydrolysis and proton countertransport, thus playing a central role in Ca(2+) homeostasis and muscle contractility. Proton countertransport via deprotonation of transport site residue Glu309 is a critical first step in SERCA activation because it accelerates the E2-E1 structural transition. Previous studies have suggested that flipping of Glu309 toward the cytosol constitutes the primary mechanism for Glu309 deprotonation, but no conclusive data to support this hypothesis have been published. Therefore, we performed three independent 1 μs molecular dynamics simulations of the E2 state protonated at transport site residues Glu309, Glu771, and Glu908. Structural analysis and pKa calculations showed that Glu309 deprotonation occurs by an inward-to-outward side-chain transition. We also found that Glu309 deprotonation and proton countertransport occur through transient (~113 ps) water wires connecting Glu309 with the cytosol. Although both mechanisms are operational, we found that transient water wire formation, and not Glu309 flipping, is the primary mechanism for Glu309 deprotonation and translocation of protons to the cytosol. The outward-to-inward transition of protonated Glu309 and the presence of water wires suggest that protons from the cytosol might be passively transported to the lumen via Glu309. However, structural analysis indicates that passive SR proton leakage into the lumen unlikely occurs through Glu309 in the E2 state. These findings provide a time-resolved visualization of the first step in the molecular mechanism of SERCA activation and proton transport across the SR.

  15. The Throw-and-Catch Model of Human Gait: Evidence from Coupling of Pre-Step Postural Activity and Step Location

    PubMed Central

    Bancroft, Matthew J.; Day, Brian L.

    2016-01-01

    Postural activity normally precedes the lift of a foot from the ground when taking a step, but its function is unclear. The throw-and-catch hypothesis of human gait proposes that the pre-step activity is organized to generate momentum for the body to fall ballistically along a specific trajectory during the step. The trajectory is appropriate for the stepping foot to land at its intended location while at the same time being optimally placed to catch the body and regain balance. The hypothesis therefore predicts a strong coupling between the pre-step activity and step location. Here we examine this coupling when stepping to visually-presented targets at different locations. Ten healthy, young subjects were instructed to step as accurately as possible onto targets placed in five locations that required either different step directions or different step lengths. In 75% of trials, the target location remained constant throughout the step. In the remaining 25% of trials, the intended step location was changed by making the target jump to a new location 96 ms ± 43 ms after initiation of the pre-step activity, long before foot lift. As predicted by the throw-and-catch hypothesis, when the target location remained constant, the pre-step activity led to body momentum at foot lift that was coupled to the intended step location. When the target location jumped, the pre-step activity was adjusted (median latency 223 ms) and prolonged (on average by 69 ms), which altered the body’s momentum at foot lift according to where the target had moved. We conclude that whenever possible the coupling between the pre-step activity and the step location is maintained. This provides further support for the throw-and-catch hypothesis of human gait. PMID:28066208

  16. Step activity and stride-to-stride fluctuations are negatively correlated in individuals with transtibial amputation

    PubMed Central

    Kent, Jenny A.; Stergiou, Nicholas; Wurdeman, Shane R.

    2016-01-01

    Background Variability occurs naturally from stride to stride in healthy gait. It has been shown that individuals with lower limb loss have significantly increased stride-to-stride fluctuations during walking. This is considered indicative of movement disorganization and is associated with less healthy movement. Given that lower limb prosthesis users perform on average less physical activity than able bodied individuals, the purpose of this study was to determine whether increased fluctuations also correspond to a reduced level of activity in daily life. Methods Twenty-two transtibial amputees wore an activity monitor (Actigraph, Pensacola, FL, USA) for 3 weeks. Lower limb kinematics during treadmill walking were measured using a 12-camera motion capture system. The largest Lyapunov exponent (λ) was calculated bilaterally at the ankle, knee and hip to quantify the stride-to-stride fluctuations of the lower limb joints. Pearson correlations were used to identify the relationships between the average daily step count over the 3 week collection period and λ. Findings Significant, moderate negative correlations between daily step count and λ were found at the intact ankle (r = 0.57, P = 0.005), and the knee on the affected side (r = 0.44, P = 0.038). No such correlation was found at any other lower limb joint. Interpretation The negative correlation evident at these two joints demonstrates that increased stride-to-stride fluctuations are related to decreased activity levels, however it remains unclear whether these changes in the stride-to-stride fluctuations promote decreased activity or whether less active individuals do not gain sufficient motor learning experience to achieve a skilled movement. PMID:26319219

  17. On the Total Energy Deposition Between Periodically Occurring Activations of the Aurora

    NASA Technical Reports Server (NTRS)

    Spann, James F., Jr.; Germany, G. A.; Parks, G. K.; Brittnacher, M. J.; Winglee, R. W.

    1998-01-01

    Total energy deposition in the northern latitudes is used in models to determine the state of the magnetosphere. It is known that on occasion, a series of intensifications of the aurora occur that are regularly spaced. The energy profile of the total energy deposited reflects this occurance. What can be said of the state of the magnetosphere based on these profiles. We present the result of a study which looks at several of these periods when a series of intensifications occur. Conclusions as to what the magnetosphere may be doing are presented.

  18. One step conversion of toxic beta-asarone from Acorus calamus into 1-(2,4,5-trimethoxyphenyl)-1,2-dihydroxypropane and asaronaldehyde occurring in Piper clusii.

    PubMed

    Sinha, A K; Joshi, B P; Dogra, R

    2001-01-01

    1-(2,4,5-Trimethoxyphenyl)-1,2-dihydroxypropane (2), a natural phenylpropanoid occurring in Piper clusii, has been synthesized for the first time from toxic beta-asarone (1) of Acorus calamus with osmium tetroxide, while 1 with osmium tetroxide (catalytic amount) in presence of sodium metaperiodate furnished the asaronaldehyde (3) in high yield.

  19. Molybdenum metallization, and step-induced defects in active-matrix liquid crystal displays

    NASA Astrophysics Data System (ADS)

    Quli, Farhat Abbas

    The objective of this work was to identify the causes of the step-induced preferential etching which occurs during the patterning of molybdenum (Mo) interconnects for the source/drain line metallization of the thin-film transistor array of active matrix liquid crystal displays. The morphology of Mo films deposited on steps under various conditions using sputtering and electron beam physical vapor deposition (EB-PVD) was studied to identify the causes of preferential etching, and determine processing conditions leading to defect-free interconnects. It was found that columnar growth domains grown from the steps were misaligned with the columnar growth from the substrate, causing the creation of high-angle grain boundaries where the columns impinged upon one another. This boundary region is believed to be responsible for the preferential etching in the Mo films. Columnar growth of silicon dioxide, an amorphous film, did not result in preferential etching due to the lack of grain boundaries. Neon (Ne) sputtering of Mo did not lead to amorphous films due to higher film bombardment during Ne sputtering, as reported by other researchers. Instead, the low rate of deposition during Ne sputtering was found to cause the incorporation of high amounts of impurities that lead to amorphization of the growing film. At extremely low rates and high impurity concentrations, it was found that the film grew in a fcc rather than bcc structure. Mo deposited under high levels of argon ion bombardment was found to have an isotropic rather than columnar morphology which led to interconnects that were free from preferential etching. The maximum ratio of depositing atoms to bombarding ions necessary to modify the microstructure was found to be 1.5 for Mo deposited by EB-PVD at 400°C substrate temperature and --600 volts substrate bias. The processing window for bias sputtering conditions leading to an isotropic morphology was also identified. Thermally induced grain growth in metal films was

  20. An Interactive Classroom Activity Demonstrating Reaction Mechanisms and Rate-Determining Steps

    ERIC Educational Resources Information Center

    Jennings, Laura D.; Keller, Steven W.

    2005-01-01

    An interactive classroom activity that includes two-step reaction of unwrapping and eating chocolate candies is described which brings not only the reaction intermediate, but also the reactants and products into macroscopic view. The qualitative activation barriers of both steps can be adjusted independently.

  1. Accelerometer steps/day translation of moderate-to-vigorous activity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Physical activity (PA) guidelines are typically communicated in terms of duration, frequency, and intensity, e.g., 30 minutes/day of moderate-to-vigorous physical activity (MVPA) on at least 5 days/week. Step counters can be used to collect objective PA expressed as steps/day; howeverc the associat...

  2. Quantitative modeling of the molecular steps underlying shut-off of rhodopsin activity in rod phototransduction

    PubMed Central

    Kraft, Timothy W.

    2016-01-01

    Purpose To examine the predictions of alternative models for the stochastic shut-off of activated rhodopsin (R*) and their implications for the interpretation of experimentally recorded single-photon responses (SPRs) in mammalian rods. Theory We analyze the transitions that an activated R* molecule undergoes as a result of successive phosphorylation steps and arrestin binding. We consider certain simplifying cases for the relative magnitudes of the reaction rate constants and derive the probability distributions for the time to arrestin binding. In addition to the conventional model in which R* catalytic activity declines in a graded manner with successive phosphorylations, we analyze two cases in which the activity is assumed to occur not via multiple small steps upon each phosphorylation but via a single large step. We refer to these latter two cases as the binary R* shut-off and three-state R* shut-off models. Methods We simulate R*’s stochastic reactions numerically for the three models. In the simplifying cases for the ratio of rate constants in the binary and three-state models, we show that the probability distribution of the time to arrestin binding is accurately predicted. To simulate SPRs, we then integrate the differential equations for the downstream reactions using a standard model of the rod outer segment that includes longitudinal diffusion of cGMP and Ca2+. Results Our simulations of SPRs in the conventional model of graded shut-off of R* conform closely to the simulations in a recent study. However, the gain factor required to account for the observed mean SPR amplitude is higher than can be accounted for from biochemical experiments. In addition, a substantial minority of the simulated SPRs exhibit features that have not been reported in published experiments. Our simulations of SPRs using the model of binary R* shut-off appear to conform closely to experimental results for wild type (WT) mouse rods, and the required gain factor conforms to

  3. Characterization of pectinase activity for enology from yeasts occurring in Argentine Bonarda grape

    PubMed Central

    Merín, María Gabriela; Martín, María Carolina; Rantsiou, Kalliopi; Cocolin, Luca; de Ambrosini, Vilma Inés Morata

    2015-01-01

    Pectinolytic enzymes are greatly important in winemaking due to their ability to degrade pectic polymers from grape, contributing to enhance process efficiency and wine quality. This study aimed to analyze the occurrence of pectinolytic yeasts during spontaneous fermentation of Argentine Bonarda grape, to select yeasts that produce extracellular pectinases and to characterize their pectinolytic activity under wine-like conditions. Isolated yeasts were grouped using PCR-DGGE and identified by partial sequencing of 26S rRNA gene. Isolates comprised 7 genera, with Aureobasidium pullulans as the most predominant pectinolytic species, followed by Rhodotorula dairenensis and Cryptococcus saitoi. No pectinolytic activity was detected among ascomycetous yeasts isolated on grapes and during fermentation, suggesting a low occurrence of pectinolytic yeast species in wine fermentation ecosystem. This is the first study reporting R. dairenensis and Cr. saitoi species with pectinolytic activity. R. dairenensis GM-15 produced pectinases that proved to be highly active at grape pH, at 12 °C, and under ethanol and SO2 concentrations usually found in vinifications (pectinase activity around 1.1 U/mL). This strain also produced cellulase activity at 12 °C and pH 3.5, but did not produce β-glucosidase activity under these conditions. The strain showed encouraging enological properties for its potential use in low-temperature winemaking. PMID:26413065

  4. Characterization of pectinase activity for enology from yeasts occurring in Argentine Bonarda grape.

    PubMed

    Merín, María Gabriela; Martín, María Carolina; Rantsiou, Kalliopi; Cocolin, Luca; de Ambrosini, Vilma Inés Morata

    2015-01-01

    Pectinolytic enzymes are greatly important in winemaking due to their ability to degrade pectic polymers from grape, contributing to enhance process efficiency and wine quality. This study aimed to analyze the occurrence of pectinolytic yeasts during spontaneous fermentation of Argentine Bonarda grape, to select yeasts that produce extracellular pectinases and to characterize their pectinolytic activity under wine-like conditions. Isolated yeasts were grouped using PCR-DGGE and identified by partial sequencing of 26S rRNA gene. Isolates comprised 7 genera, with Aureobasidium pullulans as the most predominant pectinolytic species, followed by Rhodotorula dairenensis and Cryptococcus saitoi. No pectinolytic activity was detected among ascomycetous yeasts isolated on grapes and during fermentation, suggesting a low occurrence of pectinolytic yeast species in wine fermentation ecosystem. This is the first study reporting R. dairenensis and Cr. saitoi species with pectinolytic activity. R. dairenensis GM-15 produced pectinases that proved to be highly active at grape pH, at 12 °C, and under ethanol and SO2 concentrations usually found in vinifications (pectinase activity around 1.1 U/mL). This strain also produced cellulase activity at 12 °C and pH 3.5, but did not produce β-glucosidase activity under these conditions. The strain showed encouraging enological properties for its potential use in low-temperature winemaking.

  5. Activity measurements of technically enhanced naturally occurring radionuclides (TENORM) in phosphogypsum.

    PubMed

    Luca, A; Margineanu, R; Sahagia, M; Wätjen, A C

    2009-05-01

    Phosphogypsum is a by-product of the phosphoric acid based fertilizer industry; it can be used in agriculture and to make building materials. Phosphogypsum is radioactive due to the presence of technically enhanced naturally occurring radionuclides (TENORM) and its environmental impact is a major concern of the public authorities. The Radionuclide Metrology Laboratory from IFIN-HH participated at the IAEA-CU-2007-06-CCRI(II)-S5 Supplementary Comparison for the Determination of TENORM in phosphogypsum. The measurement procedures and the discussion of results and problems encountered are presented.

  6. Peak tornado activity is occurring earlier in the heart of "Tornado Alley"

    NASA Astrophysics Data System (ADS)

    Long, John A.; Stoy, Paul C.

    2014-09-01

    Tornado frequency may increase as the factors that contribute to severe convection are altered by a changing climate. Attributing changes in tornado frequency to observed global climate change is complicated because observational effort has increased over time, but studies of the seasonal distribution of tornado activity may avoid sampling biases. We demonstrate that peak tornado activity has shifted 7 days earlier in the year over the past six decades in the central and southern US Great Plains, the area with the highest global incidence of tornado activity. Results are largely unrelated to large-scale climate oscillations, and observed climate trends cannot fully account for observations, which suggest that changes to regional climate dynamics should be further investigated. Tornado preparedness efforts at individual to national levels should be cognizant of the trend toward earlier peak tornado activity across the heart of "Tornado Alley".

  7. Trigonelline, a naturally occurring constituent of green coffee beans behind the mutagenic activity of roasted coffee?

    PubMed

    Wu, X; Skog, K; Jägerstad, M

    1997-07-14

    Trigonelline and amino acids are natural components in green coffee beans. Model systems mimicking coffee roasting were used to produce heated samples of trigonelline, amino acids and glucose. Trigonelline and amino acids were heated separately or in combinations for 20 min at 250 degrees C. The results of bacteria mutation assays (Salmonella typhimurium strains TA 98, YG 1024 and YG 1029) showed that trigonelline, alone or in combination with most of the single amino acids and mixtures of amino acids, yielded potent mutagenic activity. Of the singly heated compounds, the highest mutagenic activity was found for trigonelline. The mutagenic activity detected with metabolic activation of the heated trigonelline samples indicated that the mutagenic compounds might be amines; however, higher mutagenic activity was found for trigonelline and its combinations without metabolic activation, which suggests that other types of mutagens (direct-acting) were predominant. High-performance liquid chromatographic analysis of some of the heated samples did not reveal the presence of any known mutagenic heterocyclic amine.

  8. Dicer-2-dependent activation of Culex Vago occurs via the TRAF-Rel2 signaling pathway.

    PubMed

    Paradkar, Prasad N; Duchemin, Jean-Bernard; Voysey, Rhonda; Walker, Peter J

    2014-04-01

    Despite their importance as vectors of human and livestock diseases, relatively little is known about innate antiviral immune pathways in mosquitoes and other insects. Previous work has shown that Culex Vago (CxVago), which is induced and secreted from West Nile virus (WNV)-infected mosquito cells, acts as a functional homolog of interferon, by activating Jak-STAT pathway and limiting virus replication in neighbouring cells. Here we describe the Dicer-2-dependent pathway leading to WNV-induced CxVago activation. Using a luciferase reporter assay, we show that a NF-κB-like binding site in CxVago promoter region is conserved in mosquito species and is responsible for induction of CxVago expression following WNV infection. Using dsRNA-based gene knockdown, we show that the NF-κB ortholog, Rel2, plays significant role in the signaling pathway that activates CxVago in mosquito cells in vitro and in vivo. Using similar approaches, we also show that TRAF, but not TRAF-3, is involved in activation of Rel2 after viral infection. Overall the study shows that a conserved signaling pathway, which is similar to mammalian interferon activation pathway, is responsible for the induction and antiviral activity of CxVago.

  9. Active tactile sampling by an insect in a step-climbing paradigm

    PubMed Central

    Krause, André F.; Dürr, Volker

    2012-01-01

    Many insects actively explore their near-range environment with their antennae. Stick insects (Carausius morosus) rhythmically move their antennae during walking and respond to antennal touch by repetitive tactile sampling of the object. Despite its relevance for spatial orientation, neither the spatial sampling patterns nor the kinematics of antennation behavior in insects are understood. Here we investigate unrestrained bilateral sampling movements during climbing of steps. The main objectives are: (1) How does the antennal contact pattern relate to particular object features? (2) How are the antennal joints coordinated during bilateral tactile sampling? We conducted motion capture experiments on freely climbing insects, using steps of different height. Tactile sampling was analyzed at the level of antennal joint angles. Moreover, we analyzed contact patterns on the surfaces of both the obstacle and the antenna itself. Before the first contact, both antennae move in a broad, mostly elliptical exploratory pattern. After touching the obstacle, the pattern switches to a narrower and faster movement, caused by higher cycle frequencies and lower cycle amplitudes in all joints. Contact events were divided into wall- and edge-contacts. Wall contacts occurred mostly with the distal third of the flagellum, which is flexible, whereas edge contacts often occurred proximally, where the flagellum is stiff. The movement of both antennae was found to be coordinated, exhibiting bilateral coupling of functionally analogous joints [e.g., left head-scape (HS) joint with right scape-pedicel (SP) joint] throughout tactile sampling. In comparison, bilateral coupling between homologous joints (e.g., both HS joints) was significantly weaker. Moreover, inter-joint coupling was significantly weaker during the contact episode than before. In summary, stick insects show contact-induced changes in frequency, amplitude and inter-joint coordination during tactile sampling of climbed obstacles

  10. Enzymatic digestion of alkaline-sulfite pretreated sugar cane bagasse and its correlation with the chemical and structural changes occurring during the pretreatment step.

    PubMed

    Mendes, Fernanda M; Laurito, Debora F; Bazzeggio, Mariana; Ferraz, André; Milagres, Adriane M F

    2013-01-01

    Sugar cane bagasse is recalcitrant to enzymatic digestion, which hinders the efficient conversion of its polysaccharides into fermentable sugars. Alkaline-sulfite pretreatment was used to overcome the sugar cane bagasse recalcitrance. Chemical and structural changes that occurred during the pretreatment were correlated with the efficiency of the enzymatic digestion of the polysaccharides. The first 30 min of pretreatment, which removed approximately half of the initial lignin and 30% of hemicellulose seemed responsible for a significant enhancement of the cellulose conversion level, which reached 64%. After the first 30 min of pretreatment, delignification increased slightly, and hemicellulose removal was not enhanced; however, acid groups continued to be introduced into the residual lignin. Water retention values were 145% to the untreated bagasse and 210% to the bagasse pretreated for 120 min and fiber widths increased from 10.4 to 30 μm, respectively. These changes were responsible for an additional increase in the efficiency of enzymatic hydrolysis of the cellulose, which reached 92% with the 120 min pretreated sample.

  11. Understanding walking activity in multiple sclerosis: step count, walking intensity and uninterrupted walking activity duration related to degree of disability.

    PubMed

    Neven, An; Vanderstraeten, Annelien; Janssens, Davy; Wets, Geert; Feys, Peter

    2016-09-01

    In multiple sclerosis (MS), physical activity (PA) is most commonly measured as number of steps, while also walking intensity and walking activity duration are keys for a healthy lifestyle. The aim of this study was to investigate (1) the number of steps persons with MS (PwMS) take; (2) the number of steps they take at low and moderate intensity; and (3) their walking activity duration for 2, 3, 6, 10, 12 and 14 uninterrupted minutes; all related to the degree of disability. 64 PwMS participated, distinguished in a mild (n = 31) and moderate MS subgroup (n = 34) based on their ambulatory dysfunction (Disease Steps). Standardized clinical tests were performed, and step data from the StepWatch Activity Monitor were collected for seven consecutive days. The results showed that (1) step count in PwMS was lower than PA recommendations, and is negatively influenced by a higher disability degree. (2) No walking was registered during 77 % of the day. PwMS are making steps for 22 % at low and only 1 % at moderate intensity. (3) Both MS subgroups rarely walk for more than six uninterrupted minutes, especially not at moderate intensity. PwMS need to be encouraged to make steps at moderate intensity, and to make steps for longer periods of time (minimal ten uninterrupted minutes).

  12. Activation of Müller cells occurs during retinal degeneration in RCS rats.

    PubMed

    Zhao, Tong Tao; Tian, Chun Yu; Yin, Zheng Qin

    2010-01-01

    Müller cells can be activated and included in different functions under many kinds of pathological conditions, however, the status of Müller cells in retinitis pigmentosa are still unknown. Using immunohistochemisty, Western blots and co-culture, we found that Müller cells RCS rats, a classic model of RP, could be activated during the progression of retinal degeneration. After being activated at early stage, Müller cells began to proliferate and hypertrophy, while at later stages, they formed a local 'glial seal' in the subretinal space. As markers of Müller cells activation, the expression of GFAP and ERK increased significantly with progression of retinal degeneration. Co-cultures of normal rat Müller cells and mixed RCS rat retinal cells show that Müller cells significantly increase GFAP and ERK in response to diffusable factors from the degenerting retina, which implies that Müller cells activation is a secondary response to retinal degeneration.

  13. Evidence that endoplasmic reticulum (ER) stress and caspase-4 activation occur in human neutrophils.

    PubMed

    Binet, François; Chiasson, Sonia; Girard, Denis

    2010-01-01

    Apoptosis can result from activation of three major pathways: the extrinsic, the intrinsic, and the most recently identified endoplasmic reticulum (ER) stress-mediated pathway. While the two former pathways are known to be operational in human polymorphonuclear neutrophils (PMNs), the existence of the ER stress-mediated pathway, generally involving caspase-4, has never been reported in these cells. Recently, we have documented that arsenic trioxide (ATO) induced apoptosis in human PMNs by a mechanism that needs to be further investigated. In this study, using immunofluorescence and electron microscopy, we present evidence of ER alterations in PMNs activated by the ER stress inducer arsenic trioxide (ATO). Several key players of the unfolded protein response, including GRP78, GADD153, ATF6, XBP1 and eIF2alpha are expressed and activated in PMNs treated with ATO or other ER stress inducers. Although caspase-4 is expressed and activated in neutrophils, treatment with a caspase-4 inhibitor did not attenuate the pro-apoptotic effect of ATO at a concentration that reverses caspase-4 processing and activation. Our results demonstrate for the first time that the ER stress-mediated apoptotic pathway operates in human neutrophils.

  14. Naturally occurring active N-domain of human angiotensin I-converting enzyme.

    PubMed Central

    Deddish, P A; Wang, J; Michel, B; Morris, P W; Davidson, N O; Skidgel, R A; Erdös, E G

    1994-01-01

    Angiotensin I-converting enzyme (ACE, kininase II) is a single-chain protein containing two active site domains (named N- and C-domains according to position in the chain). ACE is bound to plasma membranes by its C-terminal hydrophobic transmembrane anchor. Ileal fluid, rich in ACE activity, obtained from patients after surgical colectomy was used as the source. Column chromatography, including modified affinity chromatography on lisinopril-Sepharose, yielded homogeneous ACE after only a 45-fold purification. N-terminal sequencing of ileal ACE and partial sequencing of CNBr fragments revealed the presence of an intact N terminus but only a single N-domain active site, ending between residues 443 and 559. Thus, ileal-fluid ACE is a unique enzyme differing from the widely distributed two-domain somatic enzyme or the single C-domain testicular (germinal) ACE. The molecular mass of ileal ACE is 108 kDa and when deglycosylated, the molecular mass is 68 kDa, indicating extensive glycosylation (37% by weight). In agreement with the results reported with recombinant variants of ACE, the ileal enzyme is less Cl(-)-dependent than somatic ACE; release of the C-terminal dipeptide from a peptide substrate was optimal in only 10 mM Cl-. In addition to hydrolyzing at the C-terminal end of peptides, ileal ACE efficiently cleaved the protected N-terminal tripeptide from the luteinizing hormone-releasing hormone and its congener 6-31 times faster, depending on the Cl- concentration, than the C-domain in recombinant testicular ACE. Thus we have isolated an active human ACE consisting of a single N-domain. We suggest that there is a bridge section of about 100 amino acids between the active N- and C-domains of somatic ACE where it may be proteolytically cleaved to liberate the active N-domain. These findings have potential relevance and importance in the therapeutic application of ACE inhibitors. PMID:8052664

  15. Validity of the Fitbit activity tracker for measuring steps in community-dwelling older adults

    PubMed Central

    Paul, Serene S; Tiedemann, Anne; Hassett, Leanne M; Ramsay, Elisabeth; Kirkham, Catherine; Chagpar, Sakina; Sherrington, Catherine

    2015-01-01

    Background Commercially available activity monitors, such as the Fitbit, may encourage physical activity. However, the accuracy of the Fitbit in older adults remains unknown. This study aimed to determine (1) the criterion validity of Fitbit step counts compared to visual count and ActiGraph accelerometer step counts and (2) the accuracy of ActiGraph step counts compared to visual count in community-dwelling older people. Methods Thirty-two community-dwelling adults aged over 60 wore Fitbit and ActiGraph devices simultaneously during a 2 min walk test (2MWT) and then during waking hours over a 7-day period. A physiotherapist counted the steps taken during the 2MWT. Results There was excellent agreement between Fitbit and visually counted steps (intraclass correlation coefficient (ICC2,1)=0.88, 95% CI 0.76 to 0.94) from the 2MWT, and good agreement between Fitbit and ActiGraph (ICC2,1=0.66, 95% CI 0.41 to 0.82), and between ActiGraph and visually counted steps (ICC2,1=0.60, 95% CI 0.33 to 0.79). There was excellent agreement between the Fitbit and ActiGraph in average steps/day over 7 days (ICC2,1=0.94, 95% CI 0.88 to 0.97). Percentage agreement was closest for Fitbit steps compared to visual count (mean 0%, SD 4%) and least for Fitbit average steps/day compared to the ActiGraph (mean 13%, SD 25%). Conclusions The Fitbit accurately tracked steps during the 2MWT, but the ActiGraph appeared to underestimate steps. There was strong agreement between Fitbit and ActiGraph counted steps. The Fitbit tracker is sufficiently accurate to be used among community-dwelling older adults to monitor and give feedback on step counts. PMID:27900119

  16. Activation of Endothelial Nitric Oxide (eNOS) Occurs through Different Membrane Domains in Endothelial Cells

    PubMed Central

    Tran, Jason; Magenau, Astrid; Rodriguez, Macarena; Rentero, Carles; Royo, Teresa; Enrich, Carlos; Thomas, Shane R.; Grewal, Thomas; Gaus, Katharina

    2016-01-01

    Endothelial cells respond to a large range of stimuli including circulating lipoproteins, growth factors and changes in haemodynamic mechanical forces to regulate the activity of endothelial nitric oxide synthase (eNOS) and maintain blood pressure. While many signalling pathways have been mapped, the identities of membrane domains through which these signals are transmitted are less well characterized. Here, we manipulated bovine aortic endothelial cells (BAEC) with cholesterol and the oxysterol 7-ketocholesterol (7KC). Using a range of microscopy techniques including confocal, 2-photon, super-resolution and electron microscopy, we found that sterol enrichment had differential effects on eNOS and caveolin-1 (Cav1) colocalisation, membrane order of the plasma membrane, caveolae numbers and Cav1 clustering. We found a correlation between cholesterol-induced condensation of the plasma membrane and enhanced high density lipoprotein (HDL)-induced eNOS activity and phosphorylation suggesting that cholesterol domains, but not individual caveolae, mediate HDL stimulation of eNOS. Vascular endothelial growth factor (VEGF)-induced and shear stress-induced eNOS activity was relatively independent of membrane order and may be predominantly controlled by the number of caveolae on the cell surface. Taken together, our data suggest that signals that activate and phosphorylate eNOS are transmitted through distinct membrane domains in endothelial cells. PMID:26977592

  17. Activation of Endothelial Nitric Oxide (eNOS) Occurs through Different Membrane Domains in Endothelial Cells.

    PubMed

    Tran, Jason; Magenau, Astrid; Rodriguez, Macarena; Rentero, Carles; Royo, Teresa; Enrich, Carlos; Thomas, Shane R; Grewal, Thomas; Gaus, Katharina

    2016-01-01

    Endothelial cells respond to a large range of stimuli including circulating lipoproteins, growth factors and changes in haemodynamic mechanical forces to regulate the activity of endothelial nitric oxide synthase (eNOS) and maintain blood pressure. While many signalling pathways have been mapped, the identities of membrane domains through which these signals are transmitted are less well characterized. Here, we manipulated bovine aortic endothelial cells (BAEC) with cholesterol and the oxysterol 7-ketocholesterol (7KC). Using a range of microscopy techniques including confocal, 2-photon, super-resolution and electron microscopy, we found that sterol enrichment had differential effects on eNOS and caveolin-1 (Cav1) colocalisation, membrane order of the plasma membrane, caveolae numbers and Cav1 clustering. We found a correlation between cholesterol-induced condensation of the plasma membrane and enhanced high density lipoprotein (HDL)-induced eNOS activity and phosphorylation suggesting that cholesterol domains, but not individual caveolae, mediate HDL stimulation of eNOS. Vascular endothelial growth factor (VEGF)-induced and shear stress-induced eNOS activity was relatively independent of membrane order and may be predominantly controlled by the number of caveolae on the cell surface. Taken together, our data suggest that signals that activate and phosphorylate eNOS are transmitted through distinct membrane domains in endothelial cells.

  18. Parental Influence on the Physical Activity of Chinese Children: Do Gender Differences Occur?

    ERIC Educational Resources Information Center

    Lijuan, Wang; Jiancui, Sun; Suzhe, Zhao

    2017-01-01

    This study aimed to examine the association among parental moderate-to-vigorous physical activity (MVPA), parental support, and the MVPA of children by gender. Participants comprised of 172 boys and 151 girls aged seven to 11 years old from three primary schools in Shanghai. Their parents were also included as research respondents. Accelerometers…

  19. Induction of Apoptosis in Human Leukemia Cells by Grape Seed Extract Occurs via Activation of JNK

    PubMed Central

    Gao, Ning; Budhraja, Amit; Cheng, Senping; Yao, Hua; Zhang, Zhuo; Shi, Xianglin

    2009-01-01

    Purpose To characterize the functional role of JNK and other apoptotic pathways in grape seed extract (GSE)-induced apoptosis in human leukemia cells by using pharmacologic and genetic approaches. Experimental Design Jurkat cells were treated with various concentrations of GSE for 12 h and 24 h, or with 50 μg/ml of GSE for various time intervals, after which apoptosis, caspase activation, and cell signaling pathways were evaluated. Parallel studies were performed in U937 and HL-60 human leukemia cells. Results Exposure of Jurkat cells to GSE resulted in dose- and time-dependent increase in apoptosis and caspase activation, events associated with the pronounced increase in Cip1/p21 protein level. Furthermore, treatment of Jurkat cells with GSE resulted in marked increase in levels of phospho-JNK. Conversely, interruption of the JNK pathway by pharmacological inhibitor (e.g. SP600125) or genetic (e.g. siRNA) approaches displayed significant protection against GSE mediated lethality in Jurkat cells. Conclusions The result of the present study showed that GSE induces apoptosis in Jurkat cells through a process that involves sustained JNK activation and Cip1/p21 up-regulation, culminating in caspase activation. PMID:19118041

  20. Using naturally occurring polysaccharides to align molecules with nonlinear optical activity

    NASA Technical Reports Server (NTRS)

    Prasthofer, Thomas

    1996-01-01

    The Biophysics and Advanced Materials Branch of the Microgravity Science and Applications Division at Marshall Space Flight Center has been investigating polymers with the potential for nonlinear optical (NLO) applications for a number of years. Some of the potential applications for NLO materials include optical communications, computing, and switching. To this point the branch's research has involved polydiacetylenes, phthalocyanins, and other synthetic polymers which have inherent NLO properties. The aim of the present research is to investigate the possibility of using naturally occurring polymers such as polysaccharides or proteins to trap and align small organic molecules with useful NLO properties. Ordering molecules with NLO properties enhances 3rd order nonlinear effects and is required for 2nd order nonlinear effects. Potential advantages of such a system are the flexibility to use different small molecules with varying chemical and optical properties, the stability and cost of the polymers, and the ability to form thin, optically transparent films. Since the quality of any polymer films depends on optimizing ordering and minimizing defects, this work is particularly well suited for microgravity experiments. Polysaccharide and protein polymers form microscopic crystallites which must align to form ordered arrays. The ordered association of crystallites is disrupted by gravity effects and NASA research on protein crystal growth has demonstrated that low gravity conditions can improve crystal quality.

  1. Step-rate thresholds for physical activity intensity in persons with multiple sclerosis.

    PubMed

    Agiovlasitis, Stamatis; Motl, Robert W

    2014-01-01

    This study examined whether the relationship between metabolic equivalent units (METs) and step-rate is altered in persons with multiple sclerosis (MS) and developed step-rate thresholds for activity intensity for these persons. Participants were 24 persons with MS (20 women; age = 44 ± 12) and 24 healthy persons without MS (20 women; age = 41 ± 11). The MS group was divided using the 12-item MS Walking Scale (MSWS-12) into two walking impairment subgroups: (a) minimal (n = 13, MSWS-12 ≤ 12.5) and (b) mild-moderate (n = 11, MSWS-12 > 12.5). METs were measured with spirometry and step-rate with hand-tally. Step-rate, height, group, the step-rate by group interaction, and the square of step-rate significantly predicted METs. At a given height, the step-rate thresholds at 3 and 6 METs were lower for persons with minimal impairment than persons without MS and even lower for persons with mild-moderate impairment. The relationship between METs and step-rate is altered in persons with MS, lowering their step-rate thresholds for activity intensity, especially for persons with MS who have higher levels of walking impairment.

  2. Antiviral Activity of a Small Molecule Deubiquitinase Inhibitor Occurs via Induction of the Unfolded Protein Response

    PubMed Central

    Perry, Jeffrey W.; Ahmed, Mohammad; Chang, Kyeong-Ok; Donato, Nicholas J.; Showalter, Hollis D.; Wobus, Christiane E.

    2012-01-01

    Ubiquitin (Ub) is a vital regulatory component in various cellular processes, including cellular responses to viral infection. As obligate intracellular pathogens, viruses have the capacity to manipulate the ubiquitin (Ub) cycle to their advantage by encoding Ub-modifying proteins including deubiquitinases (DUBs). However, how cellular DUBs modulate specific viral infections, such as norovirus, is poorly understood. To examine the role of DUBs during norovirus infection, we used WP1130, a small molecule inhibitor of a subset of cellular DUBs. Replication of murine norovirus in murine macrophages and the human norovirus Norwalk virus in a replicon system were significantly inhibited by WP1130. Chemical proteomics identified the cellular DUB USP14 as a target of WP1130 in murine macrophages, and pharmacologic inhibition or siRNA-mediated knockdown of USP14 inhibited murine norovirus infection. USP14 is a proteasome-associated DUB that also binds to inositol-requiring enzyme 1 (IRE1), a critical mediator of the unfolded protein response (UPR). WP1130 treatment of murine macrophages did not alter proteasome activity but activated the X-box binding protein-1 (XBP-1) through an IRE1-dependent mechanism. In addition, WP1130 treatment or induction of the UPR also reduced infection of other RNA viruses including encephalomyocarditis virus, Sindbis virus, and La Crosse virus but not vesicular stomatitis virus. Pharmacologic inhibition of the IRE1 endonuclease activity partially rescued the antiviral effect of WP1130. Taken together, our studies support a model whereby induction of the UPR through cellular DUB inhibition blocks specific viral infections, and suggest that cellular DUBs and the UPR represent novel targets for future development of broad spectrum antiviral therapies. PMID:22792064

  3. Antiviral activity of a small molecule deubiquitinase inhibitor occurs via induction of the unfolded protein response.

    PubMed

    Perry, Jeffrey W; Ahmed, Mohammad; Chang, Kyeong-Ok; Donato, Nicholas J; Showalter, Hollis D; Wobus, Christiane E

    2012-01-01

    Ubiquitin (Ub) is a vital regulatory component in various cellular processes, including cellular responses to viral infection. As obligate intracellular pathogens, viruses have the capacity to manipulate the ubiquitin (Ub) cycle to their advantage by encoding Ub-modifying proteins including deubiquitinases (DUBs). However, how cellular DUBs modulate specific viral infections, such as norovirus, is poorly understood. To examine the role of DUBs during norovirus infection, we used WP1130, a small molecule inhibitor of a subset of cellular DUBs. Replication of murine norovirus in murine macrophages and the human norovirus Norwalk virus in a replicon system were significantly inhibited by WP1130. Chemical proteomics identified the cellular DUB USP14 as a target of WP1130 in murine macrophages, and pharmacologic inhibition or siRNA-mediated knockdown of USP14 inhibited murine norovirus infection. USP14 is a proteasome-associated DUB that also binds to inositol-requiring enzyme 1 (IRE1), a critical mediator of the unfolded protein response (UPR). WP1130 treatment of murine macrophages did not alter proteasome activity but activated the X-box binding protein-1 (XBP-1) through an IRE1-dependent mechanism. In addition, WP1130 treatment or induction of the UPR also reduced infection of other RNA viruses including encephalomyocarditis virus, Sindbis virus, and La Crosse virus but not vesicular stomatitis virus. Pharmacologic inhibition of the IRE1 endonuclease activity partially rescued the antiviral effect of WP1130. Taken together, our studies support a model whereby induction of the UPR through cellular DUB inhibition blocks specific viral infections, and suggest that cellular DUBs and the UPR represent novel targets for future development of broad spectrum antiviral therapies.

  4. Nitro Derivatives of Naturally Occurring β-Asarone and Their Anticancer Activity

    PubMed Central

    Shenvi, Suvarna; Diwakar, Latha; Reddy, G. Chandrasekara

    2014-01-01

    β-Asarone (2, 4, 5-trimethoxy-(Z)-1-propenylbenzene) was obtained from Acorus calamus. Nitration of β-asarone with AgNO2/I2 in ether yielded 1-(2, 4, 5-trimethoxy phenyl)-2-nitropropene (1) but with NaNO2/I2 in ethylene glycol obtained 1-(2, 4, 5-trimethoxy phenyl)-1-nitropropene (2). Compound 2 was prepared for the first time and characterized using IR, 1H-NMR, 13C-NMR, and GC-MS spectra and it was converted into 1-(2, 4, 5-trimethoxy) phenyl-1-propanone (3) using modified Nef reaction. Based on 1D NOESY experiments, compounds 1 and 2 have been assigned E configuration. Compounds 1 and 2 were subjected to cytotoxic activity using five human cancer cell lines, namely, MCF-7, SW-982, HeLa, PC-3, and IMR-32 by MTT assay. Except in breast cancer line (MCF-7) compound 2 exhibited five- to tenfold increase in activity compared to β-asarone and twofold increase over compound 1. PMID:25383224

  5. Immunomodulatory activity of Sulforaphane, a naturally occurring isothiocyanate from broccoli (Brassica oleracea).

    PubMed

    Thejass, P; Kuttan, G

    2007-08-01

    The effect of Sulforaphane on the immune system was studied using BALB/c mice. Intraperitoneal administration of five doses of Sulforaphane (500 microg/dose/animal/day) was found to enhance the total WBC count (12,950 cells/mm3) on 9th day. Bone marrow cellularity (23 x 10(6) cells/femur) and number of alpha-esterase positive cells (1346.66/4000 cells) were also increased by the administration of Sulforaphane. Treatment with Sulforaphane along with the antigen, sheep red blood cells (SRBC), produced an enhancement in the circulating antibody titre and the number of plaque forming cells (PFC) in the spleen. Maximum number of PFC (315.83 PFC/10(6) spleen cells) was obtained on the 6th day. Administration of Sulforaphane also showed an enhancement in the phagocytic activity of peritoneal macrophages. Moreover administration of Sulforaphane significantly reduced the elevated level of TNF-alpha production by LPS stimulated macrophages. These results indicate the immunomodulatory activity of Sulforaphane.

  6. Antitumor and antimicrobial activities of some hetero aromatic benzofurans derived from naturally occurring visnagin.

    PubMed

    El-Nakkady, Sally S; Roaiah, Hanaa F; El-Serwy, Weam S; Soliman, Abdel Mohsen; El-Moez, Sherein I Abd; Abdel-Rahman, Adel A H

    2012-01-01

    Bromination of visnaginone (1) yielded the dibromo derivative (2), which upon methylation with methyl iodide gave 1-(2,7-dibromo-4,6-dimethoxybenzofuran-5-yl) ethanone (3). Compound (3) reacted with dimethylformamide dimethylacetal to give (4). The reaction of (3) with aromatic aldehydes namely (vanillin, benzaldehyde and 3-anisaldehyde) in ammonium acetate, malononitrile and/or butyric cyanoanhydride gave the 2-amino substituted nicotinonitriles (5a-c) and the 2-hydroxyl substituted nicotinonitriles (7a-c), respectively, while in piperidine gave (E)-1-(2,7-dibromo-4,6-dimethoxybenzofuran-5-yl)-3-(substituted)prop-2-en-l-one (11a-c). (5a) was hydrolyzed with sulfuric acid on cold to give the nicotinic acid derivative (6a). When compound (3) reacted with hydrazines and aromatic amines, it gave the Schiff bases (8a,b) and (10a,b), respectively. (8b) reacted with thioglycolic acid to give the thiazolidin-4-one (9b). When (11a-c) reacted with thiourea, it gave the pyrimidine derivatives (12a-c). (11a,b) also reacted with butyric cyanoanhydride and hydroxylamine hydrochloride to give (13a,b) and (15a,b), respectively. When the carboxylate (13a) was treated with 2,4-dinitroaniline, it gave the carboxamide (14a). Compounds (11b,c) reacted with hydrazine derivatives (hydrazine hydrate and phenylhydrazine) yielding the substituted pyrazole derivatives (16b,c) and (17b,c), respectively. All the structures of the synthesized compounds were elucidated by elemental analyses and spectral data. The newly synthesized benzofuran compounds showed a strong to moderate cytotoxicity against liver HEPG2 cancer cell line compared to 5-fluorouracil and doxorubicin (the anticancer agents). Compounds (2, 6a, 13a, 14a, 16c and 17b) were the most active compounds in descending order. The synthesized compounds were also tested for their antimicrobial activity. Compound (10b) showed the highest activity against all the tested strains followed by 6, 10a, 5a, 8b and 7a in descending order.

  7. Antimutagenic activities of naturally occurring polyamines in Chinese hamster ovary cell in vitro

    SciTech Connect

    Cozzi, R.; Perticone, P.; Bona, R.; Polani, S. )

    1991-01-01

    Spermine and spermidine, ubiquitous polyamines present in bacteria and animal cells, are also involved in cell growth. Since they interact with the double helix, they can stabilize the DNA molecule. Recent evidence of the antimutagenic and anticarcinogenic capacity of spermine has focused attention on the he mechanism(s) by which such agents can protect cells from induced damages. In the present paper the authors show the ability of spermine and spermidine to decrease the level of sister chromatid exchanges induced in Chinese hamster ovary cells cultivated in vitro, by treating them with Psoralen + UVA irradiation (able to induce mainly monoadducts and DNA cross-links). Two different mechanisms of polyamine action can be invoked to explain the preservative activity of this class of agents.

  8. Measuring steps with the Fitbit activity tracker: an inter-device reliability study.

    PubMed

    Dontje, Manon L; de Groot, Martijn; Lengton, Remko R; van der Schans, Cees P; Krijnen, Wim P

    2015-01-01

    Activity trackers like Fitbit are used for self-tracking of physical activity by an increasing number of individuals. Comparing physical activity scores with peers can contribute to the desired behavioural change. However, for meaningful social comparison a high inter-device reliability is paramount. This study aimed to determine the inter-device reliability of Fitbit activity trackers in measuring steps. Ten activity trackers (Fitbit Ultra) were worn by a single person (male, 46 years) during eight consecutive days. Inter-device reliability was assessed on three different levels of aggregation (minutes, hours, days) with various methods, including intra-class correlation coefficient (ICC), Bland-Altman plots, limits of agreement (LOA) and Mixed Model Analysis. Results showed that the inter-device reliability of the Fitbit in measuring steps is good at all levels of aggregation (minutes, hours, days), but especially when steps were measured per day. This implies that individuals can reliably compare their daily physical activity scores with peers.

  9. Naturally-occurring changes in social-cognitive factors modify change in physical activity during early adolescence

    PubMed Central

    Dowda, Marsha; McIver, Kerry L.; Saunders, Ruth P.; Pate, Russell R.

    2017-01-01

    Purpose To determine whether naturally-occurring changes in children’s motives and beliefs are associated with the steep decline in physical activity observed from childhood to early adolescence. Methods Latent growth modeling was applied in longitudinal tests of social-cognitive influences, and their interactions, on physical activity in a large cohort of boys and girls evaluated annually between 5th and 7th grades. Results Measurement equivalence of motives and beliefs was confirmed between boys and girls. After adjustment for gender and maturity differences, physical activity declined less in children who reported the least decreases in self-efficacy for overcoming barriers to activity and perceived parental support. Physical activity also declined less in students who persistently felt they had more parental and friend support for activity compared to those who reported the largest decrease in support from friends. After further adjustment for race, the decline in physical activity was less in those who had the largest decrease in perceived barriers and maintained a favorable perception of their neighborhood environment. Changes in enjoyment and social motives were unrelated to change in physical activity. Conclusion Using an objective measure of physical activity, we confirm that naturally-occurring changes in children’s beliefs about barriers to physical activity and their ability to overcome them, as well as perceptions of their neighborhood environment and social support, are concurrent with age-related declines in children’s physical activity. The longitudinal findings confirm these putative social-cognitive mediators as plausible, interacting targets of interventions designed to mitigate the marked decline in physical activity that occurs during the transition between elementary and middle schools. PMID:28187192

  10. Deformation of the Calabrian Arc subduction complex and its relation to STEP activity at depth.

    NASA Astrophysics Data System (ADS)

    Polonia, Alina; Wortel, Rinus; Nijholt, Nicolai; Govers, Rob; Torelli, Luigi

    2015-04-01

    Propagating tear faults at the edge of subducted slabs ("Subduction transform edge propagator", STEP) are an intrinsic part of lithospheric plate dynamics. The surface expression of a STEP is generally not known yet, and is expected to vary significantly from one region to the other. We choose the Sicily -Calabria-Ionian Sea region, of which the lithosphere-upper mantle structure has the characteristics of a STEP zone, as a study area. The area has a very prominent accretionary wedge, the formation and subsequent deformation of which presumably were affected by the STEP activity at depth. In this contribution, we use seismic data on the near surface structure and deformation in combination with numerical model results to investigate the relation between deep STEP activity and near surface expression. Prominent features in the surface tectonics are the Malta escarpment (with predominantly normal faulting), the newly identified Ionian Fault and Alfeo-Etna fault system, and a distinct longitudinal division of the wedge into a western and an eastern lobe (Polonia et al., Tectonics, 2011). The two lobes are characterized by different structural style, deformation rates and basal detachment depths. Numerical model results indicate that the regional lithospheric structure, such as the orientation of the eastern passive (albeit subsequently activated) margin of Sicily relative to the Calabrian subduction zone, has a profound effect on possible fault activity along the Malta escarpment. Fault activity along the above primary fault structures may have varied in time, implying the possibility of intermittent activity. Interpreting seismicity in the context of a possible STEP, and the accompanying deformation zone at or near the surface, is not (yet) straightforward. Although direct evidence for recognizing all aspects of STEP activity is - as usual - lacking, a comparison with two well-known STEP regions, the northern part of the Tonga subduction zone and southern part of the

  11. Lipotoxicity in steatohepatitis occurs despite an increase in tricarboxylic acid cycle activity

    PubMed Central

    Patterson, Rainey E.; Kalavalapalli, Srilaxmi; Williams, Caroline M.; Nautiyal, Manisha; Mathew, Justin T.; Martinez, Janie; Reinhard, Mary K.; McDougall, Danielle J.; Rocca, James R.; Yost, Richard A.; Cusi, Kenneth; Garrett, Timothy J.

    2016-01-01

    The hepatic tricarboxylic acid (TCA) cycle is central to integrating macronutrient metabolism and is closely coupled to cellular respiration, free radical generation, and inflammation. Oxidative flux through the TCA cycle is induced during hepatic insulin resistance, in mice and humans with simple steatosis, reflecting early compensatory remodeling of mitochondrial energetics. We hypothesized that progressive severity of hepatic insulin resistance and the onset of nonalcoholic steatohepatitis (NASH) would impair oxidative flux through the hepatic TCA cycle. Mice (C57/BL6) were fed a high-trans-fat high-fructose diet (TFD) for 8 wk to induce simple steatosis and NASH by 24 wk. In vivo fasting hepatic mitochondrial fluxes were determined by 13C-nuclear magnetic resonance (NMR)-based isotopomer analysis. Hepatic metabolic intermediates were quantified using mass spectrometry-based targeted metabolomics. Hepatic triglyceride accumulation and insulin resistance preceded alterations in mitochondrial metabolism, since TCA cycle fluxes remained normal during simple steatosis. However, mice with NASH had a twofold induction (P < 0.05) of mitochondrial fluxes (μmol/min) through the TCA cycle (2.6 ± 0.5 vs. 5.4 ± 0.6), anaplerosis (9.1 ± 1.2 vs. 16.9 ± 2.2), and pyruvate cycling (4.9 ± 1.0 vs. 11.1 ± 1.9) compared with their age-matched controls. Induction of the TCA cycle activity during NASH was concurrent with blunted ketogenesis and accumulation of hepatic diacylglycerols (DAGs), ceramides (Cer), and long-chain acylcarnitines, suggesting inefficient oxidation and disposal of excess free fatty acids (FFA). Sustained induction of mitochondrial TCA cycle failed to prevent accretion of “lipotoxic” metabolites in the liver and could hasten inflammation and the metabolic transition to NASH. PMID:26814015

  12. Cis-Golgi cisternal assembly and biosynthetic activation occur sequentially in plants and algae.

    PubMed

    Donohoe, Bryon S; Kang, Byung-Ho; Gerl, Mathias J; Gergely, Zachary R; McMichael, Colleen M; Bednarek, Sebastian Y; Staehelin, L Andrew

    2013-05-01

    The cisternal progression/maturation model of Golgi trafficking predicts that cis-Golgi cisternae are formed de novo on the cis-side of the Golgi. Here we describe structural and functional intermediates of the cis cisterna assembly process in high-pressure frozen algae (Scherffelia dubia, Chlamydomonas reinhardtii) and plants (Arabidopsis thaliana, Dionaea muscipula; Venus flytrap) as determined by electron microscopy, electron tomography and immuno-electron microscopy techniques. Our findings are as follows: (i) The cis-most (C1) Golgi cisternae are generated de novo from cisterna initiators produced by the fusion of 3-5 COPII vesicles in contact with a C2 cis cisterna. (ii) COPII vesicles fuel the growth of the initiators, which then merge into a coherent C1 cisterna. (iii) When a C1 cisterna nucleates its first cisterna initiator it becomes a C2 cisterna. (iv) C2-Cn cis cisternae grow through COPII vesicle fusion. (v) ER-resident proteins are recycled from cis cisternae to the ER via COPIa-type vesicles. (vi) In S. dubia the C2 cisternae are capable of mediating the self-assembly of scale protein complexes. (vii) In plants, ∼90% of native α-mannosidase I localizes to medial Golgi cisternae. (viii) Biochemical activation of cis cisternae appears to coincide with their conversion to medial cisternae via recycling of medial cisterna enzymes. We propose how the different cis cisterna assembly intermediates of plants and algae may actually be related to those present in the ERGIC and in the pre-cis Golgi cisterna layer in mammalian cells.

  13. Cis-Golgi cisternal assembly and biosynthetic activation occur sequentially in plants and algae

    PubMed Central

    Donohoe, Bryon S.; Kang, Byung-Ho; Gerl, Mathias J.; Gergely, Zachary R.; McMichael, Colleen M.; Bednarek, Sebastian Y.; Staehelin, L. Andrew

    2013-01-01

    The cisternal progression/maturation model of Golgi trafficking predicts that cis-Golgi cisternae are formed de novo on the cis-side of the Golgi. Here we describe structural and functional intermediates of the cis cisterna assembly process in high-pressure frozen algae (Scherffelia dubia, Chlamydomonas reinhardtii) and plants (Arabidopsis thaliana, Dionaea muscipula; Venus Flytrap) as determined by electron microscopy, electron tomography and immuno-electron microscopy techniques. Our findings are as follows: (1) The cis-most (C1) Golgi cisternae are generated de novo from cisterna initiators produced by the fusion of 3–5 COPII vesicles in contact with a C2 cis cisterna. (2) COPII vesicles fuel the growth of the initiators, which then merge into a coherent C1 cisterna. (3) When a C1 cisterna nucleates its first cisterna initiator it becomes a C2 cisterna. (4) C2-Cn cis cisternae grow through COPII vesicle fusion. (5) ER-resident proteins are recycled from cis cisternae to the ER via COPIa-type vesicles. (6) In S. dubia the C2 cisternae are capable of mediating the self-assembly of scale protein complexes. (7) In plants, ~90% of native α-mannosidase I localizes to medial Golgi cisternae. (8) Biochemical activation of cis cisternae appears to coincide with their conversion to medial cisternae via recycling of medial cisterna enzymes. We propose how the different cis cisterna assembly intermediates of plants and algae may actually be related to those present in the ERGIC and in the pre-cis Golgi cisterna layer in mammalian cells. PMID:23369235

  14. Lipotoxicity in steatohepatitis occurs despite an increase in tricarboxylic acid cycle activity.

    PubMed

    Patterson, Rainey E; Kalavalapalli, Srilaxmi; Williams, Caroline M; Nautiyal, Manisha; Mathew, Justin T; Martinez, Janie; Reinhard, Mary K; McDougall, Danielle J; Rocca, James R; Yost, Richard A; Cusi, Kenneth; Garrett, Timothy J; Sunny, Nishanth E

    2016-04-01

    The hepatic tricarboxylic acid (TCA) cycle is central to integrating macronutrient metabolism and is closely coupled to cellular respiration, free radical generation, and inflammation. Oxidative flux through the TCA cycle is induced during hepatic insulin resistance, in mice and humans with simple steatosis, reflecting early compensatory remodeling of mitochondrial energetics. We hypothesized that progressive severity of hepatic insulin resistance and the onset of nonalcoholic steatohepatitis (NASH) would impair oxidative flux through the hepatic TCA cycle. Mice (C57/BL6) were fed a high-trans-fat high-fructose diet (TFD) for 8 wk to induce simple steatosis and NASH by 24 wk. In vivo fasting hepatic mitochondrial fluxes were determined by(13)C-nuclear magnetic resonance (NMR)-based isotopomer analysis. Hepatic metabolic intermediates were quantified using mass spectrometry-based targeted metabolomics. Hepatic triglyceride accumulation and insulin resistance preceded alterations in mitochondrial metabolism, since TCA cycle fluxes remained normal during simple steatosis. However, mice with NASH had a twofold induction (P< 0.05) of mitochondrial fluxes (μmol/min) through the TCA cycle (2.6 ± 0.5 vs. 5.4 ± 0.6), anaplerosis (9.1 ± 1.2 vs. 16.9 ± 2.2), and pyruvate cycling (4.9 ± 1.0 vs. 11.1 ± 1.9) compared with their age-matched controls. Induction of the TCA cycle activity during NASH was concurrent with blunted ketogenesis and accumulation of hepatic diacylglycerols (DAGs), ceramides (Cer), and long-chain acylcarnitines, suggesting inefficient oxidation and disposal of excess free fatty acids (FFA). Sustained induction of mitochondrial TCA cycle failed to prevent accretion of "lipotoxic" metabolites in the liver and could hasten inflammation and the metabolic transition to NASH.

  15. Step-based translation of physical activity guidelines in the Lower Mississippi Delta.

    PubMed

    Harrington, Deirdre M; Tudor-Locke, Catrine; Champagne, Catherine M; Broyles, Stephanie T; Harsha, David W; Kennedy, Betty M; Johnson, William D; Allen, Ray; Katzmarzyk, Peter T

    2011-08-01

    To determine how many steps·day(-1) equate to current moderate-to-vigorous physical activity (MVPA) guidelines in a population from the Lower Mississippi Delta (LMD) of the United States, 58 overweight adults wore an Actigraph accelerometer (GT3X) for up to 2 weeks. Min·day(-1) in MVPA was a good predictor of steps·day(-1) (r(2) = 0.62; p < 0.001; linear regression), such that 30 min of daily MVPA equated to 9154 steps·day(-1) (mixed-model approach). Using receiver operating characteristic analysis, sensitivity and specificity were optimized at 8357 steps·day(-1). Results indicate that overweight residents of the LMD should be accumulating at least 8300-9100 steps·day(-1) to meet the recommendation of 30 min·day(-1) MVPA.

  16. Reiterative AP2a activity controls sequential steps in the neural crest gene regulatory network.

    PubMed

    de Crozé, Noémie; Maczkowiak, Frédérique; Monsoro-Burq, Anne H

    2011-01-04

    The neural crest (NC) emerges from combinatorial inductive events occurring within its progenitor domain, the neural border (NB). Several transcription factors act early at the NB, but the initiating molecular events remain elusive. Recent data from basal vertebrates suggest that ap2 might have been critical for NC emergence; however, the role of AP2 factors at the NB remains unclear. We show here that AP2a initiates NB patterning and is sufficient to elicit a NB-like pattern in neuralized ectoderm. In contrast, the other early regulators do not participate in ap2a initiation at the NB, but cooperate to further establish a robust NB pattern. The NC regulatory network uses a multistep cascade of secreted inducers and transcription factors, first at the NB and then within the NC progenitors. Here we report that AP2a acts at two distinct steps of this cascade. As the earliest known NB specifier, AP2a mediates Wnt signals to initiate the NB and activate pax3; as a NC specifier, AP2a regulates further NC development independent of and downstream of NB patterning. Our findings reconcile conflicting observations from various vertebrate organisms. AP2a provides a paradigm for the reiterated use of multifunctional molecules, thereby facilitating emergence of the NC in vertebrates.

  17. Enriching step-based product information models to support product life-cycle activities

    NASA Astrophysics Data System (ADS)

    Sarigecili, Mehmet Ilteris

    The representation and management of product information in its life-cycle requires standardized data exchange protocols. Standard for Exchange of Product Model Data (STEP) is such a standard that has been used widely by the industries. Even though STEP-based product models are well defined and syntactically correct, populating product data according to these models is not easy because they are too big and disorganized. Data exchange specifications (DEXs) and templates provide re-organized information models required in data exchange of specific activities for various businesses. DEXs show us it would be possible to organize STEP-based product models in order to support different engineering activities at various stages of product life-cycle. In this study, STEP-based models are enriched and organized to support two engineering activities: materials information declaration and tolerance analysis. Due to new environmental regulations, the substance and materials information in products have to be screened closely by manufacturing industries. This requires a fast, unambiguous and complete product information exchange between the members of a supply chain. Tolerance analysis activity, on the other hand, is used to verify the functional requirements of an assembly considering the worst case (i.e., maximum and minimum) conditions for the part/assembly dimensions. Another issue with STEP-based product models is that the semantics of product data are represented implicitly. Hence, it is difficult to interpret the semantics of data for different product life-cycle phases for various application domains. OntoSTEP, developed at NIST, provides semantically enriched product models in OWL. In this thesis, we would like to present how to interpret the GD & T specifications in STEP for tolerance analysis by utilizing OntoSTEP.

  18. Development of a real time activity monitoring Android application utilizing SmartStep.

    PubMed

    Hegde, Nagaraj; Melanson, Edward; Sazonov, Edward

    2016-08-01

    Footwear based activity monitoring systems are becoming popular in academic research as well as consumer industry segments. In our previous work, we had presented developmental aspects of an insole based activity and gait monitoring system-SmartStep, which is a socially acceptable, fully wireless and versatile insole. The present work describes the development of an Android application that captures the SmartStep data wirelessly over Bluetooth Low energy (BLE), computes features on the received data, runs activity classification algorithms and provides real time feedback. The development of activity classification methods was based on the the data from a human study involving 4 participants. Participants were asked to perform activities of sitting, standing, walking, and cycling while they wore SmartStep insole system. Multinomial Logistic Discrimination (MLD) was utilized in the development of machine learning model for activity prediction. The resulting classification model was implemented in an Android Smartphone. The Android application was benchmarked for power consumption and CPU loading. Leave one out cross validation resulted in average accuracy of 96.9% during model training phase. The Android application for real time activity classification was tested on a human subject wearing SmartStep resulting in testing accuracy of 95.4%.

  19. Resisted side-stepping: the effect of posture on hip abductor muscle activation

    PubMed Central

    Berry, Justin W.; Lee, Theresa S.; Foley, Hanna D.; Lewis, Cara L.

    2016-01-01

    Study Design Controlled laboratory study, repeated-measures design. Objectives To compare hip abductor muscle activity and hip and knee joint kinematics in the moving limb to the stance limb during resisted side-stepping and also to determine if muscle activity was affected by the posture (upright standing versus squat) used to perform the exercise. Background Hip abductor weakness has been associated with a variety of lower extremity injuries. Resisted side-stepping is often used as an exercise to increase strength and endurance of the hip abductors. Exercise prescription would benefit from knowing the relative muscle activity level generated in each limb and for different postures during the side-stepping exercise. Methods Twenty-four healthy adults participated in this study. Kinematics and surface electromyographic (EMG) data from the gluteus maximus, gluteus medius, and tensor fascia lata (TFL) were collected as participants performed side-stepping with a resistive band around the ankle while maintaining each of 2 postures: 1) upright standing and 2) squat. Results Mean normalized EMG signal amplitude of the gluteus maximus, gluteus medius, and TFL was higher in the stance limb than the moving limb (P≤.001). Gluteal muscle activity was higher, while TFL muscle activity was lower, in the squat posture compared to the upright standing posture (P<.001). Hip abduction excursion was greater in the stance limb than in the moving limb (P<.001). Conclusions The 3 hip abductor muscles respond differently to the posture variations of side-stepping exercise in healthy individuals. When prescribing resisted side-stepping exercises, therapists should consider the differences in hip abductor activation across limbs and variations in trunk posture. PMID:26161629

  20. Physical activity, functional capacity, and step variability during walking in people with lower-limb amputation.

    PubMed

    Lin, Suh-Jen; Winston, Katie D; Mitchell, Jill; Girlinghouse, Jacob; Crochet, Karleigh

    2014-01-01

    Physical activity is important for general health. For an individual with amputation to sustain physical activity, certain functional capacity might be needed. Gait variability is related to the incidence of falls. This study explored the relationship between physical activity and a few common performance measures (six-minute walk test, step length variability, step width variability, and comfortable walking speed) in individuals with unilateral lower-limb amputation. Twenty individuals completed the study (age: 50±11yrs). Twelve of them had transtibial amputation, seven had transfemoral amputation, and one had through-knee amputation. Gait data was collected by the GaitRite instrumented walkway while participants performed a 3-min comfortable walking trial followed by a six-minute walk test. Physical activity was indicated by the mean of 7-day step counts via a pedometer. Gait variability was calculated by the coefficient of variation. Pearson correlation analysis was conducted between physical activity level and the 4 performance measures. Significance level was set at 0.05. Physical activity correlates strongly to comfortable walking speed (r=0.76), six-minute walk distance (r=0.67), and correlates fairly to step width variability (r=0.44). On the contrary, physical activity is inversely related to step length variability of the prosthetic leg (r=-0.46) and of the sound leg (r=-0.47). Having better functional capacity and lateral stability might enable an individual with lower-limb amputation to engage in a higher physical activity level, or vise versa. However, our conclusions are only preliminary as limited by the small sample size.

  1. Step-based translation of physical activity guidelines in the Lower Mississippi Delta

    Technology Transfer Automated Retrieval System (TEKTRAN)

    To determine how many steps/day equate to current moderate-to-vigorous physical activity (MVPA) guidelines in a population from the Lower Mississippi Delta (LMD) of the United States, 58 overweight adults wore an Actigraph accelerometer (GT3X) for up to two weeks. Minutes/day in MVPA was a good pred...

  2. Middle School Physical Education Physical Activity Quantification: A Pedometer Steps/Min Guideline

    ERIC Educational Resources Information Center

    Scruggs, Philip W.

    2007-01-01

    The objective of the study was to improve physical activity (PA) surveillance of the Healthy People 2010 Objective 22:10 (i.e., 50% of the lesson time engaged in PA) by establishing a pedometer steps/min guideline to quantify time engaged in PA during physical education. A sample of 180 middle school students had their PA measured via pedometry…

  3. Pedometer-Measured Physical Activity of Adults with Intellectual Disability: Predicting Weekly Step Counts

    ERIC Educational Resources Information Center

    Temple, Viviene A.; Stanish, Heidi I.

    2009-01-01

    Pedometers are objective, inexpensive, valid, and reliable measures of physical activity. The minimum number of days of pedometer monitoring needed to estimate average weekly step counts was investigated. Seven days of pedometer data were collected from 154 ambulatory men and women ("ns" = 88 and 66, respectively) with intellectual disability.…

  4. Identifying Activity Levels and Steps in People with Stroke using a Novel Shoe-Based Sensor

    PubMed Central

    Fulk, George D.; Edgar, S. Ryan; Bierwirth, Rebecca; Hart, Phil; Lopez-Meyer, Paulo; Sazonov, Edward

    2012-01-01

    Background/Purpose Advances in sensory technologies provides a method to accurately assess activity levels of people with stroke in their community. This information could be used to determine the effectiveness of rehabilitation interventions as well as provide behavioral enhancing feedback. The purpose of this study was to assess the accuracy of a novel shoe-based sensor system (SmartShoe) to identify different functional postures and steps in people with stroke. The SmartShoe system consists of five force sensitive resistors built into a flexible insole and an accelerometer on the back of the shoe. Pressure and acceleration data are sent via Bluetooth to a smart phone. Methods Participants with stroke wore the SmartShoe while they performed activities of daily living (ADL) in sitting, standing and walking. Data from four participants were used to develop a multi-layer perceptron artificial neural network (ANN) to identify sitting, standing, and walking. A signal-processing algorithm used data from the pressure sensors to estimate number of steps taken while walking. The accuracy, precision and recall of the ANN for identifying the three functional postures were calculated using data from a different set of participants. Agreement between steps identified by SmartShoe and actual steps taken was analyzed using the Bland Altman method. Results The SmartShoe was able to accurately identify sitting, standing and walking. Accuracy, precision and recall were all greater than 95%. The mean difference between steps identified by SmartShoe and actual steps was less than 1 step. Discussion The SmartShoe was able to accurately identify different functional postures using a unique combination of pressure and acceleration data in people with stroke as they performed different ADLs. There was a strong level of agreement between actual steps taken and steps identified using the SmartShoe. Further study is needed to determine if the SmartShoe could be used to provide valid

  5. Synthesis and insecticidal activity of novel hydrazone compounds derived from a naturally occurring lignan podophyllotoxin against Mythimna separata (Walker).

    PubMed

    Wang, Yi; Yu, Xiang; Zhi, Xiaoyan; Xiao, Xiao; Yang, Chun; Xu, Hui

    2014-06-15

    In continuation of our program aimed at the discovery and development of natural-product-based insecticidal agents, a series of novel hydrazone derivatives of podophyllotoxin, which is a naturally occurring aryltetralin lignan and isolated as the main secondary metabolite from the roots and rhizomes of Podophyllum species, were synthesized and evaluated as insecticidal agents against the pre-third-instar larvae of oriental armyworm, Mythimna separata (Walker) in vivo at 1mg/mL. Especially compounds 8i, 8j, 8t, and 8u showed the more potent insecticidal activity with the final mortality rates greater than 60%.

