The potentially beneficial central nervous system activity profile of ivacaftor and its metabolites.

PubMed

Schneider, Elena K; McQuade, Rachel M; Carbone, Vincenzo C; Reyes-Ortega, Felisa; Wilson, John W; Button, Brenda; Saito, Ayame; Poole, Daniel P; Hoyer, Daniel; Li, Jian; Velkov, Tony

2018-01-01

Ivacaftor-lumacaftor and ivacaftor are two new breakthrough cystic fibrosis transmembrane conductance modulators. The interactions of ivacaftor and its two metabolites hydroxymethylivacaftor (iva-M1) and ivacaftorcarboxylate (iva-M6) with neurotransmitter receptors were investigated in radioligand binding assays. Ivacaftor displayed significant affinity to the 5-hydroxytryptamine (5-HT; serotonin) 5-HT 2C receptor (p K i =6.06±0.03), β 3 -adrenergic receptor (p K i =5.71±0.07), δ-opioid receptor (p K i =5.59±0.06) and the dopamine transporter (p K i =5.50±0.20); iva-M1 displayed significant affinity to the 5-HT 2C receptor (p K i =5.81±0.04) and the muscarinic M3 receptor (p K i =5.70±0.10); iva-M6 displayed significant affinity to the 5-HT 2A receptor (p K i =7.33±0.05). The in vivo central nervous system activity of ivacaftor (40 mg·kg -1 intraperitoneally for 21 days) was assessed in a chronic mouse model of depression. In the forced swim test, the ivacaftor-treated group displayed decreased immobility (52.8±7.6 s), similarly to fluoxetine (33.8±11.0 s), and increased climbing/swimming activity (181.5±9.2 s). In the open field test, ivacaftor produced higher locomotor activity than the fluoxetine group, measured both as mean number of paw touches (ivacaftor 81.1±9.6 versus fluoxetine 57.9±9.5) and total distance travelled (ivacaftor 120.6±16.8 cm versus fluoxetine 84.5±16.0 cm) in 600 s. Treatment of 23 cystic fibrosis patients with ivacaftor-lumacaftor resulted in significant improvements in quality of life (including anxiety) in all five domains of the AweScoreCF questionnaire (p=0.092-0.096). Our findings suggest ivacaftor displays potential clinical anxiolytic and stimulating properties, and may have beneficial effects on mood.

High Resolution Displays Using NCAP Liquid Crystals

NASA Astrophysics Data System (ADS)

Macknick, A. Brian; Jones, Phil; White, Larry

1989-07-01

Nematic curvilinear aligned phase (NCAP) liquid crystals have been found useful for high information content video displays. NCAP materials are liquid crystals which have been encapsulated in a polymer matrix and which have a light transmission which is variable with applied electric fields. Because NCAP materials do not require polarizers, their on-state transmission is substantially better than twisted nematic cells. All dimensional tolerances are locked in during the encapsulation process and hence there are no critical sealing or spacing issues. By controlling the polymer/liquid crystal morphology, switching speeds of NCAP materials have been significantly improved over twisted nematic systems. Recent work has combined active matrix addressing with NCAP materials. Active matrices, such as thin film transistors, have given displays of high resolution. The paper will discuss the advantages of NCAP materials specifically designed for operation at video rates on transistor arrays; applications for both backlit and projection displays will be discussed.

Catch the wave: prairie dogs assess neighbours’ awareness using contagious displays

PubMed Central

Hare, James F.; Campbell, Kevin L.; Senkiw, Robert W.

2014-01-01

The jump–yip display of black-tailed prairie dogs (Cynomys ludovicianus) is contagious, spreading through a prairie dog town as ‘the wave’ through a stadium. Because contagious communication in primates serves to assess conspecific social awareness, we investigated whether instigators of jump–yip bouts adjusted their behaviour relative to the response of conspecifics recruited to display bouts. Increased responsiveness of neighbouring town members resulted in bout initiators devoting a significantly greater proportion of time to active foraging. Contagious jump–yips thus function to assess neighbours’ alertness, soliciting social information to assess effective conspecific group size in real time and reveal active probing of conspecific awareness consistent with theory of mind in these group-living rodents. PMID:24403324

Improved bread-baking process using Saccharomyces cerevisiae displayed with engineered cyclodextrin glucanotransferase.

PubMed

Shim, Jae-Hoon; Seo, Nam-Seok; Roh, Sun-Ah; Kim, Jung-Wan; Cha, Hyunju; Park, Kwan-Hwa

2007-06-13

A bread-baking process was developed using a potential novel enzyme, cyclodextrin glucanotransferase[3-18] (CGTase[3-18]), that had previously been engineered to have enhanced hydrolyzing activity with little cyclodextrin (CD) formation activity toward starch. CGTase[3-18] was primarily manipulated to be displayed on the cell surface of Saccharomyces cerevisiae. S. cerevisiae carrying pdeltaCGT integrated into the chromosome exhibited starch-hydrolyzing activity at the same optimal pH and temperature as the free enzyme. Volumes of the bread loaves and rice cakes prepared using S. cerevisiae/pdeltaCGT increased by 20% and 45%, respectively, with no detectable CD. Retrogradation rates of the bread and rice cakes decreased significantly during storage. In comparison to the wild type, S. cerevisiae/pdeltaCGT showed improved viability during four freeze-thaw cycles. The results indicated that CGTase[3-18] displayed on the surface of yeast hydrolyzed starch to glucose and maltose that can be used more efficiently for yeast fermentation. Therefore, display of an antistaling enzyme on the cell surface of yeast has potential for enhancing the baking process.

Antioxidant and anti-inflammatory caffeoyl phenylpropanoid and secoiridoid glycosides from Jasminum nervosum stems, a Chinese folk medicine.

PubMed

Guo, Zhi-Yong; Li, Ping; Huang, Wen; Wang, Jian-Jun; Liu, Yu-Jing; Liu, Bo; Wang, Ye-Ling; Wu, Shi-Biao; Kennelly, Edward J; Long, Chun-Lin

2014-10-01

Eight compounds including four caffeoyl phenylpropanoid glycosides, jasnervosides A-D (1-4), one monoterpenoid glycoside, jasnervoside E (5), and three secoiridoid glycosides, jasnervosides F-H (10-12), were isolated from the stems of Jasminum nervosum Lour. (Oleaceae), along with four known compounds, poliumoside (6), verbascoside (7), α-l-rhamnopyranosyl-(1→3)-O-(α-l-rhamnopyranosyl(1→6)-1-O-E-caffeoyl-β-d-glucopyranoside (8), and jaspolyanthoside (9). Their structures were elucidated on the basis of their physicochemical and spectroscopic properties. Compounds 1, 2, 4 and 11 displayed potent antioxidant activities in the DPPH assay, while 2 and 3 displayed good activities against LPS-induced TNF-α and IL-1β production in BV2 cells. Compounds 1-5 and 10-12 were evaluated for their cytotoxic activities against three human cancer cell lines (A-549, Bel-7402, and HCT-8), but none displayed significant activity. Copyright © 2014 Elsevier Ltd. All rights reserved.

High-performance magnetic carbon materials in dye removal from aqueous solutions

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

Gao, Xiaoming, E-mail: dawn1026@163.com; Zhang, Yu; Dai, Yuan

To obtain a novel adsorbent with excellent adsorption capacity and convenient magnetic separation property, magnetic activated semi-coke was prepared by KOH activation method and further modified by FeCl{sub 3}. The surface morphology, physical structure, chemical properties and textural characteristics of unmodified semi-coke, KOH-modified semi-coke and magnetic activated semi-coke were characterized by scanning electron microscopy, X-ray powder diffraction, N{sub 2} adsorption-desorption measurement, and electronic differential system. The adsorption characteristics of the magnetic activated semi-coke were explored for the removal of methyl orang (MO), methylene blue (MB), congo red (CR), acid fuchsin (AF), and rhodamine B (RB) from aqueous solution. The effectsmore » of adsorption parameters, including adsorbent dosage, pH and contact time, were investigated by comparing the adsorption properties of the magnetic activated semi-coke to RB. The result showed that the magnetic activated semi-coke displayed excellent dispersion, convenient separation and high adsorption capacity. The adsorption experiment data indicated that the pseudosecond order model and the Langmuir model could well explain the adsorption processes of RB on the magnetic activated semi-coke, and the maximum adsorption capacity (q{sub m}) was 526.32 mg/g. The values of thermodynamic parameters (ΔG°, ΔH° and ΔS°) indicated that the adsorption process depended on the temperature of the aqueous phase, and it was spontaneous and exothermic in nature. As the addition of the magnetic activated semi-coke, the color of the solution significantly faded. Subsequently, fast aggregation of the magnetic activated semi-coke from their homogeneous dispersion in the presence of an external magnetic field could be happened. So, the magnetic activated semi-coke displayed excellent dispersion, convenient separation and high adsorption capacity. - Graphical abstract: As the addition of the magnetic activated semi-coke, the color of the solution significantly faded. Subsequently, fast aggregation of the magnetic activated semi-coke from their homogeneous dispersion in the presence of an external magnetic field could be happened. So, the magnetic activated semi-coke displayed excellent dispersion, convenient separation and high adsorption capacity. Display Omitted.« less

Cobalt-doping-induced synthesis of ceria nanodisks and their significantly enhanced catalytic activity.

PubMed

Guo, Xiao-Hui; Mao, Chao-Chao; Zhang, Ji; Huang, Jun; Wang, Wa-Nv; Deng, Yong-Hui; Wang, Yao-Yu; Cao, Yong; Huang, Wei-Xin; Yu, Shu-Hong

2012-05-21

High-quality cobalt-doped ceria nanostructures with triangular column, triangular slab, and disklike shapes are synthesized by tuning the doping amount of cobalt nitrate in a facile hydrothermal reaction. The cobalt-doped ceria nanodisks display significantly enhanced catalytic activity in CO oxidation due to exposed highly active crystal planes and the presence of numerous surface defects. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Display of fungal hydrophobin on the Pichia pastoris cell surface and its influence on Candida antarctica lipase B

PubMed Central

Wang, Pan; He, Jie; Sun, Yufei; Reynolds, Matthew; Zhang, Li; Han, Shuangyan; Liang, Shuli; Sui, Haixin; Lin, Ying

2016-01-01

To modify the Pichia pastoris cell surface, two classes of hydrophobins, SC3 from Schizophyllum commune and HFBI from Trichoderma reesei, were separately displayed on the cell wall. There was an observable increase in the hydrophobicity of recombinant strains. Candida antarctica lipase B (CALB) was then co-displayed on the modified cells, generating strains GS115/SC3-61/CALB-51 and GS115/HFBI-61/CALB-51. Interestingly, the hydrolytic and synthetic activities of strain GS115/HFBI-61/CALB-51 increased by 37% and 109%, respectively, but decreased by 26% and 43%, respectively, in strain GS115/SC3-61/CALB-51 compared with the hydrophobin-minus recombinant strain GS115/CALB-GCW51. The amount of glycerol by-product from the transesterification reaction adsorbed on the cell surface was significantly decreased following hydrophobin modification, removing the glycerol barrier and allowing substrates to access the active sites of lipases. Electron micrographs indicated that the cell wall structures of both recombinant strains appeared altered, including changes to the inner glucan layer and outer mannan layer. These results suggest that the display of hydrophobins can change the surface structure and hydrophobic properties of P. pastoris, and affect the catalytic activities of CALB displayed on the surface of P. pastoris cells. PMID:26969039

Discovery of novel Ponatinib analogues for reducing KDR activity as potent FGFRs inhibitors.

PubMed

Liu, Yang; Peng, Xia; Guan, Xiaocong; Lu, Dong; Xi, Yong; Jin, Shiyu; Chen, Hui; Zeng, Limin; Ai, Jing; Geng, Meiyu; Hu, Youhong

2017-01-27

FGF receptors (FGFRs) are tyrosine kinases that are overexpressed in diverse tumors by genetic alterations such as gene amplifications, somatic mutations and translocations. Owing to this characteristic, FGFRs are attractive targets for cancer treatment. It has been demonstrated that most multi-targeted, ATP competitive tyrosine kinase inhibitors are active against FGFRs as well as other kinases. The design of new and more selective inhibitors of FGFRs, which might be reduced off-target and side effects, is a difficult yet significant challenge. The results of the current investigation, show that novel Ponatinib analogues are highly active as FGFR inhibitors and that they possess reduced kinase insert domain receptor (KDR) activities. Observations made in a structure and activity relationship (SAR) investigation led to the development of a promising, orally available lead compound 4, which displays a 50-100 fold in vitro selectivity for inhibition of FGFR1-3 over KDR. In addition, biological evaluation of compound 4 showed that it displays significant antitumor activities in FGFR1-amplificated H1581 and FGFR2-amplificated SNU-16 xenograft models. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

JTEC panel on display technologies in Japan

NASA Technical Reports Server (NTRS)

Tannas, Lawrence E., Jr.; Glenn, William E.; Credelle, Thomas; Doane, J. William; Firester, Arthur H.; Thompson, Malcolm

1992-01-01

This report is one in a series of reports that describes research and development efforts in Japan in the area of display technologies. The following are included in this report: flat panel displays (technical findings, liquid crystal display development and production, large flat panel displays (FPD's), electroluminescent displays and plasma panels, infrastructure in Japan's FPD industry, market and projected sales, and new a-Si active matrix liquid crystal display (AMLCD) factory); materials for flat panel displays (liquid crystal materials, and light-emissive display materials); manufacturing and infrastructure of active matrix liquid crystal displays (manufacturing logistics and equipment); passive matrix liquid crystal displays (LCD basics, twisted nematics LCD's, supertwisted nematic LCD's, ferroelectric LCD's, and a comparison of passive matrix LCD technology); active matrix technology (basic active matrix technology, investment environment, amorphous silicon, polysilicon, and commercial products and prototypes); and projection displays (comparison of Japanese and U.S. display research, and technical evaluation of work).

Structure-Based Predictions of Activity Cliffs

PubMed Central

Husby, Jarmila; Bottegoni, Giovanni; Kufareva, Irina; Abagyan, Ruben; Cavalli, Andrea

2015-01-01

In drug discovery, it is generally accepted that neighboring molecules in a given descriptors' space display similar activities. However, even in regions that provide strong predictability, structurally similar molecules can occasionally display large differences in potency. In QSAR jargon, these discontinuities in the activity landscape are known as ‘activity cliffs’. In this study, we assessed the reliability of ligand docking and virtual ligand screening schemes in predicting activity cliffs. We performed our calculations on a diverse, independently collected database of cliff-forming co-crystals. Starting from ideal situations, which allowed us to establish our baseline, we progressively moved toward simulating more realistic scenarios. Ensemble- and template-docking achieved a significant level of accuracy, suggesting that, despite the well-known limitations of empirical scoring schemes, activity cliffs can be accurately predicted by advanced structure-based methods. PMID:25918827

Miniaturized LEDs for flat-panel displays

NASA Astrophysics Data System (ADS)

Radauscher, Erich J.; Meitl, Matthew; Prevatte, Carl; Bonafede, Salvatore; Rotzoll, Robert; Gomez, David; Moore, Tanya; Raymond, Brook; Cok, Ronald; Fecioru, Alin; Trindade, António Jose; Fisher, Brent; Goodwin, Scott; Hines, Paul; Melnik, George; Barnhill, Sam; Bower, Christopher A.

2017-02-01

Inorganic light emitting diodes (LEDs) serve as bright pixel-level emitters in displays, from indoor/outdoor video walls with pixel sizes ranging from one to thirty millimeters to micro displays with more than one thousand pixels per inch. Pixel sizes that fall between those ranges, roughly 50 to 500 microns, are some of the most commercially significant ones, including flat panel displays used in smart phones, tablets, and televisions. Flat panel displays that use inorganic LEDs as pixel level emitters (μILED displays) can offer levels of brightness, transparency, and functionality that are difficult to achieve with other flat panel technologies. Cost-effective production of μILED displays requires techniques for precisely arranging sparse arrays of extremely miniaturized devices on a panel substrate, such as transfer printing with an elastomer stamp. Here we present lab-scale demonstrations of transfer printed μILED displays and the processes used to make them. Demonstrations include passive matrix μILED displays that use conventional off-the shelf drive ASICs and active matrix μILED displays that use miniaturized pixel-level control circuits from CMOS wafers. We present a discussion of key considerations in the design and fabrication of highly miniaturized emitters for μILED displays.

The Fungal Metabolite, Pyrrocidine A, induces Apoptosis in HEPG2 Hepatocytes and PK15 Renal Cells

USDA-ARS?s Scientific Manuscript database

Pyrrocidines are polyketide-amino acid-derived antibiotics produced by Acremonium zeae, a prevalent seed-borne endophyte of corn. Pyrrocidines exhibit potent activity against Gram-positive bacteria, including drug resistant strains, and display significant activity against Candida albicans, as well...

GENETIC BASIS OF ACTIVITY METABOLISM. I. INHERITANCE OF SPEED, STAMINA, AND ANTIPREDATOR DISPLAYS IN THE GARTER SNAKE THAMNOPHIS SIRTALIS.

PubMed

Garland, Theodore

1988-03-01

Recent conceptual advances in physiological ecology emphasize the potential selective importance of whole-animal performance. Empirical studies of locomotor performance in reptiles have revealed surprising amounts of individual variation in speed and stamina. The present study is the first in a series examining the genetic basis of variation in locomotor performance, activity metabolism, and associated behaviors in garter snakes. Maximal sprint crawling speed, treadmill endurance, and antipredator displays (Arnold and Bennett, 1984; exhibited as snakes reached exhaustion on the treadmill) were measured for approximately six offspring (presumed to be full siblings) from each of 46 wild-caught gravid garter snakes (Thamnophis sirtalis). Each character was measured on two days; all were individually repeatable. Correlations of these characters with body mass, snout-vent length, age at testing, litter size, dam mass, and dam snout-vent length were removed by computing residuals from multiple-regression equations. These residuals were used in subsequent genetic analyses. Approximate coefficients of variation of residuals were 17% for speed, 48% for endurance, and 31% for antipredator displays. Broad-sense heritabilities were significant for all characters: speed h 2 = 0.58; stamina h 2 = 0.70; antipredator display h 2 = 0.42. All three residual characters showed positive and statistically significant phenotypic correlations (r = 0.19-0.36). Genetic correlations (estimated and tested by restricted maximum likelihood) among residuals were positive and highly significant between speed and endurance (0.58), but nonsignificant between speed and antipredator display (0.43), and between endurance and antipredator display (0.26). All environmental correlations were nonsignificant. These data suggest that, contrary to expectations based on previous physiological studies, there may be no necessary evolutionary trade-off between speed and stamina in these animals. This tentative conclusion will have important implications for future theoretical studies of the evolution of locomotor performance and associated antipredator behaviors. © 1988 The Society for the Study of Evolution.

AMLCD cockpit: promise and payoffs

NASA Astrophysics Data System (ADS)

Snow, Michael P.; Jackson, Timothy W.; Meyer, Frederick M.; Reising, John M.; Hopper, Darrel G.

1999-08-01

The active matrix liquid crystal display (AMLCD) has become the preferred flight instrument technology in avionics multifunction display applications. Current bubble canopy fighter cockpit applications involve sizes up to 7.8 X 7.8 in. active display. Dual use avionics versions of AMLCD technology are now as large as 6.7 X 6.7 in. active display area in the ARINC D sized color multifunction display (MFD). This is the standard instrument in all new Boeing transport aircraft and is being retrofitted into the C-17A. A special design of the ARINC D instrument is used in the Space Shuttle cockpit upgrade. Larger sizes of AMLCD were desired when decisions were made in the early 1990s for the F-22. Commercial AMLCD technology has now produced monitors at 1280 X 1024 resolution (1.3 megapixels) in sizes of 16 to 21 in. diagonal. Each of these larger AMLCDs has more information carrying capacity than the entire F-22A cockpit instrument panel shipset, comprising six separate smaller AMLCDs (1.2 megapixels total). The larger AMLCDs are being integrated into airborne mission crewstations for use in dim ambient lighting conditions. It is now time to identify and address the technology challenges of upgrading these larger AMLCDs for sunlight readable application and of developing concepts for their integration into advanced bubble canopy fighter cockpits. The overall goals are to significantly increase the informational carrying capacity to bring both sensor and information fusion into the cockpit and, thereby, to enable a significant increase in warfighter situational awareness and effectiveness. A research cockpit was built using specialized versions of the IBM 16.1 in and two smaller 10 in. AMLCDs to examine human factors and display design issues associated with these next-generation AMLCD cockpit displays. This cockpit was later upgraded to allow greater reconfigurability and flexibility in the display hardware used to conduct part- task mission simulations. The objective optical characterization of the AMLCDs used in this simulator and the cockpit design are described. Display formats under consideration for test in this cockpit are described together with some of the basic human factors engineering issues involved. Studies conducted in this cockpit will be part of an ongoing joint effort of the hardware-focused aerospace displays team and the pilot-focused human factors team in the Air Force Research Laboratory's Crew System Interface Division. The objective of these studies is to ascertain the payoffs of the large AMLCD promise in combat cockpits.

Chloroplast-expressed MSI-99 in tobacco improves disease resistance and displays inhibitory effect against rice blast fungus.

PubMed

Wang, Yun-Peng; Wei, Zheng-Yi; Zhang, Yu-Ying; Lin, Chun-Jing; Zhong, Xiao-Fang; Wang, Yue-Lin; Ma, Jing-Yong; Ma, Jian; Xing, Shao-Chen

2015-03-02

Rice blast is a major destructive fungal disease that poses a serious threat to rice production and the improvement of blast resistance is critical to rice breeding. The antimicrobial peptide MSI-99 has been suggested as an antimicrobial peptide conferring resistance to bacterial and fungal diseases. Here, a vector harboring the MSI-99 gene was constructed and introduced into the tobacco chloroplast genome via particle bombardment. Transformed plants were obtained and verified to be homoplastomic by PCR and Southern hybridization. In planta assays demonstrated that the transgenic tobacco plants displayed an enhanced resistance to the fungal disease. The evaluation of the antimicrobial activity revealed that the crude protein extracts from the transgenic plants manifested an antimicrobial activity against E. coli, even after incubation at 120 °C for 20 min, indicating significant heat stability of MSI-99. More importantly, the MSI-99-containing protein extracts were firstly proved in vitro and in vivo to display significant suppressive effects on two rice blast isolates. These findings provide a strong basis for the development of new biopesticides to combat rice blast.

Ultrahigh-definition dynamic 3D holographic display by active control of volume speckle fields

NASA Astrophysics Data System (ADS)

Yu, Hyeonseung; Lee, Kyeoreh; Park, Jongchan; Park, Yongkeun

2017-01-01

Holographic displays generate realistic 3D images that can be viewed without the need for any visual aids. They operate by generating carefully tailored light fields that replicate how humans see an actual environment. However, the realization of high-performance, dynamic 3D holographic displays has been hindered by the capabilities of present wavefront modulator technology. In particular, spatial light modulators have a small diffraction angle range and limited pixel number limiting the viewing angle and image size of a holographic 3D display. Here, we present an alternative method to generate dynamic 3D images by controlling volume speckle fields significantly enhancing image definition. We use this approach to demonstrate a dynamic display of micrometre-sized optical foci in a volume of 8 mm × 8 mm × 20 mm.

Interpreting population estimates of birds following pesticide applications--behavior of male starlings exposed to an organophosphate pesticide

USGS Publications Warehouse

Grue, C.E.; Shipley, B.J.; Ralph, C. John; Scott, J. Michael

1981-01-01

We determined activity budgets for 10 pairs of captive male Starlings between 7 May and 18 July 1980. Our objective was to quantify changes in behavior after exposure to an organophosphate (OP) pesticide and to assess the impact of changes in behavior on the interpretation of population estimates of birds following pesticide applications. We observed each pair of males for an hour at 07:30 and 09:30 for four days and classified their behavior into one of four categories: flying, perching, foraging, or singing and displaying. At 06:30 on day 2, one male received a single oral dose of 2.5 mg dicrotophos (3-hydroxy-N, N-dimethyl-cis-crotonamide dimethyl phosphate) per kg of body weight; the other male received an equivalent exposure of corn oil. Changes in the activity budgets of OP-dosed and control males were compared using t-tests. Activity of OP-dosed males was significantly (P _ 0.05) reduced within the 2-4 h following exposure. OP-dosed males spent more time perching (46.1%) than controls and less time flying (-96.6%), foraging (-28.5%), and singing and displaying (-49.5%). The frequency of perching (-75.3%), flying (-83.8%), foraging (-54.1%), and singing and displaying (- 59.2%) was significantly reduced. Activity in OP-dosed males returned to normal by 26-28 h posttreatment. Results suggest that movement and vocalization may be significantly reduced in birds exposed to organophosphate and carbamate pesticides. Conventional censusing techniques and population estimating procedures may, therefore, be inadequate to assess changes in bird populations after pesticide applications because of the difficulty in separating decreases in density due to mortality or emigration from reductions in activity.

Tidal, daily, and lunar-day activity cycles in the marine polychaete Nereis virens.

PubMed

Last, Kim S; Bailhache, Thierry; Kramer, Cas; Kyriacou, Charalambos P; Rosato, Ezio; Olive, Peter J W

2009-02-01

The burrow emergence activity of the wild caught ragworm Nereis virens Sars associated with food prospecting was investigated under various photoperiodic (LD) and simulated tidal cycles (STC) using a laboratory based actograph. Just over half (57%) of the animals under LD with STC displayed significant tidal (approximately 12.4 h) and/or lunar-day (approximately 24.8 h) activity patterns. Under constant light (LL) plus a STC, 25% of all animals were tidal, while one animal responded with a circadian (24.2 h) activity rhythm suggestive of cross-modal entrainment where the environmental stimulus of one period entrains rhythmic behavior of a different period. All peaks of activity under a STC, apart from that of the individual cross-modal entrainment case, coincided with the period of tank flooding. Under only LD without a STC, 49% of the animals showed nocturnal (approximately 24 h) activity. When animals were maintained under free-running LL conditions, 15% displayed significant rhythmicity with circatidal and circadian/circalunidian periodicities. Although activity cycles in N. virens at the population level are robust, at the individual level they are particularly labile, suggesting complex biological clock-control with multiple clock output pathways.

Comparative evaluation of monocular augmented-reality display for surgical microscopes.

PubMed

Rodriguez Palma, Santiago; Becker, Brian C; Lobes, Louis A; Riviere, Cameron N

2012-01-01

Medical augmented reality has undergone much development recently. However, there is a lack of studies quantitatively comparing the different display options available. This paper compares the effects of different graphical overlay systems in a simple micromanipulation task with "soft" visual servoing. We compared positioning accuracy in a real-time visually-guided task using Micron, an active handheld tremor-canceling microsurgical instrument, using three different displays: 2D screen, 3D screen, and microscope with monocular image injection. Tested with novices and an experienced vitreoretinal surgeon, display of virtual cues in the microscope via an augmented reality injection system significantly decreased 3D error (p < 0.05) compared to the 2D and 3D monitors when confounding factors such as magnification level were normalized.

Antimicrobial Active Clothes Display No Adverse Effects on the Ecological Balance of the Healthy Human Skin Microflora

PubMed Central

Hoefer, Dirk; Hammer, Timo R.

2011-01-01

The progressive public use of antimicrobial clothes has raised issues concerning skin health. A placebo-controlled side-to-side study was run with antimicrobial clothes versus fabrics of similar structure but minus the antimicrobial activity, to evaluate possible adverse effects on the healthy skin microflora. Sixty volunteers were enrolled. Each participant received a set of form-fitting T-shirts constructed in 2 halves: an antibacterial half, displaying activities of 3–5 log-step reductions due to silver-finishes or silver-loaded fibres and a nonantibacterial control side. The microflora of the scapular skin was analyzed weekly for opportunistic and pathogenic microorganisms over six weeks. The antibacterial halves did not disturb the microflora in number or composition, whereas a silver-containing deodorant displayed a short-term disturbance. Furthermore, parameters of skin morphology and function (TEWL, pH, moisture) did not show any significant shifts. In summary, antimicrobial clothes did not show adverse effects on the ecological balance of the healthy skin microflora. PMID:22363849

Using Temporal Fill Factor to Reduce Frame Reconstruction Rates

NASA Technical Reports Server (NTRS)

Larimer, James; Balram, Nikhil; Gille, Jennifer; Luszcz, Jeffery

1997-01-01

The newer active matrix display technologies such as TFT-LCD, DMD, PDP maintain their pixel values through the entire frame time, presenting a 100% temporal fill factor, in contrast to the duty cycle produced by the phosphor impulse response of the CRT. This sample-and-hold characteristic can be exploited to lower the displayed frame rate without affecting visual quality. The lower frame rate results in significantly lower transmission bandwidth, power, and cost.

Abstracts of ARI Research Publications, FY 1977

DTIC Science & Technology

1980-04-01

significant part of the job and (b) the amount of preparation needed. Excluding technical skill specialty activities , the jobs of company corianders in...ground sensors (UGS). When personnel or vehicle movements 4 activate a UGS in the vicinity, a monitor display elsewhere indicates the activation . This...Operators were able to detect more targets during periods of low target activity than during periods of high target activity . However, accuracy of

New Materials and Device Designs for Organic Light-Emitting Diodes

NASA Astrophysics Data System (ADS)

O'Brien, Barry Patrick

Research and development of organic materials and devices for electronic applications has become an increasingly active area. Display and solid-state lighting are the most mature applications and, and products have been commercially available for several years as of this writing. Significant efforts also focus on materials for organic photovoltaic applications. Some of the newest work is in devices for medical, sensor and prosthetic applications. Worldwide energy demand is increasing as the population grows and the standard of living in developing countries improves. Some studies estimate as much as 20% of annual energy usage is consumed by lighting. Improvements are being made in lightweight, flexible, rugged panels that use organic light emitting diodes (OLEDs), which are particularly useful in developing regions with limited energy availability and harsh environments. Displays also benefit from more efficient materials as well as the lighter weight and ruggedness enabled by flexible substrates. Displays may require different emission characteristics compared with solid-state lighting. Some display technologies use a white OLED (WOLED) backlight with a color filter, but these are more complex and less efficient than displays that use separate emissive materials that produce the saturated colors needed to reproduce the entire color gamut. Saturated colors require narrow-band emitters. Full-color OLED displays up to and including television size are now commercially available from several suppliers, but research continues to develop more efficient and more stable materials. This research program investigates several topics relevant to solid-state lighting and display applications. One project is development of a device structure to optimize performance of a new stable Pt-based red emitter developed in Prof Jian Li's group. Another project investigates new Pt-based red, green and blue emitters for lighting applications and compares a red/blue structure with a red/green/blue structure to produce light with high color rendering index. Another part of this work describes the fabrication of a 14.7" diagonal full color active-matrix OLED display on plastic substrate. The backplanes were designed and fabricated in the ASU Flexible Display Center and required significant engineering to develop; a discussion of that process is also included.

Towards highly stable polymer electronics (Conference Presentation)

NASA Astrophysics Data System (ADS)

Nikolka, Mark; Nasrallah, Iyad; Broch, Katharina; Sadhanala, Aditya; Hurhangee, Michael; McCulloch, Iain; Sirringhaus, Henning

2016-11-01

Due to their ease of processing, organic semiconductors are promising candidates for applications in high performance flexible displays and fast organic electronic circuitry. Recently, a lot of advances have been made on organic semiconductors exhibiting surprisingly high performance and carrier mobilities exceeding those of amorphous silicon. However, there remain significant concerns about their operational and environmental stability, particularly in the context of applications that require a very high level of threshold voltage stability, such as active-matrix addressing of organic light-emitting diode (OLED) displays. Here, we report a novel technique for dramatically improving the operational stress stability, performance and uniformity of high mobility polymer field-effect transistors by the addition of specific small molecule additives to the polymer semiconductor film. We demonstrate for the first time polymer FETs that exhibit stable threshold voltages with threshold voltage shifts of less than 1V when subjected to a constant current operational stress for 1 day under conditions that are representative for applications in OLED active matrix displays. The approach constitutes in our view a technological breakthrough; it also makes the device characteristics independent of the atmosphere in which it is operated, causes a significant reduction in contact resistance and significantly improves device uniformity. We will discuss in detail the microscopic mechanism by which the molecular additives lead to this significant improvement in device performance and stability.

Biologically active cannabinoids from high-potency Cannabis sativa.

PubMed

Radwan, Mohamed M; Elsohly, Mahmoud A; Slade, Desmond; Ahmed, Safwat A; Khan, Ikhlas A; Ross, Samir A

2009-05-22

Nine new cannabinoids (1-9) were isolated from a high-potency variety of Cannabis sativa. Their structures were identified as (+/-)-4-acetoxycannabichromene (1), (+/-)-3''-hydroxy-Delta((4'',5''))-cannabichromene (2), (-)-7-hydroxycannabichromane (3), (-)-7R-cannabicoumarononic acid A (4), 5-acetyl-4-hydroxycannabigerol (5), 4-acetoxy-2-geranyl-5-hydroxy-3-n-pentylphenol (6), 8-hydroxycannabinol (7), 8-hydroxycannabinolic acid A (8), and 2-geranyl-5-hydroxy-3-n-pentyl-1,4-benzoquinone (9) through 1D and 2D NMR spectroscopy, GC-MS, and HRESIMS. The known sterol beta-sitosterol-3-O-beta-d-glucopyranosyl-6'-acetate was isolated for the first time from cannabis. Compounds 6 and 7 displayed significant antibacterial and antifungal activities, respectively, while 5 displayed strong antileishmanial activity.

Enhanced anti-cancer activities of a gold(III) pyrrolidinedithiocarbamato complex incorporated in a biodegradable metal-organic framework.

PubMed

Sun, Raymond Wai-Yin; Zhang, Ming; Li, Dan; Li, Mian; Wong, Alice Sze-Tsai

2016-10-01

An anti-cancer active gold(III) pyrrolidinedithiocarbamato complex [(PDTC)Au III Cl 2 ] (1) has been synthesized and characterized by means of X-ray crystallography. Compared to the pyrrolidinedithiocarbamate ligand itself, this gold(III) complex displays an up to 33-fold higher anti-cancer potency towards a panel of cancer cell lines including the cisplatin-resistant ovarian carcinoma cell line (A2780cis). As demonstrated by a set of Transwell® assay-based cytotoxicity experiments, incorporating this gold(III) complex in a zinc-based biodegradable metal-organic framework (MOF) displays a significant enhancement in anti-cancer activity towards A2780cis than the gold(III) complex alone. Copyright © 2016 Elsevier Inc. All rights reserved.

Self-Relevance Appraisal Influences Facial Reactions to Emotional Body Expressions

PubMed Central

Grèzes, Julie; Philip, Léonor; Chadwick, Michèle; Dezecache, Guillaume; Soussignan, Robert; Conty, Laurence

2013-01-01

People display facial reactions when exposed to others' emotional expressions, but exactly what mechanism mediates these facial reactions remains a debated issue. In this study, we manipulated two critical perceptual features that contribute to determining the significance of others' emotional expressions: the direction of attention (toward or away from the observer) and the intensity of the emotional display. Electromyographic activity over the corrugator muscle was recorded while participants observed videos of neutral to angry body expressions. Self-directed bodies induced greater corrugator activity than other-directed bodies; additionally corrugator activity was only influenced by the intensity of anger expresssed by self-directed bodies. These data support the hypothesis that rapid facial reactions are the outcome of self-relevant emotional processing. PMID:23405230

Synthesis and biological evaluation of platensimycin analogs

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

Shen, Hong C.; Ding, Fa-Xiang; Singh, Sheo B.

2009-07-23

Platensimycin (1) displays antibacterial activity due to its inhibition of the elongation condensing enzyme (FabF), a novel mode of action that could potentially lead to a breakthrough in developing a new generation of antibiotics. The medicinal chemistry efforts were focused on the modification of the enone moiety of platensimycin and several analogs showed significant activity against FabF and possess antibacterial activity.

Antimicrobial activity of pyrrocidines from Acremonium zeae against endophytes and pathogens of maize.

PubMed

Wicklow, Donald T; Poling, Stephen M

2009-01-01

Acremonium zeae produces pyrrocidines A and B, which are polyketide-amino acid-derived antibiotics, and is recognized as a seedborne protective endophyte of maize which augments host defenses against microbial pathogens causing seedling blights and stalk rots. Pyrrocidine A displayed significant in vitro activity against Aspergillus flavus and Fusarium verticillioides in assays performed using conidia as inoculum, with pyrrocidine A being more active than B. In equivalent assays performed with conidia or hyphal cells as inoculum, pyrrocidine A revealed potent activity against major stalk and ear rot pathogens of maize, including F. graminearum, Nigrospora oryzae, Stenocarpella (Diplodia) maydis, and Rhizoctonia zeae. Pyrrocidine A displayed significant activity against seed-rotting saprophytes A. flavus and Eupenicillium ochrosalmoneum, as well as seed-infecting colonists of the phylloplane Alternaria alternata, Cladosporium cladosporioides, and Curvularia lunata, which produces a damaging leaf spot disease. Protective endophytes, including mycoparasites which grow asymptomatically within healthy maize tissues, show little sensitivity to pyrrocidines. Pyrrocidine A also exhibited potent activity against Clavibacter michiganense subsp. nebraskense, causal agent of Goss's bacterial wilt of maize, and Bacillus mojaviense and Pseudomonas fluorescens, maize endophytes applied as biocontrol agents, but were ineffective against the wilt-producing bacterium Pantoea stewartii.

Design, synthesis and antibacterial activity of cinnamaldehyde derivatives as inhibitors of the bacterial cell division protein FtsZ.

PubMed

Li, Xin; Sheng, Juzheng; Huang, Guihua; Ma, Ruixin; Yin, Fengxin; Song, Di; Zhao, Can; Ma, Shutao

2015-06-05

In an attempt to discover potential antibacterial agents against the increasing bacterial resistance, novel cinnamaldehyde derivatives as FtsZ inhibitors were designed, synthesized and evaluated for their antibacterial activity against nine significant pathogens using broth microdilution method, and their cell division inhibitory activity against four representative strains. In the in vitro antibacterial activity, the newly synthesized compounds generally displayed better efficacy against Staphylococcus aureus ATCC25923 than the others. In particular, compounds 3, 8 and 10 exerted superior or comparable activity to all the reference drugs. In the cell division inhibitory activity, all the compounds showed the same trend as their in vitro antibacterial activity, exhibiting better activity against S. aureus ATCC25923 than the other strains. Additionally, compounds 3, 6, 7 and 8 displayed potent cell division inhibitory activity with an MIC value of below 1 μg/mL, over 256-fold better than all the reference drugs. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

In vitro evaluation of the antioxidant potential, phenolic and flavonoid contents of the stem bark ethanol extract of Anogeissus leiocarpus.

PubMed

Olugbami, J O; Gbadegesin, M A; Odunola, O A

2014-09-01

Plant-derived antioxidants with free radical scavenging activities can be relevant as chemopreventive agents against the numerous diseases associated with free radicals and reactive oxygen species. Some phytoconstituents possess antioxidant activities in biological systems. On this basis, we evaluated the antioxidant potential, and determined the total phenolic and flavonoid contents of the e thanol e xtract of the s tem bark of A nogeissus l eiocarpus [ EESAL ]. Antioxidant assays carried out include: 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, phosphomolybdate, β-carotene bleaching, ferric reducing, and hydroxyl radical scavenging activities. Results of DPPH assay showed no significant difference ( p < 0.001) between EESAL and butylated hydroxyanisole [BHA], while EESAL exhibited a significantly ( p < 0.001) higher activity than BHT [butylated hydroxytoluene]. Phosphomolybdate method recorded a total antioxidant capacity of 190.00 ± 70.53 µg butylated hydroxytoluene equivalents [BHTE]/mg dry extract, while β-carotene bleaching assay gave percent antioxidant activities of both EESAL and BHT as 81.46±1.62 and 80.90±1.39 respectively. Ferric reducing abilities of both EESAL and ascorbic acid increased in a concentration-dependent manner with EESAL displaying a significantly ( p < 0.001) higher reductive activity than vitamin C. EESAL displayed a significantly higher hydroxyl radical scavenging activity as compared with BHT at the lowest concentration with no significant difference at the highest concentration. Total phenolic and flavonoid contents of EESAL were obtained as 608.10 ± 2.12 µg GAE/mg and 78.96 ± 3.37 µg QE/mg respectively. Taken together, the free radical scavenging and antioxidant activity of EESAL is likely due to its high phenolic content with complementary effects of the flavonoid components.

Three dimensional audio versus head down TCAS displays

NASA Technical Reports Server (NTRS)

Begault, Durand R.; Pittman, Marc T.

1994-01-01

The advantage of a head up auditory display was evaluated in an experiment designed to measure and compare the acquisition time for capturing visual targets under two conditions: Standard head down traffic collision avoidance system (TCAS) display, and three-dimensional (3-D) audio TCAS presentation. Ten commercial airline crews were tested under full mission simulation conditions at the NASA Ames Crew-Vehicle Systems Research Facility Advanced Concepts Flight Simulator. Scenario software generated targets corresponding to aircraft which activated a 3-D aural advisory or a TCAS advisory. Results showed a significant difference in target acquisition time between the two conditions, favoring the 3-D audio TCAS condition by 500 ms.

Antihyperglucolipidaemic and anticarbonyl stress properties in green, yellow and red sweet bell peppers (Capsicum annuum L.).

PubMed

Shukla, Srishti; Kumar, Dommati Anand; Anusha, Sanga Venkata; Tiwari, Ashok Kumar

2016-01-01

Effect of aqueous methanol extract of different colour sweet bell peppers (Capsicum annuum L.) on parameters of diabesity and carbonyl stress was analysed in vitro. Yellow pepper displayed significantly (p < 0.001) higher intestinal α-glucosidase inhibitory activity than green and red pepper. Porcine pancreatic lipase inhibitory activity was significantly (p < 0.01) high in yellow and red pepper than in green pepper. Green and red pepper inhibited vesperlysine-type advanced glycation end products (AGEs) more potently than yellow pepper; however, pentosidine-type AGEs were similarly inhibited by all three peppers. Yellow and red pepper inhibited lipid peroxidation more potently (p < 0.01) than green pepper. Total polyphenol content and free radicals scavenging activities in yellow and red bell peppers were higher than in green pepper. Total flavonoid content was high in green pepper than that present in yellow and red peppers. Green pepper displayed presence of proanthocyanins; however, oligomeric anthocyanins were detected in yellow and red peppers.

Epitope selection from an uncensored peptide library displayed on avian leukosis virus.

PubMed

Khare, Pranay D; Rosales, Ana G; Bailey, Kent R; Russell, Stephen J; Federspiel, Mark J

2003-10-25

Phage display libraries have provided an extraordinarily versatile technology to facilitate the isolation of peptides, growth factors, single chain antibodies, and enzymes with desired binding specificities or enzymatic activities. The overall diversity of peptides in phage display libraries can be significantly limited by Escherichia coli protein folding and processing machinery, which result in sequence censorship. To achieve an optimal diversity of displayed eukaryotic peptides, the library should be produced in the endoplasmic reticulum of eukaryotic cells using a eukaryotic display platform. In the accompanying article, we presented experiments that demonstrate that polypeptides of various sizes could be efficiently displayed on the envelope glycoproteins of a eukaryotic virus, avian leukosis virus (ALV), and the displayed polypeptides could efficiently attach to cognate receptors without interfering with viral attachment and entry into susceptible cells. In this study, methods were developed to construct a model library of randomized eight amino acid peptides using the ALV eukaryotic display platform and screen the library for specific epitopes using immobilized antibodies. A virus library with approximately 2 x 10(6) different members was generated from a plasmid library of approximately 5 x 10(6) diversity. The sequences of the randomized 24 nucleotide/eight amino acid regions of representatives of the plasmid and virus libraries were analyzed. No significant sequence censorship was observed in producing the virus display library from the plasmid library. Different populations of peptide epitopes were selected from the virus library when different monoclonal antibodies were used as the target. The results of these two studies clearly demonstrate the potential of ALV as a eukaryotic platform for the display and selection of eukaryotic polypeptides libraries.

Functional evolution and structural conservation in chimeric cytochromes p450: calibrating a structure-guided approach.

PubMed

Otey, Christopher R; Silberg, Jonathan J; Voigt, Christopher A; Endelman, Jeffrey B; Bandara, Geethani; Arnold, Frances H

2004-03-01

Recombination generates chimeric proteins whose ability to fold depends on minimizing structural perturbations that result when portions of the sequence are inherited from different parents. These chimeric sequences can display functional properties characteristic of the parents or acquire entirely new functions. Seventeen chimeras were generated from two CYP102 members of the functionally diverse cytochrome p450 family. Chimeras predicted to have limited structural disruption, as defined by the SCHEMA algorithm, displayed CO binding spectra characteristic of folded p450s. Even this small population exhibited significant functional diversity: chimeras displayed altered substrate specificities, a wide range in thermostabilities, up to a 40-fold increase in peroxidase activity, and ability to hydroxylate a substrate toward which neither parent heme domain shows detectable activity. These results suggest that SCHEMA-guided recombination can be used to generate diverse p450s for exploring function evolution within the p450 structural framework.

Discovery and evaluation of novel anti-inflammatory derivatives of natural bioactive curcumin

PubMed Central

Zhang, Yali; Jiang, Xin; Peng, Kesong; Chen, Chengwei; Fu, Lili; Wang, Zhe; Feng, Jianpeng; Liu, Zhiguo; Zhang, Huajie; Liang, Guang; Pan, Zheer

2014-01-01

Curcumin is a natural active product that has various pharmacological activities such as anti-inflammatory effects. Here, we report the synthesis and evaluation of 34 monocarbonyl curcumin analogs as novel anti-inflammatory agents. Among the analogs, the symmetrical heterocyclic type displayed the strongest inhibition of lipopolysaccharide (LPS)-stimulated expression of pro-inflammatory cytokines in macrophages. Analogs S1–S5 and AS29 reduced tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) production in a dose-dependent manner and also displayed excellent stability and low cytotoxicity in vitro. In addition, analog S1 dose-dependently inhibited LPS-induced extracellular signal-regulated kinase (ERK) phosphorylation. Furthermore, analogs S1 and S4 displayed a significant protective effect on LPS-induced septic death in mouse models, with 40% and 50% survival rates, respectively. These data demonstrate that the heterocyclic monocarbonyl curcumin analogs have potential therapeutic effects in acute inflammatory diseases. PMID:25395833

Fabrication of fully transparent nanowire transistors for transparent and flexible electronics

NASA Astrophysics Data System (ADS)

Ju, Sanghyun; Facchetti, Antonio; Xuan, Yi; Liu, Jun; Ishikawa, Fumiaki; Ye, Peide; Zhou, Chongwu; Marks, Tobin J.; Janes, David B.

2007-06-01

The development of optically transparent and mechanically flexible electronic circuitry is an essential step in the effort to develop next-generation display technologies, including `see-through' and conformable products. Nanowire transistors (NWTs) are of particular interest for future display devices because of their high carrier mobilities compared with bulk or thin-film transistors made from the same materials, the prospect of processing at low temperatures compatible with plastic substrates, as well as their optical transparency and inherent mechanical flexibility. Here we report fully transparent In2O3 and ZnO NWTs fabricated on both glass and flexible plastic substrates, exhibiting high-performance n-type transistor characteristics with ~82% optical transparency. These NWTs should be attractive as pixel-switching and driving transistors in active-matrix organic light-emitting diode (AMOLED) displays. The transparency of the entire pixel area should significantly enhance aperture ratio efficiency in active-matrix arrays and thus substantially decrease power consumption.

Fabrication of fully transparent nanowire transistors for transparent and flexible electronics.

PubMed

Ju, Sanghyun; Facchetti, Antonio; Xuan, Yi; Liu, Jun; Ishikawa, Fumiaki; Ye, Peide; Zhou, Chongwu; Marks, Tobin J; Janes, David B

2007-06-01

The development of optically transparent and mechanically flexible electronic circuitry is an essential step in the effort to develop next-generation display technologies, including 'see-through' and conformable products. Nanowire transistors (NWTs) are of particular interest for future display devices because of their high carrier mobilities compared with bulk or thin-film transistors made from the same materials, the prospect of processing at low temperatures compatible with plastic substrates, as well as their optical transparency and inherent mechanical flexibility. Here we report fully transparent In(2)O(3) and ZnO NWTs fabricated on both glass and flexible plastic substrates, exhibiting high-performance n-type transistor characteristics with approximately 82% optical transparency. These NWTs should be attractive as pixel-switching and driving transistors in active-matrix organic light-emitting diode (AMOLED) displays. The transparency of the entire pixel area should significantly enhance aperture ratio efficiency in active-matrix arrays and thus substantially decrease power consumption.