  6. T Cell Receptor-induced Activation and Apoptosis In Cycling Human T Cells Occur throughout the Cell Cycle

    PubMed Central

    Karas, Michael; Zaks, Tal Z.; JL, Liu; LeRoith, Derek

    1999-01-01

    Previous studies have found conflicting associations between susceptibility to activation-induced cell death and the cell cycle in T cells. However, most of the studies used potentially toxic pharmacological agents for cell cycle synchronization. A panel of human melanoma tumor-reactive T cell lines, a CD8+ HER-2/neu-reactive T cell clone, and the leukemic T cell line Jurkat were separated by centrifugal elutriation. Fractions enriched for the G0–G1, S, and G2–M phases of the cell cycle were assayed for T cell receptor-mediated activation as measured by intracellular Ca2+ flux, cytolytic recognition of tumor targets, and induction of Fas ligand mRNA. Susceptibility to apoptosis induced by recombinant Fas ligand and activation-induced cell death were also studied. None of the parameters studied was specific to a certain phase of the cell cycle, leading us to conclude that in nontransformed human T cells, both activation and apoptosis through T cell receptor activation can occur in all phases of the cell cycle. PMID:10588669

  7. Cytotoxic activities of naturally occurring oleanane-, ursane-, and lupane-type triterpenes on HepG2 and AGS cells

    PubMed Central

    Yang, Heejung; Kim, Hyun Woo; Kim, Young Choong; Sung, Sang Hyun

    2017-01-01

    Background: It is well known that the naturally occurring modified triterpenes in plants have a wide diversity of chemical structures and biological functions. The lupane-, oleanane-, and ursane-type triterpenes are the three major members of natural triterpenes with a wide range of biological properties. A systematic approach is necessary to review their structures and biological activities according to the backbones and the different substituents. Objective: Thirty lupane-(L1-7), oleanane-(O1-14), and ursane-type (U1-9) triterpenes with structural diversity were examined to evaluate their cytotoxic activities against two cancer cell lines, human hepatocellular carcinoma (HepG2) and AGS cells. Materials and Methods: They were isolated from Hedera helix, Juglans sinensis, and Pulsatilla koreana using a series of column chromatography methods and were treated to evaluate their cytotoxic activities against HepG2 and AGS human gastric adenocarcinoma cell. Further, two triterpenes showing the most potent activities were subjected to the apoptotic screening assay using flow cytometry. Results: The polar groups, such as an oxo group at C-1, a free hydroxyl at C-2, C-3, or C-23, and a carboxylic moiety at C-28, as well as the type of backbone, explicitly increased the cytotoxic activity on two cancer cells. O5 and U5 showed significantly the potent cytotoxic activity in comparison to other glycosidic triterpenes. In annexin-V/propidium iodide (PI) staining assay, the percentage of late apoptosis (annexin-V+/PI+) 12 and 24 h after treatment with O5 and U5 at 25 μM increased from 14.5% to 93.1% and from 46.4% to 49.1%, respectively, in AGS cells. The cytotoxicity induced by O5 showed a significant difference compared to U5 for 12 and 24 h. Conclusion: In the study, we can suggest the potent moieties which influence their cytotoxic activities against two cancer cells. The polar groups at C-1, C-2, C-3, C-23, and C-28 and the linkage of sugar moieties influenced the

  8. Active flow control over a backward-facing step using plasma actuation

    NASA Astrophysics Data System (ADS)

    Ruisi, R.; Zare-Behtash, H.; Kontis, K.; Erfani, R.

    2016-09-01

    Due to the more stringent aviation regulations on fuel consumption and noise reduction, the interest for smaller and mechanically less complex devices for flow separation control has increased. Plasma actuators are currently among the most studied typology of devices for active flow control purposes due to their small size and lightweight. In this study, a single dielectric barrier discharge (SDBD) actuator is used on a backward-facing step to assess its effects on the separated turbulent shear layer and its reattachment location. A range of actuating modulation frequencies, related to the natural frequencies of shear layer instability (flapping) and vortex shedding instability, are examined. The particle image velocimetry technique is used to analyse the flow over the step and the reattachment location. The bulk-flow experiments show negligible effects both on the shear layer and on the reattachment location for every frequency considered, and the actuator is not able to induce a sufficient velocity increase at the step separation point.

  9. Validity and Reliability of Fitbit Flex for Step Count, Moderate to Vigorous Physical Activity and Activity Energy Expenditure

    PubMed Central

    Sushames, Ashleigh; Edwards, Andrew; Thompson, Fintan; McDermott, Robyn; Gebel, Klaus

    2016-01-01

    Objectives To examine the validity and reliability of the Fitbit Flex against direct observation for measuring steps in the laboratory and against the Actigraph for step counts in free-living conditions and for moderate-to-vigorous physical activity (MVPA) and activity energy expenditure (AEE) overall. Methods Twenty-five adults (12 females, 13 males) wore a Fitbit Flex and an Actigraph GT3X+ during a laboratory based protocol (including walking, incline walking, running and stepping) and free-living conditions during a single day period to examine measurement of steps, AEE and MVPA. Twenty-four of the participants attended a second session using the same protocol. Results Intraclass correlations (ICC) for test-retest reliability of the Fitbit Flex were strong for walking (ICC = 0.57), moderate for stair stepping (ICC = 0.34), and weak for incline walking (ICC = 0.22) and jogging (ICC = 0.26). The Fitbit significantly undercounted walking steps in the laboratory (absolute proportional difference: 21.2%, 95%CI 13.0–29.4%), but it was more accurate, despite slightly over counting, for both jogging (6.4%, 95%CI 3.7–9.0%) and stair stepping (15.5%, 95%CI 10.1–20.9%). The Fitbit had higher coefficients of variation (Cv) for step counts compared to direct observation and the Actigraph. In free-living conditions, the average MVPA minutes were lower in the Fitbit (35.4 minutes) compared to the Actigraph (54.6 minutes), but AEE was greater from the Fitbit (808.1 calories) versus the Actigraph (538.9 calories). The coefficients of variation were similar for AEE for the Actigraph (Cv = 36.0) and Fitbit (Cv = 35.0), but lower in the Actigraph (Cv = 25.5) for MVPA against the Fitbit (Cv = 32.7). Conclusion The Fitbit Flex has moderate validity for measuring physical activity relative to direct observation and the Actigraph. Test-rest reliability of the Fitbit was dependant on activity type and had greater variation between sessions compared to the Actigraph. Physical

  10. Muscle Activation Patterns in Infants with Myelomeningocele Stepping on a Treadmill

    PubMed Central

    Sansom, Jennifer K.; Teulier, Caroline; Smith, Beth A.; Moerchen, Victoria; Muraszko, Karin; Ulrich, Beverly D.

    2013-01-01

    Purpose To characterize how infants with myelomeningocele (MMC) activate lower limb muscles over the first year of life, without practice, while stepping on a motorized treadmill. Methods Twelve infants with MMC were tested longitudinally at 1, 6, 12 months. Electromyography (EMG) was used to collect data from the tibialis anterior (TA), lateral gastrocnemius (LG), rectus femoris (RF), biceps femoris (BF). Results Across the first year, infants showed no EMG activity for ~50% of the stride cycle w/poor rhythmicity and timing of muscles, when activated. Single muscle activation predominated; agonist-antagonist co-activation was low. Probability of individual muscle activity across the stride decreased w/age. Conclusions Infants with MMC show high variability in timing and duration of muscle activity, few complex combinations, and very little change over time. PMID:23685739

  11. Statistical analysis on activation and photo-bleaching of step-wise multi-photon activation fluorescence of melanin

    NASA Astrophysics Data System (ADS)

    Gu, Zetong; Lai, Zhenhua; Zhang, Xi; Yin, Jihao; DiMarzio, Charles A.

    2015-03-01

    Melanin is regarded as the most enigmatic pigments/biopolymers found in most organisms. We have shown previously that melanin goes through a step-wise multi-photon absorption process after the fluorescence has been activated with high laser intensity. No melanin step-wise multi-photon activation fluorescence (SMPAF) can be obtained without the activation process. The step-wise multi-photon activation fluorescence has been observed to require less laser power than what would be expected from a non-linear optical process. In this paper, we examined the power dependence of the activation process of melanin SMPAF at 830nm and 920nm wavelengths. We have conducted research using varying the laser power to activate the melanin in a point-scanning mode for multi-photon microscopy. We recorded the fluorescence signals and position. A sequence of experiments indicates the relationship of activation to power, energy and time so that we can optimize the power level. Also we explored regional analysis of melanin to study the spatial relationship in SMPAF and define three types of regions which exhibit differences in the activation process.

  12. A rapidly occurring compensatory decrease in physical activity counteracts diet-induced weight loss in female monkeys.

    PubMed

    Sullivan, Elinor L; Cameron, Judy L

    2010-04-01

    To study changes in energy balance occurring during the initial phases of dieting, 18 adult ovariectomized female monkeys were placed on a low-fat diet, and available calories were reduced by 30% compared with baseline consumption for 1 mo. Surprisingly, there was not significant weight loss; however, daily activity level (measured by accelerometry) decreased soon after diet initiation and reached statistical significance by the 4th wk of dieting (18 +/- 5.6% decrease, P = 0.02). During a 2nd mo of dieting, available calories were reduced by 60% compared with baseline consumption, leading to 6.4 +/- 1.7% weight loss and further suppression of activity. Metabolic rate decreased by 68 +/- 12 kcal/day, with decreased activity accounting for 41 +/- 9 kcal/day, and the metabolic activity of the weight lost accounting for 21 +/- 5 kcal/day. A second group of three monkeys was trained to run on a treadmill for 1 h/day, 5 days/wk, at 80% maximal capacity, leading to increased calorie expenditure of 69.6 +/- 10.7 kcal/day (equivalent to 49 kcal/day for 7 days). We conclude that a diet-induced decrease in physical activity is the primary mechanism the body uses to defend against diet-induced weight loss, and undertaking a level of exercise that is recommended to counteract weight gain and promote weight loss is able to prevent the compensatory decrease in physical activity-associated energy expenditure that slows diet-induced weight loss.

  13. A Nonselective Cyclooxygenase Inhibitor Enhances the Activity of Vinblastine in a Naturally-Occurring Canine Model of Invasive Urothelial Carcinoma

    PubMed Central

    Knapp, Deborah W.; Ruple-Czerniak, Audrey; Ramos-Vara, José A.; Naughton, James F.; Fulkerson, Christopher M.; Honkisz, Sonia I.

    2016-01-01

    Background: Chemotherapy is expected to remain an important part of invasive urothelial carcinoma (UC) treatment. Strategies to enhance chemotherapy efficacy are needed. Objective: To determine the chemotherapy-enhancing effects of a nonselective cyclooxygenase (COX) inhibitor on vinblastine in a naturally-occurring canine model of invasive UC. Methods: With IACUC approval, privately-owned dogs with naturally-occurring histologically-diagnosed invasive UC, expected survival ≥6 weeks, and informed owner consent were randomly allocated to receive vinblastine (2.5 mg/m2 intravenously every 2 weeks) plus piroxicam (0.3 mg/kg daily per os) or vinblastine alone (same dose) with the option to receive piroxicam alone when vinblastine failed. Scheduled evaluations included physical exam, standard laboratory analyses, thoracic radiography, abdominal ultrasonography, and standardized measurement of urinary tract tumors. Results: Dogs receiving vinblastine alone (n = 27) and vinblastine-piroxicam (n = 24) were similar in age, sex, breed, tumor stage, and grade. Remission occurred more frequently (P <  0.02) with vinblastine-piroxicam (58.3%) than with vinblastine alone (22.2%). The median progression free interval was 143 days with vinblastine alone and 199 days with the combination. Interestingly, the overall median survival time was significantly longer (P <  0.03) in dogs receiving vinblastine alone followed by piroxicam alone (n = 20, 531 days) than in dogs receiving the combination (299 days). Treatment was well tolerated in both arms. Conclusions: Piroxicam significantly enhanced the activity of vinblastine in dogs with UC where the cancer closely mimics the human condition, clearly justifying further study. The study suggest the potential importance of tracking COX inhibitor use in patients in clinical trials as COX inhibitors could affect treatment response. PMID:27376143

  14. Fusion activity of African henipavirus F proteins with a naturally occurring start codon directly upstream of the signal peptide.

    PubMed

    Weis, Michael; Behner, Laura; Binger, Tabea; Drexler, Jan Felix; Drosten, Christian; Maisner, Andrea

    2015-04-02

    Compared to the fusion proteins of pathogenic Nipah and Hendra viruses, the F protein of prototype African henipavirus GH-M74a displays a drastically reduced surface expression and fusion activity. A probable reason for limited F expression is the unusually long sequence located between the gene start and the signal peptide (SP) not present in other henipaviruses. Such a long pre-SP extension can prevent efficient ER translocation or protein maturation and processing. As its truncation can therefore enhance surface expression, the recent identification of a second in-frame start codon directly upstream of the SP in another African henipavirus F gene (GH-UP28) raised the question if such a naturally occurring minor sequence variation can lead to the synthesis of a pre-SP truncated translation product, thereby increasing the production of mature F proteins. To test this, we analyzed surface expression and biological activity of F genes carrying the second SP-proximal start codon of GH-UP28. Though we observed minor differences in the expression levels, introduction of the additional start codon did not result in an increased fusion activity, even if combined with further mutations in the pre-SP region. Thus, limited bioactivity of African henipavirus F protein is maintained even after sequence changes that alter the gene start allowing the production of F proteins without an unusually long pre-SP.

  15. One-step electrochemical synthesis of a graphene–ZnO hybrid for improved photocatalytic activity

    SciTech Connect

    Wei, Ang; Xiong, Li; Sun, Li; Liu, Yanjun; Li, Weiwei; Lai, Wenyong; Liu, Xiangmei; Wang, Lianhui; Huang, Wei; Dong, Xiaochen

    2013-08-01

    Graphical abstract: - Highlights: • Graphene–ZnO hybrid was synthesized by one-step electrochemical deposition. • Graphene–ZnO hybrid presents a special structure and wide UV–vis absorption spectra. • Graphene–ZnO hybrid exhibits an exceptionally higher photocatalytic activity for the degradation of dye methylene blue. - Abstract: A graphene–ZnO (G-ZnO) hybrid was synthesized by one-step electrochemical deposition. During the formation of ZnO nanostructure by cathodic electrochemical deposition, the graphene oxide was electrochemically reduced to graphene simultaneously. Scanning electron microscope images, X-ray photoelectron spectroscopy, X-ray diffraction, Raman spectra, and UV–vis absorption spectra indicate the resulting G-ZnO hybrid presents a special structure and wide UV–vis absorption spectra. More importantly, it exhibits an exceptionally higher photocatalytic activity for the degradation of dye methylene blue than that of pure ZnO nanostructure under both ultraviolet and sunlight irradiation.

  16. Regulation of the voltage-insensitive step of HERG activation by extracellular pH.

    PubMed

    Zhou, Qinlian; Bett, Glenna C L

    2010-06-01

    Human ether-à-go-go-related gene (HERG, Kv11.1, KCNH2) voltage-gated K(+) channels dominate cardiac action potential repolarization. In addition, HERG channels play a role in neuronal and smooth cell excitability as well as cancer pathology. Extracellular pH (pH(o)) is modified during myocardial ischemia, inflammation, and respiratory alkalosis, so understanding the response of HERG channels to changes in pH is of clinical significance. The relationship between pH(o) and HERG channel gating appears complex. Acidification has previously been reported to speed, slow, or have no effect on activation. We therefore undertook comprehensive analysis of the effect of pH(o) on HERG channel activation. HERG channels have unique and complex activation gating characteristics with both voltage-sensitive and voltage-insensitive steps in the activation pathway. Acidosis decreased the activation rate, suppressed peak current, and altered the sigmoidicity of gating near threshold potentials. At positive voltages, where the voltage-insensitive transition is rate limiting, pH(o) modified the voltage-insensitive step with a pK(a) similar to that of histidine. Hill coefficient analysis was incompatible with a coefficient of 1 but was well described by a Hill coefficient of 4. We derived a pH(o)-sensitive term for a five-state Markov model of HERG channel gating. This model demonstrates the mechanism of pH(o) sensitivity in HERG channel activation. Our experimental data and mathematical model demonstrate that the pH(o) sensitivity of HERG channel activation is dominated by the pH(o) sensitivity of the voltage-insensitive step, in a fashion that is compatible with the presence of at least one proton-binding site on each subunit of the channel tetramer.

  17. Superoxide dismutase activity of the naturally occurring human serum albumin-copper complex without hydroxyl radical formation.

    PubMed

    Kato, Ryunosuke; Akiyama, Matofusa; Kawakami, Hiroyoshi; Komatsu, Teruyuki

    2014-01-01

    The superoxide radical anion (O2(.-)) is biologically toxic and contributes to the pathogenesis of various diseases. Here we describe the superoxide dismutase (SOD) activity of human serum albumin (HSA) complexed with a single Cu(II) ion at the N-terminal end (HSA-Cu complex). The structure of this naturally occurring copper-coordinated blood serum protein has been characterized by several physicochemical measurements. The O2(.-) dismutation ability of the HSA-Cu (1:1) complex is almost the same as that of the well-known SOD mimics, such as Mn(III) -tetrakis(N-methylpyridinium)porphyrin. Interestingly, the HSA-Cu complex does not induce a subsequent Fenton reaction to produce the hydroxyl radical (OH(.)), which is one of the most harmful reactive oxygen species.

  18. Regularized two-step brain activity reconstruction from spatiotemporal EEG data

    NASA Astrophysics Data System (ADS)

    Alecu, Teodor I.; Voloshynovskiy, Sviatoslav; Pun, Thierry

    2004-10-01

    We are aiming at using EEG source localization in the framework of a Brain Computer Interface project. We propose here a new reconstruction procedure, targeting source (or equivalently mental task) differentiation. EEG data can be thought of as a collection of time continuous streams from sparse locations. The measured electric potential on one electrode is the result of the superposition of synchronized synaptic activity from sources in all the brain volume. Consequently, the EEG inverse problem is a highly underdetermined (and ill-posed) problem. Moreover, each source contribution is linear with respect to its amplitude but non-linear with respect to its localization and orientation. In order to overcome these drawbacks we propose a novel two-step inversion procedure. The solution is based on a double scale division of the solution space. The first step uses a coarse discretization and has the sole purpose of globally identifying the active regions, via a sparse approximation algorithm. The second step is applied only on the retained regions and makes use of a fine discretization of the space, aiming at detailing the brain activity. The local configuration of sources is recovered using an iterative stochastic estimator with adaptive joint minimum energy and directional consistency constraints.

  19. A Recently Established Murine Model of Nasal Polyps Demonstrates Activation of B Cells, as Occurs in Human Nasal Polyps.

    PubMed

    Kim, Dong-Young; Lee, Sun Hye; Carter, Roderick G; Kato, Atsushi; Schleimer, Robert P; Cho, Seong H

    2016-08-01

    Animal model systems are invaluable for examining human diseases. Our laboratory recently established a mouse model of nasal polyps (NPs) and investigated similarities and differences between this mouse model and human NPs. We especially focus on the hypothesis that B cell activation occurs during NP generation in the murine model. After induction of ovalbumin-induced allergic rhinosinusitis, 6% ovalbumin and Staphylococcus aureus enterotoxin B (10 ng) were instilled into the nasal cavity of mice three times per week for 8 weeks. The development of structures that somewhat resemble NPs (which we will refer to as NPs) was confirmed by hematoxylin and eosin staining. The mRNA and protein levels of various inflammatory cell markers and mediators were measured by real-time PCR in nasal tissue and by ELISA in nasal lavage fluid (NLF), respectively. Total Ig isotype levels in NLF were also quantitated using the Mouse Ig Isotyping Multiplex kit (EMD Millipore, Billerica, MA) on a Luminex 200 instrument (Life Technologies, Grand Island, NY). Similar to human NPs, there were significant increases in gene expression of inflammatory cell markers, such as CD19, CD138, CD11c, and mast cell protease-6 in nasal tissue samples of the NP group compared with those of the control group. In further investigations of B cell activation, mRNA expressions of B cell activating factor and a proliferation-inducing ligand were found to be significantly increased in mouse NP tissue. B cell-activating factor protein concentration and IgA and IgG1 levels in NLF were significantly higher in the NP group compared with the control group. In this study, the NP mouse model demonstrated enhanced B cell responses, which are reminiscent of B cell responses in human NPs.

  20. Discerning the antioxidant mechanism of rapanone: A naturally occurring benzoquinone with iron complexing and radical scavenging activities.

    PubMed

    de la Vega-Hernández, Karen; Antuch, Manuel; Cuesta-Rubio, Osmany; Núñez-Figueredo, Yanier; Pardo-Andreu, Gilberto L

    2017-05-01

    Oxidative stress resulting from iron and reactive oxygen species (ROS) homeostasis breakdown has been implicated in several diseases. Therefore, molecules capable of binding iron and/or scavenging ROS may be reasonable strategies for protecting cells. Rapanone is a naturally occurring hydroxyl-benzoquinone with a privileged chelating structure. In this work, we addressed the antioxidant properties of rapanone concerning its iron-chelating and scavenging activities, and its protective potential against iron and tert-butyl hydroperoxide-induced damage to mitochondria. Experimental determinations revealed the formation of rapanone-Fe(II)/Fe(III) complexes. Additionally, the electrochemical assays indicated that rapanone oxidized Fe(II) and O2(-), thus inhibiting Fenton-Haber-Weiss reactions. Furthermore, rapanone displayed an increased 2,2-diphenyl-1-picrylhydrazyl radical scavenging ability in the presence of Fe(II). The above results explained the capacity of rapanone to provide near-full protection against iron and tert-butyl hydroperoxide induced mitochondrial lipid peroxidation in energized organelles, which fail under non-energized condition. We postulate that rapanone affords protection against iron and reactive oxygen species by means of both iron chelating and iron-stimulated free radical scavenging activity.

  1. One-step purification of a functional, constitutively activated form of visual arrestin.

    PubMed

    Huang, Li; Mao, Xiang; Abdulaev, Najmoutin G; Ngo, Tony; Liu, Wei; Ridge, Kevin D

    2012-03-01

    Desensitization of agonist-activated G protein-coupled receptors (GPCRs) requires phosphorylation followed by the binding of arrestin, a ~48 kDa soluble protein. While crystal structures for the inactive, 'basal' state of various arrestins are available, the conformation of 'activated' arrestin adopted upon interaction with activated GPCRs remains unknown. As a first step towards applying high-resolution structural methods to study arrestin conformation and dynamics, we have utilized the subtilisin prodomain/Profinity eXact™ fusion-tag system for the high-level bacterial expression and one-step purification of wild-type visual arrestin (arrestin 1) as well as a mutant form (R175E) of the protein that binds to non-phosphorylated, light-activated rhodopsin (Rho∗). The results show that both prodomain/Profinity eXact™ fusion-tagged wild-type and R175E arrestins can be expressed to levels approaching 2-3 mg/l in Luria-Bertani media, and that the processed, tag-free mature forms can be purified to near homogeneity using a Bio-Scale™ Mini Profinity eXact™ cartridge on the Profinia™ purification system. Functional analysis of R175E arrestin generated using this approach shows that it binds to non-phosphorylated rhodopsin in a light-dependent manner. These findings should facilitate the structure determination of this 'constitutively activated' state of arrestin 1 as well as the monitoring of conformational changes upon interaction with Rho∗.

  2. Corticosterone targets distinct steps of synaptic transmission via concentration specific activation of mineralocorticoid and glucocorticoid receptors.

    PubMed

    Chatterjee, Sreejata; Sikdar, Sujit K

    2014-02-01

    Hippocampal neurons are affected by chronic stress and have a high density of cytoplasmic mineralocorticoid and glucocorticoid receptors (MR and GR). Detailed studies on the genomic effects of the stress hormone corticosterone at physiologically relevant concentrations on different steps in synaptic transmission are limited. In this study, we tried to delineate how activation of MR and GR by different concentrations of corticosterone affects synaptic transmission at various levels. The effect of 3-h corticosterone (25, 50, and 100 nM) treatment on depolarization-mediated calcium influx, vesicular release and properties of miniature excitatory post-synaptic currents (mEPSCs) were studied in cultured hippocampal neurons. Activation of MR with 25 nM corticosterone treatment resulted in enhanced depolarization-mediated calcium influx via a transcription-dependent process and increased frequency of mEPSCs with larger amplitude. On the other hand, activation of GR upon 100 nM corticosterone treatment resulted in increase in the rate of vesicular release via the genomic actions of GR. Furthermore, GR activation led to significant increase in the frequency of mEPSCs with larger amplitude and faster decay. Our studies indicate that differential activation of the dual receptor system of MR and GR by corticosterone targets the steps in synaptic transmission differently.

  3. Effects of processing steps on the phenolic content and antioxidant activity of beer.

    PubMed

    Leitao, Céline; Marchioni, Eric; Bergaentzlé, Martine; Zhao, Minjie; Didierjean, Luc; Taidi, Behnam; Ennahar, Saïd

    2011-02-23

    A new analytical method (liquid chromatography-antioxidant, LC-AOx) was used that is intended to separate beer polyphenols and to determine the potential antioxidant activity of these constituents after they were allowed to react online with a buffered solution of the radical cation 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS(•+)). Using the LC-AOx method, it was possible to demonstrate that the extent of the antioxidant activity was very much dependent on the phenolic compound considered. The method was also applied to the analysis of beer extracts and allowed the evaluation of their antioxidant activity at different steps of beer processing: brewing, boiling, and fermentation. This study showed that the total antioxidant activity remained unchanged throughout beer processing, as opposed to the polyphenolic content, which showed a 3-fold increase. Hopping and fermentation steps were the main causes of this increase. However, the increase measured after fermentation was attributed to a better extraction of polyphenols due to the presence of ethanol, rather than to a real increase in their content. Moreover, this method allowed the detection of three unknown antioxidant compounds, which accounted for 64 ± 4% of the total antioxidant activity of beer and were individually more efficient than caffeic acid and epicatechin.

  4. Template-activated strategy toward one-step coating silica colloidal microspheres with sliver.

    PubMed

    Wang, Ke; Zhang, Xiaoli; Niu, Chunyu; Wang, Yongqiang

    2014-01-22

    Template-activated strategy was developed to coat silica (SiO2) colloidal microspheres with silver in one step, based on one-pot hydrothermal treatment of silver nitrate, PVP (poly(vinyl pyrrolidone)), and SiO2 colloidal microspheres in ammonia solution. In our reaction system, the surface of SiO2 colloidal microspheres was continually activated with negative-charged SiO(-) groups in ammonia solution, which accumulated [Ag(NH3)2](+) or Ag(+) ions around the SiO2 colloidal microspheres through electrostatic attraction; thereafter these ions could be reduced into Ag nanoparticles in situ by the weak reducer PVP in the solution, and then acted as seeds for the subsequent complete silver coating with the reaction proceeding. Therefore, the traditional three steps for complete silver coating, including prior surface modification, seeding, and subsequent growing, were effectively integrated into one step. The experimental results exhibited that perfect SiO2/Ag core/shell composite microspheres were successfully synthesized through optimizing the reaction parameters like the solvent ingredient, reducer, and the reaction temperature. Additionally, these obtained uniform composite microspheres were further used as SERS substrate by using R6G and thiram as probe molecules, and showed excellent trace detection of these organic chemicals in solution.

  5. Ankle Instability Effects on Joint Position Sense When Stepping Across the Active Movement Extent Discrimination Apparatus

    PubMed Central

    Witchalls, Jeremy; Waddington, Gordon; Blanch, Peter; Adams, Roger

    2012-01-01

    Context Individuals with and without functional ankle instability have been tested for deficits in lower limb proprioception with varied results. Objective To determine whether a new protocol for testing participants' joint position sense during stepping is reliable and can detect differences between participants with unstable and stable ankles. Design Descriptive laboratory study. Setting University clinical laboratory. Patients or Other Participants Sample of convenience involving 21 young adult university students and staff. Ankle stability was categorized by score on the Cumberland Ankle Instability Tool; 13 had functional ankle instability, 8 had healthy ankles. Intervention(s) Test-retest of ankle joint position sense when stepping onto and across the Active Movement Extent Discrimination Apparatus twice, separated by an interim test, standing still on the apparatus and moving only 1 ankle into inversion. Main Outcome Measure(s) Difference in scores between groups with stable and unstable ankles and between test repeats. Results Participants with unstable ankles were worse at differentiating between inversion angles underfoot in both testing protocols. On repeated testing with the stepping protocol, performance of the group with unstable ankles was improved (Cohen d = 1.06, P = .006), whereas scores in the stable ankle group did not change in the second test (Cohen d = 0.04, P = .899). Despite this improvement, the unstable group remained worse at differentiating inversion angles on the stepping retest (Cohen d = 0.99, P = .020). Conclusions The deficits on proprioceptive tests shown by individuals with functional ankle instability improved with repeated exposure to the test situation. The learning effect may be the result of systematic exposure to ankle-angle variation that led to movement-specific learning or increased confidence when stepping across the apparatus. PMID:23182010

  6. Key programmatic steps and activities for implementing the Uranium Mill Tailings Remedial Action Project. [UMTRA Project

    SciTech Connect

    Not Available

    1985-07-01

    The Uranium Mill Tailings Radiation Control Act of 1978 (UMTRCA) was enacted based upon findings by Congress that uranium mill tailings located at active and inactive hazard to the public, and that protection of the public health, safety and welfare, and the regulations of interstate commerce, require that every reasonable effort be made to provide for the stabilization, disposal, and control in a safe and environmentally sound manner of such tailings in order to prevent or minimize radon diffusion into the environment and to prevent or minimize other environmental hazards from such tailings.'' A general understanding of the steps leading to elimination of the hazards associated with designated uranium mill tailings sites, and the parties involved in that effort, are presented in this document. A representative schedule is also presented in this document to show both program sequence and activity interdependence. Those activities that have the most potential to influence program duration, because of the significant amount of additional time that may be required, include identification and selection of a suitable site, field data collection delays due to weather, actual acquisition of the designated or alternate disposal site, construction delays due to weather, and site licensing. This document provides an understanding of the steps, the sequence, the parties involved, and a representative duration of activities leading to remedial action and cleanup at the designated inactive uranium mill tailings sites. 10 refs., 5 figs., 1 tab.

  7. K-ras activation occurs frequently in mucinous adenocarcinomas and rarely in other common epithelial tumors of the human ovary.

    PubMed Central

    Enomoto, T.; Weghorst, C. M.; Inoue, M.; Tanizawa, O.; Rice, J. M.

    1991-01-01

    To explore the role of mutational activation of members of the ras family of cellular protooncogenes in the development of human ovarian neoplasms, a series of 37 ovarian tumors from Japanese patients was studied. These included 30 common epithelial tumors (1 mucinous tumor of borderline malignancy, 7 mucinous adenocarcinomas, and 22 nonmucinous carcinomas: 10 serous, 3 clear cell, 8 endometrioid, and 1 undifferentiated), 5 tumors of germ cell origin, and 2 sex cord/stromal cell tumors. Polymerase chain reaction was performed from selected areas of deparaffinized sections of formalin-fixed paraffin-embedded tissue, and the presence of activating point mutations in codons 12, 13, and 61 of the H-, N-, and K-ras genes was probed by dot-blot hybridization analysis with mutation specific oligonucleotides. Mutations in K-ras were also looked for by direct genomic sequencing. The overall frequency of ras gene mutations was 10/37 (27%). Mutations were detected only in K-ras, and were found in most of the mucinous tumors, including the one such tumor of borderline malignancy (6/8; 75%). In one mucinous adenocarcinoma, two mutations were detected in paraffin-embedded material that had not previously been found in high molecular weight DNA isolated from frozen tissue from the same case. K-ras mutations occurred significantly more frequently in mucinous tumors (6/8, 75%) than in serous carcinomas (2/10, 20%; P = 0.031) or in all nonmucinous types of epithelial ovarian tumors combined (3/22, 14%; P = 0.0031). Images Figure 1 Figure 2 PMID:1656759

  8. Influence of naturally occurring dissolved organic matter, colloids, and cations on nanofiltration of pharmaceutically active and endocrine disrupting compounds.

    PubMed

    Sadmani, A H M Anwar; Andrews, Robert C; Bagley, David M

    2014-12-01

    This study examined the rejection of selected pharmaceutically active (PhAC) and endocrine disrupting compounds (EDCs) when using nanofiltration as a function of naturally occurring dissolved organic matter (DOM), colloidal particles, cations and their interactions. Lake Ontario water served as a source of natural DOM and colloidal particles. PhAC/EDC rejection experiments were conducted using raw Lake Ontario water and Lake Ontario water that was pre-treated with either ultrafiltration to remove colloidal particles, or fluidized ion exchange resins to remove DOM. Additionally, the concentration of cations (Ca(2+), Mg(2+), and Na(+)) in the raw and pre-treated water matrices was varied. While ionic PhACs and EDCs exhibited high rejections from all the water matrices examined, neutral compounds were most effectively rejected in water containing DOM and no colloids, and least effectively rejected from colloid-containing water with increased cations but no DOM. The presence of DOM significantly improved compound rejection and the increase in cation concentration significantly decreased rejection. The presence of colloids had comparatively little effect except to mitigate the impact of increased cation concentration, apparently providing some cation-buffering capacity. The sequence in which constituents are removed from waters during treatment may significantly impact PhAC and EDC removal, especially of neutral compounds.

  9. Elementary steps for charge transport in DNA: thermal activation vs. tunneling

    NASA Astrophysics Data System (ADS)

    Berlin, Yuri A.; Burin, Alexander L.; Ratner, Mark A.

    2002-01-01

    Using stacks of Watson-Crick base pairs as an important example of multichromophoric molecular assemblies, we studied charge migration in DNA with special emphasis on the mechanism of hole hopping between neighboring guanines (G) connected by the adenine-thymine (AT) bridge. The tight-binding model proposed for this elementary step shows that for short AT bridges, hole transfer between two G bases proceeds via quantum mechanical tunneling. By contrast, hopping over long bridges requires thermal activation. The condition for crossover between tunneling and thermal activation near room temperature is specified and applies to the analysis of experimental data. We show that thermal activation dominates, if the bridge between two G bases contains more than three AT pairs. Our theoretical findings predict that the replacement of AT base pairs by GC pairs increases the efficiency of hole transport only in the case of short base pair sequences. For long sequences, however, the opposite effect is expected.

  10. Preparation of functionalized and metal-impregnated activated carbon by a single-step activation method

    NASA Astrophysics Data System (ADS)

    Dastgheib, Seyed A.; Ren, Jianli; Rostam-Abadi, Massoud; Chang, Ramsay

    2014-01-01

    A rapid method to prepare functionalized and metal-impregnated activated carbon from coal is described in this paper. A mixture of ferric chloride and a sub-bituminous coal was used to demonstrate simultaneous coal activation, chlorine functionalization, and iron/iron oxides impregnation in the resulting porous carbon products. The FeCl3 concentration in the mixture, the method to prepare the FeCl3-coal mixture (solid mixing or liquid impregnation), and activation atmosphere and temperature impacted the surface area and porosity development, Cl functionalization, and iron species impregnation and dispersion in the carbon products. Samples activated in nitrogen or a simulated flue gas at 600 or 1000 °C for 1-2 min had surface areas up to ∼800 m2/g, bulk iron contents up to 18 wt%, and surface chlorine contents up to 27 wt%. Potential catalytic and adsorption application of the carbon materials was explored in catalytic wet air oxidation (CWAO) of phenol and adsorption of ionic mercury from aqueous solutions. Results indicated that impregnated activated carbons outperformed their non-impregnated counterparts in both the CWAO and adsorption tests.

  11. Effect of rubber flooring on dairy cattle stepping behavior and muscle activity.

    PubMed

    Rajapaksha, Eranda; Winkler, Christoph; Tucker, Cassandra B

    2015-04-01

    Use of compressible flooring, such as rubber, has increased on dairy farms. Rubber improves locomotion and is well used by cattle in preference experiments that combine walking and standing. Previous work has found that rubber is particularly beneficial for lame animals, perhaps because a softer material is particularly useful when a single hoof is compromised. The goal of this work was to evaluate the effect of flooring while standing, because cattle in freestall housing spend 40 to 50% of their time engaged in this behavior. In a 2 × 2 design, cows (n = 16) were evaluated on 4 standing surfaces that varied in terms of both floor type (concrete or rubber) and presentation [same floor under all 4 legs (all 4 legs on either concrete or rubber) or a rough surface under only one hind leg and the other 3 legs on concrete or rubber] in a crossover design. Surface electromyograms were used to evaluate muscle fatigue, total activity, and movement of muscle activity between legs during 1 h of standing. Muscle fatigue was evaluated in 2 contexts: (1) static contractions when cows continuously transferred weight to each hind leg, before and after 1 h of standing, and (2) dynamic contractions associated with steps during 1 h on treatment surfaces. In addition, stepping rate, time between each consecutive step, and the latency to lie down after testing were measured. No interaction between floor type and presentation was found. Presentation had a significant effect; when one hind leg was on a rough surface, cattle took 1.7 times more steps with this leg and the non-rough hind leg had 1.2 times more muscle activity, compared with when all 4 legs were on the same surface. These changes are consistent with movement away from concrete with protrusions. When standing on rubber, muscle-activity movements among legs remained stable (0.6-0.7 movements per min) over 1 h but increased on concrete (0.6-0.9 movements per min), indicating that, like humans, cattle may sway to counteract

  12. Active Flow Control on Laminar flow over a Backward facing step

    NASA Astrophysics Data System (ADS)

    Mushyam, Aditya; Bergada, Josep M.

    2015-09-01

    In the present study, two dimensional flow over a backward-facing step in laminar flow regime with application of active flow control (AFC) technique is analysed. The aim of the present work is to gauge the effectiveness of implementing AFC to reduce drag and study its effects on flow characteristics. In order to analyse the influence of AFC on the boundary layer and the downstream vortex shedding, two different kinds of AFC techniques have been used in this study namely zero net mass flow actuators and fluidic actuators. A parametric non dimensional analysis has been carried out by varying the frequency from 0.025 to 0.1 and jet amplitude from 0.05 and 1. Four different positions of the groove were simulated; groove was respectively located at 0.024a, 0.047a, 0.072a and 0.097a, measured upstream from the right side upper edge. Three different non dimensional groove widths 0.023a, 0.048a and 0.073a were also evaluated, where a is the step height. The idea behind this study was to determine an optimal configuration to reduce the drag on the step and to suppress the vortex dissipation in the wake of the step. It was observed that when using an AFC frequency ± 10% of the vortex shedding one, was causing the maximum drag reduction. When comparing the effects of zero net mass flow actuators with the fluidic actuators, it was observed that zero net mass flow actuators were more effective.

  13. Trade-off between frequency and precision during stepping movements: Kinematic and BOLD brain activation patterns.

    PubMed

    Martínez, Martin; Valencia, Miguel; Vidorreta, Marta; Luis, Elkin O; Castellanos, Gabriel; Villagra, Federico; Fernández-Seara, Maria A; Pastor, Maria A

    2016-05-01

    The central nervous system has the ability to adapt our locomotor pattern to produce a wide range of gait modalities and velocities. In reacting to external pacing stimuli, deviations from an individual preferred cadence provoke a concurrent decrease in accuracy that suggests the existence of a trade-off between frequency and precision; a compromise that could result from the specialization within the control centers of locomotion to ensure a stable transition and optimal adaptation to changing environment. Here, we explore the neural correlates of such adaptive mechanisms by visually guiding a group of healthy subjects to follow three comfortable stepping frequencies while simultaneously recording their BOLD responses and lower limb kinematics with the use of a custom-built treadmill device. In following the visual stimuli, subjects adopt a common pattern of symmetric and anti-phase movements across pace conditions. However, when increasing the stimulus frequency, an improvement in motor performance (precision and stability) was found, which suggests a change in the control mode from reactive to predictive schemes. Brain activity patterns showed similar BOLD responses across pace conditions though significant differences were observed in parietal and cerebellar regions. Neural correlates of stepping precision were found in the insula, cerebellum, dorsolateral pons and inferior olivary nucleus, whereas neural correlates of stepping stability were found in a distributed network, suggesting a transition in the control strategy across the stimulated range of frequencies: from unstable/reactive at lower paces (i.e., stepping stability managed by subcortical regions) to stable/predictive at higher paces (i.e., stability managed by cortical regions). Hum Brain Mapp 37:1722-1737, 2016. © 2016 Wiley Periodicals, Inc.

  14. Physical Activity Measurement Device Agreement: Pedometer Steps/Minute and Physical Activity Time

    ERIC Educational Resources Information Center

    Scruggs, Philip W.; Mungen, Jonathan D.; Oh, Yoonsin

    2010-01-01

    The purpose of this study was to examine agreement between the Walk4Life DUO pedometer (W4L; Walk4Life, Plainfield, Illinois, USA) and two criterion instruments in the measurement of physical activity. Participants (N = 189, M = 16.74 years, SD = 0.99) in high school physical education concurrently wore the DUO (i.e., comparison instrument) and…

  15. The metabolic activation and nucleic acid adducts of naturally-occurring carcinogens: recent results with ethyl carbamate and the spice flavors safrole and estragole.

    PubMed Central

    Miller, J. A.; Miller, E. C.

    1983-01-01

    A small (approximately 30) but varied group of organic and inorganic compounds appear to be carcinogenic in both humans and experimental animals. A much larger number and wider variety of chemical carcinogens, primarily synthetic organic compounds, are known for experimental animals. These agents include a small (approximately 30) and varied group of metabolites of green plants and fungi. Many more of these carcinogens must exist in the living world. As with the synthetic carcinogens, the majority of these naturally occurring carcinogens are procarcinogens that require metabolic conversion into reactive electrophilic and mutagenic ultimate carcinogens. These strong electrophiles combine covalently and non-enzymatically with nucleophilic sites in DNAs, RNAs, proteins, and small molecules in target tissues. One or more of the DNA adducts appear to initiate carcinogenesis in an irreversible manner. The subsequent promotion step leading to gross tumours may be completed by further administration of carcinogen or by treatment with non-carcinogenic promoters. Roles for the RNA and protein adducts in the carcinogenic process have not been excluded. Recent data on the metabolic activation and reactivity in vivo of the naturally occurring carcinogens ethyl carbamate and certain of the alkenylbenzene spice flavours are illustrative of these principles. These agents can initiate the carcinogenic process in male mouse liver with small doses given prior to weaning. Subsequent growth of the liver and male hormonal factors appear to function as promoters leading to gross hepatic tumors after one year. Reactive electrophilic metabolites of ethyl carbamate and of safrole and estragole and their nucleic acid adducts formed during initiation in mouse liver have been characterized. PMID:6191767

  16. Validity and reliability of the activPAL3 for measuring posture and stepping in adults and young people.

    PubMed

    Sellers, Ceri; Dall, Philippa; Grant, Margaret; Stansfield, Ben

    2016-01-01

    Characterisation of free-living physical activity requires the use of validated and reliable monitors. This study reports an evaluation of the validity and reliability of the activPAL3 monitor for the detection of posture and stepping in both adults and young people. Twenty adults (median 27.6y; IQR22.6y) and 8 young people (12.0y; IQR4.1y) performed standardised activities and activities of daily living (ADL) incorporating sedentary, upright and stepping activity. Agreement, specificity and positive predictive value were calculated between activPAL3 outcomes and the gold-standard of video observation. Inter-device reliability was calculated between 4 monitors. Sedentary and upright times for standardised activities were within ±5% of video observation as was step count (excluding jogging) for both adults and young people. Jogging step detection accuracy reduced with increasing cadence >150stepsmin(-1). For ADLs, sensitivity to stepping was very low for adults (40.4%) but higher for young people (76.1%). Inter-device reliability was either good (ICC(1,1)>0.75) or excellent (ICC(1,1)>0.90) for all outcomes. An excellent level of detection of standardised postures was demonstrated by the activPAL3. Postures such as seat-perching, kneeling and crouching were misclassified when compared to video observation. The activPAL3 appeared to accurately detect 'purposeful' stepping during ADL, but detection of smaller stepping movements was poor. Small variations in outcomes between monitors indicated that differences in monitor placement or hardware may affect outcomes. In general, the detection of posture and purposeful stepping with the activPAL3 was excellent indicating that it is a suitable monitor for characterising free-living posture and purposeful stepping activity in healthy adults and young people.

  17. Analysis of mitogen-activated protein kinase activation by naturally occurring splice variants of TrkC, the receptor for neurotrophin-3.

    PubMed

    Gunn-Moore, F J; Williams, A G; Tavaré, J M

    1997-02-15

    TrkC is a receptor tyrosine kinase that binds neurotrophin-3 (NT-3) with high affinity. A number of naturally occurring splice variants of TrkC exist, including one (TrkC kil4) with a 14 amino acid insertion between subdomains VII and VIII of the tyrosine kinase domain. This kinase insert blocks the ability of NT-3 to stimulate neurite outgrowth in PC12 cells and proliferation in fibroblasts. The inserts also block the ability of TrkC to form a high-affinity complex with Shc and phospholipase C gamma (PLC gamma) and the activation of PtdIns 3-kinase, and attenuates the sustained activation of mitogen-activated protein kinase (MAPK). In the current study we set out to determine whether the attenuation of the activation of MAPK by the insert was the result of the inability of TrkC to activate the Shc-Ras pathway, PtdIns 3-kinase activation, PLC gamma activation, or a combination thereof. Experiments with the use of cell-permeant inhibitors argue against a major role for PLC gamma and PtdIns 3-kinase in the activation of MAPK by TrkC. The introduction of the 14 amino acid kinase insert appeared to slow the kinetics of NT-3-stimulated Shc phosphorylation and Shc-Grb2 association and reduce their magnitude; an effect which was associated with a delayed, and only transient, activation of MAPK. Taken together, our data suggest that the apparent defect in MAPK activation caused by the kinase insert may result predominantly from an inhibition of high-affinity Shc binding, although a role for PLC gamma and PtdIns 3-kinase cannot be completely excluded.

  18. Single molecule analysis reveals reversible and irreversible steps during spliceosome activation

    PubMed Central

    Hoskins, Aaron A; Rodgers, Margaret L; Friedman, Larry J; Gelles, Jeff; Moore, Melissa J

    2016-01-01

    The spliceosome is a complex machine composed of small nuclear ribonucleoproteins (snRNPs) and accessory proteins that excises introns from pre-mRNAs. After assembly the spliceosome is activated for catalysis by rearrangement of subunits to form an active site. How this rearrangement is coordinated is not well-understood. During activation, U4 must be released to allow U6 conformational change, while Prp19 complex (NTC) recruitment is essential for stabilizing the active site. We used multi-wavelength colocalization single molecule spectroscopy to directly observe the key events in Saccharomyces cerevisiae spliceosome activation. Following binding of the U4/U6.U5 tri-snRNP, the spliceosome either reverses assembly by discarding tri-snRNP or proceeds to activation by irreversible U4 loss. The major pathway for NTC recruitment occurs after U4 release. ATP stimulates both the competing U4 release and tri-snRNP discard processes. The data reveal the activation mechanism and show that overall splicing efficiency may be maintained through repeated rounds of disassembly and tri-snRNP reassociation. DOI: http://dx.doi.org/10.7554/eLife.14166.001 PMID:27244240

  19. One-step preparation of magnetic recyclable quinary graphene hydrogels with high catalytic activity.

    PubMed

    Zhang, Junshuai; Yao, Tongjie; Guan, Chenchen; Zhang, Nanxi; Huang, Xin; Cui, Tieyu; Wu, Jie; Zhang, Xiao

    2017-04-01

    Metal nanoparticles (NPs) displayed overwhelming superiority in catalysis towards the corresponding bulk-phase materials; nevertheless, how to further improve catalytic activity was still an ongoing subject. Herein, we have combined one-step redox reaction and following freeze-dried technology to construct the quinary reduced graphene oxide nanosheets (rGS)/Fe2O3-PdPt/polypyrrole (PPy) hydrogels. Compared with traditional catalysts, their catalytic property was improved via two ways: construction of three-dimensional (3D) rGS hydrogels instead of two-dimensional rGS and synthesis of bimetallic alloys instead of monometallic NPs. The highly dispersed PdPt with diameter as small as 3.2nm uniformly loaded on hydrogel surface. Due to special interconnected and porous structure, the reactants were easily adsorbed in hydrogels and contacted with PdPt alloys. To explain the contributions of bimetallic alloys and 3D rGS structure on enhanced catalytic activity, the catalytic property of quinary hydrogels was compared with reference samples. Besides superior activity, they also displayed good reusability, since hydrogels could be magnetically recycled owing to the existence of Fe2O3 NPs.

  20. A facile one-step solvothermal synthesis of bismuth phosphate-graphene nanocomposites with enhanced photocatalytic activity.

    PubMed

    Wang, Chao; Zhang, Gehong; Zhang, Chao; Wu, Miaomiao; Yan, Ming; Fan, Weiqiang; Shi, Weidong

    2014-12-01

    A facile one-step solvothermal approach was developed to synthesize BiPO4-graphene (BP-RGO) nanocomposites using ethylene glycol/water as the solvent and reducing agent. During the solvothermal reaction, both the effective reduction of graphene oxide (GO) and the growth of rod-shaped BiPO4 as well as its deposition on graphene occurred simultaneously. The as-obtained BP-2%RGO nanocomposite showed the highest photocatalytic activity toward the photodegradation of methyl orange (MO), which was about 2.0 and 1.5 times as high as that of pure BiPO4 and physical mixture of BiPO4 and graphene, respectively. The enhanced photocatalytic activity of BP-2%RGO nanocomposite is attributed to a larger surface area, much increased adsorption capacity, and more effective charge transportations and separations arisen from the introduction of graphene along with the intimate interfacial contact between BiPO4 and graphene. This work highlights the significant effect of solvothermal method and introduction of graphene on the photoactivity of graphene-based nanocomposites. It is expected that this method could aid to fabricate more efficient graphene-based photocatalysts with improved interfacial contact and photocatalytic performance for environmental remediation.

  1. a Three-Step Spatial-Temporal Clustering Method for Human Activity Pattern Analysis

    NASA Astrophysics Data System (ADS)

    Huang, W.; Li, S.; Xu, S.

    2016-06-01

    How people move in cities and what they do in various locations at different times form human activity patterns. Human activity pattern plays a key role in in urban planning, traffic forecasting, public health and safety, emergency response, friend recommendation, and so on. Therefore, scholars from different fields, such as social science, geography, transportation, physics and computer science, have made great efforts in modelling and analysing human activity patterns or human mobility patterns. One of the essential tasks in such studies is to find the locations or places where individuals stay to perform some kind of activities before further activity pattern analysis. In the era of Big Data, the emerging of social media along with wearable devices enables human activity data to be collected more easily and efficiently. Furthermore, the dimension of the accessible human activity data has been extended from two to three (space or space-time) to four dimensions (space, time and semantics). More specifically, not only a location and time that people stay and spend are collected, but also what people "say" for in a location at a time can be obtained. The characteristics of these datasets shed new light on the analysis of human mobility, where some of new methodologies should be accordingly developed to handle them. Traditional methods such as neural networks, statistics and clustering have been applied to study human activity patterns using geosocial media data. Among them, clustering methods have been widely used to analyse spatiotemporal patterns. However, to our best knowledge, few of clustering algorithms are specifically developed for handling the datasets that contain spatial, temporal and semantic aspects all together. In this work, we propose a three-step human activity clustering method based on space, time and semantics to fill this gap. One-year Twitter data, posted in Toronto, Canada, is used to test the clustering-based method. The results show that the

  2. A resolution expressing the sense of the Senate on steps the Government of Iran must take before further bilateral negotiations between the Government of Iran and the United States Government occur.

    THOMAS, 113th Congress

    Sen. Cruz, Ted [R-TX

    2014-01-06

    01/06/2014 Referred to the Committee on Foreign Relations. (text of measure as introduced: CR S30) (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:

  3. Vindoline Formation in Shoot Cultures of Catharanthus roseus is Synchronously Activated with Morphogenesis Through the Last Biosynthetic Step

    PubMed Central

    Campos-Tamayo, Freddy; Hernández-Domínguez, Elizabeta; Vázquez-Flota, Felipe

    2008-01-01

    Background and Aims The Madagascar periwinkle (Catharanthus roseus) produces the monoterpenoid alkaloid vindoline, which requires a specialized cell organization present only in the aerial tissues. Vindoline content can be affected by photoperiod and this effect seems to be associated with the morphogenetic capacity of branches; this association formed the basis of the study reported here. Methods Vindoline-producing in vitro shoot cultures were exposed either to continuous light or a 16-h photoperiod regime. New plantlet formation and alkaloid biosynthesis were analysed throughout a culture cycle. Key Results In cultures under the photoperiod, the formation of new plantlets occurred in a more synchronized fashion as compared to those under continuous light. The accumulation of vindoline in cultures under the photoperiod occurred in co-ordination with plantlet formation, in constrast to cultures under continuous light, and coincided with a peak of activity of deacetylvindoline acetyl CoA acetyltransferase (DAT), the enzyme that catalyses the last step in vindoline biosynthesis. When new plantlet formation was blocked in cultures under the photoperiod by treatment with phytoregulators, vindoline synthesis was also reduced via an effect on DAT activity. No association between plantlet formation and other biosynthetic enzymes, such as tryptophan decarboxylase (TDC) and deacetoxyvindoline 4-hydroxylase (D4H), was found. Effects of light treatment on vindoline synthesis were not mediated by ORCA-3 proteins (which are involved in the induction of alkaloid synthesis in response to elicitation), suggesting that the presence of a different set of regulatory proteins. Conclusions The data suggest that vindoline biosynthesis is associated with morphogenesis in shoot cultures of C. roseus. PMID:18587132

  4. These Shoes Are Made for Walking: Sensitivity Performance Evaluation of Commercial Activity Monitors under the Expected Conditions and Circumstances Required to Achieve the International Daily Step Goal of 10,000 Steps

    PubMed Central

    O’Connell, Sandra; ÓLaighin, Gearóid; Kelly, Lisa; Murphy, Elaine; Beirne, Sorcha; Burke, Niall; Kilgannon, Orlaith; Quinlan, Leo R.

    2016-01-01

    Introduction Physical activity is a vitally important part of a healthy lifestyle, and is of major benefit to both physical and mental health. A daily step count of 10,000 steps is recommended globally to achieve an appropriate level of physical activity. Accurate quantification of physical activity during conditions reflecting those needed to achieve the recommended daily step count of 10,000 steps is essential. As such, we aimed to assess four commercial activity monitors for their sensitivity/accuracy in a prescribed walking route that reflects a range of surfaces that would typically be used to achieve the recommended daily step count, in two types of footwear expected to be used throughout the day when aiming to achieve the recommended daily step count, and in a timeframe required to do so. Methods Four commercial activity monitors were worn simultaneously by participants (n = 15) during a prescribed walking route reflective of surfaces typically encountered while achieving the daily recommended 10,000 steps. Activity monitors tested were the Garmin Vivofit ™, New Lifestyles’ NL-2000 ™ pedometer, Withings Smart Activity Monitor Tracker (Pulse O2) ™, and Fitbit One ™. Results All activity monitors tested were accurate in their step detection over the variety of different surfaces tested (natural lawn grass, gravel, ceramic tile, tarmacadam/asphalt, linoleum), when wearing both running shoes and hard-soled dress shoes. Conclusion All activity monitors tested were accurate in their step detection sensitivity and are valid monitors for physical activity quantification over the variety of different surfaces tested, when wearing both running shoes and hard-soled dress shoes, and over a timeframe necessary for accumulating the recommended daily step count of 10,000 steps. However, it is important to consider the accuracy of activity monitors, particularly when physical activity in the form of stepping activities is prescribed as an intervention in the

  5. Activation of GSK-3β and Caspase-3 Occurs in Nigral Dopamine Neurons during the Development of Apoptosis Activated by a Striatal Injection of 6-Hydroxydopamine

    PubMed Central

    Hernandez-Baltazar, Daniel; Mendoza-Garrido, Maria E.; Martinez-Fong, Daniel

    2013-01-01

    The 6-Hydroxydopamine (6-OHDA) rat model of Parkinson's disease is essential for a better understanding of the pathological processes underlying the human disease and for the evaluation of promising therapeutic interventions. This work evaluated whether a single striatal injection of 6-OHDA causes progressive apoptosis of dopamine (DA) neurons and activation of glycogen synthase kinase 3β (GSK-3β) and caspase-3 in the substantia nigra compacta (SNc). The loss of DA neurons was shown by three neuron markers; tyrosine hydroxylase (TH), NeuN, and β-III tubulin. Apoptosis activation was determined using Apostain and immunostaining against cleaved caspase-3 and GSK-3β pY216. We also explored the possibility that cleaved caspase-3 is produced by microglia and astrocytes. Our results showed that the 6-OHDA caused loss of nigral TH(+) cells, progressing mainly in rostrocaudal and lateromedial directions. In the neostriatum, a severe loss of TH(+) terminals occurred from day 3 after lesion. The disappearance of TH(+) cells was associated with a decrease in NeuN and β-III tubulin immunoreactivity and an increase in Apostain, cleaved caspase-3, and GSK-3β pY216 in the SNc. Apostain immunoreactivity was observed from days 3 to 21 postlesion. Increased levels of caspase-3 immunoreactivity in TH(+) cells were detected from days 1 to 15, and the levels then decreased to day 30 postlesion. The cleaved caspase-3 also collocated with microglia and astrocytes indicating its participation in glial activation. Our results suggest that caspase-3 and GSK-3β pY216 activation might participate in the DA cell death and that the active caspase-3 might also participate in the neuroinflammation caused by the striatal 6-OHDA injection. PMID:23940672

  6. Inhibition of cyclooxygenase activity reduces rotavirus infection at a postbinding step.

    PubMed

    Rossen, John W A; Bouma, Janneke; Raatgeep, Rolien H C; Büller, Hans A; Einerhand, Alexandra W C

    2004-09-01

    Elevated levels of prostaglandins (PGs), products of cyclooxygenases (COXs), are found in the plasma and stool of rotavirus-infected children. We sought to determine the role of COXs, PGs, and the signal transduction pathways involved in rotavirus infection to elucidate possible new targets for antiviral therapy. Human intestinal Caco-2 cells were infected with human rotavirus Wa or simian rotavirus SA-11. COX-2 mRNA expression and secreted PGE2 levels were determined at different time points postinfection, and the effect of COX inhibitors on rotavirus infection was studied by an immunofluorescence assay (IFA). To reveal the signal transduction pathways involved, the effect of MEK, protein kinase A (PKA), p38 mitogen-activated protein kinase (MAPK), and NF-kappaB inhibitors on rotavirus infection was analyzed. In infected Caco-2 cells, increased COX-2 mRNA expression and secreted PGE2 levels were detected. Indomethacin (inhibiting both COX-1 and COX-2) and specific COX-1 and COX-2 inhibitors reduced rotavirus infection by 85 and 50%, respectively, as measured by an IFA. Indomethacin reduced virus infection at a postbinding step early in the infection cycle, inhibiting virus protein synthesis. Indomethacin did not seem to affect viral RNA synthesis. Inhibitors of MEK, PKA, p38 MAPK, and NF-kappaB decreased rotavirus infection by at least 40%. PGE2 counteracted the effect of the COX and PKA inhibitors but not of the MEK, p38 MAPK, and NF-kappaB inhibitors. Conclusively, COXs and PGE2 are important mediators of rotavirus infection at a postbinding step. The ERK1/2 pathway mediated by PKA is involved in COX induction by rotavirus infection. MAPK and NF-kappaB pathways are involved in rotavirus infection but in a PGE2-independent manner. This report offers new perspectives in the search for therapeutic agents in treatment of severe rotavirus-mediated diarrhea in children.

  7. Mechanochemical activation of vincamine mediated by linear polymers: assessment of some "critical" steps.

    PubMed

    Hasa, Dritan; Perissutti, Beatrice; Grassi, Mario; Chierotti, Michele R; Gobetto, Roberto; Ferrario, Valerio; Lenaz, Davide; Voinovich, Dario

    2013-09-27

    The aim of the research was to investigate three "critical steps" that deserve particular attention during the mechanochemical activation of vincamine. The first step consisted in the selection of the best polymeric carrier/most affine stabiliser between linear PVP and NaCMC by using the GRID and the GRID based AutoDock software packages which permit to calculate their surface features and interactions. Moreover, the calculation of the partial and total solubility parameters supported the results obtained by GRID and AutoDock software. Then, after the selection of linear PVP-K30 as the suitable carrier, the influence of process and formulation variables on the amorphisation degree and solubility enhancement was studied, to select the most suitable process conditions and formulation parameters. Subsequently, the best performing samples were widely characterised using XRPD, TEM and SSNMR (including the proton relaxation ((1)H T1 NMR) time) techniques. These studies highlighted that all the coground samples were nanocrystalline solid dispersions indicating a dramatic difference between the amorphisation capacities of linear PVP-K30 and cross-linked PVP, used in previous analogous experiences. In particular, (13)C, (15)N and (1)H T1 NMR data point to a description of the system as a dispersion of nanocrystals in the polymer. In these dispersions vincamine is in a disordered crystalline state due to extensive interactions and contacts with PVP-K30 but the main hydrogen bonding motif characterising its packing remains. Again, differently from cross-linked PVP, dissolution studies revealed that linear PVP-K30 was able to promote a complete in vitro solubilisation of vincamine in some coground samples. What is more important, by using a linear polymer, drug-to-polymer and milling time variables appeared less influent on the solid state and in vitro properties of the composites. Finally, stability studies conducted for a period of 1year highlighted the high physical

  8. Two-step chromatography purification of IgGs possessing sialidase activity from human blood serum.

    PubMed

    Kit, Yury; Bilyy, Rostyslav; Korniy, Nataliya; Tomin, Andriy; Chop'yak, Valentyna; Tolstyak, Yaroslav; Antonyuk, Volodymyr; Stoika, Rostyslav

    2015-03-01

    Sialation of cell surface is known to be tightly connected with tumorigenicity, invasiveness, metastatic potential and clearance of aged cells, while sialation of immunoglobulin G (IgG) molecules determines their anti-inflammatory properties. Recently, we have found for the first time IgG-antibodies possessing sialidase-like activity (sialylic abzyme) in blood serum of multiple myeloma and systemic lupus erythematosis patients. This abzyme was detected in a pool of IgGs purified by a typical procedure including immunoglobulin's precipitation with ammonium sulfate and following chromatography on protein G-Sepharose column. Here we describe a novel matrix for affinity purification of sialylic abzyme that is based on using bovine submandibular gland mucin conjugated to Sepharose matrix (mucin-Sepharose). This matrix preferentially binds sialidase-like IgGs from a pool of sialidase-active fraction of proteins precipitated with 50% ammonium sulfate from blood serum of the systemic lupus erythematosis patients. That allowed us to develop a new scheme of double-step chromatography purification of sialidase-like IgGs from human blood serum.

  9. Preparation of native cellulose-AgCl fiber with antimicrobial activity through one-step electrospinning.

    PubMed

    Wang, Shaojun; Zhang, Xiaomin; Luo, Ting; Zhu, Jin; Su, Shengpei

    2017-02-01

    The native Cellulose-AgCl fiber have been firstly fabricated by one-step electrospinning of cellulose solution with poly(vinyl pyrrolidone) (PVP) and AgNO3. X-ray diffraction, Scanning electron microscopy (SEM), Energy dispersive spectrometer, Thermo-gravimetric analysis and Fourier transform infrared are used to characterize the crystal structure, morphology and composition of cellulose-AgCl nanocomposites. The results of SEM indicate that the size of AgCl in cellulose fiber matrix is able to be adjusted by the addition of Polyvinylpyrrolidone (PVP). The antimicrobial activity of the nanocomposites fiber is also tested against the model microbes E. coli (Gram-negative) and S. aureus (Gram-positive). The results indicate that cellulose-AgCl nanocomposites have a good antimicrobial activity, which is improving with the decrease of AgCl size in fiber matrix. This work provides a novel and simple way to adjust the AgCl size in electrospinning cellulose matrix which can be applied as functional biomaterials.

  10. Targeted antigen delivery and activation of dendritic cells in vivo: steps towards cost effective vaccines.

    PubMed

    Tacken, Paul J; Figdor, Carl G

    2011-02-01

    During the past decade, the immunotherapeutic potential of ex vivo generated professional antigen presenting dendritic cells (DCs) has been explored in the clinic. Albeit safe, clinical results have thus far been limited. A major disadvantage of current cell-based dendritic cell (DC) therapies, preventing universal implementation of this form of immunotherapy, is the requirement that vaccines need to be tailor made for each individual. Targeted delivery of antigens to DC surface receptors in vivo would circumvent this laborious and expensive ex vivo culturing steps involved with these cell-based therapies. In addition, the opportunity to target natural and often rare DC subsets in vivo might have advantages over loading more artificial ex vivo cultured DCs. Preclinical studies show targeting antigens to DCs effectively induces humoral responses, while cellular responses are induced provided a DC maturation or activation stimulus is co-administered. Here, we discuss strategies to target antigens to distinct DC subsets and to simultaneously employ adjuvants to activate these cells to induce immunity.

  11. Hypothyroidism Enhanced Ectonucleotidases and Acetylcholinesterase Activities in Rat Synaptosomes can be Prevented by the Naturally Occurring Polyphenol Quercetin.

    PubMed

    Baldissarelli, Jucimara; Santi, Adriana; Schmatz, Roberta; Abdalla, Fátima Husein; Cardoso, Andréia Machado; Martins, Caroline Curry; Dias, Glaecir R Mundstock; Calgaroto, Nicéia Spanholi; Pelinson, Luana Paula; Reichert, Karine Paula; Loro, Vania Lucia; Morsch, Vera Maria Melchiors; Schetinger, Maria Rosa Chitolina

    2017-01-01

    Thyroid hormones have an influence on the functioning of the central nervous system. Furthermore, the cholinergic and purinergic systems also are extensively involved in brain function. In this context, quercetin is a polyphenol with antioxidant and neuroprotective properties. This study investigated the effects of (MMI)-induced hypothyroidism on the NTPDase, 5'-nucleotidase, adenosine deaminase (ADA), and acetylcholinesterase (AChE) activities in synaptosomes of rats and whether the quercetin can prevent it. MMI at a concentration of 20 mg/100 mL was administered for 90 days in the drinking water. The animals were divided into six groups: control/water (CT/W), control/quercetin 10 mg/kg, control/quercetin 25 mg/kg, methimazole/water (MMI/W), methimazole/quercetin 10 mg/kg (MMI/Q10), and methimazole/quercetin 25 mg/kg (MMI/Q25). On the 30th day, hormonal dosing was performed to confirm hypothyroidism, and the animals were subsequently treated with 10 or 25 mg/kg quercetin for 60 days. NTPDase activity was not altered in the MMI/W group. However, treatment with quercetin decreased ATP and ADP hydrolysis in the MMI/Q10 and MMI/Q25 groups. 5'-nucleotidase activity increased in the MMI/W group, but treatments with 10 or 25 mg/kg quercetin decreased 5'-nucleotidase activity. ADA activity decreased in the CT/25 and MMI/Q25 groups. Furthermore, AChE activity was reduced in all groups with hypothyroidism. In vitro tests also demonstrated that quercetin per se decreased NTPDase, 5'-nucleotidase, and AChE activities. This study demonstrated changes in the 5'-nucleotidase and AChE activities indicating that purinergic and cholinergic neurotransmission are altered in this condition. In addition, quercetin can alter these parameters and may be a promising natural compound with important neuroprotective actions in hypothyroidism.