Usability inspection to improve an electronic provincial medication repository.

PubMed

Kitson, Nicole A; Price, Morgan; Bowen, Michael; Lau, Francis

2013-01-01

Medication errors are a significant source of actual and potential harm for patients. Community medication records have the potential to reduce medication errors, but they can also introduce unintended consequences when there is low fit to task (low cognitive fit). PharmaNet is a provincially managed electronic repository that contains the records for community-based pharmacy-dispensed medications in British Columbia. This research explores the usability of PharmaNet, as a representative community-based medication repository. We completed usability inspections of PharmaNet through vendor applications. Vendor participants were asked to complete activity-driven scenarios, which highlighted aspects of medication management workflow. Screen recording was later reviewed. Heuristics were applied to explore usability issues and improvement opportunities. Usability inspection was conducted with four PharmaNet applications. Ninety-six usability issues were identified; half of these had potential implications for patient safety. These were primarily related to login and logout procedures; display of patient name; display of medications; update and display of alert information; and the changing or discontinuation of medications. PharmaNet was designed primarily to support medication dispensing and billing activities by community pharmacies, but is also used to support care providers with monitoring and prescribing activities. As such, some of the features do not have a strong fit for other clinical activities. To improve fit, we recommend: having a Current Medications List and Displaying Medication Utilization Charts.

Vetiver Essential Oil in Cosmetics: What Is New?

PubMed Central

Burger, Pauline; Landreau, Anne; Watson, Marie; Janci, Laurent; Cassisa, Viviane; Kempf, Marie; Azoulay, Stéphane; Fernandez, Xavier

2017-01-01

Background: Vetiver is a key ingredient for the perfume industry nowadays. However, with the constant and rapid changes of personal tastes, this appeal could vanish and this sector could decline quite quickly. New dissemination paths need to be found to tap this valuable resource. Methods: In this way, its potential use in cosmetics either as an active ingredient per se (with cosmeceutical significance or presenting antimicrobial activity) has hence been explored in vitro. Results: In this contribution, we demonstrated that vetiver essential oil displays no particularly significant and innovative cosmetic potential value in formulations apart from its scent already largely exploited. However, evaluated against twenty bacterial strains and two Candida species using the in vitro microbroth dilution method, vetiver oil demonstrated notably some outstanding activities against Gram-positive strains and against one Candida glabrata strain. Conclusions: Based on these findings, vetiver essential oil appears to be an appropriate aspirant for the development of an antimicrobial agent for medicinal purposes and for the development of a cosmetic ingredient used for its scent and displaying antimicrobial activity as an added value. PMID:28930256

Extreme mobility in the Late Pleistocene? Comparing limb biomechanics among fossil Homo, varsity athletes and Holocene foragers.

PubMed

Shaw, Colin N; Stock, Jay T

2013-04-01

Descriptions of Pleistocene activity patterns often derive from comparisons of long bone diaphyseal robusticity across contemporaneous fossilized hominins. The purpose of this study is to augment existing understanding of Pleistocene hominin mobility patterns by interpreting fossil variation through comparisons with a) living human athletes with known activity patterns, and b) Holocene foragers where descriptions of group-level activity patterns are available. Relative tibial rigidity (midshaft tibial rigidity (J)/midshaft humeral rigidity (J)) was compared amongst Levantine and European Neandertals, Levantine and Upper Palaeolithic Homo sapiens, Holocene foragers and living human athletes and controls. Cross-country runners exhibit significantly (p<0.05) greater relative tibial rigidity compared with swimmers, and higher values compared with controls. In contrast, swimmers displayed significantly (p<0.05) lower relative tibial rigidity than both runners and controls. While variation exists among all Holocene H. sapiens, highly terrestrially mobile Later Stone Age (LSA) southern Africans and cross-country runners display the highest relative tibial rigidity, while maritime Andaman Islanders and swimmers display the lowest, with controls falling between. All fossil hominins displayed relative tibial rigidity that exceeded, or was similar to, the highly terrestrially mobile Later Stone Age southern Africans and modern human cross-country runners. The more extreme skeletal structure of most Neandertals and Levantine H. sapiens, as well as the odd Upper Palaeolithic individual, appears to reflect adaptation to intense and/or highly repetitive lower limb (relative to upper limb) loading. This loading may have been associated with bipedal travel, and appears to have been more strenuous than that encountered by even university varsity runners, and Holocene foragers with hunting grounds 2000-3000 square miles in size. Skeletal variation among the athletes and foraging groups is consistent with known or inferred activity profiles, which support the position that the Pleistocene remains reflect adaptation to extremely active and mobile lives. Copyright © 2013 Elsevier Ltd. All rights reserved.

Amorphous silicon thin film transistor active-matrix organic light-emitting diode displays fabricated on flexible substrates

NASA Astrophysics Data System (ADS)

Nichols, Jonathan A.

Organic light-emitting diode (OLED) displays are of immense interest because they have several advantages over liquid crystal displays, the current dominant flat panel display technology. OLED displays are emissive and therefore are brighter, have a larger viewing angle, and do not require backlights and filters, allowing thinner, lighter, and more power efficient displays. The goal of this work was to advance the state-of-the-art in active-matrix OLED display technology. First, hydrogenated amorphous silicon (a-Si:H) thin film transistor (TFT) active-matrix OLED pixels and arrays were designed and fabricated on glass substrates. The devices operated at low voltages and demonstrated that lower performance TFTs could be utilized in active-matrix OLED displays, possibly allowing lower cost processing and the use of polymeric substrates. Attempts at designing more control into the display at the pixel level were also made. Bistable (one bit gray scale) active-matrix OLED pixels and arrays were designed and fabricated. Such pixels could be used in novel applications and eventually help reduce the bandwidth requirements in high-resolution and large-area displays. Finally, a-Si:H TFT active-matrix OLED pixels and arrays were fabricated on a polymeric substrate. Displays fabricated on a polymeric substrates would be lightweight; flexible, more rugged, and potentially less expensive to fabricate. Many of the difficulties associated with fabricating active-matrix backplanes on flexible substrates were studied and addressed.

Head Worn Display System for Equivalent Visual Operations

NASA Technical Reports Server (NTRS)

Cupero, Frank; Valimont, Brian; Wise, John; Best. Carl; DeMers, Bob

2009-01-01

Head-Worn Displays or so-called, near-to-eye displays have potentially significant advantages in terms of cost, overcoming cockpit space constraints, and for the display of spatially-integrated information. However, many technical issues need to be overcome before these technologies can be successfully introduced into commercial aircraft cockpits. The results of three activities are reported. First, the near-to-eye display design, technological, and human factors issues are described and a literature review is presented. Second, the results of a fixed-base piloted simulation, investigating the impact of near to eye displays on both operational and visual performance is reported. Straight-in approaches were flown in simulated visual and instrument conditions while using either a biocular or a monocular display placed on either the dominant or non-dominant eye. The pilot's flight performance, visual acuity, and ability to detect unsafe conditions on the runway were tested. The data generally supports a monocular design with minimal impact due to eye dominance. Finally, a method for head tracker system latency measurement is developed and used to compare two different devices.

The novel oral glucan synthase inhibitor SCY-078 shows in vitro activity against sessile and planktonic Candida spp.

PubMed

Marcos-Zambrano, Laura Judith; Gómez-Perosanz, Marta; Escribano, Pilar; Bouza, Emilio; Guinea, Jesús

2017-07-01

We studied the antifungal activity of SCY-078 (an orally bioavailable 1,3-β -d- glucan synthesis inhibitor), micafungin and fluconazole against the planktonic and sessile forms of 178 Candida and non- Candida isolates causing fungaemia in patients recently admitted to a large European hospital. The in vitro activity of SCY-078, micafungin and fluconazole against the planktonic form of the isolates was assessed using EUCAST EDef 7.3 and CLSI M27-A3. Antibiofilm activity was assessed using the XTT reduction assay. SCY-078 and micafungin showed potent in vitro activity against Candida and non- Candida isolates. The in vitro activity of both drugs was similar, but SYC-078 displayed significantly lower MIC values than micafungin against Candida parapsilosis and non- Candida isolates, whereas micafungin displayed significantly lower MIC values for the remaining species ( P  <0.001). In contrast, SCY-078 and micafungin showed essentially the same activity against the biofilms with the exception of Candida glabrata , in which the micafungin sessile MIC values were significantly lower ( P  <0.001). These observations were confirmed by assessing biofilm structure by scanning electron microscopy after antifungal treatment. Our study showed that the high in vitro activity of SCY-078 against invasive Candida isolates in both sessile and planktonic forms is comparable to that of micafungin. © The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Synthesis and quantitative structure-antifungal activity relationships of clovane derivatives against Botrytis cinerea.

PubMed

Saiz-Urra, Liane; Racero, Juan C; Macías-Sáchez, Antonio J; Hernández-Galán, Rosario; Hanson, James R; Perez-Gonzalez, Maykel; Collado, Isidro G

2009-03-25

Twenty-three clovane derivatives, nine described here for the first time, bearing substituents on carbon C-2, have been synthesized and evaluated for their in vitro antifungal activity against the phytopathogenic fungus Botrytis cinerea. The results showed that compounds 9, 14, 16, and 18 bearing nitrogen atoms in the chain attached at C-2 displayed potent antifungal activity, whereas mercapto derivatives 13, 19, and 22 displayed low activity. The antifungal activity showed a clear structure-activity relationship (SAR) trend, which confirmed the importance of the nature of the C-2 chain on the antifungal activity. On the basis of these observations, the metabolism of compounds 8 and 14 by the fungus B. cinerea, and the metabolism of other clovanes by this fungus, described previously, a pro-drug action mechanism for 2-alkoxyclovane compounds is proposed. Quantitative structure-activity relationship (QSAR) studies were performed to rationalize the results and to suggest further optimization, using a topological sub-structural molecular design (TOPS-MODE) approach. The model displayed good fit and predictive capability, describing 85.5% of the experimental variance, with a standard deviation of 9.502 and yielding high values of cross-validation determination coefficients (q2CV-LOO = 0.784 and q2boot = 0.673). The most significant variables were the spectral moments weighted by bond dipole moment (Dip), hydrophobicity (Hyd), and the combined dipolarity/polarizability Abraham molecular descriptor (Ab-pi2H).

Interest of active posturography to detect age-related and early Parkinson's disease-related impairments in mediolateral postural control.

PubMed

Bonnet, Cédrick T; Delval, Arnaud; Defebvre, Luc

2014-11-15

Patients with Parkinson's disease display impairments of postural control most particularly in active, challenging conditions. The objective of the present study was to analyze early signs of disease-related and also age-related impairments in mediolateral body extension and postural control. Fifty-five participants (18 Hoehn and Yahr stage 2 patients in the off-drug condition, 18 healthy elderly control subjects, and 19 young adults) were included in the study. The participants performed a quiet stance task and two active tasks that analyzed the performance in mediolateral body motion: a limit of stability and a rhythmic weight shift task. As expected, the patients displayed significantly lower and slower body displacement (head, neck, lower back, center of pressure) than elderly control subjects when performing the two body excursion tasks. However, the behavioral variability in both tasks was similar between the groups. Under these active conditions, the patients showed significantly lower contribution of the hip postural control mechanisms compared with the elderly control subjects. Overall, the patients seemed to lower their performance in order to prevent a mediolateral postural instability. However, these patients, at an early stage of their disease, were not unstable in quiet stance. Complementarily, elderly control subjects displayed slower body performance than young adults, which therefore showed an additional age-related impairment in mediolateral postural control. Overall, the study illustrated markers of age-related and Parkinson's disease impairments in mediolateral postural control that may constrain everyday activities in elderly adults and even more in patients with Parkinson's disease. Copyright © 2014 the American Physiological Society.

Activation of the Wnt/β-catenin pathway in pancreatic beta cells during the compensatory islet hyperplasia in prediabetic mice

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

Maschio, D. A.; Oliveira, R. B.; Santos, M. R.

The Wnt/β-catenin signaling pathway, also known as the canonical Wnt pathway, plays a role in cell proliferation and differentiation in several tissues/organs. It has been recently described in humans a relationship between type 2 diabetes (T2DM) and mutation in the gene encoding the transcription factor TCF7L2 associated to the Wnt/β-catenin pathway. In the present study, we demonstrated that hyperplastic pancreatic islets from prediabetic mice fed a high-fat diet (HFD) for 60 d displayed nuclear translocation of active β-catenin associated with significant increases in protein content and gene expression of β-catenin as well as of cyclins D1, D2 and c-Myc (target genesmore » of the Wnt pathway) but not of Tcf7l2 (the transcription factor). Meanwhile, these alterations were not observed in pancreatic islets from 30 d HFD-fed mice, that do not display significant beta cell hyperplasia. These data suggest that the Wnt/β-catenin pathway is activated in pancreatic islets during prediabetes and may play a role in the induction of the compensatory beta cell hyperplasia observed at early phase of T2DM. - Highlights: • Exposure to high-fat diet for 60 days induced prediabetes and beta cell mass expansion. • Hyperplastic pancreatic islets displayed nuclear translocation of active β-catenin. • Hyperplastic islets showed increased expression of target genes of the Wnt/β-catenin pathway. • Wnt/β-catenin pathway is activated during compensatory beta cell hyperplasia in mice.« less

POLYGALACTURONASE INVOLVED IN EXPANSION1 functions in cell elongation and flower development in Arabidopsis.

PubMed

Xiao, Chaowen; Somerville, Chris; Anderson, Charles T

2014-03-01

Pectins are acidic carbohydrates that comprise a significant fraction of the primary walls of eudicotyledonous plant cells. They influence wall porosity and extensibility, thus controlling cell and organ growth during plant development. The regulated degradation of pectins is required for many cell separation events in plants, but the role of pectin degradation in cell expansion is poorly defined. Using an activation tag screen designed to isolate genes involved in wall expansion, we identified a gene encoding a putative polygalacturonase that, when overexpressed, resulted in enhanced hypocotyl elongation in etiolated Arabidopsis thaliana seedlings. We named this gene POLYGALACTURONASE INVOLVED IN EXPANSION1 (PGX1). Plants lacking PGX1 display reduced hypocotyl elongation that is complemented by transgenic PGX1 expression. PGX1 is expressed in expanding tissues throughout development, including seedlings, roots, leaves, and flowers. PGX1-GFP (green fluorescent protein) localizes to the apoplast, and heterologously expressed PGX1 displays in vitro polygalacturonase activity, supporting a function for this protein in apoplastic pectin degradation. Plants either overexpressing or lacking PGX1 display alterations in total polygalacturonase activity, pectin molecular mass, and wall composition and also display higher proportions of flowers with extra petals, suggesting PGX1's involvement in floral organ patterning. These results reveal new roles for polygalacturonases in plant development.

Deletion of Gpr55 Results in Subtle Effects on Energy Metabolism, Motor Activity and Thermal Pain Sensation.

PubMed

Bjursell, Mikael; Ryberg, Erik; Wu, Tingting; Greasley, Peter J; Bohlooly-Y, Mohammad; Hjorth, Stephan

2016-01-01

The G-protein coupled receptor 55 (GPR55) is activated by cannabinoids and non-cannabinoid molecules and has been speculated to play a modulatory role in a large variety of physiological and pathological processes, including in metabolically perturbed states. We therefore generated male mice deficient in the gene coding for the cannabinoid/lysophosphatidylinositol (LPI) receptor Gpr55 and characterized them under normal dietary conditions as well as during high energy dense diet feeding followed by challenge with the CB1 receptor antagonist/GPR55 agonist rimonabant. Gpr55 deficient male mice (Gpr55 KO) were phenotypically indistinguishable from their wild type (WT) siblings for the most part. However, Gpr55 KO animals displayed an intriguing nocturnal pattern of motor activity and energy expenditure (EE). During the initial 6 hours of the night, motor activity was significantly elevated without any significant effect observed in EE. Interestingly, during the last 6 hours of the night motor activity was similar but EE was significantly decreased in the Gpr55 KO mice. No significant difference in motor activity was detected during daytime, but EE was lower in the Gpr55 KO compared to WT mice. The aforementioned patterns were not associated with alterations in energy intake, daytime core body temperature, body weight (BW) or composition, although a non-significant tendency to increased adiposity was seen in Gpr55 KO compared to WT mice. Detailed analyses of daytime activity in the Open Field paradigm unveiled lower horizontal activity and rearing time for the Gpr55 KO mice. Moreover, the Gpr55 KO mice displayed significantly faster reaction time in the tail flick test, indicative of thermal hyperalgesia. The BW-decreasing effect of rimonabant in mice on long-term cafeteria diet did not differ between Gpr55 KO and WT mice. In conclusion, Gpr55 deficiency is associated with subtle effects on diurnal/nocturnal EE and motor activity behaviours but does not appear per se critically required for overall metabolism or behaviours.

Augmented Central Pain Processing in Vulvodynia

PubMed Central

Hampson, Johnson P.; Reed, Barbara D.; Clauw, Daniel J.; Bhavsar, Rupal; Gracely, Richard H.; Haefner, Hope K.; Harris, Richard E.

2013-01-01

Vulvodynia (VVD) is a chronic pain disorder, wherein women display sensitivity to evoked stimuli at the vulva and/or spontaneous vulvar pain. Our previous work suggests generalized hyperalgesia in this population, however little is known about central neurobiological factors that may influence pain in VVD. Here we investigated local (vulvar) and remote (thumb) pressure evoked pain processing in 24 VVD patients compared to 13 age-matched, pain-free healthy controls (HC). As a positive control we also examined thumb pressure pain in 24 fibromyalgia (FM) patients. The VVD and FM patients displayed overlapping insular brain activations that were greater than HC, in response to thumb stimulation (P<0.005 corrected). Compared to HC, VVD participants displayed greater levels of activation during thumb stimulation within the insula, dorsal mid-cingulate, posterior cingulate and thalamus (P<0.005 corrected). Significant differences between VVD subgroups (primary versus secondary and provoked versus unprovoked) were seen within the posterior cingulate with thumb stimulation, and within the precuneus region with vulvar stimulation (provoked versus unprovoked only). The augmented brain activation in VVD patients in response to a stimulus remote from the vulva suggests central neural pathology in this disorder. Moreover, differing central activity between VVD subgroups suggests heterogeneous pathologies within this diagnosis. PMID:23578957

Pixel structures to compensate nonuniform threshold voltage and mobility of polycrystalline silicon thin-film transistors using subthreshold current for large-size active matrix organic light-emitting diode displays

NASA Astrophysics Data System (ADS)

Na, Jun-Seok; Kwon, Oh-Kyong

2014-01-01

We propose pixel structures for large-size and high-resolution active matrix organic light-emitting diode (AMOLED) displays using a polycrystalline silicon (poly-Si) thin-film transistor (TFT) backplane. The proposed pixel structures compensate the variations of the threshold voltage and mobility of the driving TFT using the subthreshold current. The simulated results show that the emission current error of the proposed pixel structure B ranges from -2.25 to 2.02 least significant bit (LSB) when the variations of the threshold voltage and mobility of the driving TFT are ±0.5 V and ±10%, respectively.

Neural correlates of reward processing in adults with 22q11 deletion syndrome.

PubMed

van Duin, Esther D A; Goossens, Liesbet; Hernaus, Dennis; da Silva Alves, Fabiana; Schmitz, Nicole; Schruers, Koen; van Amelsvoort, Therese

2016-01-01

22q11.2 deletion syndrome (22q11DS) is caused by a microdeletion on chromosome 22q11.2 and associated with an increased risk to develop psychosis. The gene coding for catechol-O-methyl-transferase (COMT) is located at the deleted region, resulting in disrupted dopaminergic neurotransmission in 22q11DS, which may contribute to the increased vulnerability for psychosis. A dysfunctional motivational reward system is considered one of the salient features in psychosis and thought to be related to abnormal dopaminergic neurotransmission. The functional anatomy of the brain reward circuitry has not yet been investigated in 22q11DS. This study aims to investigate neural activity during anticipation of reward and loss in adult patients with 22q11DS. We measured blood-oxygen-level dependent (BOLD) activity in 16 patients with 22q11DS and 12 healthy controls during a monetary incentive delay task using a 3T Philips Intera MRI system. Data were analysed using SPM8. During anticipation of reward, the 22q11DS group alone displayed significant activation in bilateral middle frontal and temporal brain regions. Compared to healthy controls, significantly less activation in bilateral cingulate gyrus extending to premotor, primary motor and somatosensory areas was found. During anticipation of loss, the 22q11DS group displayed activity in the left middle frontal gyrus and anterior cingulate cortex, and relative to controls, they showed reduced brain activation in bilateral (pre)cuneus and left posterior cingulate. Within the 22q11DS group, COMT Val hemizygotes displayed more activation compared to Met hemizygotes in right posterior cingulate and bilateral parietal regions during anticipation of reward. During anticipation of loss, COMT Met hemizygotes compared to Val hemizygotes showed more activation in bilateral insula, striatum and left anterior cingulate. This is the first study to investigate reward processing in 22q11DS. Our preliminary results suggest that people with 22q11DS engage a fronto-temporal neural network. Compared to healthy controls, people with 22q11DS primarily displayed reduced activity in medial frontal regions during reward anticipation. COMT hemizygosity affects responsivity of the reward system in this condition. Alterations in reward processing partly underlain by the dopamine system may play a role in susceptibility for psychosis in 22q11DS.

Mice deficient in PKCbeta and apolipoprotein E display decreased atherosclerosis.

PubMed

Harja, Evis; Chang, Jong Sun; Lu, Yan; Leitges, Michael; Zou, Yu Shan; Schmidt, Ann Marie; Yan, Shi-Fang

2009-04-01

Endothelial activation is a central initiating event in atheroma formation. Evidence from our laboratory and others has demonstrated links between activation of early growth response-1 (Egr-1) and atherosclerosis and also has demonstrated that activated protein kinase C (PKC) betaII is a critical upstream regulator of Egr-1 in response to vascular stress. We tested the role of PKCbeta in regulating key events linked to atherosclerosis and show that the aortas of apoE(-/-) mice display an age-dependent increase in PKCbetaII antigen in membranous fractions vs. C57BL/6 animals with a approximately 2-fold increase at age 6 wk and a approximately 4.5-fold increase at age 24 wk. Consistent with important roles for PKCbeta in atherosclerosis, a significant decrease in atherosclerotic lesion area was evident in PKCbeta(-/-)/apoE(-/-) vs. apoE(-/-) mice by approximately 5-fold, in parallel with significantly reduced vascular transcripts for Egr-1 and matrix metalloproteinase (MMP)-2 antigen and activity vs. apoE(-/-) mice. Significant reduction in atherosclerosis of approximately 2-fold was observed in apoE(-/-) mice fed ruboxistaurin chow (PKCbeta inhibitor) vs. vehicle. In primary murine and human aortic endothelial cells, the PKCbeta-JNK mitogen-activated protein kinase pathway importantly contributes to oxLDL-mediated induction of MMP2 expression. Blockade of PKCbeta may be beneficial in mitigating endothelial perturbation and atherosclerosis.

The impact of computer display height and desk design on muscle activity during information technology work by young adults.

PubMed

Straker, L; Pollock, C; Burgess-Limerick, R; Skoss, R; Coleman, J

2008-08-01

Computer display height and desk design are believed to be important workstation features and are included in international standards and guidelines. However, the evidence base for these guidelines is lacking a comparison of neck/shoulder muscle activity during computer and paper tasks and whether forearm support can be provided by desk design. This study measured the spinal and upper limb muscle activity in 36 young adults whilst they worked in different computer display, book and desk conditions. Display height affected spinal muscle activity with paper tasks resulting in greater mean spinal and upper limb muscle activity. A curved desk resulted in increased proximal muscle activity. There was no substantial interaction between display and desk.

Design and synthesis of positional isomers of 5 and 6-bromo-1-[(phenyl)sulfonyl]-2-[(4-nitrophenoxy)methyl]-1H-benzimidazoles as possible antimicrobial and antitubercular agents.

PubMed

Ranjith, P Karuvalam; Rajeesh, P; Haridas, Karickal R; Susanta, Nayak K; Row, Tayur N Guru; Rishikesan, R; Kumari, N Suchetha

2013-09-15

In this Letter, we report the structure-activity relationship (SAR) studies on series of positional isomers of 5(6)-bromo-1-[(phenyl)sulfonyl]-2-[(4-nitrophenoxy)methyl]-1H-benzimidazoles derivatives 7(a-j) and 8(a-j) synthesized in good yields and characterized by (1)H NMR, (13)C NMR and mass spectral analyses. The crystal structure of 7a was evidenced by X-ray diffraction study. The newly synthesized compounds were evaluated for their in vitro antibacterial activity against Staphylococcus aureus, (Gram-positive), Escherichia coli and Klebsiella pneumoniae (Gram-negative), antifungal activity against Candida albicans, Aspergillus flavus and Rhizopus sp. and antitubercular activity against Mycobacterium tuberculosis H37Rv, Mycobacterium smegmatis, Mycobacterium fortuitum and MDR-TB strains. The synthesized compounds displayed interesting antimicrobial activity. The compounds 7b, 7e and 7h displayed significant activity against Mycobacterium tuberculosis H37Rv strain. Copyright © 2013 Elsevier Ltd. All rights reserved.

Evaluation of force-torque displays for use with space station telerobotic activities

NASA Technical Reports Server (NTRS)

Hendrich, Robert C.; Bierschwale, John M.; Manahan, Meera K.; Stuart, Mark A.; Legendre, A. Jay

1992-01-01

Recent experiments which addressed Space Station remote manipulation tasks found that tactile force feedback (reflecting forces and torques encountered at the end-effector through the manipulator hand controller) does not improve performance significantly. Subjective response from astronaut and non-astronaut test subjects indicated that force information, provided visually, could be useful. No research exists which specifically investigates methods of presenting force-torque information visually. This experiment was designed to evaluate seven different visual force-torque displays which were found in an informal telephone survey. The displays were prototyped in the HyperCard programming environment. In a within-subjects experiment, 14 subjects nullified forces and torques presented statically, using response buttons located at the bottom of the screen. Dependent measures included questionnaire data, errors, and response time. Subjective data generally demonstrate that subjects rated variations of pseudo-perspective displays consistently better than bar graph and digital displays. Subjects commented that the bar graph and digital displays could be used, but were not compatible with using hand controllers. Quantitative data show similar trends to the subjective data, except that the bar graph and digital displays both provided good performance, perhaps do to the mapping of response buttons to display elements. Results indicate that for this set of displays, the pseudo-perspective displays generally represent a more intuitive format for presenting force-torque information.

Pilots strategically compensate for display enlargements in surveillance and flight control tasks.

PubMed

Stelzer, Emily Muthard; Wickens, Christopher D

2006-01-01

Experiments were conducted to assess the impact of display size on flight control, airspace surveillance, and goal-directed target search. Research of 3-D displays has shown that display scale compression influences the perception of flight path deviation, though less is known about the causes that drive this effect. In addition, research on attention-based tasks has shown that information displaced to significant eccentricities can amplify effort, but it is unclear whether the effect generates a performance difference in complex displays. In Experiment 1, 16 pilots completed a low-fidelity flight control task under single- and dual-axis control. In Experiment 2, the control task from Experiment 1 was scaled up to a more realistic flight environment, and pilots performed hazard surveillance and target search tasks. For flight control, pilots exhibited less path error and greater stick activity with a large display, which was attributed both to greater enhanced resolution and to the fact that larger depictions of error lead to greater urgency in correcting deviations. Size did not affect hazard surveillance or search, as pilots were adaptive in altering scanning patterns in response to the enlargement of the displays. Although pilots were adaptive to display changes in search and surveillance, display size reduction diminished estimates of flight path deviation and control performance because of lowered resolution and control urgency. Care should be taken when manipulating display size, as size reduction can diminish control performance.

The Effect of NEXRAD Image Looping and National Convective Weather Forecast Product on Pilot Decision Making in the Use of a Cockpit Weather Information Display

NASA Technical Reports Server (NTRS)

Burgess, Malcolm A.; Thomas, Rickey P.

2004-01-01

This experiment investigated improvements to cockpit weather displays to better support the hazardous weather avoidance decision-making of general aviation pilots. Forty-eight general aviation pilots were divided into three equal groups and presented with a simulated flight scenario involving embedded convective activity. The control group had access to conventional sources of pre-flight and in-flight weather products. The two treatment groups were provided with a weather display that presented NEXRAD mosaic images, graphic depiction of METARs, and text METARs. One treatment group used a NEXRAD image looping feature and the second group used the National Convective Weather Forecast (NCWF) product overlaid on the NEXRAD display. Both of the treatment displays provided a significant increase in situation awareness but, they provided incomplete information required to deal with hazardous convective weather conditions, and would require substantial pilot training to permit their safe and effective use.

A system for the management, display and integration of pre-hospital healthcare activity in the deployed environment.

PubMed

Grant, Simon; Wheatley, R J

2014-12-01

To create and implement a system through which pre-hospital healthcare activity across an entire operational theatre could be made available in real-time to support healthcare delivery, governance and assurance activity. An IT-based system was created that could display, manage and integrate the pre-hospital healthcare activity on Op HERRICK 18. The system was based on the Defence Medical Services Common Assurance Framework and run through Microsoft Office SharePoint. Pre-hospital healthcare activity was made available and visible across an operational theatre. This supported delivery, assurance and governance at any time. Activity from each medical facility could be integrated and display automatically improving theatre wide situational awareness. The availability of information resulted in a shift towards a more continuous process of assurance and governance rather than reliance on inherently threatening and increasingly intermittent inspection regimes. The ability to review healthcare activity remotely at anytime significantly improves the validity of assurance possible for a deployed force. Governance activity can be more responsive and less reliant on the fixed timescale and datasets of reports from outlying medical facilities. However, assurance and governance authorities must not allow such a wealth of information to impact local leadership and innovation through a perception of, or actual, micro-management. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Ubiquitous Nature of Fluoroquinolones: The Oscillation between Antibacterial and Anticancer Activities

PubMed Central

Schweizer, Frank

2017-01-01

Fluoroquinolones are synthetic antibacterial agents that stabilize the ternary complex of prokaryotic topoisomerase II enzymes (gyrase and Topo IV), leading to extensive DNA fragmentation and bacteria death. Despite the similar structural folds within the critical regions of prokaryotic and eukaryotic topoisomerases, clinically relevant fluoroquinolones display a remarkable selectivity for prokaryotic topoisomerase II, with excellent safety records in humans. Typical agents that target human topoisomerases (such as etoposide, doxorubicin and mitoxantrone) are associated with significant toxicities and secondary malignancies, whereas clinically relevant fluoroquinolones are not known to exhibit such propensities. Although many fluoroquinolones have been shown to display topoisomerase-independent antiproliferative effects against various human cancer cells, those that are significantly active against eukaryotic topoisomerase show the same DNA damaging properties as other topoisomerase poisons. Empirical models also show that fluoroquinolones mediate some unique immunomodulatory activities of suppressing pro-inflammatory cytokines and super-inducing interleukin-2. This article reviews the extended roles of fluoroquinolones and their prospects as lead for the unmet needs of “small and safe” multimodal-targeting drug scaffolds. PMID:29112154

Higher anterior knee laxity influences the landing biomechanics displayed by pubescent girls.

PubMed

Wild, Catherine Y; Munro, Bridget J; Steele, Julie R

2017-01-01

Despite an increase in anterior knee laxity (AKL) during the adolescent growth spurt in girls, it is unknown whether landing biomechanics are affected by this change. This study investigated whether pubescent girls with higher AKL displayed differences in their lower limb strength or landing biomechanics when performing a horizontal leap movement compared to girls with lower AKL. Forty-six pubescent girls (10-13 years) were tested at the time of their peak height velocity (PHV). Passive AKL was quantified and used to classify participants into higher (HAKL; peak displacement > 4 mm) and lower (LAKL; peak displacement < 3 mm) AKL groups (n = 15/group). Three-dimensional kinematics, ground reaction forces (GRF) and muscle activation patterns were assessed during a horizontal leap landing. HAKL participants displayed significantly (P < 0.05) reduced hip abduction, increased hip abduction moments, as well as earlier hamstring muscle and later tibialis anterior activation compared to LAKL participants. Girls with HAKL displayed compensatory landing biomechanics, which are suggested to assist the functional stability of their knees during this dynamic task. Further research is warranted, however, to confirm or refute this notion.

Promiscuous activity of the LXR antagonist GSK2033 in a mouse model of fatty liver disease

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

Griffett, Kristine; Burris, Thomas P., E-mail: burristp@slu.edu

The liver X receptor (LXR) functions as a receptor for oxysterols and plays a critical role in the regulation of glucose and lipid metabolism. We recently described a synthetic LXR inverse agonist that displayed efficacy in treatment of hepatic steatosis in a mouse model of non-alcoholic fatty liver disease (NAFLD). This compound, SR9238, was designed to display liver specificity so as to avoid potential detrimental effects on reverse cholesterol transport in peripheral tissues. Here, we examined the effects of a LXR antagonist/inverse agonist, GSK2033, which displays systemic exposure. Although GSK2033 performed as expected in cell-based models as a LXR inversemore » agonist, it displayed unexpected activity in the mouse NAFLD model. The expression of lipogenic enzyme genes such as fatty acid synthase and sterol regulatory binding protein 1c were induced rather than suppressed and no effect on hepatic steatosis was found. Further characterization of the specificity of GSK2033 revealed that it displayed a significant degree of promiscuity, targeting a number of other nuclear receptors that could clearly alter hepatic gene expression. - Highlights: • The LXR antagonist GSK2033 suppresses the expression of lipogenic genes FASN and SREBF1 in HepG2 cells. • GSK2033 exhibits sufficient exposure to perform animal experiments targeting the liver. • GSK2033 has fails to suppress hepatic Fasn and Srebf1 expression in an animal model of non-alcoholic fatty liver disease. • GSK2033 may regulate the activity of several nuclear receptors.« less

Use of a Data-Linked Weather Information Display and Effects on Pilot Navigation Decision Making in a Piloted Simulation Study

NASA Technical Reports Server (NTRS)

Yuchnovicz, Daniel E.; Novacek, Paul F.; Burgess, Malcolm A.; Heck, Michael L.; Stokes, Alan F.

2001-01-01

This study provides recommendations to the FAA and to prospective manufacturers based on an exploration of the effects of data link weather displays upon pilot decision performance. An experiment was conducted with twenty-four current instrument rated pilots who were divided into two equal groups and presented with a challenging but realistic flight scenario involving weather containing significant embedded convective activity. All flights were flown in a full-mission simulation facility within instrument meteorological conditions. The inflight weather display depicted NexRad images, graphical METARs and textual METARs. The objective was to investigate the potential for misuse of a weather display, and incorporate recommendations for the design and use of these displays. The primary conclusion of the study found that the inflight weather display did not improve weather avoidance decision making. Some of the reasons to support this finding include: the pilot's inability to easily perceive their proximity to the storms, increased workload and difficulty in deciphering METAR textual data. The compelling nature of a graphical weather display caused many pilots to reduce their reliance on corroborating weather information from other sources. Minor changes to the weather display could improve the ability of a pilot to make better decisions on hazard avoidance.

Characterization of crosstalk in stereoscopic display devices.

PubMed

Zafar, Fahad; Badano, Aldo

2014-12-01

Many different types of stereoscopic display devices are used for commercial and research applications. Stereoscopic displays offer the potential to improve performance in detection tasks for medical imaging diagnostic systems. Due to the variety of stereoscopic display technologies, it remains unclear how these compare with each other for detection and estimation tasks. Different stereo devices have different performance trade-offs due to their display characteristics. Among them, crosstalk is known to affect observer perception of 3D content and might affect detection performance. We measured and report the detailed luminance output and crosstalk characteristics for three different types of stereoscopic display devices. We recorded the effect of other issues on recorded luminance profiles such as viewing angle, use of different eye wear, and screen location. Our results show that the crosstalk signature for viewing 3D content can vary considerably when using different types of 3D glasses for active stereo displays. We also show that significant differences are present in crosstalk signatures when varying the viewing angle from 0 degrees to 20 degrees for a stereo mirror 3D display device. Our detailed characterization can help emulate the effect of crosstalk in conducting computational observer image quality assessment evaluations that minimize costly and time-consuming human reader studies.

Do temperamentally shy children process emotion differently than nonshy children? Behavioral, psychophysiological, and gender differences in reticent preschoolers.

PubMed

Theall-Honey, Laura A; Schmidt, Louis A

2006-04-01

We examined regional brain electrical activity (EEG), heart rate, and subjective responses at rest and during the presentation of videoclips designed to elicit a range of emotions (e.g., sadness, anger, happiness, fear) among a sample of healthy 4-year-old children selected for temperamental shyness. We found that shy children exhibited significantly greater relative right central EEG activation at rest and during the presentation of the fear-eliciting videoclip than nonshy children. Shy females displayed greater relative right mid-frontal EEG activation during the sad, happy, and fear videoclips than shy males who displayed greater relative left mid-frontal EEG activation. These results (1) suggest that recent frontal EEG activation/emotion models might be gender-specific and (2) appear to provide the first empirical evidence for recent theoretical notions linking the origins and maintenance of temperamental shyness in children to difficulty in regulating fear responses. Copyright (c) 2006 Wiley Periodicals, Inc.

Physiological Costs of Repetitive Courtship Displays in Cockroaches Handicap Locomotor Performance

PubMed Central

Mowles, Sophie L.; Jepson, Natalie M.

2015-01-01

Courtship displays are typically thought to have evolved via female choice, whereby females select mates based on the characteristics of a display that is expected to honestly reflect some aspect of the male’s quality. Honesty is typically enforced by mechanistic costs and constraints that limit the level at which a display can be performed. It is becoming increasingly apparent that these costs may be energetic costs involved in the production of dynamic, often repetitive displays. A female attending to such a display may thus be assessing the physical fitness of a male as an index of his quality. Such assessment would provide information on his current physical quality as well as his ability to carry out other demanding activities, qualities with which a choosy female should want to provision her offspring. In the current study we use courtship interactions in the Cuban burrowing cockroach, Byrsotria fumigata to directly test whether courtship is associated with a signaler’s performance capacity. Males that had produced courtship displays achieved significantly lower speeds and distances in locomotor trials than non-courting control males. We also found that females mated more readily with males that produced a more vigorous display. Thus, males of this species have developed a strategy where they produce a demanding courtship display, while females choose males based on their ability to produce this display. Courtship displays in many taxa often involve dynamic repetitive actions and as such, signals of stamina in courtship may be more widespread than previously thought. PMID:26606147

European display scene

NASA Astrophysics Data System (ADS)

Bartlett, Christopher T.

2000-08-01

The manufacture of Flat Panel Displays (FPDs) is dominated by Far Eastern sources, particularly in Active Matrix Liquid Crystal Displays (AMLCD) and Plasma. The United States has a very powerful capability in micro-displays. It is not well known that Europe has a very active research capability which has lead to many innovations in display technology. In addition there is a capability in display manufacturing of organic technologies as well as the licensed build of Japanese or Korean designs. Finally, Europe has a display systems capability in military products which is world class.

Year-round effects of a four-week randomized controlled trial using different types of feedback on employees' physical activity.

PubMed

Van Hoye, Karen; Wijtzes, Anne I; Lefevre, Johan; De Baere, Stijn; Boen, Filip

2018-04-12

This follow-up study investigated the year-round effects of a four-week randomized controlled trial using different types of feedback on employees' physical activity, including a need-supportive coach intervention. Participants (n = 227) were randomly assigned to a Minimal Intervention Group (MIG; no feedback), a Pedometer Group (PG; feedback on daily steps only), a Display Group (DG; feedback on daily steps, on daily moderate-to-vigorous physical activity [MVPA] and on total energy expenditure [EE]), or a Coaching Group (CoachG; same as DG with need supportive coaching). Daily physical activity level (PAL; Metabolic Equivalent of Task [MET]), number of daily steps, daily minutes of moderate to vigorous physical activity (MVPA), active daily EE (EE > 3 METs) and total daily EE were measured at five time points: before the start of the 4-week intervention, one week after the intervention, and 3, 6, and 12 months after the intervention. For minutes of MVPA, MIG showed higher mean change scores compared with the DG. For steps and daily minutes of MVPA, significantly lower mean change scores emerged for MIG compared with the PG. Participants of the CoachG showed significantly higher change scores in PAL, steps, minutes of MVPA, active EE, total EE compared with the MIG. As hypothesized, participants of the CoachG had significantly higher mean change scores in PAL and total EE compared with groups that only received feedback. However, no significant differences were found for steps, minutes of MVPA and active EE between CoachG and PG. Receiving additional need-supportive coaching resulted in a higher PAL and active EE compared with measurement (display) feedback only. These findings suggest to combine feedback on physical activity with personal coaching in order to facilitate long-term behavioral change. When it comes to increasing steps, minutes of MVPA or active EE, a pedometer constitutes a sufficient tool. Clinical Trails.gov NCT01432327 . Date registered: 12 September 2011.

fMRI: blood oxygen level-dependent activation during a working memory-selective attention task in children born extremely preterm.

PubMed

Griffiths, Silja Torvik; Gundersen, Hilde; Neto, Emanuel; Elgen, Irene; Markestad, Trond; Aukland, Stein M; Hugdahl, Kenneth

2013-08-01

Extremely preterm (EPT)/extremely low-birth-weight (ELBW) children attaining school age and adolescence often have problems with executive functions such as working memory and selective attention. Our aim was to investigate a hypothesized difference in blood oxygen level-dependent (BOLD) activation during a selective attention-working memory task in EPT/ELBW children as compared with term-born controls. A regional cohort of 28 EPT/ELBW children and 28 term-born controls underwent functional magnetic resonance imaging (fMRI) scanning at 11 y of age while performing a combined Stroop n-back task. Group differences in BOLD activation were analyzed with Statistical Parametric Mapping 8 analysis software package, and reaction times (RTs) and response accuracy (RA) were compared in a multifactorial ANOVA test. The BOLD activation pattern in the preterm group involved the same areas (cingulate, prefrontal, and parietal cortexes), but all areas displayed significantly less activation than those in the control group, particularly when the cognitive load was increased. The RA results corresponded with the activation data in that the preterm group had significantly fewer correct responses. No group difference was found regarding RTs. Children born EPT/ELBW displayed reduced working memory and selective attention capacity as compared with term-born controls. These impairments had neuronal correlates with reduced BOLD activation in areas responsible for online stimulus monitoring, working memory, and cognitive control.

Dynamic, diagnostic, and pharmacological radionuclide studies of the esophagus in achalasia

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

Rozen, P.; Gelfond, M.; Zaltzman, S.

1982-08-01

The esophagus was evaluated in 15 patients with achalasia by continuous gamma camera imaging following ingestion of a semi-solid meal labeled with /sup 99m/Tc. The images were displayed and recorded on a simple computerized data processing/display system. Subsequent cine mode images of esophageal emptying demonstrated abnormalities of the body of the esophagus not reflected by the manometric examination. Computer-generated time-activity curves representing specific regions of interest were better than manometry in evaluating the results of myotomy, dilatation, and drug therapy. Isosorbide dinitrate significantly improved esophageal emptying.

Synthetic scaffold coating with adeno-associated virus encoding BMP2 to promote endogenous bone repair.

PubMed

Dupont, Kenneth M; Boerckel, Joel D; Stevens, Hazel Y; Diab, Tamim; Kolambkar, Yash M; Takahata, Masahiko; Schwarz, Edward M; Guldberg, Robert E

2012-03-01

Biomaterial scaffolds functionalized to stimulate endogenous repair mechanisms via the incorporation of osteogenic cues offer a potential alternative to bone grafting for the treatment of large bone defects. We first quantified the ability of a self-complementary adeno-associated viral vector encoding bone morphogenetic protein 2 (scAAV2.5-BMP2) to enhance human stem cell osteogenic differentiation in vitro. In two-dimensional culture, scAAV2.5-BMP2-transduced human mesenchymal stem cells (hMSCs) displayed significant increases in BMP2 production and alkaline phosphatase activity compared with controls. hMSCs and human amniotic-fluid-derived stem cells (hAFS cells) seeded on scAAV2.5-BMP2-coated three-dimensional porous polymer Poly(ε-caprolactone) (PCL) scaffolds also displayed significant increases in BMP2 production compared with controls during 12 weeks of culture, although only hMSC-seeded scaffolds displayed significantly increased mineral formation. PCL scaffolds coated with scAAV2.5-BMP2 were implanted into critically sized immunocompromised rat femoral defects, both with or without pre-seeding of hMSCs, representing ex vivo and in vivo gene therapy treatments, respectively. After 12 weeks, defects treated with acellular scAAV2.5-BMP2-coated scaffolds displayed increased bony bridging and had significantly higher bone ingrowth and mechanical properties compared with controls, whereas defects treated with scAAV2.5-BMP2 scaffolds pre-seeded with hMSCs failed to display significant differences relative to controls. When pooled, defect treatment with scAAV2.5-BMP2-coated scaffolds, both with or without inclusion of pre-seeded hMSCs, led to significant increases in defect mineral formation at all time points and increased mechanical properties compared with controls. This study thus presents a novel acellular bone-graft-free endogenous repair therapy for orthotopic tissue-engineered bone regeneration.

Frontal gamma noise power and cognitive domains in schizophrenia.

PubMed

Díez, Alvaro; Suazo, Vanessa; Casado, Pilar; Martín-Loeches, Manuel; Perea, María Victoria; Molina, Vicente

2014-01-30

The cognitive deficit profile is different among individuals with schizophrenia. We quantified the amount of electroencephalographic activity unlocked to stimuli onset (noise power) over frontal regions regarding deficit in cognitive domains. Forty-six patients with schizophrenia and 27 healthy controls underwent clinical, cognitive and electrophysiological assessments. Noise power studies may be considered complementary but not equivalent to induced power studies. We compared gamma and theta noise power magnitude during a P300 paradigm between subsets of patients divided according to cognitive deficit in key domains and controls. Patients displayed higher gamma noise power activity at Fz site and significantly lower performance in all cognitive domains when compared to controls. The subset of patients with cognitive deficit for working memory and problem solving/executive functions domains displayed significantly higher frontal-lateral noise power values in comparison to the subset of patients without cognitive deficit and controls. Patients with significant cognitive deficits in domains with greater frontal contribution are also characterized by an abnormally higher gamma band noise power over the frontal region. Our data may endorse various biological subsets within schizophrenia, characterized by the presence or absence of a significant cognitive deficit in frontal domains. © 2013 Published by Elsevier Ireland Ltd.

Toward reducing immunogenicity of enzyme replacement therapy: altering the specificity of human β-glucuronidase to compensate for α-iduronidase deficiency.

PubMed

Chuang, Huai-Yao; Suen, Ching-Shu; Hwang, Ming-Jing; Roffler, Steve R

2015-11-01

Enzyme replacement therapy (ERT) is an effective treatment for many patients with lysosomal storage disorders caused by deficiency in enzymes involved in cell metabolism. However, immune responses that develop against the administered enzyme in some patients can hinder therapeutic efficacy and cause serious side effects. Here we investigated the feasibility of a general approach to decrease ERT immunogenicity by altering the specificity of a normal endogenous enzyme to compensate for a defective enzyme. We sought to identify human β-glucuronidase variants that display α-iduronidase activity, which is defective in mucopolysaccharidosis (MPS) type I patients. A human β-glucuronidase library was screened by the Enzyme Cleavable Surface-Tethered All-purpose Screen sYstem to isolate variants that exhibited 100-290-fold greater activity against the α-iduronidase substrate 4-methylumbelliferyl α-l-iduronide and 7900-24 500-fold enzymatic specificity shift when compared with wild-type β-glucuronidase. In vitro treatment of MPS I cells with the β-glucuronidase variants significantly restored lysosome appearance similar to treatment with α-iduronidase. Our study suggests that β-glucuronidase variants can be isolated to display α-iduronidase activity and produce significant phenotype improvement of MPS I cells. This strategy may represent a possible approach to produce enzymes that display therapeutic benefits with potentially less immunogenicity. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Operator Influence of Unexploded Ordnance Sensor Technologies

DTIC Science & Technology

2007-03-01

chart display ActiveX control Mscomct2.dll – date/time display ActiveX control Pnpscr.dll – Systran SCRAMNet replicated shared memory device...response value database rgm_p2.dll – Phase 2 shared memory API and implementation Commercial components StripM.ocx – strip chart display ActiveX

Glucosensing capacity in rainbow trout liver displays day-night variations possibly related to melatonin action.

PubMed

Conde-Sieira, Marta; Patiño, Marcos A López; Míguez, Jesús M; Soengas, José L

2012-09-01

To assess whether the glucosensing capacity in peripheral (liver and Brockmann bodies) and central (hypothalamus and hindbrain) locations of rainbow trout displays day-night variations in its response to changes in circulating glucose levels, we evaluated the response of parameters related to glucosensing [glucose, glycogen and glucose 6-phosphate levels, activities of glucokinase (GK), glycogen synthetase (GSase) and pyruvate kinase (PK), and mRNA abundance of GK, glucose transporter 2 (GLUT2), and K(ATP) channel subunits Kir6.x-like and sulfonylurea receptor (SUR)-like] in fish subjected to hyperglycemic treatment under night or day conditions. No day-night significant variations were noticed in the glucosensing capacity of the hypothalamus, hindbrain and Brockmann bodies. In contrast, a clear differential response was noticed in the liver, where glucose levels, GK activity (and mRNA levels) and GSase activity displayed increased values during the day in hyperglycemic fish compared with controls, and lower (GK mRNA levels) or non-existent (glucose, GK and GSase activities, and Kir6.x-like mRNA levels) values during the night. A similar decrease in parameters related to glucosensing in the liver was observed when fish under day conditions were treated with melatonin, suggesting a modulatory role of melatonin in day-night changes of the glucosensing response in the same tissue.

The mouse liver displays daily rhythms in the metabolism of phospholipids and in the activity of lipid synthesizing enzymes.

PubMed

Gorné, Lucas D; Acosta-Rodríguez, Victoria A; Pasquaré, Susana J; Salvador, Gabriela A; Giusto, Norma M; Guido, Mario Eduardo

2015-02-01

The circadian system involves central and peripheral oscillators regulating temporally biochemical processes including lipid metabolism; their disruption leads to severe metabolic diseases (obesity, diabetes, etc). Here, we investigated the temporal regulation of glycerophospholipid (GPL) synthesis in mouse liver, a well-known peripheral oscillator. Mice were synchronized to a 12:12 h light-dark (LD) cycle and then released to constant darkness with food ad libitum. Livers collected at different times exhibited a daily rhythmicity in some individual GPL content with highest levels during the subjective day. The activity of GPL-synthesizing/remodeling enzymes: phosphatidate phosphohydrolase 1 (PAP-1/lipin) and lysophospholipid acyltransferases (LPLATs) also displayed significant variations, with higher levels during the subjective day and at dusk. We evaluated the temporal regulation of expression and activity of phosphatidylcholine (PC) synthesizing enzymes. PC is mainly synthesized through the Kennedy pathway with Choline Kinase (ChoK) as a key regulatory enzyme or through the phosphatidylethanolamine (PE) N-methyltransferase (PEMT) pathway. The PC/PE content ratio exhibited a daily variation with lowest levels at night, while ChoKα and PEMT mRNA expression displayed maximal levels at nocturnal phases. Our results demonstrate that mouse liver GPL metabolism oscillates rhythmically with a precise temporal control in the expression and/or activity of specific enzymes.

Safety implications of providing real-time feedback to distracted drivers.

PubMed

Donmez, Birsen; Boyle, Linda Ng; Lee, John D

2007-05-01

A driving simulator study was conducted to assess whether real-time feedback on a driver's state can influence the driver's interaction with in-vehicle information systems (IVIS). Previous studies have shown that IVIS tasks can undermine driver safety by increasing driver distraction. Thus, mitigating driver distraction using a feedback mechanism appears promising. This study was designed to test real-time feedback that alerts drivers based on their off-road eye glances. Feedback was displayed in two display locations (vehicle-centered, and IVIS-centered) to 16 young and 13 middle-aged drivers. Distraction was observed as problematic for both age groups with delayed responses to a lead vehicle-braking event as indicated by delayed accelerator releases. Significant benefits were not observed for braking and steering behavior for this experiment, but there was a significant change in drivers' interaction with IVIS. When given feedback on their distracted state, drivers looked at the in-vehicle display less frequently regardless of where feedback was displayed in the vehicle. This indicates that real-time feedback based on the driver state can positively alter driver's engagement in distracting activities, helping them attend better to the roadway.

Deletion of Gpr55 Results in Subtle Effects on Energy Metabolism, Motor Activity and Thermal Pain Sensation

PubMed Central

Ryberg, Erik; Wu, Tingting; Greasley, Peter J.; Bohlooly-Y, Mohammad; Hjorth, Stephan

2016-01-01

The G-protein coupled receptor 55 (GPR55) is activated by cannabinoids and non-cannabinoid molecules and has been speculated to play a modulatory role in a large variety of physiological and pathological processes, including in metabolically perturbed states. We therefore generated male mice deficient in the gene coding for the cannabinoid/lysophosphatidylinositol (LPI) receptor Gpr55 and characterized them under normal dietary conditions as well as during high energy dense diet feeding followed by challenge with the CB1 receptor antagonist/GPR55 agonist rimonabant. Gpr55 deficient male mice (Gpr55 KO) were phenotypically indistinguishable from their wild type (WT) siblings for the most part. However, Gpr55 KO animals displayed an intriguing nocturnal pattern of motor activity and energy expenditure (EE). During the initial 6 hours of the night, motor activity was significantly elevated without any significant effect observed in EE. Interestingly, during the last 6 hours of the night motor activity was similar but EE was significantly decreased in the Gpr55 KO mice. No significant difference in motor activity was detected during daytime, but EE was lower in the Gpr55 KO compared to WT mice. The aforementioned patterns were not associated with alterations in energy intake, daytime core body temperature, body weight (BW) or composition, although a non-significant tendency to increased adiposity was seen in Gpr55 KO compared to WT mice. Detailed analyses of daytime activity in the Open Field paradigm unveiled lower horizontal activity and rearing time for the Gpr55 KO mice. Moreover, the Gpr55 KO mice displayed significantly faster reaction time in the tail flick test, indicative of thermal hyperalgesia. The BW-decreasing effect of rimonabant in mice on long-term cafeteria diet did not differ between Gpr55 KO and WT mice. In conclusion, Gpr55 deficiency is associated with subtle effects on diurnal/nocturnal EE and motor activity behaviours but does not appear per se critically required for overall metabolism or behaviours. PMID:27941994

Effect of exercise dosages on adiposity indices in overweight girls.

PubMed

Kellam, Stephanie; Olvera, Norma; Leung, Patrick; Liu, Jian; Smith, Dennis

2013-01-01

The primary purpose of this study was to determine the impact of two exercise dosages on reducing adiposity in minority girls. Sixty-two overweight Hispanic and African-American girls participated in one of two intense summer interventions in Houston, TX: Intervention A (exposure to about 40 hours physical activities) or Intervention B (exposure to 60 hours of physical activities). Adiposity indices (percent body fat, waist circumference, body mass index) were taken pre- and post-intervention. Intervention B had a significantly greater decrease in adiposity indicators (p= 0.006) when compared to Intervention A. Waist circumference displayed the most significant decrease (p = 0.001). Both interventions significantly increased daily minutes of moderate-to-vigorous physical activity (p= 0.020). Intense physical activity interventions may effectively reduce abdominal fat in minority girls.

Associations between patterns of active commuting and socioeconomic factors in women with fibromyalgia: the al-Ándalus project.

PubMed

Herrador-Colmenero, Manuel; Álvarez-Gallardo, Inmaculada C; Segura-Jiménez, Víctor; Estévez-López, Fernando; Soriano-Maldonado, Alberto; Ruiz-Montero, Pedro J; Tercedor, Pablo; Girela-Rejón, María José; Delgado-Fernández, Manuel; Chillón, Palma

2016-01-01

The aims of this study were to know whether active commuting behaviour differs between fibromyalgia patients and controls, and to test whether active commuting is associated with socioeconomic factors in this population. This cross-sectional study included 459 women with fibromyalgia (52.2 years) and 214 female control participants (51.3 years) from Andalusia (southern Spain). Participants reported patterns of active commuting and socioeconomic factors (civil status, accompaniment at home, living with, educational level, and current occupational and professional status). On the age group <51 years, women with fibromyalgia revealed a significant higher percentage of active commuting for the variable active worker commuters than control group (p<0.05). On the age group ≥51 years, control group displayed a significant higher percentage of active commuting for commuting to local shops, super-market and active commuters variables (all, p<0.05). Women with fibromyalgia who lived alone were more active commuters in comparison to either those living accompanied, or living with both partner and children, only partner and only children (all, p<0.05). The prevalence of active commuting was similar in women with fibromyalgia and controls aged <51 years. However, fibromyalgia participants aged ≥51 years displayed differences: fibromyalgia women who lived alone were more active commuters than those living accompanied; family demands were inversely associated with commuting patterns. Policies focused on reducing family demands for fibromyalgia patients (i.e. social help on housework, childcare or overprotection) might facilitate the inclusion of daily active behaviours.

Preictal Activity of Subicular, CA1, and Dentate Gyrus Principal Neurons in the Dorsal Hippocampus before Spontaneous Seizures in a Rat Model of Temporal Lobe Epilepsy

PubMed Central

Fujita, Satoshi; Toyoda, Izumi; Thamattoor, Ajoy K.

2014-01-01

Previous studies suggest that spontaneous seizures in patients with temporal lobe epilepsy might be preceded by increased action potential firing of hippocampal neurons. Preictal activity is potentially important because it might provide new opportunities for predicting when a seizure is about to occur and insight into how spontaneous seizures are generated. We evaluated local field potentials and unit activity of single, putative excitatory neurons in the subiculum, CA1, CA3, and dentate gyrus of the dorsal hippocampus in epileptic pilocarpine-treated rats as they experienced spontaneous seizures. Average action potential firing rates of neurons in the subiculum, CA1, and dentate gyrus, but not CA3, increased significantly and progressively beginning 2–4 min before locally recorded spontaneous seizures. In the subiculum, CA1, and dentate gyrus, but not CA3, 41–57% of neurons displayed increased preictal activity with significant consistency across multiple seizures. Much of the increased preictal firing of neurons in the subiculum and CA1 correlated with preictal theta activity, whereas preictal firing of neurons in the dentate gyrus was independent of theta. In addition, some CA1 and dentate gyrus neurons displayed reduced firing rates preictally. These results reveal that different hippocampal subregions exhibit differences in the extent and potential underlying mechanisms of preictal activity. The finding of robust and significantly consistent preictal activity of subicular, CA1, and dentate neurons in the dorsal hippocampus, despite the likelihood that many seizures initiated in other brain regions, suggests the existence of a broader neuronal network whose activity changes minutes before spontaneous seizures initiate. PMID:25505320

Antifeedant activity of quassinoids.

PubMed

Leskinen, V; Polonsky, J; Bhatnagar, S

1984-10-01

The antifeedant activity of 13 quassinoids of different structural types has been studied against the Mexican bean beetle (Epilachna varivestis Mulsant) 4th instar larvae and the southern armyworm (Spodoptera eridania Crawer) 5th instar larvae. All quassinoids tested displayed significant activity against the Mexican bean beetle and, thus, do not reveal a simple structure-activity relationship. Five quassinoids were active against the southern armyworm. Interestingly, four of these-bruceantin (I), glaucarubinone (VI), isobruceine A (VIII), and simalikalactone D (XI)-possess the required structural features for antineoplastic activity. The noncytotoxic quassin (X) is an exception; it is active against both pests.

In vitro anticancer activity, toxicity and structure-activity relationships of phyllostictine A, a natural oxazatricycloalkenone produced by the fungus Phyllosticta cirsii

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

Le Calve, Benjamin; Lallemand, Benjamin; Perrone, Carmen

2011-07-01

The in vitro anticancer activity and toxicity of phyllostictine A, a novel oxazatricycloalkenone recently isolated from a plant-pathogenic fungus (Phyllosticta cirsii) was characterized in six normal and five cancer cell lines. Phyllostictine A displays in vitro growth-inhibitory activity both in normal and cancer cells without actual bioselectivity, while proliferating cells appear significantly more sensitive to phyllostictine A than non-proliferating ones. The main mechanism of action by which phyllostictine displays cytotoxic effects in cancer cells does not seem to relate to a direct activation of apoptosis. In the same manner, phyllostictine A seems not to bind or bond with DNA asmore » part of its mechanism of action. In contrast, phyllostictine A strongly reacts with GSH, which is a bionucleophile. The experimental data from the present study are in favor of a bonding process between GSH and phyllostictine A to form a complex though Michael attack at C=C bond at the acrylamide-like system. Considering the data obtained, two new hemisynthesized phyllostictine A derivatives together with three other natural phyllostictines (B, C and D) were also tested in vitro in five cancer cell lines. Compared to phyllostictine A, the two derivatives displayed a higher, phyllostictines B and D a lower, and phyllostictine C an almost equal, growth-inhibitory activity, respectively. These results led us to propose preliminary conclusions in terms of the structure-activity relationship (SAR) analyses for the anticancer activity of phyllostictine A and its related compounds, at least in vitro.« less

Large holographic 3D display for real-time computer-generated holography

NASA Astrophysics Data System (ADS)

Häussler, R.; Leister, N.; Stolle, H.

2017-06-01

SeeReal's concept of real-time holography is based on Sub-Hologram encoding and tracked Viewing Windows. This solution leads to significant reduction of pixel count and computation effort compared to conventional holography concepts. Since the first presentation of the concept, improved full-color holographic displays were built with dedicated components. The hologram is encoded on a spatial light modulator that is a sandwich of a phase-modulating and an amplitude-modulating liquid-crystal display and that modulates amplitude and phase of light. Further components are based on holographic optical elements for light collimation and focusing which are exposed in photopolymer films. Camera photographs show that only the depth region on which the focus of the camera lens is set is in focus while the other depth regions are out of focus. These photographs demonstrate that the 3D scene is reconstructed in depth and that accommodation of the eye lenses is supported. Hence, the display is a solution to overcome the accommodationconvergence conflict that is inherent for stereoscopic 3D displays. The main components, progress and results of the holographic display with 300 mm x 200 mm active area are described. Furthermore, photographs of holographic reconstructed 3D scenes are shown.

Orally available stilbene derivatives as potent HDAC inhibitors with antiproliferative activities and antitumor effects in human tumor xenografts.

PubMed

Kachhadia, Virendra; Rajagopal, Sridharan; Ponpandian, Thanasekaran; Vignesh, Radhakrishnan; Anandhan, Karnambaram; Prabhu, Daivasigamani; Rajendran, Praveen; Nidhyanandan, Saranya; Roy, Anshu Mittal; Ahamed, Fakrudeen Ali; Surendran, Narayanan; Rajagopal, Sriram; Narayanan, Shridhar; Gopalan, Balasubramanian

2016-01-27

Herein we report the synthesis and activity of a novel class of HDAC inhibitors based on 2, 3-diphenyl acrylic acid derivatives. The compounds in this series have shown to be potent HDAC inhibitors possessing significant antiproliferative activity. Further compounds in this series were subjected to metabolic stability in human liver microsomes (HLM), mouse liver microsomes (MLM), and exhibits promising stability in both. These efforts culminated with the identification of a developmental candidate (5a), which displayed desirable PK/PD relationships, significant efficacy in the xenograft models and attractive ADME profiles. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

In vitro and in vivo antileishmanial and trypanocidal studies of new N-benzene- and N-naphthalenesulfonamide derivatives.

PubMed

Galiana-Roselló, Cristina; Bilbao-Ramos, Pablo; Dea-Ayuela, M Auxiliadora; Rolón, Miriam; Vega, Celeste; Bolás-Fernández, Francisco; García-España, Enrique; Alfonso, Jorge; Coronel, Cathia; González-Rosende, M Eugenia

2013-11-27

We report in vivo and in vitro antileishmanial and trypanocidal activities of a new series of N-substituted benzene and naphthalenesulfonamides 1-15. Compounds 1-15 were screened in vitro against Leishmania infantum , Leishmania braziliensis , Leishmania guyanensis , Leishmania amazonensis , and Trypanosoma cruzi . Sulfonamides 6e, 10b, and 10d displayed remarkable activity and selectivity toward T. cruzi epimastigotes and amastigotes. 6e showed significant trypanocidal activity on parasitemia in a murine model of acute Chagas disease. Moreover, 6e, 8c, 9c, 12c, and 14d displayed interesting IC50 values against Leishmania spp promastigotes as well as L. amazonensis and L. infantum amastigotes. 9c showed excellent in vivo activity (up to 97% inhibition of the parasite growth) in a short-term treatment murine model for acute infection by L. infantum. In addition, the effect of compounds 9c and 14d on tubulin as potential target was assessed by confocal microscopy analysis applied to L. infantum promastigotes.

A new model of the distal convoluted tubule

PubMed Central

Ko, Benjamin; Mistry, Abinash C.; Hanson, Lauren; Mallick, Rickta; Cooke, Leslie L.; Hack, Bradley K.; Cunningham, Patrick

2012-01-01

The Na+-Cl− cotransporter (NCC) in the distal convoluted tubule (DCT) of the kidney is a key determinant of Na+ balance. Disturbances in NCC function are characterized by disordered volume and blood pressure regulation. However, many details concerning the mechanisms of NCC regulation remain controversial or undefined. This is partially due to the lack of a mammalian cell model of the DCT that is amenable to functional assessment of NCC activity. Previously reported investigations of NCC regulation in mammalian cells have either not attempted measurements of NCC function or have required perturbation of the critical without a lysine kinase (WNK)/STE20/SPS-1-related proline/alanine-rich kinase regulatory pathway before functional assessment. Here, we present a new mammalian model of the DCT, the mouse DCT15 (mDCT15) cell line. These cells display native NCC function as measured by thiazide-sensitive, Cl−-dependent 22Na+ uptake and allow for the separate assessment of NCC surface expression and activity. Knockdown by short interfering RNA confirmed that this function was dependent on NCC protein. Similar to the mammalian DCT, these cells express many of the known regulators of NCC and display significant baseline activity and dimerization of NCC. As described in previous models, NCC activity is inhibited by appropriate concentrations of thiazides, and phorbol esters strongly suppress function. Importantly, they display release of WNK4 inhibition of NCC by small hairpin RNA knockdown. We feel that this new model represents a critical tool for the study of NCC physiology. The work that can be accomplished in such a system represents a significant step forward toward unraveling the complex regulation of NCC. PMID:22718890

Association between rotation-related impairments and activity type in people with and without low back pain

PubMed Central

Weyrauch, Stephanie A.; Bohall, Sara C.; Sorensen, Christopher J.; Van Dillen, Linda R.

2015-01-01

Objective To determine if people with low back pain (LBP) who regularly participated in a rotation-related activity displayed more rotation-related impairments than people without LBP who did and did not participate in the activity. Design Secondary analysis of data from a case-control study. Setting Musculoskeletal analysis laboratory at an academic medical center. Participants A convenience sample of 55 participants with LBP who participated in a rotation-related sport, 26 back healthy controls who participated in a rotation-related sport (BHC+RRS) and 42 back healthy controls who did not participate in a rotation-related sport (BHC-RRS). Participants were matched based on age, gender, and activity level. Interventions Not applicable. Main Outcome Measures The total number of rotation-related impairments and asymmetric rotation-related impairments identified during a standardized clinical examination. Results Compared to the BHC-RRS group, both the LBP and BHC+RRS groups displayed significantly more (1) rotation-related impairments (LBP: p<.001; BHC+RRS: p=.015) (2) asymmetric rotation-related impairments (LBP: p=.006; BHC+RRS: p=.020) and (3) rotation-related impairments with trunk movement tests (LBP: p=.002; BHC+RRS: p<.001). The LBP group had significantly more rotation-related impairments with extremity movement tests than both of the back healthy groups (BHC+RRS: p=.011; BHC-RRS: p<.001). Conclusions LBP and BHC+RRS groups demonstrated a similar number of total rotation-related impairments and asymmetric rotation-related impairments, and these numbers were greater than those of the BHC-RRS group. Compared to people without LBP, people with LBP displayed more rotation-related impairments when moving an extremity. These findings suggest that impairments associated with extremity movements may be associated with having a LBP condition. PMID:25933914

Mitochondrial complex I and NAD(P)H oxidase are major sources of exacerbated oxidative stress in pressure-overloaded ischemic-reperfused hearts.

PubMed

Mozaffari, Mahmood S; Baban, Babak; Liu, Jun Yao; Abebe, Worku; Sullivan, Jennifer C; El-Marakby, Ahmed

2011-03-01

We tested the hypothesis that pressure overload exacerbates oxidative stress associated with augmented mitochondrial permeability transition (MPT) pore opening and cell death in ischemic-reperfused hearts. Pressure overload decreased the level of reduced glutathione but increased nitrotyrosine and 8-hydroxydeoxyguanosine levels in ischemic-reperfused hearts. The activity of catalase, but not superoxide dismutase (SOD), was lower in ischemic-reperfused hearts perfused at higher pressure. Mitochondria from ischemic-reperfused hearts subjected to higher perfusion pressure displayed significantly greater [³H]-2-deoxyglucose-6-P entrapment suggestive of greater MPT pore opening and consistent with greater necrosis and apoptosis. Tempol (SOD mimetic) reduced infarct size in both groups but it remained greater in the higher pressure group. By contrast, uric acid (peroxynitrite scavenger) markedly reduced infarct size at higher pressure, effectively eliminating the differential between the two groups. Inhibition of xanthine oxidase, with allopurinol, reduced infarct size but did not eliminate the differential between the two groups. However, amobarbital (inhibitor of mitochondrial complex I) or apocynin [inhibitor of NAD(P)H oxidase] reduced infarct size at both pressures and also abrogated the differential between the two groups. Consistent with the effect of apocynin, pressure-overloaded hearts displayed significantly higher NAD(P)H oxidase activity. Furthermore, pressure-overloaded hearts displayed increased nitric oxide synthase activity which, along with increased propensity to superoxide generation, may underlie uric acid-induced cardioprotection. In conclusion, increased oxidative and nitrosative stress, coupled with lack of augmented SOD and catalase activities, contributes importantly to the exacerbating impact of pressure overload on MPT pore opening and cell death in ischemic-reperfused hearts.

Positive association between leptin serum levels and disease activity on endoscopy in inflammatory bowel disease: A case-control study

PubMed Central

Trejo-Vazquez, Fabiola; Garza-Veloz, Idalia; Villela-Ramirez, Gabriela Alejandra; Ortiz-Castro, Yolanda; Mauricio-Saucedo, Panfilo; Cardenas-Vargas, Edith; Diaz-Baez, Mariana; Cid-Baez, Miguel A.; Castañeda-Miranda, Rodrigo; Ortiz-Rodriguez, Jose Manuel; Solis-Sanchez, Luis Octavio; Martinez-Fierro, Margarita L.

2018-01-01

Inflammatory bowel disease (IBD) includes ulcerative colitis (UC), Crohn's disease (CD) and indeterminate colitis. As these subtypes of IBD display important differences in the behavior of the natural course of the disease, the identification of non-invasive markers for IBD is important. The aim of the present study was to evaluate the serum levels of 10 adipokines and their association with endoscopic activity in IBD. The 10-protein profile (C-peptide, ghrelin, gastric inhibitory polypeptide, glucagon-like peptide-1, glucagon, insulin, leptin, plasminogen activator inhibitor-1, resistin and visfatin) was evaluated using serum from 53 participants (23 UC and 11 CD patients, as well as 19 controls) from Zacatecas (Mexico) by using the Bio-Plex Pro Human Diabetes 10-Plex Panel (Bio-Rad Laboratories, Inc.). Compared with those in the controls, leptin levels were significantly lower in patients with IBD (P=4.9×10−4). In addition, serum leptin displayed differences between groups with and without disease activity on endoscopy (P<0.001). Among the study population, serum leptin levels of <5,494 pg/ml significantly increased the odds of IBD by 12.8-fold [odds ratio (OR)=12.8, 95% confidence interval (CI)=3.04–53.9, P=0.001]. In addition, patients with serum leptin levels of <2,498 pg/ml displayed 5.8-fold greater odds of disease activity on endoscopy among the study population (OR=5.8, 95% CI=1.52–22.4, P=0.013). No differences in the serum levels of the remaining proteins were identified between the groups. Among the study population, serum leptin was associated with an increased risk of IBD and with disease activity on endoscopy. Additional studies will be necessary to validate the use of leptin as a non-invasive biomarker of IBD severity. PMID:29545852

Physical correction filter for improving the optical quality of an image

NASA Technical Reports Server (NTRS)

Lee, S. Y. (Inventor)

1975-01-01

A family of physical correction filters is described. Each filter is designed to correct image content of a photographed scene of limited resolution and includes a first filter element with a pinhole through which light passes to a differential amplifier. A second filter element through which light passes through one or more openings, whose geometric configuration is a function of the cause of the resolution loss included. The light, passing through the second filter element, is also supplied to the differential amplifier whose output is used to activate an optical display or recorder to reproduce a photograph or display of the scene in the original photograph or display of the scene in the original photograph with resolution which is significantly greater than that characterizing the original photograph.

Spacesuit Data Display and Management System

NASA Technical Reports Server (NTRS)

Hall, David G.; Sells, Aaron; Shah, Hemal

2009-01-01

A prototype embedded avionics system has been designed for the next generation of NASA extra-vehicular-activity (EVA) spacesuits. The system performs biomedical and other sensor monitoring, image capture, data display, and data transmission. An existing NASA Phase I and II award winning design for an embedded computing system (ZIN vMetrics - BioWATCH) has been modified. The unit has a reliable, compact form factor with flexible packaging options. These innovations are significant, because current state-of-the-art EVA spacesuits do not provide capability for data displays or embedded data acquisition and management. The Phase 1 effort achieved Technology Readiness Level 4 (high fidelity breadboard demonstration). The breadboard uses a commercial-grade field-programmable gate array (FPGA) with embedded processor core that can be upgraded to a space-rated device for future revisions.

Image quality evaluation for smart-phone displays at lighting levels of indoor and outdoor conditions

NASA Astrophysics Data System (ADS)

Gong, Rui; Xu, Haisong; Wang, Binyu; Luo, Ming Ronnier

2012-08-01

The image quality of two active matrix organic light emitting diode (AMOLED) smart-phone displays and two in-plane switching (IPS) ones was visually assessed at two levels of ambient lighting conditions corresponding to indoor and outdoor applications, respectively. Naturalness, colorfulness, brightness, contrast, sharpness, and overall image quality were evaluated via psychophysical experiment by categorical judgment method using test images selected from different application categories. The experimental results show that the AMOLED displays perform better on colorfulness because of their wide color gamut, while the high pixel resolution and high peak luminance of the IPS panels help the perception of brightness, contrast, and sharpness. Further statistical analysis of ANOVA indicates that ambient lighting levels have significant influences on the attributes of brightness and contrast.

Draft standard for color AMLCDs in U.S. military aircraft

NASA Astrophysics Data System (ADS)

Hopper, Darrel G.; Dolezal, William K.; Schur, Keith; Liccione, John W.

1994-06-01

Flight instruments have begun to use color active liquid crystal displays (AMLCDs), signaling the beginning of a significant transition from electromechanical and cathode ray tube display designs to AMLCD designs. We have the opportunity with this new technology to establish common products capable of meeting user requirements for sunlight-readable, color and gray scale-capable, high-pixel-count, flat-panel displays for weapon systems. The Wright Laboratory is leading the development of standard and specification documentation for this new generation of display modules based on requirements for U.S. military aircraft. These requirements are similar in many ways to those of both the civil aviation and automotive industries. Accordingly, commonality with these applications is incorporated, where possible, along with the requirements for all military combat applications. Industry and government organizations are involved in this process through workshops and draft review processes. Military procurement specifications for combat system applications may use this information as a source of recommended best practice for this new generation of digital flat panel displays. The draft standard will be revised based upon continuing feedback by early 1995.

The Effect of Ownship Information and NexRad Resolution on Pilot Decision Making in the Use of a Cockpit Weather Information Display

NASA Technical Reports Server (NTRS)

Novacek, Paul F.; Burgess, Malcolm A.; Heck, Michael L.; Stokes, Alan F.; Stough, H. Paul, III (Technical Monitor)

2001-01-01

A two-phase experiment was conducted to explore the effects of data-link weather displays upon pilot decision performance. The experiment was conducted with 49 instrument rated pilots who were divided into four groups and placed in a simulator with a realistic flight scenario involving weather containing convective activity. The inflight weather display depicted NEXRAD images, with graphical and textual METARs over a moving map display. The experiment explored the effect of weather information, ownship position symbology and NEXRAD cell size resolution. The phase-two experiment compared two groups using the data-linked weather display with ownship position symbology. These groups were compared to the phase-one group that did not have ownship position symbology. The phase-two pilots were presented with either large NEXRAD cell size (8 km) or small cell size (4 km). Observations noted that the introduction of ownship symbology did not appear to significantly impact the decision making process, however, the introduction of ownship did reduce workload. Additionally, NEXRAD cell size resolution did appear to influence the tactical decision making process.

Display technologies; Proceedings of the Meeting, National Chiao Tung Univ., Hsinchu, Taiwan, Dec. 17, 18, 1992

NASA Astrophysics Data System (ADS)

Chen, Shu-Hsia; Wu, Shin-Tson

1992-10-01

A broad range of interdisciplinary subjects related to display technologies is addressed, with emphasis on high-definition displays, CRTs, projection displays, materials for display application, flat-panel displays, display modeling, and polymer-dispersed liquid crystals. Particular attention is given to a CRT approach to high-definition television display, a superhigh-resolution electron gun for color display CRT, a review of active-matrix liquid-crystal displays, color design for LCD parameters in projection and direct-view applications, annealing effects on ZnS:TbF3 electroluminescent devices prepared by RF sputtering, polycrystalline silicon thin film transistors with low-temperature gate dielectrics, refractive index dispersions of liquid crystals, a new rapid-response polymer-dispersed liquid-crystal material, and improved liquid crystals for active-matrix displays using high-tilt-orientation layers. (No individual items are abstracted in this volume)

Correlates of spreading depolarization in human scalp electroencephalography

PubMed Central

Drenckhahn, Christoph; Winkler, Maren K. L.; Major, Sebastian; Scheel, Michael; Kang, Eun-Jeung; Pinczolits, Alexandra; Grozea, Cristian; Hartings, Jed A.; Woitzik, Johannes

2012-01-01

It has been known for decades that suppression of spontaneous scalp electroencephalographic activity occurs during ischaemia. Trend analysis for such suppression was found useful for intraoperative monitoring during carotid endarterectomy, or as a screening tool to detect delayed cerebral ischaemia after aneurismal subarachnoid haemorrhage. Nevertheless, pathogenesis of such suppression of activity has remained unclear. In five patients with aneurismal subarachnoid haemorrhage and four patients with decompressive hemicraniectomy after malignant hemispheric stroke due to middle cerebral artery occlusion, we here performed simultaneously full-band direct and alternating current electroencephalography at the scalp and direct and alternating current electrocorticography at the cortical surface. After subarachnoid haemorrhage, 275 slow potential changes, identifying spreading depolarizations, were recorded electrocorticographically over 694 h. Visual inspection of time-compressed scalp electroencephalography identified 193 (70.2%) slow potential changes [amplitude: −272 (−174, −375) µV (median quartiles), duration: 5.4 (4.0, 7.1) min, electrocorticography–electroencephalography delay: 1.8 (0.8, 3.5) min]. Intervals between successive spreading depolarizations were significantly shorter for depolarizations with electroencephalographically identified slow potential change [33.0 (27.0, 76.5) versus 53.0 (28.0, 130.5) min, P = 0.009]. Electroencephalography was thus more likely to display slow potential changes of clustered than isolated spreading depolarizations. In contrast to electrocorticography, no spread of electroencephalographic slow potential changes was seen, presumably due to superposition of volume-conducted electroencephalographic signals from widespread cortical generators. In two of five patients with subarachnoid haemorrhage, serial magnetic resonance imaging revealed large delayed infarcts at the recording site, while electrocorticography showed clusters of spreading depolarizations with persistent depression of spontaneous activity. Alternating current electroencephalography similarly displayed persistent depression of spontaneous activity, and direct current electroencephalography slow potential changes riding on a shallow negative ultraslow potential. Isolated spreading depolarizations with depression of both spontaneous electrocorticographic and electroencephalographic activity displayed significantly longer intervals between successive spreading depolarizations than isolated depolarizations with only depression of electrocorticographic activity [44.0 (28.0, 132.0) min, n = 96, versus 30.0 (26.5, 51.5) min, n = 109, P = 0.001]. This suggests fusion of electroencephalographic depression periods at high depolarization frequency. No propagation of electroencephalographic depression was seen between scalp electrodes. Durations/magnitudes of isolated electroencephalographic and corresponding electrocorticographic depression periods correlated significantly. Fewer spreading depolarizations were recorded in patients with malignant hemispheric stroke but characteristics were similar to those after subarachnoid haemorrhage. In conclusion, spreading depolarizations and depressions of spontaneous activity display correlates in time-compressed human scalp direct and alternating current electroencephalography that may serve for their non-invasive detection. PMID:22366798

Cell wall structure suitable for surface display of proteins in Saccharomyces cerevisiae.

PubMed

Matsuoka, Hiroyuki; Hashimoto, Kazuya; Saijo, Aki; Takada, Yuki; Kondo, Akihiko; Ueda, Mitsuyoshi; Ooshima, Hiroshi; Tachibana, Taro; Azuma, Masayuki

2014-02-01

A display system for adding new protein functions to the cell surfaces of microorganisms has been developed, and applications of the system to various fields have been proposed. With the aim of constructing a cell surface environment suitable for protein display in Saccharomyces cerevisiae, the cell surface structures of cell wall mutants were investigated. Four cell wall mutant strains were selected by analyses using a GFP display system via a GPI anchor. β-Glucosidase and endoglucanase II were displayed on the cell surface in the four mutants, and their activities were evaluated. mnn2 deletion strain exhibited the highest activity for both the enzymes. In particular, endoglucanase II activity using carboxymethylcellulose as a substrate in the mutant strain was 1.9-fold higher than that of the wild-type strain. In addition, the activity of endoglucanase II released from the mnn2 deletion strain by Zymolyase 20T treatment was higher than that from the wild-type strain. The results of green fluorescent protein (GFP) and endoglucanase displays suggest that the amounts of enzyme displayed on the cell surface were increased by the mnn2 deletion. The enzyme activity of the mnn2 deletion strain was compared with that of the wild-type strain. The relative value (mnn2 deletion mutant/wild-type strain) of endoglucanase II activity using carboxymethylcellulose as a substrate was higher than that of β-glucosidase activity using p-nitrophenyl-β-glucopyranoside as a substrate, suggesting that the cell surface environment of the mnn2 deletion strain facilitates the binding of high-molecular-weight substrates to the active sites of the displayed enzymes. Copyright © 2014 John Wiley & Sons, Ltd.

Identification and characterization of a salivary-pellicle-binding peptide by phage display.

PubMed

Cukkemane, Nivedita; Bikker, Floris J; Nazmi, Kamran; Brand, Henk S; Veerman, Enno C I

2014-05-01

Dental biofilms are associated with oral diseases, making their control necessary. One way to control them is to prevent initial bacterial adherence to the salivary pellicle and thereby eventually decrease binding of late colonizing potential pathogens. The goal of this study was to generate a salivary-pellicle-binding peptide (SPBP) with antifouling activity towards primary colonizing bacteria. In order to achieve this goal we aimed to: (i) identify novel SPBPs by phage display; (ii) characterize the binding and antifouling properties of the selected SPBPs. A library of 2×10(9) phages displaying a random sequence of 12-mer peptides was used to identify peptides that bound selectively to the in vitro salivary pellicle. Three rounds of panning resulted in the selection of 10 pellicle-binding phages, each displaying a novel peptide sequence. The peptides were synthesized and their binding to the in vitro salivary pellicle was characterized in the presence and absence of calcium ions and Tween-20. The antifouling property of hydroxyapatite (HA) and saliva-coated HA discs treated with and without SPBPs were evaluated against Streptococcus gordonii. Ten unique SPBPs were identified using the phage display. One of these peptides, SPBP 10 (NSAAVRAYSPPS), exhibited significant binding to the in vitro salivary pellicle which was neither influenced by calcium ions, nor affected by up to 0.5% Tween-20. Its antifouling property against S. gordonii was significantly higher on the treated surfaces than on untreated surfaces. Use of the phage display library enabled us to find a specific SPBP with antifouling property towards S. gordonii. Copyright © 2014 Elsevier Ltd. All rights reserved.

Hazard alerting and situational awareness in advanced air transport cockpits

NASA Technical Reports Server (NTRS)

Hansman, R. John; Wanke, Craig; Kuchar, James; Mykityshyn, Mark; Hahn, Edward; Midkiff, Alan

1993-01-01

Advances in avionics and display technology have significantly changed the cockpit environment in current 'glass cockpit' aircraft. Recent developments in display technology, on-board processing, data storage, and datalinked communications are likely to further alter the environment in second and third generation 'glass cockpit' aircraft. The interaction of advanced cockpit technology with human cognitive performance has been a major area of activity within the MIT Aeronautical Systems Laboratory. This paper presents an overview of the MIT Advanced Cockpit Simulation Facility. Several recent research projects are briefly reviewed and the most important results are summarized.

Dynamic, diagnostic, and pharmacological radionuclide studies of the esophagus in achalasia: correlation with manometric measurements

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

Rozen, P.; Gelfond, M.; Zaltzman, S.

1982-08-01

The esophagus was evaluated in 15 patients with achalasia by continuous gamma camera imaging following ingestion of a semi-solid meal labeled with /sup 99//sup m/Tc. The images were displayed and recorded on a simple computerized data processing/display system. Subsequent cine' mode images of esophagela emptying demonstrated abnormalities of the body of the esophagus not reflected by the manometric examination. Computer-generated time-activity curves representing specific regions of interest were better than manometry in evaluating the results of myotomy, dilatation, and drug therapy. Isosorbide dinitrate significantly improved esophageal emptying.

Assessment of urinary inhibitor or promoter activity in uric acid nephrolithiasis

PubMed Central

Doizi, Steeve; Rodgers, Kathy; Poindexter, John; Sakhaee, Khashayar; Maalouf, Naim M.

2017-01-01

Purpose To assess the presence of a reduced inhibitor activity or an increased promoter activity in urine of idiopathic uric acid stone formers (IUASF) compared to non-stone formers (NSF) independent of urinary pH. Methods 30 IUASF, 9 obese NSF and 12 lean NSF collected 24-hour urine under metabolic diet. Three urine aliquots per subject were used to assess spontaneous nucleation (SN, de novo crystal formation), crystal growth (CG) using a 0.1 mg/mL seed of anhydrous uric acid (UA) and steady state (SS) of UA solubility using a 5 mg/mL seed of UA (assessing maximum amount of UA dissolvable in urine). All experiments were conducted for 6 hours at a constant pH of 5.0. UA concentration was measured in filtered aliquots at 0, 3 and 6 hours. Results At baseline, 24-hour urinary pH was significantly lower and UA saturation significantly higher in IUASF. No significant SN occurred and a similar SS UA concentration was reached in the three groups. IUASF and lean NSF displayed a similar decrease in UA concentration during CG, while obese NSF started with higher UA concentration and consequently displayed higher magnitude of decrease in UA concentration for CG. Conclusions This study suggests that there is no significant difference between IUASF and NSF in terms of promoter or inhibitor activity in whole urine against UA stone formation when urine pH is maintained constant. The findings suggest that UA stone formation is dictated by a high urinary saturation with respect to UA, driven primarily by a low urine pH. PMID:26723865

In vitro bioactive analysis and antioxidant activity of two species of seaweeds from the Gulf of Mannar.

PubMed

Chakraborty, Kajal; Raola, Vamshi Krishna

2017-09-25

Evaluation of in vitro standard antioxidant assays, such as 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azino-bis-3 ethylbenzothiozoline-6-sulphonic acid diammonium salt (ABTS + ) radical scavenging, lipid peroxidation inhibitory (or thiobarbituric acid formation inhibitory activity) and ferrous ion (Fe +2 ) chelating activities of different solvent extracts of seaweeds, Jania rubens and Kappaphycus alvarezii collected from the Gulf of Mannar of the Peninsular India, were carried out. The methodology utilised bioactivity-guided extraction of seaweed with effective solvent comprised classical chromatographic and spectroscopic techniques. The ethyl acetate extraction of seaweeds displayed significantly greater antioxidant activity than dichloromethane and n-hexane extraction. Bioactivity-guided chromatographic separation of the ethyl acetate extract of seaweeds with potentially greater antioxidant activities, yielded 6α-methoxy-4bβ-methyl-7β-vinyl-1,2,3,4,4a,4b,5,6,7,8,8a,9-dodecahydro-2β-phenanthrenol (1) from J. rubens, whereas K. alvarezii yielded 2β-ethyl-9-oxo-5α-vinyl-1,2,5,5a,6,7,8,9-octahydroheptalene-10,1-carbolactone (2) and methyl-2-ethyl-9-oxo-5α-vinyl-1,2,5,5a,6,7,10,10a-octahydroheptalene-1α-carboxylate (3). Compound 1 displayed significantly greater DPPH scavenging activities (IC 50 0.22 mg/mL) than α-tocopherol (IC 50 0.63 mg/mL). The order of DPPH radical-scavenging activities were compounds 1 > 2 > 3.

Elevated Apoptosis in the Liver of Dairy Cows with Ketosis.

PubMed

Du, Xiliang; Chen, Liang; Huang, Dan; Peng, Zhicheng; Zhao, Chenxu; Zhang, Yuming; Zhu, Yiwei; Wang, Zhe; Li, Xinwei; Liu, Guowen

2017-01-01

Dairy cows with ketosis are characterized by oxidative stress and hepatic damage. The aim of this study was to investigate hepatic oxidative stress and the apoptotic status of ketotic cows, as well as the underlying apoptosis pathway. The blood aspartate aminotransferase (AST), alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH) and gamma-glutamyl transferase (GGT) activities and the haptoglobin (HP), serum amyloid A (SAA) and serum apoptotic cytokeratin 18 neo-epitope M30 (CK18 M30) concentrations were determined by commercially available kits and ELISA kits, respectively. Liver histology, TUNEL and Oil red O staining were performed in liver tissue samples. TG contents were measured using an enzymatic kit; Caspase 3 assays were carried out using the Caspase 3 activity assay kit; oxidation and antioxidant markers were measured using biochemical kits; apoptosis pathway were determined by qRT-PCR and western blot. Ketotic cows displayed hepatic fat accumulation. The hepatic malondialdehyde (MDA) content was significantly increased, but the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were markedly decreased in ketotic cows compared with control cows, indicating that ketotic cows displayed severe oxidative stress. Significantly higher serum levels of the hepatic damage markers AST, ALT, GGT and GLDH were observed in ketotic cows than in control cows. The blood concentration of the apoptotic marker CK18 M30 and the number of TUNEL-positive cells in the liver of ketotic cows were 1.19- and 2.61-fold, respectively, higher than the values observed in control cows. Besides, Caspase 3 activity was significantly increased in the liver of ketosis cows. Importantly, the levels of phosphorylated c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38MAPK) were significantly increased but the level of phosphorylated extracellular signal-regulated kinase1/2 (ERK1/2) was markedly decreased, which further promoted tumor protein 53 (p53) expression and inhibited nuclear factor E2-related factor 2 (Nrf2) expression. The apoptosis-related molecules p21, MDM2, Caspase 3, Caspase 9 and Bax were expressed at significantly higher levels in ketotic cows than in healthy cows, whereas the anti-apoptosis molecule Bcl-2 was expressed at significantly lower levels. Based on these results, ketotic cows display severe hepatic oxidative stress. The hepatic MAPK-p53-Nrf2 apoptotic pathway is over induced and partially mediated apoptotic damage in the liver. © 2017 The Author(s). Published by S. Karger AG, Basel.

Active and passive distraction using a head-mounted display helmet: effects on cold pressor pain in children.

PubMed

Dahlquist, Lynnda M; McKenna, Kristine D; Jones, Katia K; Dillinger, Lindsay; Weiss, Karen E; Ackerman, Claire Sonntag

2007-11-01

The current study tested the effectiveness of interactive versus passive distraction that was delivered via a virtual reality type head-mounted display helmet for children experiencing cold pressor pain. Forty children, aged 5 to 13 years, underwent 1 or 2 baseline cold pressor trials followed by interactive distraction and passive distraction trials in counterbalanced order. Pain threshold and pain tolerance. Children who experienced either passive or interactive distraction demonstrated significant improvements in both pain tolerance and pain threshold relative to their baseline scores. In contrast, children who underwent a second cold pressor trial without distraction showed no significant improvements in pain tolerance or threshold. Although both distraction conditions were effective, the interactive distraction condition was significantly more effective. Implications for the treatment of children's distress during painful medical procedures are discussed. (PsycINFO Database Record (c) 2007 APA, all rights reserved).

Comparison of Thoracic and Lumbar Erector Spinae Muscle Activation Before and After a Golf Practice Session.

PubMed

Sorbie, Graeme G; Grace, Fergal M; Gu, Yaodong; Baker, Julien S; Ugbolue, Ukadike C

2017-08-01

Lower back pain is commonly associated with golfers. The study aimed: to determine whether thoracic- and lumbar-erector-spinae muscle display signs of muscular fatigue after completing a golf practice session, and to examine the effect of the completed practice session on club head speed, ball speed and absolute carry distance performance variables. Fourteen right-handed male golfers participated in the laboratory-based-study. Surface electromyography (EMG) data was collected from the lead and trail sides of the thoracic- and lumbar-erector-spinae muscle. Normalized root mean squared (RMS) EMG activation levels and performance variables for the golf swings were compared before and after the session. Fatigue was assessed using median frequency (MDF) and RMS during the maximum voluntary contraction (MVC) performed before and after the session. No significant differences were observed in RMS thoracic- and lumbar-erector-spinae muscle activation levels during the five phases of the golf swing and performance variables before and after the session (p > .05). Significant changes were displayed in MDF and RMS when comparing the MVC performed before and after the session (p < .05). Fatigue was evident in the trail side of the erector-spinae muscle after the session.

Bio-nanocapsules displaying various immunoglobulins as an active targeting-based drug delivery system.

PubMed

Tatematsu, Kenji; Iijima, Masumi; Yoshimoto, Nobuo; Nakai, Tadashi; Okajima, Toshihide; Kuroda, Shun'ichi

2016-04-15

The bio-nanocapsule (BNC) is an approximately 30-nm particle comprising the hepatitis B virus (HBV) envelope L protein and a lipid bilayer. The L protein harbors the HBV-derived infection machinery; therefore, BNC can encapsulate payloads such as drugs, nucleic acids, and proteins and deliver them into human hepatocytes specifically in vitro and in vivo. To diversify the possible functions of BNC, we generated ZZ-BNC by replacing the domain indispensable for the human hepatotrophic property of BNC (N-terminal region of L protein) with the tandem form of the IgG Fc-binding Z domain of Staphylococcus aureus protein A. Thus, the ZZ-BNC is an active targeting-based drug delivery system (DDS) nanocarrier that depends on the specificity of the IgGs displayed. However, the Z domain limits the animal species and subtypes of IgGs that can be displayed on ZZ-BNC. In this study, we introduced into BNC an Ig κ light chain-binding B1 domain of Finegoldia magna protein L (protein-L B1 domain) and an Ig Fc-binding C2 domain of Streptococcus species protein G (protein-G C2 domain) to produce LG-BNC. The LL-BNC was constructed in a similar way using a tandem form of the protein-L B1 domain. Both LG-BNC and LL-BNC could display rat IgGs, mouse IgG1, human IgG3, and human IgM, all of which not binding to ZZ-BNC, and accumulate in target cells in an antibody specificity-dependent manner. Thus, these BNCs could display a broad spectrum of Igs, significantly improving the prospects for BNCs as active targeting-based DDS nanocarriers. We previously reported that ZZ-BNC, bio-nanocapsule deploying the IgG-binding Z domain of protein A, could display cell-specific antibody in an oriented immobilization manner, and act as an active targeting-based DDS nanocarrier. Since the Z domain can only bind to limited types of Igs, we generated BNCs deploying other Ig-binding domains: LL-BNC harboring the tandem form of Ig-binding domain of protein L, and LG-BNC harboring the Ig binding domains of protein L and protein G sequentially. Both BNCs could display a broader spectrum of Igs than does the ZZ-BNC. When these BNCs displayed anti-CD11c IgG or anti-EGFR IgG, both of which cannot bind to Z domain, they could bind to and then enter their respective target cells. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Genotypic and phenotypic characterization of Cryptococcus flavescens, beneficial biocontrol agents for controlling Fusarium head blight of wheat

USDA-ARS?s Scientific Manuscript database

Cryptococcus flavescens strain OH182.9_3C (3C) previously displayed significant biological control activity against Fusarium head blight, a globally important disease of wheat; however, the diversity within C. flavescens has not been previously characterized. Multilocus sequence typing was performed...