  12. Protocol for the "four steps to control your fatigue (4-STEPS)" randomised controlled trial: a self-regulation based physical activity intervention for patients with unexplained chronic fatigue

    PubMed Central

    2012-01-01

    Background Unexplained Chronic Fatigue is a medical condition characterized by the presence of persistent, severe and debilitating medically unexplained fatigue, leading to impaired functioning and lower quality of life. Research suggests that physical activity can contribute to the reduction of fatigue and other somatic symptoms and can thus significantly improve physical functioning and quality of life in these patients. Based on the self-regulation (SR) theory of behaviour change, we developed a brief physical activity program for patients suffering from unexplained chronic fatigue which focuses on the training of self-regulation skills, the "4-STEPS to control your fatigue" program. Methods/Design This is a multi-centre, randomised controlled trial (RCT) that will be carried out in local primary care centres and at the Portuguese Fibromyalgia and Chronic Fatigue Syndrome Patients Association. Patients aged between 18 and 65 and fulfilling operationalized criteria for Idiopathic Chronic Fatigue (ICF) and Chronic Fatigue Syndrome (CFS) will be recruited and randomly allocated to standard care (SC) or standard care plus a self-regulation based physical activity program (4-STEPS). Patients will be assessed at baseline, after the intervention (3 months) and at 12 months follow-up. The primary outcome is fatigue severity. Discussion The results of the RCT will provide information about the effectiveness of a brief self-regulation intervention for promoting physical activity in patients with unexplained chronic fatigue. If the program proves to be effective, it may be considered as an adjunctive treatment for these patients. Trial Registration ISRCTN: ISRCTN70763996 PMID:22429404

  13. Ross River Virus Disease Activity Associated With Naturally Occurring Nontidal Flood Events in Australia: A Systematic Review.

    PubMed

    Tall, Julie A; Gatton, Michelle L; Tong, Shilu

    2014-11-01

    Ross River virus (RRV) disease is the most common and widespread mosquito-borne disease in Australia, resulting in considerable health and economic cost to communities. While naturally occurring nontidal flood events may enhance mosquito abundance, little is known about the impact of such events on RRV transmission. This article critically reviews the existing evidence for an association between naturally occurring nontidal flood events and RRV transmission. A systematic literature search was conducted on RRV transmission related to flooding and inundation from rain and riverine overflow. Overall, the evidence to support a positive association between flooding and RRV outbreaks is largely circumstantial, with the literature mostly reporting only coincidental occurrence between the two. However, for the Murray River, river flow and height (surrogates of flooding) were positively and significantly associated with RRV transmission. The association between nontidal flooding and RRV transmission has not been studied comprehensively. More frequent flood events arising from climate change may result in increased outbreaks of RRV disease. Understanding the link between flood events and RRV transmission is necessary if resources for mosquito spraying and public health warnings are to be used more effectively and efficiently.

  14. GATA Factor Regulation in Excess Nitrogen Occurs Independently of Gtr-Ego Complex-Dependent TorC1 Activation

    PubMed Central

    Tate, Jennifer J.; Georis, Isabelle; Rai, Rajendra; Vierendeels, Fabienne; Dubois, Evelyne; Cooper, Terrance G.

    2015-01-01

    The TorC1 protein kinase complex is a central component in a eukaryotic cell’s response to varying nitrogen availability, with kinase activity being stimulated in nitrogen excess by increased intracellular leucine. This leucine-dependent TorC1 activation requires functional Gtr1/2 and Ego1/3 complexes. Rapamycin inhibition of TorC1 elicits nuclear localization of Gln3, a GATA-family transcription activator responsible for the expression of genes encoding proteins required to transport and degrade poor nitrogen sources, e.g., proline. In nitrogen-replete conditions, Gln3 is cytoplasmic and Gln3-mediated transcription minimal, whereas in nitrogen limiting or starvation conditions, or after rapamycin treatment, Gln3 is nuclear and transcription greatly increased. Increasing evidence supports the idea that TorC1 activation may not be as central to nitrogen-responsive intracellular Gln3 localization as envisioned previously. To test this idea directly, we determined whether Gtr1/2- and Ego1/3-dependent TorC1 activation also was required for cytoplasmic Gln3 sequestration and repressed GATA factor-mediated transcription by abolishing the Gtr-Ego complex proteins. We show that Gln3 is sequestered in the cytoplasm of gtr1Δ, gtr2Δ, ego1Δ, and ego3Δ strains either long term in logarithmically glutamine-grown cells or short term after refeeding glutamine to nitrogen-limited or -starved cells; GATA factor−dependent transcription also was minimal. However, in all but a gtr1Δ, nuclear Gln3 localization in response to nitrogen limitation or starvation was adversely affected. Our data demonstrate: (i) Gtr-Ego-dependent TorC1 activation is not required for cytoplasmic Gln3 sequestration in nitrogen-rich conditions; (ii) a novel Gtr-Ego-TorC1 activation-independent mechanism sequesters Gln3 in the cytoplasm; (iii) Gtr and Ego complex proteins participate in nuclear Gln3-Myc13 localization, heretofore unrecognized functions for these proteins; and (iv) the importance of

  15. Thermally activated step motion observed by HREM at a (113) symmetric tilt grain boundary in Al.

    SciTech Connect

    Merkle, K. L.; Thompson, L. J.; Phillipp, F.; Materials Science Division; Max-Planck-Inst.

    2002-11-01

    Grain-boundary migration is demonstrated to proceed by lateral propagation of a small step in a (113), [110] symmetric Al tilt grain-boundary. In-situ high-resolution (transmission) electron microscopy (HREM) at 523K allowed the study of atomic-scale detail at video rates during the migration process. The grain-boundary translational states on both sides of the step are identical, which leads to a step dislocation. This defect can move laterally by a combination of climb and glide. Dynamic HREM images indicate considerable atomic agitation within the dislocation core. A detailed temporal analysis of the step movements shows small random displacements of the dislocation core.

  16. Naturally Occurring Changes in Time Spent Watching Television Are Inversely Related to Frequency of Physical Activity during Early Adolescence

    ERIC Educational Resources Information Center

    Motl, Robert W.; McAuley, Edward; Birnbaum, Amanda S.; Lytle, Leslie A.

    2006-01-01

    In this longitudinal study, we examined the relationship between changes in time spent watching television and playing video games with frequency of leisure-time physical activity across a 2-year period among adolescent boys and girls (N=4594). Latent growth modelling indicated that a decrease in time spent watching television was associated with…

  17. Identification of a small molecule inhibitor that stalls splicing at an early step of spliceosome activation

    PubMed Central

    Sidarovich, Anzhalika; Will, Cindy L; Anokhina, Maria M; Ceballos, Javier; Sievers, Sonja; Agafonov, Dmitry E; Samatov, Timur; Bao, Penghui; Kastner, Berthold; Urlaub, Henning; Waldmann, Herbert; Lührmann, Reinhard

    2017-01-01

    Small molecule inhibitors of pre-mRNA splicing are important tools for identifying new spliceosome assembly intermediates, allowing a finer dissection of spliceosome dynamics and function. Here, we identified a small molecule that inhibits human pre-mRNA splicing at an intermediate stage during conversion of pre-catalytic spliceosomal B complexes into activated Bact complexes. Characterization of the stalled complexes (designated B028) revealed that U4/U6 snRNP proteins are released during activation before the U6 Lsm and B-specific proteins, and before recruitment and/or stable incorporation of Prp19/CDC5L complex and other Bact complex proteins. The U2/U6 RNA network in B028 complexes differs from that of the Bact complex, consistent with the idea that the catalytic RNA core forms stepwise during the B to Bact transition and is likely stabilized by the Prp19/CDC5L complex and related proteins. Taken together, our data provide new insights into the RNP rearrangements and extensive exchange of proteins that occurs during spliceosome activation. DOI: http://dx.doi.org/10.7554/eLife.23533.001 PMID:28300534

  18. Steps to Self-Determination: A Curriculum To Help Adolescents Learn To Achieve Their Goals. Student Activity Book.

    ERIC Educational Resources Information Center

    Field, Sharon; Hoffman, Alan

    This student activity book includes worksheets that secondary students with and without disabilities can use to complete each activity in the "Steps to Self-Determination" curriculum. The program is meant to assist students in learning more about themselves and developing the skills they need to achieve their goals, getting support from family and…

  19. Activation and Desensitization of Peripheral Muscle and Neuronal Nicotinic Acetylcholine Receptors by Selected, Naturally-Occurring Pyridine Alkaloids

    PubMed Central

    Green, Benedict T.; Lee, Stephen T.; Welch, Kevin D.; Cook, Daniel; Kem, William R.

    2016-01-01

    Teratogenic alkaloids can cause developmental defects due to the inhibition of fetal movement that results from desensitization of fetal muscle-type nicotinic acetylcholine receptors (nAChRs). We investigated the ability of two known teratogens, the piperidinyl-pyridine anabasine and its 1,2-dehydropiperidinyl analog anabaseine, to activate and desensitize peripheral nAChRs expressed in TE-671 and SH-SY5Y cells. Activation-concentration response curves for each alkaloid were obtained in the same multi-well plate. To measure rapid desensitization, cells were first exposed to five potentially-desensitizing concentrations of each alkaloid in log10 molar increments from 10 nM to 100 µM and then to a fixed concentration of acetylcholine (ACh), which alone produces near-maximal activation. The fifty percent desensitization concentration (DC50) was calculated from the alkaloid concentration-ACh response curve. Agonist fast desensitization potency was predicted by the agonist potency measured in the initial response. Anabaseine was a more potent desensitizer than anabasine. Relative to anabaseine, nicotine was more potent to autonomic nAChRs, but less potent to the fetal neuromuscular nAChRs. Our experiments have demonstrated that anabaseine is more effective at desensitizing fetal muscle-type nAChRs than anabasine or nicotine and, thus, it is predicted to be more teratogenic. PMID:27384586

  20. Antimicrobial activity of plumbagin, a naturally occurring naphthoquinone from Plumbago rosea, against Staphylococcus aureus and Candida albicans.

    PubMed

    Nair, Sweatha V; Baranwal, Gaurav; Chatterjee, Maitrayee; Sachu, Arun; Vasudevan, Anil Kumar; Bose, Chinchu; Banerji, Asoke; Biswas, Raja

    2016-06-01

    Candida albicans and Staphylococcus aureus are opportunistic pathogens. Despite causing a number of independent infections, both pathogens can co-infect to cause urinary tract infections, skin infections, biofilm associated infections, sepsis and pneumonia. Infections of these two pathogens especially their biofilm associated infections are often difficult to treat using currently available anti-bacterial and anti-fungal agents. In order to identify a common anti-microbial agent which could confer a broad range of protection against their infections, we screened several phytochemicals and identified plumbagin (5-hydroxy-2-methyl-1,4-naphthoquinone), a phytochemical from Plumbago species as a potent antimicrobial agent against S. aureus and C. albicans, with a minimum inhibitory concentration of 5μg/ml. Antimicrobial activity of plumbagin was validated using an ex-vivo porcine skin model. For better understanding of the antimicrobial activity of plumbagin, a Drosophila melanogaster infection model was used, where D. melanogaster was infected using S. aureus and C. albicans, or with both organisms. The fly's survival rate was dramatically increased when infected flies were treated using plumbagin. Further, plumbagin was effective in preventing and dispersing catheter associated biofilms formed by these pathogens. The overall results of this work provides evidence that plumbagin, possesses an excellent antimicrobial activity which should be explored further for the treatment of S. aureus and C. albicans infections.

  1. Protein Immobilization on Carbon Nanotubes Via a Two-Step Process of Diimide-Activated Amidation

    SciTech Connect

    Jiang, Kuiyang; Schadler, Linda S.; Siegel, Richard W.; Zhang, Xinjie; Zhang, Haifeng; Terrones, Mauricio

    2004-11-06

    Carbon nanotubes exhibit interesting electrical, structural and mechanical properties that make them highly promising nanoscale building blocks for the construction of novel functional materials. Many potential applications have been proposed, such as conductive and high-strength composites, field emission displays, fuel cells, sensors, and hydrogen storage media. In addition, biosensors for detecting abnormalities and bio-fuel cells for embedded devices are among the most exciting applications. In order to create the synergy between the biomolecules and nanotubes required to realize these applications, biomolecules, such as proteins and DNAs, must be connected to the carbon nanotubes. This connection can be non-covalent interaction or covalent bonding. There have been several reports on the immobilization of biomolecules on carbon nanotubes, and most of them use non-covalent interaction. The best stability, accessibility and selectivity, however, will be achieved through covalent bonding because of its capability to control the location of the biomolecule, improve stability, accessibility and selectivity and reduce leaching. In the present study, we report the covalent bonding of proteins to nitrogen-doped multiwalled carbon nanotubes (CNx MWNTs) via a two-step process of diimide-activated amidation between the carboxylic acid groups on CNx MWNTs and the amine groups on proteins.

  2. Non-Nutrient, Naturally Occurring Phenolic Compounds with Antioxidant Activity for the Prevention and Treatment of Periodontal Diseases

    PubMed Central

    Varela-López, Alfonso; Bullón, Pedro; Giampieri, Francesca; Quiles, José L.

    2015-01-01

    One of the main factors able to explain the pathophysiological mechanism of inflammatory conditions that occur in periodontal disease is oxidative stress. Given the emerging understanding of this relationship, host-modulatory therapies using antioxidants could be interesting to prevent or slow the breakdown of soft and hard periodontal tissues. In this context, non-nutrient phenolic compounds of various foods and plants have received considerable attention in the last decade. Here, studies focusing on the relationship between different compounds of this type with periodontal disease have been collected. Among them, thymoquinone, coenzyme Q (CoQ), mangiferin, resveratrol, verbascoside and some flavonoids have shown to prevent or ameliorate periodontal tissues damage in animal models. However evidence regarding this effect in humans is poor and only limited to topical treatments with CoQ and catechins. Along with animal experiments, in vitro studies indicate that possible mechanisms by which these compounds might exert their protective effects include antioxidative properties, oxygen and nitrogen scavenging abilities, and also inhibitory effects on cell signaling cascades related to inflammatory processes which have an effect on RNS or ROS production as well as on antioxidant defense systems. PMID:26783837

  3. Skin-mimetic chromatography for prediction of human percutaneous absorption of biologically active compounds occurring in medicinal plant extracts.

    PubMed

    Stepnik, Katarzyna; Malinowska, Irena

    2017-04-01

    The main aim of this study was to predict quantitatively human percutaneous absorption of chosen compounds commonly occurring in plants which can be used as medicinal extracts in the drug and beauty industries. The most important human percutaneous descriptors, i.e. logKp (logarithm of the water/skin partition coefficient) and logJmax (logarithm of the maximum flux of solutes penetrating the skin), of fatty acids and polyphenols were determined using both in vitro and in silico methods. For in vitro determination of human percutaneous absorption, micellar liquid chromatography based on hexadecyltrimethylammonium bromide, sodium dodecyl sulfate and polyoxyethylene (23) lauryl ether (Brij35) was used. Human percutaneous absorption was characterized by entirely new QSAR/QRAR models based on retention, lipophilic, steric and electronic data as well as on the linear free energy relationship parameters. Many different correlations between human skin absorption and different physicochemical parameters were performed, e.g. the in silico estimated logKp value was correlated with the retention parameter logkw (logarithm of the retention factor extrapolated to pure water) from the systems imitating a cutaneous environment (R(2)  = 0.92). Moreover, the influence of lipophilicity on percutaneous absorption was examined. The obtained correlation was excellent (R(2)  = 0.95).

  4. Non-Nutrient, Naturally Occurring Phenolic Compounds with Antioxidant Activity for the Prevention and Treatment of Periodontal Diseases.

    PubMed

    Varela-López, Alfonso; Bullón, Pedro; Giampieri, Francesca; Quiles, José L

    2015-06-24

    One of the main factors able to explain the pathophysiological mechanism of inflammatory conditions that occur in periodontal disease is oxidative stress. Given the emerging understanding of this relationship, host-modulatory therapies using antioxidants could be interesting to prevent or slow the breakdown of soft and hard periodontal tissues. In this context, non-nutrient phenolic compounds of various foods and plants have received considerable attention in the last decade. Here, studies focusing on the relationship between different compounds of this type with periodontal disease have been collected. Among them, thymoquinone, coenzyme Q (CoQ), mangiferin, resveratrol, verbascoside and some flavonoids have shown to prevent or ameliorate periodontal tissues damage in animal models. However evidence regarding this effect in humans is poor and only limited to topical treatments with CoQ and catechins. Along with animal experiments, in vitro studies indicate that possible mechanisms by which these compounds might exert their protective effects include antioxidative properties, oxygen and nitrogen scavenging abilities, and also inhibitory effects on cell signaling cascades related to inflammatory processes which have an effect on RNS or ROS production as well as on antioxidant defense systems.

  5. Very High Concentrations of Active Intracellular Phosphorylated Emtricitabine in Neonates (ANRS 12109 Trial, Step 2)▿

    PubMed Central

    Hirt, Déborah; Pruvost, Alain; Ekouévi, Didier K.; Urien, Saïk; Arrivé, Elise; Kone, Mamourou; Nerrienet, Eric; Nyati, Mandisa; Gray, Glenda; Kruy, Leang Sim; Blanche, Stéphane; Dabis, François; Tréluyer, Jean-Marc

    2011-01-01

    Our objective was to investigate neonatal emtricitabine (FTC) plasma and intracellular pharmacokinetics. The study was designed as a phase I/II prospective trial in two sequential steps evaluating the combination of tenofovir disoproxil fumarate (TDF) and FTC for the prevention of mother-to-child-transmission (PMTCT) of HIV. HIV-1-infected pregnant women received two tablets of TDF (300 mg) and FTC (200 mg) at onset of labor and then one tablet daily for 7 days postpartum. Based on the data obtained in the first part of the Tenofovir/Emtricitabine in Africa and Asia (TEmAA) Study, single doses of 2 mg/kg of FTC and 13 mg/kg of TDF were given to the neonates within 12 h after birth. A total of 540 FTC plasma concentrations and 44 active intracellular phosphorylated metabolite FTC-TP concentrations were taken from the 36 enrolled women and their neonates. Concentrations were measured by the liquid chromatography-tandem mass spectrometry (LC-MS/MS) method and analyzed by a population approach. The proposed dose obtained by simulations based on plasma drug concentrations was confirmed. However, median FTC-TP exposures were, respectively, 5.9 and 6.8 times higher in the fetus and the neonate than in the adult. High FTC-TP concentrations were observed in the four children who had serious adverse events (SAEs), but the link between FTC-TP concentrations and SAEs in children was not formally identified. The exposure to the active form of FTC was high in neonates despite plasma drug concentrations equivalent to those in adults. Our results are similar to those obtained with zidovudine or lamivudine. PMID:21464241

  6. Injury-induced GR-1+ macrophage expansion and activation occurs independently of CD4 T-cell influence.

    PubMed

    O'Leary, Fionnuala M; Tajima, Goro; Delisle, Adam J; Ikeda, Kimiko; Dolan, Sinead M; Hanschen, Marc; Mannick, John A; Lederer, James A

    2011-08-01

    Burn injury initiates an enhanced inflammatory condition referred to as the systemic inflammatory response syndrome or the two-hit response phenotype. Prior reports indicated that macrophages respond to injury and demonstrate a heightened reactivity to Toll-like receptor stimulation. Since we and others observed a significant increase in splenic GR-1 F4/80 CD11b macrophages in burn-injured mice, we wished to test if these macrophages might be the primary macrophage subset that shows heightened LPS reactivity. We report here that burn injury promoted higher level TNF-α expression in GR-1, but not GR-1 macrophages, after LPS activation both in vivo and ex vivo. We next tested whether CD4 T cells, which are known to suppress injury-induced inflammatory responses, might control the activation and expansion of GR-1 macrophages. Interestingly, we found that GR-1 macrophage expansion and LPS-induced TNF-α expression were not significantly different between wild-type and CD4 T cell-deficient CD4(-/-) mice. However, further investigations showed that LPS-induced TNF-α production was significantly influenced by CD4 T cells. Taken together, these data indicate that GR-1 F4/80 CD11b macrophages represent the primary macrophage subset that expands in response to burn injury and that CD4 T cells do not influence the GR-1 macrophage expansion process, but do suppress LPS-induced TNF-α production. These data suggest that modulating GR-1 macrophage activation as well as CD4 T cell responses after severe injury may help control the development of systemic inflammatory response syndrome and the two-hit response phenotype.

  7. Effector and Naturally Occurring Regulatory T Cells Display No Abnormalities in Activation Induced Cell Death in NOD Mice

    PubMed Central

    Kaminitz, Ayelet; Yolcu, Esma S.; Askenasy, Enosh M.; Stein, Jerry; Yaniv, Isaac; Shirwan, Haval; Askenasy, Nadir

    2011-01-01

    Background Disturbed peripheral negative regulation might contribute to evolution of autoimmune insulitis in type 1 diabetes. This study evaluates the sensitivity of naïve/effector (Teff) and regulatory T cells (Treg) to activation-induced cell death mediated by Fas cross-linking in NOD and wild-type mice. Principal Findings Both effector (CD25−, FoxP3−) and suppressor (CD25+, FoxP3+) CD4+ T cells are negatively regulated by Fas cross-linking in mixed splenocyte populations of NOD, wild type mice and FoxP3-GFP tranegenes. Proliferation rates and sensitivity to Fas cross-linking are dissociated in Treg cells: fast cycling induced by IL-2 and CD3/CD28 stimulation improve Treg resistance to Fas-ligand (FasL) in both strains. The effector and suppressor CD4+ subsets display balanced sensitivity to negative regulation under baseline conditions, IL-2 and CD3/CD28 stimulation, indicating that stimulation does not perturb immune homeostasis in NOD mice. Effective autocrine apoptosis of diabetogenic cells was evident from delayed onset and reduced incidence of adoptive disease transfer into NOD.SCID by CD4+CD25− T cells decorated with FasL protein. Treg resistant to Fas-mediated apoptosis retain suppressive activity in vitro. The only detectable differential response was reduced Teff proliferation and upregulation of CD25 following CD3-activation in NOD mice. Conclusion These data document negative regulation of effector and suppressor cells by Fas cross-linking and dissociation between sensitivity to apoptosis and proliferation in stimulated Treg. There is no evidence that perturbed AICD in NOD mice initiates or promotes autoimmune insulitis. PMID:21738739

  8. Zn2+-dependent Activation of the Trk Signaling Pathway Induces Phosphorylation of the Brain-enriched Tyrosine Phosphatase STEP

    PubMed Central

    Poddar, Ranjana; Rajagopal, Sathyanarayanan; Shuttleworth, C. William; Paul, Surojit

    2016-01-01

    Excessive release of Zn2+ in the brain is implicated in the progression of acute brain injuries. Although several signaling cascades have been reported to be involved in Zn2+-induced neurotoxicity, a potential contribution of tyrosine phosphatases in this process has not been well explored. Here we show that exposure to high concentrations of Zn2+ led to a progressive increase in phosphorylation of the striatal-enriched phosphatase (STEP), a component of the excitotoxic-signaling pathway that plays a role in neuroprotection. Zn2+-mediated phosphorylation of STEP61 at multiple sites (hyperphosphorylation) was induced by the up-regulation of brain-derived neurotropic factor (BDNF), tropomyosin receptor kinase (Trk) signaling, and activation of cAMP-dependent PKA (protein kinase A). Mutational studies further show that differential phosphorylation of STEP61 at the PKA sites, Ser-160 and Ser-221 regulates the affinity of STEP61 toward its substrates. Consistent with these findings we also show that BDNF/Trk/PKA mediated signaling is required for Zn2+-induced phosphorylation of extracellular regulated kinase 2 (ERK2), a substrate of STEP that is involved in Zn2+-dependent neurotoxicity. The strong correlation between the temporal profile of STEP61 hyperphosphorylation and ERK2 phosphorylation indicates that loss of function of STEP61 through phosphorylation is necessary for maintaining sustained ERK2 phosphorylation. This interpretation is further supported by the findings that deletion of the STEP gene led to a rapid and sustained increase in ERK2 phosphorylation within minutes of exposure to Zn2+. The study provides further insight into the mechanisms of regulation of STEP61 and also offers a molecular basis for the Zn2+-induced sustained activation of ERK2. PMID:26574547

  9. Sesamin: A Naturally Occurring Lignan Inhibits CYP3A4 by Antagonizing the Pregnane X Receptor Activation.

    PubMed

    Lim, Yun-Ping; Ma, Chia-Yun; Liu, Cheng-Ling; Lin, Yu-Hsien; Hu, Miao-Lin; Chen, Jih-Jung; Hung, Dong-Zong; Hsieh, Wen-Tsong; Huang, Jin-Ding

    2012-01-01

    Inconsistent expression and regulation of drug-metabolizing enzymes (DMEs) are common causes of adverse drug effects in some drugs with a narrow therapeutic index (TI). An important cytochrome, cytochrome P450 3A4 (CYP3A4), is predominantly regulated by a nuclear receptor, pregnane X receptor (PXR). Sesamin, a major lignan constituent in sesame seeds and oil, exhibits a variety of biological functions; however, the effect of sesamin on the modulation of CYP3A4 is not well understood. In this study, the effects of sesamin on the PXR-CYP3A4 pathway were characterized, as well as the underlying mechanisms of those effects. Sesamin potently attenuated CYP3A4 induction in a dose-dependent manner by blocking the activation of PXR. The PXR inducer-mediated inhibition of CYP3A4 was further evidenced by the ability of sesamin to attenuate the effects of several PXR ligands in the CYP3A4 reporter assay. Further mechanistic studies showed that sesamin inhibited PXR by interrupting the interacting with coregulators. These results may lead to the development of new therapeutic and dietary approaches to reduce the frequency of inducer-drug interaction. Sesamin was established as a novel inhibitor of PXR and may be useful for modulating DMEs expression and drug efficacies. Modification of CYP3A4 expression and activity by consumption of sesamin may have important implications for drug safety.

  10. Subchronic oral toxicity and cardiovascular safety pharmacology studies of resveratrol, a naturally occurring polyphenol with cancer preventive activity

    PubMed Central

    Johnson, W.D.; Morrissey, R.L.; Usborne, A.L.; Kapetanovic, I.; Crowell, J.A.; Muzzio, M.; McCormick, D.L.

    2011-01-01

    To characterize the subchronic oral toxicity of resveratrol, CD rats received daily gavage doses of 0, 200, 400, or 1000 mg resveratrol/kg/day, and beagle dogs received daily capsule doses of 0, 200, 600, or 1200 mg resveratrol/kg/day for 90 days. Resveratrol induced only minimal toxicity, consisting of dose-related reductions in body weight gain in female rats and both sexes of dogs, and a statistically significant increase in bilirubin levels in rats at the 1000 mg/kg/day dose. Clinical observations, hematology, ophthalmology, neurotoxicity evaluations (functional observational batteries), organ weights, and gross pathology provided no biologically significant evidence of resveratrol toxicity in either species. In rats, the high dose of resveratrol reduced the incidence of cardiomyopathy; no other microscopic changes were seen. Histopathologic changes in dogs were limited to minimal inflammatory infiltrates in the kidney and urinary bladder, which were not considered toxicologically significant. A cardiovascular safety pharmacology (telemetry) study in dogs revealed no evidence of resveratrol toxicity. Based on body weight effects, the No Observed Adverse Effect Level (NOAEL) for resveratrol was 200 mg/kg/day in rats and 600 mg/kg/day in dogs. The apparent cardioprotective activity of resveratrol in rats demonstrates that its potentially beneficial activities may extend beyond efficacy in cancer prevention. PMID:21939727

  11. Where does brain neural activation in aesthetic responses to visual art occur? Meta-analytic evidence from neuroimaging studies.

    PubMed

    Boccia, M; Barbetti, S; Piccardi, L; Guariglia, C; Ferlazzo, F; Giannini, A M; Zaidel, D W

    2016-01-01

    Here we aimed at finding the neural correlates of the general aspect of visual aesthetic experience (VAE) and those more strictly correlated with the content of the artworks. We applied a general activation likelihood estimation (ALE) meta-analysis to 47 fMRI experiments described in 14 published studies. We also performed four separate ALE analyses in order to identify the neural substrates of reactions to specific categories of artworks, namely portraits, representation of real-world-visual-scenes, abstract paintings, and body sculptures. The general ALE revealed that VAE relies on a bilateral network of areas, and the individual ALE analyses revealed different maximal activation for the artworks' categories as function of their content. Specifically, different content-dependent areas of the ventral visual stream are involved in VAE, but a few additional brain areas are involved as well. Thus, aesthetic-related neural responses to art recruit widely distributed networks in both hemispheres including content-dependent brain areas of the ventral visual stream. Together, the results suggest that aesthetic responses are not independent of sensory, perceptual, and cognitive processes.

  12. Stepping motor controller

    DOEpatents

    Bourret, Steven C.; Swansen, James E.

    1984-01-01

    A stepping motor is microprocessingly controlled by digital circuitry which monitors the output of a shaft encoder adjustably secured to the stepping motor and generates a subsequent stepping pulse only after the preceding step has occurred and a fixed delay has expired. The fixed delay is variable on a real-time basis to provide for smooth and controlled deceleration.

  13. Stepping motor controller

    DOEpatents

    Bourret, S.C.; Swansen, J.E.

    1982-07-02

    A stepping motor is microprocessor controlled by digital circuitry which monitors the output of a shaft encoder adjustably secured to the stepping motor and generates a subsequent stepping pulse only after the preceding step has occurred and a fixed delay has expired. The fixed delay is variable on a real-time basis to provide for smooth and controlled deceleration.

  14. SALSA: A Regulator of the Early Steps of Complement Activation on Mucosal Surfaces.

    PubMed

    Reichhardt, Martin Parnov; Meri, Seppo

    2016-01-01

    Complement is present mainly in blood. However, following mechanical damage or inflammation, serous exudates enter the mucosal surfaces. Here, the complement proteins interact with other endogenous molecules to keep microbes from entering the parenteral tissues. One of the mucosal proteins known to interact with the early complement components of both the classical and the lectin pathway is the salivary scavenger and agglutinin (SALSA). SALSA is also known as deleted in malignant brain tumors 1 and gp340. It is found both attached to the epithelium and secreted into the surrounding fluids of most mucosal surfaces. SALSA has been shown to bind directly to C1q, mannose-binding lectin, and the ficolins. Through these interactions SALSA regulates activation of the complement system. In addition, SALSA interacts with surfactant proteins A and D, secretory IgA, and lactoferrin. Ulcerative colitis and Crohn's disease are examples of diseases, where complement activation in mucosal tissues may occur. This review describes the latest advances in our understanding of how the early complement components interact with the SALSA molecule. Furthermore, we discuss how these interactions may affect disease propagation on mucosal surfaces in immunological and inflammatory diseases.

  15. Sensory feedback induced by front-leg stepping entrains the activity of central pattern generators in caudal segments of the stick insect walking system.

    PubMed

    Borgmann, Anke; Hooper, Scott L; Büschges, Ansgar

    2009-03-04

    Legged locomotion results from a combination of central pattern generating network (CPG) activity and intralimb and interlimb sensory feedback. Data on the neural basis of interlimb coordination are very limited. We investigated here the influence of stepping in one leg on the activities of neighboring-leg thorax-coxa (TC) joint CPGs in the stick insect (Carausius morosus). We used a new approach combining single-leg stepping with pharmacological activation of segmental CPGs, sensory stimulation, and additional stepping legs. Stepping of a single front leg could activate the ipsilateral mesothoracic TC CPG. Activation of the metathoracic TC CPG required that both ipsilateral front and middle legs were present and that one of these legs was stepping. Unlike the situation in real walking, ipsilateral mesothoracic and metathoracic TC CPGs activated by front-leg stepping fired in phase with the front-leg stepping. Local (intralimb) sensory feedback from load sensors could override this intersegmental influence of front-leg stepping, shifting retractor motoneuron activity relative to the front-leg step cycle and thereby uncoupling them from front-leg stepping. These data suggest that front-leg stepping in isolation would result in in-phase activity of all ipsilateral legs, and functional stepping gaits (in which the three ipsilateral legs do not step in synchrony) emerge because of local load sensory feedback overriding this in-phase influence.

  16. In Vitro and In Vivo Antibacterial Activities of Patchouli Alcohol, a Natural-occurring Tricyclic Sesquiterpene against Helicobacter pylori Infection.

    PubMed

    Xu, Y F; Lian, D W; Chen, Y Q; Cai, Y F; Zheng, Y F; Fan, P L; Ren, W K; Fu, L J; Li, Y C; Xie, J H; Cao, H Y; Tan, B; Su, Z R; Huang, P

    2017-03-20

    This study further evaluated the in vitro and in vivo anti-Helicobacter pylori activity and potential underlying mechanism of patchouli alcohol (PA), a tricyclic sesquiterpene. In in vitro assay, the capacities of PA to inhibit and kill H. pylori were tested on three standard strains at different pH values and 12 clinical isolates. The effects of PA on H. pylori adhesion (and its alpA, alpB and babA genes), motility (and its flaA and flaB genes), ultrastructure and flagellation were investigated. Moreover, the H. pylori resistance and post-antibiotic effect (PAE) of PA were determined. Furthermore, the in vivo effects of PA on H. pylori eradication and gastritis were examined. Results showed that MICs of PA against three standard strains (pH 5.3-9) and twelve clinical isolates were 25-75 and 12.5-50 μg/ml, respectively. The killing kinetics of PA were time- and concentration- dependent, and its MBCs were 25-75 μg/ml. Besides, H. pylori adhesion, motility, ultrastructure and flagellation were significantly suppressed. PA also remarkably inhibited the expression of adhesion genes (alpA and alpB), and motility genes (flaA and flaB). Furthermore, PA treatment caused a long PAE and less bacterial resistance as compared with clarithromycin and metronidazole. The in vivo study showed that PA can effectively eradicate H. pylori, inhibit gastritis, and suppress the expression of inflammatory mediators (Cox-2, Il-1β, Tnf-α and Inos). In conclusion, PA can efficiently kill H. pylori, interfere with its infection process and attenuate gastritis with less bacterial resistance, making it a potential candidate for new drug development.

  17. Desulphurization performance of TiO2-modified activated carbon by a one-step carbonization-activation method.

    PubMed

    Zhang, Chuanjun; Yang, Danni; Jiang, Xia; Jiang, Wenju

    2016-08-01

    In this study, TiO2 powder was used as the additive to directly blend with raw bituminous coal and coking coal for preparing modified activated carbon (Ti/AC) by one-step carbonization-activation method. The Ti/AC samples were prepared through blending with different ratios of TiO2 (0-12 wt%) and their desulphurization performance was evaluated. The results show that the desulphurization activity of all Ti/AC samples was higher than that of the blank one, and the highest breakthrough sulphur capacity was obtained at 200.55 mg/g C when the blending ratio of TiO2 was 6 wt%. The Brunauer-Emmett-Temer results show that the micropores were dominant in the Ti/AC samples, and their textual properties did not change evidently compared with the blank one. The X-ray photoelectron spectroscopy results show that the loaded TiO2 could influence the relative content of surface functional groups, with slightly higher content of π-π* transitions groups on the Ti/AC samples, and the relative contents of C=O and π-π* transitions groups decreased evidently after the desulphurization process. The X-ray diffraction results show that the anatase TiO2 and rutile TiO2 co-existed on the surface of the Ti/AC samples. After the desulphurization process, TiO2 phases did not change and Ti(SO4)2 was not observed on the Ti/AC samples, while sulphate was the main desulphurization product. It can be assumed that SO2 could be catalytically oxidized into SO3 by TiO2 indirectly, rather than TiO2 directly reacted with SO2 to Ti(SO4)2.

  18. Online mutability of step direction during rapid stepping reactions evoked by postural perturbation.

    PubMed

    Tripp, Bryan P; McIlroy, William E; Maki, Brian E

    2004-03-01

    Stepping reactions are often triggered rapidly in response to loss of balance. It has been unclear whether spatial step parameters are defined at time of step-initiation or whether they can be modulated online, during step execution, in response to sensory feedback about the evolving state of instability. This study explored the capacity to actively alter step direction subsequent to step initiation in six healthy young-adult subjects. To elicit forward-step reactions, subjects were released suddenly from a tethered forward lean. A second perturbation (medio-lateral support-surface translation) was applied at lags of 0-200 ms. Active reaction to the second perturbation was determined primarily through analysis of swing-leg hip-abductor activation. In addition, to gauge the biomechanical consequence of the changes in muscle activation, we compared the measured medio-lateral swing-foot displacement to that predicted by a simple passive mechanical model. Perturbations at 0-100 ms lag evoked active medio-lateral swing-foot deviation, allowing balance to be recovered with a single step. However, when the second perturbation occurred near foot-off (200-ms lag), there was no evidence of active alteration of step direction and subjects typically required additional steps to recover balance. The results suggest that step direction can be reparameterized during early stages of stepping reactions, but that step direction was not actively modulated in response to perturbation arising near start of swing phase.

  19. Security: Step by Step

    ERIC Educational Resources Information Center

    Svetcov, Eric

    2005-01-01

    This article provides a list of the essential steps to keeping a school's or district's network safe and sound. It describes how to establish a security architecture and approach that will continually evolve as the threat environment changes over time. The article discusses the methodology for implementing this approach and then discusses the…

  20. Comparison of morphology of active cyclic steps created by turbidity currents on Squamish Delta, British Columbia, Canada with flume experiments

    NASA Astrophysics Data System (ADS)

    Yokokawa, Miwa; Yamamoto, Shinya; Higuchi, Hiroyuki; Hughes Clarke, John E.; Izumi, Norihiro

    2015-04-01

    Upper-flow-regime bedforms, such as cyclic steps and antidunes, have been reported to be formed by turbidity currents. Their formative conditions are, however, not fully understood because of the difficulty of field surveys in the deep sea. Field observations of turbidity currents and seabed topography on the Squamish delta in Howe Sound, British Columbia, Canada have been undertaken which found bedwaves actively migrating in the upstream direction in channels formed on the prodelta slope. Their topography and behavior suggest that they are cyclic steps formed by turbidity currents. Because Squamish delta is as shallow as around 150 m, and easy to access compared with general submarine canyons, it is thought to be one of the best places for studying characteristics of cyclic steps formed by turbidity currents through field observations. In this study, we have analyzed configurations of cyclic steps with the use of data obtained in the field observation of 2011, and compare them with the data from the flume experiments. On the prodelta slope, three major active channels are clearly developed. In addition to the sonar survey, a 600 kHz ADCP was installed in 150m of water just seaward of the termination of the North Channel. In addition, 1200kHz ADCP and 500kHz M3s are suspended from the research vessel in 60 m of water and 300 m distance from the delta edge. We selected images showing large daily differences. The steps move vigorously at the upper 600m parts of the prodelta slope, so that we measured the steps in this area. From the profiles perpendicular to the bedwave crest lines through the center of channels, wavelength and wave height for each step, mean slope were measured on the software for quantitative image analyses manually. Wave steepness for each step was calculated using the wavelength and wave height measured as above. The mean slope ranges from 6.8° ~ 2.7° (more proximal, steeper), mean wavelength and wave heights of steps range from 24.5 to 87.6m

  1. Hydrodesulfurization on Transition Metal Catalysts: Elementary Steps of C-S Bond Activation and Consequences of Bifunctional Synergies

    NASA Astrophysics Data System (ADS)

    Yik, Edwin Shyn-Lo

    The presence of heteroatoms (e.g. S, N) in crude oil poses formidable challenges in petroleum refining processes as a result of their irreversible binding on catalytically active sites at industrially relevant conditions. With increasing pressures from legislation that continues to lower the permissible levels of sulfur content in fuels, hydrodesulfurization (HDS), the aptly named reaction for removing heteroatoms from organosulfur compounds, has become an essential feedstock pretreatment step to remove deleterious species from affecting downstream processing. Extensive research in the area has identified the paradigm catalysts for desulfurization; MoSx or WSx, promoted with Co or Ni metal; however, despite the vast library of both empirical and fundamental studies, a clear understanding of site requirements, the elementary steps of C-S hydrogenolysis, and the properties that govern HDS reactivity and selectivity have been elusive. While such a lack of rigorous assessments has not prevented technological advancements in the field of HDS catalysis, fundamental interpretations can inform rational catalyst and process design, particularly in light of new requirements for "deep" desulfurization and in the absence of significant hydrotreatment catalyst developments in recent decades. We report HDS rates of thiophene, which belongs to a class of compounds that are most resistant to sulfur removal (i.e. substituted alkyldibenzothiophenes), over a range of industrially relevant temperatures and pressures, measured at differential conditions and therefore revealing their true kinetic origins. These rates, normalized by the number of exposed metal atoms, on various SiO 2-supported, monometallic transition metals (Re, Ru, Pt), range several orders of magnitude. Under relevant HDS conditions, Pt and Ru catalysts form a layer of chemisorbed sulfur on surfaces of a metallic bulk, challenging reports that assume the latter exists as its pyrite sulfide phase during reaction. While

  2. [Spinal cord stepping electrostimulation as a method for recovery of locomotor activity in vertebrogenic myelopathies].

    PubMed

    Shapkova, E Iu; Mushkin, A Iu

    2002-01-01

    The paper summarizes accumulated data on the parameters effective in calling alternate leg stepping and the areas of application of spinal cord electrostimulation, as well as the results of its application to restore locomotor capacities (tetra- and bipedal walking) of paralyzed patients.

  3. Using pedometers for measuring and increasing physical activity in children and adolescents: The next step

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The science and practice of step counting in children (typically aged 6-11 years) and adolescents (typically aged 12-19 years) has evolved rapidly over a relatively brief period with the commercial availability of research-grade pedometers and accelerometers. Recent reviews have summarized considera...

  4. Naturally occurring insecticides.

    PubMed Central

    Soloway, S B

    1976-01-01

    Naturally occurring insecticides are abundant and varied in their effects, though but a few are articles of commerce. Even for these, pyrethrum, nicotine, rotenone, hellebore, ryania, and sabadilla, there is a paucity of information on mammalian toxicology and environmental effects. In general, these materials are characterized favorably by low acute toxicity and ready dissipation in nature. Unfavorable aspects of natural insecticides are the contained mixture of active and inactive components and the low active ingredient content on a crop yield basis pointing to a high unit cost. Natural insecticides can serve additionally as leads to unnatural mimics, of which the commercially successful synthetic pyrethroids are prime examples. The chemical nature, relationship of insecticidal activity to chemical structure, occurrence, production, and utilization, registered uses, metabolism, and insect and mammalian toxicity are reviewed. PMID:789058

  5. A One-Step System for Convenient and Flexible Assembly of Transcription Activator-Like Effector Nucleases (TALENs).

    PubMed

    Zhao, Jinlong; Sun, Wenye; Liang, Jing; Jiang, Jing; Wu, Zhao

    2016-09-01

    Transcription activator-like effector nucleases (TALENs) are powerful tools for targeted genome editing in diverse cell types and organisms. However, the highly identical TALE repeat sequences make it challenging to assemble TALEs using conventional cloning approaches, and multiple repeats in one plasmid are easily catalyzed for homologous recombination in bacteria. Although the methods for TALE assembly are constantly improving, these methods are not convenient because of laborious assembly steps or large module libraries, limiting their broad utility. To overcome the barrier of multiple assembly steps, we report a one-step system for the convenient and flexible assembly of a 180 TALE module library. This study is the first demonstration to ligate 9 mono-/dimer modules and one circular TALEN backbone vector in a one step process, generating 9.5 to 18.5 repeat sequences with an overall assembly rate higher than 50%. This system makes TALEN assembly much simpler than the conventional cloning of two DNA fragments because this strategy combines digestion and ligation into one step using circular vectors and different modules to avoid gel extraction. Therefore, this system provides a convenient tool for the application of TALEN-mediated genome editing in scientific studies and clinical trials.

  6. Improved Reproducibility for Perovskite Solar Cells with 1 cm(2) Active Area by a Modified Two-Step Process.

    PubMed

    Shen, Heping; Wu, Yiliang; Peng, Jun; Duong, The; Fu, Xiao; Barugkin, Chog; White, Thomas P; Weber, Klaus; Catchpole, Kylie R

    2017-02-22

    With rapid progress in recent years, organohalide perovskite solar cells (PSC) are promising candidates for a new generation of highly efficient thin-film photovoltaic technologies, for which up-scaling is an essential step toward commercialization. In this work, we propose a modified two-step method to deposit the CH3NH3PbI3 (MAPbI3) perovskite film that improves the uniformity, photovoltaic performance, and repeatability of large-area perovskite solar cells. This method is based on the commonly used two-step method, with one additional process involving treating the perovskite film with concentrated methylammonium iodide (MAI) solution. This additional treatment is proved to be helpful for tailoring the residual PbI2 level to an optimal range that is favorable for both optical absorption and inhibition of recombination. Scanning electron microscopy and photoluminescence image analysis further reveal that, compared to the standard two-step and one-step methods, this method is very robust for achieving uniform and pinhole-free large-area films. This is validated by the photovoltaic performance of the prototype devices with an active area of 1 cm(2), where we achieved the champion efficiency of ∼14.5% and an average efficiency of ∼13.5%, with excellent reproducibility.

  7. Metabolic and Energy Cost of Sitting, Standing, and a Novel Sitting/Stepping Protocol in Recreationally Active College Students

    PubMed Central

    FOUNTAINE, CHARLES J.; JOHANN, JOSH; SKALKO, CRAIG; LIGUORI, GARY A.

    2016-01-01

    The purpose of this study was to compare the differences in metabolic and energy cost (MEC) of college students while seated, standing, and during a sitting/stepping protocol. Participants were assessed via indirect calorimetry for 20 min in each of the following conditions: 1) seated in a standard office chair, 2) standing in place, and 3) a sitting/stepping protocol in which participants performed 1 min of stepping in place at 90 bpm, sat for 9 min, then repeated the stepping and sitting sequence once more. Participants completed each of the 3 trials in the aforementioned order, preceded with a 3 min acclimation period in each condition. A significant difference in MEC was observed between the 3 conditions, p < 0.001. Pairwise comparisons indicated that the sitting/stepping protocol resulted in significantly greater MEC than the seated and standing conditions (p < 0.001). Additionally, the standing protocol resulted in significantly greater MEC than the seated protocol (p < 0.001). The significant differences and large effect sizes between conditions indicate that interspersing sedentary bouts with brief activity can substantially increase MEC. Broader application of these findings may provide health promotion professionals with novel strategies to reduce sedentary behavior and improve health. PMID:27182423

  8. Naturally Occurring Food Toxins

    PubMed Central

    Dolan, Laurie C.; Matulka, Ray A.; Burdock, George A.

    2010-01-01

    Although many foods contain toxins as a naturally-occurring constituent or, are formed as the result of handling or processing, the incidence of adverse reactions to food is relatively low. The low incidence of adverse effects is the result of some pragmatic solutions by the US Food and Drug Administration (FDA) and other regulatory agencies through the creative use of specifications, action levels, tolerances, warning labels and prohibitions. Manufacturers have also played a role by setting limits on certain substances and developing mitigation procedures for process-induced toxins. Regardless of measures taken by regulators and food producers to protect consumers from natural food toxins, consumption of small levels of these materials is unavoidable. Although the risk for toxicity due to consumption of food toxins is fairly low, there is always the possibility of toxicity due to contamination, overconsumption, allergy or an unpredictable idiosyncratic response. The purpose of this review is to provide a toxicological and regulatory overview of some of the toxins present in some commonly consumed foods, and where possible, discuss the steps that have been taken to reduce consumer exposure, many of which are possible because of the unique process of food regulation in the United States. PMID:22069686

  9. Influence of Active Site Conformations on the Hydride Transfer step of the Thymidylate Synthase Reaction Mechanism

    PubMed Central

    Świderek, Katarzyna; Kohen, Amnon; Moliner, Vicent

    2015-01-01

    The hydride transfer from C6 of tetrahydrofolate to the reaction’s exocyclic methylene-dUMP intermediate is the rate limiting step in thymidylate synthase (TSase) catalysis. This step has been studied by means of QM/MM Molecular Dynamics simulations to generate the corresponding free energy surfaces. The use of two different initial X-ray structures has allowed exploring different conformational spaces and exploring the existence of chemical paths with not only different reactivities, but also different reaction mechanisms. The results confirm that this chemical conversion takes place preferentially via a concerted mechanism where the hydride transfer is conjugated to thiol-elimination from the product. The findings also confirm the labile character of the substrate-enzyme covalent bond established between the C6 of the nucleotide substrate and a conserved cysteine residue. The calculations also reproduce and rationalize a normal H/T 2° kinetic isotope effect measured for that step. From a computational point of view, the results demonstrate that the use of an incomplete number of coordinates to describe the real reaction coordinate can render biased results. PMID:25868526

  10. The effect of timing electrical stimulation to robotic-assisted stepping on neuromuscular activity and associated kinematics.

    PubMed

    Askari, Sina; Chao, TeKang; de Leon, Ray D; Won, Deborah S

    2013-01-01

    Results of previous studies raise the question of how timing neuromuscular functional electrical stimulation (FES) to limb movements during stepping might alter neuromuscular control differently than patterned stimulation alone. We have developed a prototype FES system for a rodent model of spinal cord injury (SCI) that times FES to robotic treadmill training (RTT). In this study, one group of rats (n = 6) was trained with our FES+RTT system and received stimulation of the ankle flexor (tibialis anterior [TA]) muscle timed according to robot-controlled hind-limb position (FES+RTT group); a second group (n = 5) received a similarly patterned stimulation, randomly timed with respect to the rats' hind-limb movements, while they were in their cages (randomly timed stimulation [RS] group). After 4 wk of training, we tested treadmill stepping ability and compared kinematic measures of hind-limb movement and electromyography (EMG) activity in the TA. The FES+RTT group stepped faster and exhibited TA EMG profiles that better matched the applied stimulation profile during training than the RS group. The shape of the EMG profile was assessed by "gamma," a measure that quantified the concentration of EMG activity during the early swing phase of the gait cycle. This gamma measure was 112% higher for the FES+RTT group than for the RS group. The FES+RTT group exhibited burst-to-step latencies that were 41% shorter and correspondingly exhibited a greater tendency to perform ankle flexion movements during stepping than the RS group, as measured by the percentage of time the hind limb was either dragging or in withdrawal. The results from this study support the hypothesis that locomotor training consisting of FES timed to hind-limb movement improves the activation of hind-limb muscle more so than RS alone. Our rodent FES+RTT system can serve as a tool to help further develop this combined therapy to target appropriate neurophysiological changes for locomotor control.

  11. Intrinsic activity and poisoning rate for HCOOH oxidation at Pt(100) and vicinal surfaces containing monoatomic (111) steps.

    PubMed

    Grozovski, Vitali; Climent, Víctor; Herrero, Enrique; Feliu, Juan M

    2009-08-03

    Pulsed voltammetry is used to study formic acid oxidation on Pt(2n-1,1,1) surfaces and determine the effects of the size of the (100) terrace and the (111) step density on the reaction mechanism. The intrinsic activity of the electrode through the active intermediate reaction path (j(theta=) (0)), as well as the rate constant for the CO formation (k(ads)), are calculated from the current transients obtained at different potentials. For surfaces with wide terraces, j(theta=) (0) and k(ads) are almost insensitive to the step density, which suggests that step and terrace sites have a similar activity for this reaction. For narrow terraces (n<6), the intrinsic activity diminishes. The dependence of the reaction rates on the electrode potential is also elucidated. The CO formation only takes place in a narrow potential window, very close to the potential of zero total charge, while the direct oxidation takes place even when the surface is covered by anions. The different behavior for both reactions suggests that the adsorption mode of formic acid is different for each path.

  12. “Auto-anti-IgE”: Naturally occurring IgG anti-IgE antibodies may inhibit allergen-induced basophil activation

    PubMed Central

    Chan, Yih-Chih; Ramadani, Faruk; Santos, Alexandra F.; Pillai, Prathap; Ohm-Laursen, Line; Harper, Clare E.; Fang, Cailong; Dodev, Tihomir S.; Wu, Shih-Ying; Ying, Sun; Corrigan, Christopher J.; Gould, Hannah J.

    2014-01-01

    Background Naturally occurring IgE-specific IgG autoantibodies have been identified in patients with asthma and other diseases, but their spectrum of functions is poorly understood. Objective Address the hypothesis that: (i) IgG anti-IgE autoantibodies are detectable in the serum of all subjects but elevated in asthmatic patients regardless of atopic status as compared with controls; (ii) some activate IgE-sensitized basophils; and (iii) some inhibit allergen-induced basophil activation. Methods IgE-specific IgG autoantibodies were detected and quantified in sera using ELISA. Sera were examined for their ability to activate IgE-sensitized human blood basophils in the presence and absence of allergen using a basophil activation test, and to inhibit allergen binding to specific IgE on a rat basophilic cell line stably expressing human FcεRI. Results IgG autoantibodies binding to both free and FcεRI-bound IgE were detected in patients with atopic and non-atopic asthma, as well as controls. While some were able to activate IgE-sensitised basophils, others inhibited allergen-induced basophil activation, at least partly by inhibiting binding of IgE to specific allergen. Conclusion Naturally occurring IgG anti-IgE autoantibodies may inhibit, as well as induce, basophil activation. They act in a manner distinct from therapeutic IgG anti-IgE antibodies such as omalizumab. They may at least partly explain why atopic subjects who make allergen-specific IgE never develop clinical symptoms, and why omalizumab therapy is of variable clinical benefit in severe atopic asthma. PMID:25112697

  13. Activation and exhaustion of antigen-specific CD8(+) T cells occur in different splenic compartments during infection with Plasmodium berghei.

    PubMed

    Bayarsaikhan, Ganchimeg; Miyakoda, Mana; Yamamoto, Kazuo; Kimura, Daisuke; Akbari, Masoud; Yuda, Masao; Yui, Katsuyuki

    2017-06-01

    The spleen is the major organ in which T cells are primed during infection with malaria parasites. However, little is known regarding the dynamics of the immune responses and their localization within the splenic tissue during malaria infection. We examined murine CD8(+) T cell responses during infection with Plasmodium berghei using recombinant parasites expressing a model antigen ovalbumin (OVA) protein and compared the responses with those elicited by Listeria monocytogenes expressing the same antigen. OVA-specific CD8(+) T cells were mainly activated in the white pulp of the spleen during malaria infection, as similarly observed during Listeria infection. However, the fates of these activated CD8(+) T cells were distinct. During infection with malaria parasites, activated CD8(+) T cells preferentially accumulated in the red pulp and/or marginal zone, where cytokine production of OVA-specific CD8(+) T cells decreased, and the expression of multiple inhibitory receptors increased. These cells preferentially underwent apoptosis, suggesting that T cell exhaustion mainly occurred in the red pulp and/or marginal zone. However, during Listeria infection, OVA-specific CD8(+) T cells only transiently expressed inhibitory receptors in the white pulp and maintained their ability to produce cytokines and become memory cells. These results highlighted the distinct fates of CD8(+) T cells during infection with Plasmodium parasites and Listeria, and suggested that activation and exhaustion of specific CD8(+) T cells occurred in distinct spleen compartments during infection with malaria parasites.

  14. NF-κB activation induced by hepatitis A virus and Newcastle disease virus occurs by different pathways depending on the structural pattern of viral nucleic acids.

    PubMed

    Paulmann, Dajana; Bortmann, Simone; Grimm, Florian; Berk, Iris; Kraemer, Leena; Vallbracht, Angelika; Dotzauer, Andreas

    2014-07-01

    NF-κB is activated by hepatitis B virus and hepatitis C virus and is assumed to contribute to viral persistence, leading to the development of hepatocellular cancer by inhibition of apoptosis mediated by cytotoxic T cells. Whether hepatitis A virus (HAV), which does not cause chronic infection, activates NF-κB is a topic of controversy. Here, we confirm that HAV activates NF-κB and show that HAV enhances the activation of NF-κB by poly(I-C), but it inhibits the activation of NF-κB by Newcastle disease virus (NDV), a paramyxovirus. In addition, HAV inhibits NF-κB activation induced by overexpressed MAVS (mitochondrial antiviral signaling protein). We conclude from these findings that NF-κB induction occurs in cells infected with HAV by dsRNA, independently of mitochondrial-transduced RIG-I/MDA-5 signaling, whereas the induction of NF-κB in cells infected by NDV is mediated by RIG-I signaling, independenly of viral dsRNA. This is supported by experiments in which the different RNA inducers of RIG-I and MDA-5 are sequestered and which also show that poly(I-C) and HAV, but not NDV, are functionally equivalent in inducing NF-κB activity. Furthermore, we demonstrate that HAV interferes with the protein kinase R (PKR) activity and PKR activation induced by dsRNA, and that HAV-induced activation of NF-κB therefore does not take place via the PKR-induced pathway. As assumed for hepatitis B and C virus infections, NF-κB activation could attenuate the effects of cytotoxic T cells and may contribute to prolonged as well as relapsing courses of hepatitis A.

  15. Two step novel hydrogen system using additives to enhance hydrogen release from the hydrolysis of alane and activated aluminum

    SciTech Connect

    Zidan, Ragaiy; Teprovich, Joseph A.; Motyka, Theodore

    2015-12-01

    A system for the generation of hydrogen for use in portable power systems is set forth utilizing a two-step process that involves the thermal decomposition of AlH.sub.3 (10 wt % H.sub.2) followed by the hydrolysis of the activated aluminum (Al*) byproduct to release additional H.sub.2. Additionally, a process in which water is added directly without prior history to the AlH.sub.3:PA composite is also disclosed.

  16. Active faults crossing trunk pipeline routes: some important steps to avoid disaster

    NASA Astrophysics Data System (ADS)

    Besstrashnov, V. M.; Strom, A. L.

    2011-05-01

    Assessment of seismic strong motion hazard produced by earthquakes originating within causative fault zones allows rather low accuracy of localisation of these structures that can be provided by indirect evidence of fault activity. In contrast, the relevant accuracy of localisation and characterisation of active faults, capable of surface rupturing, can be achieved solely by the use of direct evidence of fault activity. This differentiation requires strict definition of what can be classified as "active fault" and the normalisation of methods used for identification and localisation of active faults crossing oil and natural gas trunk pipelines.

  17. Cryo-EM structure of a human spliceosome activated for step 2 of splicing.

    PubMed

    Bertram, Karl; Agafonov, Dmitry E; Liu, Wen-Ti; Dybkov, Olexandr; Will, Cindy L; Hartmuth, Klaus; Urlaub, Henning; Kastner, Berthold; Stark, Holger; Lührmann, Reinhard

    2017-02-16

    Spliceosome rearrangements facilitated by RNA helicase PRP16 before catalytic step two of splicing are poorly understood. Here we report a 3D cryo-electron microscopy structure of the human spliceosomal C complex stalled directly after PRP16 action (C*). The architecture of the catalytic U2-U6 ribonucleoprotein (RNP) core of the human C* spliceosome is very similar to that of the yeast pre-Prp16 C complex. However, in C* the branched intron region is separated from the catalytic centre by approximately 20 Å, and its position close to the U6 small nuclear RNA ACAGA box is stabilized by interactions with the PRP8 RNase H-like and PRP17 WD40 domains. RNA helicase PRP22 is located about 100 Å from the catalytic centre, suggesting that it destabilizes the spliced mRNA after step two from a distance. Comparison of the structure of the yeast C and human C* complexes reveals numerous RNP rearrangements that are likely to be facilitated by PRP16, including a large-scale movement of the U2 small nuclear RNP.

  18. Changes in muscle activation patterns in response to enhanced sensory input during treadmill stepping in infants born with myelomeningocele

    PubMed Central

    Pantall, Annette; Teulier, Caroline; Ulrich, Beverly D.

    2013-01-01

    Infants with myelomeningocele (MMC) increase step frequency in response to modifications to the treadmill surface. The aim was to investigate how these modifications impacted the electromyographic (EMG) patterns. We analyzed EMG from 19 infants aged 2–10 months, with MMC at the lumbosacral level. We supported infants upright on the treadmill for 12 trials, each 30 seconds long. Modifications included visual flow, unloading, weights, Velcro and lcriction. Surface electrodes recorded EMG from tibialis anterior, lateral gastrocnemius, rectus femoris and biceps femoris. We determined muscle bursts for each stride cycle and from these calculated various parameters. Results indicated that each of the five sensory conditions generated different motor patterns. Visual flow and friction which we previously reported increased step frequency impacted lateral gastrocnemius most. Weights, which significantly decreased step frequency increased burst duration and co-activity of the proximal muscles. We also observed an age effect, with all conditions increasing muscle activity in younger infants whereas in older infants visual flow and unloading stimulated most activity. In conclusion, we have demonstrated that infants with myelomeningocele at levels which impact the myotomes of major locomotor muscles find ways to respond and adapt their motor output to changes in sensory input. PMID:23158017

  19. "Naturally occurring asbestos

    NASA Astrophysics Data System (ADS)

    Cagnard, F.; Lahondère, D.; Blein, O.; Lahfid, A.; Wille, G.

    2012-04-01

    The term asbestos refers to six silicate minerals from amphibole and serpentine groups. By definition, it consists in bundles of thin and flexible long fibers, with high-tensile strength, and chemical and heat resistance. In contrast to asbestos found within commercial products and mining, the specific term ''naturally occurring asbestos'' (NOA) refers to asbestiform minerals occurring within rocks or soils that can be released by human activities or weathering processes. The fact that the exposure to asbestos is related to lung pathologies is now widely demonstrated (e.g. asbestosis, mesothelioma and lung cancer). However, if health risks associated with exposure to NOA exist, they are not yet well documented. The crystallization of natural asbestos occurs in specific Mg-rich lithologies associated with peculiar structural and metamorphic conditions. By recognizing and combining such specific geologic criteria, the presence or the absence of asbestos in bedrock terrains can be reasonably predicted and maps of NOA hazard can be drawn. We present here new results of geological mapping and petrological study concerning the evaluation of the NOA hazard in the Alps and Corsica, in France. The three folds approach consists in (1) a determination of lithologies with potential NOA from a bibliographic compilation and extraction of target zones from a geological geodatabase (2) a geological mapping of the target zones followed by a petrological characterization of sampled asbestiform minerals in the laboratory (optical microscopy, TEM, SEM, and Raman spectroscopy technics), and (3) the drawing of the final map of NOA hazard, at regional-scale. Occurrence criteria can be retained as follows: 1. NOA are abundant in the internal zones of the Alps and Corsica, especially within ophiolitic complexes. Natural asbestos are mostly concentrated within ultramafic rocks but can also occur within basic lithologies such as Mg-metagabbros, metabasalts and meta-pillow-lavas, 2. Asbestos

  20. Thigh Muscle Activity, Knee Motion, and Impact Force During Side-Step Pivoting in Agility-Trained Female Basketball Players

    PubMed Central

    Wilderman, Danielle R; Ross, Scott E; Padua, Darin A

    2009-01-01

    Context: Improving neuromuscular control of hamstrings muscles might have implications for decreasing anterior cruciate ligament injuries in females. Objective: To examine the effects of a 6-week agility training program on quadriceps and hamstrings muscle activation, knee flexion angles, and peak vertical ground reaction force. Design: Prospective, randomized clinical research trial. Setting: Sports medicine research laboratory. Patients or Other Participants: Thirty female intramural basketball players with no history of knee injury (age  =  21.07 ± 2.82 years, height  =  171.27 ± 4.66 cm, mass  =  66.36 ± 7.41 kg). Intervention(s): Participants were assigned to an agility training group or a control group that did not participate in agility training. Participants in the agility training group trained 4 times per week for 6 weeks. Main Outcome Measure(s): We used surface electromyography to assess muscle activation for the rectus femoris, vastus medialis oblique, medial hamstrings, and lateral hamstrings for 50 milliseconds before initial ground contact and while the foot was in contact with the ground during a side-step pivot maneuver. Knee flexion angles (at initial ground contact, maximum knee flexion, knee flexion displacement) and peak vertical ground reaction force also were assessed during this maneuver. Results: Participants in the training group increased medial hamstrings activation during ground contact after the 6-week agility training program. Both groups decreased their vastus medialis oblique muscle activation during ground contact. Knee flexion angles and peak vertical ground reaction force did not change for either group. Conclusions: Agility training improved medial hamstrings activity in female intramural basketball players during a side-step pivot maneuver. Agility training that improves hamstrings activity might have implications for reducing anterior cruciate ligament sprain injury associated with side-step pivots. PMID

  1. Steps for Improving Physical Activity Orientation Among Health-care Providers of Older Cardiovascular Patients

    PubMed Central

    2014-01-01

    Attaining appropriate levels of physical activity can have many potential physiological and psychological benefits in older adults with cardiovascular disease. However, these individuals often report low levels of physical activity and high levels of sedentary behavior. Older adults encounter many potential “barriers” to physical activity, but numerous studies have demonstrated the ability to positively influence this important health behavior using well-established behavior change theories and models. The information provided in this review is directed at health-care providers who have the potential to impact physical activity behaviors during regular, often brief, clinical interactions. In addition to providing the latest physical activity recommendations, this update will provide a brief summary of some of the more widely used behavioral skills and strategies for promoting physical activity in older adults with cardiovascular disease. PMID:25396112

  2. The effect of an active arm action on heart rate and predicted VO(2max) during the Chester step test.

    PubMed

    Elliott, Dave; Abt, Grant; Barry, Tim

    2008-04-01

    This study examined whether the predictive outcomes of the Chester step test (CST) would be influenced by arm dynamics. Participants completed the CST on two separate occasions, once using active arms and once using passive arms. Results revealed that when compared to the passive arm protocol, the use of active arms led to a mean increase in heart rate of approximately 7 beats per minute across all of the incremental stages. However, this increase had little impact upon predicted VO(2max). Consequently, these results indicate that when performing the CST, participants are able to adopt an arm action that is compatible with personal preference.

  3. Putting one step before the other: distinct activation pathways for Cdk1 and Cdk2 bring order to the mammalian cell cycle.

    PubMed

    Merrick, Karl A; Fisher, Robert P

    2010-02-15

    Eukaryotic cell division is controlled by the activity of cyclin-dependent kinases (CDKs). Cdk1 and Cdk2, which function at different stages of the mammalian cell cycle, both require cyclin-binding and phosphorylation of the activation (T-) loop for full activity, but differ with respect to the order in which the two steps occur in vivo. To form stable complexes with either of its partners-cyclins A and B-Cdk1 must be phosphorylated on its T-loop, but that phosphorylation in turn depends on the presence of cyclin. Cdk2 can follow a kinetically distinct path to activation in which T-loop phosphorylation precedes cyclin-binding, and thereby out-compete the more abundant Cdk1 for limiting amounts of cyclin A. Mathematical modeling suggests this could be a principal basis for the temporal ordering of CDK activation during S phase, which may dictate the sequence in which replication origins fire. Still to be determined are how: (1) the activation machinery discriminates between closely related CDKs, and (2) coordination of the cell cycle is affected when this mechanism of pathway insulation breaks down.

  4. Subretinal recombinant tissue plasminogen activator and pneumatic displacement for the management of subretinal hemorrhage occurring after anti-VEGF injections for wet AMD.

    PubMed

    Tognetto, Daniele; Skiadaresi, Eirini; Cecchini, Paolo; Ravalico, Giuseppe

    2011-01-01

    We describe three cases of submacular hemorrhage that occurred two to four days after anti-VEGF intravitreal injection for occult choroidal neovascularisation in age-related macular degeneration and their management with 25 gauge pars plana vitrectomy with injection of subretinal recombinant tissue plasminogen activator (rTPA) followed by fluid-air exchange and postoperative prone position. Vitrectomy, subretinal rTPA injection and fluid-gas exchange apply as a safe and effective treatment in these cases. Functional results seem to be positive especially if surgical treatment is promptly performed.

  5. Narrative increases step counts during active video game play among children

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Active video games (AVGs) capable of inducing physical activity (PA) level offer a novel alternative to child obesity. Unfortunately, children's motivation to play AVG decreases quickly, underscoring the need to find new methods to maintain their engagement. According to narrative transportation th...

  6. Next Step for STEP

    SciTech Connect

    Wood, Claire; Bremner, Brenda

    2013-08-09

    The Siletz Tribal Energy Program (STEP), housed in the Tribe’s Planning Department, will hire a data entry coordinator to collect, enter, analyze and store all the current and future energy efficiency and renewable energy data pertaining to administrative structures the tribe owns and operates and for homes in which tribal members live. The proposed data entry coordinator will conduct an energy options analysis in collaboration with the rest of the Siletz Tribal Energy Program and Planning Department staff. An energy options analysis will result in a thorough understanding of tribal energy resources and consumption, if energy efficiency and conservation measures being implemented are having the desired effect, analysis of tribal energy loads (current and future energy consumption), and evaluation of local and commercial energy supply options. A literature search will also be conducted. In order to educate additional tribal members about renewable energy, we will send four tribal members to be trained to install and maintain solar panels, solar hot water heaters, wind turbines and/or micro-hydro.

  7. Co-occurring increases of calcium and organellar reactive oxygen species determine differential activation of antioxidant and defense enzymes in Ulva compressa (Chlorophyta) exposed to copper excess.