Transcendental Meditation and Progressive Relaxation: Their Physiological Effects.

ERIC Educational Resources Information Center

Throll, D. A.

1982-01-01

Measured oxygen consumption, subjects' respiration rate, heart rate, and blood pressure before and after learned Transcendental Meditation (TM) or Jacobson's Progressive Relaxation. Found TM group displayed more significant decreases during meditation and activity, explained primarily in terms of greater amount of time the TM group spent on their…

PED/PEA-15 Controls Fibroblast Motility and Wound Closure by ERK1/2-Dependent Mechanisms

PubMed Central

Buonomo, Roberta; Giacco, Ferdinando; Vasaturo, Angela; Caserta, Sergio; Guido, Stefano; Pagliara, Valentina; Garbi, Corrado; Mansueto, Gelsomina; Cassese, Angela; Perruolo, Giuseppe; Oriente, Francesco; Miele, Claudia; Beguinot, Francesco; Formisano, Pietro

2012-01-01

Cell migration is dependent on the control of signaling events that play significant roles in creating contractile force and in contributing to wound closure. We evaluated wound closure in fibroblasts from mice overexpressing (TgPED) or lacking ped/pea-15 (KO), a gene overexpressed in patients with type 2 diabetes. Cultured skin fibroblasts isolated from TgPED mice showed a significant reduction in the ability to recolonize wounded area during scratch assay, compared to control fibroblasts. This difference was observed both in the absence and in the presence of mytomicin C, an inhibitor of mitosis. In time-lapse experiments, TgPED fibroblasts displayed about twofold lower velocity and diffusion coefficient, as compared to controls. These changes were accompanied by reduced spreading and decreased formation of stress fibers and focal adhesion plaques. At the molecular level, TgPED fibroblasts displayed decreased RhoA activation and increased abundance of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2). Inhibition of ERK1/2 activity by PD98059 restored RhoA activation, cytoskeleton organization and cell motility, and almost completely rescued wound closure of TgPED fibroblasts. Interestingly, skin fibroblasts isolated from KO mice displayed an increased wound closure ability. In vivo, healing of dorsal wounds was delayed in TgPED and accelerated in KO mice. Thus, PED/PEA-15 may affect fibroblast motility by a mechanism, at least in part, mediated by ERK1/2. J. Cell. Physiol. 227: 2106–2116, 2012. © 2011 Wiley Periodicals, Inc. PMID:21780113

Visual Phonetic Processing Localized Using Speech and Non-Speech Face Gestures in Video and Point-Light Displays

PubMed Central

Bernstein, Lynne E.; Jiang, Jintao; Pantazis, Dimitrios; Lu, Zhong-Lin; Joshi, Anand

2011-01-01

The talking face affords multiple types of information. To isolate cortical sites with responsibility for integrating linguistically relevant visual speech cues, speech and non-speech face gestures were presented in natural video and point-light displays during fMRI scanning at 3.0T. Participants with normal hearing viewed the stimuli and also viewed localizers for the fusiform face area (FFA), the lateral occipital complex (LOC), and the visual motion (V5/MT) regions of interest (ROIs). The FFA, the LOC, and V5/MT were significantly less activated for speech relative to non-speech and control stimuli. Distinct activation of the posterior superior temporal sulcus and the adjacent middle temporal gyrus to speech, independent of media, was obtained in group analyses. Individual analyses showed that speech and non-speech stimuli were associated with adjacent but different activations, with the speech activations more anterior. We suggest that the speech activation area is the temporal visual speech area (TVSA), and that it can be localized with the combination of stimuli used in this study. PMID:20853377

Differential activation of G-proteins by mu-opioid receptor agonists.

PubMed

Saidak, Zuzana; Blake-Palmer, Katherine; Hay, Debbie L; Northup, John K; Glass, Michelle

2006-03-01

We investigated the ability of the activated mu-opioid receptor (MOR) to differentiate between myristoylated G(alphai1) and G(alphaoA) type G(alpha) proteins, and the maximal activity of a range of synthetic and endogenous agonists to activate each G(alpha) protein. Membranes from HEK293 cells stably expressing transfected MOR were chaotrope extracted to denature endogenous G-proteins and reconstituted with specific purified G-proteins. The G(alpha) subunits were generated in bacteria and were demonstrated to be recognised equivalently to bovine brain purified G(alpha) protein by CB(1) cannabinoid receptors. The ability of agonists to catalyse the MOR-dependent GDP/[(35)S]GTP(gamma)S exchange was then compared for G(alphai1) and G(alphaoA). Activation of MOR by DAMGO produced a high-affinity saturable interaction for G(alphaoA) (K(m)=20+/-1 nM) but a low-affinity interaction with G(alphai1) (K(m)=116+/-12 nM). DAMGO, met-enkephalin and leucine-enkephalin displayed maximal G(alpha) activation among the agonists evaluated. Endomorphins 1 and 2, methadone and beta-endorphin activated both G(alpha) to more than 75% of the maximal response, whereas fentanyl partially activated both G-proteins. Buprenorphine and morphine demonstrated a statistically significant difference between the maximal activities between G(alphai1) and G(alphaoA). Interestingly, DAMGO, morphine, endomorphins 1 and 2, displayed significant differences in the potencies for the activation of the two G(alpha). Differences in maximal activity and potency, for G(alphai1) versus G(alphaoA), are both indicative of agonist selective activation of G-proteins in response to MOR activation. These findings may provide a starting point for the design of drugs that demonstrate greater selectivity between these two G-proteins and therefore produce a more limited range of effects.

Differential activation of G-proteins by μ-opioid receptor agonists

PubMed Central

Saidak, Zuzana; Blake-Palmer, Katherine; Hay, Debbie L; Northup, John K; Glass, Michelle

2006-01-01

We investigated the ability of the activated μ-opioid receptor (MOR) to differentiate between myristoylated Gαi1 and GαoA type Gα proteins, and the maximal activity of a range of synthetic and endogenous agonists to activate each Gα protein. Membranes from HEK293 cells stably expressing transfected MOR were chaotrope extracted to denature endogenous G-proteins and reconstituted with specific purified G-proteins. The Gα subunits were generated in bacteria and were demonstrated to be recognised equivalently to bovine brain purified Gα protein by CB1 cannabinoid receptors. The ability of agonists to catalyse the MOR-dependent GDP/[35S]GTPγS exchange was then compared for Gαi1 and GαoA. Activation of MOR by DAMGO produced a high-affinity saturable interaction for GαoA (Km=20±1 nM) but a low-affinity interaction with Gαi1 (Km=116±12 nM). DAMGO, met-enkephalin and leucine-enkephalin displayed maximal Gα activation among the agonists evaluated. Endomorphins 1 and 2, methadone and β-endorphin activated both Gα to more than 75% of the maximal response, whereas fentanyl partially activated both G-proteins. Buprenorphine and morphine demonstrated a statistically significant difference between the maximal activities between Gαi1 and GαoA. Interestingly, DAMGO, morphine, endomorphins 1 and 2, displayed significant differences in the potencies for the activation of the two Gα. Differences in maximal activity and potency, for Gαi1 versus GαoA, are both indicative of agonist selective activation of G-proteins in response to MOR activation. These findings may provide a starting point for the design of drugs that demonstrate greater selectivity between these two G-proteins and therefore produce a more limited range of effects. PMID:16415903

NLRP3 inflammasome activation mediates fatigue-like behaviors in mice via neuroinflammation.

PubMed

Zhang, Ziteng; Ma, Xiujuan; Xia, Zhenna; Chen, Jikuai; Liu, Yangang; Chen, Yongchun; Zhu, Jiangbo; Li, Jinfeng; Yu, Huaiyu; Zong, Ying; Lu, Guocai

2017-09-01

Numerous experimental and clinical studies have suggested that the interaction between the immune system and the brain plays an important role in the pathophysiology of chronic fatigue syndrome (CFS). The NLRP3 inflammasome is an important part of the innate immune system. This complex regulates proinflammatory cytokine interleukin-1β (IL-1β) maturation, which triggers different kinds of immune-inflammatory reactions. We employed repeated forced swims to establish a model of CFS in mice. NLRP3 knockout (KO) mice were also used to explore NLRP3 inflammasome activation in the mechanisms of CFS, using the same treatment. After completing repeated swim tests, the mice displayed fatigue-like behaviors, including locomotor activity and reduced fall-off time on the rota-rod test, which was accompanied by significantly higher mature IL-1β level in the prefrontal cortex (PFC) and malondialdehyde (MDA) level in serum. We also found increased NLRP3 protein expression, NLRP3 inflammasome formation and increased mature IL-1β production in the PFC, relative to untreated mice. The NLRP3 KO mice displayed significantly moderated fatigue behaviors along with decreased PFC and serum IL-1β levels under the same treatment. These findings demonstrated the involvement of NLRP3 inflammasome activation in the mechanism of swimming-induced fatigue. Future therapies targeting the NLRP3/IL-1β pathway may have significant potential for fatigue prevention and treatment. Copyright © 2017. Published by Elsevier Ltd.

Long-term effects on symptoms by reducing electric fields from visual display units.

PubMed

Oftedal, G; Nyvang, A; Moen, B E

1999-10-01

The purpose of the study was to see whether the results of an earlier study [ie, that skin symptoms were reduced by reducing electric fields from visual display units (VDU)] could be reproduced or not. In addition, an attempt was made to determine whether eye symptoms and symptoms from the nervous system could be reduced by reducing VDU electric fields. The study was designed as a controlled double-blind intervention. The electric fields were reduced by using electric-conducting screen filters. Forty-two persons completed the study while working at their ordinary job, first 1 week with no filter, then 3 months with an inactive filter and then 3 months with an active filter (or in reverse order). The inactive filters were identical to the active ones, except that their ground cables were replaced by empty plastic insulation. The inactive filters did not reduce the fields from the VDU. The fields were significantly lower with active filters than with inactive filters. Most of the symptoms were statistically significantly less pronounced in the periods with the filters when compared with the period with no filter. This finding can be explained by visual effects and psychological effects. No statistically significant difference in symptom severeness was observed between the period with an inactive filter and the one with an active filter. The study does not support the hypothesis that skin, eye, or nervous system symptoms can be reduced by reducing VDU electric fields.

Lordosis facilitated by GPER-1 receptor activation involves GnRH-1, progestin and estrogen receptors in estrogen-primed rats.

PubMed

Domínguez-Ordóñez, R; Garcia-Juárez, M; Lima-Hernández, F J; Gómora-Arrati, P; Domínguez-Salazar, E; Blaustein, J D; Etgen, A M; González-Flores, O

2018-02-01

The present study assessed the participation of membrane G-protein coupled estrogen receptor 1 (GPER-1) and gonadotropin releasing hormone 1 (GnRH-1) receptor in the display of lordosis induced by intracerebroventricular (icv) administration of G1, a GPER-1 agonist, and by unesterified 17β-estradiol (free E 2 ). In addition, we assessed the participation of both estrogen and progestin receptors in the lordosis behavior induced by G1 in ovariectomized (OVX), E 2 -benzoate (EB)-primed rats. In Experiment 1, icv injection of G1 induced lordosis behavior at 120 and 240min. In Experiment 2, icv injection of the GPER-1 antagonist G15 significantly reduced lordosis behavior induced by either G1 or free E 2 . In addition, Antide, a GnRH-1 receptor antagonist, significantly depressed G1 facilitation of lordosis behavior in OVX, EB-primed rats. Similarly, icv injection of Antide blocked the stimulatory effect of E 2 on lordosis behavior. In Experiment 3, systemic injection of either tamoxifen or RU486 significantly reduced lordosis behavior induced by icv administration of G1 in OVX, EB-primed rats. The results suggest that GnRH release activates both estrogen and progestin receptors and that this activation is important in the chain of events leading to the display of lordosis behavior in response to activation of GPER-1 in estrogen-primed rats. Copyright © 2018 Elsevier Inc. All rights reserved.

Creation of active TIM barrel enzymes through genetic fusion of half-barrel domain constructs derived from two distantly related glycosyl hydrolases.

PubMed

Sharma, Prerna; Kaila, Pallavi; Guptasarma, Purnananda

2016-12-01

Diverse unrelated enzymes that adopt the beta/alpha (or TIM) barrel topology display similar arrangements of beta/alpha units placed in a radial eight-fold symmetry around the barrel's axis. The TIM barrel was originally thought to be a single structural domain; however, it is now thought that TIM barrels arose from duplication and fusion of smaller half-barrels consisting of four beta/alpha units. We describe here the design, expression and purification, as well as characterization of folding, activity and stability, of chimeras of two TIM barrel glycosyl hydrolases, made by fusing different half-barrel domains derived from an endoglucanase from Clostridium cellulolyticum, CelCCA and a beta-glucosidase from Pyrococcus furiosus, CelB. We show that after refolding following purification from inclusion bodies, the two half-barrel fusion chimeras (CelCCACelB and CelBCelCCA) display catalytic activity although they assemble into large soluble oligomeric aggregated species containing chains of mixed beta and alpha structure. CelBCelCCA displays hyperthermophile-like structural stability as well as significant stability to chemical denaturation (C m of 2.6 m guanidinium hydrochloride), whereas CelCCACelB displays mesophile-like stability (T m of ~ 71 °C). The endoglucanase activities of both chimeras are an order of magnitude lower than those of CelB or CelCCA, whereas the beta-glucosidase activity of CelBCelCCA is about two orders of magnitude lower than that of CelB. The chimera CelCCACelB shows no beta-glucosidase activity. Our results demonstrate that half-barrel domains from unrelated sources can fold, assemble and function, with scope for improvement. Pyrococcus furiosus beta-glucosidase (CelB, EC: 3.2.1.21). Clostridium cellulolyticum endoglucanase A (CelCCA, EC: 3.2.1.4). © 2016 Federation of European Biochemical Societies.

CLINICAL SURFACES - Activity-Based Computing for Distributed Multi-Display Environments in Hospitals

NASA Astrophysics Data System (ADS)

Bardram, Jakob E.; Bunde-Pedersen, Jonathan; Doryab, Afsaneh; Sørensen, Steffen

A multi-display environment (MDE) is made up of co-located and networked personal and public devices that form an integrated workspace enabling co-located group work. Traditionally, MDEs have, however, mainly been designed to support a single “smart room”, and have had little sense of the tasks and activities that the MDE is being used for. This paper presents a novel approach to support activity-based computing in distributed MDEs, where displays are physically distributed across a large building. CLINICAL SURFACES was designed for clinical work in hospitals, and enables context-sensitive retrieval and browsing of patient data on public displays. We present the design and implementation of CLINICAL SURFACES, and report from an evaluation of the system at a large hospital. The evaluation shows that using distributed public displays to support activity-based computing inside a hospital is very useful for clinical work, and that the apparent contradiction between maintaining privacy of medical data in a public display environment can be mitigated by the use of CLINICAL SURFACES.

Emissive flat panel displays: A challenge to the AMLCD

NASA Astrophysics Data System (ADS)

Walko, R. J.

According to some sources, flat panel displays (FPD's) for computers will represent a 20-40 billion dollar industry by the end of the decade and could leverage up to 100-200 billion dollars in computer sales. Control of the flat panel display industry could be a significant factor in the global economy if FPD's manage to tap into the enormous audio/visual consumer market. Japan presently leads the world in active matrix liquid crystal display (AMLCD) manufacturing, the current leading FPD technology. The AMLCD is basically a light shutter which does not emit light on its own, but modulates the intensity of a separate backlight. However, other technologies, based on light emitting phosphors, could eventually challenge the AMLCD's lead position. These light-emissive technologies do not have the size, temperature and viewing angle limitations of AMLCD's. In addition, they could also be less expensive to manufacture, and require a smaller capital outlay for a manufacturing plant. An overview of these alternative technologies is presented.

The CD14+CD16+ Inflammatory Monocyte Subset Displays Increased Mitochondrial Activity and Effector Function During Acute Plasmodium vivax Malaria

PubMed Central

Antonelli, Lis R. V.; Leoratti, Fabiana M. S.; Costa, Pedro A. C.; Rocha, Bruno C.; Diniz, Suelen Q.; Tada, Mauro S.; Pereira, Dhelio B.; Teixeira-Carvalho, Andrea; Golenbock, Douglas T.; Gonçalves, Ricardo; Gazzinelli, Ricardo T.

2014-01-01

Infection with Plasmodium vivax results in strong activation of monocytes, which are important components of both the systemic inflammatory response and parasite control. The overall goal of this study was to define the role of monocytes during P. vivax malaria. Here, we demonstrate that P. vivax–infected patients display significant increase in circulating monocytes, which were defined as CD14+CD16− (classical), CD14+CD16+ (inflammatory), and CD14loCD16+ (patrolling) cells. While the classical and inflammatory monocytes were found to be the primary source of pro-inflammatory cytokines, the CD16+ cells, in particular the CD14+CD16+ monocytes, expressed the highest levels of activation markers, which included chemokine receptors and adhesion molecules. Morphologically, CD14+ were distinguished from CD14lo monocytes by displaying larger and more active mitochondria. CD14+CD16+ monocytes were more efficient in phagocytizing P. vivax-infected reticulocytes, which induced them to produce high levels of intracellular TNF-α and reactive oxygen species. Importantly, antibodies specific for ICAM-1, PECAM-1 or LFA-1 efficiently blocked the phagocytosis of infected reticulocytes by monocytes. Hence, our results provide key information on the mechanism by which CD14+CD16+ cells control parasite burden, supporting the hypothesis that they play a role in resistance to P. vivax infection. PMID:25233271

Pupil measures of alertness and mental load

NASA Technical Reports Server (NTRS)

Backs, Richard W.; Walrath, Larry C.

1988-01-01

A study of eight adults given active and passive search tasks showed that evoked pupillary response was sensitive to information processing demands. In particular, large pupillary diameter was observed in the active search condition where subjects were actively processing information relevant to task performance, as opposed to the passive search (control) condition where subjects passively viewed the displays. However, subjects may have simply been more aroused in the active search task. Of greater importance was that larger pupillary diameter, corresponding to longer search time, was observed for noncoded than for color-coded displays in active search. In the control condition, pupil diameter was larger with the color displays. The data indicate potential usefulness of pupillary responses in evaluating the information processing requirements of visual displays.

Selective anti-tumor activity of the novel fluoropyrimidine polymer F10 towards G48a orthotopic GBM tumors.

PubMed

Gmeiner, William H; Lema-Tome, Carla; Gibo, Denise; Jennings-Gee, Jamie; Milligan, Carol; Debinski, Waldemar

2014-02-01

F10 is a novel anti-tumor agent with minimal systemic toxicity in vivo and which displays strong cytotoxicity towards glioblastoma (GBM) cells in vitro. Here we investigate the cytotoxicity of F10 towards GBM cells and evaluate the anti-tumor activity of locally-administered F10 towards an orthotopic xenograft model of GBM. The effects of F10 on thymidylate synthase (TS) inhibition and Topoisomerase 1 (Top1) cleavage complex formation were evaluated using TS activity assays and in vivo complex of enzyme bioassays. Cytotoxicity of F10 towards normal brain was evaluated using cortices from embryonic (day 18) mice. F10 displays minimal penetrance of the blood-brain barrier and was delivered by intra-cerebral (i.c.) administration and prospective anti-tumor response towards luciferase-expressing G48a human GBM tumors in nude mice was evaluated using IVIS imaging. Histological examination of tumor and normal brain tissue was used to assess the selectivity of anti-tumor activity. F10 is cytotoxic towards G48a, SNB-19, and U-251 MG GBM cells through dual targeting of TS and Top1. F10 is not toxic to murine primary neuronal cultures. F10 is well-tolerated upon i.c. administration and induces significant regression of G48a tumors that is dose-dependent. Histological analysis from F10-treated mice revealed tumors were essentially completely eradicated in F10-treated mice while vehicle-treated mice displayed substantial infiltration into normal tissue. F10 displays strong efficacy for GBM treatment with minimal toxicity upon i.c. administration establishing F10 as a promising drug-candidate for treating GBM in human patients.

Cooking techniques improve the levels of bioactive compounds and antioxidant activity in kale and red cabbage.

PubMed

Murador, Daniella Carisa; Mercadante, Adriana Zerlotti; de Rosso, Veridiana Vera

2016-04-01

The aim of this study is to investigate the effects of different home cooking techniques (boiling, steaming, and stir-frying) in kale and red cabbage, on the levels of bioactive compounds (carotenoids, anthocyanins and phenolic compounds) determined by high-performance liquid chromatography coupled with photodiode array and mass spectrometry detectors (HPLC-DAD-MS(n)), and on the antioxidant activity evaluated by ABTS, ORAC and cellular antioxidant activity (CAA) assays. The steaming technique resulted in a significant increase in phenolic content in kale (86.1%; p<0.001) whereas in red cabbage it was significantly reduced (34.6%; p<0.001). In the kale, steaming resulted in significant increases in antioxidant activity levels in all of the evaluation methods. In the red cabbage, boiling resulted in a significant increase in antioxidant activity using the ABTS assay but resulted in a significant decrease using the ORAC assay. According to the CAA assay, the stir-fried sample displayed the highest levels of antioxidant activity. Copyright © 2015 Elsevier Ltd. All rights reserved.

Norepinephrine Transporter Heterozygous Knockout Mice Exhibit Altered Transport and Behavior

PubMed Central

Fentress, HM; Klar, R; Krueger, JK; Sabb, T; Redmon, SN; Wallace, NM; Shirey-Rice, JK; Hahn, MK

2013-01-01

The norepinephrine (NE) transporter (NET) regulates synaptic NE availability for noradrenergic signaling in the brain and sympathetic nervous system. Although genetic variation leading to a loss of NET expression has been implicated in psychiatric and cardiovascular disorders, complete NET deficiency has not been found in people, limiting the utility of NET knockout mice as a model for genetically-driven NET dysfunction. Here, we investigate NET expression in NET heterozygous knockout male mice (NET+/−), demonstrating that they display an ~50% reduction in NET protein levels. Surprisingly, these mice display no significant deficit in NET activity, assessed in hippocampal and cortical synaptosomes. We found that this compensation in NET activity was due to enhanced activity of surface-resident transporters, as opposed to surface recruitment of NET protein or compensation through other transport mechanisms, including serotonin, dopamine or organic cation transporters. We hypothesize that loss of NET protein in the NET+/− mouse establishes an activated state of existing, surface NET proteins. NET+/− mice exhibit increased anxiety in the open field and light-dark box and display deficits in reversal learning in the Morris Water Maze. These data suggest recovery of near basal activity in NET+/− mice appears to be insufficient to limit anxiety responses or support cognitive performance that might involve noradrenergic neurotransmission. The NET+/− mice represent a unique model to study the loss and resultant compensatory changes in NET that may be relevant to behavior and physiology in human NET deficiency disorders. PMID:24102798

Mechanobiocatalysis: Modulating Enzymatic Activity with Mechanical Force

DTIC Science & Technology

2015-09-28

displayed by enzymes and other materials. It was demonstrated that the application of forces to enzymes properly outfitted with polymers resulted in...distortions at the active sites of the corresponding enzymes . For example, polymer-protein composites were found to display photophysical properties that...intrinsic activities displayed by enzymes and other materials. It was demonstrated that the application of forces to enzymes properly outfitted with polymers

Allosteric Partial Inhibition of Monomeric Proteases. Sulfated Coumarins Induce Regulation, not just Inhibition, of Thrombin

PubMed Central

Verespy III, Stephen; Mehta, Akul Y.; Afosah, Daniel; Al-Horani, Rami A.; Desai, Umesh R.

2016-01-01

Allosteric partial inhibition of soluble, monomeric proteases can offer major regulatory advantages, but remains a concept on paper to date; although it has been routinely documented for receptors and oligomeric proteins. Thrombin, a key protease of the coagulation cascade, displays significant conformational plasticity, which presents an attractive opportunity to discover small molecule probes that induce sub-maximal allosteric inhibition. We synthesized a focused library of some 36 sulfated coumarins to discover two agents that display sub-maximal efficacy (~50%), high potency (<500 nM) and high selectivity for thrombin (>150-fold). Michaelis-Menten, competitive inhibition, and site-directed mutagenesis studies identified exosite 2 as the site of binding for the most potent sulfated coumarin. Stern-Volmer quenching of active site-labeled fluorophore suggested that the allosteric regulators induce intermediate structural changes in the active site as compared to those that display ~80–100% efficacy. Antithrombin inactivation of thrombin was impaired in the presence of the sulfated coumarins suggesting that allosteric partial inhibition arises from catalytic dysfunction of the active site. Overall, sulfated coumarins represent first-in-class, sub-maximal inhibitors of thrombin. The probes establish the concept of allosteric partial inhibition of soluble, monomeric proteins. This concept may lead to a new class of anticoagulants that are completely devoid of bleeding. PMID:27053426

Capsaicin Displays Anti-Proliferative Activity against Human Small Cell Lung Cancer in Cell Culture and Nude Mice Models via the E2F Pathway

PubMed Central

Hardman, W. Elaine; Luo, Haitao; Chen, Yi C.; Carpenter, A. Betts; Lau, Jamie K.; Dasgupta, Piyali

2010-01-01

Background Small cell lung cancer (SCLC) is characterized by rapid progression and low survival rates. Therefore, novel therapeutic agents are urgently needed for this disease. Capsaicin, the active ingredient of chilli peppers, displays anti-proliferative activity in prostate and epidermoid cancer in vitro. However, the anti-proliferative activity of capsaicin has not been studied in human SCLCs. The present manuscript fills this void of knowledge and explores the anti-proliferative effect of capsaicin in SCLC in vitro and in vivo. Methodology/Principal Findings BrdU assays and PCNA ELISAs showed that capsaicin displays robust anti-proliferative activity in four human SCLC cell lines. Furthermore, capsaicin potently suppressed the growth of H69 human SCLC tumors in vivo as ascertained by CAM assays and nude mice models. The second part of our study attempted to provide insight into molecular mechanisms underlying the anti-proliferative activity of capsaicin. We found that the anti-proliferative activity of capsaicin is correlated with a decrease in the expression of E2F-responsive proliferative genes like cyclin E, thymidylate synthase, cdc25A and cdc6, both at mRNA and protein levels. The transcription factor E2F4 mediated the anti-proliferative activity of capsaicin. Ablation of E2F4 levels by siRNA methodology suppressed capsaicin-induced G1 arrest. ChIP assays demonstrated that capsaicin caused the recruitment of E2F4 and p130 on E2F-responsive proliferative promoters, thereby inhibiting cell proliferation. Conclusions/Significance Our findings suggest that the anti-proliferative effects of capsaicin could be useful in the therapy of human SCLCs. PMID:20421925

Dextran Sulfate Sodium-Induced Colonic Histopathology, but not Altered Epithelial Ion Transport, Is Reduced by Inhibition of Phosphodiesterase Activity

PubMed Central

Diaz-Granados, Natalia; Howe, Kathryn; Lu, Jun; McKay, Derek M.

2000-01-01

Inhibition of phosphodiesterase (PDE) activity is beneficial in models of arthritis and airway inflammation. Here we assessed the ability of PDE inhibitors to modulate colitis by exposing mice to 4% (w/v) dextran sulfate sodium (DSS) drinking water for 5 days with or without rolipram, an inhibitor of PDE type 4, or the nonselective PDE inhibitor, pentoxifylline (both at 5 mg/kg, i.p., twice daily). Controls received saline, vehicle, or drug only. Colonic histology, myeloperoxidase (MPO) and tumor necrosis factor-α (TNF-α) levels, and epithelial ion transport (baseline and stimulated by electrical nerve stimulation, carbachol, and forskolin) were examined. DSS-treated mice displayed a variable diarrhea, significant histopathology in the mid-distal colon, elevated MPO activity, and reduced (>50%) responses to all three pro-secretory stimuli. Treatment with rolipram, and to a lesser extent pentoxifylline, significantly reduced the severity of the colonic histopathology and MPO levels. Neither PDE inhibitor had any affect on the diminished ion transport events caused by DSS-induced colitis. However, although stimulated ion transport events were still reduced 3 days after DSS treatment, colonic segments from DSS + rolipram-treated mice displayed enhanced recovery in their secretory responsiveness, particularly to carbachol. These findings indicate that specific PDE4 inhibition can significantly reduce the tissue damage that accompanies colitis and enhance recovery of normal colonic function. PMID:10854237

Using an electronic activity monitor system as an intervention modality: A systematic review.

PubMed

Lewis, Zakkoyya H; Lyons, Elizabeth J; Jarvis, Jessica M; Baillargeon, Jacques

2015-06-24

Obesity is a growing global health concern that may lead to cardiovascular disease, type II diabetes, and cancer. Several systematic reviews have shown that technology is successful in combating obesity through increased physical activity, but there is no known review on interventions that use an electronic activity monitor system (EAMS). EAMSs are defined as a wearable device that objectively measures lifestyle physical activity and can provide feedback, beyond the display of basic activity count information, via the monitor display or through a partnering application to elicit continual self-monitoring of activity behavior. These devices improve upon standard pedometers because they have the ability to provide visual feedback on activity progression, verbal encouragement, and social comparison. This systematic review aimed to synthesize the efficacy and feasibility results of EAMSs within published physical activity interventions. Electronic databases and journal references were searched for relevant articles. Data sources included CINAHL, Cochrane CENTRAL, Medline Ovid, PsycINFO, and clinicaltrials.gov. Out of the 1,574 retrieved, 11 articles met the inclusion criteria. These articles were reviewed for quality and content based on a risk of bias tool and intervention components. Most articles were determined to be of medium quality while two were of low quality, and one of high quality. Significant pre-post improvements in the EAMS group were found in five of nine studies for physical activity and in four of five studies for weight. One found a significant increase in physical activity and two studies found significant weight loss in the intervention group compared with the comparator group. The EAMS interventions appear to be feasible with most studies reporting continual wear of the device during waking hours and a higher retention rate of participants in the EAMS groups. These studies provide preliminary evidence suggesting that EAMS can increase physical activity and decrease weight significantly, but their efficacy compared to other interventions has not yet been demonstrated. More high-quality randomized controlled trials are needed to evaluate the overall effect of EAMS, examine which EAMS features are most effective, and determine which populations are most receptive to an EAMS.

Silicon containing ibuprofen derivatives with antioxidant and anti-inflammatory activities: An in vivo and in silico study.

PubMed

Pérez, David J; Díaz-Reval, M Irene; Obledo-Benicio, Fernando; Zakai, Uzma I; Gómez-Sandoval, Zeferino; Razo-Hernández, Rodrigo Said; West, Robert; Sumaya-Martínez, María Teresa; Pineda-Urbina, Kayim; Ramos-Organillo, Ángel

2017-11-05

There are many chronic diseases related with inflammation. The chronic inflammation can produce other problems as cancer. Therefore, it is necessary to design drugs with better anti-inflammatory activity than those in the clinic. Likewise, these could be used in chronic treatments with minimum adverse effects. The amide or ester functionality in combination with the insertion of a silyl alkyl moiety is able to improve some drug properties. In this context, the evaluation of a group of silicon containing ibuprofen derivatives (SCIDs) as antioxidants and anti-inflammatory agents is reported. Antioxidant activity was evaluated by the 2,2-Diphenyl-1-picrylhydrazyl (DPPH⨪), 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic) acid (ABTS • + ) and the Fe(II) chelating ability methods. The anti-inflammatory activity was determined by using the carrageenan induced rat paw edema. The gastrotoxic profile of the SCIDs that displayed significant anti-inflammatory activity was determined by the indomethacin induced ulceration method. The SCIDs performed better than ibuprofen as chelating agents for Fe(II) and as scavengers for the free radicals DPPH• and ABTS • + . On the anti-inflammatory test, compound 4a inhibited the edema up to 87%, while 4d &10b achieved significant inflammation inhibition at a lower effective dose 50 (ED 50 ) than ibuprofen´s. None of the SCIDs endowed with anti-inflammatory activity, showed significant gastrotoxic effects with respect to those displayed by ibuprofen. Based on the experimental results and aided by the theoretical docking approach, it was possible to rationalize how the SCIDs may bind to cyclooxygenase isoforms and helped to explain their reduced gastrotoxicity. The evaluated effects were improved in SCIDs with respect to ibuprofen. Copyright © 2017 Elsevier B.V. All rights reserved.

Assessment of Innovative Emergency Department Information Displays in a Clinical Simulation Center

PubMed Central

McGeorge, Nicolette; Hegde, Sudeep; Berg, Rebecca L.; Guarrera-Schick, Theresa K.; LaVergne, David T.; Casucci, Sabrina N.; Hettinger, A. Zachary; Clark, Lindsey N.; Lin, Li; Fairbanks, Rollin J.; Benda, Natalie C.; Sun, Longsheng; Wears, Robert L.; Perry, Shawna; Bisantz, Ann

2016-01-01

The objective of this work was to assess the functional utility of new display concepts for an emergency department information system created using cognitive systems engineering methods, by comparing them to similar displays currently in use. The display concepts were compared to standard displays in a clinical simulation study during which nurse-physician teams performed simulated emergency department tasks. Questionnaires were used to assess the cognitive support provided by the displays, participants’ level of situation awareness, and participants’ workload during the simulated tasks. Participants rated the new displays significantly higher than the control displays in terms of cognitive support. There was no significant difference in workload scores between the display conditions. There was no main effect of display type on situation awareness, but there was a significant interaction; participants using the new displays showed improved situation awareness from the middle to the end of the session. This study demonstrates that cognitive systems engineering methods can be used to create innovative displays that better support emergency medicine tasks, without increasing workload, compared to more standard displays. These methods provide a means to develop emergency department information systems—and more broadly, health information technology—that better support the cognitive needs of healthcare providers. PMID:27974881

Controlled randomised trial of visual biofeedback versus muscle training without a visual display for intractable constipation.

PubMed Central

Koutsomanis, D; Lennard-Jones, J E; Roy, A J; Kamm, M A

1995-01-01

Training to contract the abdominal muscles effectively and to relax the pelvic floor during defecation straining helps some patients with severe constipation. Hitherto all such training has used a visible or audible signal of sphincter muscle activity as a biofeedback method to assist in relaxation. A randomised controlled trial comparing the outcome of muscular training without any biofeedback device with the same training supplemented by an electromyographic (EMG) record visible to the patient is reported. Significant symptomatic improvement was noted and electromyographic measurements confirmed a decrease in pelvic floor muscle activity during defecation straining after treatment in both groups. The outcome was similar in the two treatment groups. Muscular coordination training using personal instruction and encouragement without a visual display is thus a potentially successful treatment suitable for outpatient use by paramedical personnel. PMID:7672690

Driving Method for Compensating Reliability Problem of Hydrogenated Amorphous Silicon Thin Film Transistors and Image Sticking Phenomenon in Active Matrix Organic Light-Emitting Diode Displays

NASA Astrophysics Data System (ADS)

Shin, Min-Seok; Jo, Yun-Rae; Kwon, Oh-Kyong

2011-03-01

In this paper, we propose a driving method for compensating the electrical instability of hydrogenated amorphous silicon (a-Si:H) thin film transistors (TFTs) and the luminance degradation of organic light-emitting diode (OLED) devices for large active matrix OLED (AMOLED) displays. The proposed driving method senses the electrical characteristics of a-Si:H TFTs and OLEDs using current integrators and compensates them by an external compensation method. Threshold voltage shift is controlled a using negative bias voltage. After applying the proposed driving method, the measured error of the maximum emission current ranges from -1.23 to +1.59 least significant bit (LSB) of a 10-bit gray scale under the threshold voltage shift ranging from -0.16 to 0.17 V.

Aerobic Fitness and Body Mass Index in Individuals with Schizophrenia: Implications for Neurocognition and Daily Functioning

PubMed Central

Kimhy, David; Vakhrusheva, Julia; Bartels, Matthew N.; Armstrong, Hilary F.; Ballon, Jacob S.; Khan, Samira; Chang, Rachel W.; Hansen, Marie C.; Ayanruoh, Lindsey; Smith, Edward E.; Sloan, Richard P.

2014-01-01

Previous reports indicate that among healthy individuals low Aerobic Fitness (AF) and high Body-Mass Index (BMI) predict poor neurocognition and daily-functioning. It is unknown whether these associations extend to disorders characterized by poor neurocognition, such as schizophrenia. Therefore, we compared AF and BMI in individuals with schizophrenia and non-clinical controls, and then within the schizophrenia group we examined the links between AF, BMI, neurocognition and daily-functioning. Thirty-two individuals with schizophrenia and 64 gender- and age-matched controls completed assessments of AF (indexed by VO2max) and BMI. The former also completed measures of neurocognition, daily-functioning and physical activity. The schizophrenia group displayed significantly lower AF and higher BMI. In the schizophrenia group, AF was significantly correlated with overall neurocognition (r=0.57), along with executive functioning, working memory, social cognition, and processing speed. A hierarchical regression analysis indicated that AF accounted for 22% of the neurocognition variance. Furthermore, AF was significantly correlated with overall daily-functioning (r=0.46). In contrast, BMI displayed significant inverse correlations with neurocognition, but no associations to daily-functioning. AF was significantly correlated physical activity. The authors discuss the potential use of AF-enhancing interventions to improve neurocognitive and daily-functioning in schizophrenia, along with putative neurobiological mechanisms underlying these links, including Brain-Derived Neurotrophic Factor. PMID:25219618

P50 Suppression in Children with Selective Mutism: A Preliminary Report

ERIC Educational Resources Information Center

Henkin, Yael; Feinholz, Maya; Arie, Miri; Bar-Haim, Yair

2010-01-01

Evidence suggests that children with selective mutism (SM) display significant aberrations in auditory efferent activity at the brainstem level that may underlie inefficient auditory processing during vocalization, and lead to speech avoidance. The objective of the present study was to explore auditory filtering processes at the cortical level in…

Novel 3-Nitro-1H-1,2,4-triazole-based Amides and Sulfonamides as Potential anti-Trypanosomal Agents

PubMed Central

Papadopoulou, Maria V.; Bloomer, William D.; Rosenzweig, Howard S.; Chatelain, Eric; Kaiser, Marcel; Wilkinson, Shane R.; McKenzie, Caroline; Ioset, Jean-Robert

2012-01-01

A series of novel 3-nitro-1H-1,2,4-triazole-(and in some cases 2-nitro-1H-imidazole)-based amides and sulfonamides were characterized for their in vitro anti-trypanosomal and antileishmanial activities as well as mammalian toxicity. Out of 36 compounds tested, 29 (mostly 3-nitro-1H-1,2,4-triazoles) displayed significant activity against T. cruzi intracellular amastigotes (IC50 ranging from 28 nM to 3.72 μM) without concomitant toxicity to L6 host cells (selectivity 66 to 2782). Twenty three of these active compounds were more potent (up to 58 fold) than the reference drug benznidazole, tested in parallel. In addition, 9 nitrotriazoles which were moderately active (0.5 μM ≤ IC50 < 6.0 μM) against T. b. rhodesiense trypomastigotes, were 5 to 31 fold more active against bloodstream-form T. b. brucei trypomastigotes engineered to overexpress NADH-dependent nitroreductase (TbNTR). Finally, 3 nitrotriazoles displayed a moderate activity against the axenic form of Leishmania donovani. Therefore, 3-nitro-1H-1,2,4-triazole-based amides and sulfonamides are potent anti-trypanosomal agents. PMID:22550999

Photo-inducible cytotoxic and clastogenic activities of 3,6-di-substituted acridines obtained by acylation of proflavine.

PubMed

Benchabane, Yohann; Di Giorgio, Carole; Boyer, Gérard; Sabatier, Anne-Sophie; Allegro, Diane; Peyrot, Vincent; De Méo, Michel

2009-06-01

The cytotoxicity and photo-enhanced cytotoxicity of a series of 18 3,6-di-substituted acridines were evaluated on both tumour CHO cells and human normal keratinocytes, and compared to their corresponding clastogenicity as assessed by the micronucleus assay. Compounds 2f tert-butyl N-[(6-tert-butoxycarbonylamino)acridin-3-yl]carbamate and 2d N-[6-(pivalamino)acridin-3-yl]pivalamide displayed a specific cytotoxicity on CHO cells. These results suggested that the two derivatives could be considered as interesting candidates for anticancer chemotherapy and hypothesized that the presence of 1,1-dimethylethyl substituents was responsible for a strong nonclastogenic cytotoxicity. Compounds 2b and 2c, on the contrary, displayed a strong clastogenicity. They indicated that the presence of nonbranched aliphatic chains on positions 3 and 6 of the acridine rings tended to induce a significant clastogenic effect. Finally, they established that most of the acridine compounds could be photo-activated by UVA-visible rays and focussed on the significant role of light irradiation on their biological properties.

Expert Financial Advice Neurobiologically “Offloads” Financial Decision-Making under Risk

PubMed Central

Engelmann, Jan B.; Capra, C. Monica; Noussair, Charles; Berns, Gregory S.

2009-01-01

Background Financial advice from experts is commonly sought during times of uncertainty. While the field of neuroeconomics has made considerable progress in understanding the neurobiological basis of risky decision-making, the neural mechanisms through which external information, such as advice, is integrated during decision-making are poorly understood. In the current experiment, we investigated the neurobiological basis of the influence of expert advice on financial decisions under risk. Methodology/Principal Findings While undergoing fMRI scanning, participants made a series of financial choices between a certain payment and a lottery. Choices were made in two conditions: 1) advice from a financial expert about which choice to make was displayed (MES condition); and 2) no advice was displayed (NOM condition). Behavioral results showed a significant effect of expert advice. Specifically, probability weighting functions changed in the direction of the expert's advice. This was paralleled by neural activation patterns. Brain activations showing significant correlations with valuation (parametric modulation by value of lottery/sure win) were obtained in the absence of the expert's advice (NOM) in intraparietal sulcus, posterior cingulate cortex, cuneus, precuneus, inferior frontal gyrus and middle temporal gyrus. Notably, no significant correlations with value were obtained in the presence of advice (MES). These findings were corroborated by region of interest analyses. Neural equivalents of probability weighting functions showed significant flattening in the MES compared to the NOM condition in regions associated with probability weighting, including anterior cingulate cortex, dorsolateral PFC, thalamus, medial occipital gyrus and anterior insula. Finally, during the MES condition, significant activations in temporoparietal junction and medial PFC were obtained. Conclusions/Significance These results support the hypothesis that one effect of expert advice is to “offload” the calculation of value of decision options from the individual's brain. PMID:19308261

Effects of temperature and medium composition on inhibitory activities of gossypol-related compounds against aflatoxigenic fungi.

PubMed

Mellon, J E; Dowd, M K; Beltz, S B

2013-07-01

To investigate the effects of temperature and medium composition on growth/aflatoxin inhibitory activities of terpenoids gossypol, gossypolone and apogossypolone against Aspergillus flavus and A. parasiticus. The compounds were tested at a concentration of 100 μg ml(-1) in a Czapek Dox (Czapek) agar medium at 25, 31 and 37°C. Increased incubation temperature marginally increased growth inhibition caused by these compounds, but reduced the aflatoxin inhibition effected by gossypol. Gossypolone and apogossypolone retained good aflatoxin inhibitory activity against A. flavus and A. parasiticus at higher incubation temperatures. However, increased temperature also significantly reduced aflatoxin production in control cultures. The effects of the terpenoids on fungal growth and aflatoxin production against the same fungi were also determined in Czapek, Czapek with a protein/amino acid addendum and yeast extract sucrose (YES) media. Growth of these fungi in the protein-supplemented Czapek medium or in the YES medium greatly reduced the growth inhibition effects of the terpenoids. Apogossypolone displayed strong anti-aflatoxigenic activity in the Czapek medium, but this activity was significantly reduced in the protein-amended Czapek and YES media. Gossypol, which displayed little to no aflatoxin inhibitory activity in the Czapek medium, did yield significant anti-aflatoxigenic activity in the YES medium. Incubation temperature and media composition are important parameters involved in the regulation of aflatoxin production in A. flavus and A. parasiticus. These parameters also affect the potency of growth and aflatoxin inhibitory activities of these gossypol-related compounds against aflatoxigenic fungi. Studies utilizing gossypol-related compounds as inhibitory agents of biological activities should be interpreted with caution due to compound interaction with multiple components of the test system, especially serum proteins. Published [2013]. This article is a U.S. Government work and is in the public domain in the USA.

Mumijo Traditional Medicine: Fossil Deposits from Antarctica (Chemical Composition and Beneficial Bioactivity)

PubMed Central

Aiello, Anna; Fattorusso, Ernesto; Menna, Marialuisa; Vitalone, Rocco; Schröder, Heinz C.; Müller, Werner E. G.

2011-01-01

Mumijo is a widely used traditional medicine, especially in Russia, Altai Mountains, Mongolia, Iran Kasachstan and in Kirgistan. Mumijo preparations have been successfully used for the prevention and treatment of infectious diseases; they display immune-stimulating and antiallergic activity as well. In the present study, we investigate the chemical composition and the biomedical potential of a Mumijo(-related) product collected from the Antarctica. The yellow material originates from the snow petrels, Pagodroma nivea. Extensive purification and chemical analysis revealed that the fossil samples are a mixture of glycerol derivatives. In vitro experiments showed that the Mumijo extract caused in cortical neurons a strong neuroprotective effect against the apoptosis-inducing amyloid peptide fragment β-fragment 25–35 (Aβ25–35). In addition, the fraction rich in glycerol ethers/wax esters displayed a significant growth-promoting activity in permanent neuronal PC12 cells. It is concluded that this new Mumijo preparation has distinct and marked neuroprotective activity, very likely due to the content of glycerol ether derivatives. PMID:18996940

Characterizing Depression Issues on Sina Weibo.

PubMed

Tian, Xianyun; Batterham, Philip; Song, Shuang; Yao, Xiaoxu; Yu, Guang

2018-04-16

The prevalence of depression has increased significantly over the past few years both in developed and developing countries. However, many people with symptoms of depression still remain untreated or undiagnosed. Social media may be a tool to help researchers and clinicians to identify and support individuals who experience depression. More than 394,000,000 postings were collected from China's most popular social media website, Sina Weibo. 1000 randomly selected depression-related postings was coded and analyzed to learn the themes of these postings, and a text classifier was built to identify the postings indicating depression. The identified depressed users were compared with the general population on demographic characteristics, diurnal patterns, and patterns of emoticon usage. We found that disclosure of depression was the most popular theme; depression displayers were more engaged with social media compared to non-depression displayers, the depression postings showed geographical variations, depression displayers tended to be active during periods of leisure and sleep, and depression displayers used negative emoticons more frequently than non-depression displayers. This study offers a broad picture of depression references on China's social media, which may be cost effectively developed to detect and help individuals who may suffer from depression disorders.

Simultaneous bioremediation and biodetection of mercury ion through surface display of carboxylesterase E2 from Pseudomonas aeruginosa PA1.

PubMed

Yin, Kun; Lv, Min; Wang, Qiaoning; Wu, Yixuan; Liao, Chunyang; Zhang, Weiwei; Chen, Lingxin

2016-10-15

Mercury is a toxic heavy metal and presents significant threats to organisms and natural ecosystems. Recently, the mercury remediation as well as its detection by environmental-friendly biotechnology has received increasing attention. In this study, carboxylesterase E2 from mercury-resistant strain Pseudomonas aeruginosa PA1 has been successfully displayed on the outer membrane of Escherichia coli Top10 bacteria to simultaneously adsorb and detect mercury ion (Hg(2+)). The transmission electron microscopy analysis shows that Hg(2+) can be absorbed by carboxylesterase E2 and accumulated on the outer membrane of surface-displayed E. coli bacteria. The adsorption of Hg(2+) followed a physicochemical, equilibrated and saturatable mechanism, which well fits the traditional Langmuir adsorption model. The surface-displayed system can be regenerated through regulating pH values. As its activity can be inhibited by Hg(2+), carboxylesterase E2 has been used to detect the concentration of Hg(2+) in water samples. The developed surface display system will be of great potential in the simultaneous bioremediation and biodetection of environmental mercury pollution. Copyright © 2016 Elsevier Ltd. All rights reserved.