    PubMed

    Gonzalez, Alberto; Vera, Jeannette; Castro, Jorge; Dennett, Geraldine; Mellado, Macarena; Morales, Bernardo; Correa, Juan A; Moenne, Alejandra

    2010-10-01

    In order to analyse copper-induced calcium release and (reactive oxygen species) ROS accumulation and their role in antioxidant and defense enzymes activation, the marine alga Ulva compressa was exposed to 10 µM copper for 7 d. The level of calcium, extracellular hydrogen peroxide (eHP), intracellular hydrogen peroxide (iHP) and superoxide anions (SA) as well as the activities of ascorbate peroxidase (AP), glutathione reductase (GR), glutathione-S-transferase (GST), phenylalanine ammonia lyase (PAL) and lipoxygenase (LOX) were determined. Calcium release showed a triphasic pattern with peaks at 2, 3 and 12 h. The second peak was coincident with increases in eHP and iHP and the third peak with the second increase of iHP. A delayed wave of SA occurred after day 3 and was not accompanied by calcium release. The accumulation of iHP and SA was mainly inhibited by organellar electron transport chains inhibitors (OETCI), whereas calcium release was inhibited by ryanodine. AP activation ceased almost completely after the use of OETCI. On the other hand, GR and GST activities were partially inhibited, whereas defense enzymes were not inhibited. In contrast, PAL and LOX were inhibited by ryanodine, whereas AP was not inhibited. Thus, copper stress induces calcium release and organellar ROS accumulation that determine the differential activation of antioxidant and defense enzymes.

  8. Steps toward validity in active living research: research design that limits accusations of physical determinism.

    PubMed

    Riggs, William

    2014-03-01

    "Active living research" has been accused of being overly "physically deterministic" and this article argues that urban planners must continue to evolve research and address biases in this area. The article first provides background on how researchers have dealt with the relationship between the built environment and health over years. This leads to a presentation of how active living research might be described as overly deterministic. The article then offers lessons for researchers planning to embark in active-living studies as to how they might increase validity and minimize criticism of physical determinism.

  9. Increased Back-Bonding Explains Step-Edge Reactivity and Particle Size Effect for CO Activation on Ru Nanoparticles.

    PubMed

    Foppa, Lucas; Copéret, Christophe; Comas-Vives, Aleix

    2016-12-28

    Carbon monoxide is a ubiquitous molecule, a key feedstock and intermediate in chemical processes. Its adsorption and activation, typically carried out on metallic nanoparticles (NPs), are strongly dependent on the particle size. In particular, small NPs, which in principle contain more corner and step-edge atoms, are surprisingly less reactive than larger ones. Hereby, first-principles calculations on explicit Ru NP models (1-2 nm) show that both small and large NPs can present step-edge sites (e.g., B5 and B6 sites). However, such sites display strong particle-size-dependent reactivity because of very subtle differences in local chemical bonding. State-of-the-art crystal orbital Hamilton population analysis allows a detailed molecular orbital picture of adsorbed CO on step-edges, which can be classified as flat (η(1) coordination) and concave (η(2) coordination) sites. Our analysis shows that the CO π-metal dπ hybrid band responsible for the electron back-donation is better represented by an oxygen lone pair on flat sites, whereas it is delocalized on both C and O atoms on concave sites, increasing the back-bonding on these sites compared to flat step-edges or low-index surface sites. The bonding analysis also rationalizes why CO cleavage is easier on step-edge sites of large NPs compared to small ones irrespective of the site geometry. The lower reactivity of small NPs is due to the smaller extent of the Ru-O interaction in the η(2) adsorption mode, which destabilizes the η(2) transition-state structure for CO direct cleavage. Our findings provide a molecular understanding of the reactivity of CO on NPs, which is consistent with the observed particle size effect.

  10. 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.

  11. 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

  12. Anti-allergic effect of the naturally-occurring conjugated linolenic acid isomer, jacaric acid, on the activated human mast cell line-1

    PubMed Central

    LIU, WAI NAM; LEUNG, KWOK NAM

    2015-01-01

    The present study aimed to investigate the immunomodulatory effect of jacaric acid, a naturally-occurring conjugated linolenic acid isomer that can be found in jacaranda seed oil, on the activated human mast cell line-1 (HMC-1). Our previous studies have demonstrated that jacaric acid only exerted minimal, if any, cytotoxicity on normal murine cells. In the present study, jacaric acid at concentrations ≤100 µM did not exhibit direct cytotoxicity on human peripheral blood mononuclear cells after 72 h of incubation, as determined by the MTT reduction assay. By contrast, jacaric acid could alleviate the calcium ionophore A23187 and phorbol 12-myristate 13-acetate-triggered allergic response in the HMC-1 cells at concentrations that were non-cytotoxic to the HMC-1 cells. Following pre-treatment with jacaric acid, the secretion of two inflammatory mediators, β-N-acetylglucosaminidase and tryptase, as well as the T helper 2 cytokines [interleukin (IL)-4 and IL-13] was significantly reduced in HMC-1 cells. The alleviation of allergic response was accompanied by downregulation of the matrix metalloproteinase-2 and −9 proteins and upregulation of the tissue inhibitor of metalloproteinase-1 protein. Collectively, the results indicated that the naturally-occurring jacaric acid exhibits a suppressive effect on the allergic response in activated human mast cells in vitro, and this could not be attributed to the direct cytotoxicity of jacaric acid on the treated cells. PMID:26623027

  13. Anti-allergic effect of the naturally-occurring conjugated linolenic acid isomer, jacaric acid, on the activated human mast cell line-1.

    PubMed

    Liu, Wai Nam; Leung, Kwok Nam

    2015-11-01

    The present study aimed to investigate the immunomodulatory effect of jacaric acid, a naturally-occurring conjugated linolenic acid isomer that can be found in jacaranda seed oil, on the activated human mast cell line-1 (HMC-1). Our previous studies have demonstrated that jacaric acid only exerted minimal, if any, cytotoxicity on normal murine cells. In the present study, jacaric acid at concentrations ≤100 µM did not exhibit direct cytotoxicity on human peripheral blood mononuclear cells after 72 h of incubation, as determined by the MTT reduction assay. By contrast, jacaric acid could alleviate the calcium ionophore A23187 and phorbol 12-myristate 13-acetate-triggered allergic response in the HMC-1 cells at concentrations that were non-cytotoxic to the HMC-1 cells. Following pre-treatment with jacaric acid, the secretion of two inflammatory mediators, β-N-acetylglucosaminidase and tryptase, as well as the T helper 2 cytokines [interleukin (IL)-4 and IL-13] was significantly reduced in HMC-1 cells. The alleviation of allergic response was accompanied by downregulation of the matrix metalloproteinase-2 and -9 proteins and upregulation of the tissue inhibitor of metalloproteinase-1 protein. Collectively, the results indicated that the naturally-occurring jacaric acid exhibits a suppressive effect on the allergic response in activated human mast cells in vitro, and this could not be attributed to the direct cytotoxicity of jacaric acid on the treated cells.

  14. Calculating Transition Energy Barriers and Characterizing Activation States for Steps of Fusion

    PubMed Central

    Ryham, Rolf J.; Klotz, Thomas S.; Yao, Lihan; Cohen, Fredric S.

    2016-01-01

    We use continuum mechanics to calculate an entire least energy pathway of membrane fusion, from stalk formation, to pore creation, and through fusion pore enlargement. The model assumes that each structure in the pathway is axially symmetric. The static continuum stalk structure agrees quantitatively with experimental stalk architecture. Calculations show that in a stalk, the distal monolayer is stretched and the stored stretching energy is significantly less than the tilt energy of an unstretched distal monolayer. The string method is used to determine the energy of the transition barriers that separate intermediate states and the dynamics of two bilayers as they pass through them. Hemifusion requires a small amount of energy independently of lipid composition, while direct transition from a stalk to a fusion pore without a hemifusion intermediate is highly improbable. Hemifusion diaphragm expansion is spontaneous for distal monolayers containing at least two lipid components, given sufficiently negative diaphragm spontaneous curvature. Conversely, diaphragms formed from single-component distal monolayers do not expand without the continual injection of energy. We identify a diaphragm radius, below which central pore expansion is spontaneous. For larger diaphragms, prior studies have shown that pore expansion is not axisymmetric, and here our calculations supply an upper bound for the energy of the barrier against pore formation. The major energy-requiring deformations in the steps of fusion are: widening of a hydrophobic fissure in bilayers for stalk formation, splay within the expanding hemifusion diaphragm, and fissure widening initiating pore formation in a hemifusion diaphragm. PMID:26958888

  15. Engineering Escherichia coli for Soluble Expression and Single Step Purification of Active Human Lysozyme

    PubMed Central

    Lamppa, John W.; Tanyos, Sam A.; Griswold, Karl E.

    2012-01-01

    Genetically engineered variants of human lysozyme represent promising leads in the battle against drug-resistant bacterial pathogens, but early stage development and testing of novel lysozyme variants is constrained by the lack of a robust, scalable and facile expression system. While wild type human lysozyme is reportedly produced at 50 – 80 kg per hectare of land in recombinant rice, this plant-based system is not readily scaled down to bench top production, and it is therefore not suitable for development and characterization of novel lysozyme variants. Here, we describe a novel and efficient expression system capable of producing folded, soluble and functional human lysozyme in E. coli cells. To achieve this goal, we simultaneously co-express multiple protein folding chaperones as well as harness the lysozyme inhibitory protein, Ivy. Our strategy exploits E. coli’s ease of culture, short doubling time, and facile genetics to yield upwards of 30 mg/L of soluble lysozyme in a bioreactor system, a 3000-fold improvement over prior efforts in E. coli. Additionally, molecular interactions between lysozyme and a his-tagged Ivy allows for one-step purification by IMAC chromatography, yielding as much as 21 mg/L of purified enzyme. We anticipate that our expression and purification platform will facilitate further development of engineered lysozymes having utility in disease treatment and other practical applications. PMID:23220215

  16. Calculating Transition Energy Barriers and Characterizing Activation States for Steps of Fusion.

    PubMed

    Ryham, Rolf J; Klotz, Thomas S; Yao, Lihan; Cohen, Fredric S

    2016-03-08

    We use continuum mechanics to calculate an entire least energy pathway of membrane fusion, from stalk formation, to pore creation, and through fusion pore enlargement. The model assumes that each structure in the pathway is axially symmetric. The static continuum stalk structure agrees quantitatively with experimental stalk architecture. Calculations show that in a stalk, the distal monolayer is stretched and the stored stretching energy is significantly less than the tilt energy of an unstretched distal monolayer. The string method is used to determine the energy of the transition barriers that separate intermediate states and the dynamics of two bilayers as they pass through them. Hemifusion requires a small amount of energy independently of lipid composition, while direct transition from a stalk to a fusion pore without a hemifusion intermediate is highly improbable. Hemifusion diaphragm expansion is spontaneous for distal monolayers containing at least two lipid components, given sufficiently negative diaphragm spontaneous curvature. Conversely, diaphragms formed from single-component distal monolayers do not expand without the continual injection of energy. We identify a diaphragm radius, below which central pore expansion is spontaneous. For larger diaphragms, prior studies have shown that pore expansion is not axisymmetric, and here our calculations supply an upper bound for the energy of the barrier against pore formation. The major energy-requiring deformations in the steps of fusion are: widening of a hydrophobic fissure in bilayers for stalk formation, splay within the expanding hemifusion diaphragm, and fissure widening initiating pore formation in a hemifusion diaphragm.

  17. Antioxidant components of naturally-occurring oils exhibit marked anti-inflammatory activity in epithelial cells of the human upper respiratory system

    PubMed Central

    2011-01-01

    Background The upper respiratory tract functions to protect lower respiratory structures from chemical and biological agents in inspired air. Cellular oxidative stress leading to acute and chronic inflammation contributes to the resultant pathology in many of these exposures and is typical of allergic disease, chronic sinusitis, pollutant exposure, and bacterial and viral infections. Little is known about the effective means by which topical treatment of the nose can strengthen its antioxidant and anti-inflammatory defenses. The present study was undertaken to determine if naturally-occurring plant oils with reported antioxidant activity can provide mechanisms through which upper respiratory protection might occur. Methods Controlled exposure of the upper respiratory system to ozone and nasal biopsy were carried out in healthy human subjects to assess mitigation of the ozone-induced inflammatory response and to assess gene expression in the nasal mucosa induced by a mixture of five naturally-occurring antioxidant oils - aloe, coconut, orange, peppermint and vitamin E. Cells of the BEAS-2B and NCI-H23 epithelial cell lines were used to investigate the source and potential intracellular mechanisms of action responsible for oil-induced anti-inflammatory activity. Results Aerosolized pretreatment with the mixed oil preparation significantly attenuated ozone-induced nasal inflammation. Although most oil components may reduce oxidant stress by undergoing reduction, orange oil was demonstrated to have the ability to induce long-lasting gene expression of several antioxidant enzymes linked to Nrf2, including HO-1, NQO1, GCLm and GCLc, and to mitigate the pro-inflammatory signaling of endotoxin in cell culture systems. Nrf2 activation was demonstrated. Treatment with the aerosolized oil preparation increased baseline levels of nasal mucosal HO-1 expression in 9 of 12 subjects. Conclusions These data indicate that selected oil-based antioxidant preparations can effectively

  18. Effects of synthetic and naturally occurring flavonoids on Na sup + , K sup + -ATPase: Aspects of the structure-activity relationship and action mechanism

    SciTech Connect

    Hirano, T.; Oka, K.; Akiba, M. )

    1989-01-01

    A comparative study was made of the effects of 15 synthetic and naturally occurring flavonoids on the hydrolytic activity of Na{sup +}, K{sup +} -adenosine triphosphatase (ATPase). Twelve of the flavonoids examined were mono-hydroxy or mono-methoxy derivatives. All inhibited Na{sup +}, K{sup +} -ATPase from dog kidney cortex when present at concentrations from 40-1000 {mu}M. Flavones possessing cyclohexyl instead of the phenyl group were the most potent with IC{sub 50} at 257-320 {mu}M. Structure-activity relationships were observed among the following mono-substituted flavones as: (i) 2-cyclohexyl-benzopyran-4-one {much gt} 2-phenyl-benzopyran-4-one; (ii) 2-cyclohexyl-7-hydroxybenzopyran-4-one {gt} 2-cyclohexyl-6-hydroxy-benzopyran-4-one {gt} 2-cyclohexyl-5-hydroxybenzopyran-4-one. Some flavonoids showing potent inhibitory activity were also examined for ouabain-displacement activity on human erythrocytes. Hardly and of the flavonoids were able to block ({sup 3}H) ouabain binding to erythrocytes. These results suggest that the mechanism by which flavonoid block Na{sup +}, K{sup +} -ATPase is not related to the cardiac glycoside-specific binding site(s) of this enzyme.

  19. Steps Forward: Review and Recommendations for Research on Walkability, Physical Activity and Cardiovascular Health.

    PubMed

    Lovasi, Gina S; Grady, Stephanie; Rundle, Andrew

    2012-01-01

    Built environments that support walking and other physical activities have the potential to reduce cardiovascular disease (CVD). Walkable neighborhoods-characterized by density, land use diversity, and well-connected transportation networks-have been linked to more walking, less obesity, and lower coronary heart disease risk. Yet ongoing research on pedestrian-friendly built environments has the potential to address important gaps. While much of the literature has focused on urban form and planning characteristics, additional aspects of street-scapes, such as natural and architectural amenities, should also be considered. Promising future directions include (1) integration of multiple built environment measures that facilitate an understanding of how individuals perceive and act within their environment; (2) examination of both the daily physical activities that are most feasibly influenced by the local environment and those more deliberate or vigorous patterns of physical activity that are most predictive of CVD; (3) consideration of multiple pathways that could mediate a link between walkability and CVD, including not only physical activity, but also air quality improvements from reduced vehicle mileage and enhanced neighborhood social cohesion from unplanned interactions; (4) testing competing hypotheses that may explain interactions of built environment characteristics with each other and with personal barriers to walking; (5) stronger conceptualization of the multiple neighborhoods or activity spaces that structure opportunities for physical activity throughout the day; (6) collecting and strategically analyzing longitudinal data to support causal inference; and (7) studying neighborhood preferences and selection to move beyond biased assessments of neighborhood health effects. While walkability has been linked to health-related behaviors and CVD risk factors, the implications of the observed correlations are not yet clear. New theoretical insights

  20. Steps Forward: Review and Recommendations for Research on Walkability, Physical Activity and Cardiovascular Health

    PubMed Central

    Lovasi, Gina S.; Grady, Stephanie; Rundle, Andrew

    2012-01-01

    Built environments that support walking and other physical activities have the potential to reduce cardiovascular disease (CVD). Walkable neighborhoods—characterized by density, land use diversity, and well-connected transportation networks—have been linked to more walking, less obesity, and lower coronary heart disease risk. Yet ongoing research on pedestrian-friendly built environments has the potential to address important gaps. While much of the literature has focused on urban form and planning characteristics, additional aspects of street-scapes, such as natural and architectural amenities, should also be considered. Promising future directions include (1) integration of multiple built environment measures that facilitate an understanding of how individuals perceive and act within their environment; (2) examination of both the daily physical activities that are most feasibly influenced by the local environment and those more deliberate or vigorous patterns of physical activity that are most predictive of CVD; (3) consideration of multiple pathways that could mediate a link between walkability and CVD, including not only physical activity, but also air quality improvements from reduced vehicle mileage and enhanced neighborhood social cohesion from unplanned interactions; (4) testing competing hypotheses that may explain interactions of built environment characteristics with each other and with personal barriers to walking; (5) stronger conceptualization of the multiple neighborhoods or activity spaces that structure opportunities for physical activity throughout the day; (6) collecting and strategically analyzing longitudinal data to support causal inference; and (7) studying neighborhood preferences and selection to move beyond biased assessments of neighborhood health effects. While walkability has been linked to health-related behaviors and CVD risk factors, the implications of the observed correlations are not yet clear. New theoretical insights

  1. Accurate stepping on a narrow path: mechanics, EMG, and motor cortex activity in the cat

    PubMed Central

    Farrell, Brad J.; Bulgakova, Margarita A.; Sirota, Mikhail G.; Prilutsky, Boris I.

    2015-01-01

    How do cats manage to walk so graciously on top of narrow fences or windowsills high above the ground while apparently exerting little effort? In this study we investigated cat full-body mechanics and the activity of limb muscles and motor cortex during walking along a narrow 5-cm path on the ground. We tested the hypotheses that during narrow walking 1) lateral stability would be lower because of the decreased base-of-support area and 2) the motor cortex activity would increase stride-related modulation because of imposed demands on lateral stability and paw placement accuracy. We measured medio-lateral and rostro-caudal dynamic stability derived from the extrapolated center of mass position with respect to the boundaries of the support area. We found that cats were statically stable in the frontal plane during both unconstrained and narrow-path walking. During narrow-path walking, cats walked slightly slower with more adducted limbs, produced smaller lateral forces by hindlimbs, and had elevated muscle activities. Of 174 neurons recorded in cortical layer V, 87% of forelimb-related neurons (from 114) and 90% of hindlimb-related neurons (from 60) had activities during narrow-path walking distinct from unconstrained walking: more often they had a higher mean discharge rate, lower depth of stride-related modulation, and/or longer period of activation during the stride. These activity changes appeared to contribute to control of accurate paw placement in the medio-lateral direction, the width of the stride, rather than to lateral stability control, as the stability demands on narrow-path and unconstrained walking were similar. PMID:26354314

  2. Using Concept Mapping to Identify Action Steps for Physical Activity Promotion in Cancer Treatment

    ERIC Educational Resources Information Center

    Fitzpatrick, Sean Joseph; Zizzi, Sam J.

    2014-01-01

    Background: The benefits of exercise during and after cancer treatment represent research areas that have received increased attention throughout the past 2 decades. Numerous benefits have been observed for cancer survivors who are physically active, yet oncologists have been slow to incorporate exercise counseling into practice. Purpose: The…

  3. Managing Low-Back Pain: Steps To Optimize Function and Hasten Return to Activity.

    ERIC Educational Resources Information Center

    Drezner, Jonathan A.; Herring, Stanley A.

    2001-01-01

    Low-back pain (LBP) in active people is common and recurrent. This paper describes: the natural history and clinical course of LBP; anatomy and biomechanics of LBP; what causes pain; diagnosis; initial treatment (e.g., pain and inflammation control, bed rest, and exercises); rehabilitation (e.g., lumbar stabilization exercises, conditioning, and…

  4. Steps in reductive activation of the disulfide-generating enzyme Ero1p

    PubMed Central

    Heldman, Nimrod; Vonshak, Ohad; Sevier, Carolyn S; Vitu, Elvira; Mehlman, Tevie; Fass, Deborah

    2010-01-01

    Ero1p is the primary catalyst of disulfide bond formation in the yeast endoplasmic reticulum (ER). Ero1p contains a pair of essential disulfide bonds that participate directly in the electron transfer pathway from substrate thiol groups to oxygen. Remarkably, elimination of certain other Ero1p disulfides by mutation enhances enzyme activity. In particular, the C150A/C295A Ero1p mutant exhibits increased thiol oxidation in vitro and in vivo and interferes with redox homeostasis in yeast cells by hyperoxidizing the ER. Inhibitory disulfides of Ero1p are thus important for enzyme regulation. To visualize the differences between de-regulated and wild-type Ero1p, we determined the crystal structure of Ero1p C150A/C295A. The structure revealed local changes compared to the wild-type enzyme around the sites of mutation, but no conformational transitions within 25 Å of the active site were observed. To determine how the C150—C295 disulfide nonetheless participates in redox regulation of Ero1p, we analyzed using mass spectrometry the changes in Ero1p disulfide connectivity as a function of time after encounter with reducing substrates. We found that the C150—C295 disulfide sets a physiologically appropriate threshold for enzyme activation by guarding a key neighboring disulfide from reduction. This study illustrates the diverse and interconnected roles that disulfides can play in redox regulation of protein activity. PMID:20669236

  5. A Two-Step Strategy to Enhance Activity of Low Potency Peptides

    PubMed Central

    Krishnaji, Subrahmanian Tarakkad; Krishnamurthy, Vijay M.; Lin, Wei-En; Fortin, Jean-Philippe; Kumar, Krishna; Kopin, Alan S.

    2014-01-01

    Novel strategies are needed to expedite the generation and optimization of peptide probes targeting G protein-coupled receptors (GPCRs). We have previously shown that membrane tethered ligands (MTLs), recombinant proteins comprised of a membrane anchor, an extracellular linker, and a peptide ligand can be used to identify targeted receptor modulators. Although MTLs provide a useful tool to identify and/or modify functionally active peptides, a major limitation of this strategy is the reliance on recombinant protein expression. We now report the generation and pharmacological characterization of prototype peptide-linker-lipid conjugates, synthetic membrane anchored ligands (SMALs), which are designed as mimics of corresponding MTLs. In this study, we systematically compare the activity of selected peptides as MTLs versus SMALs. As prototypes, we focused on the precursor proteins of mature Substance P (SubP) and Cholecystokinin 4 (CCK4), specifically non-amidated SubP (SubP-COOH) and glycine extended CCK4 (CCK4-Gly-COOH). As low affinity soluble peptides these ligands each presented a challenging test case for assessment of MTL/SMAL technology. For each ligand, MTLs and corresponding SMALs showed agonist activity and comparable subtype selectivity. In addition, our results illustrate that membrane anchoring increases ligand potency. Furthermore, both MTL and SMAL induced signaling can be blocked by specific non-peptide antagonists suggesting that the anchored constructs may be orthosteric agonists. In conclusion, MTLs offer a streamlined approach for identifying low activity peptides which can be readily converted to higher potency SMALs. The ability to recapitulate MTL activity with SMALs extends the utility of anchored peptides as probes of GPCR function. PMID:25391026

  6. Naturally occurring chemical carcinogens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Natural products are chemicals found in nature which have unique pharmacological effects. Humans are exposed to many of these bioactive naturally occurring chemicals via the air breathed, the water drunk and the food eaten. Exposure also occurs in clinical settings. Naturally occurring chemicals ...

  7. Development of an mHealth Intervention (iSTEP) to Promote Physical Activity among People Living with HIV

    PubMed Central

    Montoya, Jessica L.; Wing, David; Knight, Adam; Moore, David J.; Henry, Brook L.

    2015-01-01

    A randomized controlled trial is being conducted in the United States to test the efficacy of a personalized interactive mobile health intervention (iSTEP) designed to increase physical activity (PA) and improve neurocognitive functioning among HIV-positive persons. This article describes an initial qualitative study performed to develop iSTEP for the HIV-positive population, including assessment of PA barriers and facilitators. Two focus groups, with 9 and 12 unique HIV-positive individuals, respectively, were administered to evaluate barriers limiting PA and potential iSTEP content created to encourage greater PA. Group discussions revealed prominent PA barriers, including HIV symptoms (neuropathy, lipoatrophy), antiretroviral medication effects, and fatigue; significant PA facilitators included self-monitoring and family support. Participants provided feedback on strategies to increase PA and expressed positive support for a mobile intervention adapted to personal priorities. These findings will assist the development of novel PA interventions focused on treating the epidemic of HIV-associated neurocognitive disorders. PMID:26307212

  8. Transcription factors GAF and HSF act at distinct regulatory steps to modulate stress-induced gene activation.

    PubMed

    Duarte, Fabiana M; Fuda, Nicholas J; Mahat, Dig B; Core, Leighton J; Guertin, Michael J; Lis, John T

    2016-08-01

    The coordinated regulation of gene expression at the transcriptional level is fundamental to development and homeostasis. Inducible systems are invaluable when studying transcription because the regulatory process can be triggered instantaneously, allowing the tracking of ordered mechanistic events. Here, we use precision run-on sequencing (PRO-seq) to examine the genome-wide heat shock (HS) response in Drosophila and the function of two key transcription factors on the immediate transcription activation or repression of all genes regulated by HS. We identify the primary HS response genes and the rate-limiting steps in the transcription cycle that GAGA-associated factor (GAF) and HS factor (HSF) regulate. We demonstrate that GAF acts upstream of promoter-proximally paused RNA polymerase II (Pol II) formation (likely at the step of chromatin opening) and that GAF-facilitated Pol II pausing is critical for HS activation. In contrast, HSF is dispensable for establishing or maintaining Pol II pausing but is critical for the release of paused Pol II into the gene body at a subset of highly activated genes. Additionally, HSF has no detectable role in the rapid HS repression of thousands of genes.

  9. Time-Resolved Single-Step Protease Activity Quantification Using Nanoplasmonic Resonator Sensors

    DTIC Science & Technology

    2010-01-25

    benign prostatic hyper- plasia ( BPH ) more often than cancer.26,27 The lack of specificity causes a high false-positive rate and often leads to costly...B.; Isaacs, J. T. Prostate -Specific Antigen-Activated Thapsigargin Prodrug as Targeted Therapy for Prostate Cancer. J. Natl. Cancer Inst. 2003, 95...metal nanoparticle aggregates, which is the most commonly used SERS substrate,7 have dem- onstrated detection sensitivity up to single molecule level

  10. Step behaviour and autonomic nervous system activity in multiparous dairy cows during milking in a herringbone milking system.

    PubMed

    Kézér, F L; Kovács, L; Tőzsér, J

    2015-08-01

    Behavioural and cardiac responses of multiparous dairy cows (n=24) during milking in a 2×4 stall herringbone milking system were evaluated in this study. Heart rate (HR), parasympathetic tone index (high frequency component, HF) of heart rate variability and sympathovagal balance indicator LF/HF ratio (the ratio of the low frequency (LF) and the HF component) were analysed. Measurement periods were established as follows: (1) standing calm (baseline), (2) udder preparation, (3) milking, (4) waiting after milking in the milking stall and (5) in the night (2 h after milking). Step behaviour was recorded and calculated per minute for the three phases of the milking process (udder preparation, milking and waiting after milking). HR was higher during udder preparation and milking compared with baseline (P=0.03, 0.027, respectively). HF was significantly lower than baseline levels during waiting in the milking stall after milking (P=0.009), however, during udder preparation, milking and 2 h after milking did not differ from baseline (P>0.05, in either case). LF/HF during the three phases of the milking process differed neither from baseline levels nor from each other. Steps occurred more often during waiting after milking than during udder preparation (P=0.042) or during milking (23; P=0.017). Our results suggest that the milking procedure itself was not stressful for these animals. After milking (following the removal of the last teat cup and before leaving the milking stall), both decreased parasympathetic tone (lower HF) and increased stepping rate indicated a sensitive period for animals during this phase.

  11. Activated full-length myosin-X moves processively on filopodia with large steps toward diverse two-dimensional directions

    PubMed Central

    Sato, Osamu; Jung, Hyun Suk; Komatsu, Satoshi; Tsukasaki, Yoshikazu; Watanabe, Tomonobu M.; Homma, Kazuaki; Ikebe, Mitsuo

    2017-01-01

    Myosin-X, (Myo 10), is an unconventional myosin that transports the specific cargos to filopodial tips, and is associated with the mechanism underlying filopodia formation and extension. To clarify the innate motor characteristic, we studied the single molecule movement of a full-length myosin-X construct with leucine zipper at the C-terminal end of the tail (M10FullLZ) and the tail-truncated myosin-X without artificial dimerization motif (BAP-M101–979HMM). M10FullLZ localizes at the tip of filopodia like myosin-X full-length (M10Full). M10FullLZ moves on actin filaments in the presence of PI(3,4,5)P3, an activator of myosin-X. Single molecule motility analysis revealed that the step sizes of both M10FullLZ and BAP-M101–979HMM are widely distributed on single actin filaments that is consistent with electron microscopy observation. M10FullLZ moves on filopodial actin bundles of cells with a mean step size (~36 nm), similar to the step size on single actin filaments (~38 nm). Cartesian plot analysis revealed that M10FullLZ meandered on filopodial actin bundles to both x- and y- directions. These results suggest that the lever-arm of full-length myosin-X is flexible enough to processively steps on different actin filaments within the actin bundles of filopodia. This characteristic of myosin-X may facilitate actin filament convergence for filopodia production. PMID:28287133

  12. Three-step preparation and purification of phosphorus-33-labeled creatine phosphate of high specific activity

    SciTech Connect

    Savabi, F.; Geiger, P.J.; Bessman, S.P.

    1984-03-01

    Rabbit heart mitochondria were used as a source of enzymes for the synthesis of phosphorus-labeled creatine phosphate. This method is based on the coupled reaction between mitochondrial oxidative phosphorylation and mitochondrial-bound creatine kinase. It is possible to convert more than 90% of the inorganic phosphate (P/sub i/) to creatine phosphate. The method used only small amounts of adenine nucleotides which led to a product with only slight nucleotide contamination. This could be removed by activated charcoal extraction. For further purification, a method for the removal of residual P/sub i/ is described. 20 references.

  13. Single-step process to prepare CeO2 nanotubes with improved catalytic activity.

    PubMed

    González-Rovira, Leandro; Sánchez-Amaya, José M; López-Haro, Miguel; del Rio, Eloy; Hungría, Ana B; Midgley, Paul; Calvino, José J; Bernal, Serafín; Botana, F Javier

    2009-04-01

    CeO(2) nanotubes have been grown electrochemically using a porous alumina membrane as a template. The resulting material has been characterized by means of scanning electron microscopy (SEM), X-ray energy dispersive spectroscopy, high-angle annular dark-field scanning transmission electron microscopy tomography, high-resolution electron microscopy (HREM), and electron energy loss spectroscopy. According to SEM, the outer diameter of the nanotubes corresponds to the pore size (200 nm) of the alumina membrane, and their length ranges between 30 and 40 microm. HREM images have revealed that the width of the nanotube walls is about 6 nm. The catalytic activity of these novel materials for the CO oxidation reaction is compared to that of a polycrystalline powder CeO(2) sample prepared by a conventional route. The activity of the CeO(2) nanotubes is shown to be in the order of 400 times higher per gram of oxide at 200 degrees C (77.2 x 10(-2) cm(3) CO(2) (STP)/(gxs) for the nanotube-shaped CeO(2) and 0.16 x 10(-2) cm(3) CO(2) (STP)/(gxs) for the powder CeO(2)).

  14. A Step Towards Seascape Scale Conservation: Using Vessel Monitoring Systems (VMS) to Map Fishing Activity

    PubMed Central

    Witt, Matthew J.; Godley, Brendan J.

    2007-01-01

    Background Conservation of marine ecosystems will require a holistic understanding of fisheries with concurrent spatial patterns of biodiversity. Methodology/Principal Findings Using data from the UK Government Vessel Monitoring System (VMS) deployed on UK-registered large fishing vessels we investigate patterns of fisheries activity on annual and seasonal scales. Analysis of VMS data shows that regions of the UK European continental shelf (i.e. Western Channel and Celtic Sea, Northern North Sea and the Goban Spur) receive consistently greater fisheries pressure than the rest of the UK continental shelf fishing zone. Conclusions/Significance VMS provides a unique and independent method from which to derive patterns of spatially and temporally explicit fisheries activity. Such information may feed into ecosystem management plans seeking to achieve sustainable fisheries while minimising putative risk to non-target species (e.g. cetaceans, seabirds and elasmobranchs) and habitats of conservation concern. With multilateral collaboration VMS technologies may offer an important solution to quantifying and managing ecosystem disturbance, particularly on the high-seas. PMID:17971874

  15. Stepping Out of the Shade: Control of Neuronal Activity by the Scaffold Protein Kidins220/ARMS

    PubMed Central

    Scholz-Starke, Joachim; Cesca, Fabrizia

    2016-01-01

    The correct functioning of the nervous system depends on the exquisitely fine control of neuronal excitability and synaptic plasticity, which relies on an intricate network of protein-protein interactions and signaling that shapes neuronal homeostasis during development and in adulthood. In this complex scenario, Kinase D interacting substrate of 220 kDa/ankyrin repeat-rich membrane spanning (Kidins220/ARMS) acts as a multi-functional scaffold protein with preferential expression in the nervous system. Engaged in a plethora of interactions with membrane receptors, cytosolic signaling components and cytoskeletal proteins, Kidins220/ARMS is implicated in numerous cellular functions including neuronal survival, neurite outgrowth and maturation and neuronal activity, often in the context of neurotrophin (NT) signaling pathways. Recent studies have highlighted a number of cell- and context-specific roles for this protein in the control of synaptic transmission and neuronal excitability, which are at present far from being completely understood. In addition, some evidence has began to emerge, linking alterations of Kidins220 expression to the onset of various neurodegenerative diseases and neuropsychiatric disorders. In this review, we present a concise summary of our fragmentary knowledge of Kidins220/ARMS biological functions, focusing on the mechanism(s) by which it controls various aspects of neuronal activity. We have tried, where possible, to discuss the available evidence in the wider context of NT-mediated regulation, and to outline emerging roles of Kidins220/ARMS in human pathologies. PMID:27013979

  16. Mitogen-Activated Protein Kinase Activity Is Not Essential for the First Step of Nuclear Reprogramming in Bovine Somatic Cell Nuclear Transfer.

    PubMed

    Tani, Tetsuya; Kato, Yoko

    2017-03-07

    For reprogramming a somatic nucleus during mammalian cloning, metaphase of the second meiotic division (MII) oocytes has been widely used as recipient cytoplasm. High activity of maturation-promoting factor (MPF) and mitogen-activated protein kinase (MAPK) is believed to accelerate the remodeling and/or reprogramming of a somatic nucleus introduced into the ooplasm by somatic cell nuclear transfer. We demonstrated previously that the first step in nuclear reprogramming is not directly regulated by MPF and MAPK because activated oocytes in which MPF activity is diminished and MAPK activity is maintained can develop to the blastocyst stage after receiving an M phase somatic nucleus in bovine cloning. In this study, our aim was to test whether MAPK activity is necessary for the first step in nuclear reprogramming and/or chromatin remodeling (phosphorylation of histone H3 at Ser3, trimethylation of histone H3 at Lys 9, and acetylation of histone H3 at Lys14) in bovine somatic cloning. We found that it was not necessary, and neither was MPF activity.

  17. New synthetic routes to chain-extended selenium, sulfur, and nitrogen analogues of the naturally occurring glucosidase inhibitor salacinol and their inhibitory activities against recombinant human maltase glucoamylase.

    PubMed

    Liu, Hui; Nasi, Ravindranath; Jayakanthan, Kumarasamy; Sim, Lyann; Heipel, Heather; Rose, David R; Pinto, B Mario

    2007-08-17

    Six heteroanalogues (X = S, Se, NH) of the naturally occurring glucosidase inhibitor salacinol, containing polyhydroxylated, acyclic chains of 6-carbons, were synthesized for structure-activity studies with different glycosidase enzymes. The target zwitterionic compounds were synthesized by means of nucleophilic attack of the PMB-protected 1,4-anhydro-4-seleno-, 1,4-anhydro-4-thio-, and 1,4-anhydro-4-imino-D-arabinitols at the least hindered carbon atom of 1,3-cyclic sulfates. These 1,3-cyclic sulfates were derived from D-glucose and D-galactose, and significantly, they utilized butane diacetal as the protecting groups for the trans 2,3-diequatorial positions. Deprotection of the coupled products proceeded smoothly, unlike in previous attempts with different protecting groups, and afforded the target selenonium, sulfonium, and ammonium sulfates with different stereochemistry at the stereogenic centers. The four new heterosubstituted compounds (X = Se, NH) inhibited recombinant human maltase glucoamylase (MGA), one of the key intestinal enzymes involved in the breakdown of glucose oligosaccharides in the small intestine. The two selenium derivatives each had Ki values of 0.10 microM, giving the most active compounds to date in this general series of zwitterionic glycosidase inhibitors. The two nitrogen compounds also inhibited MGA but were less active, with Ki values of 0.8 and 35 microM. The compounds in which X = S showed Ki values of 0.25 and 0.17 microM. Comparison of these data with those reported previously for related compounds reinforces the requirements for an effective inhibitor of MGA. With respect to chain extension, the configurations at C-2' and C-4' are critical for activity, the configuration at C-3', bearing the sulfate moiety, being unimportant. It would also appear that the configuration at C-5' is important but the relationship is dependent on the heteroatom.

  18. A survey of faith leaders concerning health promotion and the level of healthy living activities occurring in faith communities in Scotland.

    PubMed

    Fagan, Donna M; Kiger, Alice; van Teijlingen, Edwin

    2010-12-01

    Faith groups constitute a growing health promotion partner in North America where they help increase community capacity. However, in the United Kingdom this collaboration is seemingly far less developed. This study sought to find evidence of health promotion in faith communities and examine perceptions and attitudes concerning health promotion among faith leaders. It also sought to establish the level to which health-promoting activities currently occur in, and are organized by, places of worship in one Scottish city, Dundee. The authors distributed a self-administered questionnaire to representatives of all faith communities in Dundee (response rate 71%, n = 50). The survey identified existing, well-formed community groups, some of whom already engaged in health-promoting activities, and shared similar interests with health promotion professionals. Generally, faith leaders were positive towards the concept of health promotion and many considered health promotion to be compatible with their mission. Not all denominations were equally involved in health promotion activities, for example, some conducted annual one-off activities, while others had well-established walking groups or exercise classes. The responses suggest a degree of readiness by faith communities to engage, if invited, in health promotion programmes. These results also indicate that faith groups may constitute untapped resources, poised to contribute to local health promotion efforts. The article concludes that as the National Health Service (NHS) invests in community-based health initiatives that can have long-term sustainability, it is reasonable to make links between what is happening in North America, the interest in health promotion reported by faith leaders in this study and the possibilities for their participation in voluntary sector community health partnerships.

  19. Numerical study of active flow control over a hypersonic backward-facing step using supersonic jet in near space

    NASA Astrophysics Data System (ADS)

    Guo, Guang-ming; Liu, Hong; Zhang, Bin

    2017-03-01

    Near space has been paid more and more attentions in recent years due to its militarily application value. Direct simulation Monte Carlo (DSMC) which is one of the most successful particle simulation methods in treating rarefied gas dynamics is employed to investigate the flow characteristics of a hypersonic backward-facing step (BFS) under active flow control using supersonic jet in near space. The numerical tool is validated by an experimental flow of dual cusped-plate model, shock wave structures from the numerical simulation are shown in quite good agreement with the experimental result. The influence of altitude and active flow control on BFS flow are then studied in detail. Three parameters, i.e. boundary layer thickness, recirculation region length, and lean angle of the primary recirculation region that is first defined to describe recirculation region shape, are used to evaluate the flow characteristics of every case computed. The numerical results indicate that the main effect of vertical jet upstream of the step is the enhancement of boundary layer thickness downstream of the jet slot, then, it shows a weak influence on recirculation region length and a negligible effect on lean angle. Conversely, the horizontal jet near the step edge can greatly change the recirculation region length by adjusting jetting angle, but it only has a weak influence both on boundary layer thickness and on lean angle for every jetting angle considered. A significant finding is that the recirculation region length is decreased severely in near space compared with experimental and numerical results presented in the open literature.

  20. Two-Step Bipolar Electrochemistry: Generation of Composition Gradient and Visual Screening of Electrocatalytic Activity.

    PubMed

    Termebaf, Hajar; Shayan, Mohsen; Kiani, Abolfazl

    2015-12-08

    Bipolar electrochemistry (BE) is employed for both creating electrocatalysts composition gradient and visual screening of the prepared composition on a single substrate in just two experiment runs. In a series of proof-of-principle experiments, we demonstrate gradient electrodeposition of Ni-Cu using BE; then the electrocatalytic activity of the prepared composition gradient toward the hydrogen evolution reaction (HER) is visually screened in the BE system using array of BPEs. Moreover, the morphology and the chemical composition of the Ni-Cu gradient are screened along the length of the bipolar electrode (BPE). By measuring the potential gradient over the BPE, it is also demonstrated that by controlling the concentration of the metals precursor and the supporting electrolyte, the length of the bipolar electrodeposited gradient can be controlled.

  1. The flavonoid paradox: conjugation and deconjugation as key steps for the biological activity of flavonoids.

    PubMed

    Perez-Vizcaino, Francisco; Duarte, Juan; Santos-Buelga, Celestino

    2012-07-01

    Flavonoids have been proposed to exert beneficial effects in the prevention of a large number of diseases, including cancer, cardiovascular disease, and neurodegenerative disorders. Paradoxically, despite the most representative flavonoid--quercetin--exerting biologically demonstrable systemic effects, it is not found in plasma after oral administration and its circulating metabolites show weak activity in vitro. The current available evidence indicates that quercetin is extensively metabolized into methylated and glucurono- and sulfo-conjugated metabolites, which are the plasma circulating forms; and glucurono-, but not sulfo-conjugates, can be hydrolyzed at the vascular level, yielding the parent aglycone which accumulates in tissues. Thus conjugation is a reversible process and, at least regarding the vasodilator and antihypertensive effects, the conjugation-deconjugation cycle appears to be an absolute requirement. Glucuronidated derivatives transport quercetin and its methylated form, and deliver to the tissues the free aglycone, which is the final effector.

  2. Internal recycle to improve denitrification in a step feed anoxic/aerobic activated sludge system.

    PubMed

    Boyle, C A; McKenzie, C J; Morgan, S

    2009-01-01

    During periods of low load (weekends and holidays) the Mangere wastewater treatment plant effluent has breached the summer consent conditions for total nitrogen. The purpose of this research was to determine if an internal recycle would improve nitrogen removal in the anoxic/aerobic activated sludge reactors sufficient to meet the summer resource consent standard. The recycle returned nitrate rich mixed liquor from the downstream aerobic zone back to the initial anoxic zone, thus potentially improving denitrification. A full scale trial showed that installation of the internal recycle on each RC would have satisfied the resource consent for total nitrogen in most cases over the three summer resource consent periods since the upgrade. However, further modifications of the internal recycle would be required to ensure that consent conditions were satisfied at all times and to improve the consistency of the results.

  3. In vivo kinematic comparison between mobile-bearing and fixed-bearing total knee arthroplasty during step-up activity.

    PubMed

    Okamoto, Nobukazu; Nakamura, Eiichi; Nishioka, Hiroaki; Karasugi, Tatsuki; Okada, Tatsuya; Mizuta, Hiroshi

    2014-12-01

    Mobile-bearing total knee arthroplasty (TKA) expects high conformity and low contact stress. It is designed to correct the rotational mismatch between femoral and tibial components. We examined the difference in weight-bearing knee kinematics in patients with mobile-bearing and fixed-bearing TKA performing step-up activities. We randomly assigned 40 knees (37 patients) to mobile-bearing TKA (n=20) or fixed-bearing TKA (n=20). Using fluoroscopic imaging we evaluated knee kinematics during step-up activity one year after surgery. The total extent of rotation was not different for the two TKAs. Due to the axial rotation of the polyethylene insert, patients with mobile-bearing TKA had a wider range of absolute axial rotation. The position of the medial and the lateral condyles was significantly more posterior in the fixed-bearing TKA. There were only minor kinematic differences between the two TKAs. The polyethylene insert in the mobile-bearing TKA moved as designed especially with respect to the self-alignment feature.

  4. Study protocol: using the Q-STEPS to assess and improve the quality of physical activity programmes for the elderly

    PubMed Central

    2012-01-01

    Background Aging is one of the most important and obvious phenomenon observed in our society. In the past years, there has been a growing concern in designing physical activity (PA) programmes for elderly people, because evidence suggests that such health promotion interventions may reduce the deleterious effects of the ageing process. Accordingly, a growing body of literature points to the importance of a sound approach to planning and evaluation in order to improve the quality of PA programmes. However, while numerous PA programmes have been designed for the elderly in recent years, their evaluation has been scarce. Quality management processes and tools provide a practical way for organisations to assess, identify and shed light on the areas requiring improvement. The Quality Self-assessment Tool for Exercise Programmes for Seniors (Q-STEPS) seems to provide a framework tailored to evaluate PA programmes for the elderly. Findings The primary purpose of this study is 1) to determine feasibility, acceptability and usability of the Q-STEPS. Secondary purposes of the study are: 2) to examine the quality of the PA programmes for elderly people developed by the Portuguese Local Administration over a three-year period of self-assessments in terms of: a) Enabler domains (Leadership, Policy and Strategy, People, Partnership and Resources, Processes); b) Result domains (Customer Results, People Results, Society Results and Key Performance Results); 3) to estimate the association between the use of Q-STEPS and some indicators relating to the elderly participants, during the three self-assessments, such as: attendance rates, physical fitness, health-related quality of life and the elderly’s perceived quality of the programme. The study will be conducted in PA programmes for elderly adults from mainland Portuguese municipalities over a three-year period. The project will adopt a participative quality improvement approach that features annual learning cycles of: 1) self

  5. [Photoreactivating Activity of Bioluminescence: Repair of UV-damaged DNA of Escherichia coli Occurs with Assistance of lux-Genes of Marine Bacteria].

    PubMed

    Zavilgelsky, G B; Melkina, O E; Kotova, V Yu; Konopleva, M N; Manukhov, I V; Pustovoit, K Ss

    2015-01-01

    The UV resistance of luminescent bacteria Escherichia coli AB1886 uvrA6 (pLeo1) containing the plasmid with luxCDABE genes of marine bacteria Photobacterium leiognathi is approximately two times higher than the UV resistance of non-luminous bacteria E. coli AB1886 uvrA6. Introduction of phr::kan(r) mutations (a defect in the functional activity of photolyase) into the genome of E. coli AB1886 uvrA6 (pLeo1) completely removes the high UV resistance of the cells. Therefore, photoreactivation that involves bacterial photolyase contributes mainly to the bioluminescence-induced DNA repair. It is shown that photoreactivating activity of bioluminescence of P. leiognathi is about 2.5 times lower compared with that one induced by a light source with λ > 385 nm. It is also shown that an increase in the bioluminescence intensity, induced by UV radiation in E. coli bacterial cells with a plasmid containing the luxCD ABE genes under RecA-LexA-regulated promoters, occurs only 25-30 min later after UV irradiation of cells and does not contribute to DNA repair. A quorum sensing regulatory system is not involved in the DNA repair by photolyase.

  6. Pentaprobe: a comprehensive sequence for the one-step detection of DNA-binding activities.

    PubMed

    Kwan, Ann H Y; Czolij, Robert; Mackay, Joel P; Crossley, Merlin

    2003-10-15

    The rapid increase in the number of novel proteins identified in genome projects necessitates simple and rapid methods for assigning function. We describe a strategy for determining whether novel proteins possess typical sequence-specific DNA-binding activity. Many proteins bind recognition sequences of 5 bp or less. Given that there are 4(5) possible 5 bp sites, one might expect the length of sequence required to cover all possibilities would be 4(5) x 5 or 5120 nt. But by allowing overlaps, utilising both strands and using a computer algorithm to generate the minimum sequence, we find the length required is only 516 base pairs. We generated this sequence as six overlapping double-stranded oligonucleotides, termed pentaprobe, and used it in gel retardation experiments to assess DNA binding by both known and putative DNA-binding proteins from several protein families. We have confirmed binding by the zinc finger proteins BKLF, Eos and Pegasus, the Ets domain protein PU.1 and the treble clef N- and C-terminal fingers of GATA-1. We also showed that the N-terminal zinc finger domain of FOG-1 does not behave as a typical DNA-binding domain. Our results suggest that pentaprobe, and related sequences such as hexaprobe, represent useful tools for probing protein function.

  7. New paradigms for understanding and step changes in treating active and chronic, persistent apicomplexan infections

    PubMed Central

    McPhillie, Martin; Zhou, Ying; El Bissati, Kamal; Dubey, Jitender; Lorenzi, Hernan; Capper, Michael; Lukens, Amanda K; Hickman, Mark; Muench, Stephen; Verma, Shiv Kumar; Weber, Christopher R.; Wheeler, Kelsey; Gordon, James; Sanders, Justin; Moulton, Hong; Wang, Kai; Kim, Taek-Kyun; He, Yuqing; Santos, Tatiana; Woods, Stuart; Lee, Patty; Donkin, David; Kim, Eric; Fraczek, Laura; Lykins, Joseph; Esaa, Farida; Alibana-Clouser, Fatima; Dovgin, Sarah; Weiss, Louis; Brasseur, Gael; Wirth, Dyann; Kent, Michael; Hood, Leroy; Meunieur, Brigitte; Roberts, Craig W.; Hasnain, S. Samar; Antonyuk, Svetlana V.; Fishwick, Colin; McLeod, Rima

    2016-01-01

    Toxoplasma gondii, the most common parasitic infection of human brain and eye, persists across lifetimes, can progressively damage sight, and is currently incurable. New, curative medicines are needed urgently. Herein, we develop novel models to facilitate drug development: EGS strain T. gondii forms cysts in vitro that induce oocysts in cats, the gold standard criterion for cysts. These cysts highly express cytochrome b. Using these models, we envisioned, and then created, novel 4-(1H)-quinolone scaffolds that target the cytochrome bc1 complex Qi site, of which, a substituted 5,6,7,8-tetrahydroquinolin-4-one inhibits active infection (IC50, 30 nM) and cysts (IC50, 4 μM) in vitro, and in vivo (25 mg/kg), and drug resistant Plasmodium falciparum (IC50, <30 nM), with clinically relevant synergy. Mutant yeast and co-crystallographic studies demonstrate binding to the bc1 complex Qi site. Our results have direct impact on improving outcomes for those with toxoplasmosis, malaria, and ~2 billion persons chronically infected with encysted bradyzoites. PMID:27412848

  8. Differential activity of candidate microbicides against early steps of HIV-1 infection upon complement virus opsonization

    PubMed Central

    2010-01-01

    Background HIV-1 in genital secretions may be opsonized by several molecules including complement components. Opsonized HIV-1 by complement enhances the infection of various mucosal target cells, such as dendritic cells (DC) and epithelial cells. Results We herein evaluated the effect of HIV-1 complement opsonization on microbicide candidates' activity, by using three in vitro mucosal models: CCR5-tropic HIV-1JR-CSF transcytosis through epithelial cells, HIV-1JR-CSF attachment on immature monocyte-derived dendritic cells (iMDDC), and infectivity of iMDDC by CCR5-tropic HIV-1BaL and CXCR4-tropic HIV-1NDK. A panel of 10 microbicide candidates [T20, CADA, lectines HHA & GNA, PVAS, human lactoferrin, and monoclonal antibodies IgG1B12, 12G5, 2G12 and 2F5], were investigated using cell-free unopsonized or opsonized HIV-1 by complements. Only HHA and PVAS were able to inhibit HIV trancytosis. Upon opsonization, transcytosis was affected only by HHA, HIV-1 adsorption on iMDDC by four molecules (lactoferrin, IgG1B12, IgG2G5, IgG2G12), and replication in iMDDC of HIV-1BaL by five molecules (lactoferrin, CADA, T20, IgG1B12, IgG2F5) and of HIV-1NDK by two molecules (lactoferrin, IgG12G5). Conclusion These observations demonstrate that HIV-1 opsonization by complements may modulate in vitro the efficiency of candidate microbicides to inhibit HIV-1 infection of mucosal target cells, as well as its crossing through mucosa. PMID:20546571

  9. a Step Towards Dynamic Scene Analysis with Active Multi-View Range Imaging Systems

    NASA Astrophysics Data System (ADS)

    Weinmann, M.; Jutzi, B.

    2012-07-01

    Obtaining an appropriate 3D description of the local environment remains a challenging task in photogrammetric research. As terrestrial laser scanners (TLSs) perform a highly accurate, but time-dependent spatial scanning of the local environment, they are only suited for capturing static scenes. In contrast, new types of active sensors provide the possibility of simultaneously capturing range and intensity information by images with a single measurement, and the high frame rate also allows for capturing dynamic scenes. However, due to the limited field of view, one observation is not sufficient to obtain a full scene coverage and therefore, typically, multiple observations are collected from different locations. This can be achieved by either placing several fixed sensors at different known locations or by using a moving sensor. In the latter case, the relation between different observations has to be estimated by using information extracted from the captured data and then, a limited field of view may lead to problems if there are too many moving objects within it. Hence, a moving sensor platform with multiple and coupled sensor devices offers the advantages of an extended field of view which results in a stabilized pose estimation, an improved registration of the recorded point clouds and an improved reconstruction of the scene. In this paper, a new experimental setup for investigating the potentials of such multi-view range imaging systems is presented which consists of a moving cable car equipped with two synchronized range imaging devices. The presented setup allows for monitoring in low altitudes and it is suitable for getting dynamic observations which might arise from moving cars or from moving pedestrians. Relying on both 3D geometry and 2D imagery, a reliable and fully automatic approach for co-registration of captured point cloud data is presented which is essential for a high quality of all subsequent tasks. The approach involves using sparse point

  10. Participant Adherence Indicators Predict Changes in Blood Pressure, Anthropometric Measures, and Self-Reported Physical Activity in a Lifestyle Intervention: HUB City Steps

    ERIC Educational Resources Information Center

    Thomson, Jessica L.; Landry, Alicia S.; Zoellner, Jamie M.; Connell, Carol; Madson, Michael B.; Molaison, Elaine Fontenot; Yadrick, Kathy

    2015-01-01

    The objective of this secondary analysis was to evaluate the utility of several participant adherence indicators for predicting changes in clinical, anthropometric, dietary, fitness, and physical activity (PA) outcomes in a lifestyle intervention, HUB City Steps, conducted in a southern, African American cohort in 2010. HUB City Steps was a…

  11. Steps to Health in Cognitive Aging: Effects of Physical Activity on Spatial Attention and Executive Control in the Elderly.

    PubMed

    Condello, Giancarlo; Forte, Roberta; Falbo, Simone; Shea, John B; Di Baldassarre, Angela; Capranica, Laura; Pesce, Caterina

    2017-01-01

    The purpose of this study was to investigate whether physical activity (PA) habits may positively impact performance of the orienting and executive control networks in community-dwelling aging individuals and diabetics, who are at risk of cognitive dysfunction. To this aim, we tested cross-sectionally whether age, ranging from late middle-age to old adulthood, and PA level independently or interactively predict different facets of the attentional performance. Hundred and thirty female and male individuals and 22 adults with type 2 diabetes aged 55-84 years were recruited and their daily PA (steps) was objectively measured by means of armband monitors. Participants performed a multifunctional attentional go/no-go reaction time (RT) task in which spatial attention was cued by means of informative direct cues of different sizes followed by compound stimuli with local and global target features. The performance efficiency of the orienting networks was estimated by computing RT differences between validly and invalidly cued trials, that of the executive control networks by computing local switch costs that are RT differences between switch and non-switch trials in mixed blocks of global and local target trials. In regression analyses performed on the data of non-diabetic elderlies, overall RTs and orienting effects resulted jointly predicted by age and steps. Age predicted overall RTs in low-active individuals, but orienting effects and response errors in high-active individuals. Switch costs were predicted by age only, with larger costs at older age. In the analysis conducted with the 22 diabetics and 22 matched non-diabetic elderlies, diabetic status and daily steps predicted longer and shorter RTs, respectively. Results suggest that high PA levels exert beneficial, but differentiated effects on processing speed and attentional networks performance in aging individuals that partially counteract the detrimental effects of advancing age and diabetic status. In

  12. Steps to Health in Cognitive Aging: Effects of Physical Activity on Spatial Attention and Executive Control in the Elderly

    PubMed Central

    Condello, Giancarlo; Forte, Roberta; Falbo, Simone; Shea, John B.; Di Baldassarre, Angela; Capranica, Laura; Pesce, Caterina

    2017-01-01

    The purpose of this study was to investigate whether physical activity (PA) habits may positively impact performance of the orienting and executive control networks in community-dwelling aging individuals and diabetics, who are at risk of cognitive dysfunction. To this aim, we tested cross-sectionally whether age, ranging from late middle-age to old adulthood, and PA level independently or interactively predict different facets of the attentional performance. Hundred and thirty female and male individuals and 22 adults with type 2 diabetes aged 55–84 years were recruited and their daily PA (steps) was objectively measured by means of armband monitors. Participants performed a multifunctional attentional go/no-go reaction time (RT) task in which spatial attention was cued by means of informative direct cues of different sizes followed by compound stimuli with local and global target features. The performance efficiency of the orienting networks was estimated by computing RT differences between validly and invalidly cued trials, that of the executive control networks by computing local switch costs that are RT differences between switch and non-switch trials in mixed blocks of global and local target trials. In regression analyses performed on the data of non-diabetic elderlies, overall RTs and orienting effects resulted jointly predicted by age and steps. Age predicted overall RTs in low-active individuals, but orienting effects and response errors in high-active individuals. Switch costs were predicted by age only, with larger costs at older age. In the analysis conducted with the 22 diabetics and 22 matched non-diabetic elderlies, diabetic status and daily steps predicted longer and shorter RTs, respectively. Results suggest that high PA levels exert beneficial, but differentiated effects on processing speed and attentional networks performance in aging individuals that partially counteract the detrimental effects of advancing age and diabetic status. In

  13. One-step green synthesis of non-hazardous dicarboxyl cellulose flocculant and its flocculation activity evaluation.

    PubMed

    Zhu, Hangcheng; Zhang, Yong; Yang, Xiaogang; Liu, Hongyi; Shao, Lan; Zhang, Xiumei; Yao, Juming

    2015-10-15

    The waste management of used flocculants is a thorny issue in the field of wastewater treatment. To natural cellulose based flocculants, utilization of hazardous cellulose solvent and simplification of synthetic procedure are the two urgent problems needing to be further improved. In this work, a series of natural dicarboxyl cellulose flocculants (DCCs) were one-step synthesized via Schiff-base route. The cellulose solvent (NaOH/Urea solution) was utilized during the synthesis process. The full-biodegradable flocculants avoid causing secondary pollution to environment. The chemical structure and solution property of the DCC products were characterized by FT-IR, (1)H NMR, (13)C NMR, TGA, FESEM, charge density and ζ-potential. Kaolin suspension and effluent from paper mill were selected to evaluate the flocculation activity of the DCCs. Their flocculation performance was compared with that of commercial cationic polyacrylamide and poly aluminium chloride flocculants. The positive results showed that the NaOH/Urea solvent effectively promoted the dialdehyde cellulose (DAC) conversion to DCC in the one-step synthesis reaction. The DCCs with the carboxylate content more than 1 mmol/g exhibited steady flocculation performance to kaolin suspension in the broad pH range from 4 to 10. Its flocculation capacity to the effluent from paper mill also showed excellent.

  14. Adrenergic activation of melatonin secretion in ovine pineal explants in short-term superfusion culture occurs via protein synthesis independent and dependent phenomena.

    PubMed

    Lewczuk, Bogdan; Ziółkowska, Natalia; Prusik, Magdalena; Przybylska-Gornowicz, Barbara

    2014-01-01

    The ovine pineal is generally considered as an interesting model for the study on adrenergic regulation of melatonin secretion due to some functional similarities with this gland in the human. The present investigations, performed in the superfusion culture of pineal explants, demonstrated that the norepinephrine-induced elevation of melatonin secretion in ovine pinealocytes comprised of two subsequent periods: a rapid increase phase and a slow increase phase. The first one included the quick rise in release of N-acetylserotonin and melatonin, occurring parallel to elevation of NE concentration in the medium surrounding explants. This rapid increase phase was not affected by inhibition of translation. The second, slow increase phase began after NE level had reached the maximum concentration in the culture medium and lasted about two hours. It was completely abolished by the treatment with translation inhibitors. The obtained results showed for the first time that the regulation of N-acetylserotonin synthesis in pinealocytes of some species like the sheep involves the on/off mechanism, which is completely independent of protein synthesis and works very fast. They provided strong evidence pointing to the need of revision of the current opinion that arylalkylamines N-acetyltransferase activity in pinealocytes is controlled exclusively by changes in enzyme abundance.

  15. Design, Development, and Formative Evaluation of a Smartphone Application for Recording and Monitoring Physical Activity Levels: The 10,000 Steps "iStepLog"

    ERIC Educational Resources Information Center

    Kirwan, Morwenna; Duncan, Mitch J.; Vandelanotte, Corneel; Mummery, W. Kerry

    2013-01-01

    Objectives: Limited research exists addressing the development of health-related smartphone apps, a new and potentially effective health promotion delivery strategy. This article describes the development and formative evaluation of a smartphone app associated with a physical activity promotion website. Methods: A combination of qualitative and…

  16. Monitoring Step Activity During Task-Oriented Circuit Training in High-Functioning Chronic Stroke Survivors: A Proof-of-Concept Feasibility Study

    PubMed Central

    2016-01-01

    Objective To explore the amount of practice and progression during task-oriented circuit training (TOCT) in chronic stroke survivors; to test the use of pedometers and observation-based measures in detecting step activity; to verify the possible correlation between step activity and locomotor function improvements. Methods Six community-dwelling chronic stroke survivors underwent 10 TOCT sessions (2 hours/each) over 2 weeks in which they were trained both on a treadmill and on six task-oriented workstations (W1–W6). During the sessions, they wore a piezoelectric pedometer and step activities were recorded. Outcome measures were as follows: % of activities during which pedometers worked properly; pedometer-based measures (total step counts, treadmill steps, workstation steps—total and W2,W3,W5,W6); observation-based measures (number of repetitions in task W1 and W4); walking speed changes measured by the 10-m walking test (10MWT) and walking endurance changes (6-minute walking test) after TOCT. Results During TOCT sessions (n=57), activities were recorded through pedometer-based measures in 4 out of the 6 patients. The total amount of step activity was 5,980.05±1,968.39 steps (54.29% in task-oriented workstations, 37.67% on treadmill, and 8.03% during breaks). Exercise progression was highlighted significantly by observational measures (W1, W4). A positive correlation was observed between increased gait speed and observational stair step repetitions progression (W1) (r=0.91, p=0.01) or pedometer-based tandem exercise step progression (W3) (r=0.98, p=0.01). Conclusion TOCT can be considered a high-intensity, progressive intervention to restore locomotor function in chronic stroke survivors. Pedometer-based measures might help in quantifying TOCT's volume of practice; however, further investigations are required. PMID:28119828

  17. Effects of Stroke on Ipsilesional End-Effector Kinematics in a Multi-Step Activity of Daily Living

    PubMed Central

    Gulde, Philipp; Hughes, Charmayne Mary Lee; Hermsdörfer, Joachim

    2017-01-01

    Background: Stroke frequently impairs activities of daily living (ADL) and deteriorates the function of the contra- as well as the ipsilesional limbs. In order to analyze alterations of higher motor control unaffected by paresis or sensory loss, the kinematics of ipsilesional upper limb movements in patients with stroke has previously been analyzed during prehensile movements and simple tool use actions. By contrast, motion recording of multi-step ADL is rare and patient-control comparisons for movement kinematics are largely lacking. Especially in clinical research, objective quantification of complex externally valid tasks can improve the assessment of neurological impairments. Methods: In this preliminary study we employed three-dimensional motion recording and applied kinematic analysis in a multi-step ADL (tea-making). The trials were examined with respect to errors and sub-action structure, durations, path lengths (PLs), peak velocities, relative activity (RA) and smoothness. In order to check for specific burdens the sub-actions of the task were extracted and compared. To examine the feasibility of the approach, we determined the behavioral and kinematic metrics of the (ipsilesional) unimanual performance of seven chronic stroke patients (64a ± 11a, 3 with right/4 with left brain damage (LBD), 2 with signs of apraxia, variable severity of paresis) and compared the results with data of 14 neurologically healthy age-matched control participants (70a ± 7a). Results: T-tests revealed that while the quantity and structure of sub-actions of the task were similar. The analysis of end-effector kinematics was able to detect clear group differences in the associated parameters. Specifically, trial duration (TD) was increased (Cohen’s d = 1.77); the RA (Cohen’s d = 1.72) and the parameters of peak velocities (Cohen’s d = 1.49/1.97) were decreased in the patient group. Analysis of the task’s sub-actions repeated measures analysis of variance (rmANOVA) revealed

  18. Two-step activation of paper batteries for high power generation: design and fabrication of biofluid- and water-activated paper batteries

    NASA Astrophysics Data System (ADS)

    Lee, Ki Bang

    2006-11-01

    Two-step activation of paper batteries has been successfully demonstrated to provide quick activation and to supply high power to credit card-sized biosystems on a plastic chip. A stack of a magnesium layer (an anode), a fluid guide (absorbent paper), a highly doped filter paper with copper chloride (a cathode) and a copper layer as a current collector is laminated between two transparent plastic films into a high power biofluid- and water-activated battery. The battery is activated by two-step activation: (1) after placing a drop of biofluid/water-based solution on the fluid inlet, the surface tension first drives the fluid to soak the fluid guide; (2) the fluid in the fluid guide then penetrates into the heavily doped filter paper with copper chloride to start the battery reaction. The fabricated half credit card-sized battery was activated by saliva, urine and tap water and delivered a maximum voltage of 1.56 V within 10 s after activation and a maximum power of 15.6 mW. When 10 kΩ and 1 KΩ loads are used, the service time with water, urine and saliva is measured as more than 2 h. An in-series battery of 3 V has been successfully tested to power two LEDs (light emitting diodes) and an electric driving circuit. As such, this high power paper battery could be integrated with on-demand credit card-sized biosystems such as healthcare test kits, biochips, lab-on-a-chip, DNA chips, protein chips or even test chips for water quality checking or chemical checking.

  19. One-step synthesis, characterization, and visible light photocatalytic activity of pure and Zn-doped SnO2 nanoparticles

    NASA Astrophysics Data System (ADS)

    Madhan, D.; Rajkumar, P.; Rajeshwaran, P.; Sivarajan, A.; Sangeetha, M.

    2015-08-01

    A one-step microwave irradiation route was used to synthesize undoped and Zn-doped SnO2 nanoparticles for the first time. The morphologies, structures and optical properties of the as-prepared samples were characterized by X-ray powder diffraction, field emission scanning electron microscopy (FESEM), energy-dispersive X-ray spectroscopy, UV-Vis spectra and photoluminescence spectra analysis. The results clearly revealed that both the pure and doped samples had a tetragonal rutile-type structure and a space group of P42/mnm have formed directly during the microwave irradiation process. FESEM studies illustrate that both the pristine and Zn-doped SnO2 form in spherical-shaped morphology with an average diameter around 41-32 nm, which is in good agreement with the average crystallite sizes calculated by Scherrer's formula. Optical studies reveal that both pristine and Zn-doped SnO2 direct transitions occur with the bandgap energies in the range of 3.43-3.26 eV. The photocatalytic activities of the pure and Zn-doped SnO2 samples were evaluated by the degradation of methylene blue rhodamine B in an aqueous solution under visible light irradiation. The photocatalytic activity and reusability of Zn (10 wt%)-doped SnO2 was much higher than that of the pure SnO2. The improvement mechanism by zinc doping was also discussed.

  20. Quantitative Characterization of the Activation Steps of Mannan-binding Lectin (MBL)-associated Serine Proteases (MASPs) Points to the Central Role of MASP-1 in the Initiation of the Complement Lectin Pathway*

    PubMed Central

    Megyeri, Márton; Harmat, Veronika; Major, Balázs; Végh, Ádám; Balczer, Júlia; Héja, Dávid; Szilágyi, Katalin; Datz, Dániel; Pál, Gábor; Závodszky, Péter; Gál, Péter; Dobó, József

    2013-01-01

    Mannan-binding lectin (MBL)-associated serine proteases, MASP-1 and MASP-2, have been thought to autoactivate when MBL/ficolin·MASP complexes bind to pathogens triggering the complement lectin pathway. Autoactivation of MASPs occurs in two steps: 1) zymogen autoactivation, when one proenzyme cleaves another proenzyme molecule of the same protease, and 2) autocatalytic activation, when the activated protease cleaves its own zymogen. Using recombinant catalytic fragments, we demonstrated that a stable proenzyme MASP-1 variant (R448Q) cleaved the inactive, catalytic site Ser-to-Ala variant (S646A). The autoactivation steps of MASP-1 were separately quantified using these mutants and the wild type enzyme. Analogous mutants were made for MASP-2, and rate constants of the autoactivation steps as well as the possible cross-activation steps between MASP-1 and MASP-2 were determined. Based on the rate constants, a kinetic model of lectin pathway activation was outlined. The zymogen autoactivation rate of MASP-1 is ∼3000-fold higher, and the autocatalytic activation of MASP-1 is about 140-fold faster than those of MASP-2. Moreover, both activated and proenzyme MASP-1 can effectively cleave proenzyme MASP-2. MASP-3, which does not autoactivate, is also cleaved by MASP-1 quite efficiently. The structure of the catalytic region of proenzyme MASP-1 R448Q was solved at 2.5 Å. Proenzyme MASP-1 R448Q readily cleaves synthetic substrates, and it is inhibited by a specific canonical inhibitor developed against active MASP-1, indicating that zymogen MASP-1 fluctuates between an inactive and an active-like conformation. The determined structure provides a feasible explanation for this phenomenon. In summary, autoactivation of MASP-1 is crucial for the activation of MBL/ficolin·MASP complexes, and in the proenzymic phase zymogen MASP-1 controls the process. PMID:23386610

  1. STEPS TOWARD UNVEILING THE TRUE POPULATION OF ACTIVE GALACTIC NUCLEI: PHOTOMETRIC CHARACTERIZATION OF ACTIVE GALACTIC NUCLEI IN COSMOS

    SciTech Connect

    Schneider, Evan E.; Impey, Christopher D.; Trump, Jonathan R.

    2013-04-01

    Using a physically motivated, model-based active galactic nucleus (AGN) characterization technique, we fit a large sample of X-ray-selected AGNs with known spectroscopic redshifts from the Cosmic Evolution Survey field. We identify accretion disks in the spectral energy distributions of broad- and narrow-line AGNs, and infer the presence or absence of host galaxy light in the SEDs. Based on infrared and UV excess AGN selection techniques, our method involves fitting a given SED with a model consisting of three components: infrared power-law emission, optical-UV accretion disk emission, and host galaxy emission. Each component can be varied in relative contribution, and a reduced chi-square minimization routine is used to determine the optimum parameters for each object. Using this technique, both broad- and narrow-line AGNs fall within well-defined and plausible bounds on the physical parameters of the model, allowing trends with luminosity and redshift to be determined. In particular, based on our sample of spectroscopically confirmed AGNs, we find that approximately 95% of the broad-line AGNs and 50% of the narrow-line AGNs in our sample show evidence of an accretion disk, with maximum disk temperatures ranging from 1 to 10 eV. Because this fitting technique relies only on photometry, we hope to apply it in future work to the characterization and eventually the selection of fainter AGNs than are accessible in wide-field spectroscopic surveys, and thus probe a population of less luminous and/or higher redshift objects without prior redshift or X-ray data. With the abundant availability of photometric data from large surveys, the ultimate goal is to use this technique to create large samples that will complement and complete AGN catalogs selected by X-ray emission alone.

  2. Deuterium-oxide-induced histamine release from basophils of allergic subjects. I. Responsiveness to deuterium oxide requires an activation step

    SciTech Connect

    Kazimierczak, W.; Plaut, M.; Knauer, K.A.; Meier, H.L.; Lichtenstein, L.M.

    1984-04-01

    Basophils from many atopic persons, and especially asthmatic patients, have been shown to release histamine in response to 44% deuterium oxide (D2O), whereas basophils from nonatopic persons do not release histamine. The present experiments analyzed the mechanisms by which D/sub 2/O mediated release. It was found that although D/sub 2/O induced release from washed leukocytes, it failed to induce release from whole blood or from leukocytes that had sedimented but had not been washed. The kinetics of release after washing were rapid and were equivalent regardless of the temperature at which cells were sedimented (O degrees or 37 degrees C). Washed cells became desensitized to the action of D/sub 2/O within 30 to 60 min at 37 degrees C, whereas unwashed leukocytes did not become desensitized. Serum or plasma inhibited D/sub 2/O-induced release, although high concentrations (1/5) were less inhibitory than lower ones (1/10 to 1/100). Basophils from D/sub 2/O responders also released histamine in response to a ''platelet enhancing factor'' (PEF), whereas those from D/sub 2/O nonresponders did not. As with D/sub 2/O-mediated release, PEF-mediated release occurred only with washed leukocytes, desensitized within 30 to 60 min at 37 degrees C, and was inhibited by serum. These results suggest that D/sub 2/O induces histamine release by augmenting the effects of an endogenous activation mechanism, and that PEF acts on the same (D/sub 2/O-responsive) donors to augment this activation mechanism. Cell activation, as well as desensitization of this activation mechanism, occurs rapidly when basophils are washed free of plasma inhibitors and placed at 37 degrees C.

  3. In vitro screening of inhibition of PPAR-γ activity as a first step in identification of potential breast carcinogens.

    PubMed

    Kopp, T I; Lundqvist, J; Petersen, R K; Oskarsson, A; Kristiansen, K; Nellemann, C; Vogel, U

    2015-11-01

    Alcohol consumption and increased estrogen levels are major risk factors for breast cancer, and peroxisome proliferator-activated receptor γ (PPAR-γ) plays an important role in alcohol-induced breast cancer. PPAR-γ activity is inhibited by ethanol, leading to increased aromatase activity and estrogen biosynthesis ultimately leading to breast cancer. If other organic solvents inhibit PPAR-γ activity, they should also lead to increased oestrogen biosynthesis and thus be potential breast carcinogens. Ten commonly used hydrophilic organic solvents were first tested in a cell-based screening assay for inhibitory effects on PPAR-γ transactivation. The chemicals shown to inhibit PPAR-γ were tested with vectors encoding PPAR-γ with deleted AB domains and only the ligand-binding domain to rule out unspecific toxicity. Next, the effects on biosynthesis of estradiol, testosterone and oestrone sulphate were measured in the H295R steroidogenesis assay after incubation with the chemicals. Ethylene glycol, ethyl acetate, and dimethyl sulphoxide inhibited PPAR-γ transactivation in a dose-dependent manner. The inhibitory effect on PPAR-γ was specific for PPAR-γ since the AB domain of PPAR-γ was required for the inhibitory effect. In the second step, ethylene glycol significantly increased production of oestradiol by 19% (p < 0.05) and ethyl acetate inhibited production of testosterone (p < 0.05). We here show that screening of 10 commonly used organic solvents for the ability to inhibit PPAR-γ transactivation followed by a well-established steroidogenesis assay for production of sex hormones in exposed H295 R cells may provide a screening tool for potential breast carcinogens. This initial screening thus identified ethylene glycol and possibly ethyl acetate as potential breast carcinogens.

  4. Multiple Steps of Phosphorylation of Activated Rhodopsin Can Account for the Reproducibility of Vertebrate Rod Single-photon Responses

    PubMed Central

    Hamer, R.D.; Nicholas, S.C.; Tranchina, D.; Liebman, P.A.; Lamb, T.D.

    2003-01-01

    Single-photon responses (SPRs) in vertebrate rods are considerably less variable than expected if isomerized rhodopsin (R*) inactivated in a single, memoryless step, and no other variability-reducing mechanisms were available. We present a new stochastic model, the core of which is the successive ratcheting down of R* activity, and a concomitant increase in the probability of quenching of R* by arrestin (Arr), with each phosphorylation of R* (Gibson, S.K., J.H. Parkes, and P.A. Liebman. 2000. Biochemistry. 39:5738–5749.). We evaluated the model by means of Monte-Carlo simulations of dim-flash responses, and compared the response statistics derived from them with those obtained from empirical dim-flash data (Whitlock, G.G., and T.D. Lamb. 1999. Neuron. 23:337–351.). The model accounts for four quantitative measures of SPR reproducibility. It also reproduces qualitative features of rod responses obtained with altered nucleotide levels, and thus contradicts the conclusion that such responses imply that phosphorylation cannot dominate R* inactivation (Rieke, F., and D.A. Baylor. 1998a. Biophys. J. 75:1836–1857; Field, G.D., and F. Rieke. 2002. Neuron. 35:733–747.). Moreover, the model is able to reproduce the salient qualitative features of SPRs obtained from mouse rods that had been genetically modified with specific pathways of R* inactivation or Ca2+ feedback disabled. We present a theoretical analysis showing that the variability of the area under the SPR estimates the variability of integrated R* activity, and can provide a valid gauge of the number of R* inactivation steps. We show that there is a heretofore unappreciated tradeoff between variability of SPR amplitude and SPR duration that depends critically on the kinetics of inactivation of R* relative to the net kinetics of the downstream reactions in the cascade. Because of this dependence, neither the variability of SPR amplitude nor duration provides a reliable estimate of the underlying variability

  5. Implementing Behavioral Activation and Life-Steps for Depression and HIV Medication Adherence in a Community Health Center

    PubMed Central

    Magidson, Jessica F.; Seitz-Brown, C. J.; Safren, Steven A.; Daughters, Stacey B.

    2014-01-01

    Antiretroviral therapy to treat HIV/AIDS has substantially improved clinical outcomes among patients living with HIV/AIDS, but only in the presence of very consistent adherence. One of the most prevalent and impactful individual-level predictors of poor adherence is depressive symptoms, even at subthreshold levels. Evidence-based cognitive behavioral interventions exist to address improvements in depressive symptoms and adherence in this population, yet these techniques have largely been designed and tested as individual treatments for delivery in mental health settings. This presents a significant challenge when transporting these techniques to medical settings where other formats for delivery may be more appropriate (i.e., groups, less frequent visits) and few hands-on resources exist to guide this process. As such, primary aims of this study were to adapt and implement evidence-based cognitive behavioral techniques for depression (behavioral activation; BA) and HIV medication adherence (Life-Steps) that have potential for dissemination in an outpatient community health center. The intervention incorporated feedback from health center staff and utilized a modular, group format that did not rely on sequential session attendance. Feasibility was examined over 8 weeks (n = 13). Preliminary effects on depression, health-related quality of life, and medication adherence were examined and exit interviews were conducted with a subset of participants (n = 4) to inform future modifications. Treatment descriptions and recommendations for effective clinical implementation based on patient and clinician feedback are provided along with case material of two individual patients and an example group session. Current efforts are an important next step for disseminating evidence-based techniques for depression and HIV medication adherence to community health center or AIDS service organization settings. PMID:25419102

  6. One-step synthesis of redox-active polymer/AU nanocomposites for electrochemical immunoassay of multiplexed tumor markers.

    PubMed

    Liu, Zhimin; Rong, Qinfeng; Ma, Zhanfang; Han, Hongliang

    2015-03-15

    In this work, a simple and sensitive multiplexed immunoassay protocol for simultaneous electrochemical determination of alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) was designed using redox-active nanocomposites. As the redox-active species, the poly(o-phenylenediamine) (POPD)/Au nanocomposite and poly(vinyl ferrocene-2-aminothiophenol) (poly(VFc-ATP))/Au nanocomposite were obtained by one-step method which HAuCl4 was used as the oxidant. With Au nanoparticles (AuNPs), the nanocomposites were successful to immobilize labeled anti-CEA and anti-AFP as the immunosensing probes. The proposed electrochemical immunoassay enabled the simultaneous monitoring of AFP and CEA in a wide range of 0.01-100ngmL(-1). The detection limits was 0.006ngmL(-1) for CEA and 0.003ngmL(-1) for AFP (S/N=3). The assay results of serum samples with the proposed method were well consistent with the reference values from standard ELISA method. And the negligible cross-reactivity between the two analytes makes it possesses potential promise in clinical diagnosis.

  7. Repetition Blindness Occurs in Nonwords

    ERIC Educational Resources Information Center

    Harris, Catherine L.; Morris, Alison L.

    2004-01-01

    Theorists have predicted that repetition blindness (RB) should be absent for nonwords because they do not activate preexisting mental types. The authors hypothesized that RB would be observed for nonwords because RB can occur at a sublexical level. Four experiments showed that RB is observed for word-nonword pairs (noon noof), orthographically…

  8. The contribution of golf to daily physical activity recommendations: how many steps does it take to complete a round of golf?

    PubMed

    Kobriger, Samantha L; Smith, Jay; Hollman, John H; Smith, Aynsley M

    2006-08-01

    To quantify the number of steps adults take during an 18-hole round of golf, we recruited 42 healthy volunteers (12 men and 30 women aged 30-80 years) with established United States Golf Association handicaps to complete an 18-hole round of golf on each of 3 municipal golf courses. Subjects walked each course while wearing a pedometer to record step data. Analysis revealed that each golfer took a mean +/- SD 11,948 +/- 1781 steps per 18-hole round of golf. Regardless of handicap level, sex, or course played, most subjects exceeded 10,000 steps during a typical round of golf. Consequently, in most cases, walking 18 holes of golf will meet the recommendation to accumulate 10,000 steps per day as part of a general physical activity plan.

  9. Mesoporous-activated carbon prepared from chitosan flakes via single-step sodium hydroxide activation for the adsorption of methylene blue.

    PubMed

    Marrakchi, F; Ahmed, M J; Khanday, W A; Asif, M; Hameed, B H

    2017-05-01

    In this work, mesoporous-activated carbon (CSAC) was prepared from chitosan flakes (CS) via single-step sodium hydroxide activation for the adsorption of methylene blue (MB). CSAC was prepared using different impregnation ratios of NaOH:CS (1:1, 2:1, 3:1, and 4:1) at 800°C for 90min. The adsorption performance of CSAC was evaluated for MB at different adsorption variables, such MB initial concentrations (25-400mg/L), solution pH (3-11), and temperature (30-50°C). The adsorption isotherm data of CSAC-MB were well fitted to Langmuir model with a maximum adsorption capacity 143.53mg/g at 50°C. Best representation of kinetic data was obtained by the pseudo-second order model. CSAC exhibited excellent adsorption uptake for MB and can potentially be used for other cationic dyes.

  10. PHOEBE - step by step manual

    NASA Astrophysics Data System (ADS)

    Zasche, P.

    2016-03-01

    An easy step-by-step manual of PHOEBE is presented. It should serve as a starting point for the first time users of PHOEBE analyzing the eclipsing binary light curve. It is demonstrated on one particular detached system also with the downloadable data and the whole procedure is described easily till the final trustworthy fit is being reached.

  11. The Devon Active Villages Evaluation (DAVE) trial of a community-level physical activity intervention in rural south-west England: a stepped wedge cluster randomised controlled trial

    PubMed Central

    2014-01-01

    Background The majority of adults are not meeting the guidelines for physical activity despite activity being linked with numerous improvements to long-term health. In light of this, researchers have called for more community-level interventions. The main objective of the present study was to evaluate whether a community-level physical activity intervention increased the activity levels of rural communities. Methods 128 rural villages (clusters) were randomised to receive the intervention in one of four time periods between April 2011 and December 2012. The Devon Active Villages intervention provided villages with 12 weeks of physical activity opportunities for all age groups, including at least three different types of activities per village. Each village received an individually tailored intervention, incorporating a local needs-led approach. Support was provided for a further 12 months following the intervention. The evaluation study used a stepped wedge cluster randomised controlled trial design. All 128 villages were measured at each of five data collection periods using a postal survey. The primary outcome of interest was the proportion of adults reporting sufficient physical activity to meet internationally recognised guidelines. Minutes spent in moderate-and-vigorous activity per week was analysed as a secondary outcome. To compare between intervention and control modes, random effects linear regression and marginal logistic regression models were implemented for continuous and binary outcomes respectively. Results 10,412 adults (4693 intervention, 5719 control) completed the postal survey (response rate 32.2%). The intervention did not increase the odds of adults meeting the physical activity guideline (adjusted OR 1.02, 95% CI: 0.88 to 1.17; P = 0.80), although there was weak evidence of an increase in minutes of moderate-and-vigorous-intensity activity per week (adjusted mean difference = 171, 95% CI: -16 to 358; P = 0.07). The

  12. Combination of granular activated carbon adsorption and deep-bed filtration as a single advanced wastewater treatment step for organic micropollutant and phosphorus removal.

    PubMed

    Altmann, Johannes; Rehfeld, Daniel; Träder, Kai; Sperlich, Alexander; Jekel, Martin

    2016-04-01

    Adsorption onto granular activated carbon (GAC) is an established technology in water and advanced wastewater treatment for the removal of organic substances from the liquid phase. Besides adsorption, the removal of particulate matter by filtration and biodegradation of organic substances in GAC contactors has frequently been reported. The application of GAC as both adsorbent for organic micropollutant (OMP) removal and filter medium for solids retention in tertiary wastewater filtration represents an energy- and space saving option, but has rarely been considered because high dissolved organic carbon (DOC) and suspended solids concentrations in the influent of the GAC adsorber put a significant burden on this integrated treatment step and might result in frequent backwashing and unsatisfactory filtration efficiency. This pilot-scale study investigates the combination of GAC adsorption and deep-bed filtration with coagulation as a single advanced treatment step for simultaneous removal of OMPs and phosphorus from secondary effluent. GAC was assessed as upper filter layer in dual-media downflow filtration and as mono-media upflow filter with regard to filtration performance and OMP removal. Both filtration concepts effectively removed suspended solids and phosphorus, achieving effluent concentrations of 0.1 mg/L TP and 1 mg/L TSS, respectively. Analysis of grain size distribution and head loss within the filter bed showed that considerable head loss occurred in the topmost filter layer in downflow filtration, indicating that most particles do not penetrate deeply into the filter bed. Upflow filtration exhibited substantially lower head loss and effective utilization of the whole filter bed. Well-adsorbing OMPs (e.g. benzotriazole, carbamazepine) were removed by >80% up to throughputs of 8000-10,000 bed volumes (BV), whereas weakly to medium adsorbing OMPs (e.g. primidone, sulfamethoxazole) showed removals <80% at <5,000 BV. In addition, breakthrough behavior was

  13. Back-stepping active disturbance rejection control design for integrated missile guidance and control system via reduced-order ESO.

    PubMed

    Xingling, Shao; Honglun, Wang

    2015-07-01

    This paper proposes a novel composite integrated guidance and control (IGC) law for missile intercepting against unknown maneuvering target with multiple uncertainties and control constraint. First, by using back-stepping technique, the proposed IGC law design is separated into guidance loop and control loop. The unknown target maneuvers and variations of aerodynamics parameters in guidance and control loop are viewed as uncertainties, which are estimated and compensated by designed model-assisted reduced-order extended state observer (ESO). Second, based on the principle of active disturbance rejection control (ADRC), enhanced feedback linearization (FL) based control law is implemented for the IGC model using the estimates generated by reduced-order ESO. In addition, performance analysis and comparisons between ESO and reduced-order ESO are examined. Nonlinear tracking differentiator is employed to construct the derivative of virtual control command in the control loop. Third, the closed-loop stability for the considered system is established. Finally, the effectiveness of the proposed IGC law in enhanced interception performance such as smooth interception course, improved robustness against multiple uncertainties as well as reduced control consumption during initial phase are demonstrated through simulations.

  14. One-step preparation of Fe3O4/Pd@polypyrrole composites with enhanced catalytic activity and stability.

    PubMed

    Zhang, Hui; Liu, Yang; Wu, Jie; Xin, Baifu

    2016-08-15

    Core/shell Fe3O4/Pd@polypyrrole (PPy) composites with a Fe3O4 core and a PPy shell embedding Pd nanoparticles were prepared in one-step. The diameter of highly dispersed Pd nanoparticles was as small as 2.9nm owing to coordination interaction generated between Pd(2+) ions and amino groups on PPy chains. The outer PPy shell was only 6.8nm: on one hand, the coverage was beneficial to improving the stability of resulting composites; on the other hand, the shell was thin enough to permit free contact between embedding Pd nanoparticles and reactants. Additionally, the as-prepared Fe3O4/Pd@PPy composites displayed good magnetic separation property due to incorporation of Fe3O4 nanospheres. Based on above merits, they served as suitable catalyst candidates. Their catalytic performance and reusability were evaluated by reduction of 4-nitrophenol with sodium borohydride as reducing agent. Compared with traditional Fe3O4/Pd composites, Fe3O4/Pd@PPy composites not only showed superior catalytic activity; but also exhibited much better stability in successive cycling tests.

  15. One-step in situ synthesis of graphene–TiO{sub 2} nanorod hybrid composites with enhanced photocatalytic activity

    SciTech Connect

    Sun, Mingxuan Li, Weibin; Sun, Shanfu; He, Jia; Zhang, Qiang; Shi, Yuying

    2015-01-15

    Chemically bonded graphene/TiO{sub 2} nanorod hybrid composites with superior dispersity were synthesized by a one-step in situ hydrothermal method using graphene oxide (GO) and TiO{sub 2} (P25) as the starting materials. The as-prepared samples were characterized by XRD, XPS, TEM, FE-SEM, EDX, Raman, N{sub 2} adsorption, and UV–vis DRS techniques. Enhanced light absorption and a red shift of absorption edge were observed for the composites in the ultraviolet–visible diffuse reflectance spectroscopy (UV–vis DRS). Their effective photocatalytic activity was evaluated by the photodegradation of methylene blue under visible light irradiation. An enhancement of photocatalytic performance was observed over graphene/TiO{sub 2} nanorod hybrid composite photocatalysts, as 3.7 times larger than that of pristine TiO{sub 2} nanorods. This work demonstrated that the synthesis of TiO{sub 2} nanorods and simultaneous conversion of GO to graphene “without using reducing agents” had shown to be a rapid, direct and clean approach to fabricate chemically bonded graphene/TiO{sub 2} nanorod hybrid composites with enhanced photocatalytic performance.

  16. A New Two-Step Approach for Hands-On Teaching of Gene Technology: Effects on Students' Activities During Experimentation in an Outreach Gene Technology Lab

    NASA Astrophysics Data System (ADS)

    Scharfenberg, Franz-Josef; Bogner, Franz X.

    2011-08-01

    Emphasis on improving higher level biology education continues. A new two-step approach to the experimental phases within an outreach gene technology lab, derived from cognitive load theory, is presented. We compared our approach using a quasi-experimental design with the conventional one-step mode. The difference consisted of additional focused discussions combined with students writing down their ideas (step one) prior to starting any experimental procedure (step two). We monitored students' activities during the experimental phases by continuously videotaping 20 work groups within each approach ( N = 131). Subsequent classification of students' activities yielded 10 categories (with well-fitting intra- and inter-observer scores with respect to reliability). Based on the students' individual time budgets, we evaluated students' roles during experimentation from their prevalent activities (by independently using two cluster analysis methods). Independently of the approach, two common clusters emerged, which we labeled as `all-rounders' and as `passive students', and two clusters specific to each approach: `observers' as well as `high-experimenters' were identified only within the one-step approach whereas under the two-step conditions `managers' and `scribes' were identified. Potential changes in group-leadership style during experimentation are discussed, and conclusions for optimizing science teaching are drawn.

  17. Early steps of active DNA demethylation initiated by ROS1 glycosylase require three putative helix-invading residues.

    PubMed

    Parrilla-Doblas, Jara Teresa; Ponferrada-Marín, María Isabel; Roldán-Arjona, Teresa; Ariza, Rafael R

    2013-10-01

    Active DNA demethylation is crucial for epigenetic control, but the underlying enzymatic mechanisms are incompletely understood. REPRESSOR OF SILENCING 1 (ROS1) is a 5-methylcytosine (5-meC) DNA glycosylase/lyase that initiates DNA demethylation in plants through a base excision repair process. The enzyme binds DNA nonspecifically and slides along the substrate in search of 5-meC. In this work, we have used homology modelling and biochemical analysis to gain insight into the mechanism of target location and recognition by ROS1. We have found that three putative helix-intercalating residues (Q607, R903 and M905) are required for processing of 5-meC:G pairs, but dispensable for excision of mismatched 5-meC. Mutant proteins Q607A, R903A and M905G retain the capacity to process an abasic site opposite G, thus suggesting that all three residues play a critical role in early steps of the base extrusion process and likely contribute to destabilization of 5-meC:G pairs. While R903 and M905 are not essential for DNA binding, mutation of Q607 abrogates stable binding to both methylated and nonmethylated DNA. However, the mutant protein Q607A can form stable complexes with DNA substrates containing blocked ends, which suggests that Q607 intercalates into the helix and inhibits sliding. Altogether, our results suggest that ROS1 uses three predicted helix-invading residues to actively interrogate DNA in search for 5-meC.

  18. Identification of GATA2 and AP-1 activator elements within the enhancer VNTR occurring in intron 5 of the human SIRT3 gene

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Human SIRT3 gene contains an intronic VNTR enhancer. A T > C transition occurring in the second repeat of each VNTR allele implies the presence/absence of a putative GATA binding motif. A partially overlapping AP-1 site, not affected by the transition, was also identified. Aims of the present study ...

  19. Multiple stage miniature stepping motor

    DOEpatents

    Niven, William A.; Shikany, S. David; Shira, Michael L.

    1981-01-01

    A stepping motor comprising a plurality of stages which may be selectively activated to effect stepping movement of the motor, and which are mounted along a common rotor shaft to achieve considerable reduction in motor size and minimum diameter, whereby sequential activation of the stages results in successive rotor steps with direction being determined by the particular activating sequence followed.

  20. Positive feedback of NR2B-containing NMDA receptor activity is the initial step toward visual imprinting: a model for juvenile learning.

    PubMed

    Nakamori, Tomoharu; Sato, Katsushige; Kinoshita, Masae; Kanamatsu, Tomoyuki; Sakagami, Hiroyuki; Tanaka, Kohichi; Ohki-Hamazaki, Hiroko

    2015-01-01

    Imprinting in chicks is a good model for elucidating the processes underlying neural plasticity changes during juvenile learning. We recently reported that neural activation of a telencephalic region, the core region of the hyperpallium densocellulare (HDCo), was critical for success of visual imprinting, and that N-Methyl-D-aspartic (NMDA) receptors containing the NR2B subunit (NR2B/NR1) in this region were essential for imprinting. Using electrophysiological and multiple-site optical imaging techniques with acute brain slices, we found that long-term potentiation (LTP) and enhancement of NR2B/NR1 currents in HDCo neurons were induced in imprinted chicks. Enhancement of NR2B/NR1 currents as well as an increase in surface NR2B expression occurred even following a brief training that was too weak to induce LTP or imprinting behavior. This means that NR2B/NR1 activation is the initial step of learning, well before the activation of alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors which induces LTP. We also showed that knockdown of NR2B/NR1 inhibited imprinting, and inversely, increasing the surface NR2B expression by treatment with a casein kinase 2 inhibitor successfully reduced training time required for imprinting. These results suggest that imprinting stimuli activate post-synaptic NR2B/NR1 in HDCo cells, increase NR2B/NR1 signaling through up-regulation of its expression, and induce LTP and memory acquisition. The study investigated the neural mechanism underlying juvenile learning. In the initial stage of chick imprinting, NMDA receptors containing the NMDA receptor subunit 2B (NR2B) are activated, surface expression of NR2B/NR1 (NMDA receptor subunit 1) is up-regulated, and consequently long-term potentiation is induced in the telencephalic neurons. We suggest that the positive feedback in the NR2B/NR1 activation is a unique process of juvenile learning, exhibiting rapid memory acquisition.

  1. Biophysics of active vesicle transport, an intermediate step that couples excitation and exocytosis of serotonin in the neuronal soma.

    PubMed

    De-Miguel, Francisco F; Santamaría-Holek, Iván; Noguez, Paula; Bustos, Carlos; Hernández-Lemus, Enrique; Rubí, J Miguel

    2012-01-01

    Transmitter exocytosis from the neuronal soma is evoked by brief trains of high frequency electrical activity and continues for several minutes. Here we studied how active vesicle transport towards the plasma membrane contributes to this slow phenomenon in serotonergic leech Retzius neurons, by combining electron microscopy, the kinetics of exocytosis obtained from FM1-43 dye fluorescence as vesicles fuse with the plasma membrane, and a diffusion equation incorporating the forces of local confinement and molecular motors. Electron micrographs of neurons at rest or after stimulation with 1 Hz trains showed cytoplasmic clusters of dense core vesicles at 1.5±0.2 and 3.7±0.3 µm distances from the plasma membrane, to which they were bound through microtubule bundles. By contrast, after 20 Hz stimulation vesicle clusters were apposed to the plasma membrane, suggesting that transport was induced by electrical stimulation. Consistently, 20 Hz stimulation of cultured neurons induced spotted FM1-43 fluorescence increases with one or two slow sigmoidal kinetics, suggesting exocytosis from an equal number of vesicle clusters. These fluorescence increases were prevented by colchicine, which suggested microtubule-dependent vesicle transport. Model fitting to the fluorescence kinetics predicted that 52-951 vesicles/cluster were transported along 0.60-6.18 µm distances at average 11-95 nms(-1) velocities. The ATP cost per vesicle fused (0.4-72.0), calculated from the ratio of the ΔG(process)/ΔG(ATP), depended on the ratio of the traveling velocity and the number of vesicles in the cluster. Interestingly, the distance-dependence of the ATP cost per vesicle was bistable, with low energy values at 1.4 and 3.3 µm, similar to the average resting distances of the vesicle clusters, and a high energy barrier at 1.6-2.0 µm. Our study confirms that active vesicle transport is an intermediate step for somatic serotonin exocytosis by Retzius neurons and provides a quantitative method

  2. Biophysics of Active Vesicle Transport, an Intermediate Step That Couples Excitation and Exocytosis of Serotonin in the Neuronal Soma

    PubMed Central

    De-Miguel, Francisco F.; Santamaría-Holek, Iván; Noguez, Paula; Bustos, Carlos; Hernández-Lemus, Enrique; Rubí, J. Miguel

    2012-01-01

    Transmitter exocytosis from the neuronal soma is evoked by brief trains of high frequency electrical activity and continues for several minutes. Here we studied how active vesicle transport towards the plasma membrane contributes to this slow phenomenon in serotonergic leech Retzius neurons, by combining electron microscopy, the kinetics of exocytosis obtained from FM1-43 dye fluorescence as vesicles fuse with the plasma membrane, and a diffusion equation incorporating the forces of local confinement and molecular motors. Electron micrographs of neurons at rest or after stimulation with 1 Hz trains showed cytoplasmic clusters of dense core vesicles at 1.5±0.2 and 3.7±0.3 µm distances from the plasma membrane, to which they were bound through microtubule bundles. By contrast, after 20 Hz stimulation vesicle clusters were apposed to the plasma membrane, suggesting that transport was induced by electrical stimulation. Consistently, 20 Hz stimulation of cultured neurons induced spotted FM1-43 fluorescence increases with one or two slow sigmoidal kinetics, suggesting exocytosis from an equal number of vesicle clusters. These fluorescence increases were prevented by colchicine, which suggested microtubule-dependent vesicle transport. Model fitting to the fluorescence kinetics predicted that 52–951 vesicles/cluster were transported along 0.60–6.18 µm distances at average 11–95 nms−1 velocities. The ATP cost per vesicle fused (0.4–72.0), calculated from the ratio of the ΔGprocess/ΔGATP, depended on the ratio of the traveling velocity and the number of vesicles in the cluster. Interestingly, the distance-dependence of the ATP cost per vesicle was bistable, with low energy values at 1.4 and 3.3 µm, similar to the average resting distances of the vesicle clusters, and a high energy barrier at 1.6–2.0 µm. Our study confirms that active vesicle transport is an intermediate step for somatic serotonin exocytosis by Retzius neurons and provides a quantitative

  3. Characterization and lead adsorption properties of activated carbons prepared from cotton stalk by one-step H3PO4 activation.

    PubMed

    Li, Kunquan; Zheng, Zheng; Li, Ye

    2010-09-15

    Activated carbons were prepared from cotton stalk by one-step H(3)PO(4) activation and used as adsorbent for the removal of lead(II). Taguchi experimental design method was used to optimize the preparation of the adsorbents. The results showed that the optimized conditions were: impregnation with a 50% (w/v) phosphoric acid solution with a mass ratio of 3:2 and activation temperature at 500 degrees C for 60 min with the rate of achieving the activation temperature equal to 10 degrees C min(-1). The cotton stalk activated carbon (CSAC) prepared at these conditions have 1.43 mmol g(-1) acidic surface groups and 1570 m(2) g(-1) BET surface area. Adsorption isotherms for lead(II) on the adsorbents were measured by conducting a series of batch adsorption experiments. The Langmuir maximum adsorption amount of lead(II) on CSAC was more than 119 mg g(-1), which was superior to the ordinary commercial activated carbon (CAC) on the market. Compared with the CAC, the CSAC had a wider applicable pH range from 3.5 to 6.5 for lead(II) uptake. The final pH values at equilibrium after adsorption were lower than the initial pH value, indicating that the ion-exchange process was involved in the adsorption. This is also confirmed by the result that the increase of acidic surface groups favored the adsorption process. Thermodynamic study indicated that the adsorption was a spontaneous and endothermic process.

  4. Relating photosynthetic activity of BSCs from spectral indices: a first step to upscale BSC role on carbon fluxes

    NASA Astrophysics Data System (ADS)

    Rodriguez-Caballero, Emilio; Chamizo, Sonia; Miralles, Isabel; Ortega, Raul; Luna, Lourdes; Cantón, Yolanda

    2014-05-01

    Arid and semiarid ecosystems are water limited environments where water availability is the main limiting factor controlling vegetation cover, productivity and ecosystem function. However, bare areas of these systems are usually covered by a thin layer of photoautrophic communities of microorganisms comprising cyanobacteria, algae, microfungi, lichens or bryophytes, so called biological soil crusts (BSCs), which may cover up to 70 % of the soil surface in these areas. These BSCs are capable to survive long drought periods, during which their physiological activity ceases, and become active just after rainfall or even after dew or fog events, thus triggering their photosynthetic activity. So, they play an active role in C storage in arid ecosystems, where they are considered the main agent of nutrient input on bare areas. Moreover, the carbon (C) stored in soils covered by BSCs may constitute an important nutrient surplus for soil microbial communities or vegetation. Thus, having accurate continuous information about C stocks and C fluxes in soils covered by BSCs, at ecosystems scale, constitutes a relevant issue for scientists and researchers from many different disciplines, and is crucial for assessing the impacts of increasing atmospheric CO2 concentration on global environmental change. Remote sensing images and derived vegetation indices are presented as one of the most promising tools to achieve this goal, since they provide spatially explicit information with high temporal resolution. So that, quantifying the photosynthetic activity on BSC areas using remote sensing data constitutes an essential step to advance in the knowledge about the role of arid and semiarid regions in global C balance. In this study we analyzed the potential of the most widely used vegetation indices to estimate gross photosynthesis (GP) in BSCs. To achieve this objective, GP was calculated, after a rainfall event on different BSCs and on bare field plots, as the sum of net primary

  5. Synergistic activation of transcription is mediated by the N-terminal domain of Drosophila fushi tarazu homeoprotein and can occur without DNA binding by the protein.

    PubMed Central

    Ananthan, J; Baler, R; Morrissey, D; Zuo, J; Lan, Y; Weir, M; Voellmy, R

    1993-01-01

    Synergistic activation of transcription by Drosophila segmentation genes in tissue culture cells provides a model with which to study combinatorial regulation. We examined the synergistic activation of an engrailed-derived promoter by the pair-rule proteins paired (PRD) and fushi tarazu (FTZ). Synergistic activation by PRD requires regions of the homeodomain or adjacent sequences, and that by FTZ requires the first 171 residues. Surprisingly, deletion of the FTZ homeodomain does not reduce the capacity of the protein for synergistic activation, although this mutation abolishes any detectable DNA-binding activity. This finding suggests that FTZ can function through protein-protein interactions with PRD or other components of the homeoprotein transcription complex, adding a new layer of mechanisms that could underlie the functional specificities and combinatorial regulation of homeoproteins. Images PMID:8095092

  6. Activities and Stabilities of Au-Modified Stepped-Pt Single-Crystal Electrodes as Model Cathode Catalysts in Polymer Electrolyte Fuel Cells.

    PubMed

    Kodama, Kensaku; Jinnouchi, Ryosuke; Takahashi, Naoko; Murata, Hajime; Morimoto, Yu

    2016-03-30

    The purpose of this study is to test the concept of protecting vulnerable sites on cathode catalysts in polymer electrolyte fuel cells. Pt single-crystal surfaces were modified by depositing Au atoms selectively on (100) step sites and their electrocatalytic activities for oxygen reduction reaction (ORR) and stabilities against potential cycles were examined. The ORR activities were raised by 70% by the Au modifications, and this rise in the activity was ascribed to enhanced local ORR activities on Pt(111) terraces by the surface Au atoms. The Au modifications also stabilized the Pt surfaces against potential cycles by protecting the low-coordinated (100) step sites from surface reorganizations. Thus, the surface modification by selective Au depositions on vulnerable sites is a promising method to enhance both the ORR activity and durability of the catalysts.

  7. Suppression of Canine Dendritic Cell Activation/Maturation and Inflammatory Cytokine Release by Mesenchymal Stem Cells Occurs Through Multiple Distinct Biochemical Pathways.

    PubMed

    Wheat, William H; Chow, Lyndah; Kurihara, Jade N; Regan, Daniel P; Coy, Jonathan W; Webb, Tracy L; Dow, Steven W

    2017-02-15

    Mesenchymal stem cells (MSC) represent a readily accessible source of cells with potent immune modulatory activity. MSC can suppress ongoing inflammatory responses by suppressing T cell function, while fewer studies have examined the impact of MSC on dendritic cell (DC) function. The dog spontaneous disease model represents an important animal model with which to evaluate the safety and effectiveness of cellular therapy with MSC. This study evaluated the effects of canine MSC on the activation and maturation of canine monocyte-derived DC, as well as mechanisms underlying these effects. Adipose-derived canine MSC were cocultured with canine DC, and the MSC effects on DC maturation and activation were assessed by flow cytometry, cytokine ELISA, and confocal microscopy. We found that canine MSC significantly suppressed lipopolysaccharide (LPS)-stimulated upregulation of DC activation markers such as major histocompatibility class II (MHCII), CD86, and CD40. Furthermore, pretreatment of MSC with interferon gamma (IFNγ) augmented this suppressive activity. IFNγ-activated MSC also significantly reduced LPS-elicited DC secretion of tumor necrosis factor alpha without reducing secretion of interleukin-10. The suppressive effect of IFNγ-treated MSC on LPS-induced DC activation was mediated by soluble factors secreted by both MSC and DC. Pathways of DC functional suppression included programmed death ligand-1 expression and secretion of nitrous oxide, prostaglandin E2, and adenosine by activated MSC. Coculture of DC with IFNγ-treated MSC maintained DC in an immature state and prolonged DC antigen uptake during LPS maturation stimulus. Taken together, canine MSC are capable of potently suppressing DC function in a potentially inflammatory microenvironment through several separate immunological pathways and confirm the potential for immune therapy with MSC in canine immune-mediated disease models.

  8. Gypenoside XLIX, a naturally occurring gynosaponin, PPAR-alpha dependently inhibits LPS-induced tissue factor expression and activity in human THP-1 monocytic cells

    SciTech Connect

    Huang, Tom Hsun-Wei; Van Hoan Tran; Roufogalis, Basil D.; Li Yuhao . E-mail: yuhao@pharm.usyd.edu.au

    2007-01-01

    Tissue factor (TF) is involved not only in the progression of atherosclerosis and other cardiovascular diseases, but is also associated with tumor growth, metastasis, and angiogenesis and hence may be an attractive target for directed cancer therapeutics. Gynostemma pentaphyllum (GP) is widely used in the treatment of various cardiovascular diseases including atherosclerosis, as well as cancers. Gypenoside (Gyp) XLIX, a dammarane-type glycoside, is one of the prominent components in GP. We have recently reported Gyp XLIX to be a potent peroxisome proliferator-activated receptor (PPAR)-alpha activator. Here we demonstrate that Gyp XLIX (0-300 {mu}M) concentration dependently inhibited TF promoter activity after induction by the inflammatory stimulus lipopolysaccharide (LPS) in human monocytic THP-1 cells transfected with promoter reporter constructs pTF-LUC. Furthermore, Gyp XLIX inhibited LPS-induced TF mRNA and protein overexpression in THP-1 monocyte cells. Its inhibition of LPS-induced TF hyperactivity was further confirmed by chromogenic enzyme activity assay. The activities of Gyp XLIX reported in this study were similar to those of Wy-14643, a potent synthetic PPAR-alpha activator. Furthermore, the Gyp XLIX-induced inhibitory effect on TF luciferase activity was completely abolished in the presence of the PPAR-alpha selective antagonist MK-886. The present findings suggest that Gyp XLIX inhibits LPS-induced TF overexpression and enhancement of its activity in human THP-1 monocytic cells via PPAR-alpha-dependent pathways. The data provide new insights into the basis of the use of the traditional Chinese herbal medicine G. pentaphyllum for the treatment of cardiovascular and inflammatory diseases, as well as cancers.

  9. Aucubin, a naturally occurring iridoid glycoside inhibits TNF-α-induced inflammatory responses through suppression of NF-κB activation in 3T3-L1 adipocytes.

    PubMed

    Park, Kyoung Sik

    2013-06-01

    Obesity is closely associated with a state of chronic, low-grade inflammation characterized by abnormal cytokine production and activation of inflammatory signaling pathways in adipose tissue. Tumor necrosis factor (TNF)-α is chronically elevated in adipose tissues of obese rodents and humans. Increased levels of TNF-α are implicated in the induction of atherogenic adipokines, such as plasminogen activator inhibitor (PAI)-1, adipose-tissue-derived monocyte chemoattractant protein (MCP)-1, and interleukin (IL)-6. Aucubin, an iridoid glycoside existing in medicinal plants, has been reported to show an anti-inflammatory activity by suppression of TNF-α production in murine macrophages. The present study is aimed to investigate the effects of aucubin on TNF-α-induced atherogenic changes of the adipokines in differentiated 3T3-L1 cells. Aucubin significantly inhibited TNF-α-induced secretion and mRNA synthesis of the atherogenic adipokines including PAI-1, MCP-1, and IL-6. Further investigation of the molecular mechanism revealed that pretreatment with aucubin suppressed extracellular signal-regulated kinase (ERK) activation, inhibitory kappa Bα (IκBα) degradation, and subsequent nuclear factor kappa B (NF-κB) activation. These findings suggest that aucubin may improve obesity-induced atherosclerosis by attenuating TNF-α-induced inflammatory responses.

  10. Adaptation of glutathion-peroxidase activity to oxidative stress occurs in children but not in adult patients with end-stage renal failure undergoing hemodialysis.

    PubMed

    Sommerburg, O; Grune, T; Ehrich, J H H; Siems, W G

    2002-07-01

    Lipid peroxidation (LPO) products formed after reaction of free radicals with membrane lipids are involved in the pathogenesis of cardiac diseases. Also in patients with end-stage renal disease (ESRD) LPO was shown to be accelerated and concentrations of non-enzymatic antioxidants were measured lower than in control subjects. However, up to now only limited knowledge about the role of antioxidant enzymes was available. Whether or not activity of those antioxidants might be induced due to oxidative stress in ESRD patients is not known. To answer the question the activity of 3 enzymatic antioxidants, superoxide dismutase (SOD), catalase (CAT), and glutathion peroxidase (GPx), was measured in red blood cells of the ESRD patients undergoing hemodialysis (2 groups: children and adults) and matching controls. LPO in these subjects was determined by measurement of the LPO product 4-hydroxynonenal (HNE) in blood plasma. Plasma HNE was significantly increased by factor 3 in both patient groups children and adults compared to the control groups. The activity of the enzymatic antioxidants was measured differently. While SOD was significantly lower in patients (children and adults) than in the matching controls this was not the case for catalase and GPx. While GPx activity in adult patients was comparable to that in the control groups (childrens and adults), the GPx in children with ESRD was almost twice as high than in the other groups. Since children were shown to have higher levels of glutathion, activated GPx might be a sign of adaptation of these children to the increased rate of oxidation.

  11. PHYSICAL EFFECTS OCCURRING DURING GENERATION AND AMPLIFICATION OF LASER RADIATION: Kinetic model of the active medium of an XeCl laser pumped by an electron beam

    NASA Astrophysics Data System (ADS)

    Boĭchenko, A. M.; Derzhiev, V. I.; Zhidkov, A. G.; Yakovlenko, Sergei I.

    1989-02-01

    Kinetic models of active media of an XeCl laser are developed for the case when these media are diluted by various buffer gases (helium, neon, argon) and the laser is pumped by an electron beam. The results of the calculations are in satisfactory agreement with experimental data.

  12. Phytochemical screening, antioxidant and antibacterial activities of extracts prepared from different tissues of Schinus terebinthifolius Raddi that occurs in the coast of Bahia, Brazil

    PubMed Central

    D’Sousa’ Costa, Cinara Oliveira; Ribeiro, Paulo Roberto; Loureiro, Marta Bruno; Simões, Rafael Conceição; de Castro, Renato Delmondez; Fernandez, Luzimar Gonzaga

    2015-01-01

    Background: Schinus terebinthifolius is widely used in traditional medicine by Brazilian quilombola and indigenous communities for treatment of several diseases. Extracts from different tissues are being used to produce creams to treat cervicitis and cervicovaginitis. However, most studies are limited to the assessment of the essential oils and extracts obtained from the leaves. Objective: The aim was to evaluate antioxidant and antibacterial activities, to assess the phytochemical profile and to quantify total phenolic compounds of various extracts prepared from S. terebinthifolius grown in the coast of Bahia, Brazil. Materials and Methods: Extracts were obtained by hot continuous extraction (soxhlet) and by maceration. Quantification of phenolic compounds was performed using the Folin-Ciocalteu method and antioxidant properties were assessed by 2,2-diphenyl-1-picrylhydrazyl radical scavenging assay. Phytochemical screening was performed as described by in the literature and antibacterial activity against Enterococcus faecalis (ATCC 29212) was determined by the microdilution broth assay. Results: Extraction method greatly affected the metabolite profile of the extracts. Antioxidant activity varied between 21.92% and 85.76%, while total phenols ranged between 5.44 and 309.03 mg EAG/g of extract. Leaf extract obtained with soxhlet showed minimum inhibitory concentration (MIC) of 15.62 μg/mL, while stem extract obtained by maceration was able to inhibit the growth of E. faecalis at 62.5 μg/mL. Stem bark extracts showed a MIC of 500 μg/mL for both extraction methods, while no inhibition was observed for fruit extracts. Conclusion: In general, total phenolic content, antioxidant and antibacterial activities were higher in samples obtained by soxhlet. Our results provide important clues in order to identify alternative sources of bioactive compounds that can be used to develop new drugs. PMID:26246739

  13. Patterns of Naturally Occurring Restriction Map Variation, Dopa Decarboxylase Activity Variation and Linkage Disequilibrium in the Ddc Gene Region of Drosophila Melanogaster

    PubMed Central

    Aquadro, C. F.; Jennings-Jr, R. M.; Bland, M. M.; Laurie, C. C.; Langley, C. H.

    1992-01-01

    Forty-six second-chromosome lines of Drosophila melanogaster isolated from five natural populations were surveyed for restriction map variation in a 65-kb region surrounding the gene (Ddc) encoding dopa decarboxylase (DDC). Sixty-nine restriction sites were scored, 13 of which were polymorphic. Average heterozygosity per nucleotide was estimated to be 0.005. Eight large (0.7-5.0 kb) inserts, two small inserts (100 and 200 bp) and three small deletions (100-300 bp) were also observed across the 65-kb region. We see no evidence for a reduction in either nucleotide heterozygosity or insertion/deletion variation in the central 26-kb segment containing Ddc and a dense cluster of lethal complementation groups and transcripts (>/=9 genes) compared to that seen in the adjacent regions (totaling 39 kb) in which only a single gene and transcript has been detected, or to that observed for other gene regions in D. melanogaster. The distribution of restriction site variation shows no significant departure from that expected under an equilibrium neutral model. However insertions and deletions show a significant departure from neutrality in that they are too rare in frequency, consistent with them being deleterious on average. Significant linkage disequilibrium among variants exists across much of the 65-kb region. Lower regional rates of recombination combined with the influence of polymorphic chromosomal inversions, rather than epistatic selection among genes in the dense cluster, probably are sufficient explanations for the creation and/or maintenance of the linkage disequilibrium observed in the Ddc region. We have also assayed adult DDC enzyme activity in these same lines. Twofold variation in activity among lines is observed within our sample. Significant associations are observed between level of DDC enzyme activity and restriction map variants. Surprisingly, one line with a 5.0-kb insert within an intron and one line with a 1.5-kb insert near the 5' end of Ddc each show

  14. Glucose de-repression by yeast AMP-activated protein kinase SNF1 is controlled via at least two independent steps.

    PubMed

    García-Salcedo, Raúl; Lubitz, Timo; Beltran, Gemma; Elbing, Karin; Tian, Ye; Frey, Simone; Wolkenhauer, Olaf; Krantz, Marcus; Klipp, Edda; Hohmann, Stefan

    2014-04-01

    The AMP-activated protein kinase, AMPK, controls energy homeostasis in eukaryotic cells but little is known about the mechanisms governing the dynamics of its activation/deactivation. The yeast AMPK, SNF1, is activated in response to glucose depletion and mediates glucose de-repression by inactivating the transcriptional repressor Mig1. Here we show that overexpression of the Snf1-activating kinase Sak1 results, in the presence of glucose, in constitutive Snf1 activation without alleviating glucose repression. Co-overexpression of the regulatory subunit Reg1 of the Glc-Reg1 phosphatase complex partly restores glucose regulation of Snf1. We generated a set of 24 kinetic mathematical models based on dynamic data of Snf1 pathway activation and deactivation. The models that reproduced our experimental observations best featured (a) glucose regulation of both Snf1 phosphorylation and dephosphorylation, (b) determination of the Mig1 phosphorylation status in the absence of glucose by Snf1 activity only and (c) a regulatory step directing active Snf1 to Mig1 under glucose limitation. Hence it appears that glucose de-repression via Snf1-Mig1 is regulated by glucose via at least two independent steps: the control of activation of the Snf1 kinase and directing active Snf1 to inactivating its target Mig1.

  15. Peak Muscle Activation, Joint Kinematics, and Kinetics during Elliptical and Stepping Movement Pattern on a Precor Adaptive Motion Trainer

    ERIC Educational Resources Information Center

    Rogatzki, Matthew J.; Kernozek, Thomas W.; Willson, John D.; Greany, John F.; Hong, Di-An; Porcari, John P.

    2012-01-01

    Kinematic, kinetic, and electromyography data were collected from the biceps femoris, rectus femoris (RF), gluteus maximus, and erector spinae (ES) during a step and elliptical exercise at a standardized workload with no hand use. Findings depicted 95% greater ankle plantar flexion (p = 0.01), 29% more knee extension (p = 0.003), 101% higher peak…

  16. PHYSICAL EFFECTS OCCURRING DURING GENERATION AND AMPLIFICATION OF LASER RADIATION: Discharge energy balance in the nitrogen-containing active medium of an electron-beam-controlled CO laser

    NASA Astrophysics Data System (ADS)

    Dolinina, V. I.; Koterov, V. N.; Pyatakhin, Mikhail V.; Urin, B. M.

    1989-02-01

    Numerical methods were used to investigate theoretically the dynamics of the energy balance of a discharge in a CO-N2 mixture, taking into account the mutual influence of the distributions of the electron energy and of the populations of the molecules over the vibrational levels. It was shown that this influence plays a decisive part in substantially redistributing the pump energy between the vibrational levels of the CO and N2 molecules in favor of the N2 molecules. A stabilizing action of the nitrogen on the thermal regime of the CO laser-active medium was discovered and the range of optimal CO:N2 ratios was determined.

  17. Synergism between insecticides permethrin and propoxur occurs through activation of presynaptic muscarinic negative feedback of acetylcholine release in the insect central nervous system.

    PubMed

    Corbel, Vincent; Stankiewicz, Maria; Bonnet, Julien; Grolleau, Françoise; Hougard, Jean Marc; Lapied, Bruno

    2006-07-01

    Although synergism between pesticides has been widely documented, the physiological mechanisms by which an insecticide synergizes another remains unclear. Toxicological and electrophysiological studies were carried out on two susceptible pest species (the mosquito Culex quinquefasciatus and the cockroach Periplaneta americana) to understand better the physiological process involved in pyrethroid and carbamate interactions. Larval bioassays were conducted with the susceptible reference strain SLAB of C. quinquefasciatus to assess the implication of multi-function oxidases and non-specific esterases in insecticide detoxification and synergism. Results showed that the general theory of synergism (competition between pesticides for a common detoxification enzyme) was unlikely to occur in the SLAB strain since the level of synergy recorded between permethrin and propoxur was unchanged in the presence of piperonyl butoxide and tribufos, two inhibitors of oxidases and esterases, respectively (synergism ratios were similar with and without synergists). We also showed that addition of a sub-lethal concentration of nicotine significantly increased the toxicity of permethrin and propoxur at the lower range of the dose-mortality regression lines, suggesting the manifestation of important physiological disruptions at synaptic level. The effects of both permethrin and propoxur were studied on the cercal-afferent giant-interneuron synapses in the terminal abdominal ganglion of the cockroach P. americana using the single-fibre oil-gap method. We demonstrated that permethrin and propoxur increased drastically the ACh concentration within the synaptic cleft, which thereby stimulated a negative feedback of ACh release. Atropine, a muscarinic receptor antagonist, reversed the effect of permethrin and propoxur mixtures. This demonstrates the implication of the presynaptic muscarinic receptors in the negative feedback regulation process and in synergism. Based on these findings, we

  18. Demonstration That Mast Cells, T Cells, and B Cells Bearing the Activating Kit Mutation D816V Occur in Clusters within the Marrow of Patients with Mastocytosis

    PubMed Central

    Taylor, Marcia L.; Sehgal, Devinder; Raffeld, Mark; Obiakor, Harold; Akin, Cem; Mage, Rose G.; Metcalfe, Dean D.

    2004-01-01

    Mastocytosis is characterized by focal heterotypic clusters of mast cells and lymphocytes in the bone marrow and by a somatically acquired activating Kit mutation, D816V. The relationship of the occurrence of this mutation to the heterotypic clusters of mast cells and lymphocytes in bone marrow is unknown. We hypothesized that these two unique features of mastocytosis were related. To explore this hypothesis, laser capture microdissected mast cells, B cells, and T cells, from both lesional and non-lesional areas of bone marrow biopsy tissues from patients with mastocytosis, were examined for the D816V mutation in their DNA, using HinfI restriction digestion of nested PCR products amplified from extracts of dissected cells. The D816V mutation was detected in mast cells, B cells, and T cells from lesional but not non-lesional areas of bone marrow tissues. B cells obtained from lesional areas of tissue were also assessed for clonality and were found to at least represent an oligoclonal population. Thus, mast cells and lymphocytes within focal aggregates in the bone marrow of those with mastocytosis are more frequently positive for the codon 816 activating mutation. Further, the B cell population is oligoclonal, suggesting that clonal proliferation is unlikely to be the basis of clustering. PMID:15507672

  19. Osmoregulation in Lilium pollen grains occurs via modulation of the plasma membrane H+ ATPase activity by 14-3-3 proteins.

    PubMed

    Pertl, Heidi; Pöckl, Magdalena; Blaschke, Christian; Obermeyer, Gerhard

    2010-12-01

    To allow successful germination and growth of a pollen tube, mature and dehydrated pollen grains (PGs) take up water and have to adjust their turgor pressure according to the water potential of the surrounding stigma surface. The turgor pressure of PGs of lily (Lilium longiflorum) was measured with a modified pressure probe for simultaneous recordings of turgor pressure and membrane potential to investigate the relation between water and electrogenic ion transport in osmoregulation. Upon hyperosmolar shock, the turgor pressure decreased, and the plasma membrane (PM) hyperpolarizes in parallel, whereas depolarization of the PM was observed with hypoosmolar treatment. An acidification and alkalinization of the external medium was monitored after hyper- and hypoosmotic treatments, respectively, and pH changes were blocked by vanadate, indicating a putative role of the PM H(+) ATPase. Indeed, an increase in PM-associated 14-3-3 proteins and an increase in PM H(+) ATPase activity were detected in PGs challenged by hyperosmolar medium. We therefore suggest that in PGs the PM H(+) ATPase via modulation of its activity by 14-3-3 proteins is involved in the regulation of turgor pressure.

  20. Osmoregulation in Lilium Pollen Grains Occurs via Modulation of the Plasma Membrane H+ ATPase Activity by 14-3-3 Proteins1[C][W][OA

    PubMed Central

    Pertl, Heidi; Pöckl, Magdalena; Blaschke, Christian; Obermeyer, Gerhard

    2010-01-01

    To allow successful germination and growth of a pollen tube, mature and dehydrated pollen grains (PGs) take up water and have to adjust their turgor pressure according to the water potential of the surrounding stigma surface. The turgor pressure of PGs of lily (Lilium longiflorum) was measured with a modified pressure probe for simultaneous recordings of turgor pressure and membrane potential to investigate the relation between water and electrogenic ion transport in osmoregulation. Upon hyperosmolar shock, the turgor pressure decreased, and the plasma membrane (PM) hyperpolarizes in parallel, whereas depolarization of the PM was observed with hypoosmolar treatment. An acidification and alkalinization of the external medium was monitored after hyper- and hypoosmotic treatments, respectively, and pH changes were blocked by vanadate, indicating a putative role of the PM H+ ATPase. Indeed, an increase in PM-associated 14-3-3 proteins and an increase in PM H+ ATPase activity were detected in PGs challenged by hyperosmolar medium. We therefore suggest that in PGs the PM H+ ATPase via modulation of its activity by 14-3-3 proteins is involved in the regulation of turgor pressure. PMID:20974894

  1. Heterolytic Activation of C-H Bonds on Cr(III)-O Surface Sites Is a Key Step in Catalytic Polymerization of Ethylene and Dehydrogenation of Propane.

    PubMed

    Conley, Matthew P; Delley, Murielle F; Núñez-Zarur, Francisco; Comas-Vives, Aleix; Copéret, Christophe

    2015-06-01

    We describe the reactivity of well-defined chromium silicates toward ethylene and propane. The initial motivation for this study was to obtain a molecular understanding of the Phillips polymerization catalyst. The Phillips catalyst contains reduced chromium sites on silica and catalyzes the polymerization of ethylene without activators or a preformed Cr-C bond. Cr(II) sites are commonly proposed active sites in this catalyst. We synthesized and characterized well-defined chromium(II) silicates and found that these materials, slightly contaminated with a minor amount of Cr(III) sites, have poor polymerization activity and few active sites. In contrast, chromium(III) silicates have 1 order of magnitude higher activity. The chromium(III) silicates initiate polymerization by the activation of a C-H bond of ethylene. Density functional theory analysis of this process showed that the C-H bond activation step is heterolytic and corresponds to a σ-bond metathesis type process. The same well-defined chromium(III) silicate catalyzes the dehydrogenation of propane at elevated temperatures with activities similar to those of a related industrial chromium-based catalyst. This reaction also involves a key heterolytic C-H bond activation step similar to that described for ethylene but with a significantly higher energy barrier. The higher energy barrier is consistent with the higher pKa of the C-H bond in propane compared to the C-H bond in ethylene. In both cases, the rate-determining step is the heterolytic C-H bond activation.

  2. Activation of gene expression by herpes simplex virus type 1 ICP0 occurs at the level of mRNA synthesis.

    PubMed Central

    Jordan, R; Schaffer, P A

    1997-01-01

    ICP0 is a nuclear phosphoprotein involved in the activation of herpes simplex virus type 1 (HSV-1) gene expression during lytic infection and reactivation from viral latency. Although available evidence suggests that ICP0 acts at the level of transcription, definitive studies specifically addressing this issue have not been reported. In the present study we measured the ability of ICP0 to activate gene expression (i) from promoters representing the major kinetic classes of viral genes in transient expression assays and (ii) from the same promoters during viral infection at multiplicities of infection ranging from 0.1 to 5.0 PFU/cell. The levels of synthesis and steady-state accumulation of mRNA, mRNA stability, and levels of protein synthesis were compared in cells transfected with a reporter plasmid in the presence and absence of ICP0 and in cells infected with wild-type HSV-1 or an ICP0 null mutant, n212. In transient expression assays and during viral infection at all multiplicities tested, the levels of steady-state mRNA and protein were significantly lower in the absence of ICP0, indicating that ICP0 activates gene expression at the level of mRNA accumulation. In transient expression assays and during infection at low multiplicities (< 1 PFU/cell) in the presence or absence of ICP0, marked increases in the levels of viral mRNAs accompanied by proportional increases in the levels of protein synthesis were observed with increasing multiplicity. At a high multiplicity (5 PFU/cell) in the presence or absence of ICP0, mRNA levels did not increase as a function of multiplicity and changes in the levels of protein were no longer related to changes in the levels of mRNA. Collectively, these tests indicate that transcription of viral genes is rate limiting at low multiplicities and that translation is rate limiting at high multiplicities, independent of ICP0. Consistent with the lower levels of mRNA detected in the absence of ICP0, the rates of transcription initiation

  3. Fabrication of platy apatite nanocrystals loaded with TiO2 nanoparticles by two-step emulsion method and their photocatalytic activity.

    PubMed

    Iwasaki, Mitsunobu; Miyamoto, Yuki; Ito, Seishiro; Furuzono, Tsutomu; Park, Won-Kyu

    2008-10-15

    Nanometer-sized TiO(2) island structure on the platy hydroxyapatite nanocrystals (HAp) has been accomplished by two-step emulsion process. At the first step, platy HAp nanocrystals, of which size was in the range of 70-200 nm after heat-treatment at 1078 K for 1 h, were prepared using the W/O emulsion system. Before the second step, HAp nanocrystals were immersed in NaH(2)PO(4) solution for the formation of hydroxyl group on their surface. In the following, titanium tetraisopropoxide reacted with the hydroxyl group of HAp surface to form TiO(2) nanoparticles on the surface of HAp nanocrystals, which were dispersed in the micrometer-sized methanol droplets of polyethylene cetylether-cyclohexane mixture (methanol/oil emulsion). The resulting hydroxyapatite nanocrystals loaded with TiO(2) nanoparticles showed the high photocatalytic activity comparing to the commercial TiO(2) catalyst.

  4. Depletion of Intracellular Thiols and Increased Production of 4-Hydroxynonenal that Occur During Cryopreservation of Stallion Spermatozoa Lead to Caspase Activation, Loss of Motility, and Cell Death.

    PubMed

    Martin Muñoz, Patricia; Ortega Ferrusola, Cristina; Vizuete, Guillermo; Plaza Dávila, Maria; Rodriguez Martinez, Heriberto; Peña, Fernando J

    2015-12-01

    Oxidative stress has been linked to sperm death and the accelerated senescence of cryopreserved spermatozoa. However, the molecular mechanisms behind this phenomenon remain poorly understood. Reactive oxygen species (ROS) are considered relevant signaling molecules for sperm function, only becoming detrimental when ROS homeostasis is lost. We hereby hypothesize that a major component of the alteration of ROS homeostasis in cryopreserved spermatozoa is the exhaustion of intrinsic antioxidant defense mechanisms. To test this hypothesis, semen from seven stallions was frozen using a standard technique. The parameters of sperm quality (motility, velocity, and membrane integrity) and markers of sperm senescence (caspase 3, 4-hydroxynonenal, and mitochondrial membrane potential) were assessed before and after cryopreservation. Changes in the intracellular thiol content were also monitored. Cryopreservation caused significant increases in senescence markers as well as dramatic depletion of intracellular thiols to less than half of the initial values (P < 0.001) postthaw. Interestingly, very high and positive correlations were observed among thiol levels with sperm functionality postthaw: total motility (r = 0.931, P < 0.001), progressive motility (r = 0.904, P < 0.001), and percentage of live spermatozoa without active caspase 3 (r = 0.996, P < 0.001). In contrast, negative correlations were detected between active caspase 3 and thiol content both in living (r = -0.896) and dead (r = -0.940) spermatozoa; additionally, 4-hydroxynonenal levels were negatively correlated with thiol levels (r = -0.856). In conclusion, sperm functionality postthaw correlates with the maintenance of adequate levels of intracellular thiols. The accelerated senescence of thawed spermatozoa is related to oxidative and electrophilic stress induced by increased production of 4-hydroxynoneal in thawed samples once intracellular thiols are depleted.

  5. Editing of the Sendai virus P/C mRNA by G insertion occurs during mRNA synthesis via a virus-encoded activity.

    PubMed Central

    Vidal, S; Curran, J; Kolakofsky, D

    1990-01-01

    Two forms of the Sendai virus P/C mRNA have been predicted: one an exact copy of the viral genome, and the other with a single G insertion within a run of three G's. We directly cloned the mRNA or portions of it containing the insertion site and screened the resulting colonies with oligonucleotides that could distinguish the presence of three or four G's at this position. We found that 31% of the mRNAs did in fact contain the predicted insertion, whereas the viral genomes contained no heterogeneity at this position. A smaller fraction (7%) of the mRNA contained two to eight G's inserted at this position. The insertions also took place during RNA synthesis in vitro with purified virions but were not detected when the mRNA was expressed in vivo via a vaccinia virus recombinant. When the Sendai virus- and vaccinia virus-derived P/C mRNAs were coexpressed in the same cells under conditions in which each could be distinguished, those from the Sendai genome were altered as before, but those from the vaccinia virus genome remained unaltered. The activity that alters the mRNA is therefore likely to be coded for by the virus and cannot function in trans. Images PMID:1688384

  6. A Comparative Oncology Study of Iniparib Defines Its Pharmacokinetic Profile and Biological Activity in a Naturally-Occurring Canine Cancer Model

    PubMed Central

    Saba, Corey; Paoloni, Melissa; Mazcko, Christina; Kisseberth, William; Burton, Jenna H.; Smith, Annette; Wilson-Robles, Heather; Allstadt, Sara; Vail, David; Henry, Carolyn; Lana, Susan; Ehrhart, E. J.; Charles, Brad; Kent, Michael; Lawrence, Jessica; Burgess, Kristine; Borgatti, Antonella; Suter, Steve; Woods, Paul; Gordon, Ira; Vrignaud, Patricia; Khanna, Chand; LeBlanc, Amy K.

    2016-01-01

    Development of iniparib as an anti-cancer agent was hindered in part by lingering questions regarding its mechanism of action, the activity of its metabolites, and their potential accumulation in tumors. Due to strong similarities in metabolism of iniparib between humans and dogs, a veterinary clinical trial in pet dogs with spontaneous cancers was designed to answer specific questions pertaining to pharmacokinetic exposures and tolerability of iniparib. Dogs were treated with iniparib alone and in combination with carboplatin chemotherapy. Iniparib doses ranged between 10–70 mg/kg intravenously (IV). Plasma, tumor and normal tissue samples were collected before and at various time points scheduled after exposure for pharmacokinetic and biologic analysis. The primary endpoints included characterization of dose-limiting toxicities (DLT) and determination of the drug exposures that could be achieved in both normal and tumor tissues. Nineteen dogs were treated. DLT included fever, anorexia, diarrhea, neutropenia, and thrombocytopenia; most effects were attributable to carboplatin based on the timing of adverse event onset. The maximum tolerated dose (MTD) of iniparib was not identified. Moderate to high variability in plasma exposure was noted for iniparib and all metabolites between animals. When quantifiable, iniparib and metabolite plasma:tumor ratios were < 0.088 and <1.7, respectively. In this study, iniparib was well tolerated as a single agent and in combination with carboplatin over a range of doses. However, clinically relevant concentrations of the parent drug and selected metabolites were not detectable in canine tumor tissues at any studied dose, thus eliminating expectations for clinical responses in dogs or humans. Negative clinical trials in humans, and the uncertainties of its mechanism of action, ultimately led to the decision to stop clinical development of the drug. Nevertheless, the questions that can be asked and answered within the comparative

  7. A Comparative Oncology Study of Iniparib Defines Its Pharmacokinetic Profile and Biological Activity in a Naturally-Occurring Canine Cancer Model.