Spectral characteristics of light sources for S-cone stimulation.

PubMed

Schlegelmilch, F; Nolte, R; Schellhorn, K; Husar, P; Henning, G; Tornow, R P

2002-11-01

Electrophysiological investigations of the short-wavelength sensitive pathway of the human eye require the use of a suitable light source as a S-cone stimulator. Different light sources with their spectral distribution properties were investigated and compared with the ideal S-cone stimulator. First, the theoretical background of the calculation of relative cone energy absorption from the spectral distribution function of the light source is summarized. From the results of the calculation, the photometric properties of the ideal S-cone stimulator will be derived. The calculation procedure was applied to virtual light sources (computer generated spectral distribution functions with different medium wavelengths and spectrum widths) and to real light sources (blue and green light emitting diodes, blue phosphor of CRT-monitor, multimedia projector, LCD monitor and notebook display). The calculated relative cone absorbencies are compared to the conditions of an ideal S-cone stimulator. Monochromatic light sources with wavelengths of less than 456 nm are close to the conditions of an ideal S-cone stimulator. Spectrum widths up to 21 nm do not affect the S-cone activation significantly (S-cone activation change < 0.2%). Blue light emitting diodes with peak wavelength at 448 nm and spectrum bandwidth of 25 nm are very useful for S-cone stimulation (S-cone activation approximately 95%). A suitable display for S-cone stimulation is the Trinitron computer monitor (S-cone activation approximately 87%). The multimedia projector has a S-cone activation up to 91%, but their spectral distribution properties depends on the selected intensity. LCD monitor and notebook displays have a lower S-cone activation (< or = 74%). Carefully selecting the blue light source for S-cone stimulation can reduce the unwanted L-and M-cone activation down to 4% for M-cones and 1.5% for L-cones.

Synthesis, pharmacological activities and molecular docking studies of pyrazolyltriazoles as anti-bacterial and anti-inflammatory agents.

PubMed

Dayakar, Cherupally; Kumar, Buddana Sudheer; Sneha, Galande; Sagarika, Gudem; Meghana, Koneru; Ramakrishna, Sistla; Prakasham, Reddy Shetty; China Raju, Bhimapaka

2017-10-15

A series of novel pyrazolyl alcohols (5a-h), pyrazolyl azides (6a-h), and pyrazolyltriazoles (8a-h, 10a-p and 12a-l) were prepared and evaluated for their bioactivity (anti-bacterial and anti-inflammatory) profile. The compound 5c displayed the potent anti-bacterial activity against Micrococcus luteus (MIC 3.9 and MBC 7.81µg/mL). In vitro anti-inflammatory activity data denoted that compound 8b is effective among the tested compounds against IL-6 (IC 50 6.23μM). Docking analysis of compounds 5f, 8a-b, 8e-f and 8h displayed high binding energies for the compounds 8a-b and 8h towards TNF-α dimer (2AZ5 protein) and IL-6 (1ALU protein). In vivo anti-inflammatory activity of compounds 8b and 8h with respect to LPS induced mice model indicated that compound 8h showed significant reduction in TNF-α. Copyright © 2017 Elsevier Ltd. All rights reserved.

Synthesis and biological evaluation of febrifugine analogues.

PubMed

Mai, Huong Doan Thi; Thanh, Giang Vo; Tran, Van Hieu; Vu, Van Nam; Vu, Van Loi; Le, Cong Vinh; Nguyen, Thuy Linh; Phi, Thi Dao; Truong, Bich Ngan; Chau, Van Minh; Pham, Van Cuong

2014-12-01

A series of febrifugine analogues were designed and synthesized. Antimalarial activity evaluation of the synthetic compounds indicated that these derivatives had a strong inhibition against both chloroquine-sensitive and -resistant Plasmodium falciparum parasites. Many of them were found to be more active than febrifugine hydrochloride. The tested analogues had also a significant cytotoxicity against four cancer cell lines (KB, MCF7, LU1 and HepG2). Among the synthetic analogues, two compounds 17b and 17h displayed a moderate cytotoxicity while they exhibited a remarkable antimalarial activity.

Tyrosinase inhibitors from the wood of Artocarpus heterophyllus.

PubMed

Nguyen, Nhan Trung; Nguyen, Mai Ha Khoa; Nguyen, Hai Xuan; Bui, Ngan Kim Nguyen; Nguyen, Mai Thanh Thi

2012-11-26

From the methanolic-soluble extract of the wood of Artocarpus heterophyllus, four new flavones, artocarmins A-D (1-4), and three new chalcones, artocarmitins A-C (5-7), have been isolated together with 13 known compounds. Their structures were determined on the basis of the spectroscopic data. Compounds 1-4, 6, 7, 9-16, and 20 displayed significant tyrosinase inhibitory activity. The most active compound, morachalcone A (12) (IC50, 0.013 μM), was 3000 times more active as a tyrosinase inhibitor than a positive control, kojic acid (IC50, 44.6 μM).

2-Deoxystreptamine Conjugates by Truncation–Derivatization of Neomycin

PubMed Central

Aslam, M. Waqar; Tabares, Leandro C.; Andreoni, Alessio; Canters, Gerard W.; Rutjes, Floris P.J.T.; van Delft, Floris L.

2010-01-01

A small library of truncated neomycin-conjugates is prepared by consecutive removal of 2,6-diaminoglucose rings, oxidation-reductive amination of ribose, oxidation-conjugation of aminopyridine/aminoquinoline and finally dimerization. The dimeric conjugates were evaluated for antibacterial activity with a unique hemocyanin-based biosensor. Based on the outcome of these results, a second-generation set of monomeric conjugates was prepared and found to display significant antibacterial activity, in particular with respect to kanamycin-resistant E. coli. PMID:27713274

Is parenting a determinant of adolescent mental health? - A population based study in South India.

PubMed

Hegde, Asha; Kamath, Asha; Roy, Kallol

2015-11-10

The transitional phase encompassing the physiological and psychological changes during our lifespan is termed as adolescence. Adolescents get mislead to substance use, violence related activities, dating relationships, unhealthy lifestyle. Minimal studies are conducted in India to identify the parenting factors that affect an adolescent's mind. The aim of our study was to explore the role of parenting and social surroundings on - adolescent's mental health and involvement in violence related activities. Cross sectional study design was adopted. Semi structured questionnaire was used. Data obtained was entered and analyzed using SPSS 15. Proportions were used to report the findings. Chi-square test was used to find associations between mental health issues, involvement in violence related activities and Interpersonal Relationship (IPR) Status. Multiple logistic regressions were done to identify independent predictors of mental health. A total of 1770 adolescents participated. Proportion of adolescents with good IPR with parents reported to be having a better mental health status and low involvement in violent related activities. Schools also displayed similar effects. Neighborhood, peers did not display any significant effect on adolescent's mental health. Most significant predictor for adolescent mental health was IPR with parents and at school. The study highlights the need of a cordial environment at places which does influence the adolescent's mental health. Interventions enhancing the relationship status of adolescents with parents, at school must be carried out to observe the change in adolescent behavior.

Narciclasine as well as other Amaryllidaceae isocarbostyrils are promising GTP-ase targeting agents against brain cancers.

PubMed

Van Goietsenoven, Gwendoline; Mathieu, Véronique; Lefranc, Florence; Kornienko, Alexander; Evidente, Antonio; Kiss, Robert

2013-03-01

The anticancer activity of Amaryllidaceae isocarbostyrils is well documented. At pharmacological concentrations, that is, approximately 1 μM in vitro and approximately 10 mg/kg in vivo, narciclasine displays marked proapoptotic and cytotoxic activity, as does pancratistatin, and significant in vivo anticancer effects in various experimental models, but it is also associated with severe toxic side effects. At physiological doses, that is, approximately 50 nM in vitro and approximately 1 mg/kg in vivo, narciclasine is not cytotoxic but cytostatic and displays marked anticancer activity in vivo in experimental models of brain cancer (including gliomas and brain metastases), but it is not associated with toxic side effects. The cytostatic activity of narciclasine involves the impairment of actin cytoskeleton organization by targeting GTPases, including RhoA and the elongation factor eEF1A. We have demonstrated that chronic treatments of narciclasine (1 mg/kg) significantly increased the survival of immunodeficient mice orthotopically xenografted with highly invasive human glioblastomas and apoptosis-resistant brain metastases, including melanoma- and non-small-cell-lung cancer- (NSCLC) related brain metastases. Thus, narciclasine is a potentially promising agent for the treatment of primary brain cancers and various brain metastases. To date, efforts to develop synthetic analogs with anticancer properties superior to those of narciclasine have failed; thus, research efforts are now focused on narciclasine prodrugs. © 2012 Wiley Periodicals, Inc.

Enhancement of catalytic, reusability, and long-term stability features of Trametes versicolor IBL-04 laccase immobilized on different polymers.

PubMed

Asgher, Muhammad; Noreen, Sadia; Bilal, Muhammad

2017-02-01

In the current study, different bio-polymers such as agar-agar, polyacrylamide and gelatin were utilized as bolster materials for the immobilization of a fungal laccase through entrapment approach. Among the polymers, agar-agar matrix most firmly encapsulated the enzyme yielding significant laccase immobilization (79.65±2.55%). Immobilization prolonged the reaction time of laccase and agar-agar, polyacrylamide and gelatin entrapped laccases displayed maximum catalytic activities after 10.0, 15.0 and 10.0min of reaction, respectively, as compared to free counterpart (5.0min). It also increased the optimal temperature by 5.0-10°C and provided an alkaline shift of the pH optima to agar-agar and gelatin entrapped laccase, while, in case of polyacrylamide, optimum pH was displaced to acidic region. Kinetic data revealed that K m(app) values were slightly increased while V max values were decreased as compared to free counterpart. Polymers encapsulation led to significant improvement in activity against thermal denaturation. After 180min at 60°C, the enzymes preserved 28.1±0.9, 48.6±1.3 and 32.5±1.8% residual activities, respectively, whereas, the free enzyme was completely inactive. Immobilization enabled the enzymes to resist a number of different effectors including metal ions, inhibitors/denaturants and chelating agents. Moreover, the resulted modified laccases displayed good recycling capability for substrate-oxidation reactions in several successive batches. In summary, the tremendously improved attributes of polymers-encapsulated enzymes display a high potential for various applications in different industrial sectors. Copyright © 2016 Elsevier B.V. All rights reserved.

Anxiolytic- and Antidepressant-like Effects of the Methadone Metabolite 2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline (EMDP)

PubMed Central

Lee, Bridgin G.; Olson, Thao T.; Xie, Teresa; Xiao, Yingxian; Blendy, Julie A.; Kellar, Kenneth J.

2015-01-01

The enhancement of GABAergic and monoaminergic neurotransmission has been the mainstay of pharmacotherapy and the focus of drug-discovery for anxiety and depressive disorders for several decades. However, the significant limitations of drugs used for these disorders underscores the need for novel therapeutic targets. Neuronal nicotinic acetylcholine receptors (nAChRs) may represent one such target. For example, mecamylamine, a non-competitive antagonist of nAChRs, displays positive effects in preclinical tests for anxiolytic and antidepressant activity in rodents. In addition, nicotine elicits similar effects in rodent models, possibly by receptor desensitization. Previous studies (Xiao et al., 2001) have identified two metabolites of methadone, EMDP (2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline) and EDDP (2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine), which are considered to be inactive at opiate receptors, as relatively potent noncompetitive channel blockers of rat α3β4 nAChRs. Here, we show that these compounds are likewise highly effective blockers of human α3β4 and α4β2 nAChRs. Moreover, we show that they display relatively low affinity for opiate binding sites labeled by [3H]-naloxone. We then evaluated these compounds in rats and mice in preclinical behavioral models predictive of potential anxiolytic and antidepressant efficacy. We found that EMDP, but not EDDP, displayed robust effects predictive of anxiolytic and antidepressant efficacy without significant effects on locomotor activity. Moreover, EMDP at behaviorally active doses, unlike mecamylamine, did not produce eyelid ptosis, suggesting it may produce fewer autonomic side effects than mecamylamine. Thus, the methadone metabolite EMDP may represent a novel therapeutic avenue for the treatment of some affective disorders. PMID:26365569

Co-autodisplay of Z-domains and bovine caseins on the outer membrane of E. coli.

PubMed

Yoo, Gu; Saenger, Thorsten; Bong, Ji-Hong; Jose, Joachim; Kang, Min-Jung; Pyun, Jae-Chul

2015-12-01

In this work, two proteins, Z-domains and bovine casein, were auto-displayed on the outer membrane of the same Escherichia coli cells by co-transformation of two different auto-display vectors. On the basis of SDS-PAGE densitometry, Z-domains and bovine casein were expressed at 3.12 × 10⁵ and 1.55 × 10⁵ proteins/E. coli cell, respectively. The co-auto-displayed Z-domains had antibody-binding activity and the bovine casein had adhesive properties. E. coli with co-auto-displayed proteins were analyzed by fluorescence assisted cell sorting (FACS). E. coli with co-auto-displayed Z-domains and bovine casein aggregated due to hydrophobic interaction. For application to immunoassays, the Z-domain activity was estimated after (1) immobilizing the E. coli and (2) forming an OM layer. E. coli with co-auto-displayed two proteins that were immobilized on a polystyrene microplate had the same antibody-binding activity as did E. coli with auto-displayed Z-domains only. The OM layer from the co-transformed E. coli had Z-domains and bovine casein expressed at a 1:2 ratio from antibody-binding activity measurements. Copyright © 2015 Elsevier B.V. All rights reserved.

KML001 displays vascular disrupting properties and irinotecan combined antitumor activities in a murine tumor model.

PubMed

Moon, Chang Hoon; Lee, Seung Ju; Lee, Ho Yong; Lee, Jong Cheol; Cha, Heejeong; Cho, Wha Ja; Park, Jeong Woo; Park, Hyun Jin; Seo, Jin; Lee, Young Han; Song, Ho-Taek; Min, Young Joo

2013-01-01

KML001 is sodium metaarsenite, and has shown cytotoxic activity in human tumor cell lines. The anti-cancer mechanism of KML001 involves cancer cell destruction due to DNA damage at the telomeres of cancer cell chromosomes. In this study, we assessed the vascular disrupting properties of KML001 and investigated whether KML001 as VDA is able to increase anti-tumor activity in irinotecan combined treatment. We used a murine model of the CT26 colon carcinoma cell line. CT26 isograft mice treated intraperitoneally with 10 mg/kg KML001 displayed extensive central necrosis of tumor by 24 h. The vascular disrupting effects of KML001 were assessed by dynamic contrast enhanced magnetic resonance imaging. Gadopentetic acid-diethylene triaminepentaacetic acid contrast enhancement was markedly decreased in KML001-treated mice one day after treatment, whereas persistently high signal enhancement was observed in mice injected with saline. Rate constant K(ep) value representing capillary permeability was significantly decreased (p<0.05) in mice treated with KML001. Cytoskeletal changes of human umbilical vein endothelial cells (HUVECs) treated with 10 uM KML001 were assessed by immune blotting and confocal imaging. KML001 degraded tubulin protein in HUVECs, which may be related to vascular disrupting properties of KML001. Finally, in the mouse CT26 isograft model, KML001 combined with irinotecan significantly delayed tumor growth as compared to control and irinotecan alone. These results suggest that KML001 is a novel vascular disrupting agent, which exhibits significant vascular shut-down activity and enhances anti-tumor activity in combination with chemotherapy. These data further suggest an avenue for effective combination therapy in treating solid tumors.

KML001 Displays Vascular Disrupting Properties and Irinotecan Combined Antitumor Activities in a Murine Tumor Model

PubMed Central

Moon, Chang Hoon; Lee, Seung Ju; Lee, Ho Yong; Lee, Jong Cheol; Cha, HeeJeong; Cho, Wha Ja; Park, Jeong Woo; Park, Hyun Jin; Seo, Jin; Lee, Young Han; Song, Ho-Taek; Min, Young Joo

2013-01-01

KML001 is sodium metaarsenite, and has shown cytotoxic activity in human tumor cell lines. The anti-cancer mechanism of KML001 involves cancer cell destruction due to DNA damage at the telomeres of cancer cell chromosomes. In this study, we assessed the vascular disrupting properties of KML001 and investigated whether KML001 as VDA is able to increase anti-tumor activity in irinotecan combined treatment. We used a murine model of the CT26 colon carcinoma cell line. CT26 isograft mice treated intraperitoneally with 10 mg/kg KML001 displayed extensive central necrosis of tumor by 24 h. The vascular disrupting effects of KML001 were assessed by dynamic contrast enhanced magnetic resonance imaging. Gadopentetic acid-diethylene triaminepentaacetic acid contrast enhancement was markedly decreased in KML001-treated mice one day after treatment, whereas persistently high signal enhancement was observed in mice injected with saline. Rate constant Kep value representing capillary permeability was significantly decreased (p<0.05) in mice treated with KML001. Cytoskeletal changes of human umbilical vein endothelial cells (HUVECs) treated with 10 uM KML001 were assessed by immune blotting and confocal imaging. KML001 degraded tubulin protein in HUVECs, which may be related to vascular disrupting properties of KML001. Finally, in the mouse CT26 isograft model, KML001 combined with irinotecan significantly delayed tumor growth as compared to control and irinotecan alone. These results suggest that KML001 is a novel vascular disrupting agent, which exhibits significant vascular shut-down activity and enhances anti-tumor activity in combination with chemotherapy. These data further suggest an avenue for effective combination therapy in treating solid tumors. PMID:23326531

Endomorphin-2 analogs with C-terminal esterification produce potent systemic antinociception with reduced tolerance and gastrointestinal side effects.

PubMed

Wang, Chang-Lin; Qiu, Ting-Ting; Yang, Dai-Jun; Yuan, Bi-Yu; Han, Feng-Tong; Li, Li; Gu, Ning

2017-04-01

C-terminal esterification of opioid peptides may change their opioid activities due to the modified physicochemical properties. In the present study, the pharmacological activities of C-terminal esterified endomorphin-2 (EM-2) analogs 1-3 were characterized by in vitro metabolic stability and octanol/buffer distribution assays. Also, the antinociceptive profiles in the radiant heat paw withdrawal test and related side effects of these analogs were determined. Our results showed that all three analogs significantly increased the metabolic stability and lipophilicity. Moreover, analogs 1-3 displayed potent antinociceptive activities after intracerebroventricular (i.c.v.) administration. Analogs 1 and 3 exhibited about 2-fold higher antinociception than EM-2, and differential opioid mechanisms were involved. In addition, EM-2 at 50 μmol/kg failed to produce any significant antinociceptive activity after subcutaneous (s.c.) administration, whereas equimolar dose of analogs 1-3 produced significant analgesic effects. Analog 3 showed the highest antinociceptive activity after systemic administration, which was consistent with its in vitro stability and lipophilicity. We further evaluated the antinociceptive tolerance of analogs 1-3. In acute tolerance test, analogs 1-3 shifted the dose-response curves rightward by only 1.4-3.2 fold as determined by tolerance ratio, whereas EM-2 by 5.6-fold, demonstrating reduced antinociceptive tolerance. Also, analogs 1 and 2 decreased chronic antinociceptive tolerance by central and peripheral administration of drugs. In particular, analogs 3 displayed insignificant chronic antinociceptive tolerance. Furthermore, analogs 1-3 were less prone to induce gastrointestinal side effects at analgesic doses. The present investigation gave the evidence that C-terminal esterified modifications of EM-2 will facilitate the development of novel opioid analgesics with reduced side effects. Copyright © 2016 Elsevier Ltd. All rights reserved.

Inhibiting social support from massage-like stroking increases morphine dependence.

PubMed

Bates, M L Shawn; Emery, Michael A; Wellman, Paul J; Eitan, Shoshana

2017-12-01

Our previous studies showed that altering solely the drug experience of the cage mates with which rodents are housed affects the development of morphine dependence. In this study, we used designer receptors exclusively activated by designer drugs to artificially increase or decrease the activity of peripheral dorsal root ganglia sensory neurons expressing the G-protein-coupled receptor MRGPRB4. This is because sensory MRGPRB4-expressing neurons were shown to specifically detect the sensation of massage-like stroking resulting from social grooming, which is an important affiliative social behavior in the rodent. Blocking the sensation of social grooming in morphine-treated mice housed with drug-naive mice (i.e. morphine cage mates) significantly increased the display of jumping behavior in morphine-withdrawn animals. Activating the sensation of social grooming in morphine-treated animals housed solely with other morphine-treated animals (i.e. morphine only) did not significantly alter the display of jumping behavior in morphine-withdrawn animals. Repetitive jumping behaviors have been shown to correlate with morphine dependence. Thus, this study showed a role of social grooming in the protective effect of being housed with drug-naive mice on the development of morphine dependence. It further confirms a role of social support in the development of substance use problems.

Inhibition of Lysyl Oxidases Impairs Migration and Angiogenic Properties of Tumor-Associated Pericytes.

PubMed

Ribeiro, Aline Lopes; Kaid, Carolini; Silva, Patrícia B G; Cortez, Beatriz A; Okamoto, Oswaldo Keith

2017-01-01

Pericytes are important cellular components of the tumor microenviroment with established roles in angiogenesis and metastasis. These two cancer hallmarks are modulated by enzymes of the LOX family, but thus far, information about LOX relevance in tumor-associated pericytes is lacking. Here, we performed a comparative characterization of normal and tumoral pericytes and report for the first time the modulatory effects of LOX enzymes on activated pericyte properties. Tumoral pericytes isolated from childhood ependymoma and neuroblastoma specimens displayed angiogenic properties in vitro and expressed typical markers, including CD146, NG2, and PDGFR β . Expression of all LOX family members could be detected in both normal and tumor-associated pericytes. In most pericyte samples, LOXL3 was the family member displaying the highest transcript levels. Inhibition of LOX/LOXL activity with the inhibitor β -aminopropionitrile ( β APN) significantly reduced migration of pericytes, while proliferation rates were kept unaltered. Formation of tube-like structures in vitro by pericytes was also significantly impaired upon inhibition of LOX/LOXL activity with β APN, which induced more prominent effects in tumor-associated pericytes. These findings reveal a novel involvement of the LOX family of enzymes in migration and angiogenic properties of pericytes, with implications in tumor development and in therapeutic targeting tumor microenvironment constituents.

Inhibition of Lysyl Oxidases Impairs Migration and Angiogenic Properties of Tumor-Associated Pericytes

PubMed Central

Kaid, Carolini; Silva, Patrícia B. G.; Cortez, Beatriz A.

2017-01-01

Pericytes are important cellular components of the tumor microenviroment with established roles in angiogenesis and metastasis. These two cancer hallmarks are modulated by enzymes of the LOX family, but thus far, information about LOX relevance in tumor-associated pericytes is lacking. Here, we performed a comparative characterization of normal and tumoral pericytes and report for the first time the modulatory effects of LOX enzymes on activated pericyte properties. Tumoral pericytes isolated from childhood ependymoma and neuroblastoma specimens displayed angiogenic properties in vitro and expressed typical markers, including CD146, NG2, and PDGFRβ. Expression of all LOX family members could be detected in both normal and tumor-associated pericytes. In most pericyte samples, LOXL3 was the family member displaying the highest transcript levels. Inhibition of LOX/LOXL activity with the inhibitor β-aminopropionitrile (βAPN) significantly reduced migration of pericytes, while proliferation rates were kept unaltered. Formation of tube-like structures in vitro by pericytes was also significantly impaired upon inhibition of LOX/LOXL activity with βAPN, which induced more prominent effects in tumor-associated pericytes. These findings reveal a novel involvement of the LOX family of enzymes in migration and angiogenic properties of pericytes, with implications in tumor development and in therapeutic targeting tumor microenvironment constituents. PMID:28553358

Anti-inflammatory and antinociceptive properties of blueberry extract (Vaccinium corymbosum).

PubMed

Torri, Eliane; Lemos, Marivane; Caliari, Vinícius; Kassuya, Cândida A L; Bastos, Jairo K; Andrade, Sérgio F

2007-04-01

Blueberries are among the edible fruits that are recognized best for their potential health benefits. The crude extract from Vaccinium corymbosum was assessed in anti-inflammatory and antinociceptive models. The crude hydroalcoholic extract was administered orally at doses of 100, 200 or 300 mg kg (-1) for all the assays. In the carrageenan test, the crude extract reduced rat paw oedema by 9.8, 28.5 and 65.9%, respectively. For the histamine assay, the reductions of oedema were 70.1, 71.7 and 81.9%, respectively. In the myeloperoxidase (MPO) assay, 300 mg kg (-1) crude extract produced a significant inhibition of the MPO activity, at 6 h and 24 h after injection of carrageenan, by 42.8 and 46.2%, respectively. With the granulomatous tissue assay dexamethasone displayed significant activity, whereas the blueberry extract was inactive. For the abdominal constriction test, inhibitions of 49.0, 54.5, 53.5%, respectively, were observed for the crude extract, and 61.4% for indometacin. In the formalin test, the crude extract (200 and 300 mg kg (-1)) and indometacin inhibited only the second phase by 36.2, 35.3 and 45.8%, respectively. Considering that the crude extract of blueberry displayed antinociceptive and anti-inflammatory activity, its consumption may be helpful for the treatment of inflammatory disorders.

Head-Up Auditory Displays for Traffic Collision Avoidance System Advisories: A Preliminary Investigation

NASA Technical Reports Server (NTRS)

Begault, Durand R.

1993-01-01

The advantage of a head-up auditory display was evaluated in a preliminary experiment designed to measure and compare the acquisition time for capturing visual targets under two auditory conditions: standard one-earpiece presentation and two-earpiece three-dimensional (3D) audio presentation. Twelve commercial airline crews were tested under full mission simulation conditions at the NASA-Ames Man-Vehicle Systems Research Facility advanced concepts flight simulator. Scenario software generated visual targets corresponding to aircraft that would activate a traffic collision avoidance system (TCAS) aural advisory; the spatial auditory position was linked to the visual position with 3D audio presentation. Results showed that crew members using a 3D auditory display acquired targets approximately 2.2 s faster than did crew members who used one-earpiece head- sets, but there was no significant difference in the number of targets acquired.

Neural correlates of self-injurious behavior in Prader-Willi syndrome.

PubMed

Klabunde, Megan; Saggar, Manish; Hustyi, Kristin M; Hammond, Jennifer L; Reiss, Allan L; Hall, Scott S

2015-10-01

Individuals with Prader-Willi syndrome (PWS), a genetic disorder caused by mutations to the q11-13 region on chromosome 15, commonly show severe skin-picking behaviors that can cause open wounds and sores on the body. To our knowledge, however, no studies have examined the potential neural mechanisms underlying these behaviors. Seventeen individuals with PWS, aged 6-25 years, who showed severe skin-picking behaviors, were recruited and scanned on a 3T scanner. We used functional magnetic resonance imaging (fMRI) while episodes of skin picking were recorded on an MRI-safe video camera. Three participants displayed skin picking continuously throughout the scan, three participants did not display skin picking, and the data for one participant evidenced significant B0 inhomogeneity that could not be corrected. The data for the remaining 10 participants (six male, four female) who displayed a sufficient number of picking and nonpicking episodes were subjected to fMRI analysis. Results showed that regions involved in interoceptive, motor, attention, and somatosensory processing were activated during episodes of skin-picking behavior compared with nonpicking episodes. Scores obtained on the Self-Injury Trauma scale were significantly negatively correlated with mean activation within the right insula and left precentral gyrus. These data indicate that itch and pain processes appear to underlie skin-picking behaviors in PWS, suggesting that interoceptive disturbance may contribute to the severity and maintenance of abnormal skin-picking behaviors in PWS. Implications for treatments are discussed. © 2015 Wiley Periodicals, Inc.

Norepinephrine transporter heterozygous knockout mice exhibit altered transport and behavior.

PubMed

Fentress, H M; Klar, R; Krueger, J J; Sabb, T; Redmon, S N; Wallace, N M; Shirey-Rice, J K; Hahn, M K

2013-11-01

The norepinephrine (NE) transporter (NET) regulates synaptic NE availability for noradrenergic signaling in the brain and sympathetic nervous system. Although genetic variation leading to a loss of NET expression has been implicated in psychiatric and cardiovascular disorders, complete NET deficiency has not been found in people, limiting the utility of NET knockout mice as a model for genetically driven NET dysfunction. Here, we investigate NET expression in NET heterozygous knockout male mice (NET(+/-) ), demonstrating that they display an approximately 50% reduction in NET protein levels. Surprisingly, these mice display no significant deficit in NET activity assessed in hippocampal and cortical synaptosomes. We found that this compensation in NET activity was due to enhanced activity of surface-resident transporters, as opposed to surface recruitment of NET protein or compensation through other transport mechanisms, including serotonin, dopamine or organic cation transporters. We hypothesize that loss of NET protein in the NET(+/-) mouse establishes an activated state of existing surface NET proteins. The NET(+/-) mice exhibit increased anxiety in the open field and light-dark box and display deficits in reversal learning in the Morris water maze. These data suggest that recovery of near basal activity in NET(+/-) mice appears to be insufficient to limit anxiety responses or support cognitive performance that might involve noradrenergic neurotransmission. The NET(+/-) mice represent a unique model to study the loss and resultant compensatory changes in NET that may be relevant to behavior and physiology in human NET deficiency disorders. © 2013 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

Cholesteric Liquid Crystal Based Reflex Color Reflective Displays

NASA Astrophysics Data System (ADS)

Khan, Asad

2012-02-01

Bistable color cholesteric liquid crystal displays are unique LCDs that exhibit high reflectivity, good contrast, extremely low power operation, and are amenable to versatile roll-to-roll manufacturing. The display technology, now branded as Reflex has been in commercialized products since 1996. It has been the subject of extensive research and development globally by a variety of parties in both academic and industrial settings. Today, the display technology is in volume production for applications such as dedicated eWriters (Boogie Board), full color electronic skins (eSkin), and displays for smart cards. The flexibility comes from polymerization induced phase separation using unique materials unparalleled in any other display technology. The blend of monomers, polymers, cross linkers, and other components along with nematic liquid crystals and chiral dopants is created and processed in such ways so as to enable highly efficient manufactrable displays using ultra thin plastic substrates -- often as thin as 50μm. Other significant aspects include full color by stacking or spatial separation, night vision capability, ultra high resolution, as well as active matrix capabilities. Of particular note is the stacking approach of Reflex based displays to show full color. This approach for reflective color displays is unique to this technology. Owing to high transparency in wavelength bands outside the selective reflection band, three primarily color layers can be stacked on top of each other and reflect without interfering with other layers. This highly surprising architecture enables the highest reflectivity of any other reflective electronic color display technology. The optics, architecture, electro-topics, and process techniques will be discussed. This presentation will focus on the physics of the core technology and color, it's evolution from rigid glass based displays to flexible displays, development of products from the paradigm shifting concepts to consumer products and related markets. This is a development that spans a wide space of highly technical development and fundamental science to products and commercialization to enable the entry of the technology into consumer markets.

Relevance of Viroporin Ion Channel Activity on Viral Replication and Pathogenesis

PubMed Central

Nieto-Torres, Jose L.; Verdiá-Báguena, Carmina; Castaño-Rodriguez, Carlos; Aguilella, Vicente M.; Enjuanes, Luis

2015-01-01

Modification of host-cell ionic content is a significant issue for viruses, as several viral proteins displaying ion channel activity, named viroporins, have been identified. Viroporins interact with different cellular membranes and self-assemble forming ion conductive pores. In general, these channels display mild ion selectivity, and, eventually, membrane lipids play key structural and functional roles in the pore. Viroporins stimulate virus production through different mechanisms, and ion channel conductivity has been proved particularly relevant in several cases. Key stages of the viral cycle such as virus uncoating, transport and maturation are ion-influenced processes in many viral species. Besides boosting virus propagation, viroporins have also been associated with pathogenesis. Linking pathogenesis either to the ion conductivity or to other functions of viroporins has been elusive for a long time. This article summarizes novel pathways leading to disease stimulated by viroporin ion conduction, such as inflammasome driven immunopathology. PMID:26151305

Low Temperature Polycrystalline Silicon Thin Film Transistor Pixel Circuits for Active Matrix Organic Light Emitting Diodes

NASA Astrophysics Data System (ADS)

Fan, Ching-Lin; Lin, Yu-Sheng; Liu, Yan-Wei

A new pixel design and driving method for active matrix organic light emitting diode (AMOLED) displays that use low-temperature polycrystalline silicon thin-film transistors (LTPS-TFTs) with a voltage programming method are proposed and verified using the SPICE simulator. We had employed an appropriate TFT model in SPICE simulation to demonstrate the performance of the pixel circuit. The OLED anode voltage variation error rates are below 0.35% under driving TFT threshold voltage deviation (Δ Vth =± 0.33V). The OLED current non-uniformity caused by the OLED threshold voltage degradation (Δ VTO =+0.33V) is significantly reduced (below 6%). The simulation results show that the pixel design can improve the display image non-uniformity by compensating for the threshold voltage deviation in the driving TFT and the OLED threshold voltage degradation at the same time.

Cytotoxic and antibacterial angucycline- and prodigiosin-analogues from the deep-sea derived Streptomyces sp. SCSIO 11594.

PubMed

Song, Yongxiang; Liu, Guangfu; Li, Jie; Huang, Hongbo; Zhang, Xing; Zhang, Hua; Ju, Jianhua

2015-03-16

Two new C-glycoside angucyclines, marangucycline A (1) and marangucycline B (2), along with three known compounds, dehydroxyaquayamycin (3), undecylprodigiosin (4) and metacycloprodigiosin (5), have been identified as products of the deep-sea sediment strain Streptomyces sp. SCSIO 11594. New structures were elucidated on the basis of HRESIMS, 1D and 2D NMR analyses and comparisons to previously reported datasets. Compounds 2 and 4 displayed in vitro cytotoxicity against four cancer cell lines A594, CNE2, HepG2, MCF-7 superior to those obtained with cisplatin, the positive control. Notably, compound 2 bearing a keto-sugar displayed significant cytotoxicity against cancer cell lines with IC50 values ranging from 0.24 to 0.56 μM; An IC50 value of 3.67 μM was found when using non-cancerous hepatic cell line HL7702, demonstrating the cancer cell selectivity of 2. Compounds 1-3 were proved to have weak antibacterial activities against Enterococcus faecalis ATCC29212 with an MIC value of 64.0 μg/mL. Moreover, 3 displayed selective antibacterial activity against methicillin-resistant Staphylococcus epidermidis shhs-E1 with an MIC value of 16.0 μg/mL.

delta(9)-Tetrahydrocannabinol-dependent mice undergoing withdrawal display impaired spatial memory.

PubMed

Wise, Laura E; Varvel, Stephen A; Selley, Dana E; Wiebelhaus, Jason M; Long, Kelly A; Middleton, Lisa S; Sim-Selley, Laura J; Lichtman, Aron H

2011-10-01

Cannabis users display a constellation of withdrawal symptoms upon drug discontinuation, including sleep disturbances, irritability, and possibly memory deficits. In cannabinoid-dependent rodents, the CB(1) antagonist rimonabant precipitates somatic withdrawal and enhances forskolin-stimulated adenylyl cyclase activity in cerebellum, an effect opposite that of acutely administered ∆(9)-tetrahydrocannabinol (THC), the primary constituent in cannabis. Here, we tested whether THC-dependent mice undergoing rimonabant-precipitated withdrawal display short-term spatial memory deficits, as assessed in the Morris water maze. We also evaluated whether rimonabant would precipitate adenylyl cyclase superactivation in hippocampal and cerebellar tissue from THC-dependent mice. Rimonabant significantly impaired spatial memory of THC-dependent mice at lower doses than those necessary to precipitate somatic withdrawal behavior. In contrast, maze performance was near perfect in the cued task, suggesting sensorimotor function and motivational factors were unperturbed by the withdrawal state. Finally, rimonabant increased adenylyl cyclase activity in cerebellar, but not in hippocampal, membranes. The memory disruptive effects of THC undergo tolerance following repeated dosing, while the withdrawal state leads to a rebound deficit in memory. These results establish spatial memory impairment as a particularly sensitive component of cannabinoid withdrawal, an effect that may be mediated through compensatory changes in the cerebellum.

Reduced event-related low frequency EEG activity in patients with early onset schizophrenia and their unaffected siblings.

PubMed

Simmonite, Molly; Bates, Alan Thomas; Groom, Madeleine; Hollis, Chris; Liddle, Peter Francis

2015-04-30

Low-frequency oscillations in the electroencephalogram (EEG) have been found to be abnormal in patients with schizophrenia. It is unclear, however, whether these abnormalities are related to severity of illness or are a marker for risk. This study investigated total and evoked theta and delta activity in schizophrenia patients, unaffected siblings, and healthy controls (HCs). EEG data were recorded whilst 24 individuals with schizophrenia, 26 unaffected siblings of individuals with schizophrenia and 26 healthy control participants completed a Go/No-Go task. Event-related total activity and evoked theta and delta activity were calculated for correct hits (CH), failed inhibitions (FI) and correct inhibitions (CI) trials. Patients displayed significantly less total delta, evoked delta, total theta and evoked theta activity when compared with healthy controls. Unaffected siblings displayed abnormalities of evoked delta, but other measures were similar to those in control participants. The findings of this study add to evidence that abnormal low-frequency EEG oscillations contribute to impairments in information processing seen in schizophrenia. These findings also suggest abnormal evoked delta oscillations are associated with an increased familial risk of developing the disorder. Copyright © 2015. Published by Elsevier Ireland Ltd.

Saracatinib Impairs Head and Neck Squamous Cell Carcinoma Invasion by Disrupting Invadopodia Function

PubMed Central

Ammer, Amanda Gatesman; Kelley, Laura C.; Hayes, Karen E.; Evans, Jason V.; Lopez-Skinner, Lesly Ann; Martin, Karen H.; Frederick, Barbara; Rothschild, Brian L.; Raben, David; Elvin, Paul; Green, Tim P.; Weed, Scott A.

2010-01-01

Elevated Src kinase activity is linked to the progression of solid tumors, including head and neck squamous cell carcinoma (HNSCC). Src regulates HNSCC proliferation and tumor invasion, with the Src-targeted small molecule inhibitor saracatinib displaying potent anti-invasive effects in preclinical studies. However, the pro-invasive cellular mechanism(s) perturbed by saracatinib are unclear. The anti-proliferative and anti-invasive effects of saracatinib on HNSCC cell lines were therefore investigated in pre-clinical cell and mouse model systems. Saracatinib treatment inhibited growth, cell cycle progression and transwell Matrigel invasion in HNSCC cell lines. Dose-dependent decreases in Src activation and phosphorylation of the invasion-associated substrates focal adhesion kinase, p130 CAS and cortactin were also observed. While saracatinib did not significantly impact HNSCC tumor growth in a mouse orthotopic model of tongue squamous cell carcinoma, impaired perineural invasion and cervical lymph node metastasis was observed. Accordingly, saracatinib treatment displayed a dose-dependent inhibitory effect on invadopodia formation, extracellular matrix degradation and matrix metalloprotease 9 activation. These results suggest that inhibition of Src kinase by saracatinib impairs the pro-invasive activity of HNSCC by inhibiting Src substrate phosphorylation important for invadopodia formation and associated matrix metalloprotease activity. PMID:20505783

At-a-glance monitoring: covert observations of anesthesiologists in the operating room.

PubMed

Ford, Simon; Birmingham, Elina; King, Ashlee; Lim, Joanne; Ansermino, J Mark

2010-09-01

Patient monitoring displays are designed to improve patient safety, and yet little is known about how anesthesiologists interact with these displays. Previous studies of clinician behavior used an observer in the operating room, which may have altered behavior. We describe a covert observation technique to determine how often and for how long anesthesiologists actually look at the monitoring display during different segments of the maintenance phase of anesthesia, and to determine whether this changed with more than 1 anesthesia provider or during concomitant activities such as reading. Five staff anesthesiologists, 2 anesthesia fellows, 3 anesthesia residents, and 2 medical students were covertly videotaped across 10 dual anesthesia provider cases and 10 solo cases. Videotapes were later segmented (5 minutes postinduction [early maintenance], mid-maintenance, and immediately before the drapes came down [late maintenance]) and coded for looking behavior at the patient monitor, anesthesia chart, and other reading material. Anesthesiologists looked at the monitor in 1- to 2-second glances, performed frequently throughout the 3 segments of maintenance anesthesia. Overall, the patient monitor was looked at only 5 of the analyzed time, which is less than has previously been reported. Monitoring behavior was constant across the segments of maintenance anesthesia and was not significantly affected by the number of anesthesia providers or role (trainee vs. senior). In contrast, charting behavior and other reading material viewing changed significantly over the analyzed segments of maintenance anesthesia. The presence of "at-a-glance monitoring" has implications for the design of patient monitoring displays. Displays should be developed to optimize the information obtained from brief glances at the monitor.

Ultrastructural characteristics of fibrin clots from canine and feline platelet concentrates activated with calcium gluconate or calcium gluconate plus batroxobin.

PubMed

Silva, Raúl F; Carmona, Jorge U; Rezende, Cleuza M F

2013-04-15

The aim of this study was to use transmission electron microscopy to describe the ultrastructural characteristics of clots obtained from canine and feline platelet concentrates (PC) that had been activated with calcium gluconate (CG) or CG plus batroxobin (CGB). Platelets from fibrin clots were classified according their morphological changes. The area of the intercellular space (μm2), the area of the fibrin fibers (μm2), and the width of the fibrin fibers (μm) were determined for the dog clots. The platelet area (μm2), the area of fibrin fibers (μm2), the ratio of the minor and major axes of platelets, the ratio of the major and minor axes of platelets, and the number of α-granules found within platelets were measured for the cat clots. Cat platelets displayed full activation. Dog platelets displayed lysis with loss of normal architecture. In both species, a statistically significant difference was found (P < 0.01) between the fibrin fiber measurements in the PC clots activated with CG and CGB. The findings suggest that activation with CG caused platelet alpha granules to release their contents. In cats, fibrin production was greater when the PC was activated with CG. In dogs, activation with CG produced thick fibrin fibers.

Increased osteoblastic activity and expression of receptor activator of NF-kappaB ligand in nonuremic nephrotic syndrome.

PubMed

Freundlich, Michael; Alonzo, Evelyn; Bellorin-Font, Ezequiel; Weisinger, Jose R

2005-07-01

Patients with nephrotic syndrome (NS), even with normal GFR, often display altered mineral homeostasis and abnormal bone histology. However, the latter, mostly osteomalacia and increased bone resorption, cannot be readily explained by the prevalent concentrations of parathyroid hormone and vitamin D metabolites. The transmembrane receptor activator of NF-kappaB ligand (RANKL) of osteoblasts is essential for osteoclast formation and differentiation. Osteoblasts activity and the expression of RANKL were tested in cultures of normal human osteoblasts with sera obtained from patients with NS and normal GFR (129 +/- 26 ml/min per 1.73 m2) during relapse and remission of their NS. Osteoblasts that were cultured in vitro with sera during relapse displayed elevated concentrations of alkaline phosphatase (AP) and increased expression of RANKL. By contrast, during remission, AP concentrations were significantly lower (P < 0.05) and RANKL expression notably attenuated or absent. AP correlated with the proteinuria (r = 0.5, P < 0.05) and was not significantly affected by the therapeutic administration of corticosteroids. Whereas parathyroid hormone levels were normal (35 +/- 21 pg/ml), the serum markers of bone formation (osteocalcin and bone-specific alkaline phosphatase) were lower during relapse compared with remission. Thus, sera from patients with NS and normal GFR stimulate the activity of osteoblasts and upregulate their expression of RANKL. These alterations, more prominent during clinically active NS, are transient and reversible upon remission. These disturbances of bone biology may play an important pathogenic role in the abnormal bone histology observed in patients with NS even before a decline in GFR occurs.

Functional Role of Tyr12 in the Catalytic Activity of Novel Zeta-like Glutathione S-transferase from Acidovorax sp. KKS102.

PubMed

Shehu, Dayyabu; Alias, Zazali

2018-05-19

Glutathione S-transferases (GSTs) are a family of enzymes that function in the detoxification of variety of electrophilic substrates. In the present work, we report a novel zeta-like GST (designated as KKSG9) from the biphenyl/polychlorobiphenyl degrading organism Acidovorax sp. KKS102. KKSG9 possessed low sequence similarity but similar biochemical properties to zeta class GSTs. Functional analysis showed that the enzyme exhibits wider substrate specificity compared to most zeta class GSTs by reacting with 1-chloro-2,4-dinitrobenzene (CDNB), p-nitrobenzyl chloride (NBC), ethacrynic acid (EA), hydrogen peroxide, and cumene hydroperoxide. The enzyme also displayed dehalogenation function against dichloroacetate, permethrin, and dieldrin. The functional role of Tyr12 was also investigated by site-directed mutagenesis. The mutant (Y12C) displayed low catalytic activity and dehalogenation function against all the substrates when compared with the wild type. Kinetic analysis using NBC and GSH as substrates showed that the mutant (Y12C) displayed a higher affinity for NBC when compared with the wild type, however, no significant change in GSH affinity was observed. These findings suggest that the presence of tyrosine residue in the motif might represent an evolutionary trend toward improving the catalytic activity of the enzyme. The enzyme as well could be useful in the bioremediation of various types of organochlorine pollutants.

Pharmacological characterisation of strychnine and brucine analogues at glycine and alpha7 nicotinic acetylcholine receptors.

PubMed

Jensen, Anders A; Gharagozloo, Parviz; Birdsall, Nigel J M; Zlotos, Darius P

2006-06-06

Strychnine and brucine from the plant Strychnos nux vomica have been shown to have interesting pharmacological effects on several neurotransmitter receptors, including some members of the superfamily of ligand-gated ion channels. In this study, we have characterised the pharmacological properties of tertiary and quaternary analogues as well as bisquaternary dimers of strychnine and brucine at human alpha1 and alpha1beta glycine receptors and at a chimera consisting of the amino-terminal domain of the alpha7 nicotinic receptor (containing the orthosteric ligand binding site) and the ion channel domain of the 5-HT3A serotonin receptor. Although the majority of the analogues displayed significantly increased Ki values at the glycine receptors compared to strychnine and brucine, a few retained the high antagonist potencies of the parent compounds. However, mirroring the pharmacological profiles of strychnine and brucine, none of the analogues displayed significant selectivity between the alpha1 and alpha1beta subtypes. The structure-activity relationships for the compounds at the alpha7/5-HT3 chimera were significantly different from those at the glycine receptors. Most strikingly, quaternization of strychnine and brucine with substituents possessing different steric and electronic properties completely eliminated the activity at the glycine receptors, whereas binding affinity to the alpha7/5-HT3 chimera was retained for the majority of the quaternary analogues. This study provides an insight into the structure-activity relationships for strychnine and brucine analogues at these ligand-gated ion channels.

Novel use of a noninvasive hemodynamic monitor in a personalized, active learning simulation.

PubMed

Zoller, Jonathan K; He, Jianghua; Ballew, Angela T; Orr, Walter N; Flynn, Brigid C

2017-06-01

The present study furthered the concept of simulation-based medical education by applying a personalized active learning component. We tested this novel approach utilizing a noninvasive hemodynamic monitor with the capability to measure and display in real time numerous hemodynamic parameters in the exercising participant. Changes in medical knowledge concerning physiology were examined with a pre-and posttest. Simply by observation of one's own hemodynamic variables, the understanding of complex physiological concepts was significantly enhanced. Copyright © 2017 the American Physiological Society.

Projection type transparent 3D display using active screen

NASA Astrophysics Data System (ADS)

Kamoshita, Hiroki; Yendo, Tomohiro

2015-05-01

Equipment to enjoy a 3D image, such as a movie theater, television and so on have been developed many. So 3D video are widely known as a familiar image of technology now. The display representing the 3D image are there such as eyewear, naked-eye, the HMD-type, etc. They has been used for different applications and location. But have not been widely studied for the transparent 3D display. If transparent large 3D display is realized, it is useful to display 3D image overlaid on real scene in some applications such as road sign, shop window, screen in the conference room etc. As a previous study, to produce a transparent 3D display by using a special transparent screen and number of projectors is proposed. However, for smooth motion parallax, many projectors are required. In this paper, we propose a display that has transparency and large display area by time multiplexing projection image in time-division from one or small number of projectors to active screen. The active screen is composed of a number of vertically-long small rotate mirrors. It is possible to realize the stereoscopic viewing by changing the image of the projector in synchronism with the scanning of the beam.3D vision can be realized by light is scanned. Also, the display has transparency, because it is possible to see through the display when the mirror becomes perpendicular to the viewer. We confirmed the validity of the proposed method by using simulation.