    PubMed

    Saba, Corey; Paoloni, Melissa; Mazcko, Christina; Kisseberth, William; Burton, Jenna H; Smith, Annette; Wilson-Robles, Heather; Allstadt, Sara; Vail, David; Henry, Carolyn; Lana, Susan; Ehrhart, E J; Charles, Brad; Kent, Michael; Lawrence, Jessica; Burgess, Kristine; Borgatti, Antonella; Suter, Steve; Woods, Paul; Gordon, Ira; Vrignaud, Patricia; Khanna, Chand; LeBlanc, Amy K

    2016-01-01

    Development of iniparib as an anti-cancer agent was hindered in part by lingering questions regarding its mechanism of action, the activity of its metabolites, and their potential accumulation in tumors. Due to strong similarities in metabolism of iniparib between humans and dogs, a veterinary clinical trial in pet dogs with spontaneous cancers was designed to answer specific questions pertaining to pharmacokinetic exposures and tolerability of iniparib. Dogs were treated with iniparib alone and in combination with carboplatin chemotherapy. Iniparib doses ranged between 10-70 mg/kg intravenously (IV). Plasma, tumor and normal tissue samples were collected before and at various time points scheduled after exposure for pharmacokinetic and biologic analysis. The primary endpoints included characterization of dose-limiting toxicities (DLT) and determination of the drug exposures that could be achieved in both normal and tumor tissues. Nineteen dogs were treated. DLT included fever, anorexia, diarrhea, neutropenia, and thrombocytopenia; most effects were attributable to carboplatin based on the timing of adverse event onset. The maximum tolerated dose (MTD) of iniparib was not identified. Moderate to high variability in plasma exposure was noted for iniparib and all metabolites between animals. When quantifiable, iniparib and metabolite plasma:tumor ratios were < 0.088 and <1.7, respectively. In this study, iniparib was well tolerated as a single agent and in combination with carboplatin over a range of doses. However, clinically relevant concentrations of the parent drug and selected metabolites were not detectable in canine tumor tissues at any studied dose, thus eliminating expectations for clinical responses in dogs or humans. Negative clinical trials in humans, and the uncertainties of its mechanism of action, ultimately led to the decision to stop clinical development of the drug. Nevertheless, the questions that can be asked and answered within the comparative

  8. Stepped nozzle

    DOEpatents

    Sutton, George P.

    1998-01-01

    An insert which allows a supersonic nozzle of a rocket propulsion system to operate at two or more different nozzle area ratios. This provides an improved vehicle flight performance or increased payload. The insert has significant advantages over existing devices for increasing nozzle area ratios. The insert is temporarily fastened by a simple retaining mechanism to the aft end of the diverging segment of the nozzle and provides for a multi-step variation of nozzle area ratio. When mounted in place, the insert provides the nozzle with a low nozzle area ratio. During flight, the retaining mechanism is released and the insert ejected thereby providing a high nozzle area ratio in the diverging nozzle segment.

  9. Stepped nozzle

    DOEpatents

    Sutton, G.P.

    1998-07-14

    An insert is described which allows a supersonic nozzle of a rocket propulsion system to operate at two or more different nozzle area ratios. This provides an improved vehicle flight performance or increased payload. The insert has significant advantages over existing devices for increasing nozzle area ratios. The insert is temporarily fastened by a simple retaining mechanism to the aft end of the diverging segment of the nozzle and provides for a multi-step variation of nozzle area ratio. When mounted in place, the insert provides the nozzle with a low nozzle area ratio. During flight, the retaining mechanism is released and the insert ejected thereby providing a high nozzle area ratio in the diverging nozzle segment. 5 figs.

  10. Efficient one-step radiolabeling of monoclonal antibodies to high specific activity with Actinium-225 for alpha-particle radioimmunotherapy of cancer

    PubMed Central

    Maguire, William F.; McDevitt, Michael R.; Smith-Jones, Peter M.; Scheinberg, David A.

    2015-01-01

    Targeted alpha-particle radiation using the radioisotope 225Actinium (225Ac) is a promising form of therapy for various types of cancer. Historical obstacles to the use of 225Ac have been the difficulty in finding suitable chelators to stably attach it to targeting vehicles such as peptides and monoclonal antibodies, the low specific activities of the products, and the lack of cost-effective radiolabeling procedures. We initially solved the first problem with a procedure involving two chemical steps that has been used as a standard in preclinical and clinical studies. However, this procedure involves the loss of 90% of the input 225Ac. A more efficient, economical process is needed to facilitate the more widespread use of 225Ac. Methods We conjugated representative antibodies with two forms of 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA), as well as other chelators as controls. We developed conditions to radiolabel these constructs in one chemical step and characterized their stability, immunoreactivity, biodistribution, and therapeutic efficacy in healthy and tumor-bearing mice. Results DOTA- antibody constructs were labeled to a wide range of specific activities in one chemical step at 37 °C. Radiochemical yields were approximately 10-fold higher and specific activities were up to 30-fold higher than with the previous approach. The products retained immunoreactivity and were stable to serum challenge in vitro and in mice. Labeling kinetics of DOTA- antibody constructs linked through a benzyl isothiocyanate linkage were more favorable than those linked through a N-hydroxysuccinimide linkage. Tissue distribution was similar but not identical between the constructs. The constructs produced specific therapeutic responses in a mouse model of acute myeloid leukemia. Conclusion We have characterized an efficient, one-step radiolabeling method that produces stable, therapeutically active conjugates of antibodies with 225Ac at high specific activity

  11. Hierarchical porous carbons prepared by an easy one-step carbonization and activation of phenol-formaldehyde resins with high performance for supercapacitors

    NASA Astrophysics Data System (ADS)

    Zheng, Zhoujun; Gao, Qiuming

    Hierarchical porous carbons are prepared by an easy one-step process of carbonization and activation derived from phenol-formaldehyde resins, in which potassium hydroxide acts as both the catalyst of polymerization and the activation reagent. The simple one-step preparation saves the cost of carbons and leads to high yield. The porous carbons have high surface areas with abundant pore structures. The plenty of micropores and small mesopores increase the capacitance and make the electrolyte ions diffuse fast into the pores. These hierarchical porous carbons show high performance for supercapacitors possessing of the optimized capacitance of 234 F g -1 in aqueous electrolyte and 137 F g -1 in organic electrolyte with high capacitive retention.

  12. Design of the Steps to Health Study of Physical Activity in Survivors of Endometrial Cancer: Testing a Social Cognitive Theory Model

    PubMed Central

    Basen-Engquist, Karen; Carmack, Cindy L.; Perkins, Heidi; Hughes, Daniel; Serice, Susan; Scruggs, Stacie; Pinto, Bernardine; Waters, Andrew

    2010-01-01

    Physical activity has been shown to benefit cancer survivors' physical functioning, emotional well-being, and symptoms. Physical activity may be of particular benefit to survivors of endometrial cancer because they are more likely to be obese and sedentary than the general population, as these are risk factors for the disease, and thus experience a number of related co-morbid health problems. However, there is little research systematically studying mechanisms of physical activity adherence in cancer survivor populations. This paper describes the design of the Steps to Health study, which applies a Social Cognitive Theory-based model of endometrial cancer survivors' adoption and maintenance of exercise in the context of an intervention to increase walking or other moderate intensity cardiovascular activity. In Steps to Health we will test the influence of self-efficacy and outcome expectations on adherence to exercise recommendations, as well as studying the determinants of self-efficacy. Endometrial cancer survivors who are at least 6 months post-treatment are provided with an intervention involving print materials and telephone counseling, and complete assessments of fitness, activity, self-efficacy and outcome expectations, and determinants of self-efficacy every two months for a six month period. In addition to testing an innovative model, the Steps to Health study employs multiple assessment methods, including ecological momentary assessment, implicit tests of cognitive variables, and ambulatory monitoring of physical activity. The study results can be used to develop more effective interventions for increasing physical activity in sedentary cancer survivors by taking into account the full complement of sources of self-efficacy information and outcome expectations. PMID:21218163

  13. Examining Incentives to Promote Physical Activity Maintenance Among Hospital Employees Not Achieving 10,000 Daily Steps: A Web-Based Randomized Controlled Trial Protocol

    PubMed Central

    White, Lauren; Oh, Paul; Kwan, Matthew; Gove, Peter; Leahey, Tricia; Faulkner, Guy

    2016-01-01

    Background The economic burden of physical inactivity in Canada is estimated at Can $6.8 billion (US $5 billion) per year. Employers bear a substantial proportion of the economic costs, as they pay more for inactive workers in health care and other organizational costs. In response, many Canadian employers offer wellness programs, though these are often underutilized. While financial health incentives have been proposed as one way of increasing participation, their longer term effects (ie postintervention effects) are not clear. Objective The objective of this paper is to outline the methodology for a randomized control trial (RCT) examining the longer term impact of an existing physical activity promotion program that is enhanced by adding guaranteed rewards (Can $1 [US $0.74] per day step goal met) in a lower active hospital employee population (less than 10,000 steps per day). Methods A 12-week, parallel-arm RCT (with a 12-week postintervention follow-up) will be employed. Employees using Change4Life (a fully automated, incentive-based wellness program) and accumulating fewer than 10,000 steps per day at baseline (weeks 1 to 2) will be randomly allocated (1:1) to standard care (wellness program, accelerometer) or an intervention group (standard care plus guaranteed incentives). All study participants will be asked to wear the accelerometer and synchronize it to Change4Life daily, although only intervention group participants will receive guaranteed incentives for reaching tailored daily step count goals (Can $1 [US $0.74] per day; weeks 3 to 12). The primary study outcome will be mean proportion of participant-days step goal reached during the postintervention follow-up period (week 24). Mean proportion of participant-days step goal reached during the intervention period (week 12) will be a secondary outcome. Results Enrollment for the study will be completed in February 2017. Data analysis will commence in September 2017. Study results are to be published in

  14. One-step zymogram method for the simultaneous detection of cellulase/xylanase activity and molecular weight estimation of the enzyme.

    PubMed

    Cano-Ramírez, Claudia; Santiago-Hernández, Alejandro; Rivera-Orduña, Flor Nohemí; Pineda-Mendoza, Rosa María; Zúñiga, Gerardo; Hidalgo-Lara, María Eugenia

    2017-02-01

    Here, we describe a zymographic method for the simultaneous detection of enzymatic activity and molecular weight (MW) estimation, following a single electrophoresis step. This involved separating cellulase and xylanase activities from bacteria and fungi, obtained from different sources, such as commercial extracts, crude extract and purified proteins, under denaturing conditions, by 10% polyacrylamide gel electrophoresis, using polyacrylamide gels copolymerized with 1% (w/v) carboxymethylcellulose or beechwood xylan as substrates. Then, enzymes were refolded by treatment with 2.5% Triton X-100 in an appropriate buffer for each enzymatic activity, and visualized by Coomassie blue staining for MW estimation. Finally, Congo red staining revealed bio-active cellulase and xylanase bands after electrophoretic separation of the proteins in the preparations. This method may provide a useful additional tool for screening of particular cellulase and xylanase producers, identification and MW estimation of polypeptides that manifest these activities, and for monitoring and control of fungal and bacterial cellulase and xylanase production.

  15. Activation of extracellular signal-regulated kinases, NF-kappa B, and cyclic adenosine 5'-monophosphate response element-binding protein in lung neutrophils occurs by differing mechanisms after hemorrhage or endotoxemia.

    PubMed

    Abraham, E; Arcaroli, J; Shenkar, R

    2001-01-01

    Acute lung injury is frequently associated with sepsis or blood loss and is characterized by a proinflammatory response and infiltration of activated neutrophils into the lungs. Hemorrhage or endotoxemia result in activation of cAMP response element-binding protein (CREB) and NF-kappa B in lung neutrophils as well as increased expression of proinflammatory cytokines, such as TNF-alpha and macrophage-inflammatory peptide-2, by these cells. Activation of the extracellular regulated kinase (ERK) pathway occurs in stress responses and is involved in CREB activation. In the present experiments, hemorrhage or endotoxemia produced increased activation of mitogen-activated protein kinase kinase (MEK)1/2 and ERK2 (p42), but not of ERK1 (p44), in lung neutrophils. ERK1, ERK2, and MEK1/2 were not activated in peripheral blood neutrophils after hemorrhage or endotoxemia. Inhibition of xanthine oxidase led to further increase in the activation of MEK1/2 and ERK2 in lung neutrophils after hemorrhage, but not after endotoxemia. Alpha-adrenergic blockade before hemorrhage resulted in increased activation in lung neutrophils of MEK1/2, ERK1, ERK2, and CREB, but decreased activation of NF-kappa B. In contrast, alpha-adrenergic blockade before endotoxemia was associated with decreased activation of MEK1/2, ERK2, and CREB, but increased activation of NF-kappa B. Beta-adrenergic blockade before hemorrhage did not alter MEK1/2 or ERK1 activation in lung neutrophils, but decreased activation of ERK2 and CREB, while increasing activation of NF-kappa B. Beta-adrenergic inhibition before endotoxemia did not affect activation of MEK1/2, ERK1, ERK2, CREB, or NF-kappa B. These data indicate that the pathways leading to lung neutrophil activation after hemorrhage are different from those induced by endotoxemia.

  16. [6]-gingerol as a cancer chemopreventive agent: a review of its activity on different steps of the metastatic process.

    PubMed

    Poltronieri, Juliana; Becceneri, Amanda B; Fuzer, Angelina M; Filho, Julio Cesar C; Martin, Ana Carolina B M; Vieira, Paulo Cezar; Pouliot, Normand; Cominetti, Márcia R

    2014-04-01

    For many years, ginger or ginger root, the rhizome of the plant Zingiber officinale, has been consumed as a delicacy, medicine, or spice. Several studies have been conducted on the medicinal properties of ginger against various disorders, including cancer. Cancer is the second leading cause of death, and chemoprevention is defined as the use of natural or synthetic substances to prevent cancer initiation or progression. Evidence that ginger-derived compounds have inhibitory effects on various cancer cell types is increasingly being reported in the scientific literature. In this review we focused on the cancer chemopreventive effects of [6]-gingerol, the major pungent component of ginger, and its impact on different steps of the metastatic process.

  17. Trunk robot rehabilitation training with active stepping reorganizes and enriches trunk motor cortex representations in spinal transected rats.

    PubMed

    Oza, Chintan S; Giszter, Simon F

    2015-05-06

    Trunk motor control is crucial for postural stability and propulsion after low thoracic spinal cord injury (SCI) in animals and humans. Robotic rehabilitation aimed at trunk shows promise in SCI animal models and patients. However, little is known about the effect of SCI and robot rehabilitation of trunk on cortical motor representations. We previously showed reorganization of trunk motor cortex after adult SCI. Non-stepping training also exacerbated some SCI-driven plastic changes. Here we examine effects of robot rehabilitation that promotes recovery of hindlimb weight support functions on trunk motor cortex representations. Adult rats spinal transected as neonates (NTX rats) at the T9/10 level significantly improve function with our robot rehabilitation paradigm, whereas treadmill-only trained do not. We used intracortical microstimulation to map motor cortex in two NTX groups: (1) treadmill trained (control group); and (2) robot-assisted treadmill trained (improved function group). We found significant robot rehabilitation-driven changes in motor cortex: (1) caudal trunk motor areas expanded; (2) trunk coactivation at cortex sites increased; (3) richness of trunk cortex motor representations, as examined by cumulative entropy and mutual information for different trunk representations, increased; (4) trunk motor representations in the cortex moved toward more normal topography; and (5) trunk and forelimb motor representations that SCI-driven plasticity and compensations had caused to overlap were segregated. We conclude that effective robot rehabilitation training induces significant reorganization of trunk motor cortex and partially reverses some plastic changes that may be adaptive in non-stepping paraplegia after SCI.

  18. Friction of atomically stepped surfaces

    NASA Astrophysics Data System (ADS)

    Dikken, R. J.; Thijsse, B. J.; Nicola, L.

    2017-03-01

    The friction behavior of atomically stepped metal surfaces under contact loading is studied using molecular dynamics simulations. While real rough metal surfaces involve roughness at multiple length scales, the focus of this paper is on understanding friction of the smallest scale of roughness: atomic steps. To this end, periodic stepped Al surfaces with different step geometry are brought into contact and sheared at room temperature. Contact stress that continuously tries to build up during loading, is released with fluctuating stress drops during sliding, according to the typical stick-slip behavior. Stress release occurs not only through local slip, but also by means of step motion. The steps move along the contact, concurrently resulting in normal migration of the contact. The direction of migration depends on the sign of the step, i.e., its orientation with respect to the shearing direction. If the steps are of equal sign, there is a net migration of the entire contact accompanied by significant vacancy generation at room temperature. The stick-slip behavior of the stepped contacts is found to have all the characteristic of a self-organized critical state, with statistics dictated by step density. For the studied step geometries, frictional sliding is found to involve significant atomic rearrangement through which the contact roughness is drastically changed. This leads for certain step configurations to a marked transition from jerky sliding motion to smooth sliding, making the final friction stress approximately similar to that of a flat contact.

  19. A Step in the Right Direction: Commentary on Expected Values for Pedometer-Determined Physical Activity in Youth

    ERIC Educational Resources Information Center

    Beets, Michael W.

    2010-01-01

    The recent compilation of pedometer-determined physical activity studies of youth by Tudor-Locke and colleagues (Tudor-Locke, McClain, Hart, Sisson, & Washington, 2009) is a valuable addition to the growing field of physical activity assessment via pedometry. In this study, Tudor-Locke and colleagues presented an "expected" habitual daily…

  20. A Dual Step Transfer Model: Sport and Non-Sport Extracurricular Activities and the Enhancement of Academic Achievement

    ERIC Educational Resources Information Center

    Bradley, John L.; Conway, Paul F.

    2016-01-01

    This paper explores the influence that school sport and non-sport extracurricular activities (ssEC and nsEC) can have on academic achievement. A central thesis of this paper is that, despite the literature on the perceived and presumed benefits of school sport and of non-sport activities, theorising a model of the process by which the benefit is…

  1. STEP activation by Gαq coupled GPCRs opposes Src regulation of NMDA receptors containing the GluN2A subunit

    PubMed Central

    Tian, Meng; Xu, Jian; Lei, Gang; Lombroso, Paul J.; Jackson, Michael F.; MacDonald, John F.

    2016-01-01

    N-methyl-D-aspartate receptors (NMDARs) are necessary for the induction of synaptic plasticity and for the consolidation of learning and memory. NMDAR function is tightly regulated by functionally opposed families of kinases and phosphatases. Herein we show that the striatal-enriched protein tyrosine phosphatase (STEP) is recruited by Gαq-coupled receptors, including the M1 muscarinic acetylcholine receptor (M1R), and opposes the Src tyrosine kinase-mediated increase in the function of NMDARs composed of GluN2A. STEP activation by M1R stimulation requires IP3Rs and can depress NMDA-evoked currents with modest intracellular Ca2+ buffering. Src recruitment by M1R stimulation requires coincident NMDAR activation and can augment NMDA-evoked currents with high intracellular Ca2+ buffering. Our findings suggest that Src and STEP recruitment is contingent on differing intracellular Ca2+ dynamics that dictate whether NMDAR function is augmented or depressed following M1R stimulation. PMID:27857196

  2. Molecular Differences between a Mutase and a Phosphatase: Investigations of the Activation Step in Bacillus cereus Phosphopentomutase

    SciTech Connect

    Iverson, T.M.; Panosian, Timothy D.; Birmingham, William R.; Nannemann, David P.; Bachmann, Brian O.

    2012-05-09

    Prokaryotic phosphopentomutases (PPMs) are di-Mn{sup 2+} enzymes that catalyze the interconversion of {alpha}-D-ribose 5-phosphate and {alpha}-D-ribose 1-phosphate at an active site located between two independently folded domains. These prokaryotic PPMs belong to the alkaline phosphatase superfamily, but previous studies of Bacillus cereus PPM suggested adaptations of the conserved alkaline phosphatase catalytic cycle. Notably, B. cereus PPM engages substrates when the active site nucleophile, Thr-85, is phosphorylated. Further, the phosphoenzyme is stable throughout purification and crystallization. In contrast, alkaline phosphatase engages substrates when the active site nucleophile is dephosphorylated, and the phosphoenzyme reaction intermediate is only stably trapped in a catalytically compromised enzyme. Studies were undertaken to understand the divergence of these mechanisms. Crystallographic and biochemical investigations of the PPM{sup T85E} phosphomimetic variant and the neutral corollary PPM{sup T85Q} determined that the side chain of Lys-240 underwent a change in conformation in response to active site charge, which modestly influenced the affinity for the small molecule activator {alpha}-D-glucose 1,6-bisphosphate. More strikingly, the structure of unphosphorylated B. cereus PPM revealed a dramatic change in the interdomain angle and a new hydrogen bonding interaction between the side chain of Asp-156 and the active site nucleophile, Thr-85. This hydrogen bonding interaction is predicted to align and activate Thr-85 for nucleophilic addition to {alpha}-D-glucose 1,6-bisphosphate, favoring the observed equilibrium phosphorylated state. Indeed, phosphorylation of Thr-85 is severely impaired in the PPM{sup D156A} variant even under stringent activation conditions. These results permit a proposal for activation of PPM and explain some of the essential features that distinguish between the catalytic cycles of PPM and alkaline phosphatase.

  3. Structural Modifications of Benzimidazoles via Multi-Step Synthesis and Their Impact on Sirtuin-Inhibitory Activity.

    PubMed

    Yoon, Yeong Keng; Choon, Tan Soo

    2016-01-01

    Benzimidazole derivatives have been shown to possess sirtuin-inhibitory activity. In the continuous search for potent sirtuin inhibitors, systematic changes on the terminal benzene ring were performed on previously identified benzimidazole-based sirtuin inhibitors, to further investigate their structure-activity relationships. It was demonstrated that the sirtuin activities of these novel compounds followed the trend where meta-substituted compounds possessed markedly weaker potency than ortho- and para-substituted compounds, with the exception of halogenated substituents. Molecular docking studies were carried out to rationalize these observations. Apart from this, the methods used to synthesize the interesting compounds are also discussed.

  4. Stepping towards prevention of bone loss after stroke: a systematic review of the skeletal effects of physical activity after stroke.

    PubMed

    Borschmann, Karen; Pang, Marco Y C; Bernhardt, Julie; Iuliano-Burns, Sandra

    2012-06-01

    Bone loss after stroke is pronounced, and contributes to increased fracture risk. People who fracture after stroke experience reduced mobility and increased mortality. Physical activity can maintain or improve bone mineral density and structure in healthy older adults, likely reducing fracture risk. The purpose of this systematic review was to investigate the skeletal effects of physical activity in adults affected by stroke. A search of electronic databases was undertaken. Selection criteria of trials were • prospective and controlled • physical activity-based intervention • participants with history of stroke, and • bone-related outcome measures. Effect sizes were calculated for outcomes of paretic and nonparetic limbs. Three of 349 identified records met the inclusion criteria. Small effect sizes were found in favor of physical activity in adults with chronic stroke (n=95, 40% female, average age 63·8 years, more than one-year poststroke). Patients in intervention groups had significantly higher changes in femoral neck bone mineral density, tibial cortical thickness and trabecular bone mineral content of the paretic limb, compared with controls (P<0·05). It is not known whether these benefits reduced fracture risk. There are limited studies investigating the skeletal effect of physical activity for adults poststroke. Given the increased risk of, and poor outcomes following a fracture after stroke, randomized trials are warranted to investigate the benefits of physical activity on bone, after stroke. Interventions are likely to be beneficial if implemented soon after stroke, when bone loss appears to be rapid and pronounced.

  5. Regionally selective activation of ERK and JNK in morphine paradoxical hyperalgesia: a step toward improving opioid pain therapy.

    PubMed

    Sanna, Maria Domenica; Ghelardini, Carla; Galeotti, Nicoletta

    2014-11-01

    In addition to analgesia, opioid agonists may increase pain sensitivity under different conditions varying dose and administration pattern. While opioid hyperalgesia induced by tolerance and withdrawal is largely studied, little is known on the mechanisms underlying ultra-low dose morphine hyperalgesia. This pronociceptive response appears to play an opposing role in morphine analgesia and might have clinical relevance. Ultra-low dose morphine elicited thermal hyperalgesia through activation of μ opioid receptors. To elucidate the intracellular mechanism of morphine nociceptive behaviour, we investigated the mitogen-activated protein kinase (MAPK), crucial pathways in pain hypersensitivity. The catalytic activity of extracellular signal-regulated kinase (ERK), p38, c-Jun-N-terminal kinase (JNK), upstream modulators and transcription factors was investigated in the mouse periaqueductal grey matter (PAG), thalamus and prefrontal cortex by western blotting. Ultra-low dose morphine intensively increased pERK1 contents in the PAG and cortex and, to a lesser extent, increased cortical ERK2 and JNK phosphorylation. No involvement of p38 was detected. Morphine exposure also increased phosphorylation of cortical c-Jun whereas levels of phosphorylated cAMP response element-binding protein (CREB) remained unmodified. Blockade of protein kinase C (PKC) prevented increases in phosphorylation showing a PKC-dependent mechanism of activation. Pharmacological inhibitors of PKC, ERK, and JNK activity prevented morphine hyperalgesia. No modulation of MAPK and transcription factors' activity was detected in the thalamus. These results support the concept that selective activation of ERK and JNK on descending pathways plays an important role in ultra-low dose morphine hyperalgesia. The modulation of these signalling processes might improve pain management with opiate analgesics.

  6. The impact of strenuous group physical activity on mood states, personal views, body composition, and markers of myocardial damage in overweight/obese adults: the "Step-by-step Italy's coast to coast" trek.

    PubMed

    Mazzeschi, Claudia; Piana, Natalia; Capezzali, Daniela; Mommi, Antonella; Aiello, Cristina; Gatti, Michela; Romani, Giannermete; Buratta, Livia; Battistini, Dalila; Nasini, Giovanni; Reginato, Elisa; Urbani, Lorena; Pazzagli, Chiara; Ferri, Carla; Ambrosio, Giuseppe; De Feo, Pierpaolo

    2014-01-01

    It is clinically relevant to understand whether it is safe to recommend to trained overweight/obese people long-distance treks and whether these experiences could have a negative psychological impact or become even dangerous exposing the trekkers to the risk of clinically silent myocardial damage. To answer these questions we have performed a quantitative/qualitative study comparing the changes in mood profiles, personal views, body composition, and plasma troponin levels of 40 overweight/obese subjects with those of 36 healthy normal weight subjects after the participation in a trek of 388 km from the Adriatic to the Tyrrhenian seas trek: the "Step by step…Italy's coast to coast". The results of this study demonstrate that long-distance treks are a safe activity for trained overweight/obese people which should be recommended because they improve mood, health status, and the relationship of participants with themselves and with the regular practice of exercise with effects similar to those obtained by healthy normal weight subjects.

  7. Direct Synthesis of Protoberberine Alkaloids by Rh-Catalyzed C-H Bond Activation as the Key Step.

    PubMed

    Jayakumar, Jayachandran; Cheng, Chien-Hong

    2016-01-26

    A one-pot reaction of substituted benzaldehydes with alkyne-amines by a Rh-catalyzed C-H activation and annulation to afford various natural and unnatural protoberberine alkaloids is reported. This reaction provides a convenient route for the generation of a compound library of protoberberine salts, which recently have attracted great attention because of their diverse biological activities. In addition, pyridinium salt derivatives can also be formed in good yields from α,β-unsaturated aldehydes and amino-alkynes. This reaction proceeds with excellent regioselectivity and good functional group compatibility under mild reaction conditions by using O2 as the oxidant.

  8. Response to "A Step in the Right Direction: Commentary on Expected Values for Pedometer-Determined Physical Activity in Youth"

    ERIC Educational Resources Information Center

    Tudor-Locke, Catrine; McClain, James J.; Hart, Teresa L.; Sisson, Susan B.; Washington, Tracy L.

    2010-01-01

    As researchers and science writers, the authors are always pleased when anyone takes enough interest in their work, but this time it was especially pleasing to have inspired Beets to comment on it (Beets, 2010)! The focus of his commentary is "Expected Values for Pedometer-Determined Physical Activity in Youth" (Tudor-Locke, McClain, Hart, Sisson,…

  9. Psychosocial constructs and postintervention changes in physical activity and dietary outcomes in a lifestyle intervention, HUB City Steps, 2010

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Purpose: To examine relationships among psychosocial constructs (PSC) of behavior change and post-intervention changes in physical activity (PA) and dietary outcomes. Design: Non-controlled, pre- post-experimental intervention. Setting: Midsized, southern United States city. Subjects: 269 prima...

  10. Translation of moderate-to-vigorous physical activity recommendations into pedometer-based stepping targets in the Lower Mississippi Delta

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Lower Mississippi Delta (LMD) region of the United States is characterized by high levels of poverty, physical inactivity, obesity, and related chronic diseases. There is a pressing need to identify new strategies that will increase adherence to physical activity guidelines. Walking is an import...

  11. Steps Ahead: Adaptation of physical activity and dietary guidelines for reducing unhealthy weight gain in the Lower Misissippi Delta

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The purpose of our study was to test the effectiveness of adapting the Dietary Guidelines for Americans (2010) (DG), with and without a physical activity (PA) component, in reducing weight gain in the Lower Mississippi Delta region (LMD) of the United States. A sample of 121 White and African-Americ...

  12. Campus Walkability, Pedometer-Determined Steps, and Moderate-to-Vigorous Physical Activity: A Comparison of 2 University Campuses

    ERIC Educational Resources Information Center

    Sisson, Susan B.; Mcclain, James J.; Tudor-Locke, Catrine

    2008-01-01

    Objective and Participants: At 2 Arizona State University (ASU) campuses, the authors measured student activity and distance walked on campus, as well as student-reported walkability around the student union. Methods: Students from ASU-Polytechnic (n = 20, 33% male) and ASU-Tempe (n = 20, 60% male) recorded distance walked on campus and wore…

  13. A two step method to synthesize palladium-copper nanoparticles on reduced graphene oxide and their extremely high electrocatalytic activity for the electrooxidation of methanol and ethanol

    NASA Astrophysics Data System (ADS)

    Na, HeYa; Zhang, Lei; Qiu, HaiXia; Wu, Tao; Chen, MingXi; Yang, Nian; Li, LingZhi; Xing, FuBao; Gao, JianPing

    2015-08-01

    Palladium-copper nanoparticles (Pd-Cu NPs) supported on reduced graphene oxide (RGO) with different Pd/Cu ratios (Pd-Cu/RGO) were prepared by a two step method. The Pd-Cu/RGO hybrids were characterized by transmission electron microscopy, X-ray photoelectron spectroscopy, X-ray diffraction and thermogravimetric analyses. Cyclic voltammetry and chronoamperometry were used to investigate the electrochemical activities and stabilities of the Pd-Cu/RGO catalysts for the electro-oxidation of methanol and ethanol in alkaline media. The Pd-Cu/RGO catalysts exhibited high catalytic activities and good stabilities. This is because the catalysts have a bimetallic structure consisting of a small Pd-Cu core surrounded by a thin Pd-rich shell which improves the catalytic activities of the Pd-Cu/RGO hybrids. Thus they should be useful in direct methanol and ethanol fuel cells.

  14. Baby steps.

    PubMed

    Bader, E J; Truax, H

    1991-01-01

    The focus of the discussion of US national environmental efforts on population growth issues is on carrying capacity, the impact of the antiabortion movement, the insensitivity of some population control advocated to people of color, and congressional and presidential actions. Efforts are being made to surmount the mistrust that has characterized efforts to deal with population issues. The World Wildlife Fund, the Sierra Club, and the National Audubon Society recognize the need for population stabilization, albeit with meager budgets. Carrying capacity is the number of people the earth can sustain without rapidly depleting non-renewable resources or degrading resources necessary to sustain life. In 1970, Earth Day called for stabilization of the global population, but most celebrations of Earth Day in 1990 did not recognize this. Sensitive issues are involved, and the abortion controversy has muffled open forums on population growth. Lobbyists were successful in having the US withdraw funding for international family planning (FP) programs that had abortion components. Then Reagan eliminated all funding to the UN Fund for Population Activities, because of China's FP policies. The results for women have been disastrous. Zero Population Growth has been conducting information meetings for environmental groups. The National wildlife Federation has a new program linking population and environmental issues but will not deal with the issue of abortion. A Philadelphia editorial recommended implanted contraceptives for welfare mothers, which raised fears of the reemergence of the eugenic movement which sought involuntary sterilization or population control for the poor. Another effort was to protect the US from immigration as a way of curbing population growth. Meaningful change means education women, changing unfavorable survival conditions, and heeding the reasons women have children. Japan's FP Association criticizes population control efforts undertaken for economic and

  15. Interleukin-12 synthesis is a required step in trehalose dimycolate-induced activation of mouse peritoneal macrophages.

    PubMed Central

    Oswald, I P; Dozois, C M; Petit, J F; Lemaire, G

    1997-01-01

    Trehalose dimycolate (TDM), a glycolipid present in the cell wall of Mycobacterium spp., is a powerful immunostimulant. TDM primes murine macrophages (Mphi) to produce nitric oxide (NO) and to develop antitumoral activity upon activation with low doses of lipopolysaccharide (LPS). In this study, we investigated the ability of TDM to induce interleukin 12 (IL-12) and the role of this cytokine in TDM-induced activation of murine Mphi. RNA isolated from peritoneal exudate cells (PEC) collected at different times after TDM injection was used to determine IL-12 (p35 and p40 subunits) and gamma interferon (IFN-gamma) mRNA levels by semiquantitative reverse transcriptase-PCR. Constitutive expression of IL-12p35 was observed in PEC from untreated as well as from TDM-injected mice. In contrast, expression of the IL-12p40 subunit was almost undetectable in control PEC but was dramatically upregulated in PEC from TDM-injected mice. IL-12p40 expression peaked at 8 h and subsided to baseline levels at 39 h postinjection. TDM was also able to induce IFN-gamma expression; however, kinetics of induction of IFN-gamma was different from that of IL-12p40. Maximal levels of IFN-gamma mRNA were reached by 24 h and did not return to baseline by 4 days. In addition, pretreatment of mice with neutralizing monoclonal antibodies directed against IL-12 (C15.6.7 and C15.1.2) blocked IFN-gamma mRNA induction in PEC from TDM-treated mice. We further determined if the induction of IL-12 and/or IFN-gamma contributes to the in vivo priming effect of TDM on peritoneal Mphi. TDM-injected mice were treated in vivo with anti-IL-12 or anti-IFN-gamma (XMG.1.6) monoclonal antibodies. TDM-primed Mphi were then activated in vitro with LPS and tested for their ability to produce NO and to develop cytostatic activity toward cocultivated L1210 tumor cells. Priming of Mphi by TDM was completely blocked by in vivo neutralization of either IL-12 or IFN-gamma as demonstrated by an absence of tumoricidal activity

  16. ATP-mediated intrinsic peroxidase-like activity of Fe3O4-based nanozyme: One step detection of blood glucose at physiological pH.

    PubMed

    Vallabani, N V Srikanth; Karakoti, Ajay S; Singh, Sanjay

    2017-05-01

    Fe3O4 nanoparticles (Fe3O4 NPs), demonstrating peroxidase-like activity has garnered attention in the detection of several biomolecules, therefore, emerged as an excellent nano-biosensing agent. The intrinsic peroxidase-like activity of Fe3O4 NPs at acidic pH is the fundamental action driving the oxidation of substrates like TMB, resulting in a colorimetric product formation used in the detection of biomolecules. Hence, the detection sensitivity essentially depends on the ability of oxidation by Fe3O4 NPs in presence of H2O2. However, the limited sensitivity and pH condition constraint have been identified as the major drawbacks in the detection of biomolecules at physiological pH. Herein, we report overwhelming of the fundamental limitation of acidic pH and tuning the peroxidase-like activity of Fe3O4 NPs at physiological pH by using ATP. In presence of ATP, Fe3O4 NPs exhibited enhanced peroxidase-like activity over a wide range of pH and temperatures. Mechanistically, it was found that the ability of ATP to participate in single electron transfer reaction, through complexation with Fe3O4 NPs, results in the generation of hydroxyl radicals which are responsible for enhanced peroxidase activity at physiological pH. We utilized this ATP-mediated enhanced peroxidase-like activity of Fe3O4 NPs for single step detection of glucose with a colorimetric detection limit of 50μM. Further, we extended this single step detection method to monitor glucose level in human blood serum and detected in a time span of <5min at pH 7.4.

  17. Requirements for distinct steps of phospholipase Cgamma2 regulation, membrane-raft-dependent targeting and subsequent enzyme activation in B-cell signalling.

    PubMed Central

    Rodriguez, Rosie; Matsuda, Miho; Storey, Amy; Katan, Matilda

    2003-01-01

    Studies of PLCgamma (phospholipase Cgamma) have identified a number of regulatory components required for signalling; however, molecular mechanisms and the relationship between events leading to translocation and an increase of substrate hydrolysis have not been well defined. The addition of a membrane-targeting tag to many signal transducers results in constitutive activation, suggesting that these processes could be closely linked and difficult to dissect. The present study of PLCgamma2 regulation by cross-linking of the BCR (B-cell antigen receptor) or H2O2 stress in DT40 B-cells, demonstrated that the membrane targeting is a separate step from further changes that result in enzyme activation and substrate hydrolysis. Furthermore, we have defined the roles of different domains of PLCgamma2 and, using a panel of cell lines deficient in components linked to PLCgamma2 regulation, the involvement of signalling molecules with respect to each of the steps. We have found that only the lipid-raft-targeted Lyn-PLCgamma2 construct, unlike non-specific membrane targeting, overcame the requirement for the adapter protein BLNK (B-cell linker). The stable expression of Lyn-PLCgamma2 was not accompanied by an increase in substrate hydrolysis in resting cells, which followed stimulation and specifically required the presence and/or activation of Syk, Btk, phosphoinositide 3-kinase but not BLNK, as established using deficient cell lines or specific inhibitors. Based on mutational analysis of the specific tyrosine residues [Tyr753-->Phe (Y753F)/Y759F] and SH2 (Src homology 2) domains (R564A/R672A) in the context of Lyn-PLCgamma2, we found that Tyr753/Tyr759 were essential, whereas the PLCgamma2 SH2 domains did not have an important role in the transient activation of Lyn-PLCgamma2 but may serve to stabilize an activated form in sustained activation. PMID:12780340

  18. Low temperature one-step synthesis of rutile TiO{sub 2}/BiOCl composites with enhanced photocatalytic activity

    SciTech Connect

    Duo, Fangfang; Wang, Yawen Fan, Caimei; Mao, Xiaoming; Zhang, Xiaochao; Wang, Yunfang; Liu, Jianxin

    2015-01-15

    The rutile TiO{sub 2}/BiOCl composites were successfully fabricated by a facile one-step hydrolysis method at low temperature (50 °C). The X-ray diffraction, scanning electron microscopy, transmission electron microscopy, UV–vis diffuse reflectance spectra, Fourier transform infrared spectroscopy, Brunauer–Emmett–Teller, and X-ray photoelectron spectroscopy measurements were employed to characterize the phase structures, morphologies, optical properties, surface areas, and electronic state of the samples. The rutile TiO{sub 2}/BiOCl composites exhibited higher photocatalytic activity than pure BiOCl and rutile TiO{sub 2} for the degradation of phenol under artificial solar light irradiation. In addition, the photocatalytic mechanism has also been investigated and discussed. The enhanced photocatalytic performance of rutile TiO{sub 2}/BiOCl composites is closely related to the heterojunctions between BiOCl and rutile TiO{sub 2}, which can not only broaden the light adsorption range of BiOCl but also improve the electron–hole separation efficiency under artificial solar light irradiation. - Highlights: • Rutile TiO{sub 2}/BiOCl was prepared by a low temperature one-step hydrolysis method. • The synthetic method is quite convenient and energy-saving. • The composites exhibit enhanced photocatalytic activity on phenol degradation. • The high photocatalytic activity relates to the heterojunctions of BiOCl and TiO{sub 2}.

  19. The three-step process of self-objectification: potential implications for adolescents' body consciousness during sexual activity.

    PubMed

    Vandenbosch, Laura; Eggermont, Steven

    2014-01-01

    A three-wave panel study with intervals of six months was conducted to examine the relationships between internalization of appearance ideals, body surveillance, valuing appearance over competence, and body consciousness during sexual activity among 238 Belgian adolescents who had engaged in sexual intercourse. Consistent with predictions, structural equation modeling indicated that greater internalization of appearance ideals at Wave 1 contributed to increased body surveillance and valuing appearance over competence at Wave 2. Body surveillance at Wave 2 and internalization at Wave 1 predicted higher body consciousness during sexual activity at Wave 3. Gender did not moderate these results, as model paths were similar in strength for girls and boys. These results further implicate the consequences of internalizing sociocultural practices that objectify boys and girls regarding adolescents' initial sexual experiences.

  20. Phenanthrene Metabolism in Smokers: Use of a Two-Step Diagnostic Plot Approach to Identify Subjects with Extensive Metabolic Activation

    PubMed Central

    Wang, Jing; Zhong, Yan; Carmella, Steven G.; Hochalter, J. Bradley; Rauch, Diane; Oliver, Andrew; Jensen, Joni; Hatsukami, Dorothy K.; Upadhyaya, Pramod; Hecht, Stephen S.

    2012-01-01

    Polycyclic aromatic hydrocarbons (PAHs) in cigarette smoke are among the most likely causes of lung cancer. PAHs require metabolic activation to initiate the carcinogenic process. Phenanthrene (Phe), a noncarcinogenic PAH, was used as a surrogate of benzo[α]pyrene and related PAHs to study the metabolic activation of PAHs in smokers. A dose of 10 μg of deuterated Phe ([D10]Phe) was administered to 25 healthy smokers in a crossover design, either as an oral solution or by smoking cigarettes containing [D10]Phe. Phe was deuterated to avoid interference from environmental Phe. Intensive blood and urine sampling was performed to quantitate the formation of deuterated r-1,t-2,3,c-4-tetrahydroxy-1,2,3,4-tetrahydrophenanthrene ([D10]PheT), a biomarker of the diol epoxide metabolic activation pathway. In both the oral and smoking arms approximately 6% of the dose was metabolically converted to diol epoxides, with a large intersubject variability in the formation of [D10]PheT observed. Two diagnostic plots were developed to identify subjects with large systemic exposure and significant lung contribution to metabolic activation. The combination of the two plots led to the identification of subjects with substantial local exposure. These subjects produced, in one single pass of [D10]Phe through the lung, a [D10]PheT exposure equivalent to the systemic exposure of a typical subject and may be an indicator of lung cancer susceptibility. Polymorphisms in PAH-metabolizing genes of the 25 subjects were also investigated. The integration of phenotyping and genotyping results indicated that GSTM1-null subjects produced approximately 2-fold more [D10]PheT than did GSTM1-positive subjects. PMID:22674470

  1. Detection and Classification of Finer-Grained Human Activities Based on Stepped-Frequency Continuous-Wave Through-Wall Radar

    PubMed Central

    Qi, Fugui; Liang, Fulai; Lv, Hao; Li, Chuantao; Chen, Fuming; Wang, Jianqi

    2016-01-01

    The through-wall detection and classification of human activities are critical for anti-terrorism, security, and disaster rescue operations. An effective through-wall detection and classification technology is proposed for finer-grained human activities such as piaffe, picking up an object, waving, jumping, standing with random micro-shakes, and breathing while sitting. A stepped-frequency continuous wave (SFCW) bio-radar sensor is first used to conduct through-wall detection of finer-grained human activities; Then, a comprehensive range accumulation time-frequency transform (CRATFR) based on inverse weight coefficients is proposed, which aims to strengthen the micro-Doppler features of finer activity signals. Finally, in combination with the effective eigenvalues extracted from the CRATFR spectrum, an optimal self-adaption support vector machine (OS-SVM) based on prior human position information is introduced to classify different finer-grained activities. At a fixed position (3 m) behind a wall, the classification accuracies of six activities performed by eight individuals were 98.78% and 93.23%, respectively, for the two scenarios defined in this paper. In the position-changing experiment, an average classification accuracy of 86.67% was obtained for five finer-grained activities (excluding breathing) of eight individuals within 6 m behind the wall for the most practical scenario, a significant improvement over the 79% accuracy of the current method. PMID:27314362

  2. FusX: A Rapid One-Step Transcription Activator-Like Effector Assembly System for Genome Science.

    PubMed

    Ma, Alvin C; McNulty, Melissa S; Poshusta, Tanya L; Campbell, Jarryd M; Martínez-Gálvez, Gabriel; Argue, David P; Lee, Han B; Urban, Mark D; Bullard, Cassandra E; Blackburn, Patrick R; Man, Toni K; Clark, Karl J; Ekker, Stephen C

    2016-06-01

    Transcription activator-like effectors (TALEs) are extremely effective, single-molecule DNA-targeting molecular cursors used for locus-specific genome science applications, including high-precision molecular medicine and other genome engineering applications. TALEs are used in genome engineering for locus-specific DNA editing and imaging, as artificial transcriptional activators and repressors, and for targeted epigenetic modification. TALEs as nucleases (TALENs) are effective editing tools and offer high binding specificity and fewer sequence constraints toward the targeted genome than other custom nuclease systems. One bottleneck of broader TALE use is reagent accessibility. For example, one commonly deployed method uses a multitube, 5-day assembly protocol. Here we describe FusX, a streamlined Golden Gate TALE assembly system that (1) is backward compatible with popular TALE backbones, (2) is functionalized as a single-tube 3-day TALE assembly process, (3) requires only commonly used basic molecular biology reagents, and (4) is cost-effective. More than 100 TALEN pairs have been successfully assembled using FusX, and 27 pairs were quantitatively tested in zebrafish, with each showing high somatic and germline activity. Furthermore, this assembly system is flexible and is compatible with standard molecular biology laboratory tools, but can be scaled with automated laboratory support. To demonstrate, we use a highly accessible and commercially available liquid-handling robot to rapidly and accurately assemble TALEs using the FusX TALE toolkit. Together, the FusX system accelerates TALE-based genomic science applications from basic science screening work for functional genomics testing and molecular medicine applications.

  3. FusX: A Rapid One-Step Transcription Activator-Like Effector Assembly System for Genome Science

    PubMed Central

    Ma, Alvin C.; McNulty, Melissa S.; Poshusta, Tanya L.; Campbell, Jarryd M.; Martínez-Gálvez, Gabriel; Argue, David P.; Lee, Han B.; Urban, Mark D.; Bullard, Cassandra E.; Blackburn, Patrick R.; Man, Toni K.; Clark, Karl J.; Ekker, Stephen C.

    2016-01-01

    Transcription activator-like effectors (TALEs) are extremely effective, single-molecule DNA-targeting molecular cursors used for locus-specific genome science applications, including high-precision molecular medicine and other genome engineering applications. TALEs are used in genome engineering for locus-specific DNA editing and imaging, as artificial transcriptional activators and repressors, and for targeted epigenetic modification. TALEs as nucleases (TALENs) are effective editing tools and offer high binding specificity and fewer sequence constraints toward the targeted genome than other custom nuclease systems. One bottleneck of broader TALE use is reagent accessibility. For example, one commonly deployed method uses a multitube, 5-day assembly protocol. Here we describe FusX, a streamlined Golden Gate TALE assembly system that (1) is backward compatible with popular TALE backbones, (2) is functionalized as a single-tube 3-day TALE assembly process, (3) requires only commonly used basic molecular biology reagents, and (4) is cost-effective. More than 100 TALEN pairs have been successfully assembled using FusX, and 27 pairs were quantitatively tested in zebrafish, with each showing high somatic and germline activity. Furthermore, this assembly system is flexible and is compatible with standard molecular biology laboratory tools, but can be scaled with automated laboratory support. To demonstrate, we use a highly accessible and commercially available liquid-handling robot to rapidly and accurately assemble TALEs using the FusX TALE toolkit. Together, the FusX system accelerates TALE-based genomic science applications from basic science screening work for functional genomics testing and molecular medicine applications. PMID:26854857

  4. One-step production of biodiesel from oils with high acid value by activated Mg-Al hydrotalcite nanoparticles.

    PubMed

    Wang, Yi-Tong; Fang, Zhen; Zhang, Fan; Xue, Bao-Jin

    2015-10-01

    Activated Mg-Al hydrotalcite (HT-Ca) nanoparticles (<45 nm) were synthesized by co-precipitation and hydrothermal activation with aqueous Ca(OH)2 solution. They were characterized by various techniques including X-ray diffraction, inductively coupled plasma atomic-emission spectrometer, Brunauer-Emmett-Teller method, scanning electronic microscope-X-ray energy dispersive analysis and temperature programmed desorption method. HT-Ca presented both acidic and basic due to the formation of Mg4Al2(OH)14 · 3H2O, Mg2Al(OH)7 and AlO(OH) nanocrystals to esterify and transesterify oils with high acid value (AV). Under conditions of 5 wt% HT-Ca, 160 °C, 30/1 methanol/oil molar ratio and 4h, 93.4% Jatropha biodiesel yield was obtained at AV of 6.3 mg KOH/g with 4 cycles (biodiesel yield>86%). It was further found that it can resist free fatty acids, and biodiesel yield reached 92.9% from soybean oil with high AV of 12.1. HT-Ca catalyst showed a potential practical application for direct production of biodiesel from oils with high AV without pretreatment.

  5. Searching for Short Term Variable Active Galactic Nuclei: A Vital Step Towards Using AGN as Standard Candles

    NASA Astrophysics Data System (ADS)

    Kilts, Kelly; Gorjian, Varoujan; Rutherford, Thomas; Kohrs, Russell; Urbanowski, Vincent; Bellusci, Nina; Horton, Savannah; Jones, Dana; Jones, Kaytlyn; Pawelski, Peter; Tranum, Haley; Zhang, Emily

    2017-01-01

    Current models for accretion disk sizes of active galactic nuclei (AGN) do not match the limited observational data available, so there is an active need from the modeling community for many more accretion disk/dusty torus reverberation mapping campaigns with which to better calibrate models. Since short term variable AGN can be more easily monitored for reverberation mapping than long term variable AGN, they can begin to provide data more quickly. This project looked for short term variable AGN in the Young Stellar Object Variability (YSOVAR) survey conducted using the Spitzer Space Telescope. The YSOVAR survey targeted 12 nearby star forming regions for repeated observations. Potential AGN from the YSOVAR data were first selected by color ([3.6] - [4.5] > 0.4) and then by magnitude (m < 14) based on previous Spitzer surveys of known AGN. Since AGN share some similar color characteristics with young stars, images of each YSOVAR region were viewed to remove potential objects near concentrations of known young stellar objects since these were likely also YSOs. The spectral energy distribution (SED) for each remaining potential AGN was then examined for AGN like characteristics. Several potential short term variable AGN were found.

  6. Photo-activated ionic gelation of alginate hydrogel: real-time rheological monitoring of the two-step crosslinking mechanism.

    PubMed

    Higham, Alina K; Bonino, Christopher A; Raghavan, Srinivasa R; Khan, Saad A

    2014-07-21

    We examine the gelation of alginate undergoing ionic crosslinking upon ultraviolet (UV) irradiation using in situ dynamic rheology. Hydrogels are formed by combining alginate with calcium carbonate (CaCO3) particles and a photoacid generator (PAG). The PAG is photolyzed upon UV irradiation, resulting in the release of free calcium ions for ionic crosslinking. The viscous and elastic moduli during gelation are monitored as a function of the UV irradiation intensity, exposure time, alginate concentration, and the ratio between alginate and calcium carbonate. Gel time decreases as irradiation intensity increases because a larger concentration of PAG is photolyzed. Interestingly, dark curing, the continuing growth of microstructure in the absence of UV light, is observed. In some instances, the sample transitions from a solution to a gel during the dark curing phase. Additionally, when exposed to constant UV irradiation after the dark curing phase, samples reach the same plateau modulus as samples exposed to constant UV without dark curing, implying that dark curing does not affect the gelation mechanism. We believe the presence of dark curing is the result of the acidic environment persisting within the sample, allowing CaCO3 to dissociate, thereby releasing free Ca(2+) ions capable of binding with the available appropriate ionic blocks of the polymer chains. The growth of microstructure is then detected if the activation barrier has been crossed to release sufficient calcium ions. In this regard, we calculate a value of 30 J that represents the activation energy required to initiate gelation.

  7. Nanostructured titanium-silver coatings with good antibacterial activity and cytocompatibility fabricated by one-step magnetron sputtering

    NASA Astrophysics Data System (ADS)

    Bai, Long; Hang, Ruiqiang; Gao, Ang; Zhang, Xiangyu; Huang, Xiaobo; Wang, Yueyue; Tang, Bin; Zhao, Lingzhou; Chu, Paul K.

    2015-11-01

    Bacterial infection and loosing are serious complications for biomedical implants in the orthopedic, dental, and other biomedical fields and the ideal implants should combine good antibacterial ability and bioactivity. In this study, nanostructured titanium-silver (Ti-Ag) coatings with different Ag contents (1.2 to 21.6 at%) are prepared on Ti substrates by magnetron sputtering. As the Ag concentration is increased, the coatings change from having dense columnar crystals to sparse ones and eventually no columnar structure. The Ti-Ag coatings can effectively kill Staphylococcus aureus during the first few days and remain moderately antibacterial after immersion for 75 days. Compared to pure Ti, the Ti-Ag coatings show good cytocompatibility as indicated by good osteoblast adhesion, proliferation, intracellular total protein synthesis, and alkaline phosphatase (ALP) activity. In addition, cell spreading, collagen secretion, and extracellular matrix mineralization are promoted on the coatings with the proper Ag contents due to the nanostructured morphological features. Our results indicate that favorable antibacterial activity and osseointegration ability can be simultaneously achieved by regulating the Ag contents in Ti-Ag coatings.

  8. A novel green one-step synthesis of gold nanoparticles using crocin and their anti-cancer activities.

    PubMed

    Hoshyar, Reyhane; Khayati, Gholam Reza; Poorgholami, Maliheh; Kaykhaii, Massoud

    2016-06-01

    Functionalized nanoparticles are specifically designed to deliver drugs at tumor cells and can potentially enhance anticancer activity of drugs such as crocin. In the present study, we have applied antioxidant crocin as a reducing agent for one pot green synthesis of controlled size gold nanoparticles (AuNPs). Spherical, stable and uniform AuNPs were synthesized using crocin. These AuNPs are characterized by UV-Vis, TEM and XRD techniques. The prepared AuNPs showed surface plasm on resonance centered at 520nm with the average particle size of about 4-10nm. The anti-cancer effect of AuNPs was determined using MTT and LDH tests. The cellular data showed that these AuNPs significantly decreased cancerous cells' growth after 24 and 48hours in a time- and dose-dependent manner (P<0.05). The results suggest that such AuNPs can be synthesized simply and quickly with invaluable clinical as well as pharmaceutical activities which can help to treat human breast cancer.

  9. A novel green one-step synthesis of silver nanoparticles using chitosan: catalytic activity and antimicrobial studies

    NASA Astrophysics Data System (ADS)

    Venkatesham, Maragoni; Ayodhya, Dasari; Madhusudhan, Alle; Veera Babu, Nagati; Veerabhadram, Guttena

    2014-01-01

    Stable silver nanoparticles were synthesized using chitosan acting as both reducing and stabilizing agent without using any toxic chemicals. This reaction was carried out in an autoclave at a pressure of 15 psi and 120 °C temperature by varying the time. The influence of different parameters such as time, change of concentration of silver nitrate and concentration of chitosan on the formation of silver nanoparticles were studied. The synthesized silver nanoparticles were characterized by UV-visible spectroscopy, Fourier transform infrared, X-ray diffraction and transmission electron microscopy. The results of catalytic reduction of 4-nitrophenol by sodium borohydride in the presence of green synthesized silver nanoparticles were presented. The antimicrobial activity of silver nanoparticles was tested against Escherichia coli and Micrococcus luteus and was found to be possessing inhibiting property.

  10. Evolution of aluminide coating microstructure on nickel-base cast superalloy CM-247 in a single-step high-activity aluminizing process

    SciTech Connect

    Das, D.K.; Joshi, S.V.; Singh, V.

    1998-08-01

    This study deals with the aluminizing of a directionally cast Ni-base superalloy, namely CM-247, by a single-step process using a high-activity pack. It is observed that significant incorporation of Al into the substrate surface during aluminizing continues over a period of about 1 hour and is not restricted merely to the first few minutes, as reported in the literature. Based on the microstructural details of the coatings formed at various stages of aluminizing, it is concluded that the coating growth in the above process takes place primarily by inward Al diffusion initially, followed by an intermediate stage when the growth involves both inward Al and outward Ni diffusion. In the final stages, the outward diffusion of Ni dominates the coating formation process. The above mechanism of coating formation is different from the one that prevails in the conventional two-step high-activity coating process in that the reaction front for the formation of NiAl remains spatially stationary despite the outward diffusion of nickel during the intermediate stage. It is also shown in the present study that the content of the Al source in the pack affects the coating structure significantly. It is further demonstrated that the microstructure of the aluminide coatings depends not only on the amount of Al incorporated in the sample during aluminizing but also on the time over which the uptake of this Al takes place.

  11. A low-cost non-toxic post-growth activation step for CdTe solar cells

    NASA Astrophysics Data System (ADS)

    Major, J. D.; Treharne, R. E.; Phillips, L. J.; Durose, K.

    2014-07-01

    Cadmium telluride, CdTe, is now firmly established as the basis for the market-leading thin-film solar-cell technology. With laboratory efficiencies approaching 20 per cent, the research and development targets for CdTe are to reduce the cost of power generation further to less than half a US dollar per watt (ref. 2) and to minimize the environmental impact. A central part of the manufacturing process involves doping the polycrystalline thin-film CdTe with CdCl2. This acts to form the photovoltaic junction at the CdTe/CdS interface and to passivate the grain boundaries, making it essential in achieving high device efficiencies. However, although such doping has been almost ubiquitous since the development of this processing route over 25 years ago, CdCl2 has two severe disadvantages; it is both expensive (about 30 cents per gram) and a water-soluble source of toxic cadmium ions, presenting a risk to both operators and the environment during manufacture. Here we demonstrate that solar cells prepared using MgCl2, which is non-toxic and costs less than a cent per gram, have efficiencies (around 13%) identical to those of a CdCl2-processed control group. They have similar hole densities in the active layer (9 × 1014 cm-3) and comparable impurity profiles for Cl and O, these elements being important p-type dopants for CdTe thin films. Contrary to expectation, CdCl2-processed and MgCl2-processed solar cells contain similar concentrations of Mg; this is because of Mg out-diffusion from the soda-lime glass substrates and is not disadvantageous to device performance. However, treatment with other low-cost chlorides such as NaCl, KCl and MnCl2 leads to the introduction of electrically active impurities that do compromise device performance. Our results demonstrate that CdCl2 may simply be replaced directly with MgCl2 in the existing fabrication process, thus both minimizing the environmental risk and reducing the cost of CdTe solar-cell production.

  12. Kinetic study of an enzymic cycling system coupled to an enzymic step: determination of alkaline phosphatase activity.

    PubMed Central

    Valero, E; Varón, R; García-Carmona, F

    1995-01-01

    A kinetic study is made of a system consisting of a specific enzymic cycling assay coupled to an enzymic reaction. A kinetic analysis of this system is presented, and the accumulation of chromophore involved in the cycle is seen to be parabolic, i.e. the rate of the reaction increases continuously with constant acceleration. The system is illustrated by the measurement of alkaline phosphatase activity using beta-NADP+ as substrate. The enzymes alcohol dehydrogenase and diaphorase are used to cycle beta-NAD+ in the presence of ethanol and p-Iodonitrotetrazolium Violet. During each turn of the cycle, one molecule of the tetrazolium salt is reduced to an intensely coloured formazan. A simple procedure for evaluating the kinetic parameters involved in the system and for optimizing this cycling assay is described. The method is applicable to the measurement of any enzyme, and its amplification capacity as well as the simplicity of determining kinetic parameters enable it to be employed in enzyme immunoassays to increase the magnitude of the measured response. PMID:7619054

  13. Digital elevation models in 10 minute time steps - a status report on 4D monitoring of an active erosional scar

    NASA Astrophysics Data System (ADS)

    Kaiser, Andreas; Neugirg, Fabian; Hass, Erik; Jose, Steffen; Haas, Florian; Schmidt, Jürgen

    2016-04-01

    In erosional research a variety of processes are well understood and have been mimicked under laboratory conditions. In complex natural systems such as Alpine environments a multitude of influencing factors tend to superimpose single processes in a mixed signal which impedes a reliable interpretation. These mixed signals can already be captured by geoscientific research approaches such as sediment collectors, erosion pins or remote sensing surveys. Nevertheless, they fail to distinguish between single processes and their individual impact on slope morphology. Throughout the last two years a highly active slope of unsorted glacial deposits in the northern Alps has been monitored by repeated terrestrial laser scans roughly every three months. Resulting high resolution digital elevation models of difference were produced to identify possible seasonal patterns. By reproducing the TLS results with a physically based erosion model (EROSION 3D) ran with in situ input data from rainfall simulations and a climate station a better understanding of individual mechanism could be achieved. However, the already elaborate combination of soil science and close range remote sensing could not answer all questions concerning the slopes behaviour, especially not for freeze and thaw cycles and the winter period. Therefore, an array of three fully automatic synchronised cameras was setup to generate continuous 3D surface models. Among the main challenges faced for the system were the energy supply and durability, perspectives of the cameras to avoid shadowing and to guarantee sufficient overlap, a certain robustness to withstand rough alpine weather conditions, the scaling of each 3D model by tracked ground control points and the automatic data handling. First results show individual processes sculpting the slope's morphology but further work is required to improve automatic point cloud creation and change monitoring.

  14. Structure of the β-Galactosidase Gene from Thermus sp. Strain T2: Expression in Escherichia coli and Purification in a Single Step of an Active Fusion Protein

    PubMed Central

    Vian, Alejandro; Carrascosa, Alfonso V.; García, José L.; Cortés, Estrella

    1998-01-01

    The nucleotide sequence of both the bgaA gene, coding for a thermostable β-galactosidase of Thermus sp. strain T2, and its flanking regions was determined. The deduced amino acid sequence of the enzyme predicts a polypeptide of 645 amino acids (Mr, 73,595). Comparative analysis of the open reading frames located in the flanking regions of the bgaA gene revealed that they might encode proteins involved in the transport and hydrolysis of sugars. The observed homology between the deduced amino acid sequences of BgaA and the β-galactosidase of Bacillus stearothermophilus allows us to classify the new enzyme within family 42 of glycosyl hydrolases. BgaA was overexpressed in its active form in Escherichia coli, but more interestingly, an active chimeric β-galactosidase was constructed by fusing the BgaA protein to the choline-binding domain of the major pneumococcal autolysin. This chimera illustrates a novel approach for producing an active and thermostable hybrid enzyme that can be purified in a single step by affinity chromatography on DEAE-cellulose, retaining the catalytic properties of the native enzyme. The chimeric enzyme showed a specific activity of 191,000 U/mg at 70°C and a Km value of 1.6 mM with o-nitrophenyl-β-d-galactopyranoside as a substrate, and it retained 50% of its initial activity after 1 h of incubation at 70°C. PMID:9603833

  15. Molten Metal Explosions are Still Occurring

    DTIC Science & Technology

    2009-02-01

    recycling plant. Another recent 665 Light Metals 2009 Edited by: Geoff Bearne TMS (The Minerals, Metals & Materials Society), 2009 catastrophic...occurred recently in a recycling plant casting small ingots over a water tank. An explosion occurred that extensively damaged the machine and...have been held in Europe as a joint activity with the European Aluminium Association (EAA) and the International Aluminium Institute (IAI). These

  16. Participant adherence indicators predict changes in blood pressure, anthropometric measures, and self-reported physical activity in a lifestyle intervention: HUB city steps.

    PubMed

    Thomson, Jessica L; Landry, Alicia S; Zoellner, Jamie M; Connell, Carol; Madson, Michael B; Molaison, Elaine Fontenot; Yadrick, Kathy

    2015-02-01

    The objective of this secondary analysis was to evaluate the utility of several participant adherence indicators for predicting changes in clinical, anthropometric, dietary, fitness, and physical activity (PA) outcomes in a lifestyle intervention, HUB City Steps, conducted in a southern, African American cohort in 2010. HUB City Steps was a 6-month, community-engaged, multicomponent, noncontrolled intervention targeting hypertension risk factors. Descriptive indicators were constructed using two participant adherence measures, education session attendance (ESA) and weekly steps/day pedometer diary submission (PDS), separately and in combination. Analyses, based on data from 269 primarily African American adult participants, included bivariate tests of association and multivariable linear regression to determine significant relationships between seven adherence indicators and health outcome changes, including clinical, anthropometric, dietary, fitness, and PA measures. ESA indicators were significantly correlated with four health outcomes: body mass index (BMI), fat mass, low-density lipoprotein (LDL), and PA (-.29 ≤ r ≤ .23, p < .05). PDS indicators were significantly correlated with PA (r = .27, p < .001). Combination ESA/PDS indicators were significantly correlated with five health outcomes: BMI, percentage body fat (%BF), fat mass, LDL, and PA (r = -.26 to .29, p < .05). Results from the multivariate models indicated that the combination ESA/PDS indicators were the most significant predictors of changes for five outcomes--%BF, fat mass, LDL diastolic blood pressure (DBP), and PA--while ESA performed best for BMI only. For DBP, a one-unit increase in the continuous-categorical ESA/PDS indicator resulted in 0.3 mm Hg decrease. Implications for assessing participant adherence in community-based, multicomponent lifestyle intervention research are discussed.

  17. 4-Ketopinoresinol, a novel naturally occurring ARE activator, induces the Nrf2/HO-1 axis and protects against oxidative stress-induced cell injury via activation of PI3K/AKT signaling.

    PubMed

    Chen, Huang-Hui; Chen, Yu-Tsen; Huang, Yen-Wen; Tsai, Hui-Ju; Kuo, Ching-Chuan

    2012-03-15

    The Nrf2/ARE pathway plays an important role in inducing phase II detoxifying enzymes and antioxidant proteins and has been considered a potential target for cancer chemoprevention because it eliminates harmful reactive oxygen species or reactive intermediates generated from carcinogens. The objectives of this study were to identify novel Nrf2/ARE activators and to investigate the mechanistic signaling pathway involved in the activation of Nrf2-mediated cytoprotective effects against oxidative-induced cell injury. A stable ARE-driven luciferase reporter cell line was established to screen a potentially cytoprotective compound. 4-Ketopinoresinol (4-KPR), the (α-γ) double-cyclized type of lignan obtained from adlay (Coix lachryma-jobi L. var. ma-yuen Stapf), activates ARE-driven luciferase activity more effectively than the classical ARE activator tert-butylhydroquinone. 4-KPR treatment resulted in a transient increase in AKT phosphorylation and subsequent phosphorylation and nuclear translocation of Nrf2, along with increased expression of ARE-dependent cytoprotective genes, such as heme oxygenase-1 (HO-1), aldo-keto reductases, and glutathione synthetic enzyme. 4-KPR suppresses oxidative stress-induced DNA damage and cell death via upregulation of HO-1. Inhibition of PI3K/AKT signaling by chemical inhibitors or RNA interference not only suppressed 4-KPR-induced Nrf2/HO-1 activation, but also eliminated the cytoprotective effect against oxidative damage. These observations in an ARE-regulated gene system suggest that 4-KPR is a novel Nrf2/ARE-mediated transcription activator, activates the Nrf2/HO-1 axis, and protects against oxidative stress-induced cell injury via activation of PI3K/AKT signaling.

  18. Equine platelets inhibit E. coli growth and can be activated by bacterial lipopolysaccharide and lipoteichoic acid although superoxide anion production does not occur and platelet activation is not associated with enhanced production by neutrophils.

    PubMed

    Aktan, I; Dunkel, B; Cunningham, F M

    2013-04-15

    Activated platelets can contribute to host defense through release of products with bactericidal actions such as antimicrobial peptides and reactive oxygen species (ROS), as well as by forming heterotypic aggregates with neutrophils and enhancing their antimicrobial properties. Whilst release of vasoactive mediators from equine platelets in response to stimuli including bacterial lipopolysaccharide (LPS) has been documented, neither ROS production, nor the effects of activated platelets on equine neutrophil ROS production, have been reported. This study first sought evidence that activated equine platelets inhibit bacterial growth. Platelet superoxide production in response to stimuli including Escherichia coli-derived LPS and lipoteichoic acid (LTA) from Staphylococcus aureus was then determined. The ability of LPS and LTA to up-regulate platelet P-selectin expression and induce platelet-neutrophil aggregate formation was investigated and the effect of co-incubating activated platelets with neutrophils on superoxide production measured. Growth of E. coli was inhibited in a time-dependent manner, and to a similar extent, by addition of platelet rich plasma (PRP) or platelet poor plasma (PPP) obtained by centrifugation of PRP. Activation of platelets in PRP by addition of thrombin led to a significant increase in the inhibitory action between 0.5 and 2h. Although phorbol myristate acetate (PMA) caused superoxide production by equine platelets in a protein kinase C-dependent manner, thrombin, platelet activating factor (PAF), LPS, LTA and formyl-methionyl-leucyl phenylalanine (FMLP) were without effect. LPS and LTA did induce platelet activation, measured as an increase in P-selectin expression (% positive cells: 17±3 (un-stimulated); 63±6 (1μg/ml LPS); 64±6 (1μg/ml LTA); n=5) but not platelet superoxide production or heterotypic aggregate formation. Co-incubation of activated platelets with neutrophils did not increase neutrophil superoxide production. This

  19. Task-Oriented Exercise to Reduce Activities of Daily Living Disability in Vulnerable Older Adults: A Feasibility Study of the 3-Step Workout for Life.

    PubMed

    Liu, Chiung-Ju; Jones, Leah Y; Formyduval A, R M; Clark, Daniel O

    2016-07-01

    The purpose of this feasibility study was to evaluate the 3-Step Workout for Life program, a 10-week exercise program that included moderate-intensity muscle strength training followed by task-oriented training. Fourteen participants completed the program (mean age = 73 years; SD = 6.83). The Box and Block test (Z = -2.24, p = .03) and the 30-s chair stand test (Z = -2.21, p = .03) indicate improved physical functioning of the upper and lower extremities. More importantly, results of the function component from the Late-Life Function and Disability Instrument (Z = -2.04, p = .04) and motor skills scale from the Assessment of Motor and Process Skills (Z = -2.97, p = .003) indicate subjective and objective improvements on performing activities of daily living. Supplementing moderate-intensity muscle strength exercise with task-oriented training components is feasible. Preliminary data support the effectiveness of 3-Step Workout for Life in reducing late-life disability.

  20. Effect of balance exercise in combination with whole-body vibration on muscle activity of the stepping limb during a forward fall in older women: a randomized controlled pilot study.

    PubMed

    Ochi, Akira; Abe, Tomokazu; Yamada, Kazumasa; Ibuki, Satoko; Tateuchi, Hiroshige; Ichihashi, Noriaki

    2015-01-01

    This study investigated the effects of balance exercise combined with whole-body vibration (WBV) on step performance and lower limb muscle activity during simulated forward falls using the tether-release method in older women. Twenty older women were assigned to either a WBV plus balance exercise group (WBV, n=10) or a balance exercise without vibration group (standard balance exercise group [STE], n=10). WBV performed weight-bearing exercises on a WBV platform combined with other balance exercises as a home program, whereas STE performed the same exercises without WBV. The exercise volume was equal in both intervention groups (3×/week for 12 weeks×30 min/session). The EMG and kinematic data of the stepping leg from the balance recovery step were examined before and after the intervention. While both groups extended step length during forward falls after the intervention, only WBV increased step velocity. EMG analysis of the balance recovery step showed that both groups increased peak EMG of knee flexor and extensor muscles after intervention. After intervention, WBV increased peak EMG of the plantar flexors, which are used to exert the push-off forces just before the leg swing. Balance exercise in older women resulted in significant improvements in the balance recovery step after a simulated forward fall. WBV also had the additional benefit of improved step velocity, which was reflected in increased activity of the plantar flexors in the stepping leg.

  1. Modification of a thiol at the active site of the Ascaris suum NAD-malic enzyme results in changes in the rate-determining steps for oxidative decarboxylation of L-malate

    SciTech Connect

    Gavva, S.R.; Harris, B.G.; Cook, P.F. ); Weiss, P.M. )

    1991-06-11

    A thiol group at the malate-binding site of the NAD-malic enzyme from Ascaris suum has been modified to thiocyanate. The modified enzyme generally exhibits slight increases in K{sub NAD} and K{sub i metal} and decreases in V{sub max} as the metal size increases from Mg{sup 2+} to Mn{sup 2+} to Cd{sup 2+}, indicative of crowding in the site. The K{sub malate} value increases 10- to 30-fold, suggesting that malate does not bind optimally to the modified enzyme. Deuterium isotope effects on V and V/K{sub malate} increase with all three metal ions compared to the native enzyme concomitant with a decrease in the {sup 13}C isotope effect, suggesting a switch in the rate limitation of the hydride transfer and decarboxylation steps with hydride transfer becoming more rate limiting. The {sup 13}C effect decreases only slightly when obtained with deuterated malate, suggestive of the presence of a secondary {sup 13}C effect in the hydride transfer step, similar to data obtained with non-nicotinamide-containing dinucleotide substrates for the native enzyme (see the preceding paper in this issue). The native enzyme is inactivated in a time-dependent manner by Cd{sup 2+}. This inactivation occurs whether the enzyme alone is present or whether the enzyme is turning over with Cd{sup 2+} as the divalent metal activator. Upon inactivation, only Cd{sup 2+} ions are bound at high stoichiometry to the enzyme, which eventually becomes denatured. Conversion of the active-site thiol to thiocyanate makes it more difficult to inactivate the enzyme by treatment with Cd{sup 2+}.

  2. One-step combined focused epPCR and saturation mutagenesis for thermostability evolution of a new cold-active xylanase.

    PubMed

    Acevedo, Juan Pablo; Reetz, Manfred T; Asenjo, Juan A; Parra, Loreto P

    2017-05-01

    Enzymes active at low temperature are of great interest for industrial bioprocesses due to their high efficiency at a low energy cost. One of the particularities of naturally evolved cold-active enzymes is their increased enzymatic activity at low temperature, however the low thermostability presented in this type of enzymes is still a major drawback for their application in biocatalysis. Directed evolution of cold-adapted enzymes to a more thermostable version, appears as an attractive strategy to fulfill the stability and activity requirements for the industry. This paper describes the recombinant expression and characterization of a new and highly active cold-adapted xylanase from the GH-family 10 (Xyl-L), and the use of a novel one step combined directed evolution technique that comprises saturation mutagenesis and focused epPCR as a feasible semi-rational strategy to improve the thermostability. The Xyl-L enzyme was cloned from a marine-Antarctic bacterium, Psychrobacter sp. strain 2-17, recombinantly expressed in E. coli strain BL21(DE3) and characterized enzymatically. Molecular dynamic simulations using a homology model of the catalytic domain of Xyl-L were performed to detect flexible regions and residues, which are considered to be the possible structural elements that define the thermolability of this enzyme. Mutagenic libraries were designed in order to stabilize the protein introducing mutations in some of the flexible regions and residues identified. Twelve positive mutant clones were found to improve the T50(15) value of the enzyme, in some cases without affecting the activity at 25°C. The best mutant showed a 4.3°C increase in its T50(15). The efficiency of the directed evolution approach can also be expected to work in the protein engineering of stereoselectivity.

  3. Regioselective introduction of heteroatoms at the C-8 position of quinoline N-oxides: remote C-H activation using N-oxide as a stepping stone.

    PubMed

    Hwang, Heejun; Kim, Jinwoo; Jeong, Jisu; Chang, Sukbok

    2014-07-30

    Reported herein is the metal-catalyzed regioselective C-H functionalization of quinoline N-oxides at the 8-position: direct iodination and amidation were developed using rhodium and iridium catalytic systems, respectively. Mechanistic study of the amidation revealed that the unique regioselectivity is achieved through the smooth formation of N-oxide-chelated iridacycle and that an acid additive plays a key role in the rate-determining protodemetalation step. While this approach of remote C-H activation using N-oxide as a directing group could readily be applied to a wide range of heterocyclic substrates under mild conditions with high functional group tolerance, an efficient synthesis of zinquin ester (a fluorescent zinc indicator) was demonstrated.

  4. Synthesis of Bi2WO6/Bi2O3 composite with enhanced photocatalytic activity by a facile one-step hydrothermal synthesis route.

    PubMed

    Wang, Tianye; Zhang, Fengjun; Xiao, Guosheng; Zhong, Shuang; Lu, Cong

    2015-01-01

    In this study, the characterization and photocatalytic activity of Bi2WO6/Bi2O3 under visible-light irradiation was investigated in detail. The results suggested that Bi2WO6/Bi2O3 can be synthesized by a facile one-pot hydrothermal route using a super big 200 mL Teflon-lined autoclave with optimal sodium oleate/Bi molar ratio of 1.25. Through the characterization of Bi2WO6/Bi2O3 by X-ray diffraction, scanning electron microscopy, X-ray photoelectron spectroscopy, Fourier transform infrared, UV-vis diffuse reflectance spectra and Photoluminescence spectra, it was found that the as-prepared composite possessed smaller crystallite size and higher visible-light responsive than the pure Bi2WO6. Moreover, it was expected that the as-prepared composites exhibited enhanced photocatalytic activity for the degradation of Rhodamine B under visible-light irradiation, which could be ascribed to their improved light absorption property and the reduced recombination of the photogenerated electrons and holes during the photocatalytic reaction. In general, this study could provide a principle method to synthesize Bi2WO6/Bi2O3 with enhanced photocatalytic activity by one-step hydrothermal synthesis route for environmental purification.

  5. One-step pyrolytic synthesis of nitrogen and sulfur dual-doped porous carbon with high catalytic activity and good accessibility to small biomolecules.

    PubMed

    Gao, Weiwei; Feng, Xun; Zhang, Tianyi; Huang, Hao; Li, Jin; Song, Wenbo

    2014-01-01

    As one of promising catalysts that contain high density of active sites, N doped carbons have been extensively researched, while the reports for N, S dual-doped carbon materials are far less exhaustive. Herein, devoid of activation process and template, N, S dual-doped porous carbon (N-S-PC) was prepared for the first time via one-step pyrolysis of sodium citrate and cysteine. Possessing unique porous structure and large pore volume as well as good accessibility, N-S-PC demonstrates significantly improved electrocatalytic activity toward oxidation of ascorbic acid (AA), dopamine (DA), and uric acid (UA). In the coexisting system, the peak potential separation between AA and DA is up to 251 mV, which is much larger than for most of the other carbons. On the basis of large potential separation and high current response, selective and sensitive simultaneous determination of AA, DA, and UA was successfully accomplished by differential pulse voltammetry, displaying a linear response from 50 to 2000 μM, from 0.1 to 50 μM, and from 0.1 to 50 μM with a detection limit (S/N = 3) of 0.78, 0.02, and 0.06 μM. This work highlights the importance of N, S dual doping and hierarchical porous carbons for efficient catalysis.

  6. Luminosity progression in dart-stepped leader step formation

    NASA Astrophysics Data System (ADS)

    Wang, D.; Takagi, N.; Uman, M. A.; Jordan, D. M.

    2016-12-01

    Using a high-speed optical imaging system, we have observed the step formation bright pulse discharges occurring at the tip of dart-stepped leaders of rocket triggered lightning with a time resolution of 0.1 µs and a spatial resolution of about 1.4 m. Each of the step formation pulse discharges appeared to initiate at a location immediately below the bottom of its previous pulse discharge and to propagate in bidirectional (upward and downward) waves with a speed on the order of 107 m/s. The downward waves of the pulse discharges tended to slow down significantly after they propagated a distance of about 2 m. Based on the results observed in this study and those published in literatures, we propose a conceptual view of leader step formation.

  7. Sage Simulation Model for Technology Demonstration Convertor by a Step-by-Step Approach

    NASA Technical Reports Server (NTRS)

    Demko, Rikako; Penswick, L. Barry

    2006-01-01

    The development of a Stirling model using the 1-D Saga design code was completed using a step-by-step approach. This is a method of gradually increasing the complexity of the Saga model while observing the energy balance and energy losses at each step of the development. This step-by-step model development and energy-flow analysis can clarify where the losses occur, their impact, and suggest possible opportunities for design improvement.

  8. Naturally Occurring Radioactive Materials (NORM)

    SciTech Connect

    Gray, P.

    1997-02-01

    This paper discusses the broad problems presented by Naturally Occuring Radioactive Materials (NORM). Technologically Enhanced naturally occuring radioactive material includes any radionuclides whose physical, chemical, radiological properties or radionuclide concentration have been altered from their natural state. With regard to NORM in particular, radioactive contamination is radioactive material in an undesired location. This is a concern in a range of industries: petroleum; uranium mining; phosphorus and phosphates; fertilizers; fossil fuels; forestry products; water treatment; metal mining and processing; geothermal energy. The author discusses in more detail the problem in the petroleum industry, including the isotopes of concern, the hazards they present, the contamination which they cause, ways to dispose of contaminated materials, and regulatory issues. He points out there are three key programs to reduce legal exposure and problems due to these contaminants: waste minimization; NORM assesment (surveys); NORM compliance (training).

  9. Participant report of therapist-delivered active ingredients in a telephone-delivered brief motivational intervention predicts taking steps towards change

    PubMed Central

    Lee, Christina S.; Longabaugh, Richard; Baird, Janette; Streszak, Val; Nirenberg, Ted; Mello, Michael

    2015-01-01

    Objective Given the widespread potential for disseminating Motivational Interviewing (MI) through technology, the question of whether MI active ingredients are present when not delivered in person is critical to assure high treatment quality. The Participant Rating Form (PRF) was developed and used to evaluate therapist-delivered active ingredients in phone-delivered MI with hazardous drinking Emergency Department patients. Method A factor analysis of all PRFs completed after receiving one call (n=256) was conducted. Multiple regression analysis was used to examine whether PRF factors predicted a measure of motivation to change -- taking steps—at the second call (n=214). Results The majority of participants were male (65%), with a mean age of 32 years and with an average alcohol ASSIST (Alcohol, Smoking, and Substance Involvement Screening Test) score of 20.5 (SD = 7.1). Results of the factor analysis for the PRF revealed Relational (working collaboration) and Technical (MI behaviors) factors. After controlling for demographics, alcohol severity, and baseline readiness, the technical factor predicted self-report of increased taking steps towards change while the relational factor did not explain any additional variance. Conclusions Our study adds to the growing literature investigating patient perspectives of therapist skill as a source of information to better understand MI active ingredients. The PRF is a feasible instrument for measuring the patient’s experience of phone-based MI. Results indicate that MI active ingredients of change (relational and technical components) were present in the telephone intervention as hypothesized. Clinical Trial Registration # 01326169. PMID:26441490

  10. Stair-stepped Mound

    NASA Technical Reports Server (NTRS)

    2003-01-01

    MGS MOC Release No. MOC2-429, 22 July 2003

    This April 2003 Mars Global Surveyor (MGS) Mars Orbiter Camera (MOC) image shows a stair-stepped mound of sedimentary rock (right of center) on the floor of a large impact crater in western Arabia Terra near 11.0oN, 4.4oW. Sedimentary rock outcrops are common in the craters of this region. The repeated thickness and uniformity of the layers that make up this mound suggest that their depositional environment was one in which cyclic or episodic events occurred over some period of time. The sediments might have been deposited in a lake, or they may have settled directly out of the atmosphere. Most of the layered material was later eroded away, leaving this circular mound and the other nearby mesas and knobs. The image is illuminated by sunlight from the lower left.

  11. A one-step thermal decomposition method to prepare anatase TiO2 nanosheets with improved adsorption capacities and enhanced photocatalytic activities

    NASA Astrophysics Data System (ADS)

    Li, Wenting; Shang, Chunli; Li, Xue

    2015-12-01

    Anatase TiO2 nanosheets (NSs) with high surface area have been prepared via a one-step thermal decomposition of titanium tetraisopropoxide (TTIP) in oleylamine (OM), and their adsorption capacities and photocatalytic activities are investigated by using methylene blue (MB) and methyl orange (MO) as model pollutants. During the synthesis procedure, only one type of surfactant, oleylamine (OM), is used as capping agents and no other solvents are added. Structure and properties of the TiO2 NSs were characterized by X-ray diffraction (XRD), transmission electron microscopy (TEM), N2 adsorption analysis, UV-vis spectrum, X-ray photoelectron spectroscopy (XPS) and Photoluminescence (PL) methods. The results indicate that the TiO2 NSs possess high surface area up to 378 m2 g-1. The concentration of capping agents is found to be a key factor controlling the morphology and crystalline structure of the product. Adsorption and photodegradation experiments reveal that the prepared TiO2 NSs possess high adsorption capacities of model pollutants MB and high photocatalytic activity, showing that TiO2 NSs can be used as efficient pollutant adsorbents and photocatalytic degradation catalysts of MB in wastewater treatment.

  12. One-step fabrication of large-area ultrathin MoS2 nanofilms with high catalytic activity for photovoltaic devices.

    PubMed

    Liang, Jia; Li, Jia; Zhu, Hongfei; Han, Yuxiang; Wang, Yanrong; Wang, Caixing; Jin, Zhong; Zhang, Gengmin; Liu, Jie

    2016-09-21

    Here we report a facile one-step solution-phase process to directly grow ultrathin MoS2 nanofilms on a transparent conductive glass as a novel high-performance counter electrode for dye-sensitized solar cells. After an appropriate reaction time, the entire surface of the conductive glass substrate was uniformly covered by ultrathin MoS2 nanofilms with a thickness of only several stacked layers. Electrochemical impedance spectroscopy and cyclic voltammetry reveal that the MoS2 nanofilms possess excellent catalytic activity towards tri-iodide reduction. When used in dye-sensitized solar cells, the MoS2 nanofilms show an impressive energy conversion efficiency of 8.3%, which is higher than that of a Pt-based electrode and very promising to be a desirable alternative counter electrode. Considering their ultrathin thickness, superior catalytic activity, simple preparation process and low cost, the as-prepared MoS2 nanofilms with high photovoltaic performance are expected to be widely employed in dye-sensitized solar cells.

  13. A Naturally Occurring Mutation K220T in the Pleiotropic Activator PrfA of Listeria Monocytogenes Results in a Loss of Virulence Due to Decreasing DNA-Binding Affinity

    SciTech Connect

    Velge,P.; Herler, M.; Johansson, J.; Roches, S.; Temoin, S.; Fedorov, A.; Gracieux, P.; Almo, S.; Goebel, W.; Cossart, P.

    2007-01-01

    The sequencing of prfA, encoding the transcriptional regulator of virulence genes, in 26 low-virulence field Listeria monocytogenes strains showed that eight strains exhibited the same single amino-acid substitution: PrfAK220T. These strains exhibited no expression of PrfA-regulated proteins and thus no virulence. This substitution inactivated PrfA, since expression of the PrfAK220T mutant gene in an EGD{Delta}prfA strain did not restore the haemolytic and phosphatidylcholine phospholipase C activities, in contrast to the wild-type prfA gene. The substitution of the lysine at position 220 occurred in the helix H. However, the data showed that the PrfAK220T protein is dimerized just as well as its wild-type counterpart, but does not bind to PrfA-boxes. PrfAK220T did not form a PrfA-DNA complex in electrophoretic mobility shift assays, but low concentrations of CI complexes (PrfAK220T-RNA polymerase-DNA complex) were formed by adding RNA polymerase, suggesting that PrfA interacted with RNA polymerase in solution in the absence of DNA. Formation of some transcriptionally active complexes was confirmed by in vitro runoff transcription assays and quantitative RT-PCR. Crystallographic analyses described the structure of native PrfA and highlighted the key role of allosteric changes in the activity of PrfA and especially the role of the Lys220 in the conformation of the helix-turn-helix (HTH) motif.

  14. Classical and Alternative Activation and Metalloproteinase Expression Occurs in Foam Cell Macrophages in Male and Female ApoE Null Mice in the Absence of T and B Lymphocytes

    PubMed Central

    Hayes, Elaine Mo; Tsaousi, Aikaterini; Di Gregoli, Karina; Jenkinson, S. Rhiannon; Bond, Andrew R.; Johnson, Jason L.; Bevan, Laura; Thomas, Anita C.; Newby, Andrew C.

    2014-01-01

    Background: Rupture of advanced atherosclerotic plaques accounts for most life-threatening myocardial infarctions. Classical (M1) and alternative (M2) macrophage activation could promote atherosclerotic plaque progression and rupture by increasing production of proteases, including matrix metalloproteinases (MMPs). Lymphocyte-derived cytokines may be essential for generating M1 and M2 phenotypes in plaques, although this has not been rigorously tested until now. Methods and results: We validated the expression of M1 markers (iNOS and COX-2) and M2 markers (arginase-1, Ym-1, and CD206) and then measured MMP mRNA levels in mouse macrophages during classical and alternative activation in vitro. We then compared mRNA expression of these genes ex vivo in foam cells from subcutaneous granulomas in fat-fed immune-competent ApoE knockout (KO) and immune-compromised ApoE/Rag-1 double-KO mice, which lack all T and B cells. Furthermore, we performed immunohistochemistry in subcutaneous granulomas and in aortic root and brachiocephalic artery atherosclerotic plaques to measure the extent of M1/M2 marker and MMP protein expression in vivo. Classical activation of mouse macrophages with bacterial lipopolysaccharide in vitro increased MMPs-13, -14, and -25 but decreased MMP-19 and TIMP-2 mRNA expressions. Alternative activation with IL-4 increased MMP-19 expression. Foam cells in subcutaneous granulomas expressed all M1/M2 markers and MMPs at ex vivo mRNA and in vivo protein levels, irrespective of Rag-1 genotype. There were also similar percentages of foam cell macrophages (FCMs) carrying M1/M2 markers and MMPs in atherosclerotic plaques from ApoE KO and ApoE/Rag-1 double-KO mice. Conclusion: Classical and alternative activation leads to distinct MMP expression patterns in mouse macrophages in vitro. M1 and M2 polarization in vivo occurs in the absence of T and B lymphocytes in either granuloma or plaque FCMs. PMID:25389425

  15. The Naturally Occurring Host Defense Peptide, LL-37, and Its Truncated Mimetics KE-18 and KR-12 Have Selected Biocidal and Antibiofilm Activities Against Candida albicans, Staphylococcus aureus, and Escherichia coli In vitro

    PubMed Central

    Luo, Yu; McLean, Denise T. F.; Linden, Gerard J.; McAuley, Danny F.; McMullan, Ronan; Lundy, Fionnuala T.

    2017-01-01

    Amongst the recognized classes of naturally occurring antimicrobials, human host defense peptides are an important group with an advantage (given their source) that they should be readily translatable to medicinal products. It is also plausible that truncated versions will display some of the biological activities of the parent peptide, with the benefit that they are less costly to synthesize using solid-phase chemistry. The host defense peptide, LL-37, and two truncated mimetics, KE-18 and KR-12, were tested for their inhibitory effects and antibiofilm properties against Candida albicans, Staphylococcus aureus, and Escherichia coli, microorganisms commonly implicated in biofilm-related infections such as ventilator-associated pneumonia (VAP). Using in silico prediction tools, the truncated peptides KE-18 and KR-12 were selected for minimum inhibitory concentration (MIC) and antibiofilm testing on the basis of their favorable cationicity, hydrophobic ratio, and amphipathicity compared with the parent peptide. Two methods were analyzed for determining peptide efficacy against biofilms; a crystal violet assay and an XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] assay. The biocidal activities (measured by MIC) and antibiofilm activities (measured by a crystal violet assay) appeared to be independent. LL-37 had no biocidal action against C. albicans (MIC > 250 μg/ml) but significant effects in both biofilm-prevention and biofilm-inhibition assays. KE-18 and KR-12 yielded superior MIC values against all three microorganisms. Only KE-18 had a significant effect in the biofilm-prevention assay, which persisted even at sub-MICs. Neither of the truncated peptides were active in the biofilm-inhibition assay. KE-18 was shown to bind lipopolysaccharide as effectively as LL-37 and to bind lipoteichoic acid more effectively. None of the peptides showed hemolytic activity against human erythrocytes at the concentrations tested. KE-18 should be

  16. Step-Growth Polymerization.

    ERIC Educational Resources Information Center

    Stille, J. K.

    1981-01-01

    Following a comparison of chain-growth and step-growth polymerization, focuses on the latter process by describing requirements for high molecular weight, step-growth polymerization kinetics, synthesis and molecular weight distribution of some linear step-growth polymers, and three-dimensional network step-growth polymers. (JN)

  17. Single-step solvothermal synthesis of mesoporous Ag-TiO2-reduced graphene oxide ternary composites with enhanced photocatalytic activity.

    PubMed

    Sher Shah, Md Selim Arif; Zhang, Kan; Park, A Reum; Kim, Kwang Su; Park, Nam-Gyu; Park, Jong Hyeok; Yoo, Pil J

    2013-06-07

    With growing interest in the photocatalytic performance of TiO2-graphene composite systems, the ternary phase of TiO2, graphene, and Ag is expected to exhibit improved photocatalytic characteristics because of the improved recombination rate of photogenerated charge carriers and potential contribution of the generation of localized surface plasmon resonance at Ag sites on a surface of the TiO2-graphene binary matrix. In this work, Ag-TiO2-reduced graphene oxide ternary nanocomposites were successfully synthesized by a simple solvothermal process. In a single-step synthetic procedure, the reduction of AgNO3 and graphene oxide and the hydrolysis of titanium tetraisopropoxide were spontaneously performed in a mixed solvent system of ethylene glycol, N,N-dimethylformamide and a stoichiometric amount of water without resorting to the use of typical reducing agents. The nanocomposites were characterized by X-ray diffraction, X-ray photoelectron spectroscopy, along with different microscopic and spectroscopic techniques, enabling us to confirm the successful reduction of AgNO3 and graphite oxide to metallic Ag and reduced graphene oxide, respectively. Due to the highly facilitated electron transport of well distributed Ag nanoparticles, the synthesized ternary nanocomposite showed enhanced photocatalytic activity for degradation of rhodamine B dye under visible light irradiation.

  18. A New Two-Step Approach for Hands-On Teaching of Gene Technology: Effects on Students' Activities during Experimentation in an Outreach Gene Technology Lab

    ERIC Educational Resources Information Center

    Scharfenberg, Franz-Josef; Bogner, Franz X.

    2011-01-01

    Emphasis on improving higher level biology education continues. A new two-step approach to the experimental phases within an outreach gene technology lab, derived from cognitive load theory, is presented. We compared our approach using a quasi-experimental design with the conventional one-step mode. The difference consisted of additional focused…

  19. Efficient heterologous expression and one-step purification of fully active c-terminal histidine-tagged uridine monophosphate kinase from Mycobacterium tuberculosis.

    PubMed

    Penpassakarn, Praweenuch; Chaiyen, Pimchai; Palittapongarnpim, Prasit

    2011-11-01

    Tuberculosis has long been recognized as one of the most significant public health problems. Finding novel antituberculous drugs is always a necessary approach for controlling the disease. Mycobacterium tuberculosis pyrH gene (Rv2883c) encodes for uridine monophosphate kinase (UMK), which is a key enzyme in the uridine nucleotide interconversion pathway. The enzyme is essential for M. tuberculosis to sustain growth and hence is a potential drug target. In this study, we have developed a rapid protocol for production and purification of M. tuberculosis UMK by cloning pyrH (Rv2883c) of M. tuberculosis H37Rv with the addition of 6-histidine residues to the C-terminus of the protein, and expressing in E. coli BL21-CodonPlus (DE3)-RIPL using an auto-induction medium. The enzyme was efficiently purified by a single-step TALON cobalt affinity chromatography with about 8 fold increase in specific activity, which was determined by a coupled assay with the pyruvate kinase and lactate dehydrogenase. The molecular mass of monomeric UMK was 28.2 kDa and that of the native enzyme was 217 kDa. The enzyme uses UMP as a substrate but not CMP and TMP and activity was enhanced by GTP. Measurements of enzyme kinetics revealed the kcat value of 7.6 +/- 0.4 U mg(-1) or 0.127 +/- 0.006 sec(-1).The protocol reported here can be used for expression of M. tuberculosis UMK in large quantity for formulating a high throughput target-based assay for screening anti-tuberculosis UMK compounds.

  20. Active targeting behaviors of biotinylated pluronic/poly(lactic acid) nanoparticles in vitro through three-step biotin-avidin interaction.

    PubMed

    Xiong, Xiang Yuan; Gong, Yan Chun; Li, Zi Ling; Li, Yu Ping; Guo, Liang

    2011-01-01

    In order to prepare targeted drug carriers, previously a biotin group has been attached by our group to the end of Pluronic F87/poly(lactic acid) and Pluronic P85/poly(lactic acid) block co-polymers to obtain B-F87-PLA and B-P85-PLA, respectively. In this paper, the active targeting properties of B-F87-PLA and B-P85-PLA nanoparticles in vitro were investigated through a three-step biotin-avidin interaction by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) tests and fluorescence microscopy (FM). Two kinds of human ovarian cancer cells (OVCAR-3 and SKOV-3) and paclitaxel were chosen for the cytotoxicity tests. CA-125 antigen is over-expressed on OVCAR-3 cells but not on SKOV-3 cells. The loading and release behavior of paclitaxel loaded in B-Pluronic-PLA nanoparticles were also studied. Paclitaxel loaded in both B-F87-PLA and B-P85-PLA nanoparticles shows an initial rapid release followed by a slow release period. Compared with SKOV-3 cells, the cytotoxicity results implied that paclitaxel-loaded B-Pluronic-PLA nanoparticles were delivered more effectively to OVCAR-3 cells due to the specific interaction between the biotin groups on the surface of B-Pluronic-PLA nanoparticles and the avidin/biotinylated MAb X306/CA-125 antigen complexes on the surface of OVCAR-3 cells. The active targeting properties of B-F87-PLA nanoparticles were further confirmed by FM.

  1. One-step synthesis of Fe–N–S-tri-doped TiO{sub 2} catalyst and its enhanced visible light photocatalytic activity

    SciTech Connect

    Cheng, Xiuwen; Yu, Xiujuan; Xing, Zipeng

    2012-11-15

    Graphical abstract: FeNS-TiO{sub 2} exhibits stronger SPS response than that of pure TiO{sub 2}, indicating that the FeNS-TiO{sub 2} should have a higher separation rates of photoinduced charge carriers. Further, for the sample FeNS-TiO{sub 2} a broad shoulder SPS response can be seen at the wavelength range from 390 to 550 nm, suggesting that the light absorption in visible region of FeNS-TiO{sub 2} was greatly improved, which is beneficial to the enhancement of photocatalytic activity. Display Omitted Highlights: ► FeNS-TiO{sub 2} catalyst has been synthesized in the presence of ammonium ferrous sulfate. ► The light absorption edge of FeNS-TiO{sub 2} catalyst was red-shifted to visible region. ► The separation efficiency of photoinduced charge carriers of FeNS-TiO{sub 2} was improved. ► The activity enhanced mechanism of FeNS-TiO{sub 2} was discussed in detail. -- Abstract: Fe–N–S-tridoped TiO{sub 2} was synthesized through simple one step sol–gel reactions in the presence of ammonium ferrous sulfate. The resulting materials were characterized by X-ray diffraction, transmission electron microscopy, X-ray photoelectron spectroscopy, diffuse reflectance spectrum and surface photovoltage spectroscopy. Results revealed that Fe and S were incorporated into the lattice of TiO{sub 2} by substituting for some Ti atoms and N for O atoms in the lattice of TiO{sub 2}. Tri-doping with Fe, N and S could inhibit the phase transformation of TiO{sub 2} from anatase to rutile, restrain the growth of crystallite sizes, extended the light absorption into the visible region and separate photoinduced charge carriers. The visible photocatalytic activity of Fe–N–S-tridoped TiO{sub 2} was higher than that of N-TiO{sub 2} and P25 TiO{sub 2}. The enhanced photocatalytic activity was attributed to the small crystallite size, high crystallinity, the intense light absorption in visible region, narrow band gap and high separation efficiency of photoinduced charge carriers.

  2. Naturally Occuring Fish Poisons from Plants

    NASA Astrophysics Data System (ADS)

    Cannon, Jonathan G.; Burton, Robert A.; Wood, Steven G.; Owen, Noel L.

    2004-10-01

    Since prehistoric times, cultures throughout the world have used piscicidal (fish poisoning) plants for fishing. In recent times, scientists have identified many of the plant compounds responsible for killing the fish and have found that these compounds possess other important biological properties, such as insecticidal and anti-cancer activities. This article reviews some of the chemical research that has been performed on naturally occurring fish poisons, including plant sources, methods of use, toxicity, and mechanisms of action of piscicides.

  3. Multifaceted ability of naturally occurring polyphenols against metastatic cancer.

    PubMed

    Zhou, Qingyu; Bennett, Lunawati L; Zhou, Shufeng

    2016-04-01

    Although cancer metastases are known to be the main cause of cancer-related deaths, truly effective antimetastatic therapeutics remain scarce in clinical practice. Naturally occurring polyphenols are the most abundant antioxidants in human diets. Many of them possess chemopreventive and chemotherapeutic properties against various types of cancer. Recent advances in understanding the molecular pathways that mediate cancer development and progression have led to an increase of interest in preclinical investigations on the mechanisms underlying anticancer activity of polyphenols. In particular, an increasing number of preclinical studies using cultured cells and animal models have demonstrated the inhibitory effects of polyphenols on tumour cell invasion and metastasis, thereby highlighting the potential of polyphenols against metastatic cancer. This review specifically addresses growing evidence of the capability of polyphenols to impair the invasion and migration of tumour cells through a diverse set of mechanisms, including downregulation of expression of matrix metalloproteinases, modulation of regulators of epithelial-mesenchymal transition, interference with Met signalling, inhibition of nuclear factor-kappa B mediated transcription, and so on. Given that metastasis occurs through a multistep process in which each step is regulated by a complex network of signalling pathways, the multi-function and multi-target characteristics of polyphenols render those promising candidates for effective adjuvant therapy against metastatic cancer.

  4. When Yawning Occurs in Elephants

    PubMed Central

    Rossman, Zoë T.; Hart, Benjamin L.; Greco, Brian J.; Young, Debbie; Padfield, Clare; Weidner, Lisa; Gates, Jennifer; Hart, Lynette A.

    2017-01-01

    Yawning is a widely recognized behavior in mammalian species. One would expect that elephants yawn, although to our knowledge, no one has reported observations of yawning in any species of elephant. After confirming a behavioral pattern matching the criteria of yawning in two Asian elephants (Elephas maximus) in a zoological setting, this study was pursued with nine captive African elephants (Loxodonta africana) at a private reserve in the Western Cape, South Africa, the Knysna Elephant Park. Observations were made in June–September and in December. In the daytime, handlers managed seven of the elephants for guided interactions with visitors. At night, all elephants were maintained in a large enclosure with six having limited outdoor access. With infrared illumination, the elephants were continuously recorded by video cameras. During the nights, the elephants typically had 1–3 recumbent sleeping/resting bouts, each lasting 1–2 h. Yawning was a regular occurrence upon arousal from a recumbency, especially in the final recumbency of the night. Yawning was significantly more frequent in some elephants. Yawning was rare during the daytime and during periods of standing around in the enclosure at night. In six occurrences of likely contagious yawning, one elephant yawned upon seeing another elephant yawning upon arousal from a final recumbency; we recorded the sex and age category of the participants. The generality of yawning in both African and Asian elephants in other environments was documented in video recordings from 39 zoological facilities. In summary, the study provides evidence that yawning does occur in both African and Asian elephants, and in African elephants, yawning was particularly associated with arousal from nighttime recumbencies. PMID:28293560

  5. When Yawning Occurs in Elephants.

    PubMed

    Rossman, Zoë T; Hart, Benjamin L; Greco, Brian J; Young, Debbie; Padfield, Clare; Weidner, Lisa; Gates, Jennifer; Hart, Lynette A

    2017-01-01

    Yawning is a widely recognized behavior in mammalian species. One would expect that elephants yawn, although to our knowledge, no one has reported observations of yawning in any species of elephant. After confirming a behavioral pattern matching the criteria of yawning in two Asian elephants (Elephas maximus) in a zoological setting, this study was pursued with nine captive African elephants (Loxodonta africana) at a private reserve in the Western Cape, South Africa, the Knysna Elephant Park. Observations were made in June-September and in December. In the daytime, handlers managed seven of the elephants for guided interactions with visitors. At night, all elephants were maintained in a large enclosure with six having limited outdoor access. With infrared illumination, the elephants were continuously recorded by video cameras. During the nights, the elephants typically had 1-3 recumbent sleeping/resting bouts, each lasting 1-2 h. Yawning was a regular occurrence upon arousal from a recumbency, especially in the final recumbency of the night. Yawning was significantly more frequent in some elephants. Yawning was rare during the daytime and during periods of standing around in the enclosure at night. In six occurrences of likely contagious yawning, one elephant yawned upon seeing another elephant yawning upon arousal from a final recumbency; we recorded the sex and age category of the participants. The generality of yawning in both African and Asian elephants in other environments was documented in video recordings from 39 zoological facilities. In summary, the study provides evidence that yawning does occur in both African and Asian elephants, and in African elephants, yawning was particularly associated with arousal from nighttime recumbencies.

  6. A facile one-step solvothermal synthesis of graphene/rod-shaped TiO₂ nanocomposite and its improved photocatalytic activity.

    PubMed

    Dong, Pengyu; Wang, Yuhua; Guo, Linna; Liu, Bin; Xin, Shuangyu; Zhang, Jia; Shi, Yurong; Zeng, Wei; Yin, Shu

    2012-08-07

    Graphene sheets were obtained through solvothermal reduction of colloidal dispersion of graphene oxide in benzyl alcohol. The graphene/rod-shaped TiO(2) nanocomposite was synthesized by this novel and facile solvothermal method. During the solvothermal reaction, both the reduction of graphene oxide and the growth of rod-shaped TiO(2) nanocrystals as well as its deposition on graphene occur simultaneously. The photocatalytic activity of graphene/rod-shaped TiO(2) and graphene/spherical TiO(2) nanocomposites was compared. In the photocatalytic degradation of methyl orange (MO), the graphene/rod-shaped TiO(2) nanocomposite with the optimized graphene content of 0.48 wt% shows good stability and exhibits a significant enhancement of photocatalytic activity compared to the bare commercial TiO(2) (P25) and graphene/spherical TiO(2) nanocomposite with the same graphene content. Photocurrent experiments were performed, which demonstrate that the photocurrent of the graphene/rod-shaped TiO(2) nanocomposite electrode is about 1.2 times as high as that of the graphene/spherical TiO(2) nanocomposite electrode. The photocatalytic mechanism of graphene/rod-shaped TiO(2) nanocomposite was also discussed on the basis of the experimental results. This work is anticipated to open a possibility in the integration of graphene and TiO(2) with various morphologies for obtaining high-performance photocatalysts in addressing environmental protection issues.

  7. Step by Step: Avoiding Spiritual Bypass in 12-Step Work

    ERIC Educational Resources Information Center

    Cashwell, Craig S.; Clarke, Philip B.; Graves, Elizabeth G.

    2009-01-01

    With spirituality as a cornerstone, 12-step groups serve a vital role in the recovery community. It is important for counselors to be mindful, however, of the potential for clients to be in spiritual bypass, which likely will undermine the recovery process.

  8. Stepping Up to Science and Math

    ERIC Educational Resources Information Center

    Goldston, Dee

    2004-01-01

    "Stepping Up to Science and Math" invites teachers to step back and rethink the way they teach both of these essential subjects. Then it illustrates how teachers can step up the pace with Standards-based activities that make learning more effective and efficient. (New lessons featuring gummy worms, school buses, or the planet Mars help teachers…

  9. Segmented Coil Fails In Steps

    NASA Technical Reports Server (NTRS)

    Stedman, Ronald S.

    1990-01-01

    Electromagnetic coil degrades in steps when faults occur, continues to operate at reduced level instead of failing catastrophically. Made in segments connected in series and separated by electrically insulating barriers. Fault does not damage adjacent components or create hazard. Used to control valves in such critical applications as cooling systems of power generators and chemical process equipment, where flammable liquids or gases handled. Also adapts to electrical control of motors.

  10. Teachers: Recognize Important Steps to Reduce Cheating

    ERIC Educational Resources Information Center

    Supon, Viola

    2008-01-01

    Teachers must walk the steps and live the steps if reducing cheating is going to occur. Teachers begin this process by being cognizant and vigilant relative to administering means of measurement and assigning written work. This process includes skill acquisition in regards to: (1) acknowledging cheating, (2) purposeful planning, (3) electronic…

  11. A Step Circuit Program.

    ERIC Educational Resources Information Center

    Herman, Susan

    1995-01-01

    Aerobics instructors can use step aerobics to motivate students. One creative method is to add the step to the circuit workout. By incorporating the step, aerobic instructors can accommodate various fitness levels. The article explains necessary equipment and procedures, describing sample stations for cardiorespiratory fitness, muscular strength,…

  12. Elevation of Alanine Aminotransferase Activity Occurs after Activation of the Cell-Death Signaling Initiated by Pattern-Recognition Receptors ‎but before Activation of Cytolytic Effectors in NK or CD8+ T Cells in the Liver During Acute HCV Infection

    PubMed Central

    Choi, Youkyung H.; Jin, Nancy; Kelly, Fiona; Sakthivel, SenthilKumar K.; Yu, Tianwei

    2016-01-01

    Pattern-recognition receptors (PRRs) promote host defenses against HCV infection by binding to their corresponding adapter molecules leading to the initiation of innate immune responses including cell death. We investigated the expression of PRR genes, biomarkers of liver cell-death, and T cell and NK cell activation/inhibition-related genes in liver and serum obtained from three experimentally infected chimpanzees with acute HCV infection, and analyzed the correlation between gene expression levels and clinical profiles. Our results showed that expression of hepatic RIG-I, TLR3, TLR7, 2OAS1, and CXCL10 mRNAs was upregulated as early as 7 days post-inoculation and peaked 12 to 83 days post-inoculation. All of the three HCV infected chimpanzees exhibited significant elevations of serum alanine aminotransferase (ALT) activity between 70 and 95 days after inoculation. Elevated levels of serum cytokeratin 18 (CK-18) and caspases 3 and 7 activity coincided closely with the rise of ALT activity, and were preceded by significant increases in levels of caspase 3 and caspase 7 mRNAs in the liver. Particularly we found that significant positive auto-correlations were observed between RIG-I, TLR3, CXCL10, 2OAS1, and PD-L1 mRNA and ALT activity at 3 to 12 days before the peak of ALT activity. However, we observed substantial negative auto-correlations between T cell and NK cell activation/inhibition-related genes and ALT activity at 5 to 32 days after the peak of ALT activity. Our results indicated cell death signaling is preceded by early induction of RIG-I, TLR3, 2OAS1, and CXCL10 mRNAs which leads to elevation of ALT activity and this signaling pathway occurs before the activation of NK and T cells during acute HCV infection. Our study suggests that PRRs and type I IFN response may play a critical role in development of liver cell injury related to viral clearance during acute HCV infection. PMID:27788241

  13. Medicinal significance of naturally occurring cyclotetrapeptides.

    PubMed

    Abdalla, Muna Ali

    2016-10-01

    Bioactive natural products are serendipitous drug candidates, which stimulate synthetic approaches for improving and supporting drug discovery and development. Therefore, the search for bioactive metabolites from different natural sources continues to play an important role in fashioning new medicinal agents. Several cyclic peptides were produced by organisms, such as β-defensins, gramicidin S, and tyrocidine A, and exhibited a wide range of bioactivities, such as antiviral activity against HIV-1, influenza A viruses, or antibacterial activity. Cyclic tetrapeptides are a class of natural products that were found to have a broad range of biological activities, promising pharmacokinetic properties, as well as interesting conformational dynamics and ability of slow inter-conversion to several different structures. Cyclooligopeptides, particularly medium ring-sized peptides, were obtained from marine microorganisms and exhibited a wide range of pharmacological properties, including antimicrobial and anti-dinoflagellate activities, cytotoxicity, and inhibitory activity against enzyme sortase B. Most of the naturally occurring cyclotetrapeptides are obtained from fungi. Some natural cyclic tetrapeptides were found to inhibit histone deacetylase (HDAC), which regulate the expression of genes. These compounds are very useful as cancer therapeutics. Various analogues of the natural cyclotetrapeptides were successfully synthesized to find novel lead compounds for pharmacological and biotechnological applications. Therefore, in this review, previously reported novel natural cyclotetrapeptides are briefly discussed, along with their important biological activities as drug candidates, together with their promising therapeutic properties. Moreover, their future perspective in drug discovery as potential therapeutic agents will be determined.

  14. Intensity and duration of activity bouts decreases in healthy children between 7 and 13 years of age: a new, higher resolution method to analyze StepWatch Activity Monitor data.

    PubMed

    Tulchin-Francis, Kirsten; Stevens, Wilshaw; Jeans, Kelly A

    2014-11-01

    Assessment of physical, ambulatory, activity using accelerometer-based devices has been reported in healthy individuals across a wide range of ages, as well as in multiple patient populations. Many researchers who utilize the StepWatch Activity Monitor (SAM) rely on the default settings for data collection and analysis. A comparison was made between the standard output from the SAM software, and a novel method to evaluate all walking bouts using an Intensity-Duration-Volume (I-D-V) model in healthy children aged 7-13. 105 children without impairment wore the SAM for a total of 1691 d. Statistically significant differences were seen between 7-8-9 year olds and 10-11-12 year olds using the I-D-V model that were not seen using the standard SAM software default output. The increased sensitivity of this technique could be critical for observing the effect of various interventions on patients who experience physical limitations. This new analytical model also allows researchers to monitor activity and exercise-type behavior in a way which coincides with exercise prescription by assessing intensity, duration and volume of activity bouts.

  15. Naturally occurring products in cancer therapy

    PubMed Central

    Rajesh, E.; Sankari, Leena S.; Malathi, L.; Krupaa, Jayasri R.

    2015-01-01

    Natural products have been used for the treatment of various diseases and are becoming an important research area for drug discovery. These products, especially phytochemicals have been extensively studies and have exhibited anti-carcinogenic activities by interfering with the initiation, development and progression of cancer through the modulation of various mechanisms including cellular proliferation, differentiation, apoptosis, angiogenesis, and metastasis. This concept is gaining attention because it is a cost-effective alternative to cancer treatment. In this article, we have discussed some of the naturally occurring products used in cancer treatment. PMID:26015704

  16. Oxidations of p-alkoxyacylanilides catalyzed by human cytochrome P450 1A2: structure-activity relationships and simulation of rate constants of individual steps in catalysis.

    PubMed

    Yun, C H; Miller, G P; Guengerich, F P

    2001-04-10

    Human cytochrome P450 (P450) 1A2 is involved in the oxidation of many important drugs and carcinogens. The prototype substrate phenacetin is oxidized to an acetol as well as the O-dealkylation product [Yun, C.-H., Miller, G. P., and Guengerich, F. P. (2000) Biochemistry 39, 11319-11329]. In an effort to improve rates of catalysis of P450 1A2 enzymes, we considered a set of p-alkoxyacylanilide analogues of phenacetin and found that variations in the O-alkyl and N-acyl substituents altered the rates of the two oxidation reactions and the ratio of acetol/phenol products. Moving one methylene group of phenacetin from the O-alkyl group to the N-acyl moiety increased rates of both oxidations approximately 5-fold and improved the coupling efficiency (oxidation products formed/NADPH consumed) from 6% to 38%. Noncompetitive kinetic deuterium isotope effects of 2-3 were measured for all O-dealkylation reactions examined with wild-type P450 1A2 and the E225I mutant, which has 6-fold higher activity. A trend of decreasing kinetic deuterium isotope effect for E225I > wild-type > mutant D320A was observed for O-demethylation of p-methoxyacetanilide, which follows the trend for k(cat). The set of O-dealkylation and acetol formation results for wild-type P450 1A2 and the E225I mutant with several of the protiated and deuterated substrates were fit to a model developed for the basic catalytic cycle and a set of microscopic rate constants in which the only variable was the rate of product formation (substrate oxygenation, including hydrogen abstraction). In this model, k(cat) is considerably less than any of the microscopic rate constants and is affected by several individual rate constants, including the rate of formation of the oxygenating species, the rate of substrate oxidation by the oxygenating species, and the rates of generation of reduced oxygen species (H(2)O(2), H(2)O). This analysis of the effects of the individual rate constants provides a framework for consideration of

  17. The Stepping Stone Approach

    NASA Astrophysics Data System (ADS)

    Brumfitt, A.

    Education is a profession in its own right. It has its own parameters, passions and language. Having the responsibility both of educare and educere, education has a focus of delivering specific factual knowledge whilst drawing out the creative mind. Space Science is a special vehicle having the properties of both educare and educere. It has a magic and wonder that touches the very essence of an individual and his place in time and space; it offers the "wow" factor that all teachers strive for. Space Science is the wrapping paper for other elements in the curriculum, e.g. cross-curricula and skill-based activities, such as language development, creativity, etc. as well as the pure sciences which comprise of engineering, physics and other natural sciences from astronomy to chemistry to biology. Each of these spheres of influence are relevant from kindergarten to undergraduate studies and complement, and in addition support informal education in museums, science centers and the world of e-learning. ESA Science Education has devised the "Stepping Stone Approach" to maximize the greatest outreach to all education stakeholders in Europe. In this paper we illustrate how to best reach these target groups with very specific activities to trigger and sustain enthusiasm whilst supporting the pedagogical, subject content and skill-based needs of a prescribed curriculum.

  18. Ten Steps for Peace Education

    ERIC Educational Resources Information Center

    n/a

    2005-01-01

    This brief guide is for parents and teachers who seek to nurture the values of compassion and good will in their children?s lives. It describes ten steps or actions to promote peace and goodwill in the home, in family activities, and in school.

  19. Differential dormancy of co-occurring copepods

    NASA Astrophysics Data System (ADS)

    Ohman, Mark D.; Drits, Aleksandr V.; Elizabeth Clarke, M.; Plourde, Stéphane

    1998-08-01

    Four species of planktonic calanoid copepods that co-occur in the California Current System ( Eucalanus californicus Johnson, Rhincalanus nasutus Giesbrecht, Calanus pacificus californicus Brodsky, and Metridia pacifica Brodsky) were investigated for evidence of seasonal dormancy in the San Diego Trough. Indices used to differentiate actively growing from dormant animals included developmental stage structure and vertical distribution; activity of aerobic metabolic enzymes (Citrate Synthase and the Electron Transfer System complex); investment in depot lipids (wax esters and triacylglycerols); in situ grazing activity from gut fluorescence; and egg production rates in simulated in situ conditions. None of the 4 species exhibited a canonical calanoid pattern of winter dormancy - i.e., synchronous developmental arrest as copepodid stage V, descent into deep waters, reduced metabolism, and lack of winter reproduction. Instead, Calanus pacificus californicus has a biphasic life history in this region, with an actively reproducing segment of the population in surface waters overlying a deep dormant segment in winter. Eucalanus californicus is dormant as both adult females and copepodid V's, although winter females respond relatively rapidly to elevated food and temperature conditions; they begin feeding and producing eggs within 2-3 days. Rhincalanus nasutus appears to enter dormancy as adult females, although the evidence is equivocal. Metridia pacifica shows no evidence of dormancy, with sustained active feeding, diel vertical migration behavior, and elevated activity of metabolic enzymes in December as well as in June. The four species also differ markedly in water content, classes of storage lipids, and specific activity of Citrate Synthase. These results suggest that copepod dormancy traits and structural composition reflect diverse adaptations to regional environmental conditions rather than a uniform, canonical series of traits that remain invariant among taxa

  20. Golgi-Cox Staining Step by Step

    PubMed Central

    Zaqout, Sami; Kaindl, Angela M.

    2016-01-01

    Golgi staining remains a key method to study neuronal morphology in vivo. Since most protocols delineating modifications of the original staining method lack details on critical steps, establishing this method in a laboratory can be time-consuming and frustrating. Here, we describe the Golgi-Cox staining in such detail that should turn the staining into an easily feasible method for all scientists working in the neuroscience field. PMID:27065817

  1. Multiple rate-determining steps for nonideal and fractal kinetics.

    PubMed

    Vlad, Marcel O; Popa, Vlad T; Segal, E; Ross, John

    2005-02-17

    We show that the kinetic model of a single rate-determining step in a reaction mechanism can be extended to systems with multiple overall reactions for which the elementary reactions obey nonideal or fractal kinetics. The following assumptions are necessary: (1) The system studied is either closed or open, but no constraints exist preventing the evolution toward equilibrium. (2) Elementary reactions occur in pairs of forward and backward steps. (3) The kinetics of the elementary steps are either nonideal or fractal and are compatible with equilibrium thermodynamics. (4) The number of reaction routes is identical with the number of rate-determining steps. If these hypotheses are valid, then the overall reaction rates can be explicitly evaluated: they have a form similar to the kinetic equations for the elementary reactions and the apparent reaction orders and fractal coefficients can be expressed analytically in terms of the kinetic parameters of the elementary reactions. We derive a set of relationships which connect the equilibrium constants of the reaction routes, the corresponding overall rate coefficients, and the stoichiometric numbers of the rate-determining steps. We also derive a set of generalized Boreskov relations among the apparent activation energies of the forward and backward overall processes, the corresponding reaction enthalpies, and the stoichiometric coefficients of the rate-determining steps. If the elementary reactions obey fractal kinetics, the same is true for the rate-determining steps. The fractal exponents of the forward and backward overall reactions are linear combinations of the fractal exponents of the fractal elementary reactions. Similar to the theory of single rate-determining steps, our approach can be used for selecting suitable reaction mechanisms from experimental data.

  2. Information on stepping motors

    NASA Astrophysics Data System (ADS)

    Fongarland, G.

    1982-04-01

    The principles of the stepping motors which are often used in servomechanisms are reviewed. Variable reluctance as well as permanent magnet stepping motors are considered. Their operation is explained which includes permanent rotation, starting, stopping, and resonance effects. Several application examples, drawn from problems in automation, are outlined.

  3. STEP Experiment Requirements

    NASA Technical Reports Server (NTRS)

    Brumfield, M. L. (Compiler)

    1984-01-01

    A plan to develop a space technology experiments platform (STEP) was examined. NASA Langley Research Center held a STEP Experiment Requirements Workshop on June 29 and 30 and July 1, 1983, at which experiment proposers were invited to present more detailed information on their experiment concept and requirements. A feasibility and preliminary definition study was conducted and the preliminary definition of STEP capabilities and experiment concepts and expected requirements for support services are presented. The preliminary definition of STEP capabilities based on detailed review of potential experiment requirements is investigated. Topics discussed include: Shuttle on-orbit dynamics; effects of the space environment on damping materials; erectable beam experiment; technology for development of very large solar array deployers; thermal energy management process experiment; photovoltaic concentrater pointing dynamics and plasma interactions; vibration isolation technology; flight tests of a synthetic aperture radar antenna with use of STEP.

  4. Performance monitoring and response conflict resolution associated with choice stepping reaction tasks.

    PubMed

    Watanabe, Tatsunori; Tsutou, Kotaro; Saito, Kotaro; Ishida, Kazuto; Tanabe, Shigeo; Nojima, Ippei

    2016-11-01

    Choice reaction requires response conflict resolution, and the resolution processes that occur during a choice stepping reaction task undertaken in a standing position, which requires maintenance of balance, may be different to those processes occurring during a choice reaction task performed in a seated position. The study purpose was to investigate the resolution processes during a choice stepping reaction task at the cortical level using electroencephalography and compare the results with a control task involving ankle dorsiflexion responses. Twelve young adults either stepped forward or dorsiflexed the ankle in response to a visual imperative stimulus presented on a computer screen. We used the Simon task and examined the error-related negativity (ERN) that follows an incorrect response and the correct-response negativity (CRN) that follows a correct response. Error was defined as an incorrect initial weight transfer for the stepping task and as an incorrect initial tibialis anterior activation for the control task. Results revealed that ERN and CRN amplitudes were similar in size for the stepping task, whereas the amplitude of ERN was larger than that of CRN for the control task. The ERN amplitude was also larger in the stepping task than the control task. These observations suggest that a choice stepping reaction task involves a strategy emphasizing post-response conflict and general performance monitoring of actual and required responses and also requires greater cognitive load than a choice dorsiflexion reaction. The response conflict resolution processes appear to be different for stepping tasks and reaction tasks performed in a seated position.

  5. Detection of Steps in Single Molecule Data

    PubMed Central

    Aggarwal, Tanuj; Materassi, Donatello; Davison, Robert; Hays, Thomas; Salapaka, Murti

    2013-01-01

    Over the past few decades, single molecule investigations employing optical tweezers, AFM and TIRF microscopy have revealed that molecular behaviors are typically characterized by discrete steps or events that follow changes in protein conformation. These events, that manifest as steps or jumps, are short-lived transitions between otherwise more stable molecular states. A major limiting factor in determining the size and timing of the steps is the noise introduced by the measurement system. To address this impediment to the analysis of single molecule behaviors, step detection algorithms incorporate large records of data and provide objective analysis. However, existing algorithms are mostly based on heuristics that are not reliable and lack objectivity. Most of these step detection methods require the user to supply parameters that inform the search for steps. They work well, only when the signal to noise ratio (SNR) is high and stepping speed is low. In this report, we have developed a novel step detection method that performs an objective analysis on the data without input parameters, and based only on the noise statistics. The noise levels and characteristics can be estimated from the data providing reliable results for much smaller SNR and higher stepping speeds. An iterative learning process drives the optimization of step-size distributions for data that has unimodal step-size distribution, and produces extremely low false positive outcomes and high accuracy in finding true steps. Our novel methodology, also uniquely incorporates compensation for the smoothing affects of probe dynamics. A mechanical measurement probe typically takes a finite time to respond to step changes, and when steps occur faster than the probe response time, the sharp step transitions are smoothed out and can obscure the step events. To address probe dynamics we accept a model for the dynamic behavior of the probe and invert it to reveal the steps. No other existing method addresses

  6. Nipah virus entry can occur by macropinocytosis

    SciTech Connect

    Pernet, Olivier; Pohl, Christine; Ainouze, Michelle; Kweder, Hasan; Buckland, Robin

    2009-12-20

    Nipah virus (NiV) is a zoonotic biosafety level 4 paramyxovirus that emerged recently in Asia with high mortality in man. NiV is a member, with Hendra virus (HeV), of the Henipavirus genus in the Paramyxoviridae family. Although NiV entry, like that of other paramyxoviruses, is believed to occur via pH-independent fusion with the host cell's plasma membrane we present evidence that entry can occur by an endocytic pathway. The NiV receptor ephrinB2 has receptor kinase activity and we find that ephrinB2's cytoplasmic domain is required for entry but is dispensable for post-entry viral spread. The mutation of a single tyrosine residue (Y304F) in ephrinB2's cytoplasmic tail abrogates NiV entry. Moreover, our results show that NiV entry is inhibited by constructions and drugs specific for the endocytic pathway of macropinocytosis. Our findings could potentially permit the rapid development of novel low-cost antiviral treatments not only for NiV but also HeV.

  7. GABA-A receptor antagonists increase firing, bursting and synchrony of spontaneous activity in neuronal networks grown on microelectrode arrays: a step towards chemical "fingerprinting"

    EPA Science Inventory

    Assessment of effects on spontaneous network activity in neurons grown on MEAs is a proposed method to screen chemicals for potential neurotoxicity. In addition, differential effects on network activity (chemical "fingerprints") could be used to classify chemical modes of action....

  8. Carbon Nanotubes as Electrically Active Nanoreactors for Multi-Step Inorganic Synthesis: Sequential Transformations of Molecules to Nanoclusters and Nanoclusters to Nanoribbons.

    PubMed

    Botos, Akos; Biskupek, Johannes; Chamberlain, Thomas W; Rance, Graham A; Stoppiello, Craig T; Sloan, Jeremy; Liu, Zheng; Suenaga, Kazutomo; Kaiser, Ute; Khlobystov, Andrei N

    2016-07-06

    In organic synthesis, the composition and structure of products are predetermined by the reaction conditions; however, the synthesis of well-defined inorganic nanostructures often presents a significant challenge yielding nonstoichiometric or polymorphic products. In this study, confinement in the nanoscale cavities of single-walled carbon nanotubes (SWNTs) provides a new approach for multistep inorganic synthesis where sequential chemical transformations take place within the same nanotube. In the first step, SWNTs donate electrons to reactant iodine molecules (I2), transforming them to iodide anions (I(-)). These then react with metal hexacarbonyls (M(CO)6, M = Mo or W) in the next step, yielding anionic nanoclusters [M6I14](2-), the size and composition of which are strictly dictated by the nanotube cavity, as demonstrated by aberration-corrected high resolution transmission electron microscopy, scanning transmission electron microscopy, and energy dispersive X-ray spectroscopy. Atoms in the nanoclusters [M6I14](2-) are arranged in a perfect octahedral geometry and can engage in further chemical reactions within the nanotube, either reacting with each other leading to a new polymeric phase of molybdenum iodide [Mo6I12]n or with hydrogen sulfide gas giving rise to nanoribbons of molybdenum/tungsten disulfide [MS2]n in the third step of the synthesis. Electron microscopy measurements demonstrate that the products of the multistep inorganic transformations are precisely controlled by the SWNT nanoreactor with complementary Raman spectroscopy revealing the remarkable property of SWNTs to act as a reservoir of electrons during the chemical transformation. The electron transfer from the host nanotube to the reacting guest molecules is essential for stabilizing the anionic metal iodide nanoclusters and for their further transformation to metal disulfide nanoribbons synthesized in the nanotubes in high yield.

  9. Thymineless Death in F10-Treated AML Cells Occurs via Lipid Raft Depletion and Fas/FasL co-Localization in the Plasma Membrane with Activation of the Extrinsic Apoptotic Pathway

    PubMed Central

    Gmeiner, William H.; Jennings-Gee, Jamie; Stuart, Christopher H.; Pardee, Timothy S.

    2014-01-01

    The polymeric fluoropyrimidine F10 displays excellent anti-leukemia activity in pre-clinical models of acute myelogenous leukemia (AML) through dual targeting of thymidylate synthase and DNA topoisomerase 1. Here we report that F10 activates the extrinsic apoptotic pathway in AML cells by enhancing localization of Fas and Fas ligand (FasL) at the plasma membrane and while reducing overall lipid raft levels promotes Fas/FasL co-localization in remaining lipid rafts. The HMG-CoA synthase inhibitor simvastatin was synergistic with F10 and induced cell death via similar apoptotic processes. Our results are consistent with diverse processes activating a common apoptotic pathway characterized by reduced overall levels of lipid rafts and Fas/FasL co-localization in the plasma membrane, including in remaining lipid rafts which may play a role in both cell-survival and cell death signaling. PMID:25510486

  10. Thymineless death in F10-treated AML cells occurs via lipid raft depletion and Fas/FasL co-localization in the plasma membrane with activation of the extrinsic apoptotic pathway.

    PubMed

    Gmeiner, William H; Jennings-Gee, Jamie; Stuart, Christopher H; Pardee, Timothy S

    2015-02-01

    The polymeric fluoropyrimidine F10 displays excellent anti-leukemia activity in pre-clinical models of acute myelogenous leukemia (AML) through dual targeting of thymidylate synthase and DNA topoisomerase 1. Here we report that F10 activates the extrinsic apoptotic pathway in AML cells by enhancing localization of Fas and Fas ligand (FasL) at the plasma membrane and while reducing overall lipid raft levels promotes Fas/FasL co-localization in remaining lipid rafts. The HMG-CoA synthase inhibitor simvastatin was synergistic with F10 and induced cell death via similar apoptotic processes. Our results are consistent with diverse processes activating a common apoptotic pathway characterized by reduced overall levels of lipid rafts and Fas/FasL co-localization in the plasma membrane, including in remaining lipid rafts which may play a role in both cell-survival and cell death signaling.

  11. The Next Giant Step

    NASA Video Gallery

    Artist Robert McCall painted "The Next Giant Step" in 1979 to commemorate the heroism and courage of spaceflight pioneers. Located in the lobby of Johnson's building 2, the mural depicts America's ...

  12. CEIP Next Steps

    EPA Pesticide Factsheets

    The Clean Energy Incentive Program (CEIP) next steps document details the EPA’s outreach strategy for stakeholder input on the design and implementation of the CEIP. Additionally, this document lists provisions on the CEIP where stakeholder input is sought

  13. Introduction to naturally occurring radioactive material

    SciTech Connect

    Egidi, P.

    1997-08-01

    Naturally occurring radioactive material (NORM) is everywhere; we are exposed to it every day. It is found in our bodies, the food we eat, the places where we live and work, and in products we use. We are also bathed in a sea of natural radiation coming from the sun and deep space. Living systems have adapted to these levels of radiation and radioactivity. But some industrial practices involving natural resources concentrate these radionuclides to a degree that they may pose risk to humans and the environment if they are not controlled. Other activities, such as flying at high altitudes, expose us to elevated levels of NORM. This session will concentrate on diffuse sources of technologically-enhanced (TE) NORM, which are generally large-volume, low-activity waste streams produced by industries such as mineral mining, ore benefication, production of phosphate Fertilizers, water treatment and purification, and oil and gas production. The majority of radionuclides in TENORM are found in the uranium and thorium decay chains. Radium and its subsequent decay products (radon) are the principal radionuclides used in characterizing the redistribution of TENORM in the environment by human activity. We will briefly review other radionuclides occurring in nature (potassium and rubidium) that contribute primarily to background doses. TENORM is found in many waste streams; for example, scrap metal, sludges, slags, fluids, and is being discovered in industries traditionally not thought of as affected by radionuclide contamination. Not only the forms and volumes, but the levels of radioactivity in TENORM vary. Current discussions about the validity of the linear no dose threshold theory are central to the TENORM issue. TENORM is not regulated by the Atomic Energy Act or other Federal regulations. Control and regulation of TENORM is not consistent from industry to industry nor from state to state. Proposed regulations are moving from concentration-based standards to dose

  14. Tissue protein nitration and peripheral blood endotoxin activity are indicative of the severity of systemic organ compromise in naturally-occurring clinical cases of bacterial mastitis in Holstein dairy cows

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objective of this survey study was to determine a relationship between the intensity of tissue protein tyrosine nitration measured in samples of mammary gland, liver, pancreas and lung compared to estimated blood endotoxin (LPS) activity. Blood was collected from nine multiparous Holstein cows...

  15. Inhibition of T cell receptor signaling by cholesterol sulfate, a naturally occurring derivative of membrane cholesterol

    PubMed Central

    Wang, Feng; Beck-García, Katharina; Zorzin, Carina; Schamel, Wolfgang W. A.; Davis, Mark M.

    2016-01-01

    Most adaptive immune responses require the activation of specific T cells through the T cell antigen receptor–CD3 complex (TCR). Here we show that cholesterol sulfate (CS), a naturally occurring analog of cholesterol, inhibits CD3 ITAM phosphorylation, a crucial first step in T cell activation. Biochemical studies show that CS disrupted TCR multimers, apparently by displacing cholesterol, known to bind TCRβ. Moreover, CS-deficient mice displayed a heightened sensitivity to a self-antigen, whereas increasing CS content by intrathymic injection inhibited thymic selection, indicating that this molecule is an intrinsic regulator of thymocyte development. These results reveal a regulatory role for CS in TCR signaling and thymic selection, highlighting the importance of the membrane microenvironment in modulating cell surface receptor activation. PMID:27213689

  16. Formation of TiO2 layers on commercially pure Ti and Ti-Mo and Ti-Nb alloys by two-step thermal oxidation and their photocatalytic activity

    NASA Astrophysics Data System (ADS)

    Sado, Shota; Ueda, Takatoshi; Ueda, Kyosuke; Narushima, Takayuki

    2015-12-01

    Anatase-containing TiO2 layers were formed on commercially pure (CP) Ti and Ti-25mass%Mo (Ti-25Mo) and Ti-25mass%Nb (Ti-25Nb) alloys by two-step thermal oxidation. The first-step treatment was conducted in an Ar-1%CO atmosphere at 1073 K for 3.6 ks, and the second-step treatment was conducted in air at 673-1073 K for 10.8 ks. The second-step temperature range for anatase formation was wider in the Ti alloys than in CP Ti. Photo-induced superhydrophilicity under UV irradiation was observed for the TiO2 layers with anatase fractions ≥0.6 on CP Ti and the Ti-25Mo alloy, and with anatase fractions ≥0.18 on the Ti-25Nb alloy. The TiO2 layers on the Ti-25Nb alloy exhibited excellent photocatalytic activity in the low anatase fraction region, which is considered to be caused by the incorporation of 1-3 at% Nb into the TiO2 layers. The rate constant of methylene blue degradation showed maxima at anatase fractions of 0.6-0.9.