Central or Peripheral Delivery of an Adenosine A1 Receptor Agonist Improves Mechanical Allodynia in a Mouse Model of Painful Diabetic Neuropathy

PubMed Central

Katz, N. K.; Ryals, J. M.; Wright, D. E.

2014-01-01

Diabetic peripheral neuropathy is a common complication of diabetes mellitus, and a significant proportion of individuals suffer debilitating pain that significantly affects their quality of life. Unfortunately, symptomatic treatment options have limited efficacy, and often carry significant risk of systemic adverse effects. Activation of the adenosine A1 receptor (A1R) by the analgesic small molecule adenosine has been shown to have antinociceptive benefits in models of inflammatory and neuropathic pain. The current study used a mouse model of painful diabetic neuropathy to determine the effect of diabetes on endogenous adenosine production, and if central or peripheral delivery of adenosine receptor agonists could alleviate signs of mechanical allodynia in diabetic mice. Diabetes was induced using streptozocin in male A/J mice. Mechanical withdrawal thresholds were measured weekly to characterize neuropathy phenotype. Hydrolysis of AMP into adenosine by ectonucleotidases was determined in the dorsal root ganglia (DRG) and spinal cord at 8-weeks post-induction of diabetes. AMP, adenosine and the specific A1R agonist, N6-cyclopentyladenosine (CPA), were administered both centrally (intrathecal) and peripherally (intraplantar) to determine the effect of activation of adenosine receptors on mechanical allodynia in diabetic mice. Eight weeks post-induction, diabetic mice displayed significantly decreased hydrolysis of extracellular AMP in the DRG; at this same time, diabetic mice displayed significantly decreased mechanical withdrawal thresholds compared to nondiabetic controls. Central delivery AMP, adenosine and CPA significantly improved mechanical withdrawal thresholds in diabetic mice. Surprisingly, peripheral delivery of CPA also improved mechanical allodynia in diabetic mice. This study provides new evidence that diabetes significantly affects endogenous AMP hydrolysis, suggesting that altered adenosine production could contribute to the development of painful diabetic neuropathy. Moreover, central and peripheral activation of A1R significantly improved mechanical sensitivity, warranting further investigation into this important antinociceptive pathway as a novel therapeutic option for the treatment of painful diabetic neuropathy. PMID:25451280

Predicting Visual Consciousness Electrophysiologically from Intermittent Binocular Rivalry

PubMed Central

O’Shea, Robert P.; Kornmeier, Jürgen; Roeber, Urte

2013-01-01

Purpose We sought brain activity that predicts visual consciousness. Methods We used electroencephalography (EEG) to measure brain activity to a 1000-ms display of sine-wave gratings, oriented vertically in one eye and horizontally in the other. This display yields binocular rivalry: irregular alternations in visual consciousness between the images viewed by the eyes. We replaced both gratings with 200 ms of darkness, the gap, before showing a second display of the same rival gratings for another 1000 ms. We followed this by a 1000-ms mask then a 2000-ms inter-trial interval (ITI). Eleven participants pressed keys after the second display in numerous trials to say whether the orientation of the visible grating changed from before to after the gap or not. Each participant also responded to numerous non-rivalry trials in which the gratings had identical orientations for the two eyes and for which the orientation of both either changed physically after the gap or did not. Results We found that greater activity from lateral occipital-parietal-temporal areas about 180 ms after initial onset of rival stimuli predicted a change in visual consciousness more than 1000 ms later, on re-presentation of the rival stimuli. We also found that less activity from parietal, central, and frontal electrodes about 400 ms after initial onset of rival stimuli predicted a change in visual consciousness about 800 ms later, on re-presentation of the rival stimuli. There was no such predictive activity when the change in visual consciousness occurred because the stimuli changed physically. Conclusion We found early EEG activity that predicted later visual consciousness. Predictive activity 180 ms after onset of the first display may reflect adaption of the neurons mediating visual consciousness in our displays. Predictive activity 400 ms after onset of the first display may reflect a less-reliable brain state mediating visual consciousness. PMID:24124536

Distinct polymer architecture mediates switching of complement activation pathways at the nanosphere-serum interface: implications for stealth nanoparticle engineering.

PubMed

Hamad, Islam; Al-Hanbali, Othman; Hunter, A Christy; Rutt, Kenneth J; Andresen, Thomas L; Moghimi, S Moein

2010-11-23

Nanoparticles with surface projected polyethyleneoxide (PEO) chains in "mushroom-brush" and "brush" configurations display stealth properties in systemic circulation and have numerous applications in site-specific targeting for controlled drug delivery and release as well as diagnostic imaging. We report on the "structure-activity" relationship pertaining to surface-immobilized PEO of various configurations on model nanoparticles, and the initiation of complement cascade, which is the most ancient component of innate human immunity, and its activation may induce clinically significant adverse reactions in some individuals. Conformational states of surface-projected PEO chains, arising from the block copolymer poloxamine 908 adsorption, on polystyrene nanoparticles trigger complement activation differently. Alteration of copolymer architecture on nanospheres from mushroom to brush configuration not only switches complement activation from C1q-dependent classical to lectin pathway but also reduces the level of generated complement activation products C4d, Bb, C5a, and SC5b-9. Also, changes in adsorbed polymer configuration trigger alternative pathway activation differently and through different initiators. Notably, the role for properdin-mediated activation of alternative pathway was only restricted to particles displaying PEO chains in a transition mushroom-brush configuration. Since nanoparticle-mediated complement activation is of clinical concern, our findings provide a rational basis for improved surface engineering and design of immunologically safer stealth and targetable nanosystems with polymers for use in clinical medicine.

Sepsis-induced activation of endogenous GLP-1 system is enhanced in type 2 diabetes.

PubMed

Perl, Sivan H; Bloch, Olga; Zelnic-Yuval, Dana; Love, Itamar; Mendel-Cohen, Lior; Flor, Hadar; Rapoport, Micha J

2018-05-01

High levels of circulating GLP-1 are associated with severity of sepsis in critically ill nondiabetic patients. Whether patients with type 2 diabetes (T2D) display different activation of the endogenous GLP-1 system during sepsis and whether it is affected by diabetes-related metabolic parameters are not known. Serum levels of GLP-1 (total and active forms) and its inhibitor enzyme sDPP-4 were determined by ELISA on admission and after 2 to 4 days in 37 sepsis patients with (n = 13) and without T2D (n = 24) and compared to normal healthy controls (n = 25). Correlations between GLP-1 system activation and clinical, inflammatory, and diabetes-related metabolic parameters were performed. A 5-fold (P < .001) and 2-fold (P < .05) increase in active and total GLP-1 levels, respectively, were found on admission as compared to controls. At 2 to 4 days from admission, the level of active GLP-1 forms in surviving patients were decreased significantly (P < .005), and positively correlated with inflammatory marker CRP (r = 0.33, P = .05). T2D survivors displayed a similar but more enhanced pattern of GLP-1 response than nondiabetic survivors. Nonsurvivors demonstrate an early extreme increase of both total and active GLP-1 forms, 9.5-fold and 5-fold, respectively (P < .05). The initial and late levels of circulating GLP-1 inhibitory enzyme sDPP-4 were twice lower in all studied groups (P < .001), compared with healthy controls. Taken together, these data indicate that endogenous GLP-1 system is activated during sepsis. Patients with T2D display an enhanced and prolonged activation as compared to nondiabetic patients. Extreme early increased GLP-1 levels during sepsis indicate poor prognosis. Copyright © 2018 John Wiley & Sons, Ltd.

Effects of contaminants of emerging concern on Myzus persicae (Sulzer, Hemiptera: Aphididae) biology and on their host plant, Capsicum annuum.

PubMed

Pennington, Marcus John; Rothman, Jason A; Jones, Michael Bellinger; McFrederick, Quinn S; Gan, Jay; Trumble, John T

2018-02-08

Many countries are utilizing reclaimed wastewater for agriculture as water demands due to drought, rising temperatures, and expanding human populations. Unfortunately, wastewater often contains biologically active, pseudopersistant pharmaceuticals, even after treatment. Runoff from agriculture and effluent from wastewater treatment plants also contribute high concentrations of pharmaceuticals to the environment. This study assessed the effects of common pharmaceuticals on an agricultural pest, the aphid Myzus persicae (Sulzer, Hemiptera: Aphididae). Second instar nymphs were transferred to bell peppers (Capsicum annuum) that were grown hydroponically. Treatment plants were spiked with contaminants of emerging concern (CECs) at environmentally relevant concentrations found in reclaimed wastewater. M. persicae displayed no differences in population growth or microbial community differences due to chemical treatments. Plants, however, displayed significant growth reduction in antibiotic and mixture treatments, specifically in wet root masses. Antibiotic treatment masses were significantly reduced in the total and root wet masses. Mixture treatments displayed an overall reduction in plant root wet mass. Our results suggest that the use of reclaimed wastewater for crop irrigation would not affect aphid populations, but could hinder or delay crop production.

Change Blindness Phenomena for Virtual Reality Display Systems.

PubMed

Steinicke, Frank; Bruder, Gerd; Hinrichs, Klaus; Willemsen, Pete

2011-09-01

In visual perception, change blindness describes the phenomenon that persons viewing a visual scene may apparently fail to detect significant changes in that scene. These phenomena have been observed in both computer-generated imagery and real-world scenes. Several studies have demonstrated that change blindness effects occur primarily during visual disruptions such as blinks or saccadic eye movements. However, until now the influence of stereoscopic vision on change blindness has not been studied thoroughly in the context of visual perception research. In this paper, we introduce change blindness techniques for stereoscopic virtual reality (VR) systems, providing the ability to substantially modify a virtual scene in a manner that is difficult for observers to perceive. We evaluate techniques for semiimmersive VR systems, i.e., a passive and active stereoscopic projection system as well as an immersive VR system, i.e., a head-mounted display, and compare the results to those of monoscopic viewing conditions. For stereoscopic viewing conditions, we found that change blindness phenomena occur with the same magnitude as in monoscopic viewing conditions. Furthermore, we have evaluated the potential of the presented techniques for allowing abrupt, and yet significant, changes of a stereoscopically displayed virtual reality environment.

Transparent active matrix organic light-emitting diode displays driven by nanowire transistor circuitry.

PubMed

Ju, Sanghyun; Li, Jianfeng; Liu, Jun; Chen, Po-Chiang; Ha, Young-Geun; Ishikawa, Fumiaki; Chang, Hsiaokang; Zhou, Chongwu; Facchetti, Antonio; Janes, David B; Marks, Tobin J

2008-04-01

Optically transparent, mechanically flexible displays are attractive for next-generation visual technologies and portable electronics. In principle, organic light-emitting diodes (OLEDs) satisfy key requirements for this application-transparency, lightweight, flexibility, and low-temperature fabrication. However, to realize transparent, flexible active-matrix OLED (AMOLED) displays requires suitable thin-film transistor (TFT) drive electronics. Nanowire transistors (NWTs) are ideal candidates for this role due to their outstanding electrical characteristics, potential for compact size, fast switching, low-temperature fabrication, and transparency. Here we report the first demonstration of AMOLED displays driven exclusively by NW electronics and show that such displays can be optically transparent. The displays use pixel dimensions suitable for hand-held applications, exhibit 300 cd/m2 brightness, and are fabricated at temperatures suitable for integration on plastic substrates.

Recent patents on electrophoretic displays and materials.

PubMed

Christophersen, Marc; Phlips, Bernard F

2010-11-01

Electrophoretic displays (EPDs) have made their way into consumer products. EPDs enable displays that offer the look and form of a printed page, often called "electronic paper". We will review recent apparatus and method patents for EPD devices and their fabrication. A brief introduction into the basic display operation and history of EPDs is given, while pointing out the technological challenges and difficulties for inventors. Recently, the majority of scientific publications and patenting activity has been directed to micro-segmented EPDs. These devices exhibit high optical reflectance and contrast, wide viewing angle, and high image resolution. Micro-segmented EPDs can also be integrated with flexible transistors technologies into flexible displays. Typical particles size ranges from 200 nm to 2 micrometer. Currently one very active area of patenting is the development of full-color EPDs. We summarize the recent patenting activity for EPDs and provide comments on perceiving factors driving intellectual property protection for EPD technologies.

Pyrazole derived ultra-short antimicrobial peptidomimetics with potent anti-biofilm activity.

PubMed

Ahn, Mija; Gunasekaran, Pethaiah; Rajasekaran, Ganesan; Kim, Eun Young; Lee, Soo-Jae; Bang, Geul; Cho, Kun; Hyun, Jae-Kyung; Lee, Hyun-Ju; Jeon, Young Ho; Kim, Nam-Hyung; Ryu, Eun Kyoung; Shin, Song Yub; Bang, Jeong Kyu

2017-01-05

In this study, we report on the first chemical synthesis of ultra-short pyrazole-arginine based antimicrobial peptidomimetics derived from the newly synthesized N-alkyl/aryl pyrazole amino acids. Through the systematic tuning of hydrophobicity, charge, and peptide length, we identified the shortest peptide Py11 with the most potent antimicrobial activity. Py11 displayed greater antimicrobial activity against antibiotic-resistant bacteria, including MRSA, MDRPA, and VREF, which was approximately 2-4 times higher than that of melittin. Besides its higher selectivity (therapeutic index) toward bacterial cells than LL-37, Py11 showed highly increased proteolytic stability against trypsin digestion and maintained its antimicrobial activity in the presence of physiological salts. Interestingly, Py11 exhibited higher anti-biofilm activity against MDRPA compared to LL-37. The results from fluorescence spectroscopy and transmission electron microscopy (TEM) suggested that Py11 kills bacterial cells possibly by integrity disruption damaging the cell membrane, leading to the cytosol leakage and eventual cell lysis. Furthermore, Py11 displayed significant anti-inflammatory (endotoxin-neutralizing) activity by inhibiting LPS-induced production of nitric oxide (NO) and TNF-α. Collectively, our results suggest that Py11 may serve as a model compound for the design of antimicrobial and antisepsis agents. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Identification of novel selective V2 receptor non-peptide agonists.

PubMed

Del Tredici, Andria L; Vanover, Kim E; Knapp, Anne E; Bertozzi, Sine M; Nash, Norman R; Burstein, Ethan S; Lameh, Jelveh; Currier, Erika A; Davis, Robert E; Brann, Mark R; Mohell, Nina; Olsson, Roger; Piu, Fabrice

2008-10-30

Peptides with agonist activity at the vasopressin V(2) receptor are used clinically to treat fluid homeostasis disorders such as polyuria and central diabetes insipidus. Of these peptides, the most commonly used is desmopressin, which displays poor bioavailability as well as potent activity at the V(1b) receptor, with possible stress-related adverse effects. Thus, there is a strong need for the development of small molecule chemistries with selective V(2) receptor agonist activity. Using the functional cell-based assay Receptor Selection and Amplification Technology (R-SAT((R))), a screening effort identified three small molecule chemotypes (AC-94544, AC-88324, and AC-110484) with selective agonist activity at the V(2) receptor. One of these compounds, AC-94544, displayed over 180-fold selectivity at the V(2) receptor compared to related vasopressin and oxytocin receptors and no activity at 28 other G protein-coupled receptors (GPCRs). All three compounds also showed partial agonist activity at the V(2) receptor in a cAMP accumulation assay. In addition, in a rat model of central diabetes insipidus, AC-94544 was able to significantly reduce urine output in a dose-dependent manner. Thus, AC-94544, AC-88324, and AC-110484 represent novel opportunities for the treatment of disorders associated with V(2) receptor agonist deficiency.

The essential sequence of substance P for locomotion.

PubMed

Treptow, K; Morgenstern, R; Oehme, P; Bienert, M

1986-10-01

In rats the effect of substance P SP (1-11 and SP (5-11) heptapeptide on locomotion in open field was investigated after intrategmental application. SP (1-11) increase the locomotor activity significantly, SP (5-11) heptapeptide do not-do it. The effect of SP(1-11), SP(5-11) heptapeptide, SP(6-11) hexapeptide, and SP(1-4) tetrapeptide on the circadianly organized locomotor activity was researched after i.p. application at 11 a.m. (light phasis, low activity of rats) or 7 p.m. (dark phasis, high activity). An increased effect on locomotiou'slow activity of rats appears by SP(1-11) and SP(1-4) tetrapeptide application for several hours in light time. Both peptides display a decreasing effect on locomotion after application for several hours in dark time, too. SP(5-11) heptapeptide and SP(6-11) hexapeptide do not have any influence on locomotion. The effects of SP(1-11) are equal to results found after application into the ventral tegmental area. The experimental results display that SP acts as a regulatory peptide modulating the activity of rats by a levelling mechanism. The N-terminal SP-sequence, SP(1-4), acts in a similar manner. The effects are discussed in relation to the mediation by receptors which recognize the C- or N-terminal part of the SP molecule.

Antidyslipidemic and antioxidant effects of novel Lupeol-derived chalcones.

PubMed

Srivastava, Shishir; Sonkar, Ravi; Mishra, Sunil Kumar; Tiwari, Avinash; Balaramnavar, Vishal M; Balramnavar, Vishal; Mir, Snober; Bhatia, Gitika; Saxena, Anil K; Lakshmi, Vijai

2013-10-01

A series of Lupeol-based chalcones have been synthesized aiming to enhance the therapeutic efficacy of parent compound, the novel compounds were evaluated for their antidyslipidemic activity in triton-WR 1339 induced hyperlipidemic rats. Among the ten synthesized chalcones, the most active K4, K8, and K9 reversed the plasma levels of TC by (24, 25, 27 %), phospholipid by (25, 26, 25 %) and triacylglycerol by (27, 24, 24 %) respectively. In addition, the compounds showed significant in vitro antioxidant activity. The lipid lowering activity of these compounds were mediated through lipoprotein lipase activation (12-21 %) and enhanced post-heparin lipolytic activity (15-16 %). The compounds also displayed noteworthy inhibitory effect on 3-hydroxy-3-methyl-glutaryl reductase activity (in vitro). The in vitro effect of the most active compounds on MDI-induced adipogenesis using 3T3-L1 preadipocytes at 10 and 20 μM concentrations showed significant inhibition (20-32 %) of adipogenesis.

Effect of a Real-Time Electronic Dashboard on a Rapid Response System.

PubMed

Fletcher, Grant S; Aaronson, Barry A; White, Andrew A; Julka, Reena

2017-11-20

A rapid response system (RRS) may have limited effectiveness when inpatient providers fail to recognize signs of early patient decompensation. We evaluated the impact of an electronic medical record (EMR)-based alerting dashboard on outcomes associated with RRS activation. We used a repeated treatment study in which the dashboard display was successively turned on and off each week for ten 2-week cycles over a 20-week period on the inpatient acute care wards of an academic medical center. The Rapid Response Team (RRT) dashboard displayed all hospital patients in a single view ranked by severity score, updated in real time. The dashboard could be seen within the EMR by any provider, including RRT members. The primary outcomes were the incidence rate ratio (IRR) of all RRT activations, unexpected ICU transfers, cardiopulmonary arrests and deaths on general medical-surgical wards (wards). We conducted an exploratory analysis of first RRT activations. There were 6736 eligible admissions during the 20-week study period. There was no change in overall RRT activations (IRR = 1.14, p = 0.07), but a significant increase in first RRT activations (IRR = 1.20, p = 0.04). There were no significant differences in unexpected ICU transfers (IRR = 1.15, p = 0.25), cardiopulmonary arrests on general wards (IRR = 1.46, p = 0.43), or deaths on general wards (IRR = 0.96, p = 0.89). The introduction of the RRT dashboard was associated with increased initial RRT activations but not overall activations, unexpected ICU transfers, cardiopulmonary arrests, or death. The RRT dashboard is a novel tool to help providers recognize patient decompensation and may improve initial RRT notification.

Volatile chemical composition and bioactivity of six essential oils against the stored food insect Sitophilus zeamais Motsch. (Coleoptera Dryophthoridae).

PubMed

Bertoli, Alessandra; Conti, Barbara; Mazzoni, Valerio; Meini, Laura; Pistelli, Luisa

2012-01-01

Essential oils (EOs) of Achillea millefolium, Myrtus communis, Rosmarinus officinalis, Helichrysum italicum, Foeniculum vulgare and Lavandula angustifolia were analysed with GC-FID and GC-MS in order to define their aromatic profiles and then their toxicity and repellent activity against Sitophilus zeamais Motsch. (Coleoptera Dryophthoridae) with specific bioassays were evaluated. Results from topical applications on insects showed that all EOs had variable and significant insecticidal activity. Mortality rate never exceeded 76%. Results of repellency tests are indicated for M. communis and L. angustifolia EOs, displaying high repellent activity to S. zeamais adults.

Novel prodrugs of tegafur that display improved anticancer activity and antiangiogenic properties.

PubMed

Engel, Dikla; Nudelman, Abraham; Tarasenko, Nataly; Levovich, Inesa; Makarovsky, Igor; Sochotnikov, Segev; Tarasenko, Igor; Rephaeli, Ada

2008-01-24

New and more potent prodrugs of the 5-fluorouracyl family derived by hydroxymethylation or acyloxymethylation of 5-fluoro-1-(tetrahydro-2-furanyl)-2,4(1H,3H)-pyrimidinedione (tegafur, 1) are described. The anticancer activity of the butyroyloxymethyl-tegafur derivative 3 and not that of tegafur was attenuated by the antioxidant N-acetylcysteine, suggesting that the increased activity of the prodrug is in part mediated by an increase of reactive oxygen species. Compound 3 in an in vitro matrigel assay was found to be a more potent antiangiogenic agent than tegafur. In vivo 3 was significantly more potent than tegafur in inhibiting 4T1 breast carcinoma lung metastases and growth of HT-29 human colon carcinoma tumors in a mouse xenograft. In summary, the multifunctional prodrugs of tegafur display selectivity toward cancer cells, antiangiogenic activity, and anticancer activities in vitro and in vivo, superior to those of tegafur. 5-fluoro-1-(tetrahydro-2-furanyl)-2,4(1 H,3 H)-pyrimidinedione (tegafur, 1), the oral prodrug of 5-FU, has been widely used for treatment of gastrointestinal malignancies with modest efficacy. The aim of this study was to develop and characterize new and more potent prodrugs of the 5-FU family derived by hydroxymethylation or acyloxymethylation of tegafur. Comparison between the effect of tegafur and the new prodrugs on the viability of a variety of cancer cell lines showed that the IC50 and IC90 values of the novel prodrugs were 5-10-fold lower than those of tegafur. While significant differences between the IC50 values of tegafur were observed between the sensitive HT-29 and the resistant LS-1034 colon cancer cell lines, the prodrugs affected them to a similar degree, suggesting that they overcame drug resistance. The increased potency of the prodrugs could be attributed to the antiproliferative contribution imparted by formaldehyde and butyric acid, released upon metabolic degradation. The anticancer activity of the butyroyloxymethyl-tegafur derivative 3 and not that of tegafur was attenuated by the antioxidant N-acetylcysteine, suggesting that the increased activity of the prodrug is in part mediated by an increase of reactive oxygen species. Compound 3 in an in vitro matrigel assay was found to be a more potent antiangiogenic agent than tegafur. In vivo 3 was significantly more potent than tegafur in inhibiting 4T1 breast carcinoma lung metastases and growth of HT-29 human colon carcinoma tumors in a mouse xenograft. In summary, the multifunctional prodrugs of tegafur display selectivity toward cancer cells, antiangiogenic activity and anticancer activities in vitro and in vivo, superior to those of tegafur.

Tile-Image Merging and Delivering for Virtual Camera Services on Tiled-Display for Real-Time Remote Collaboration

NASA Astrophysics Data System (ADS)

Choe, Giseok; Nang, Jongho

The tiled-display system has been used as a Computer Supported Cooperative Work (CSCW) environment, in which multiple local (and/or remote) participants cooperate using some shared applications whose outputs are displayed on a large-scale and high-resolution tiled-display, which is controlled by a cluster of PC's, one PC per display. In order to make the collaboration effective, each remote participant should be aware of all CSCW activities on the titled display system in real-time. This paper presents a capturing and delivering mechanism of all activities on titled-display system to remote participants in real-time. In the proposed mechanism, the screen images of all PC's are periodically captured and delivered to the Merging Server that maintains separate buffers to store the captured images from the PCs. The mechanism selects one tile image from each buffer, merges the images to make a screen shot of the whole tiled-display, clips a Region of Interest (ROI), compresses and streams it to remote participants in real-time. A technical challenge in the proposed mechanism is how to select a set of tile images, one from each buffer, for merging so that the tile images displayed at the same time on the tiled-display can be properly merged together. This paper presents three selection algorithms; a sequential selection algorithm, a capturing time based algorithm, and a capturing time and visual consistency based algorithm. It also proposes a mechanism of providing several virtual cameras on tiled-display system to remote participants by concurrently clipping several different ROI's from the same merged tiled-display images, and delivering them after compressing with video encoders requested by the remote participants. By interactively changing and resizing his/her own ROI, a remote participant can check the activities on the tiled-display effectively. Experiments on a 3 × 2 tiled-display system show that the proposed merging algorithm can build a tiled-display image stream synchronously, and the ROI-based clipping and delivering mechanism can provide individual views on the tiled-display system to multiple remote participants in real-time.

Commercial golf glove effects on golf performance and forearm muscle activity.

PubMed

Sorbie, Graeme G; Darroch, Paul; Grace, Fergal M; Gu, Yaodong; Baker, Julien S; Ugbolue, Ukadike C

2017-01-01

The study aimed to determine whether or not commercial golf gloves influence performance variables and forearm muscle activity during golf play. Fifteen golfers participated in the laboratory based study, each performing 8 golf swings with a Driver and 7-iron whilst wearing a glove and 8 without wearing the glove. Club head speed, ball speed and absolute carry distance performance variables were calculated. Surface electromyography was recorded from the flexor digitorum superficialis and extensor carpi radialis brevis on both forearm muscles. Club head speed, ball speed and absolute carry distance was significantly higher when using the Driver with the glove in comparison to the Driver without the glove (p < 0.05). No significant differences were evident when using the 7-iron and no significant differences were displayed in muscle activity in either of the conditions. Findings from this study suggest that driving performance is improved when wearing a glove.

Empathy, autistic traits, and motor resonance in adults with Turner syndrome.

PubMed

Lepage, Jean-François; Lortie, Mélissa; Deal, Cheri L; Théoret, Hugo

2014-01-01

Turner syndrome is a genetic condition resulting from the partial or complete absence of an X-chromosome in phenotypic females. Individuals with Turner syndrome often display social difficulties that are reminiscent of those associated with autistic spectrum disorders (ASD), conditions associated with empathy and mirror-neuron system (MNS) deficits. The goal of the present study was (1) to investigate the extent to which adults with Turner syndrome display autistic and empathic traits, and (2) to probe the integrity of the MNS in this neurogenetic disorder. Sixteen individuals with Turner syndrome and 16 age-, sex-, and IQ-matched controls took part in a neuropsychological assessment where the Weschler Abbreviated Scale of Intelligence, the Autism Spectrum Quotient and the Empathy Quotient were administered. Functioning of the MNS was assessed by measuring motor cortex activity with transcranial magnetic stimulation during an action-observation task. Results show that individuals with Turner syndrome do not differ significantly from controls regarding autistic or empathic traits, and present normal functioning of the MNS during action observation. Correlational analysis showed a significant positive relationship between scores on the Empathy Quotient and motor facilitation during action observation, bringing further support to the hypothesis that MNS activity is related to sociocognitive competence.

Alterations in sympathetic nerve traffic in genetic haemochromatosis before and after iron depletion therapy: a microneurographic study.

PubMed

Seravalle, Gino; Piperno, Alberto; Mariani, Raffaella; Pelloni, Irene; Facchetti, Rita; Dell'Oro, Raffaella; Cuspidi, Cesare; Mancia, Giuseppe; Grassi, Guido

2016-03-21

Haemochromatosis (HH) displays a number of circulatory alterations concurring at increase cardiovascular risk. Whether these include sympathetic abnormalities in unknown. In 18 males with primary HH (age: 42.3 ± 10.4 years, mean ± SD), clinic and beat-to-beat blood pressure (BP, Finapres), heart rate (HR, EKG), and muscle sympathetic nerve activity (MSNA, microneurography) traffic were measured in the iron overload state and after iron depletion therapy. Haemochromatosis patients displayed elevated serum iron indices while other haemodynamic and metabolic variables were superimposable to ones seen in 12 healthy subjects (C). Muscle sympathetic nerve activity was significantly greater in HH than C (64.8 ± 13.3 vs. 37.8 ± 6.7 bs/100 hb, P < 0.01). Iron depletion caused a significant reduction in serum ferritin, transferrin saturation, and MSNA (from 64.8 ± 13.3 to 39.2 ± 9.2 bs/100 hb, P < 0.01) and a significant improvement in baroreflex-MSNA modulation. This was paralleled by a significant increase in the high-frequency HR variability and by a significant reduction in the low-frequency systolic BP variability components. Before after iron depletion therapy, MSNA was significantly and directly related to transferrin saturation, liver iron concentration, and iron removed, while the MSNA reductions observed after the procedure were significantly and inversely related to the baroreflex-MSNA increases detected after iron depletion. In C, all variables remained unchanged following 1 month observation. These data provide the first evidence that in HH iron overload is associated with an hyperadrenergic state and a baroreflex alteration, which are reversed by iron depletion. These findings underline the importance of iron overload in modulating sympathetic activation, possibly participating at the elevated cardiovascular risk reported in HH. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Fully Screen-Printed, Large-Area, and Flexible Active-Matrix Electrochromic Displays Using Carbon Nanotube Thin-Film Transistors.

PubMed

Cao, Xuan; Lau, Christian; Liu, Yihang; Wu, Fanqi; Gui, Hui; Liu, Qingzhou; Ma, Yuqiang; Wan, Haochuan; Amer, Moh R; Zhou, Chongwu

2016-11-22

Semiconducting single-wall carbon nanotubes are ideal semiconductors for printed electronics due to their advantageous electrical and mechanical properties, intrinsic printability in solution, and desirable stability in air. However, fully printed, large-area, high-performance, and flexible carbon nanotube active-matrix backplanes are still difficult to realize for future displays and sensing applications. Here, we report fully screen-printed active-matrix electrochromic displays employing carbon nanotube thin-film transistors. Our fully printed backplane shows high electrical performance with mobility of 3.92 ± 1.08 cm 2 V -1 s -1 , on-off current ratio I on /I off ∼ 10 4 , and good uniformity. The printed backplane was then monolithically integrated with an array of printed electrochromic pixels, resulting in an entirely screen-printed active-matrix electrochromic display (AMECD) with good switching characteristics, facile manufacturing, and long-term stability. Overall, our fully screen-printed AMECD is promising for the mass production of large-area and low-cost flexible displays for applications such as disposable tags, medical electronics, and smart home appliances.

Active-matrix OLED using 150°C a-Si TFT backplane built on flexible plastic substrate

NASA Astrophysics Data System (ADS)

Sarma, Kalluri R.; Chanley, Charles; Dodd, Sonia R.; Roush, Jared; Schmidt, John; Srdanov, Gordana; Stevenson, Matthew; Wessel, Ralf; Innocenzo, Jeffrey; Yu, Gang; O'Regan, Marie B.; MacDonald, W. A.; Eveson, R.; Long, Ke; Gleskova, Helena; Wagner, Sigurd; Sturm, James C.

2003-09-01

Flexible displays fabricated using plastic substrates have a potential for being very thin, light weight, highly rugged with greatly minimized propensity for breakage, roll-to-roll manufacturing and lower cost. The emerging OLED display media offers the advantage of being a solid state and rugged structure for flexible displays in addition to the many potential advantages of an AM OLED over the currently dominant AM LCD. The current high level of interest in flexible displays is facilitating the development of the required enabling technologies which include development of plastic substrates, low temperature active matrix device and backplane fabrication, and display packaging. In the following we will first discuss our development efforts in the PEN based plastic substrates, active matrix backplane technology, low temperature (150°C) a-Si TFT devices and an AM OLED test chip used for evaluating various candidate designs. We will then describe the design, fabrication and successful evaluation and demonstration of a 64x64 pixel AM OLED test display using a-Si TFT backplane fabricated at 150°C on the flexible plastic substrate.

Tyrosine 842 in the activation loop is required for full transformation by the oncogenic mutant FLT3-ITD.

PubMed

Kazi, Julhash U; Chougule, Rohit A; Li, Tianfeng; Su, Xianwei; Moharram, Sausan A; Rupar, Kaja; Marhäll, Alissa; Gazi, Mohiuddin; Sun, Jianmin; Zhao, Hui; Rönnstrand, Lars

2017-07-01

The type III receptor tyrosine kinase FLT3 is frequently mutated in acute myeloid leukemia. Oncogenic FLT3 mutants display constitutive activity leading to aberrant cell proliferation and survival. Phosphorylation on several critical tyrosine residues is known to be essential for FLT3 signaling. Among these tyrosine residues, Y842 is located in the so-called activation loop. The position of this tyrosine residue is well conserved in all receptor tyrosine kinases. It has been reported that phosphorylation of the activation loop tyrosine is critical for catalytic activity for some but not all receptor tyrosine kinases. The role of Y842 residue in FLT3 signaling has not yet been studied. In this report, we show that Y842 is not important for FLT3 activation or ubiquitination but plays a critical role in regulating signaling downstream of the receptor as well as controlling receptor stability. We found that mutation of Y842 in the FLT3-ITD oncogenic mutant background reduced cell viability and increased apoptosis. Furthermore, the introduction of the Y842 mutation in the FLT3-ITD background led to a dramatic reduction in in vitro colony forming capacity. Additionally, mice injected with cells expressing FLT3-ITD/Y842F displayed a significant delay in tumor formation, compared to FLT3-ITD expressing cells. Microarray analysis comparing gene expression regulated by FLT3-ITD versus FLT3-ITD/Y842F demonstrated that mutation of Y842 causes suppression of anti-apoptotic genes. Furthermore, we showed that cells expressing FLT3-ITD/Y842F display impaired activity of the RAS/ERK pathway due to reduced interaction between FLT3 and SHP2 leading to reduced SHP2 activation. Thus, we suggest that Y842 is critical for FLT3-mediated RAS/ERK signaling and cellular transformation.

Selectivity of natural, synthetic and environmental estrogens for zebrafish estrogen receptors

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

Pinto, Caroline; Grimaldi, Marina; Boulahtouf, Abdelhay

2014-10-01

Zebrafish, Danio rerio, is increasingly used as an animal model to study the effects of pharmaceuticals and environmental estrogens. As most of these estrogens have only been tested on human estrogen receptors (ERs), it is necessary to measure their effects on zebrafish ERs. In humans there are two distinct nuclear ERs (hERα and hERβ), whereas the zebrafish genome encodes three ERs, zfERα and two zfERβs (zfERβ1 and zfERβ2). In this study, we established HeLa-based reporter cell lines stably expressing each of the three zfERs. We first reported that estrogens more efficiently activate the zfERs at 28 °C as compared tomore » 37 °C, thus reflecting the physiological temperature of zebrafish in wildlife. We then showed significant differences in the ability of agonist and antagonist estrogens to modulate activation of the three zfER isotypes in comparison to hERs. Environmental compounds (bisphenol A, alkylphenols, mycoestrogens) which are hER panagonists and hERβ selective agonists displayed greater potency for zfERα as compared to zfERβs. Among hERα selective synthetic agonists, PPT did not activate zfERα while 16α-LE2 was the most zfERα selective compound. Altogether, these results confirm that all hER ligands control in a similar manner the transcriptional activity of zfERs although significant differences in selectivity were observed among subtypes. The zfER subtype selective ligands that we identified thus represent new valuable tools to dissect the physiological roles of the different zfERs. Finally, our work also points out that care has to be taken in transposing the results obtained using the zebrafish as a model for human physiopathology. - Highlights: • Zebrafish is increasingly used to study the effects of estrogens. • We assessed the activity of pharmaceutical and environmental estrogens on zfERs. • Environmental estrogens displayed greater potency for zfERα compared to zfERβs. • hERβ selective agonists displayed greater potency for zfERα compared to zfERβs. • The hERα selective agonist 16αL-E2 is the most zfERα selective compound.« less

Application of phage display for the development of a novel inhibitor of PLA2 activity in Western cottonmouth venom

PubMed Central

Titus, James K; Kay, Matthew K; Glaser, CDR Jacob J

2017-01-01

Snakebite envenomation is an important global health concern. The current standard treatment approach for snakebite envenomation relies on antibody-based antisera, which are expensive, not universally available, and can lead to adverse physiological effects. Phage display techniques offer a powerful tool for the selection of phage-expressed peptides, which can bind with high specificity and affinity towards venom components. In this research, the amino acid sequences of Phospholipase A2 (PLA2) from multiple cottonmouth species were analyzed, and a consensus peptide synthesized. Three phage display libraries were panned against this consensus peptide, crosslinked to capillary tubes, followed by a modified surface panning procedure. This high throughput selection method identified four phage clones with anti-PLA2 activity against Western cottonmouth venom, and the amino acid sequences of the displayed peptides were identified. This is the first report identifying short peptide sequences capable of inhibiting PLA2 activity of Western cottonmouth venom in vitro, using a phage display technique. Additionally, this report utilizes synthetic panning targets, designed using venom proteomic data, to mimic epitope regions. M13 phages displaying circular 7-mer or linear 12-mer peptides with antivenom activity may offer a novel alternative to traditional antibody-based therapy. PMID:29285351

Application of phage display for the development of a novel inhibitor of PLA2 activity in Western cottonmouth venom.

PubMed

Titus, James K; Kay, Matthew K; Glaser, Cdr Jacob J

2017-01-01

Snakebite envenomation is an important global health concern. The current standard treatment approach for snakebite envenomation relies on antibody-based antisera, which are expensive, not universally available, and can lead to adverse physiological effects. Phage display techniques offer a powerful tool for the selection of phage-expressed peptides, which can bind with high specificity and affinity towards venom components. In this research, the amino acid sequences of Phospholipase A 2 (PLA 2 ) from multiple cottonmouth species were analyzed, and a consensus peptide synthesized. Three phage display libraries were panned against this consensus peptide, crosslinked to capillary tubes, followed by a modified surface panning procedure. This high throughput selection method identified four phage clones with anti-PLA 2 activity against Western cottonmouth venom, and the amino acid sequences of the displayed peptides were identified. This is the first report identifying short peptide sequences capable of inhibiting PLA 2 activity of Western cottonmouth venom in vitro , using a phage display technique. Additionally, this report utilizes synthetic panning targets, designed using venom proteomic data, to mimic epitope regions. M13 phages displaying circular 7-mer or linear 12-mer peptides with antivenom activity may offer a novel alternative to traditional antibody-based therapy.

A Virtual Screen Discovers Novel, Fragment-Sized Inhibitors of Mycobacterium tuberculosis InhA

PubMed Central

Perryman, Alexander L.; Yu, Weixuan; Wang, Xin; Ekins, Sean; Forli, Stefano; Li, Shao-Gang; Freundlich, Joel S.; Tonge, Peter J.; Olson, Arthur J.

2015-01-01

Isoniazid (INH) is usually administered to treat latent Mycobacterium tuberculosis (Mtb) infections, and is used in combination therapy to treat active tuberculosis disease (TB). Unfortunately, resistance to this drug is hampering its clinical effectiveness. INH is a prodrug that must be activated by Mtb catalase peroxidase (KatG) before it can inhibit InhA (Mtb enoyl-acyl-carrier-protein reductase). Isoniazid-resistant cases of TB found in clinical settings usually involve mutations in or deletion of katG, which abrogate INH activation. Compounds that inhibit InhA without requiring prior activation by KatG would not be affected by this resistance mechanism and hence would display continued potency against these drug-resistant isolates of Mtb. Virtual screening experiments versus InhA in the GO Fight Against Malaria project (GO FAM) were designed to discover new scaffolds that display base stacking interactions with the NAD cofactor. GO FAM experiments included targets from other pathogens, including Mtb, when they had structural similarity to a malaria target. Eight of the sixteen soluble compounds identified by docking against InhA plus visual inspection were modest inhibitors and did not require prior activation by KatG. The best two inhibitors discovered are both fragment-sized compounds and displayed Ki values of 54 and 59 μM, respectively. Importantly, the novel inhibitors discovered have low structural similarity to known InhA inhibitors and, thus, help expand the number of chemotypes on which future medicinal chemistry efforts can be focused. These new fragment hits could eventually help advance the fight against INH-resistant Mtb strains, which pose a significant global health threat. PMID:25636146

Identification of inhibitory scFv antibodies targeting fibroblast activation protein utilizing phage display functional screens

PubMed Central

Zhang, Jiping; Valianou, Matthildi; Simmons, Heidi; Robinson, Matthew K.; Lee, Hyung-Ok; Mullins, Stefanie R.; Marasco, Wayne A.; Adams, Gregory P.; Weiner, Louis M.; Cheng, Jonathan D.

2013-01-01

Fibroblast activation protein (FAP) is a serine protease selectively expressed on tumor stromal fibroblasts in epithelial carcinomas and is important in cancer growth, adhesion, and metastases. As FAP enzymatic activity is a potent therapeutic target, we aimed to identify inhibitory antibodies. Using a competitive inhibition strategy, we used phage display techniques to identify 53 single-chain variable fragments (scFvs) after three rounds of panning against FAP. These scFvs were expressed and characterized for binding to FAP by surface plasmon resonance and flow cytometry. Functional assessment of these antibodies yielded an inhibitory scFv antibody, named E3, which could attenuate 35% of FAP cleavage of the fluorescent substrate Ala-Pro-7-amido-4-trifluoromethylcoumarin compared with nonfunctional scFv control. Furthermore, a mutant E3 scFv was identified by yeast affinity maturation. It had higher affinity (4-fold) and enhanced inhibitory effect on FAP enzyme activity (3-fold) than E3. The application of both inhibitory anti-FAP scFvs significantly affected the formation of 3-dimensional FAP-positive cell matrix, as demonstrated by reducing the fibronectin fiber orientation from 41.18% (negative antibody control) to 34.06% (E3) and 36.15% (mutant E3), respectively. Thus, we have identified and affinity-maturated the first scFv antibody capable of inhibiting FAP function. This scFv antibody has the potential to disrupt the role of FAP in tumor invasion and metastasis.—Zhang, J., Valianou, M., Simmons, H., Robinson, M. K., Lee, H.-O., Mullins, S. R., Marasco, W. A., Adams, G. P., Weiner, L. M., Cheng, J. D. Identification of inhibitory ScFv antibodies targeting fibroblast activation protein utilizing phage display functional screens. PMID:23104982

Synthesis, DNA binding ability and anticancer activity of 2-heteroaryl substituted benzimidazoles linked pyrrolo[2,1-c][1,4]benzodiazepine conjugates.

PubMed

Kamal, Ahmed; Pogula, Praveen Kumar; Khan, Mohammed Naseer Ahmed; Seshadri, Bobburi Naga; Sreekanth, Kokkonda

2013-08-01

As a continuation of our efforts to develop the benzimidazole-PBD conjugates as potential anticancer agents, a series of heteroaryl substituted benzimidazole linked PBD conjugates has been synthesized and evaluated for their anticancer potential in 60 human cancer cell lines. Most of the compounds exhibited promising anticancer activity and interestingly, compounds 4c and 4d displayed significant activity in most of the cell lines tested. Whereas, compound 4e showed selectivity in renal cancer cells with GI50 values of <10 and 70 nM against RXF 393 and UO-31 cell lines, respectively. Further, these compounds also showed significant DNA-binding affinity by thermal denaturation study using duplex form of calf thymus (CT) DNA.

Functional imaging of brain responses to different outcomes of hypothesis testing: revealed in a category induction task.

PubMed

Li, Fuhong; Cao, Bihua; Luo, Yuejia; Lei, Yi; Li, Hong

2013-02-01

Functional magnetic resonance imaging (fMRI) was used to examine differences in brain activation that occur when a person receives the different outcomes of hypothesis testing (HT). Participants were provided with a series of images of batteries and were asked to learn a rule governing what kinds of batteries were charged. Within each trial, the first two charged batteries were sequentially displayed, and participants would generate a preliminary hypothesis based on the perceptual comparison. Next, a third battery that served to strengthen, reject, or was irrelevant to the preliminary hypothesis was displayed. The fMRI results revealed that (1) no significant differences in brain activation were found between the 2 hypothesis-maintain conditions (i.e., strengthen and irrelevant conditions); and (2) compared with the hypothesis-maintain conditions, the hypothesis-reject condition activated the left medial frontal cortex, bilateral putamen, left parietal cortex, and right cerebellum. These findings are discussed in terms of the neural correlates of the subcomponents of HT and working memory manipulation. Copyright © 2012 Elsevier Inc. All rights reserved.

A phage display-selected peptide inhibitor of Agrobacterium vitis polygalacturonase.

PubMed

Warren, Jeremy G; Kasun, George W; Leonard, Takara; Kirkpatrick, Bruce C

2016-05-01

Agrobacterium vitis, the causal agent of crown gall of grapevine, is a threat to viticulture worldwide. A major virulence factor of this pathogen is polygalacturonase, an enzyme that degrades pectin components of the xylem cell wall. A single gene encodes for the polygalacturonase gene. Disruption of the polygalacturonase gene results in a mutant that is less pathogenic and produces significantly fewer root lesions on grapevines. Thus, the identification of peptides or proteins that could inhibit the activity of polygalacturonase could be part of a strategy for the protection of plants against this pathogen. A phage-displayed combinatorial peptide library was used to isolate peptides with a high binding affinity to A. vitis polygalacturonase. These peptides showed sequence similarity to regions of Oryza sativa (EMS66324, Japonica) and Triticum urartu (NP_001054402, wild wheat) polygalacturonase-inhibiting proteins (PGIPs). Furthermore, these panning experiments identified a peptide, SVTIHHLGGGS, which was able to reduce A. vitis polygalacturonase activity by 35% in vitro. Truncation studies showed that the IHHL motif alone is sufficient to inhibit A. vitis polygalacturonase activity. © 2015 BSPP AND JOHN WILEY & SONS LTD.

Investigation into the antioxidant and antidiabetic potential of Moringa stenopetala: identification of the active principles.

PubMed

Habtemariam, Solomon

2015-03-01

The fresh leaves of Moringa stenopetala (family, Moringaceae) are commonly eaten as cabbage while dried leaves are used as nutritional supplement and for treating a variety of disease conditions including diabetes. The present investigation into the therapeutic potential of the leaves and seeds of the plant revealed no inhibitory effect against α-glucosidase enzyme up to the concentration of 200 μg/mL but the leaves extract displayed potent DPPH (1,1-diphenyl-2- picrylhydrazyl) radical scavenging effect (IC50, 59.5 ± 4.1 μg/mL). An activity directed fractionation and isolation procedure resulted in the identification of the major antioxidant compound as rutin and minor active component, neochlorogenic acid. Both the crude extract (0.8-200 μg/mL) and rutin (0.8-200 μM) but not neochlorogenic acid displayed a concentration-dependent protection of human pancreatic β-cells (1.4E7 cells) from oxidant-induced cell death. The identification of these compounds along with their potential role in the nutritional and medicinal significance of the plant is discussed.

Unintentional Activation of Translation Equivalents in Bilinguals Leads to Attention Capture in a Cross-Modal Visual Task

PubMed Central

Singh, Niharika; Mishra, Ramesh Kumar

2015-01-01

Using a variant of the visual world eye tracking paradigm, we examined if language non- selective activation of translation equivalents leads to attention capture and distraction in a visual task in bilinguals. High and low proficient Hindi-English speaking bilinguals were instructed to programme a saccade towards a line drawing which changed colour among other distractor objects. A spoken word, irrelevant to the main task, was presented before the colour change. On critical trials, one of the line drawings was a phonologically related word of the translation equivalent of the spoken word. Results showed that saccade latency was significantly higher towards the target in the presence of this cross-linguistic translation competitor compared to when the display contained completely unrelated objects. Participants were also slower when the display contained the referent of the spoken word among the distractors. However, the bilingual groups did not differ with regard to the interference effect observed. These findings suggest that spoken words activates translation equivalent which bias attention leading to interference in goal directed action in the visual domain. PMID:25775184

Validation of three short physical activity questionnaires with accelerometers among university students in Spain.