  17. Dynamic Contacts of U2, RES, Cwc25, Prp8 and Prp45 Proteins with the Pre-mRNA Branch-Site and 3' Splice Site during Catalytic Activation and Step 1 Catalysis in Yeast Spliceosomes

    PubMed Central

    Schneider, Cornelius; Agafonov, Dmitry E.; Schmitzová, Jana; Hartmuth, Klaus; Fabrizio, Patrizia; Lührmann, Reinhard

    2015-01-01

    Little is known about contacts in the spliceosome between proteins and intron nucleotides surrounding the pre-mRNA branch-site and their dynamics during splicing. We investigated protein-pre-mRNA interactions by UV-induced crosslinking of purified yeast Bact spliceosomes formed on site-specifically labeled pre-mRNA, and analyzed their changes after conversion to catalytically-activated B* and step 1 C complexes, using a purified splicing system. Contacts between nucleotides upstream and downstream of the branch-site and the U2 SF3a/b proteins Prp9, Prp11, Hsh49, Cus1 and Hsh155 were detected, demonstrating that these interactions are evolutionarily conserved. The RES proteins Pml1 and Bud13 were shown to contact the intron downstream of the branch-site. A comparison of the Bact crosslinking pattern versus that of B* and C complexes revealed that U2 and RES protein interactions with the intron are dynamic. Upon step 1 catalysis, Cwc25 contacts with the branch-site region, and enhanced crosslinks of Prp8 and Prp45 with nucleotides surrounding the branch-site were observed. Cwc25’s step 1 promoting activity was not dependent on its interaction with pre-mRNA, indicating it acts via protein-protein interactions. These studies provide important insights into the spliceosome's protein-pre-mRNA network and reveal novel RNP remodeling events during the catalytic activation of the spliceosome and step 1 of splicing. PMID:26393790

  18. Twelve Steps to a Winning First Year

    ERIC Educational Resources Information Center

    Hodges, Karen

    2009-01-01

    This article offers 12 steps to jumpstart a new school librarian's career. Being the information specialist will be both challenging and rewarding as one undertakes a myriad of activities. These 12 steps will help a new school librarian's first year successful.

  19. Teaching Active Listening Skills to Pre-Service Speech-Language Pathologists: A First Step in Supporting Collaboration with Parents of Young Children Who Require AAC

    ERIC Educational Resources Information Center

    Thistle, Jennifer J.; McNaughton, David

    2015-01-01

    Purpose: This study examined the effect of instruction in an active listening strategy on the communication skills of pre-service speech-language pathologists (SLPs). Method: Twenty-three pre-service SLPs in their 2nd year of graduate study received a brief strategy instruction in active listening skills. Participants were videotaped during a…

  20. One-step production of a biologically active novel furan fatty acid from 7,10-dihydroxy-8(E)-octadecenoic acid

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Furan fatty acids (F-acids) gain special attentions since they are known to play important roles in biological systems including humans. Specifically F-acids are known to have strong antioxidant activity like radical scavenging activity. Although widely distributed in most biological systems, F-ac...

  1. Serotonin 5-HT3 receptor-mediated vomiting occurs via the activation of Ca2+/CaMKII-dependent ERK1/2 signaling in the least shrew (Cryptotis parva).

    PubMed

    Zhong, Weixia; Hutchinson, Tarun E; Chebolu, Seetha; Darmani, Nissar A

    2014-01-01

    Stimulation of 5-HT3 receptors (5-HT3Rs) by 2-methylserotonin (2-Me-5-HT), a selective 5-HT3 receptor agonist, can induce vomiting. However, downstream signaling pathways for the induced emesis remain unknown. The 5-HT3R channel has high permeability to extracellular calcium (Ca(2+)) and upon stimulation allows increased Ca(2+) influx. We examined the contribution of Ca(2+)/calmodulin-dependent protein kinase IIα (Ca(2+)/CaMKIIα), interaction of 5-HT3R with calmodulin, and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling to 2-Me-5-HT-induced emesis in the least shrew. Using fluo-4 AM dye, we found that 2-Me-5-HT augments intracellular Ca(2+) levels in brainstem slices and that the selective 5-HT3R antagonist palonosetron, can abolish the induced Ca(2+) signaling. Pre-treatment of shrews with either: i) amlodipine, an antagonist of L-type Ca(2+) channels present on the cell membrane; ii) dantrolene, an inhibitor of ryanodine receptors (RyRs) Ca2+-release channels located on the endoplasmic reticulum (ER); iii) a combination of their less-effective doses; or iv) inhibitors of CaMKII (KN93) and ERK1/2 (PD98059); dose-dependently suppressed emesis caused by 2-Me-5-HT. Administration of 2-Me-5-HT also significantly: i) enhanced the interaction of 5-HT3R with calmodulin in the brainstem as revealed by immunoprecipitation, as well as their colocalization in the area postrema (brainstem) and small intestine by immunohistochemistry; and ii) activated CaMKIIα in brainstem and in isolated enterochromaffin cells of the small intestine as shown by Western blot and immunocytochemistry. These effects were suppressed by palonosetron. 2-Me-5-HT also activated ERK1/2 in brainstem, which was abrogated by palonosetron, KN93, PD98059, amlodipine, dantrolene, or a combination of amlodipine plus dantrolene. However, blockade of ER inositol-1, 4, 5-triphosphate receptors by 2-APB, had no significant effect on the discussed behavioral and biochemical parameters. This study

  2. Serotonin 5-HT3 Receptor-Mediated Vomiting Occurs via the Activation of Ca2+/CaMKII-Dependent ERK1/2 Signaling in the Least Shrew (Cryptotis parva)

    PubMed Central

    Zhong, Weixia; Hutchinson, Tarun E.; Chebolu, Seetha; Darmani, Nissar A.

    2014-01-01

    Stimulation of 5-HT3 receptors (5-HT3Rs) by 2-methylserotonin (2-Me-5-HT), a selective 5-HT3 receptor agonist, can induce vomiting. However, downstream signaling pathways for the induced emesis remain unknown. The 5-HT3R channel has high permeability to extracellular calcium (Ca2+) and upon stimulation allows increased Ca2+ influx. We examined the contribution of Ca2+/calmodulin-dependent protein kinase IIα (Ca2+/CaMKIIα), interaction of 5-HT3R with calmodulin, and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling to 2-Me-5-HT-induced emesis in the least shrew. Using fluo-4 AM dye, we found that 2-Me-5-HT augments intracellular Ca2+ levels in brainstem slices and that the selective 5-HT3R antagonist palonosetron, can abolish the induced Ca2+ signaling. Pre-treatment of shrews with either: i) amlodipine, an antagonist of L-type Ca2+ channels present on the cell membrane; ii) dantrolene, an inhibitor of ryanodine receptors (RyRs) Ca2+-release channels located on the endoplasmic reticulum (ER); iii) a combination of their less-effective doses; or iv) inhibitors of CaMKII (KN93) and ERK1/2 (PD98059); dose-dependently suppressed emesis caused by 2-Me-5-HT. Administration of 2-Me-5-HT also significantly: i) enhanced the interaction of 5-HT3R with calmodulin in the brainstem as revealed by immunoprecipitation, as well as their colocalization in the area postrema (brainstem) and small intestine by immunohistochemistry; and ii) activated CaMKIIα in brainstem and in isolated enterochromaffin cells of the small intestine as shown by Western blot and immunocytochemistry. These effects were suppressed by palonosetron. 2-Me-5-HT also activated ERK1/2 in brainstem, which was abrogated by palonosetron, KN93, PD98059, amlodipine, dantrolene, or a combination of amlodipine plus dantrolene. However, blockade of ER inositol-1, 4, 5-triphosphate receptors by 2-APB, had no significant effect on the discussed behavioral and biochemical parameters. This study demonstrates

  3. A color-reaction-based rapid screening for null activity of butyrylcholinesterase: a step toward point-of-care screening for succinylcholine apnea.

    PubMed

    Nagpal, Nitish; Chowdhary, Sheemona; Bhattacharyya, Rajasri; Banerjee, Dibyajyoti

    2015-01-01

    Succinylcholine apnea happens in cases of null butyrylcholinesterase activity after administration of preintubation succinylcholine. So far, there is no such popular test that can rapidly screen null butyrylcholinesterase activity from plasma. Development of a novel method for rapid screening of null butyrylcholinesterase activity of plasma samples was the objective of the current work. Dichromate reagent was added to 1-naphthol, 2-naphthol, phenol, and para-nitrophenol in separate aliquots and watched for the color formation. Plasma samples preincubated with and without selective butyrylcholinesterase inhibitor were mixed with 1-naphthylacetate and watched for color development after addition of dichromate reagent. Fitting of 1-naphthylacetate at the active site of butyrylcholinesterase was analyzed by using tools of computational biology. It was seen that 1-naphthol formed color with dichromate reagent in a concentration-dependent manner. Other phenols did not form color with dichromate reagent even at 500-µm concentrations. Plasma sample with and without selective butyrylcholinesterase inhibitor (tetra isopropyl pyrophosphoramide) was distinguishable by color formation when incubated with 1-naphthylacetate, followed by the addition of dichromate reagent. In silico analysis also showed that 1-naphthylacetate fitted well at the active site of butyrylcholinesterase. The developed method may be used for rapid screening for null butyrylcholinesterase activity at point of care.

  4. Naturally occurring contamination in the Mancos Shale.

    PubMed

    Morrison, Stan J; Goodknight, Craig S; Tigar, Aaron D; Bush, Richard P; Gil, April

    2012-02-07

    Some uranium mill tailings disposal cells were constructed on dark-gray shale of the Upper Cretaceous Mancos Shale. Shale of this formation contains contaminants similar to those in mill tailings. To establish the contributions derived from the Mancos, we sampled 51 locations in Colorado, New Mexico, and Utah. Many of the groundwater samples were saline with nitrate, selenium, and uranium concentrations commonly exceeding 250, 000, 1000, and 200 μg/L, respectively. Higher concentrations were limited to groundwater associated with shale beds, but were not correlated with geographic area, stratigraphic position, or source of water. The elevated concentrations suggest that naturally occurring contamination should be considered when evaluating groundwater cleanup levels. At several locations, seep water was yellow or red, caused in part by dissolved organic carbon concentrations up to 280 mg/L. Most seeps had (234)U to (238)U activity ratios greater than 2, indicating preferential leaching of (234)U. Seeps were slightly enriched in (18)O relative to the meteoric water line, indicating limited evaporation. Conceptually, major ion chemical reactions are dominated by calcite dissolution following proton release from pyrite oxidation and subsequent exchange by calcium for sodium residing on clay mineral exchange sites. Contaminants are likely released from organic matter and mineral surfaces during weathering.

  5. 2-Step IMAT and 2-Step IMRT in three dimensions

    SciTech Connect

    Bratengeier, Klaus

    2005-12-15

    the additional segment as well as the integral across the segment profile was demonstrated to be an important value. This product was up to a factor of 3 larger than in the 2-D case. Even in three dimensions, the optimized 2-Step IMAT increased the homogeneity of the dose distribution in the PTV profoundly. Rules for adaptation to varying target-OAR combinations were deduced. It can be concluded that 2-Step IMAT and 2-Step IMRT are also applicable in three dimensions. In the majority of cases, weights between 0.5 and 2 will occur for the additional segment. The width-weight product of the second segment is always smaller than the normalized radius of the OAR. The width-weight product of the additional segment is strictly connected to the relevant diameter of the organ at risk and the target volume. The derived formulas can be helpful to adapt an IMRT plan to altering target shapes.

  6. Fusion-power demonstration. [Next step beyond MFTF-B

    SciTech Connect

    Henning, C.D.; Logan, B.G.; Carlson, G.A.; Neef, W.S.; Moir, R.W.; Campbell, R.B.; Botwin, R.; Clarkson, I.R.; Carpenter, T.J.

    1983-03-29

    As a satellite to the MARS (Mirror Advanced Reactor Study) a smaller, near-term device has been scoped, called the FPD (Fusion Power Demonstration). Envisioned as the next logical step toward a power reactor, it would advance the mirror fusion program beyond MFTF-B and provide an intermediate step toward commercial fusion power. Breakeven net electric power capability would be the goal such that no net utility power would be required to sustain the operation. A phased implementation is envisioned, with a deuterium checkout first to verify the plasma systems before significant neutron activation has occurred. Major tritium-related facilities would be installed with the second phase to produce sufficient fusion power to supply the recirculating power to maintain the neutral beams, ECRH, magnets and other auxiliary equipment.

  7. The next step in health behavior research: the need for ecological moderation analyses - an application to diet and physical activity at childcare

    PubMed Central

    2014-01-01

    Background The ecological perspective holds that human behavior depends on the interaction of different environmental factors and personal characteristics, but it lacks validation and operationalization. In the current paper, an ecological view was adopted to examine the interactive impact of several ecological systems on children’s dietary intake and physical activity at childcare or similar facilities. The ecological view was operationalized into three types of interaction: 1) interaction between types of childcare environment (physical, social, political, economic); 2) interaction between micro-systems (the childcare and home environment) in meso-systems; and 3) interaction between childcare environment and child characteristics. The predictive value of each of these interactions was tested based on a systematic review of the literature. Discussion Several studies support the hypothesis that the influence of the childcare environment on children’s physical activity and diet is moderated by child characteristics (age, gender), but interaction between environmental types as well as between micro-systems is hardly examined in the field of behavioral nutrition and physical activity. Qualitative studies and general child development research provide some valuable insights, but we advocate quantitative research adopting an ecological perspective on environmental influences. Summary Empirical studies operationalizing a true ecological view on diet and physical activity are scarce. Theorizing and assessment of interaction is advocated to become common practice rather than an exception in behavioral nutrition and physical activity research, in order to move the field forward. PMID:24742167

  8. Non-chemical proton-dependent steps prior to O2-activation limit Azotobacter vinelandii 3-mercaptopropionic acid dioxygenase (MDO) catalysis

    PubMed Central

    Crowell, Joshua K.; Sardar, Sinjinee; Hossain, Mohammad S.; Foss, Frank W.; Pierce, Brad S.

    2016-01-01

    3-mercaptopropionate dioxygenase from Azotobacter vinelandii (Av MDO) is a non-heme mononuclear iron enzyme that catalyzes the O2-dependent oxidation of 3-mercaptopropionate (3mpa) to produce 3-sulfinopropionic acid (3spa). With one exception, the active site residues of MDO are identical to bacterial cysteine dioxygenase (CDO). Specifically, the CDO Arg-residue (R50) is replaced by Gln (Q67) in MDO. Despite this minor active site perturbation, substrate-specificity of Av MDO is more relaxed as compared to CDO. In order to investigate the relative timing of chemical and non-chemical events in Av MDO catalysis, the pH/D-dependence of steady-state kinetic parameters (kcat and kcat/KM) and viscosity effects are measured using two different substrates [3mpa and L-cysteine (cys)]. The pL-dependent activity of Av MDO in these reactions can be rationalized assuming a diprotic enzyme model in which three ionic forms of the enzyme are present [cationic, E(z+1); neutral, Ez; and anionic, E(z−1)]. The activities observed for each substrate appear to be dominated by electrostatic interactions within the enzymatic active site. Given the similarity between MDO and the more extensively characterized mammalian CDO, a tentative model for the role of the conserved ‘catalytic triad’ is proposed. PMID:27311613

  9. Daily Rhythm of Mutualistic Pollinator Activity and Scent Emission in Ficus septica: Ecological Differentiation between Co-Occurring Pollinators and Potential Consequences for Chemical Communication and Facilitation of Host Speciation

    PubMed Central

    Conchou, Lucie; Cabioch, Léa; Rodriguez, Lillian J. V.; Kjellberg, Finn

    2014-01-01

    The mutualistic interaction between Ficus and their pollinating agaonid wasps constitutes an extreme example of plant-insect co-diversification. Most Ficus species are locally associated with a single specific agaonid wasp species. Specificity is ensured by each fig species emitting a distinctive attractive scent. However, cases of widespread coexistence of two agaonid wasp species on the same Ficus species are documented. Here we document the coexistence of two agaonid wasp species in Ficus septica: one yellow-colored and one black-colored. Our results suggest that their coexistence is facilitated by divergent ecological traits. The black species is longer-lived (a few more hours) and is hence active until later in the afternoon. Some traits of the yellow species must compensate for this advantage for their coexistence to be stable. In addition, we show that the composition of the scent emitted by receptive figs changes between sunrise and noon. The two species may therefore be exposed to somewhat different ranges of receptive fig scent composition and may consequently diverge in the way they perceive and/or respond to scents. Whether such situations may lead to host plant speciation is an open question. PMID:25105796

  10. Enrichment of the Cancer Stem Phenotype in Sphere Cultures of Prostate Cancer Cell Lines Occurs through Activation of Developmental Pathways Mediated by the Transcriptional Regulator ΔNp63α

    PubMed Central

    Portillo-Lara, Roberto; Alvarez, Mario Moisés

    2015-01-01

    Background Cancer stem cells (CSC) drive prostate cancer tumor survival and metastasis. Nevertheless, the development of specific therapies against CSCs is hindered by the scarcity of these cells in prostate tissues. Suspension culture systems have been reported to enrich CSCs in primary cultures and cell lines. However, the molecular mechanisms underlying this phenomenon have not been fully explored. Methodology/Principal Findings We describe a prostasphere assay for the enrichment of CD133+ CSCs in four commercial PCa cell lines: 22Rv1, DU145, LNCaP, and PC3. Overexpression of CD133, as determined by flow cytometric analysis, correlated with an increased clonogenic, chemoresistant, and invasive potential in vitro. This phenotype is concordant to that of CSCs in vivo. Gene expression profiling was then carried out using the Cancer Reference panel and the nCounter system from NanoString Technologies. This analysis revealed several upregulated transcripts that can be further explored as potential diagnostic markers or therapeutic targets. Furthermore, functional annotation analysis suggests that ΔNp63α modulates the activation of developmental pathways responsible for the increased stem identity of cells growing in suspension cultures. Conclusions/Significance We conclude that profiling the genetic mechanisms involved in CSC enrichment will help us to better understand the molecular pathways that underlie CSC pathophysiology. This platform can be readily adapted to enrich and assay actual patient samples, in order to design patient-specific therapies that are aimed particularly against CSCs. PMID:26110651

  11. Training in the step-down inhibitory avoidance task time-dependently increases cAMP-dependent protein kinase activity in the entorhinal cortex.

    PubMed

    Pereira, P; Ardenghi, P; Mello e Souza, T; Medina, J H; Izquierdo, I

    2001-06-01

    The cAMP/cAMP-dependent protein kinase (PKA) signaling pathway has been implicated in synaptic plasticity changes and memory consolidation. Several cortical structures are involved in the consolidation of memory for inhibitory avoidance. The aim of the present work was to observe the effects of training in the inhibitory avoidance task on the levels of PKA activity in the entorhinal, parietal and posterior cingulate cortex (EC, PARIET and PC), and the medial precentral area (Fr2) of the rat, at different post-training times (0, 1.5, 3 and 6h). PKA activity, assayed using [gamma-32P]ATP and kemptide, a selective substrate, increased in the EC 3 h after training, but no changes were observed in PARIET, PC and Fr2. These results suggest that the late phase of memory consolidation of inhibitory avoidance requires a functional PKA signaling pathway in the EC in a way that a 'peak' of PKA activity is observed.

  12. Stepped inlet optical panel

    DOEpatents

    Veligdan, James T.

    2001-01-01

    An optical panel includes stacked optical waveguides having stepped inlet facets collectively defining an inlet face for receiving image light, and having beveled outlet faces collectively defining a display screen for displaying the image light channeled through the waveguides by internal reflection.

  13. TENORM (Technologically Enhanced Naturally Occurring Radioactive Materials)

    MedlinePlus

    Jump to main content US EPA United States Environmental Protection Agency Search Search Radiation Protection Share Facebook Twitter Google+ Pinterest Contact Us Technologically Enhanced Naturally Occurring Radioactive ...

  14. Molecular dynamics simulation of the last step of a catalytic cycle: product release from the active site of the enzyme chorismate mutase from Mycobacterium tuberculosis.

    PubMed

    Choutko, Alexandra; van Gunsteren, Wilfred F

    2012-11-01

    The protein chorismate mutase MtCM from Mycobacterium tuberculosis catalyzes one of the few pericyclic reactions known in biology: the transformation of chorismate to prephenate. Chorismate mutases have been widely studied experimentally and computationally to elucidate the transition state of the enzyme catalyzed reaction and the origin of the high catalytic rate. However, studies about substrate entry and product exit to and from the highly occluded active site of the enzyme have to our knowledge not been performed on this enzyme. Crystallographic data suggest a possible substrate entry gate, that involves a slight opening of the enzyme for the substrate to access the active site. Using multiple molecular dynamics simulations, we investigate the natural dynamic process of the product exiting from the binding pocket of MtCM. We identify a dominant exit pathway, which is in agreement with the gate proposed from the available crystallographic data. Helices H2 and H4 move apart from each other which enables the product to exit from the active site. Interestingly, in almost all exit trajectories, two residues arginine 72 and arginine 134, which participate in the burying of the active site, are accompanying the product on its exit journey from the catalytic site.

  15. Novel electrochemical redox-active species: one-step synthesis of polyaniline derivative-Au/Pd and its application for multiplexed immunoassay

    NASA Astrophysics Data System (ADS)

    Wang, Liyuan; Feng, Feng; Ma, Zhanfang

    2015-11-01

    Electrochemical redox-active species play crucial role in electrochemically multiplexed immunoassays. A one-pot method for synthesizing four kinds of new electrochemical redox-active species was reported using HAuCl4 and Na2PdCl4 as dual oxidating agents and aniline derivatives as monomers. The synthesized polyaniline derivative-Au/Pd composites, namely poly(N-methyl-o-benzenediamine)-Au/Pd, poly(N-phenyl-o-phenylenediamine)-Au/Pd, poly(N-phenyl-p-phenylenediamine)-Au/Pd and poly(3,3’,5,5’-tetramethylbenzidine)-Au/Pd, exhibited electrochemical redox activity at -0.65 V, -0.3 V, 0.12 V, and 0.5 V, respectively. Meanwhile, these composites showed high H2O2 electrocatalytic activity because of the presence of Au/Pd. The as-prepared composites were used as electrochemical immunoprobes in simultaneous detection of four tumor biomarkers (carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA199), carbohydrate antigen 72-4 (CA724), and alpha fetoprotein (AFP)). This immunoassay shed light on potential applications in simultaneous gastric cancer (related biomarkers: CEA, CA199, CA724) and liver cancer diagnosis (related biomarkers: CEA, CA199, AFP). The present strategy to the synthesize redox species could be easily extended to other polymers such as polypyrrole derivatives and polythiophene derivatives. This would be of great significance in the electrochemical detection of more analytes.

  16. Simple one step synthesis of nonionic dithiol surfactants and their self-assembling with silver nanoparticles: Characterization, surface properties, biological activity

    NASA Astrophysics Data System (ADS)

    Abd-Elaal, Ali A.; Tawfik, Salah M.; Shaban, Samy M.

    2015-07-01

    Simple esterification of 2-mercaptoacetic acid and polyethylene glycol with different molecular weights was done to form the desired nonionic dithiol surfactants. The chemical structures of synthesized thiol surfactants were confirmed using FT-IR and 1H NMR spectra. The surface activity of the synthesized surfactants was determined by measurement of the surface tension at different temperatures. The surface activity measurements showed their high tendency towards adsorption and micellization. The thermodynamic parameters of micellization (ΔGmic, ΔHmic and ΔSmic) and adsorption (ΔGads, ΔGads and ΔSads) showed their tendency toward adsorption at the interfaces and also micellization in the bulk of their solutions. The nanostructure of the synthesized nonionic dithiol surfactants with silver nanoparticles was prepared and investigated using UV and TEM techniques. Screening tests of the synthesized dithiol surfactants and their nanostructure with silver nanoparticles, against gram positive bacteria (Bacillus subtilis and Microccus luteus), gram negative bacteria (Escherichia coli and Bordatella pertussis) and fungi (Aspergillus niger and Candida albicans) showed that they are highly active biocides. The presence of silver nanoparticles enhancement the biological activities of the individual synthesized nonionic dithiol surfactants.

  17. Novel electrochemical redox-active species: one-step synthesis of polyaniline derivative-Au/Pd and its application for multiplexed immunoassay.

    PubMed

    Wang, Liyuan; Feng, Feng; Ma, Zhanfang

    2015-11-18

    Electrochemical redox-active species play crucial role in electrochemically multiplexed immunoassays. A one-pot method for synthesizing four kinds of new electrochemical redox-active species was reported using HAuCl4 and Na2PdCl4 as dual oxidating agents and aniline derivatives as monomers. The synthesized polyaniline derivative-Au/Pd composites, namely poly(N-methyl-o-benzenediamine)-Au/Pd, poly(N-phenyl-o-phenylenediamine)-Au/Pd, poly(N-phenyl-p-phenylenediamine)-Au/Pd and poly(3,3',5,5'-tetramethylbenzidine)-Au/Pd, exhibited electrochemical redox activity at -0.65 V, -0.3 V, 0.12 V, and 0.5 V, respectively. Meanwhile, these composites showed high H2O2 electrocatalytic activity because of the presence of Au/Pd. The as-prepared composites were used as electrochemical immunoprobes in simultaneous detection of four tumor biomarkers (carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA199), carbohydrate antigen 72-4 (CA724), and alpha fetoprotein (AFP)). This immunoassay shed light on potential applications in simultaneous gastric cancer (related biomarkers: CEA, CA199, CA724) and liver cancer diagnosis (related biomarkers: CEA, CA199, AFP). The present strategy to the synthesize redox species could be easily extended to other polymers such as polypyrrole derivatives and polythiophene derivatives. This would be of great significance in the electrochemical detection of more analytes.

  18. The Importance of Spatiotemporal Information in Biological Motion Perception: White Noise Presented with a Step-like Motion Activates the Biological Motion Area.

    PubMed

    Callan, Akiko; Callan, Daniel; Ando, Hiroshi

    2017-02-01

    Humans can easily recognize the motion of living creatures using only a handful of point-lights that describe the motion of the main joints (biological motion perception). This special ability to perceive the motion of animate objects signifies the importance of the spatiotemporal information in perceiving biological motion. The posterior STS (pSTS) and posterior middle temporal gyrus (pMTG) region have been established by many functional neuroimaging studies as a locus for biological motion perception. Because listening to a walking human also activates the pSTS/pMTG region, the region has been proposed to be supramodal in nature. In this study, we investigated whether the spatiotemporal information from simple auditory stimuli is sufficient to activate this biological motion area. We compared spatially moving white noise, having a running-like tempo that was consistent with biological motion, with stationary white noise. The moving-minus-stationary contrast showed significant differences in activation of the pSTS/pMTG region. Our results suggest that the spatiotemporal information of the auditory stimuli is sufficient to activate the biological motion area.

  19. Novel electrochemical redox-active species: one-step synthesis of polyaniline derivative-Au/Pd and its application for multiplexed immunoassay

    PubMed Central

    Wang, Liyuan; Feng, Feng; Ma, Zhanfang

    2015-01-01

    Electrochemical redox-active species play crucial role in electrochemically multiplexed immunoassays. A one-pot method for synthesizing four kinds of new electrochemical redox-active species was reported using HAuCl4 and Na2PdCl4 as dual oxidating agents and aniline derivatives as monomers. The synthesized polyaniline derivative-Au/Pd composites, namely poly(N-methyl-o-benzenediamine)-Au/Pd, poly(N-phenyl-o-phenylenediamine)-Au/Pd, poly(N-phenyl-p-phenylenediamine)-Au/Pd and poly(3,3’,5,5’-tetramethylbenzidine)-Au/Pd, exhibited electrochemical redox activity at −0.65 V, −0.3 V, 0.12 V, and 0.5 V, respectively. Meanwhile, these composites showed high H2O2 electrocatalytic activity because of the presence of Au/Pd. The as-prepared composites were used as electrochemical immunoprobes in simultaneous detection of four tumor biomarkers (carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA199), carbohydrate antigen 72-4 (CA724), and alpha fetoprotein (AFP)). This immunoassay shed light on potential applications in simultaneous gastric cancer (related biomarkers: CEA, CA199, CA724) and liver cancer diagnosis (related biomarkers: CEA, CA199, AFP). The present strategy to the synthesize redox species could be easily extended to other polymers such as polypyrrole derivatives and polythiophene derivatives. This would be of great significance in the electrochemical detection of more analytes. PMID:26577799

  20. "There's so Much More to It than What I Initially Thought": Stepping into Researchers' Shoes with a Class Activity in a First Year Psychology Survey Course

    ERIC Educational Resources Information Center

    Tatlow-Golden, Mimi

    2015-01-01

    In psychology, it is widely agreed that research methods, although central to the discipline, are particularly challenging to learn and teach, particularly at introductory level. This pilot study explored the potential of embedding a student-conducted research activity in a one-semester undergraduate "Introduction to Psychology" survey…

  1. Increased Activity or Energy as a Primary Criterion for the Diagnosis of Bipolar Mania in DSM-5: Findings From the STEP-BD Study

    PubMed Central

    Machado-Vieira, Rodrigo; Luckenbaugh, David A.; Ballard, Elizabeth D.; Henter, Ioline D.; Tohen, Mauricio; Suppes, Trisha; Zarate, Carlos A.

    2016-01-01

    Objective DSM-5 describes “a distinct period of abnormally and persistently elevated, expansive, or irritable mood and abnormally and persistently increased activity or energy” as a primary criterion for mania. Thus, increased energy or activity is now considered a core symptom of manic and hypomanic episodes. Using data from the Systematic Treatment Enhancement Program for Bipolar Disorder study, the authors analyzed point prevalence data obtained at the initial visit to assess the diagnostic validity of this new DSM-5 criterion. The study hypothesis was that the DSM-5 criterion would alter the prevalence of mania and/or hypomania. Method The authors compared prevalence, clinical characteristics, validators, and outcome in patients meeting the DSM-5 criteria (i.e., DSM-IV criteria plus the DSM-5 criterion of increased activity or energy) and those who did not meet the new DSM-5 criterion (i.e., who only met DSM-IV criteria). Results All 4,360 participants met DSM-IV criteria for bipolar disorder, and 310 met DSM-IV criteria for a manic or hypomanic episode. When the new DSM-5 criterion of increased activity or energy was added as a coprimary symptom, the prevalence of mania and hypomania was reduced. Although minor differences were noted in clinical and concurrent validators, no changes were observed in longitudinal outcomes. Conclusions The findings confirm that including increased activity or energy as part of DSM-5 criterion A decreases the prevalence of manic and hypomanic episodes but does not affect longitudinal clinical outcomes. PMID:27523498

  2. Sundew adhesive: a naturally occurring hydrogel

    PubMed Central

    Huang, Yujian; Wang, Yongzhong; Sun, Leming; Agrawal, Richa; Zhang, Mingjun

    2015-01-01

    Bioadhesives have drawn increasing interest in recent years, owing to their eco-friendly, biocompatible and biodegradable nature. As a typical bioadhesive, sticky exudate observed on the stalked glands of sundew plants aids in the capture of insects and this viscoelastic adhesive has triggered extensive interests in revealing the implied adhesion mechanisms. Despite the significant progress that has been made, the structural traits of the sundew adhesive, especially the morphological characteristics in nanoscale, which may give rise to the viscous and elastic properties of this mucilage, remain unclear. Here, we show that the sundew adhesive is a naturally occurring hydrogel, consisting of nano-network architectures assembled with polysaccharides. The assembly process of the polysaccharides in this hydrogel is proposed to be driven by electrostatic interactions mediated with divalent cations. Negatively charged nanoparticles, with an average diameter of 231.9 ± 14.8 nm, are also obtained from this hydrogel and these nanoparticles are presumed to exert vital roles in the assembly of the nano-networks. Further characterization via atomic force microscopy indicates that the stretching deformation of the sundew adhesive is associated with the flexibility of its fibrous architectures. It is also observed that the adhesion strength of the sundew adhesive is susceptible to low temperatures. Both elasticity and adhesion strength of the sundew adhesive reduce in response to lowering the ambient temperature. The feasibility of applying sundew adhesive for tissue engineering is subsequently explored in this study. Results show that the fibrous scaffolds obtained from sundew adhesive are capable of increasing the adhesion of multiple types of cells, including fibroblast cells and smooth muscle cells, a property that results from the enhanced adsorption of serum proteins. In addition, in light of the weak cytotoxic activity exhibited by these scaffolds towards a variety of

  3. Prostaglandin synthesis in human T cells: its partial inhibition by lectins and anti-CD3 antibodies as a possible step in T cell activation.

    PubMed

    Aussel, C; Mary, D; Fehlmann, M

    1987-05-15

    The human leukemic T cell line Jurkat was used to study arachidonic acid (AA) metabolism. We demonstrated that Jurkat cells are able to convert AA into prostaglandins (PG) and thromboxanes. The presence of tritiated 6-keto-PGF1 alpha, PGE2, PGA2 (B2), and thromboxane B2 in the culture medium was shown either by thin-layer chromatography after a 4-hr incubation period of [3H]AA-prelabeled Jurkat cells or by using specific radioimmuno assays. PG synthesis was inhibited by both indomethacin and niflumic acid, two cyclooxygenase inhibitors. AA metabolism through the cyclooxygenase pathway was followed during T cell activation. T cells were activated by lectins or anti-CD3 monoclonal antibodies (mAb) to trigger the T3-Ti complex and by 12-0-tetradecanoylphorbol 13-acetate (TPA) to mimic IL 1-dependent pathways. Our results show that lectins and anti-CD3 mAb both reduce the amount of PG released by the cells, whereas TPA did not. We confirmed that a combination of TPA and lectins or TPA and anti-CD3 mAb is necessary to obtain full activation of Jurkat cells if this event is monitored by using measurement of IL 2 synthesis. In addition, lectins and anti-CD3 mAb can be replaced by the cyclooxygenase inhibitors indomethacin or niflumic acid. Indeed, a combination of TPA and one of these two drugs induced maximal IL 2 synthesis. These results thus suggest that a reduction in PG synthesis might be a prerequisite to allow the cascade of events involved in T cell activation.

  4. A robust super-paramagnetic TiO2:Fe3O4:Ag nanocomposite with enhanced photo and bio activities on polyester fabric via one step sonosynthesis.

    PubMed

    Harifi, Tina; Montazer, Majid

    2015-11-01

    High intensity ultrasound was used for the synthesis and simultaneous deposition of TiO2:Fe3O4:Ag nanocomposites on polyester surface providing a feasible route for imparting magnetic and enhanced antibacterial and self-cleaning activities with controllable hydrophilicity/hydrophobicity at low temperature. Synergistic impact of sonochemistry and physical effects of ultrasound originating from implosive collapse of bubbles were responsible for the formation and adsorption of nanomaterials on the fabric surface during ultrasound irradiation. The increase in photocatalytic activity of TiO2 was obtained attributing to the co-operation of iron oxide and silver nanoparticles nucleated on TiO2 surface boosting the electron-hole pair separation and prolonging their recombination rate. The process was further optimized in terms of reagents concentrations including Fe(2+)/TiO2 and Ag/TiO2 molar ratios using central composite design in order to achieve the best self-cleaning property of the treated fabric. The magnetic measurements indicated the super-paramagnetic behavior of the treated fabric with saturation magnetization of 4.5 (emu/g). Findings suggest the potential of the proposed facial method in producing an intelligent fabric with durable multi-functional activities that can be suitable for various applications including medical, military, bio-separation, bio-sensors, magneto graphic printing, magnetic screens and magnetic filters.

  5. Step Prototype Development Status

    NASA Astrophysics Data System (ADS)

    Mehls, C.; Bayart, C.; Bower, J.; Clarke, B.; Cox, C.; Gill, D.; Stricker, D.; Vora, N.; Wang, S.; Zhou, P.; Torii, R.; Worden, P.; Debra, D.; Dittus, H.; Loeffler, F.

    2008-09-01

    STEP, the Satellite Test of the Equivalence Principle [1], proposes to test the Equivalence Principle to a part in 1018 by comparing the free-fall acceleration of cylindrical shaped test masses [2] in Earth orbit. Magnetic bearings constrain the test mass motion to their axis of symmetry [3]. The displacement of the test masses is measured using a DC SQUID and superconducting coils [4], enabling a displacement sensitivity as small as 10-15 m. In combination with a small spring stiffness a differential acceleration sensitivity of 10-18 g is achievable. Residual satellite acceleration is reduced to better than 10-14 g by compensating satellite drag forces with thrust provided by helium gas. We report on recent progress in the development of STEP prototype flight accelerometers, in particular the development of the high precision quartz housing for the engineering inner accelerometer and the testing of SQUID and capacitive readout systems using 'brass board' accelerometer prototypes.

  6. The digital step edge

    NASA Technical Reports Server (NTRS)

    Haralick, R. M.

    1982-01-01

    The facet model was used to accomplish step edge detection. The essence of the facet model is that any analysis made on the basis of the pixel values in some neighborhood has its final authoritative interpretation relative to the underlying grey tone intensity surface of which the neighborhood pixel values are observed noisy samples. Pixels which are part of regions have simple grey tone intensity surfaces over their areas. Pixels which have an edge in them have complex grey tone intensity surfaces over their areas. Specially, an edge moves through a pixel only if there is some point in the pixel's area having a zero crossing of the second directional derivative taken in the direction of a non-zero gradient at the pixel's center. To determine whether or not a pixel should be marked as a step edge pixel, its underlying grey tone intensity surface was estimated on the basis of the pixels in its neighborhood.

  7. Micromachine Wedge Stepping Motor

    SciTech Connect

    Allen, J.J.; Schriner, H.K.

    1998-11-04

    A wedge stepping motor, which will index a mechanism, has been designed and fabricated in the surface rnicromachine SUMMiT process. This device has demonstrated the ability to index one gear tooth at a time with speeds up to 205 teeth/see. The wedge stepper motor has the following features, whi:h will be useful in a number of applications. o The ability to precisely position mechanical components. . Simple pulse signals can be used for operation. o Only 2 drive signals are requixed for operation. o Torque and precision capabilities increase with device size . The device to be indexed is restrained at all times by the wedge shaped tooth that is used for actuation. This paper will discuss the theory of operation and desi=m of the wedge stepping motor. The fabrication and testing of I he device will also be presented.

  8. One-step hydrothermal synthesis of N-doped TiO2/C nanocomposites with high visible light photocatalytic activity.

    PubMed

    Wang, Dong-Hong; Jia, Li; Wu, Xi-Lin; Lu, Li-Qiang; Xu, An-Wu

    2012-01-21

    N-doped TiO(2) nanoparticles modified with carbon (denoted N-TiO(2)/C) were successfully prepared by a facile one-pot hydrothermal treatment in the presence of L-lysine, which acts as a ligand to control the nanocrystal growth and as a source of nitrogen and carbon. As-prepared nanocomposites were characterized by thermogravimetric analysis (TGA), X-ray diffraction (XRD), transmission electron microscopy (TEM), high-resolution transmission electron microscopy (HRTEM), Raman spectroscopy, ultraviolet-visible (UV-vis) diffuse reflectance spectroscopy, X-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), electron paramagnetic resonance (EPR) spectra, and N(2) adsorption-desorption analysis. The photocatalytic activities of the as-prepared photocatalysts were measured by the degradation of methyl orange (MO) under visible light irradiation at λ≥ 400 nm. The results show that N-TiO(2)/C nanocomposites increase absorption in the visible light region and exhibit a higher photocatalytic activity than pure TiO(2), commercial P25 and previously reported N-doped TiO(2) photocatalysts. We have demonstrated that the nitrogen was doped into the lattice and the carbon species were modified on the surface of the photocatalysts. N-doping narrows the band gap and C-modification enhances the visible light harvesting and accelerates the separation of the photo-generated electrons and holes. As a consequence, the photocatalytic activity is significantly improved. The molar ratio of L-lysine/TiCl(4) and the pH of the hydrothermal reaction solution are important factors affecting the photocatalytic activity of the N-TiO(2)/C; the optimum molar ratio of L-lysine/TiCl(4) is 8 and the optimum pH is ca. 4, at which the catalyst exhibits the highest reactivity. Our findings demonstrate that the as-obtained N-TiO(2)/C photocatalyst is a better and more promising candidate than well studied N-doped TiO(2) alternatives as visible light photocatalysts for

  9. Facile One-Step Synthesis of Three-Dimensional Pd-Ag Bimetallic Alloy Networks and Their Electrocatalytic Activity toward Ethanol Oxidation.

    PubMed

    Fu, Shaofang; Zhu, Chengzhou; Du, Dan; Lin, Yuehe

    2015-07-01

    The three-dimensional palladium networks and palladium-silver bimetallic alloy networks were synthesized at room temperature on a large scale using a rapid and simple strategy. The results revealed that the morphology of the networks is not affected by the composition. We demonstrated that the as-prepared unsupported networks exhibited excellent electrochemical activity and stability toward ethanol oxidation reaction in alkaline media due to the formation of palladium-silver alloys as well as the porous nanostructures. The results indicate that the well-defined three-dimensional palladium-silver bimetallic alloy networks are promising catalysts for fuel cells.

  10. Steps toward determination of the size and structure of the broad-line region in active galactic nuclei. 6: Variability of NGC 3783 from ground-based data

    NASA Technical Reports Server (NTRS)

    Stirpe, G. M.; Winge, C.; Altieri, B.; Alloin, D.; Aguero, E. L.; Anupama, G. C.; Ashley, R.; Bertram, R.; Calderon, J. H.; Catchpole, R. M.

    1994-01-01

    The Seyfert 1 galaxy NGC 3783 was intensely monitored in several bands between 1991 December and 1992 August. This paper presents the results from the ground-based observations in the optical and near-IR bands, which complement the data set formed by the International Ultraviolet Explorer (IUE) spectra, discussed elsewhere. Spectroscopic and photometric data from several observatories were combined in order to obtain well-sampled light curves of the continuum and of H(beta). During the campaign the source underwent significant variability. The light curves of the optical continuum and of H(beta) display strong similarities to those obtained with the IUE. The near-IR flux did not vary significantly except for a slight increase at the end of the campaign. The cross-correlation analysis shows that the variations of the optical continuum have a lag of 1 day or less with respect to those of the UV continuum, with an uncertainty of is less than or equal to 4 days. The integrated flux of H(beta) varies with a delay of about 8 days. These results confirm that (1) the continuum variations occur simultaneously or with a very small lag across the entire UV-optical range, as in the Seyfert galaxy NGC 5548; and (2) the emission lines of NGC 3783 respond to ionizing continuum variations with less delay than those of NGC 5548. As observed in NGC 5548, the lag of H(beta) with respect to the continuum is greater than those of the high-ionization lines.

  11. Allergies and Asthma: They Often Occur Together

    MedlinePlus

    ... occur together. The same substances that trigger your hay fever symptoms, such as pollen, dust mites and pet ... a major risk factor for allergic asthma. Having hay fever or other allergies yourself also increases your risk ...

  12. Naturally Occurring Radon and 120(h) transfers

    EPA Pesticide Factsheets

    This page contains a discussion regarding how the presence of naturally occurring radon on closing military bases affects the United States' ability to transfer parcels under §120(h) (3) and §120(h) (4).

  13. N-doped P25 TiO2-amorphous Al2O3 composites: one-step solution combustion preparation and enhanced visible-light photocatalytic activity.

    PubMed

    Li, Fa-tang; Zhao, Ye; Hao, Ying-juan; Wang, Xiao-jing; Liu, Rui-hong; Zhao, Di-shun; Chen, Dai-mei

    2012-11-15

    Nitrogen-doped Degussa P25 TiO2-amorphous Al2O3 composites were prepared via facile solution combustion. The composites were characterised using X-ray diffraction, high-resolution transmission microscopy, scanning electron microscopy, nitrogen adsorption-desorption measurements, X-ray photoelectron spectroscopy, UV-vis light-diffusion reflectance spectrometry (DRS), zeta-potential measurements, and photoluminescence spectroscopy. The DRS results showed that TiO2 and amorphous Al2O3 exhibited absorption in the UV region. However, the Al2O3/TiO2 composite exhibited visible-light absorption, which was attributed to N-doping during high-temperature combustion and to alterations in the electronic structure of Ti species induced by the addition of Al. The optimal molar ratio of TiO2 to Al2O3 was 1.5:1, and this composite exhibited a large specific surface area of 152 m2/g, surface positive charges, and enhanced photocatalytic activity. These characteristics enhanced the degradation rate of anionic methylene orange, which was 43.6 times greater than that of pure P25 TiO2. The high visible-light photocatalytic activity was attributed to synthetic effects between amorphous Al2O3 and TiO2, low recombination efficiency of photo-excited electrons and holes, N-doping, and a large specific surface area. Experiments that involved radical scavengers indicated that OH and O2- were the main reactive species. A potential photocatalytic mechanism was also proposed.

  14. Trichotillomania and Co-occurring Anxiety

    PubMed Central

    Grant, Jon E.; Redden, Sarah A.; Leppink, Eric W.; Chamberlain, Samuel R.

    2017-01-01

    Background Trichotillomania appears to be a fairly common disorder, with high rates of co-occurring anxiety disorders. Many individuals with trichotillomania also report that pulling worsens during periods of increased anxiety. Even with these clinical links to anxiety, little research has explored whether trichotillomania with co-occurring anxiety is a meaningful subtype. Methods 165 adults with trichotillomania were examined on a variety of clinical measures including symptom severity, functioning, and comorbidity. Participants also underwent cognitive testing assessing motor inhibition and cognitive flexibility. Clinical features and cognitive functioning were compared between those with current co-occurring anxiety disorders (i.e. social anxiety, generalized anxiety disorder, panic disorder, and anxiety disorder NOS) (n=38) and those with no anxiety disorder (n=127). Results Participants with trichotillomania and co-occurring anxiety reported significantly worse hair pulling symptoms, were more likely to have co-occurring depression, and were more likely to have a first-degree relative with obsessive compulsive disorder. Those with anxiety disorders also exhibited significantly worse motor inhibitory performance on a task of motor inhibition (stop-signal task). Conclusions This study suggests that anxiety disorders affect the clinical presentation of hair pulling behavior. Further research is needed to validate our findings and to consider whether treatments should be specially tailored differently for adults with trichotillomania who have co-occurring anxiety disorders, or more pronounced cognitive impairment. PMID:27668531

  15. Step proof mass dynamics

    NASA Astrophysics Data System (ADS)

    Wiegand, M.; Scheithauer, S.; Theil, S.

    2004-05-01

    The Satellite Test of Equivalence Principle (STEP) is a joint European-US project to investigate one of the most fundamental principles in physics, the Equivalence of inertia and passive gravitational mass. As STEP matures into a flight program, the development of a precise spacecraft dynamics simulator becomes crucial. The simulator is primarily needed for design, test and verification of the drag-free control (DFC) system and the flight software. The drag-free concept involves centering the proof mass located inside a satellite. As the proof mass is free of external disturbances (drag free), it follows a purely gravitational orbit. Since the satellite is forced to follow the proof mass, it too follows the same gravitational orbit, canceling all non-gravitational forces. For the STEP Mission, the DFC system is required to attenuate any disturbance forces acting on the spacecraft to achieve residual acceleration at location of the accelerometer of less than 3×10 -14 m/s2 (rms) across the measurement bandwidth. While the simulator is based on a high-fidelity six-degree-of-freedom numerical simulation, a simplified model is used to analyze the proof mass dynamics. The stability analysis of the proof mass motion is performed by transformation of the simplified model into the standard form of the Mathieu differential equation. The stability regions of the solution are applied to choose proper values for parameters like coupling forces between satellite and proof mass as a function of spacecraft rotation. The paper describes the calculation of the spacecraft/payload dynamics and the assumptions used to derive the underlying algorithms with a special emphasis on numerical precision issues.

  16. Renal Failure Affects the Enzymatic Activities of the Three First Steps in Hepatic Heme Biosynthesis in the Acute Intermittent Porphyria Mouse

    PubMed Central

    Unzu, Carmen; Sampedro, Ana; Sardh, Eliane; Mauleón, Itsaso; Enríquez de Salamanca, Rafael; Prieto, Jesús

    2012-01-01

    Chronic kidney disease is a long-term complication in acute intermittent porphyria (AIP). The pathophysiological significance of hepatic overproduction of the porphyrin precursors aminolevulinate acid (ALA) and porphobilinogen (PBG) in chronic kidney disease is unclear. We have investigated the effect of repetitive acute attacks on renal function and the effect of total or five-sixth nephrectomy causing renal insufficiency on hepatic heme synthesis in the porphobilinogen deaminase (PBGD)-deficient (AIP) mouse. Phenobarbital challenge in the AIP-mice increased urinary porphyrin precursor excretion. Successive attacks throughout 14 weeks led to minor renal lesions with no impact on renal function. In the liver of wild type and AIP mice, 5/6 nephrectomy enhanced transcription of the first and rate-limiting ALA synthase. As a consequence, urinary PBG excretion increased in AIP mice. The PBG/ALA ratio increased from 1 in sham operated AIP animals to over 5 (males) and over 13 (females) in the 5/6 nephrectomized mice. Total nephrectomy caused a rapid decrease in PBGD activity without changes in enzyme protein level in the AIP mice but not in the wild type animals. In conclusion, high concentration of porphyrin precursors had little impact on renal function. However, progressive renal insufficiency aggravates porphyria attacks and increases the PBG/ALA ratio, which should be considered a warning sign for potentially life-threatening impairment in AIP patients with signs of renal failure. PMID:22412963

  17. Dynamic modelling of solids in a full-scale activated sludge plant preceded by CEPT as a preliminary step for micropollutant removal modelling.

    PubMed

    Baalbaki, Zeina; Torfs, Elena; Maere, Thomas; Yargeau, Viviane; Vanrolleghem, Peter A

    2016-12-24

    The presence of micropollutants in the environment has triggered research on quantifying and predicting their fate in wastewater treatment plants (WWTPs). Since the removal of micropollutants is highly related to conventional pollutant removal and affected by hydraulics, aeration, biomass composition and solids concentration, the fate of these conventional pollutants and characteristics must be well predicted before tackling models to predict the fate of micropollutants. In light of this, the current paper presents the dynamic modelling of conventional pollutants undergoing activated sludge treatment using a limited set of additional daily composite data besides the routine data collected at a WWTP over one year. Results showed that as a basis for modelling, the removal of micropollutants, the Bürger-Diehl settler model was found to capture the actual effluent total suspended solids (TSS) concentrations more efficiently than the Takács model by explicitly modelling the overflow boundary. Results also demonstrated that particular attention must be given to characterizing incoming TSS to obtain a representative solids balance in the presence of a chemically enhanced primary treatment, which is key to predict the fate of micropollutants.

  18. New photolithography stepping machine

    SciTech Connect

    Hale, L.; Klingmann, J.; Markle, D.

    1995-03-08

    A joint development project to design a new photolithography steeping machine capable of 150 nanometer overlay accuracy was completed by Ultratech Stepper and the Lawrence Livermore National Laboratory. The principal result of the project is a next-generation product that will strengthen the US position in step-and-repeat photolithography. The significant challenges addressed and solved in the project are the subject of this report. Design methods and new devices that have broader application to precision machine design are presented in greater detail while project specific information serves primarily as background and motivation.

  19. Steps to the moon

    USGS Publications Warehouse

    ,; Dale, Alvin E.

    1976-01-01

    On July 20, 1969, man walked on the surface of the Moon and began a new chapter of his studies that will eventually disclose the geologic nature of the Earth's nearest neighbor. Although he has finally reached the Moon and sampled its substance, much work and study remain before he will know the full scientific significance of the first landing. This booklet briefly summarizes the steps man has taken to understand the Moon and what he thinks he has learned to date as a result of his centuries-long speculations and studies.

  20. A Reconfigurable Stepping Motor

    NASA Astrophysics Data System (ADS)

    Rogers, Charles; Selvaggi, Richard

    2009-04-01

    Multiphase brushless actuators, commonly known as the stepper motors, are ubiquitous for many precision control applications. Developments in the microelectronics have lead to their use as efficient drive motors for modern electric vehicles. Understanding the physics and the control logic for interfacing these transducers continues to be important for scientists and engineers. An overview of the stepping motor principles and interfacing requirements is presented and a simple working model used to teach the concepts of stepper motors is described and demonstrated. This model was used to design a much larger stepper motor required to precisely rotate a massive optical system in the undergraduate advanced physics laboratory.

  1. A step toward the development of high-temperature stable ionic liquid-in-oil microemulsions containing double-chain anionic surface active ionic liquid.

    PubMed

    Rao, Vishal Govind; Banerjee, Chiranjib; Ghosh, Surajit; Mandal, Sarthak; Kuchlyan, Jagannath; Sarkar, Nilmoni

    2013-06-20

    Owing to their fascinating properties and wide range of potential applications, interest in nonaqueous microemulsions has escalated in the past decade. In the recent past, nonaqueous microemulsions containing ionic liquids (ILs) have been utilized in performing chemical reactions, preparation of nanomaterials, synthesis of nanostructured polymers, and drug delivery systems. The most promising fact about IL-in-oil microemulsions is their high thermal stability compared to that of aqueous microemulsions. Recently, surfactant-like properties of surface active ionic liquids (SAILs) have been used for preparation of microemulsions with high-temperature stability and temperature insensitivity. However, previously described methods present a limited possibility of developing IL-in-oil microemulsions with a wide range of thermal stability. With our previous work, we introduced a novel method of creating a huge number of IL-in-oil microemulsions (Rao, V. G.; Ghosh, S.; Ghatak, C.; Mandal, S.; Brahmachari, U.; Sarkar, N. J. Phys. Chem. B2012, 116, 2850-2855), composed of a SAIL as a surfactant, room-temperature ionic liquids as a polar phase, and benzene as a nonpolar phase. The use of benzene as a nonpolar solvent limits the application of the microemulsions to temperatures below 353 K. To overcome this limitation, we have synthesized N,N-dimethylethanolammonium 1,4-bis(2-ethylhexyl) sulfosuccinate (DAAOT), which was used as a surfactant. DAAOT in combination with isopropyl myristate (IPM, as an oil phase) and ILs (as a polar phase) produces a huge number of high-temperature stable IL-in-oil microemulsions. By far, this is the first report of a huge number of high-temperature stable IL-in-oil microemulsions. In particular, we demonstrate the wide range of thermal stability of [C6mim][TF2N]/DAAOT/IPM microemulsions by performing a phase behavior study, dynamic light scattering measurements, and (1)H NMR measurements and by using coumarin-480 (C-480) as a fluorescent probe

  2. ACSM Fitness Book: A Proven Step-By-Step Program from the Experts. Third Edition.

    ERIC Educational Resources Information Center

    American Coll. of Sports Medicine, Indianapolis, IN.

    This offers advice on the health benefits of regular physical activity. It includes a scientifically proven fitness test to determine one's starting point and monitor ongoing progress, offering step-by-step instructions, sample programs, and insights on nutrition, weight control, motivation, and overcoming setbacks. Seven chapters examine: (1)…

  3. A step-defined sedentary lifestyle index: <5000 steps/day.

    PubMed

    Tudor-Locke, Catrine; Craig, Cora L; Thyfault, John P; Spence, John C

    2013-02-01

    Step counting (using pedometers or accelerometers) is widely accepted by researchers, practitioners, and the general public. Given the mounting evidence of the link between low steps/day and time spent in sedentary behaviours, how few steps/day some populations actually perform, and the growing interest in the potentially deleterious effects of excessive sedentary behaviours on health, an emerging question is "How many steps/day are too few?" This review examines the utility, appropriateness, and limitations of using a reoccurring candidate for a step-defined sedentary lifestyle index: <5000 steps/day. Adults taking <5000 steps/day are more likely to have a lower household income and be female, older, of African-American vs. European-American heritage, a current vs. never smoker, and (or) living with chronic disease and (or) disability. Little is known about how contextual factors (e.g., built environment) foster such low levels of step-defined physical activity. Unfavorable indicators of body composition and cardiometabolic risk have been consistently associated with taking <5000 steps/day. The acute transition (3-14 days) of healthy active young people from higher (>10 000) to lower (<5000 or as low as 1500) daily step counts induces reduced insulin sensitivity and glycemic control, increased adiposity, and other negative changes in health parameters. Although few alternative values have been considered, the continued use of <5000 steps/day as a step-defined sedentary lifestyle index for adults is appropriate for researchers and practitioners and for communicating with the general public. There is little evidence to advocate any specific value indicative of a step-defined sedentary lifestyle index in children and adolescents.

  4. Steps toward Determination of the Size and Structure of the Broad-Line Region in Active Galactic Nuclei. IX. Ultraviolet Observations of Fairall 9

    NASA Astrophysics Data System (ADS)

    Rodríguez-Pascual, P. M.; Alloin, D.; Clavel, J.; Crenshaw, D. M.; Horne, K.; Kriss, G. A.; Krolik, J. H.; Malkan, M. A.; Netzer, H.; O'Brien, P. T.; Peterson, B. M.; Reichert, G. A.; Wamsteker, W.; Alexander, T.; Barr, P.; Blandford, R. D.; Bregman, J. N.; Carone, T. E.; Clements, S.; Courvoisier, T.-J.; Robertis, M. M. De; Dietrich, M.; Dottori, H.; Edelson, R. A.; Filippenko, A. V.; Gaskell, C. M.; Huchra, J. P.; Hutchings, J. B.; Kollatschny, W.; Koratkar, A. P.; Korista, K. T.; Laor, A.; MacAlpine, G. M.; Martin, P. G.; Maoz, D.; McCollum, B.; Morris, S. L.; Perola, G. C.; Pogge, R. W.; Ptak, R. L.; Recondo-González, M. C.; J. M. Rodríguez-Espinoza; Rokaki, E. L.; Santos-Lleó, M.; Sekiguchi, K.; Shull, J. M.; Snijders, M. A. J.; Sparke, L. S.; Stirpe, G. M.; Stoner, R. E.; Sun, W.-H.; Wagner, S. J.; Wanders, I.; Wilkes, J.; Winge, C.; Zheng, W.

    1997-05-01

    An 8 month monitoring campaign on the Seyfert 1 galaxy Fairall 9 has been conducted with the International Ultraviolet Explorer in an attempt to obtain reliable estimates of continuum-continuum and continuum-emission-line delays for a high-luminosity active galactic nucleus (AGN). While the results of this campaign are more ambiguous than those of previous monitoring campaigns on lower luminosity sources, we find general agreement with the earlier results: (1) there is no measurable lag between ultraviolet continuum bands, and (2) the measured emission-line time lags are very short. It is especially notable that the Lyα + N V emission-line lag is about 1 order of magnitude smaller than determined from a previous campaign by Clavel, Wamsteker, & Glass (1989) when Fairall 9 was in a more luminous state. In other well-monitored sources, specifically NGC 5548 and NGC 3783, the highest ionization lines are found to respond to continuum variations more rapidly than the lower ionization lines, which suggests a radially ionization-stratified broad-line region. In this case, the results are less certain, since none of the emission-line lags are very well determined. The best-determined emission line lag is Lyα + N V, for which we find that the centroid of the continuum-emission-line cross-correlation function is τcent ~ 14-20 days. We measure a lag τcent <~ 4 days for He II λ1640 this result is consistent with the ionization-stratification pattern seen in lower luminosity sources, but the relatively large uncertainties in the emission-line lags measured here cannot rule out similar lags for Lyα + N V and He II λ1640 at a high level of significance. We are unable to determine a reliable lag for C IV λ1550, but we note that the profiles of the variable parts of Lyα and C IV λ1550 are not the same, which does not support the hypothesis that the strongest variations in these two lines arise in the same region.

  5. SPAR-H Step-by-Step Guidance

    SciTech Connect

    W. J. Galyean; A. M. Whaley; D. L. Kelly; R. L. Boring

    2011-05-01

    This guide provides step-by-step guidance on the use of the SPAR-H method for quantifying Human Failure Events (HFEs). This guide is intended to be used with the worksheets provided in: 'The SPAR-H Human Reliability Analysis Method,' NUREG/CR-6883, dated August 2005. Each step in the process of producing a Human Error Probability (HEP) is discussed. These steps are: Step-1, Categorizing the HFE as Diagnosis and/or Action; Step-2, Rate the Performance Shaping Factors; Step-3, Calculate PSF-Modified HEP; Step-4, Accounting for Dependence, and; Step-5, Minimum Value Cutoff. The discussions on dependence are extensive and include an appendix that describes insights obtained from the psychology literature.

  6. Genetic demixing and evolution in linear stepping stone models

    PubMed Central

    Korolev, K. S.; Avlund, Mikkel; Hallatschek, Oskar; Nelson, David R.

    2010-01-01

    Results for mutation, selection, genetic drift, and migration in a one-dimensional continuous population are reviewed and extended. The population is described by a continuous limit of the stepping stone model, which leads to the stochastic Fisher-Kolmogorov-Petrovsky-Piscounov equation with additional terms describing mutations. Although the stepping stone model was first proposed for population genetics, it is closely related to “voter models” of interest in nonequilibrium statistical mechanics. The stepping stone model can also be regarded as an approximation to the dynamics of a thin layer of actively growing pioneers at the frontier of a colony of micro-organisms undergoing a range expansion on a Petri dish. The population tends to segregate into monoallelic domains. This segregation slows down genetic drift and selection because these two evolutionary forces can only act at the boundaries between the domains; the effects of mutation, however, are not significantly affected by the segregation. Although fixation in the neutral well-mixed (or “zero-dimensional”) model occurs exponentially in time, it occurs only algebraically fast in the one-dimensional model. An unusual sublinear increase is also found in the variance of the spatially averaged allele frequency with time. If selection is weak, selective sweeps occur exponentially fast in both well-mixed and one-dimensional populations, but the time constants are different. The relatively unexplored problem of evolutionary dynamics at the edge of an expanding circular colony is studied as well. Also reviewed are how the observed patterns of genetic diversity can be used for statistical inference and the differences are highlighted between the well-mixed and one-dimensional models. Although the focus is on two alleles or variants, q-allele Potts-like models of gene segregation are considered as well. Most of the analytical results are checked with simulations and could be tested against recent spatial

  7. Genetic demixing and evolution in linear stepping stone models

    NASA Astrophysics Data System (ADS)

    Korolev, K. S.; Avlund, Mikkel; Hallatschek, Oskar; Nelson, David R.

    2010-04-01

    Results for mutation, selection, genetic drift, and migration in a one-dimensional continuous population are reviewed and extended. The population is described by a continuous limit of the stepping stone model, which leads to the stochastic Fisher-Kolmogorov-Petrovsky-Piscounov equation with additional terms describing mutations. Although the stepping stone model was first proposed for population genetics, it is closely related to “voter models” of interest in nonequilibrium statistical mechanics. The stepping stone model can also be regarded as an approximation to the dynamics of a thin layer of actively growing pioneers at the frontier of a colony of micro-organisms undergoing a range expansion on a Petri dish. The population tends to segregate into monoallelic domains. This segregation slows down genetic drift and selection because these two evolutionary forces can only act at the boundaries between the domains; the effects of mutation, however, are not significantly affected by the segregation. Although fixation in the neutral well-mixed (or “zero-dimensional”) model occurs exponentially in time, it occurs only algebraically fast in the one-dimensional model. An unusual sublinear increase is also found in the variance of the spatially averaged allele frequency with time. If selection is weak, selective sweeps occur exponentially fast in both well-mixed and one-dimensional populations, but the time constants are different. The relatively unexplored problem of evolutionary dynamics at the edge of an expanding circular colony is studied as well. Also reviewed are how the observed patterns of genetic diversity can be used for statistical inference and the differences are highlighted between the well-mixed and one-dimensional models. Although the focus is on two alleles or variants, q -allele Potts-like models of gene segregation are considered as well. Most of the analytical results are checked with simulations and could be tested against recent spatial

  8. Specificity of a Maximal Step Exercise Test

    ERIC Educational Resources Information Center

    Darby, Lynn A.; Marsh, Jennifer L.; Shewokis, Patricia A.; Pohlman, Roberta L.

    2007-01-01

    To adhere to the principle of "exercise specificity" exercise testing should be completed using the same physical activity that is performed during exercise training. The present study was designed to assess whether aerobic step exercisers have a greater maximal oxygen consumption (max VO sub 2) when tested using an activity specific, maximal step…

  9. Ligand-bound structures of 3-deoxy-D-manno-octulosonate 8-phosphate phosphatase from Moraxella catarrhalis reveal a water channel connecting to the active site for the second step of catalysis.

    PubMed

    Dhindwal, Sonali; Priyadarshini, Priyanka; Patil, Dipak N; Tapas, Satya; Kumar, Pramod; Tomar, Shailly; Kumar, Pravindra

    2015-02-01

    KdsC, the third enzyme of the 3-deoxy-D-manno-octulosonic acid (KDO) biosynthetic pathway, catalyzes a substrate-specific reaction to hydrolyze 3-deoxy-D-manno-octulosonate 8-phosphate to generate a molecule of KDO and phosphate. KdsC is a phosphatase that belongs to the C0 subfamily of the HAD superfamily. To understand the molecular basis for the substrate specificity of this tetrameric enzyme, the crystal structures of KdsC from Moraxella catarrhalis (Mc-KdsC) with several combinations of ligands, namely metal ion, citrate and products, were determined. Various transition states of the enzyme have been captured in these crystal forms. The ligand-free and ligand-bound crystal forms reveal that the binding of ligands does not cause any specific conformational changes in the active site. However, the electron-density maps clearly showed that the conformation of KDO as a substrate is different from the conformation adopted by KDO when it binds as a cleaved product. Furthermore, structural evidence for the existence of an intersubunit tunnel has been reported for the first time in the C0 subfamily of enzymes. A role for this tunnel in transferring water molecules from the interior of the tetrameric structure to the active-site cleft has been proposed. At the active site, water molecules are required for the formation of a water bridge that participates as a proton shuttle during the second step of the two-step phosphoryl-transfer reaction. In addition, as the KDO biosynthesis pathway is a potential antibacterial target, pharmacophore-based virtual screening was employed to identify inhibitor molecules for the Mc-KdsC enzyme.

  10. A three step supercritical process to improve the dissolution rate of eflucimibe.

    PubMed

    Rodier, Elisabeth; Lochard, Hubert; Sauceau, Martial; Letourneau, Jean-Jacques; Freiss, Bernard; Fages, Jacques

    2005-10-01

    The aim of this study is to improve the dissolution properties of a poorly-soluble active substance, Eflucimibe by associating it with gamma-cyclodextrin. To achieve this objective, a new three-step process based on supercritical fluid technology has been proposed. First, Eflucimibe and cyclodextrin are co-crystallized using an anti-solvent process, dimethylsulfoxide being the solvent and supercritical carbon dioxide being the anti-solvent. Second, the co-crystallized powder is held in a static mode under supercritical conditions for several hours. This is the maturing step. Third, in a final stripping step, supercritical CO(2) is flowed through the matured powder to extract the residual solvent. The coupling of the first two steps brings about a significant synergistic effect to improve the dissolution rate of the drug. The nature of the entity obtained at the end of each step is discussed and some suggestions are made as to what happens in these operations. It is shown the co-crystallization ensures a good dispersion of both compounds and is rather insensitive to the operating parameters tested. The maturing step allows some dissolution-recrystallization to occur thus intensifying the intimate contact between the two compounds. Addition of water is necessary to make maturing effective as this is governed by the transfer properties of the medium. The stripping step allows extraction of the residual solvent but also removes some of the Eflucimibe which is the main drawback of this final stage.

  11. Young Children's Reports of when Learning Occurred

    ERIC Educational Resources Information Center

    Tang, Connie M.; Bartsch, Karen; Nunez, Narina

    2007-01-01

    This study investigated young children's reports of when learning occurred. A total of 96 4-, 5-, and 6-year-olds were recruited from suburban preschools and elementary schools. The children learned an animal fact and a body movement. A week later, children learned another animal fact and another body movement and then answered questions about…

  12. Necrobiotic xanthogranuloma occurring in an eyelid scar.

    PubMed

    Rayner, S A; Duncombe, A S; Keefe, M; Theaker, J; Manners, R M

    2008-01-01

    We present a case report of necrobiotic xanthogranuloma (NXG) in a 76-year-old Caucasian lady occurring as a nodule in a blepharoplasty scar. NXG is a rare histiocytic disease with progressive orbital and systemic features. Management options of excision biopsy or chemotherapy are discussed.

  13. Short and long access to cocaine self-administration activates tyrosine phosphatase STEP and attenuates GluN expression but differentially regulates GluA expression in the prefrontal cortex