PubMed

Rodríguez-Muñoz, Sheila; Corella, Cristina; Abarca-Sos, Alberto; Zaragoza, Javier

2017-12-01

Physical activity (PA) in university students has not been analyzed with specific questionnaires tailored to this population. Therefore, the purpose of this study was to analyze the validity of three PA questionnaires developed on other populations comparing with accelerometer values: counts and moderate to vigorous PA (MVPA) calculated with uniaxial and triaxial cut points. One hundred and forty-five university students (of whom, 92 women) from Spain wore an accelerometer GT3X or GTX+ to collect PA data of 7 full days. Three questionnaires, Physical Activity Questionnaire for Adults (PAQ-AD), Assessment of Physical Activity Questionnaire (APALQ), and the International Physical Activity Questionnaire Short Form (IPAQ-SF) were administrated jointly with the collection of accelerometer values. Finally, after the application of inclusion criteria, data from 95 participants (62 women) with a mean age of 21.96±2.33 years were analyzed to compare the instruments measures. The correlational analysis showed that PAQ-AD (0.44-0.56) and IPAQ-SF (0.26-0.69) questionnaires were significantly related to accelerometers scores: counts, uniaxial MVPA and triaxial MVPA. Conversely, APALQ displayed no significant relations for males with accelerometers scores for MVPA created with both cut points. PAQ-AD and IPAQ-SF questionnaires have shown adequate validity to use with Spanish university students. The use of counts to validate self-report data in order to reduce the variability display by MVPA created with different cut points is discussed. Finally, validated instruments to measure PA in university students will allow implementation of strategies for PA promotion based on reliable data.

A Novel Angiotensin I-Converting Enzyme Mutation (S333W) Impairs N-Domain Enzymatic Cleavage of the Anti-Fibrotic Peptide, AcSDKP

PubMed Central

Danilov, Sergei M.; Wade, Michael S.; Schwager, Sylva L.; Douglas, Ross G.; Nesterovitch, Andrew B.; Popova, Isolda A.; Hogarth, Kyle D.; Bhardwaj, Nakul; Schwartz, David E.; Sturrock, Edward D.; Garcia, Joe G. N.

2014-01-01

Background Angiotensin I-converting enzyme (ACE) has two functional N- and C-domain active centers that display differences in the metabolism of biologically-active peptides including the hemoregulatory tetrapeptide, Ac-SDKP, hydrolysed preferentially by the N domain active center. Elevated Ac-SDKP concentrations are associated with reduced tissue fibrosis. Results We identified a patient of African descent exhibiting unusual blood ACE kinetics with reduced relative hydrolysis of two synthetic ACE substrates (ZPHL/HHL ratio) suggestive of the ACE N domain center inactivation. Inhibition of blood ACE activity by anti-catalytic mAbs and ACE inhibitors and conformational fingerprint of blood ACE suggested overall conformational changes in the ACE molecule and sequencing identified Ser333Trp substitution in the N domain of ACE. In silico analysis demonstrated S333W localized in the S1 pocket of the active site of the N domain with the bulky Trp adversely affecting binding of ACE substrates due to steric hindrance. Expression of mutant ACE (S333W) in CHO cells confirmed altered kinetic properties of mutant ACE and conformational changes in the N domain. Further, the S333W mutant displayed decreased ability (5-fold) to cleave the physiological substrate AcSDKP compared to wild-type ACE. Conclusions and Significance A novel Ser333Trp ACE mutation results in dramatic changes in ACE kinetic properties and lowered clearance of Ac-SDKP. Individuals with this mutation (likely with significantly increased levels of the hemoregulatory tetrapeptide in blood and tissues), may confer protection against fibrosis. PMID:24505347

Daily rhythms of locomotor and demand-feeding activities in Schizothorax pelzami (Kessler, 1870).

PubMed

Ebrahimi, Ehsan; Kamrani, Ehsan; Heydarnejad, Mohammad Saeed; Safari, Omid

2017-01-01

A study was carried out to investigate the daily rhythms of locomotor and feeding activity of Khajoo, Schizothorax pelzami, a candidate species for freshwater aquaculture. Using self-feeder juvenile Khajoo were exposed to a 12/12 LD cycle to determine the rhythms of locomotor and feeding activity. The effects of feeding on locomotor and feeding activity of fish were also examined. Finally, the endogenous rhythmicity under different lighting condition tested. Fish displayed a strictly diurnal feeding and locomotor activities with 98% and 84% of the total activity occurred in the photophase, respectively. In scheduled feeding, both the L-group (fed in light) and the D-group (fed in the dark) showed a diurnal locomotor activity pattern. However, the L-group had a peak of locomotor activity near the feeding time, but the D-group had a scarce locomotor activity in the scatophase with no significant change at the mealtime. Most of the individuals display free-running rhythms when exposed to different lighting condition including, constant darkness, ultradian 45:45 min LD cycle and reversed DL photo cycle. Taken together the results of this study showed that both locomotor and feeding activity have diurnal rhythms in Khajoo S. pelzami, even fish feeding had taken place at night. Additionally, the free-running locomotor activity of the fish in the absence of external light stimuli, suggests the existence of an endogenous timing mechanism in this fish species.

Cinnamic acid amides from Tribulus terrestris displaying uncompetitive α-glucosidase inhibition.

PubMed

Song, Yeong Hun; Kim, Dae Wook; Curtis-Long, Marcus J; Park, Chanin; Son, Minky; Kim, Jeong Yoon; Yuk, Heung Joo; Lee, Keun Woo; Park, Ki Hun

2016-05-23

The α-glucosidase inhibitory potential of Tribulus terrestris extracts has been reported but as yet the active ingredients are unknown. This study attempted to isolate the responsible metabolites and elucidate their inhibition mechanism of α-glucosidase. By fractionating T. terristris extracts, three cinnamic acid amide derivatives (1-3) were ascertained to be active components against α-glucosidase. The lead structure, N-trans-coumaroyltyramine 1, showed significant inhibition of α-glucosidase (IC50 = 0.42 μM). Moreover, all active compounds displayed uncompetitive inhibition mechanisms that have rarely been reported for α-glucosidase inhibitors. This kinetic behavior was fully demonstrated by showing a decrease of both Km and Vmax, and Kik/Kiv ratio ranging between 1.029 and 1.053. We progressed to study how chemical modifications to the lead structure 1 may impact inhibition. An α, β-unsaturation carbonyl group and hydroxyl group in A-ring of cinnamic acid amide emerged to be critical functionalities for α-glucosidase inhibition. The molecular modeling study revealed that the inhibitory activities are tightly related to π-π interaction as well as hydrogen bond interaction between enzyme and inhibitors. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Sustained neural activity to gaze and emotion perception in dynamic social scenes

PubMed Central

Ulloa, José Luis; Puce, Aina; Hugueville, Laurent; George, Nathalie

2014-01-01

To understand social interactions, we must decode dynamic social cues from seen faces. Here, we used magnetoencephalography (MEG) to study the neural responses underlying the perception of emotional expressions and gaze direction changes as depicted in an interaction between two agents. Subjects viewed displays of paired faces that first established a social scenario of gazing at each other (mutual attention) or gazing laterally together (deviated group attention) and then dynamically displayed either an angry or happy facial expression. The initial gaze change elicited a significantly larger M170 under the deviated than the mutual attention scenario. At around 400 ms after the dynamic emotion onset, responses at posterior MEG sensors differentiated between emotions, and between 1000 and 2200 ms, left posterior sensors were additionally modulated by social scenario. Moreover, activity on right anterior sensors showed both an early and prolonged interaction between emotion and social scenario. These results suggest that activity in right anterior sensors reflects an early integration of emotion and social attention, while posterior activity first differentiated between emotions only, supporting the view of a dual route for emotion processing. Altogether, our data demonstrate that both transient and sustained neurophysiological responses underlie social processing when observing interactions between others. PMID:23202662

Pen-2 overexpression induces Aβ-42 production, memory defect, motor activity enhancement and feeding behavior dysfunction in NSE/Pen-2 transgenic mice.

PubMed

Nam, So Hee; Seo, Su Jin; Goo, Jun Seo; Kim, Jee Eun; Choi, Sun Il; Lee, Hae Ryun; Hwang, In Sik; Jee, Seung Wan; Lee, Su Hae; Bae, Chang Jun; Park, Jung Youn; Kim, Hye Sung; Shim, Sun Bo; Hwang, Dae Youn

2011-12-01

Pen-2 is a key regulator of the γ-secretase complex, which is involved in the production of the amyloid β (Aβ)-42 peptides, which ultimately lead to Alzheimer's disease (AD). While Pen-2 has been studied in vitro, Pen-2 function in vivo in the brains of transgenic (Tg) mice overexpressing human Pen-2 (hPen-2) protein has not been studied. This study aimed to determine whether Pen-2 overexpression could regulate the AD-like phenotypes in Tg mice. NSE/hPen-2 Tg mice were produced by the microinjection of the NSE/hPen-2 gene into the pronucleus of fertilized eggs. The expression of the hPen-2 gene under the control of the NSE promoter was successfully detected only in the brain and kidney tissue of NSE/hPen-2 Tg mice. Also, 12-month-old NSE/hPen-2 Tg mice displayed behavioral dysfunction in the water maze test, motor activity and feeding behavior dysfunction in food intake/water intake/motor activity monitoring system. In addition, tissue samples displayed dense staining with antibody to the Aβ-42 peptide. Furthermore, NSE/hPen-2 Tg mice exhibiting feeding behavior dysfunction were significantly more apt to display symptoms related to diabetes and obesity. These results suggest that Pen-2 overexpression in NSE/hPen-2 Tg mice may induce all the AD-like phenotypes, including behavioral deficits, motor activity and feeding behavior dysfunction, Aβ-42 peptide deposition and chronic disease induction.

Frequency-Magnitude relationships for Underwater Landslides of the Mediterranean Sea

NASA Astrophysics Data System (ADS)

Urgeles, R.; Gràcia, E.; Lo Iacono, C.; Sànchez-Serra, C.; Løvholt, F.

2017-12-01

An updated version of the submarine landslide database of the Mediterranean Sea contains 955 MTDs and 2608 failure scars showing that submarine landslides are ubiquitous features along Mediterranean continental margins. Their distribution reveals that major deltaic wedges display the larger submarine landslides, while seismically active margins are characterized by relatively small failures. In all regions, landslide size distributions display power law scaling for landslides > 1 km3. We find consistent differences on the exponent of the power law depending on the geodynamic setting. Active margins present steep slopes of the frequency-magnitude relationship whereas passive margins tend to display gentler slopes. This pattern likely responds to the common view that tectonically active margins have numerous but small failures, while passive margins have larger but fewer failures. Available age information suggests that failures exceeding 1000 km3 are infrequent and may recur every 40 kyr. Smaller failures that can still cause significant damage might be relatively frequent, with failures > 1 km3 likely recurring every 40 years. The database highlights that our knowledge of submarine landslide activity with time is limited to a few tens of thousand years. Available data suggest that submarine landslides may preferentially occur during lowstand periods, but no firm conclusion can be made on this respect, as only 149 landslides (out of 955 included in the database) have relatively accurate age determinations. The timing and regional changes in the frequency-magnitude distribution suggest that sedimentation patterns and pore pressure development have had a major role in triggering slope failures and control the sediment flux from mass wasting to the deep basin.

The effect of rubber flooring on displaying stereotypies in gilts.

PubMed

Ostović, Mario; Menčik, Sven; Kabalin, Anamaria Ekert; Gračner, Gordana Gregurić; Vučemilo, Marija; Matković, Kristina; Vukičević, Tajana Trbojević; Grahovac, Jurica; Pavičić, Zeljko

2015-01-01

The aim of the study was to assess the effect of rubber mats in service unit on displaying stereotypies in gilts. Four 28-day production cycles in all seasons were observed. Each cycle included 28 gilts housed in gestation stalls with slatted concrete floor, which was covered with adjusted mats for 14 gilts (experimental group), while the remaining 14 gilts served as controls. Display of stereotypies and other behaviours observed, mat manipulation and postural behaviours were estimated by direct 1-hour observation of gilts at 2-minute intervals after morning feed supply on days 1, 8, 15 and 28 of each cycle. During the study period, displaying stereotypies was significantly less frequent (P < 0.05) in experimental group as compared with control group. The rate of particular forms of stereotypies, i.e. vacuum chewing, bar biting and teeth grinding, was also significantly lower (P < 0.05 all) in experimental group throughout the study period. A significant negative correlation (P <.05) was found between the service unit air temperature and frequency of displaying stereotypies in control group, which could be attributed to the significantly more common standing posture (P < 0.05) in control gilts in the conditions of lower air temperature. During the cold period, experimental gilts took a lying position significantly more frequently (P < 0.05). In the experimental group of gilts there was no significant correlation (P > 0.05 all) between the frequency of displaying stereotypies and the frequency of lying and other postures observed, as well as between the stereotypy display and the air temperature. There was no significant correlation (P > 0.05 all) between the frequency of mat manipulation and displaying stereotypies in total or its particular forms, suggesting that the less pronounced stereotypy display in experimental gilts may have been influenced by factors other than those observed in the present study.

Effect of Edible and Active Coating (with Rosemary and Oregano Essential Oils) on Beef Characteristics and Consumer Acceptability.

PubMed

Vital, Ana Carolina Pelaes; Guerrero, Ana; Monteschio, Jessica de Oliveira; Valero, Maribel Velandia; Carvalho, Camila Barbosa; de Abreu Filho, Benício Alves; Madrona, Grasiele Scaramal; do Prado, Ivanor Nunes

2016-01-01

The effects of an alginate-based edible coating containing natural antioxidants (rosemary and oregano essential oils) on lipid oxidation, color preservation, water losses, texture and pH of beef steaks during 14 days of display were studied. The essential oil, edible coating and beef antioxidant activities, and beef consumer acceptability were also investigated. The edible coatings decreased lipid oxidation of the meat compared to the control. The coating with oregano was most effective (46.81% decrease in lipid oxidation) and also showed the highest antioxidant activity. The coatings significantly decreased color losses, water losses and shear force compared to the control. The coatings had a significant effect on consumer perception of odor, flavor and overall acceptance of the beef. In particular, the oregano coating showed significantly high values (approximately 7 in a 9-point scale). Active edible coatings containing natural antioxidants could improve meat product stability and therefore have potential use in the food industry.

Effect of Edible and Active Coating (with Rosemary and Oregano Essential Oils) on Beef Characteristics and Consumer Acceptability

PubMed Central

Vital, Ana Carolina Pelaes; Guerrero, Ana; Monteschio, Jessica de Oliveira; Valero, Maribel Velandia; Carvalho, Camila Barbosa; de Abreu Filho, Benício Alves; Madrona, Grasiele Scaramal; do Prado, Ivanor Nunes

2016-01-01

The effects of an alginate-based edible coating containing natural antioxidants (rosemary and oregano essential oils) on lipid oxidation, color preservation, water losses, texture and pH of beef steaks during 14 days of display were studied. The essential oil, edible coating and beef antioxidant activities, and beef consumer acceptability were also investigated. The edible coatings decreased lipid oxidation of the meat compared to the control. The coating with oregano was most effective (46.81% decrease in lipid oxidation) and also showed the highest antioxidant activity. The coatings significantly decreased color losses, water losses and shear force compared to the control. The coatings had a significant effect on consumer perception of odor, flavor and overall acceptance of the beef. In particular, the oregano coating showed significantly high values (approximately 7 in a 9-point scale). Active edible coatings containing natural antioxidants could improve meat product stability and therefore have potential use in the food industry. PMID:27504957

Injected phage-displayed-VP28 vaccine reduces shrimp Litopenaeus vannamei mortality by white spot syndrome virus infection.

PubMed

Solís-Lucero, G; Manoutcharian, K; Hernández-López, J; Ascencio, F

2016-08-01

White spot syndrome virus (WSSV) is the most important viral pathogen for the global shrimp industry causing mass mortalities with huge economic losses. Recombinant phages are capable of expressing foreign peptides on viral coat surface and act as antigenic peptide carriers bearing a phage-displayed vaccine. In this study, the full-length VP28 protein of WSSV, widely known as potential vaccine against infection in shrimp, was successfully cloned and expressed on M13 filamentous phage. The functionality and efficacy of this vaccine immunogen was demonstrated through immunoassay and in vivo challenge studies. In ELISA assay phage-displayed VP28 was bind to Litopenaeus vannamei immobilized hemocyte in contrast to wild-type M13 phage. Shrimps were injected with 2 × 10(10) cfu animal(-1) single dose of VP28-M13 and M13 once and 48 h later intramuscularly challenged with WSSV to test the efficacy of the vaccine against the infection. All dead challenged shrimps were PCR WSSV-positive. The accumulative mortality of the vaccinated and challenged shrimp groups was significantly lower (36.67%) than the unvaccinated group (66.67%). Individual phenoloxidase and superoxide dismutase activity was assayed on 8 and 48 h post-vaccination. No significant difference was found in those immunological parameters among groups at any sampled time evaluated. For the first time, phage display technology was used to express a recombinant vaccine for shrimp. The highest percentage of relative survival in vaccinated shrimp (RPS = 44.99%) suggest that the recombinant phage can be used successfully to display and deliver VP28 for farmed marine crustaceans. Copyright © 2016 Elsevier Ltd. All rights reserved.

Impact of food advertising on food purchases by students in primary and secondary schools in south-eastern Poland.

PubMed

Mazur, A; Telega, G; Kotowicz, A; Małek, H; Jarochowicz, S; Gierczak, B; Mazurkiewicz, M; Pop, T; Zajkiewicz, K; Drużbicki, M; Mazur, D

2008-09-01

The aim of the present study was to determine the impact of food advertising in primary and secondary schools on the food purchasing habits of children. All forty-four primary and secondary schools in Rzeszow, Poland were included in the investigation; 15000 children attend primary and secondary schools in the region. Schools were visited by members of the research team, who filled in a questionnaire regarding the type of food products displayed or advertised in the school shop window and recorded the presence of direct corporate advertising in the proximity of the school shop. Shop owners were asked to fill in a form describing food purchases by students within the week preceding the visit. The school principal (or one of teachers) completed a form describing the school's policy regarding food advertising and the sponsorship of school activities by food companies. Recommended foods like milk, yogurts and fruit were offered by only 40.9 % of shops. There was a correlation between foods offered in the shop and foods purchased by students. In schools, 40.9% (95% CI 25.8, 56.0%) of shop windows displayed or advertised 'healthy' foods while 9.1% (95% CI 0.0, 17.9%) of shops displayed advertisements of food companies. The difference between display of 'healthy' food in shop windows and display of food on company advertisements was significant (likelihood ratio chi2 test, P < 0.04). Type of school (primary v. secondary) was not significant factor in advertising or purchasing pattern. Educational programmes should be introduced in schools with the aim of improving the understanding of nutritional principles among pupils, teachers and parents.

Phage display of the serpin alpha-1 proteinase inhibitor randomized at consecutive residues in the reactive centre loop and biopanned with or without thrombin.

PubMed

Scott, Benjamin M; Matochko, Wadim L; Gierczak, Richard F; Bhakta, Varsha; Derda, Ratmir; Sheffield, William P

2014-01-01

In spite of the power of phage display technology to identify variant proteins with novel properties in large libraries, it has only been previously applied to one member of the serpin superfamily. Here we describe phage display of human alpha-1 proteinase inhibitor (API) in a T7 bacteriophage system. API M358R fused to the C-terminus of T7 capsid protein 10B was directly shown to form denaturation-resistant complexes with thrombin by electrophoresis and immunoblotting following exposure of intact phages to thrombin. We therefore developed a biopanning protocol in which thrombin-reactive phages were selected using biotinylated anti-thrombin antibodies and streptavidin-coated magnetic beads. A library consisting of displayed API randomized at residues 357 and 358 (P2-P1) yielded predominantly Pro-Arg at these positions after five rounds of thrombin selection; in contrast the same degree of mock selection yielded only non-functional variants. A more diverse library of API M358R randomized at residues 352-356 (P7-P3) was also probed, yielding numerous variants fitting a loose consensus of DLTVS as judged by sequencing of the inserts of plaque-purified phages. The thrombin-selected sequences were transferred en masse into bacterial expression plasmids, and lysates from individual colonies were screening for API-thrombin complexing. The most active candidates from this sixth round of screening contained DITMA and AAFVS at P7-P3 and inhibited thrombin 2.1-fold more rapidly than API M358R with no change in reaction stoichiometry. Deep sequencing using the Ion Torrent platform confirmed that over 800 sequences were significantly enriched in the thrombin-panned versus naïve phage display library, including some detected using the combined phage display/bacterial lysate screening approach. Our results show that API joins Plasminogen Activator Inhibitor-1 (PAI-1) as a serpin amenable to phage display and suggest the utility of this approach for the selection of "designer serpins" with novel reactivity and/or specificity.

Phage Display of the Serpin Alpha-1 Proteinase Inhibitor Randomized at Consecutive Residues in the Reactive Centre Loop and Biopanned with or without Thrombin

PubMed Central

Scott, Benjamin M.; Matochko, Wadim L.; Gierczak, Richard F.; Bhakta, Varsha; Derda, Ratmir; Sheffield, William P.

2014-01-01

In spite of the power of phage display technology to identify variant proteins with novel properties in large libraries, it has only been previously applied to one member of the serpin superfamily. Here we describe phage display of human alpha-1 proteinase inhibitor (API) in a T7 bacteriophage system. API M358R fused to the C-terminus of T7 capsid protein 10B was directly shown to form denaturation-resistant complexes with thrombin by electrophoresis and immunoblotting following exposure of intact phages to thrombin. We therefore developed a biopanning protocol in which thrombin-reactive phages were selected using biotinylated anti-thrombin antibodies and streptavidin-coated magnetic beads. A library consisting of displayed API randomized at residues 357 and 358 (P2–P1) yielded predominantly Pro-Arg at these positions after five rounds of thrombin selection; in contrast the same degree of mock selection yielded only non-functional variants. A more diverse library of API M358R randomized at residues 352–356 (P7–P3) was also probed, yielding numerous variants fitting a loose consensus of DLTVS as judged by sequencing of the inserts of plaque-purified phages. The thrombin-selected sequences were transferred en masse into bacterial expression plasmids, and lysates from individual colonies were screening for API-thrombin complexing. The most active candidates from this sixth round of screening contained DITMA and AAFVS at P7–P3 and inhibited thrombin 2.1-fold more rapidly than API M358R with no change in reaction stoichiometry. Deep sequencing using the Ion Torrent platform confirmed that over 800 sequences were significantly enriched in the thrombin-panned versus naïve phage display library, including some detected using the combined phage display/bacterial lysate screening approach. Our results show that API joins Plasminogen Activator Inhibitor-1 (PAI-1) as a serpin amenable to phage display and suggest the utility of this approach for the selection of “designer serpins” with novel reactivity and/or specificity. PMID:24427287

When the display matters: A multifaceted perspective on 3D geovisualizations

NASA Astrophysics Data System (ADS)

Juřík, Vojtěch; Herman, Lukáš; Šašinka, Čeněk; Stachoň, Zdeněk; Chmelík, Jiří

2017-04-01

This study explores the influence of stereoscopic (real) 3D and monoscopic (pseudo) 3D visualization on the human ability to reckon altitude information in noninteractive and interactive 3D geovisualizations. A two phased experiment was carried out to compare the performance of two groups of participants, one of them using the real 3D and the other one pseudo 3D visualization of geographical data. A homogeneous group of 61 psychology students, inexperienced in processing of geographical data, were tested with respect to their efficiency at identifying altitudes of the displayed landscape. The first phase of the experiment was designed as non-interactive, where static 3D visual displayswere presented; the second phase was designed as interactive and the participants were allowed to explore the scene by adjusting the position of the virtual camera. The investigated variables included accuracy at altitude identification, time demands and the amount of the participant's motor activity performed during interaction with geovisualization. The interface was created using a Motion Capture system, Wii Remote Controller, widescreen projection and the passive Dolby 3D technology (for real 3D vision). The real 3D visual display was shown to significantly increase the accuracy of the landscape altitude identification in non-interactive tasks. As expected, in the interactive phase there were differences in accuracy flattened out between groups due to the possibility of interaction, with no other statistically significant differences in completion times or motor activity. The increased number of omitted objects in real 3D condition was further subjected to an exploratory analysis.

Effects of Head-Mounted Display on the Oculomotor System and Refractive Error in Normal Adolescents.

PubMed

Ha, Suk-Gyu; Na, Kun-Hoo; Kweon, Il-Joo; Suh, Young-Woo; Kim, Seung-Hyun

2016-07-01

To investigate the clinical effects of head-mounted display on the refractive error and oculomotor system in normal adolescents. Sixty volunteers (age: 13 to 18 years) watched a three-dimensional movie and virtual reality application of head-mounted display for 30 minutes. The refractive error (diopters [D]), angle of deviation (prism diopters [PD]) at distance (6 m) and near (33 cm), near point of accommodation, and stereoacuity were measured before, immediately after, and 10 minutes after watching the head-mounted display. The refractive error was presented as spherical equivalent (SE). Refractive error was measured repeatedly after every 10 minutes when a myopic shift greater than 0.15 D was observed after watching the head-mounted display. The mean age of the participants was 14.7 ± 1.3 years and the mean SE before watching head-mounted display was -3.1 ± 2.6 D. One participant in the virtual reality application group was excluded due to motion sickness and nausea. After 30 minutes of watching the head-mounted display, the SE, near point of accommodation, and stereoacuity in both eyes did not change significantly (all P > .05). Immediately after watching the head-mounted display, esophoric shift was observed (0.6 ± 1.5 to 0.2 ± 1.5 PD), although it was not significant (P = .06). Transient myopic shifts of 17.2% to 30% were observed immediately after watching the head-mounted display in both groups, but recovered fully within 40 minutes after watching the head-mounted display. There were no significant clinical effects of watching head-mounted display for 30 minutes on the normal adolescent eye. Transient changes in refractive error and binocular alignment were noted, but were not significant. [J Pediatr Ophthalmol Strabismus. 2016;53(4):238-245.]. Copyright 2016, SLACK Incorporated.

Technology and design of an active-matrix OLED on crystalline silicon direct-view display for a wristwatch computer

NASA Astrophysics Data System (ADS)

Sanford, James L.; Schlig, Eugene S.; Prache, Olivier; Dove, Derek B.; Ali, Tariq A.; Howard, Webster E.

2002-02-01

The IBM Research Division and eMagin Corp. jointly have developed a low-power VGA direct view active matrix OLED display, fabricated on a crystalline silicon CMOS chip. The display is incorporated in IBM prototype wristwatch computers running the Linus operating system. IBM designed the silicon chip and eMagin developed the organic stack and performed the back-end-of line processing and packaging. Each pixel is driven by a constant current source controlled by a CMOS RAM cell, and the display receives its data from the processor memory bus. This paper describes the OLED technology and packaging, and outlines the design of the pixel and display electronics and the processor interface. Experimental results are presented.

Individual consistency in exploratory behaviour and mating tactics in male guppies

NASA Astrophysics Data System (ADS)

Kelley, Jennifer L.; Phillips, Samuel C.; Evans, Jonathan P.

2013-10-01

While behavioural plasticity is considered an adaptation to fluctuating social and environmental conditions, many animals also display a high level of individual consistency in their behaviour over time or across contexts (generally termed ‘personality’). However, studies of animal personalities that include sexual behaviour, or functionally distinct but correlated traits, are relatively scarce. In this study, we tested for individual behavioural consistency in courtship and exploratory behaviour in male guppies ( Poecilia reticulata) in two light environments (high vs. low light intensity). Based on previous work on guppies, we predicted that males would modify their behaviour from sneak mating tactics to courtship displays under low light conditions, but also that the rank orders of courtship effort would remain unchanged (i.e. highly sexually active individuals would display relatively high levels of courtship under both light regimes). We also tested for correlations between courtship and exploratory behaviour, predicting that males that had high display rates would also be more likely to approach a novel object. Although males showed significant consistency in their exploratory and mating behaviour over time (1 week), we found no evidence that these traits constituted a behavioural syndrome. Furthermore, in contrast to previous work, we found no overall effect of the light environment on any of the behaviours measured, although males responded to the treatment on an individual-level basis, as reflected by a significant individual-by-environment interaction. The future challenge is to investigate how individual consistency across different environmental contexts relates to male reproductive success.

Display format, highlight validity, and highlight method: Their effects on search performance

NASA Technical Reports Server (NTRS)

Donner, Kimberly A.; Mckay, Tim D.; Obrien, Kevin M.; Rudisill, Marianne

1991-01-01

Display format and highlight validity were shown to affect visual display search performance; however, these studies were conducted on small, artificial displays of alphanumeric stimuli. A study manipulating these variables was conducted using realistic, complex Space Shuttle information displays. A 2x2x3 within-subjects analysis of variance found that search times were faster for items in reformatted displays than for current displays. Responses to valid applications of highlight were significantly faster than responses to non or invalidly highlighted applications. The significant format by highlight validity interaction showed that there was little difference in response time to both current and reformatted displays when the highlight validity was applied; however, under the non or invalid highlight conditions, search times were faster with reformatted displays. A separate within-subject analysis of variance of display format, highlight validity, and several highlight methods did not reveal a main effect of highlight method. In addition, observed display search times were compared to search time predicted by Tullis' Display Analysis Program. Benefits of highlighting and reformatting displays to enhance search and the necessity to consider highlight validity and format characteristics in tandem for predicting search performance are discussed.

Electric Field and Lightning Observations in the Core of Category 5 Hurricane Emily

NASA Technical Reports Server (NTRS)

Blakeslee, Richard; Mach, Doug M.; Bateman, Monte G.; Bailey, Jeff C.

2007-01-01

Significant electric fields and lightning activity associated with Hurricane Emily were observed from a NASA high-altitude ER-2 aircraft on July 17, 2005 while this storm developed as a compact but intense category 5 hurricane in the Caribbean south of Cuba. The electrical measurements were acquired as part of the NASA sponsored Tropical Cloud Systems and Processes (TCSP) experiment. In addition to the electrical measurements, the aircraft's remote sensing instrument complement also included active radars, passive microwave, visible and infrared radiometers, and a temperature sounder providing details on the dynamical, microphysical, and environmental structure, characteristics and development of this intense storm. Cloud-to-ground lightning location data from Vaisala's long range lightning detection network were also acquired and displayed in real-time along with electric fields measured at the aircraft. These data and associated display also supported aircraft guidance and vectoring during the mission. During the observing period, flash rates in excess of 3 to 5 flashes per minute, as well as large electric field and field change values were observed as the storm appeared to undergo periods of intensification, especially in the northwest quadrant in the core eyewall regions. This is in contrast to most hurricanes that tend to be characterized by weak electrification and little or no lightning activity except in the outer rain bands. It should be noted that this storm also had significant lightning associated with its rain bands.

Electromyographic analyses of the erector spinae muscles during golf swings using four different clubs.

PubMed

Sorbie, Graeme G; Grace, Fergal M; Gu, Yaodong; Baker, Julien S; Ugbolue, Ukadike C

2018-04-01

The purpose of this study was to compare the electromyography (EMG) patterns of the thoracic and lumbar regions of the erector spinae (ES) muscle during the golf swing whilst using four different golf clubs. Fifteen right-handed male golfers performed a total of twenty swings in random order using the driver, 4-iron, 7-iron and pitching-wedge. Surface EMG was recorded from the lead and trail sides of the thoracic and lumbar regions of the ES muscle (T8, L1 and L5 lateral to the spinous-process). Three-dimensional high-speed video analysis was used to identify the backswing, forward swing, acceleration, early and late follow-through phases of the golf swing. No significant differences in muscle-activation levels from the lead and trail sides of the thoracic and lumbar regions of the ES muscle were displayed between the driver, 4-iron, 7-iron and pitching-wedge (P > 0.05). The highest mean thoracic and lumbar ES muscle-activation levels were displayed in the forward swing (67-99% MVC) and acceleration (83-106% MVC) phases of the swing for all clubs tested. The findings from this study show that there were no significant statistical differences between the driver, 4-iron, 7-iron and pitching-wedge when examining muscle activity from the thoracic and lumbar regions of the ES muscle.

Estrus- and steroid-induced changes in circadian rhythms in a diurnal rodent, Octodon degus.

PubMed

Labyak, S E; Lee, T M

1995-09-01

Diurnal Octodon degus exhibited marked alterations in activity and temperature in conjunction with the 3 wk estrous cycle when housed in LD12:12 light cycle. On the day of estrus, mean daily activity increases 109%, mean core temperature rises .4 degree C, activity onset is advanced 2 h, and amplitudes of both rhythms decline compared with the 3 days prior to estrus. On the day following estrus, activity onset was delayed 4.9 h, and mean activity and core temperature fell below that of the preestrus period. Ovariectomy significantly reduced mean temperature (.98 degree C) but did not significantly alter mean activity, and eliminated cyclic effects of estrus. Estrogen replacement led to a nonsignificant elevation in mean activity and core temperature with no change in the phase angle of entrainment. Progesterone replacement significantly reduced mean core temperature and mean activity, while only the phase angle difference between temperature minimum and activity onset was significantly altered. Intact degus maintained in constant darkness displayed only transient fluctuations in activity onset and temperature minimum during and after estrus. Estrogen or progesterone treatment of ovariectomized, free-running degus altered mean temperature and activity levels, but did not influence tau. Changes in phase angle of entrainment during estrus are not the result of hormone effects on the circadian clock but likely reflect increased or decreased levels of activity.

Advanced and tendencies in the development of display technologies

NASA Astrophysics Data System (ADS)

Kompanets, I. N.

2006-06-01

Advances and key display applications are discussed. Computer, compact mobile, TV and collective large screen displays are mentioned. Flat panel displays step on CRT devices to leave them behind in 2007. Materials, active matricies and applications of bright radiative field emission and organic LED displays are developing successively and pressing other technologies to be used in photo-cameras, cellular phones, auto-cars and avionics. Progress in flexible screens can substantially extend the display design and application soon. 3D display systems are under intensive development, and laser is an important unit in some vaiants of holographic and volumetric 3D displays. Value forecast of different display markets is presented.

Composition of biomineral organic matrices with special emphasis on turbot (Psetta maxima) otolith and endolymph.

PubMed

Borelli, G; Mayer-Gostan, N; Merle, P L; De Pontual, H; Boeuf, G; Allemand, D; Payan, P

2003-06-01

The soluble organic matrix (OM) of various biominerals (red coral skeleton, oyster shell, sea urchin test, turbot otolith, chicken eggshell) was extracted after demineralization with acetic acid. The protein content of the OM varies strongly from 0.02 to 1.6 microg/mg biomineral whereas proteoglycans present less variations (from 0.7 to 1.4 microg/mg biomineral). Electrophoresis of biominerals OM shows differences in their protein pattern although several bands are present in all matrices. OM of all biominerals shows carbonic anhydrase activity but no activity was detectable in the endolymph. OM of all biominerals also displays an anticalcifying activity. After separation of the OM extracts by chloroform-methanol, 80% of the anticalcifying activity was found in the methanol phase except in the urchin test. After OM precipitation with trichloracetic acid, 70% of the activities was found in the supernatants. Partial biochemical characterization suggests that the anticalcifying factor is a polyanionic and water-soluble molecule, which could be proteoglycans. The endolymph surrounding the otolith also displays an anticalcifying activity although its inhibitous activity was 50 times lower than that of the otolith OM. However, the anticalcifying activity of the endolymph is assumed by a proteic structure (80% activity precipitated with TCA treatment). Our results suggest that both carbonic anhydrase and anticalcifying activities are widespread and play a significant role in the regulation of biomineral formation. Results are discussed in relation to the calcification process that takes place at the fluid-mineral interface.

Structure-activity studies and therapeutic potential of host defense peptides of human thrombin.

PubMed

Kasetty, Gopinath; Papareddy, Praveen; Kalle, Martina; Rydengård, Victoria; Mörgelin, Matthias; Albiger, Barbara; Malmsten, Martin; Schmidtchen, Artur

2011-06-01

Peptides of the C-terminal region of human thrombin are released upon proteolysis and identified in human wounds. In this study, we wanted to investigate minimal determinants, as well as structural features, governing the antimicrobial and immunomodulating activity of this peptide region. Sequential amino acid deletions of the peptide GKYGFYTHVFRLKKWIQKVIDQFGE (GKY25), as well as substitutions at strategic and structurally relevant positions, were followed by analyses of antimicrobial activity against the Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa, the Gram-positive bacterium Staphylococcus aureus, and the fungus Candida albicans. Furthermore, peptide effects on lipopolysaccharide (LPS)-, lipoteichoic acid-, or zymosan-induced macrophage activation were studied. The thrombin-derived peptides displayed length- and sequence-dependent antimicrobial as well as immunomodulating effects. A peptide length of at least 20 amino acids was required for effective anti-inflammatory effects in macrophage models, as well as optimal antimicrobial activity as judged by MIC assays. However, shorter (>12 amino acids) variants also displayed significant antimicrobial effects. A central K14 residue was important for optimal antimicrobial activity. Finally, one peptide variant, GKYGFYTHVFRLKKWIQKVI (GKY20) exhibiting improved selectivity, i.e., low toxicity and a preserved antimicrobial as well as anti-inflammatory effect, showed efficiency in mouse models of LPS shock and P. aeruginosa sepsis. The work defines structure-activity relationships of C-terminal host defense peptides of thrombin and delineates a strategy for selecting peptide epitopes of therapeutic interest.

Design and evaluation of web-based image transmission and display with different protocols

NASA Astrophysics Data System (ADS)

Tan, Bin; Chen, Kuangyi; Zheng, Xichuan; Zhang, Jianguo

2011-03-01

There are many Web-based image accessing technologies used in medical imaging area, such as component-based (ActiveX Control) thick client Web display, Zerofootprint thin client Web viewer (or called server side processing Web viewer), Flash Rich Internet Application(RIA) ,or HTML5 based Web display. Different Web display methods have different peformance in different network environment. In this presenation, we give an evaluation on two developed Web based image display systems. The first one is used for thin client Web display. It works between a PACS Web server with WADO interface and thin client. The PACS Web server provides JPEG format images to HTML pages. The second one is for thick client Web display. It works between a PACS Web server with WADO interface and thick client running in browsers containing ActiveX control, Flash RIA program or HTML5 scripts. The PACS Web server provides native DICOM format images or JPIP stream for theses clients.

Neural Activity Associated with Visual Search for Line Drawings on AAC Displays: An Exploration of the Use of fMRI.

PubMed

Wilkinson, Krista M; Dennis, Nancy A; Webb, Christina E; Therrien, Mari; Stradtman, Megan; Farmer, Jacquelyn; Leach, Raevynn; Warrenfeltz, Megan; Zeuner, Courtney

2015-01-01

Visual aided augmentative and alternative communication (AAC) consists of books or technologies that contain visual symbols to supplement spoken language. A common observation concerning some forms of aided AAC is that message preparation can be frustratingly slow. We explored the uses of fMRI to examine the neural correlates of visual search for line drawings on AAC displays in 18 college students under two experimental conditions. Under one condition, the location of the icons remained stable and participants were able to learn the spatial layout of the display. Under the other condition, constant shuffling of the locations of the icons prevented participants from learning the layout, impeding rapid search. Brain activation was contrasted under these conditions. Rapid search in the stable display was associated with greater activation of cortical and subcortical regions associated with memory, motor learning, and dorsal visual pathways compared to the search in the unpredictable display. Rapid search for line drawings on stable AAC displays involves not just the conceptual knowledge of the symbol meaning but also the integration of motor, memory, and visual-spatial knowledge about the display layout. Further research must study individuals who use AAC, as well as the functional effect of interventions that promote knowledge about array layout.

Structure, chaperone-like activity and allergenicity profile of bovine caseins upon peroxynitrite modification: New evidences underlying mastitis pathomechanisms.

PubMed

Sadeghian, Tanaz; Tavaf, Zohreh; Oryan, Ahmad; Shokouhi, Raheleh; Pourpak, Zahra; Moosavi-Movahedi, Ali Akbar; Yousefi, Reza

2018-01-01

Mastitis, an inflammatory reaction frequently develops in response to intra-mammary bacterial infection‌‌, may induce the generation of peroxynitrite (PON)‌ which is a highly potent reactive oxygen and nitrogen species. Caseins as the intrinsically unfolded proteins seem feasible substrates to react with PON. Therefore, in the current study, structural and functional aspects of both β-casein (β-CN) and whole casein fraction (WCF) were evaluated after PON modification, using a variety of techniques. Modification of the bovine caseins with PON results in an important enhancement in the carbonyl, nitrotryptophan, nitrotyrosine and dityrosine content of these proteins‌. The results of fluorescence and far UV-CD assessments suggested significant structural alteration of caseins upon PON-modification. The chaperone-like activity of β-casein was significantly altered after PON modification. The results of scanning electron microscopy suggest that bovine caseins display unique morphological features after treatment with PON. Also, the PON-modified caseins preserved their allergenicity profile and displayed partial resistance against digestion by the pancreatic proteases. Ascorbic acid, an important antioxidant component of milk, was also capable to significantly prevent the PON-induced structural damages in bovine milk caseins. In conclusion, our results suggest that PON may have significant role in the structural and functional alteration of milk caseins. Also, the PON-induced structural damaging effects of caseins might be effectively prevented by a sufficient level of milk antioxidant components particularly by ascorbic acid. Copyright © 2017 Elsevier B.V. All rights reserved.

[Three-dimensional display simulation of lung surgery using "active shutter glasses"].

PubMed

Onuki, Takamasa; Kanzaki, Masato; Sakamoto, Kei; Kikkawa, Takuma; Isaka, Tamami; Shimizu, Toshihide; Oyama, Kunihiro; Murasugi, Masahide

2011-08-01

We have reported preoperative 3-dimensional (3D) simulation of thoracoscopic lung surgery using self-made software and internet shareware of 3D-modeler. Using "active shutter glasses", we have tried the "3D display simulation" of lung surgery. 3D display was more effective to grasp clear 3D interrelation between the bronchii and pulmonary vascular system than those in images of currently in use with the same information volume.

Pt-Pd Bimetal Popcorn Nanocrystals: Enhancing the Catalytic Performance by Combination Effect of Stable Multipetals Nanostructure and Highly Accessible Active Sites.

PubMed

Ma, Yanxia; Yin, Lisi; Cao, Guojian; Huang, Qingli; He, Maoshuai; Wei, Wenxian; Zhao, Hong; Zhang, Dongen; Wang, Mingyan; Yang, Tao

2018-04-01

Exploration of highly efficient electrocatalysts is significantly urgent for the extensive adoption of the fuel cells. Because of their high activity and super stability, Pt-Pd bimetal nanocrystals have been widely recognized as one class of promising electrocatalysts for oxygen reduction. This article presents the synthesis of popcorn-shaped Pt-Pd bimetal nanoparticles with a wide composition range through a facile hydrothermal strategy. The hollow-centered nanoparticles are surrounded by several petals and concave surfaces. By exploring the oxygen reduction reaction on the carbon supported Pt-Pd popcorns in perchloric acid solution, it is found that compared with the commercial Pt/C catalyst the present catalysts display superior catalytic performances in aspects of catalytic activity and stability. More importantly, the Pt-Pd popcorns display minor performance degradations through prolonged potential cycling. The enhanced performances can be mainly attributed to the unique popcorn structure of the Pt-Pd components, which allows the appearance and long existence of the high active sites with more accessibility. The present work highlights the key roles of accessible high active sites in the oxygen reduction reaction, which will ultimately guide the design of highly durable Pt-Pd catalysts. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Exercise Therapy for Management of Type 2 Diabetes Mellitus: Superior Efficacy of Activity Monitors over Pedometers.

PubMed

Miyauchi, Masaaki; Toyoda, Masao; Kaneyama, Noriko; Miyatake, Han; Tanaka, Eitaro; Kimura, Moritsugu; Umezono, Tomoya; Fukagawa, Masafumi

2016-01-01

We compared the efficacy of activity monitor (which displays exercise intensity and number of steps) versus that of pedometer in exercise therapy for patients with type 2 diabetes. The study subjects were divided into the activity monitor group ( n = 92) and pedometer group ( n = 95). The primary goal was improvement in hemoglobin A1c (HbA1c). The exercise target was set at 8,000 steps/day and 20 minutes of moderate-intensity exercise (≥3.5 metabolic equivalents). The activity monitor is equipped with a triple-axis accelerometer sensor capable of measuring medium-intensity walking duration, number of steps, walking distance, calorie consumption, and total calorie consumption. The pedometer counts the number of steps. Blood samples for laboratory tests were obtained during the visits. The first examination was conducted at the start of the study and repeated at 2 and 6 months. A significant difference in the decrease in HbA1c level was observed between the two groups at 2 months. The results suggest that the use of activity level monitor that displays information on exercise intensity, in addition to the number of steps, is useful in exercise therapy as it enhances the concept of exercise therapy and promotes lowering of HbA1c in diabetic patients.

Antibacterial activity of 2-alkynoic fatty acids against multidrug resistant bacteria

PubMed Central

Sanabria-Ríos, David J.; Rivera-Torres, Yaritza; Maldonado-Domínguez, Gamalier; Domínguez, Idializ; Ríos, Camille; Díaz, Damarith; Rodríguez, José W.; Altieri-Rivera, Joanne S.; Ríos-Olivares, Eddy; Cintrón, Gabriel; Montano, Nashbly; Carballeira, Néstor M.

2014-01-01

The first study aimed at determining the structural characteristics needed to prepare antibacterial 2-alkynoic fatty acids (2-AFAs) was accomplished by synthesizing several 2-AFAs and other analogues in 18-76% overall yields. Among all the compounds tested, the 2-hexadecynoic acid (2-HDA) displayed the best overall antibacterial activity against Gram-positive Staphylococcus aureus (MIC = 15.6 μg/mL), Staphylococcus saprophyticus (MIC = 15.5 μg/mL), and Bacillus cereus (MIC = 31.3 μg/mL), as well as against the Gram-negative Klebsiella pneumoniae (7.8 μg/mL) and Pseudomonas aeruginosa (MIC = 125 μg/mL). In addition, 2-HDA displayed significant antibacterial activity against methicillin-resistant S. aureus (MRSA) ATCC 43300 (MIC = 15.6 μg/mL) and clinical isolates of MRSA (MIC = 3.9 μg/mL). No direct relationship was found between the antibacterial activity of 2-AFAs and their critical micelle concentration (CMC) suggesting that the antibacterial properties of these fatty acids are not mediated by micelle formation. It was demonstrated that the presence of a triple bond at C-2 as well as the carboxylic acid moiety in 2-AFAs are important for their antibacterial activity. 2-HDA has the potential to be further evaluated for use in antibacterial formulations. PMID:24365283

An easy method for the determination of active concentrations of cholinesterase reactivators in blood samples: Application to the efficacy assessment of non quaternary reactivators compared to HI-6 and pralidoxime in VX-poisoned mice.

PubMed

Calas, André-Guilhem; Dias, José; Rousseau, Catherine; Arboléas, Mélanie; Touvrey-Loiodice, Mélanie; Mercey, Guillaume; Jean, Ludovic; Renard, Pierre-Yves; Nachon, Florian

2017-04-01

Organophosphorus nerve agents, like VX, are highly toxic due to their strong inhibition potency against acetylcholinesterase (AChE). AChE inhibited by VX can be reactivated using powerful nucleophilic molecules, most commonly oximes, which are one major component of the emergency treatment in case of nerve agent intoxication. We present here a comparative in vivo study on Swiss mice of four reactivators: HI-6, pralidoxime and two uncharged derivatives of 3-hydroxy-2-pyridinaldoxime that should more easily cross the blood-brain barrier and display a significant central nervous system activity. The reactivability kinetic profile of the oximes is established following intraperitoneal injection in healthy mice, using an original and fast enzymatic method based on the reactivation potential of oxime-containing plasma samples. HI-6 displays the highest reactivation potential whatever the conditions, followed by pralidoxime and the two non quaternary reactivators at the dose of 50 mg/kg bw. But these three last reactivators display equivalent reactivation potential at the same dose of 100 μmol/kg bw. Maximal reactivation potential closely correlates to surviving test results of VX intoxicated mice. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Efficient HOMO-LUMO separation by multiple resonance effect toward ultrapure blue thermally activated delayed fluorescence

NASA Astrophysics Data System (ADS)

Hatakeyama, Takuji; Ikuta, Toshiaki; Shiren, Kazushi; Nakajima, Kiichi; Nomura, Shintaro; Ni, Jingping

2016-09-01

Organic light-emitting diodes (OLEDs) play an important role in the new generation of flat-panel displays. Conventional OLEDs employing fluorescent materials together with triplet-triplet annihilation suffer from a relatively low internal quantum efficiency (IQE) of 62.5%. On the other hand, the IQE of OLEDs employing phosphorescent or thermally activated delayed fluorescence (TADF) materials can reach 100%. However, these materials exhibit very broad peaks with a full-width at half-maximum (FWHM) of 70-100 nm and cannot satisfy the color-purity requirements for displays. Therefore, the latest commercial OLED displays employ blue fluorescent materials with a relatively low IQE, and efficient blue emitters with a small FWHM are highly needed. In our manuscript, we present organic molecules that exhibit ultrapure blue fluorescence based on TADF. These molecules consist of three benzene rings connected by one boron and two nitrogen atoms, which establish a rigid polycyclic framework and significant localization of the highest occupied and lowest unoccupied molecular orbitals by a multiple resonance effect. An OLED device based on the new emitter exhibits ultrapure blue emission at 467 nm with an FWHM of 28 nm, Commission Internationale de l'Eclairage (CIE) coordinates of (0.12, 0.13), and an IQE of 100%, which represent record-setting performance for blue OLED devices.

Cytotoxic and Antibacterial Angucycline- and Prodigiosin- Analogues from the Deep-Sea Derived Streptomyces sp. SCSIO 11594

PubMed Central

Song, Yongxiang; Liu, Guangfu; Li, Jie; Huang, Hongbo; Zhang, Xing; Zhang, Hua; Ju, Jianhua

2015-01-01

Two new C-glycoside angucyclines, marangucycline A (1) and marangucycline B (2), along with three known compounds, dehydroxyaquayamycin (3), undecylprodigiosin (4) and metacycloprodigiosin (5), have been identified as products of the deep-sea sediment strain Streptomyces sp. SCSIO 11594. New structures were elucidated on the basis of HRESIMS, 1D and 2D NMR analyses and comparisons to previously reported datasets. Compounds 2 and 4 displayed in vitro cytotoxicity against four cancer cell lines A594, CNE2, HepG2, MCF-7 superior to those obtained with cisplatin, the positive control. Notably, compound 2 bearing a keto-sugar displayed significant cytotoxicity against cancer cell lines with IC50 values ranging from 0.24 to 0.56 μM; An IC50 value of 3.67 μM was found when using non-cancerous hepatic cell line HL7702, demonstrating the cancer cell selectivity of 2. Compounds 1–3 were proved to have weak antibacterial activities against Enterococcus faecalis ATCC29212 with an MIC value of 64.0 μg/mL. Moreover, 3 displayed selective antibacterial activity against methicillin-resistant Staphylococcus epidermidis shhs-E1 with an MIC value of 16.0 μg/mL. PMID:25786061

A study of temperature-related non-linearity at the metal-silicon interface

NASA Astrophysics Data System (ADS)

Gammon, P. M.; Donchev, E.; Pérez-Tomás, A.; Shah, V. A.; Pang, J. S.; Petrov, P. K.; Jennings, M. R.; Fisher, C. A.; Mawby, P. A.; Leadley, D. R.; McN. Alford, N.

2012-12-01

In this paper, we investigate the temperature dependencies of metal-semiconductor interfaces in an effort to better reproduce the current-voltage-temperature (IVT) characteristics of any Schottky diode, regardless of homogeneity. Four silicon Schottky diodes were fabricated for this work, each displaying different degrees of inhomogeneity; a relatively homogeneous NiV/Si diode, a Ti/Si and Cr/Si diode with double bumps at only the lowest temperatures, and a Nb/Si diode displaying extensive non-linearity. The 77-300 K IVT responses are modelled using a semi-automated implementation of Tung's electron transport model, and each of the diodes are well reproduced. However, in achieving this, it is revealed that each of the three key fitting parameters within the model display a significant temperature dependency. In analysing these dependencies, we reveal how a rise in thermal energy "activates" exponentially more interfacial patches, the activation rate being dependent on the carrier concentration at the patch saddle point (the patch's maximum barrier height), which in turn is linked to the relative homogeneity of each diode. Finally, in a review of Tung's model, problems in the divergence of the current paths at low temperature are explained to be inherent due to the simplification of an interface that will contain competing defects and inhomogeneities.

Plastic substrates for active matrix liquid crystal display incapable of withstanding processing temperature of over 200 C and method of fabrication

DOEpatents

Carey, P.G.; Smith, P.M.; Havens, J.H.; Jones, P.

1999-01-05

Bright-polarizer-free, active-matrix liquid crystal displays (AMLCDs) are formed on plastic substrates. The primary components of the display are a pixel circuit fabricated on one plastic substrate, an intervening liquid-crystal material, and a counter electrode on a second plastic substrate. The-pixel circuit contains one or more thin-film transistors (TFTs) and either a transparent or reflective pixel electrode manufactured at sufficiently low temperatures to avoid damage to the plastic substrate. Fabrication of the TFTs can be carried out at temperatures less than 100 C. The liquid crystal material is a commercially made nematic curvilinear aligned phase (NCAP) film. The counter electrode is comprised of a plastic substrate coated with a transparent conductor, such as indium-doped tin oxide (ITO). By coupling the active matrix with NCAP, a high-information content can be provided in a bright, fully plastic package. Applications include any low cost portable electronics containing flat displays where ruggedization of the display is desired. 12 figs.

Plastic substrates for active matrix liquid crystal display incapable of withstanding processing temperature of over 200.degree. C and method of fabrication

DOEpatents

Carey, Paul G.; Smith, Patrick M.; Havens, John; Jones, Phil

1999-01-01

Bright-polarizer-free, active-matrix liquid crystal displays (AMLCDs) are formed on plastic substrates. The primary components of the display are a pixel circuit fabricated on one plastic substrate, an intervening liquid-crystal material, and a counter electrode on a second plastic substrate. The-pixel circuit contains one or more thin-film transistors (TFTs) and either a transparent or reflective pixel electrode manufactured at sufficiently low temperatures to avoid damage to the plastic substrate. Fabrication of the TFTs can be carried out at temperatures less than 100.degree. C. The liquid crystal material is a commercially made nematic curvilinear aligned phase (NCAP) film. The counter electrode is comprised of a plastic substrate coated with a transparent conductor, such as indium-doped tin oxide (ITO). By coupling the active matrix with NCAP, a high-information content can be provided in a bright, fully plastic package. Applications include any low cost portable electronics containing flat displays where ruggedization of the display is desired.

Use of electromyography for the diagnosis of equine hyperkalemic periodic paresis.

PubMed Central

Robinson, J A; Naylor, J M; Crichlow, E C

1990-01-01

The use of electromyography (EMG) as a diagnostic aid for equine hyperkalemic periodic paresis (EHPP) was investigated in seven affected and seven control horses. Affected horses were confirmed positive for EHPP either by elevated serum potassium concentration with clinical signs of myotonia, or by inducing hyperkalemia and clinical signs using oral potassium chloride challenge. All horses were asymptomatic at the time EMG was performed, using bipolar fine wire needle electrodes. The myopotentials were recorded on magnetic tape and displayed on paper charts for analysis. Insertional and resting activity were recorded from the right supraspinatus, triceps, extensor carpi radialis and gluteal muscles in standing horses. Myotonic discharges were seen in six of seven affected horses but not in any of the controls. All seven affected horses and two control horses had prolonged insertional activity. Five out of seven affected horses and one control horse displayed spontaneous motor unit discharges unrelated to recording electrode movement. Myoelectrical potentials containing closely timed muscle potentials, i.e. doublets, were found in all affected horses, with four of seven affected horses also showing triplets. These potentials were not observed in any of the controls. No obvious difference in activity was observed among the four muscle sites tested. It is concluded that EMG is a safe and useful tool for diagnosing EHPP in horses not currently displaying clinical signs. Myotonic discharges and doublets appear to be the most diagnostically significant electromyographic abnormalities in EHPP affected horses. PMID:2249182

Neurochemical binding profiles of novel indole and benzofuran MDMA analogues.

PubMed

Shimshoni, Jakob A; Winkler, Ilan; Golan, Ezekiel; Nutt, David

2017-01-01

3,4-Methylenedioxy-N-methylamphetamine (MDMA) has been shown to be effective in the treatment of post-traumatic stress disorder (PTSD) in numerous clinical trials. In the present study, we have characterized the neurochemical binding profiles of three MDMA-benzofuran analogues (1-(benzofuran-5-yl)-propan-2-amine, 5-APB; 1-(benzofuran-6-yl)-N-methylpropan-2-amine, 6-MAPB; 1-(benzofuran-5-yl)-N-methylpropan-2-amine, 5-MAPB) and one MDMA-indole analogue (1-(1H-indol-5-yl)-2-methylamino-propan-1-ol, 5-IT). These compounds were screened as potential second-generation anti-PTSD drugs, against a battery of human and non-human receptors, transporters, and enzymes, and their potencies as 5-HT 2 receptor agonist and monoamine uptake inhibitors determined. All MDMA analogues displayed high binding affinities for 5-HT 2a,b,c and NE α2 receptors, as well as significant 5-HT, DA, and NE uptake inhibition. 5-APB revealed significant agonist activity at the 5-HT 2a,b,c receptors, while 6-MAPB, 5-MAPB, and 5-IT exhibited significant agonist activity at the 5-HT 2c receptor. There was a lack of correlation between the results of functional uptake and the monoamine transporter binding assay. MDMA analogues emerged as potent and selective monoamine oxidase A inhibitors. Based on 6-MAPB favorable pharmacological profile, it was further subjected to IC 50 determination for monoamine transporters. Overall, all MDMA analogues displayed higher monoamine receptor/transporter binding affinities and agonist activity at the 5-HT 2a,c receptors as compared to MDMA.

Ventral aspect of the visual form pathway is not critical for the perception of biological motion

PubMed Central

Gilaie-Dotan, Sharon; Saygin, Ayse Pinar; Lorenzi, Lauren J.; Rees, Geraint; Behrmann, Marlene

2015-01-01

Identifying the movements of those around us is fundamental for many daily activities, such as recognizing actions, detecting predators, and interacting with others socially. A key question concerns the neurobiological substrates underlying biological motion perception. Although the ventral “form” visual cortex is standardly activated by biologically moving stimuli, whether these activations are functionally critical for biological motion perception or are epiphenomenal remains unknown. To address this question, we examined whether focal damage to regions of the ventral visual cortex, resulting in significant deficits in form perception, adversely affects biological motion perception. Six patients with damage to the ventral cortex were tested with sensitive point-light display paradigms. All patients were able to recognize unmasked point-light displays and their perceptual thresholds were not significantly different from those of three different control groups, one of which comprised brain-damaged patients with spared ventral cortex (n > 50). Importantly, these six patients performed significantly better than patients with damage to regions critical for biological motion perception. To assess the necessary contribution of different regions in the ventral pathway to biological motion perception, we complement the behavioral findings with a fine-grained comparison between the lesion location and extent, and the cortical regions standardly implicated in biological motion processing. This analysis revealed that the ventral aspects of the form pathway (e.g., fusiform regions, ventral extrastriate body area) are not critical for biological motion perception. We hypothesize that the role of these ventral regions is to provide enhanced multiview/posture representations of the moving person rather than to represent biological motion perception per se. PMID:25583504

Ethanolic and aqueous extracts derived from Australian fungi inhibit cancer cell growth in vitro.

PubMed

Beattie, Karren D; Ulrich, Rahel; Grice, I Darren; Uddin, Shaikh J; Blake, Tony B; Wood, Kyle A; Steele, Jules; Iu, Fontaine; May, Tom W; Tiralongo, Evelin

2011-01-01

Fifteen Australian macrofungi were investigated for cytotoxic activity. Ethanol, cold and hot water extracts of each species were screened for cytotoxic activity against normal mouse fibroblast cells (NIH/3T3), healthy human epithelial kidney cells (HEK-293), four cancer cell lines, gastric adenocarcinoma cells (AGS), two mammary gland adenocarcinoma cells (MDA-MB-231, MCF7) and colorectal adenocarcinoma cells (HT-29) with a validated MTT assay. Most extracts derived from Omphalotus nidiformis, Cordyceps cranstounii and Cordyceps gunnii demonstrated significant cytotoxic activity toward a variety of cancer cell lines. In contrast only some extracts from Coprinus comatus, Cordyceps hawkesii, Hypholoma fasciculare, Lepista nuda, Leratiomyces ceres and Ophiocordyceps robertsii displayed significant cytotoxic activity, which was usually selective for only one or two cancer cell lines tested. The least cytotoxic species evaluated in this study were Agaricus bitorquis, Coprinopsis atrametaria, Psathyrella asperospora, Russula clelandii, Tricholoma sp. AU2 and Xerula mundroola.

Characterization and antioxidant activities of polysaccharides from thirteen boletus mushrooms.

PubMed

Zhang, Lan; Hu, Yu; Duan, Xiaoyu; Tang, Tingting; Shen, Yingbin; Hu, Bin; Liu, Aiping; Chen, Hong; Li, Cheng; Liu, Yuntao

2018-07-01

Water-soluble polysaccharides were extracted from the caps and stipes of thirteen boletus mushrooms representing five different species collected in Southwest China. Investigations of their structures and antioxidant activities allowed an evaluation of structure-function relationships. The polysaccharides were composed mainly of the monosaccharides arabinose, xylose, mannose, glucose and galactose. Most samples displayed a broad molecular weight range, with significant differences observed between the molecular weight ranges of the polysaccharides from the caps and the stipes. FT-IR spectral analysis of the polysaccharides revealed that most of polysaccharides from boletus mushrooms (except Boletus edulis) contained a pyranose ring. The antioxidant activities of the polysaccharides in stipes showed a significant correlation with their monosaccharide composition, and were also related to their molecular weight and anomeric configuration. Suillellus luridus collected in Pingwu, Mianyang, Sichuan, China had remarkably superior antioxidant activity and might be developed as a natural antioxidant. Copyright © 2018 Elsevier B.V. All rights reserved.

Volumetric 3D display with multi-layered active screens for enhanced the depth perception (Conference Presentation)

NASA Astrophysics Data System (ADS)

Kim, Hak-Rin; Park, Min-Kyu; Choi, Jun-Chan; Park, Ji-Sub; Min, Sung-Wook

2016-09-01

Three-dimensional (3D) display technology has been studied actively because it can offer more realistic images compared to the conventional 2D display. Various psychological factors such as accommodation, binocular parallax, convergence and motion parallax are used to recognize a 3D image. For glass-type 3D displays, they use only the binocular disparity in 3D depth cues. However, this method cause visual fatigue and headaches due to accommodation conflict and distorted depth perception. Thus, the hologram and volumetric display are expected to be an ideal 3D display. Holographic displays can represent realistic images satisfying the entire factors of depth perception. But, it require tremendous amount of data and fast signal processing. The volumetric 3D displays can represent images using voxel which is a physical volume. However, it is required for large data to represent the depth information on voxel. In order to simply encode 3D information, the compact type of depth fused 3D (DFD) display, which can create polarization distributed depth map (PDDM) image having both 2D color image and depth image is introduced. In this paper, a new volumetric 3D display system is shown by using PDDM image controlled by polarization controller. In order to introduce PDDM image, polarization states of the light through spatial light modulator (SLM) was analyzed by Stokes parameter depending on the gray level. Based on the analysis, polarization controller is properly designed to convert PDDM image into sectioned depth images. After synchronizing PDDM images with active screens, we can realize reconstructed 3D image. Acknowledgment This work was supported by `The Cross-Ministry Giga KOREA Project' grant from the Ministry of Science, ICT and Future Planning, Korea

Engineering the cell surface display of cohesins for assembly of cellulosome-inspired enzyme complexes on Lactococcus lactis

PubMed Central

2010-01-01

Background The assembly and spatial organization of enzymes in naturally occurring multi-protein complexes is of paramount importance for the efficient degradation of complex polymers and biosynthesis of valuable products. The degradation of cellulose into fermentable sugars by Clostridium thermocellum is achieved by means of a multi-protein "cellulosome" complex. Assembled via dockerin-cohesin interactions, the cellulosome is associated with the cell surface during cellulose hydrolysis, forming ternary cellulose-enzyme-microbe complexes for enhanced activity and synergy. The assembly of recombinant cell surface displayed cellulosome-inspired complexes in surrogate microbes is highly desirable. The model organism Lactococcus lactis is of particular interest as it has been metabolically engineered to produce a variety of commodity chemicals including lactic acid and bioactive compounds, and can efficiently secrete an array of recombinant proteins and enzymes of varying sizes. Results Fragments of the scaffoldin protein CipA were functionally displayed on the cell surface of Lactococcus lactis. Scaffolds were engineered to contain a single cohesin module, two cohesin modules, one cohesin and a cellulose-binding module, or only a cellulose-binding module. Cell toxicity from over-expression of the proteins was circumvented by use of the nisA inducible promoter, and incorporation of the C-terminal anchor motif of the streptococcal M6 protein resulted in the successful surface-display of the scaffolds. The facilitated detection of successfully secreted scaffolds was achieved by fusion with the export-specific reporter staphylococcal nuclease (NucA). Scaffolds retained their ability to associate in vivo with an engineered hybrid reporter enzyme, E. coli β-glucuronidase fused to the type 1 dockerin motif of the cellulosomal enzyme CelS. Surface-anchored complexes exhibited dual enzyme activities (nuclease and β-glucuronidase), and were displayed with efficiencies approaching 104 complexes/cell. Conclusions We report the successful display of cellulosome-inspired recombinant complexes on the surface of Lactococcus lactis. Significant differences in display efficiency among constructs were observed and attributed to their structural characteristics including protein conformation and solubility, scaffold size, and the inclusion and exclusion of non-cohesin modules. The surface-display of functional scaffold proteins described here represents a key step in the development of recombinant microorganisms capable of carrying out a variety of metabolic processes including the direct conversion of cellulosic substrates into fuels and chemicals. PMID:20840763

Efficient production of D-tagatose using a food-grade surface display system.

PubMed

Liu, Yi; Li, Sha; Xu, Hong; Wu, Lingtian; Xu, Zheng; Liu, Jing; Feng, Xiaohai

2014-07-16

D-tagatose, a functional sweetener, is commonly transformed from D-galactose by L-arabinose isomerase (L-AI). In this study, a novel type of biocatalyst, L-AI from Lactobacillus fermentum CGMCC2921 displayed on the spore surface of Bacillus subtilis 168, was developed for producing D-tagatose. The anchored L-AI, exhibiting the relatively high bioactivity, suggested that the surface display system using CotX as the anchoring protein was successfully constructed. The stability of the anchored L-AI was significantly improved. Specifically, the consolidation of thermal stability representing 87% of relative activity was retained even at 80 °C for 30 min, which remarkably favored the production of D-tagatose. Under the optimal conditions, the robust spores can convert 75% D-galactose (100 g/L) into D-tagatose after 24 h, and the conversion rate remained at 56% at the third cycle. Therefore, this biocatalysis system, which could express the target enzyme on the food-grade vector, was an alternative method for the value-added production of D-tagatose.

Identifying the cellular targets of natural products using T7 phage display.

PubMed

Piggott, Andrew M; Karuso, Peter

2016-05-04

Covering: up to the end of 2015While Nature continues to deliver a myriad of potent and structurally diverse biologically active small molecules, the cellular targets and modes of action of these natural products are rarely identified, significantly hindering their development as new chemotherapeutic agents. This article provides an introductory tutorial on the use of T7 phage display as a tool to rapidly identify the cellular targets of natural products and is aimed specifically at natural products chemists who may have only limited experience in molecular biology. A brief overview of T7 phage display is provided, including its strengths, weaknesses, and the type of problems that can and cannot be tackled with this technology. Affinity probe construction is reviewed, including linker design and natural product derivatisation strategies. A detailed description of the T7 phage biopanning procedure is provided, with valuable tips for optimising each step in the process, as well as advice for identifying and avoiding the most commonly encountered challenges and pitfalls along the way. Finally, a brief discussion is provided on techniques for validating the cellular targets identified using T7 phage display.

Iminosugars as a new class of cholinesterase inhibitors.

PubMed

Decroocq, Camille; Stauffert, Fabien; Pamlard, Olivier; Oulaïdi, Farah; Gallienne, Estelle; Martin, Olivier R; Guillou, Catherine; Compain, Philippe

2015-02-15

To further extend the scope of iminosugar biological activity, a systematic structure-activity relationship investigation has been performed by synthesizing and evaluating as cholinesterase inhibitors a library of twenty-three iminoalditols with different substitutions and stereochemistry patterns. These compounds have been evaluated in vitro for the inhibition of cholinesterases (different sources of acetylcholinesterase and butyrylcholinesterase). Some compounds have IC50 values in the micromolar range and display significant inhibition selectivity for butyrylcholinesterase over acetylcholinesterase. These are the first examples of iminosugar-based inhibitors of cholinesterases. Copyright © 2015 Elsevier Ltd. All rights reserved.

Lower limb motor restlessness in Asperger's disorder, measured using actometry.

PubMed

Tuisku, Katinka; Tani, Pekka; Nieminen-von Wendt, Taina; von Wendt, Lennart; Holi, Matti Mikael; Porkka-Heiskanen, Tarja; Lauerma, Hannu; Lindberg, Nina; Appelberg, Björn; Wahlbeck, Kristian

2004-08-30

The movement disturbances and brain imaging findings in Asperger's disorder (AD) suggest a dopaminergic deficit in movement regulation. Movement disorders of different etiologies have been quantified and specified with actometry. We compared 10 AD patients with 10 healthy controls, measuring their rest-activities by actometry. The lower limb motor activity was significantly higher in the AD group. They also displayed a rhythmic, periodic movement pattern similar to akathisia. These findings suggest a hypothesis of idiopathic akathisia and a special sensitivity to adverse effects of neuroleptic drugs.

Evaluation of viewing experiences induced by a curved three-dimensional display

NASA Astrophysics Data System (ADS)

Mun, Sungchul; Park, Min-Chul; Yano, Sumio

2015-10-01

Despite an increased need for three-dimensional (3-D) functionality in curved displays, comparisons pertinent to human factors between curved and flat panel 3-D displays have rarely been tested. This study compared stereoscopic 3-D viewing experiences induced by a curved display with those of a flat panel display by evaluating subjective and objective measures. Twenty-four participants took part in the experiments and viewed 3-D content with two different displays (flat and curved 3-D display) within a counterbalanced and within-subject design. For the 30-min viewing condition, a paired t-test showed significantly reduced P300 amplitudes, which were caused by engagement rather than cognitive fatigue, in the curved 3-D viewing condition compared to the flat 3-D viewing condition at P3 and P4. No significant differences in P300 amplitudes were observed for 60-min viewing. Subjective ratings of realness and engagement were also significantly higher in the curved 3-D viewing condition than in the flat 3-D viewing condition for 30-min viewing. Our findings support that curved 3-D displays can be effective for enhancing engagement among viewers based on specific viewing times and environments.

RGC-32 is a novel regulator of the T-lymphocyte cell cycle.

PubMed

Tegla, Cosmin A; Cudrici, Cornelia D; Nguyen, Vinh; Danoff, Jacob; Kruszewski, Adam M; Boodhoo, Dallas; Mekala, Armugam P; Vlaicu, Sonia I; Chen, Ching; Rus, Violeta; Badea, Tudor C; Rus, Horea

2015-06-01

We have previously shown that RGC-32 is involved in cell cycle regulation in vitro. To define the in vivo role of RGC-32, we generated RGC-32 knockout mice. These mice developed normally and did not spontaneously develop overt tumors. To assess the effect of RGC-32 deficiency on cell cycle activation in T cells, we determined the proliferative rates of CD4(+) and CD8(+) T cells from the spleens of RGC-32(-/-) mice, as compared to wild-type (WT, RGC-32(+/+)) control mice. After stimulation with anti-CD3/anti-CD28, CD4(+) T cells from RGC-32(-/-) mice displayed a significant increase in [(3)H]-thymidine incorporation when compared to WT mice. In addition, both CD4(+) and CD8(+) T cells from RGC-32(-/-) mice displayed a significant increase in the proportion of proliferating Ki67(+) cells, indicating that in T cells, RGC-32 has an inhibitory effect on cell cycle activation induced by T-cell receptor/CD28 engagement. Furthermore, Akt and FOXO1 phosphorylation induced in stimulated CD4(+) T-cells from RGC-32(-/-) mice were significantly higher, indicating that RGC-32 inhibits cell cycle activation by suppressing FOXO1 activation. We also found that IL-2 mRNA and protein expression were significantly increased in RGC-32(-/-) CD4(+) T cells when compared to RGC-32(+/+) CD4(+) T cells. In addition, the effect of RGC-32 on the cell cycle and IL-2 expression was inhibited by pretreatment of the samples with LY294002, indicating a role for phosphatidylinositol 3-kinase (PI3K). Thus, RGC-32 is involved in controlling the cell cycle of T cells in vivo, and this effect is mediated by IL-2 in a PI3K-dependent fashion. Copyright © 2015 Elsevier Inc. All rights reserved.

Effectiveness of Manual Therapy and Stretching for Baseball Players With Shoulder Range of Motion Deficits.

PubMed

Bailey, Lane B; Thigpen, Charles A; Hawkins, Richard J; Beattie, Paul F; Shanley, Ellen

Baseball players displaying deficits in shoulder range of motion (ROM) are at increased risk of arm injury. Currently, there is a lack of consensus regarding the best available treatment options to restore shoulder ROM. Instrumented manual therapy with self-stretching will result in clinically significant deficit reductions when compared with self-stretching alone. Controlled laboratory study. Shoulder ROM and humeral torsion were assessed in 60 active baseball players (mean age, 19 ± 2 years) with ROM deficits (nondominant - dominant, ≥15°). Athletes were randomly assigned to receive a single treatment of instrumented manual therapy plus self-stretching (n = 30) or self-stretching only (n = 30). Deficits in internal rotation, horizontal adduction, and total arc of motion were compared between groups immediately before and after a single treatment session. Treatment effectiveness was determined by mean comparison data, and a number-needed-to-treat (NNT) analysis was used for assessing the presence of ROM risk factors. Prior to intervention, players displayed significant ( P < 0.001) dominant-sided deficits in internal rotation (-26°), total arc of motion (-18°), and horizontal adduction (-17°). After the intervention, both groups displayed significant improvements in ROM, with the instrumented manual therapy plus self-stretching group displaying greater increases in internal rotation (+5°, P = 0.010), total arc of motion (+6°, P = 0.010), and horizontal adduction (+7°, P = 0.004) compared with self-stretching alone. For horizontal adduction deficits, the added use of instrumented manual therapy with self-stretching decreased the NNT to 2.2 (95% CI, 2.1-2.4; P = 0.010). Instrumented manual therapy with self-stretching significantly reduces ROM risk factors in baseball players with motion deficits when compared with stretching alone. The added benefits of manual therapy may help to reduce ROM deficits in clinical scenarios where stretching alone is ineffective.

A significant increase in both basal and maximal calcineurin activity following fluid percussion injury in the rat.

PubMed

Kurz, Jonathan E; Parsons, J Travis; Rana, Aniruddha; Gibson, Cynthia J; Hamm, Robert J; Churn, Severn B

2005-04-01

Calcineurin, a neuronally enriched, calcium-stimulated phosphatase, is an important modulator of many neuronal processes, including several that are physiologically related to the pathology of traumatic brain injury. This study examined the effects of moderate, central fluid percussion injury on the activity of this important neuronal enzyme. Animals were sacrificed at several time-points postinjury and cortical, hippocampal, and cerebellar homogenates were assayed for calcineurin activity by dephosphorylation of p-nitrophenol phosphate. A significant brain injury-dependent increase was observed in both hippocampal and cortical homogenates under both basal and maximally-stimulated reaction conditions. This increase persisted 2-3 weeks post-injury. Brain injury did not alter substrate affinity, but did induce a significant increase in the apparent maximal dephosphorylation rate. Unlike the other brain regions, no change in calcineurin activity was observed in the cerebellum following brain injury. No brain region tested displayed a significant change in calcineurin enzyme levels as determined by Western blot, demonstrating that increased enzyme synthesis was not responsible for the observed increase in activity. The data support the conclusion that fluid percussion injury results in increased calcineurin activity in the rat forebrain. This increased activity has broad physiological implications, possibly resulting in altered cellular excitability or a greater likelihood of neuronal cell death.

Identification of Breast Cancer Specific Proteolytic Activities for Targeted Prodrug Activation

DTIC Science & Technology

2006-05-01

volume of fluid that can be obtained from ECF of human breast cancers is to use a phage display approach. To accomplish this, we have designed a...affinity support, followed by a randomized protease substrate sequence and the carboxyl-terminal domain of M13 gene III. Each fusion protein was displayed ...PSMA) (35). Substrate phage can be created either as a monovalent or as pentavalent display (34). Both approaches have their own advantages and

Structural optimization of diphenylpyrimidine derivatives (DPPYs) as potent Bruton's tyrosine kinase (BTK) inhibitors with improved activity toward B leukemia cell lines.

PubMed

Zhao, Dan; Huang, Shanshan; Qu, Menghua; Wang, Changyuan; Liu, Zhihao; Li, Zhen; Peng, Jinyong; Liu, Kexin; Li, Yanxia; Ma, Xiaodong; Shu, Xiaohong

2017-01-27

A new series of diphenylpyrimidine derivatives (DPPYs) bearing various aniline side chains at the C-2 position of pyrimidine core were synthesized as potent BTK inhibitors. Most of these inhibitors displayed improved activity against B leukemia cell lines compared with lead compound spebrutinib. Subsequent studies showed that the peculiar inhibitor 7j, with IC 50 values of 10.5 μM against Ramos cells and 19.1 μM against Raji cells, also displayed slightly higher inhibitory ability than the novel agent ibrutinib. Moreover, compound 7j is not sensitive to normal cells PBMC, indicating low cell cytotoxicity. In addition, flow cytometry analysis indicated that 7j significantly induced the apoptosis of Ramos cells, and arrested the cell cycle at the G0/G1 phase. These explorations provided new clues to discover pyrimidine scaffold as more effective BTK inhibitors. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Thermosensitive polymer stabilized core-shell AuNR@Ag nanostructures as "smart" recyclable catalyst

NASA Astrophysics Data System (ADS)

Li, Dongxiang; Liu, Na; Gao, Yuanyuan; Lin, Weihong; Li, Chunfang

2017-11-01

Core-shell AuNR@Ag nanostructures were synthesized and surface-grafted with thermosensitive poly( N-isopropylacrylamide) to enhance stability and endow stimuli-responsive property. The AuNR cores showed average dimensions of 8-nm diameter and 33-nm length, while the anisotropic silver shells displayed 1-2 nm thin side and maximal 8 nm fat side. The obtained polymer-stabilized AuNR@Ag nanostructures as catalysts showed normal Arrhenius change of apparent rate constant, k app, in catalyzed reaction between 20 and 30 °C, but displayed a decrease of k app with respect to the temperature increasing between 32.5-40 °C, showing self-inhibition of the observed catalytic activity. Such "smart" self-inhibition of catalytic activity at enhanced temperature can be attributed to the thermosensitive response of the grafted polymer molecules and should be significant to control the reaction rate and avoid superheat for exothermic reactions. Such polymer-stabilized nanocatalyst also could be recovered and reused in the catalytic system. [Figure not available: see fulltext.

Physiological correlates of emotional reactivity and regulation in early adolescents.

PubMed

Latham, Melissa D; Cook, Nina; Simmons, Julian G; Byrne, Michelle L; Kettle, Jonathan W L; Schwartz, Orli; Vijayakumar, Nandita; Whittle, Sarah; Allen, Nicholas B

2017-07-01

Few studies have examined physiological correlates of emotional reactivity and regulation in adolescents, despite the occurrence in this group of significant developmental changes in emotional functioning. The current study employed multiple physiological measures (i.e., startle-elicited eyeblink and ERP, skin conductance, facial EMG) to assess the emotional reactivity and regulation of 113 early adolescents in response to valenced images. Reactivity was measured while participants viewed images, and regulation was measured when they were asked to discontinue or maintain their emotional reactions to the images. Adolescent participants did not exhibit fear-potentiated startle blink. However, they did display affect-consistent zygomatic and corrugator activity during reactivity, as well as inhibition of some of these facial patterns during regulation. Skin conductance demonstrated arousal dependent activity during reactivity, and overall decreases during regulation. These findings suggest that early adolescents display reactivity to valenced pictures, but not to startle probes. Psychophysiological patterns during emotion regulation indicate additional effort and/or attention during the regulation process. Copyright © 2017 Elsevier B.V. All rights reserved.

Identification of the Human SULT Enzymes Involved in the Metabolism of Rotigotine.

PubMed

Jia, Chaojun; Luo, Lijun; Kurogi, Katsuhisa; Yu, Juming; Zhou, Chunyang; Liu, Ming-Cheh

2016-06-01

Sulfation has been reported to be a major pathway for the metabolism and inactivation of rotigotine in vivo. The current study aimed to identify the human cytosolic sulfotransferase (SULT) enzyme(s) capable of mediating the sulfation of rotigotine. Of the 13 known human SULTs examined, 6 of them (SULT1A1, 1A2, 1A3, 1B1, 1C4, 1E1) displayed significant sulfating activities toward rotigotine. pH dependence and kinetic parameters of the sulfation of rotigotine by relevant human SULTs were determined. Of the 6 human organ samples tested, small intestine and liver cytosols displayed considerably higher rotigotine-sulfating activity than did brain, lung, and kidney. Moreover, sulfation of rotigotine was shown to occur in HepG2 human hepatoma cells and Caco-2 human colon adenocarcinoma cells under metabolic conditions. Collectively, the results obtained provided a molecular basis underlying the previous finding of the excretion of sulfated rotigotine by patients undergoing treatment with rotigotine. © 2015, The American College of Clinical Pharmacology.

Detectability of BI-RADS category 3 or higher breast lesions and reading time on mammography: comparison between 5-MP and 8-MP LCD monitors.

PubMed

Yabuuchi, Hidetake; Kawanami, Satoshi; Kamitani, Takeshi; Matsumura, Tomomi; Yamasaki, Yuzo; Morishita, Junji; Honda, Hiroshi

2017-04-01

Background Five-megapixel (MP) displays are recommended as soft copy devices for digital mammogram. An 8-MP liquid crystal display (LCD) (two 4-MP displays within one display) might offer the advantage of being able to view biplane mammography more easily than the dual planes of 5-MP LCDs. Purpose To compare detectability of Breast Imaging Reporting and Data System (BI-RADS) category 3 or higher lesions and reading time on mammography between 5- MP and 8-MP LCDs. Material and Methods The mammograms of 240 breasts of 120 patients including 60 breasts with BI-RADS category 3 or higher lesions and 180 breasts with normal or category 2 lesions were enrolled. All bilateral mammograms were displayed on bifacial 5-MP LCDs or an 8-MP LCD (two 4-MP displays within one display). Six radiologists assessed 240 breasts on each display. The observations were analyzed using receiver operating characteristic (ROC) analysis. A jack-knife method was used for statistical analysis. We employed a paired t-test to determine whether any significant differences existed in the reading time between two different displays. A P value < 0.05 was considered significant. Results The mean areas under the ROC curve obtained using 5-MP and 8-MP LCDs were 0.925 and 0.915, respectively, and there was no significant difference ( P = 0.46). There was also no significant difference in the reading time between two types of displays (57.8 min. vs. 51.5 min, P = 0.39). Conclusion The detectability of BI-RADS category 3 or higher lesions and reading time using an 8-MP LCD were comparable to those using a 5-MP LCD.

Regional brain changes in bipolar I depression: a functional magnetic resonance imaging study

PubMed Central

Altshuler, Lori; Bookheimer, Susan; Townsend, Jennifer; Proenza, Manuel A; Sabb, Fred; Mintz, Jim; Cohen, Mark S

2011-01-01

Objective To investigate neural activity in prefrontal cortex and amygdala during bipolar depression. Methods Eleven bipolar I depressed and 17 normal subjects underwent functional magnetic resonance imaging (fMRI) while performing a task known to activate prefrontal cortex and amygdala. Whole brain activation patterns were determined using statistical parametric mapping (SPM) when subjects matched faces displaying neutral or negative affect (match condition) or matched a geometric form (control condition). Contrasts for each group for the match versus control conditions were used in a second-level random effects analysis. Results Random effects between-group analysis revealed significant attenuation in right and left orbitofrontal cortex (BA47) and right dorsolateral prefrontal cortex (DLPFC) (BA9) in bipolar depressed subjects. Additionally, random effects analysis showed a significantly increased activation in left lateral orbitofrontal cortex (BA10) in the bipolar depressed versus control subjects. Within-group contrasts demonstrated significant amygdala activation in the controls and no significant amygdala activation in the bipolar depressed subjects. The amygdala between-group difference, however, was not significant. Conclusions Bipolar depression is associated with attenuated bilateral orbitofrontal (BA47) activation, attenuated right DLPFC (BA9) activation and heightened left orbitofrontal (BA10) activation. BA47 attenuation has also been reported in mania and may thus represent a trait feature of the disorder. Increased left prefrontal (BA10) activation may be a state marker to bipolar depression. Our findings suggest dissociation between mood-dependent and disease-dependent functional brain abnormalities in bipolar disorder. PMID:18837865

A tactual display aid for primary flight training

NASA Technical Reports Server (NTRS)

Gilson, R. D.

1979-01-01

A means of flight instruction is discussed. In addition to verbal assistance, control feedback was continously presented via a nonvisual means utilizing touch. A kinesthetic-tactile (KT) display was used as a readout and tracking device for a computer generated signal of desired angle of attack during the approach and landing. Airspeed and glide path information was presented via KT or visual heads up display techniques. Performance with the heads up display of pitch information was shown to be significantly better than performance with the KT pitch display. Testing without the displays showed that novice pilots who had received tactile pitch error information performed both pitch and throttle control tasks significantly better than those who had received the same information from the visual heads up display of pitch during the test series of approaches to landing.

Ferrocenyl chalcone difluoridoborates inhibit HIV-1 integrase and display low activity towards cancer and endothelial cells.

PubMed

Monserrat, Jean-Philippe; Al-Safi, Rasha I; Tiwari, Keshri Nath; Quentin, Lionel; Chabot, Guy G; Vessières, Anne; Jaouen, Gérard; Neamati, Nouri; Hillard, Elizabeth A

2011-10-15

We report here the discovery of a potent series of HIV-1 integrase (IN) inhibitors based on the ferrocenyl chalcone difluoridoborate structure. Ten new compounds have been synthesized and were generally found to have similar inhibitory activities against the IN 3' processing and strand transfer (ST) processes. IC(50) values were found to be in the low micromolar range, and significantly lower than those found for the non-coordinated ferrocenyl chalcones and other ferrocene molecules. The ferrocenyl chalcone difluoridoborates furthermore exhibited low cytotoxicity against cancer cells and low morphological activity against epithelial cells. Copyright © 2011 Elsevier Ltd. All rights reserved.

Novel 4-(4-substituted-thiazol-2-ylamino)-N-(pyridin-2-yl)-benzenesulfonamides as cytotoxic and radiosensitizing agents.

PubMed

Ghorab, Mostafa M; Ragab, Fatma A; Heiba, Helmy I; Agha, Hebaallah M; Nissan, Yassin M

2012-01-01

A series of novel 4-(4-substituted-thiazol-2-ylamino)-N-(pyridin-2-yl) benzene-sulfonamides were synthesized and screened for their cytotoxic activity against human breast cancer cell line (MCF-7). Compounds 6, 7, 9, 10, 11, and 14 displayed significant activity against MCF-7 when compared to doxorubicin, which was used as a reference drug. The synergistic effect of Gamma radiation for the most active derivatives 7, 9, and 11 was also studied and their IC(50) values markedly decreased to 11.9 μM, 11.7 μM, and 11.6 μM, respectively.

Qualitative changes in human γ-secretase underlie familial Alzheimer’s disease

PubMed Central

Szaruga, Maria; Veugelen, Sarah; Benurwar, Manasi; Lismont, Sam; Sepulveda-Falla, Diego; Lleo, Alberto; Ryan, Natalie S.; Lashley, Tammaryn; Fox, Nick C.; Murayama, Shigeo; Gijsen, Harrie

2015-01-01

Presenilin (PSEN) pathogenic mutations cause familial Alzheimer’s disease (AD [FAD]) in an autosomal-dominant manner. The extent to which the healthy and diseased alleles influence each other to cause neurodegeneration remains unclear. In this study, we assessed γ-secretase activity in brain samples from 15 nondemented subjects, 22 FAD patients harboring nine different mutations in PSEN1, and 11 sporadic AD (SAD) patients. FAD and control brain samples had similar overall γ-secretase activity levels, and therefore, loss of overall (endopeptidase) γ-secretase function cannot be an essential part of the pathogenic mechanism. In contrast, impaired carboxypeptidase-like activity (γ-secretase dysfunction) is a constant feature in all FAD brains. Significantly, we demonstrate that pharmacological activation of the carboxypeptidase-like γ-secretase activity with γ-secretase modulators alleviates the mutant PSEN pathogenic effects. Most SAD cases display normal endo- and carboxypeptidase-like γ-secretase activities. However and interestingly, a few SAD patient samples display γ-secretase dysfunction, suggesting that γ-secretase may play a role in some SAD cases. In conclusion, our study highlights qualitative shifts in amyloid-β (Aβ) profiles as the common denominator in FAD and supports a model in which the healthy allele contributes with normal Aβ products and the diseased allele generates longer aggregation-prone peptides that act as seeds inducing toxic amyloid conformations. PMID:26481686

Requirements for AMLCDs in U.S. military applications

NASA Astrophysics Data System (ADS)

Hopper, Darrel G.; Desjardins, Daniel D.

1995-06-01

Flat panel displays are fast becoming a significant source of more defense for less money. Military instruments have begun to use color active matrix liquid crystal displays (AMLCDs). This is the beginning of a significant transition from electromechanical, CRT. dichroic LCD, and electroluminescent display designs to the AMLCD designs. We have the opportunity with this new technology to establish common products capable of meeting user requirements for sunlight-readable, color and grayscale capable, high-sharpness high-pixel count, flat panel displays for military applications. The Wright Laboratory is leading the development of recommended best practice, draft guidance standard, and performance specifications for this new generation, the flat panel cockpit display generation, of display modules based on requirements for U.S. military aircraft and ground combat human system interfaces. These requirements are similar in many regards to those in both the civil aviation and automotive industries; accordingly, commonality with these civil applications is incorporated where possible, against the requirements for military combat applications. The performance requirement may be achieved by two approaches: militarization of displays made to low requirements of a large volume civil products manufacturer like Sharp or integration of displays made to high requirements by a niche market commercial vendor, like Optical Imaging Systems, Litton Systems Limited, ImageQuest Inc., and Planar Advanced Inc. teamed with Xerox PARC and Standish Industries. [Note that the niche market companies listed are commercial off-the shelf vendors, albeit for high requirement low volume customers.] Given that the performance specifications can be met for a particular military product by either approach, the choice is based on life cycle cost and a thin analysis based on initial costs alone is not acceptable as it ignores the fact that military product life cycles and procurements are 20-60 years compared to 1.5 years for civil products. Thus far there is no convincing evidence that the large volume commercial product approach for combat systems will meet the combat performance specification or be cheaper from a life cycle cost perspective. National and economic security requirements require some military/avionic-grade AMLCD production domestically (i.e. in the U.S. and/or Canada). Examples of AMLCD demand and performance requirements in U.S. military systems are provided.

Dynamic stereotypic responses of Basal Ganglia neurons to subthalamic nucleus high-frequency stimulation in the parkinsonian primate.

PubMed

Moran, Anan; Stein, Edward; Tischler, Hadass; Belelovsky, Katya; Bar-Gad, Izhar

2011-01-01

Deep brain stimulation (DBS) in the subthalamic nucleus (STN) is a well-established therapy for patients with severe Parkinson's disease (PD); however, its mechanism of action is still unclear. In this study we explored static and dynamic activation patterns in the basal ganglia (BG) during high-frequency macro-stimulation of the STN. Extracellular multi-electrode recordings were performed in primates rendered parkinsonian using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Recordings were preformed simultaneously in the STN and the globus pallidus externus and internus. Single units were recorded preceding and during the stimulation. During the stimulation, STN mean firing rate dropped significantly, while pallidal mean firing rates did not change significantly. The vast majority of neurons across all three nuclei displayed stimulation driven modulations, which were stereotypic within each nucleus but differed across nuclei. The predominant response pattern of STN neurons was somatic inhibition. However, most pallidal neurons demonstrated synaptic activation patterns. A minority of neurons across all nuclei displayed axonal activation. Temporal dynamics were observed in the response to stimulation over the first 10 seconds in the STN and over the first 30 seconds in the pallidum. In both pallidal segments, the synaptic activation response patterns underwent delay and decay of the magnitude of the peak response due to short term synaptic depression. We suggest that during STN macro-stimulation the STN goes through a functional ablation as its upper bound on information transmission drops significantly. This notion is further supported by the evident dissociation between the stimulation driven pre-synaptic STN somatic inhibition and the post-synaptic axonal activation of its downstream targets. Thus, BG output maintains its firing rate while losing the deleterious effect of the STN. This may be a part of the mechanism leading to the beneficial effect of DBS in PD.

Heart rate and heart rate variability response to the transpiration of vortex-water by Begonia Eliator plants to the air in an office during visual display terminal work.

PubMed

Johansson, Benny

2008-10-01

This study explores the effects of vortex-water transpired from indoor greenery to office air, in relation to heart rate and heart rate variability during exposure to an electromagnetic field (EMF) from a visual display terminal (VDT). The study followed a randomized prospective single group cross-over design. Fifty (50) healthy volunteers, seated in any ordinary working posture in front of a VDT. Electrocardiography was measured in five 10-minute sequential tests. The VDT was turned off during the first test and switched on for the subsequent four tests. During tests 3 and 4, one of two Begonia Eliator plants, irrigated with either tap water or vortex-rotated (active) tap water during growth, was placed adjacent to the VDT. Heart rate, heart rate variability (HRV) and power spectral density (PSD) were analyzed. The heart rate was unchanged at the start of EMF exposure. The time domain measurements indicated a significant decrease in heart rate and a significant increase in HRV, accompanied by higher vagal tone in the presence, and finally in the absence, of the active plant. PSD parameters revealed significantly higher total power, as well as an increase in low frequencies (LF) and high frequencies (HF) in the condition induced by the active plant as well as after its removal. Very low frequencies (VLF) increased at EMF exposure whereas normally HF power decreased, accompanied by a rise in LF power and LF/HF ratio. HF power was higher at exposure to the active compared to the control plant. Spectral power density diagrams revealed an intensified spectral power band at frequencies of around 0.1 Hz at the condition of both plants, indicating systemic autonomic stability. The findings suggest that the parasympathetic response was associated with reduced heart rate, implicating restoration and maintenance of metabolic energy resources mediated by an involuntary adaptation to active plant-related stimuli.

Infant brain activity while viewing facial movement of point-light displays as measured by near-infrared spectroscopy (NIRS).

PubMed

Ichikawa, Hiroko; Kanazawa, So; Yamaguchi, Masami K; Kakigi, Ryusuke

2010-09-27

Adult observers can quickly identify specific actions performed by an invisible actor from the points of lights attached to the actor's head and major joints. Infants are also sensitive to biological motion and prefer to see it depicted by a dynamic point-light display. In detecting biological motion such as whole body and facial movements, neuroimaging studies have demonstrated the involvement of the occipitotemporal cortex, including the superior temporal sulcus (STS). In the present study, we used the point-light display technique and near-infrared spectroscopy (NIRS) to examine infant brain activity while viewing facial biological motion depicted in a point-light display. Dynamic facial point-light displays (PLD) were made from video recordings of three actors making a facial expression of surprise in a dark room. As in Bassili's study, about 80 luminous markers were scattered over the surface of the actor's faces. In the experiment, we measured infant's hemodynamic responses to these displays using NIRS. We hypothesized that infants would show different neural activity for upright and inverted PLD. The responses were compared to the baseline activation during the presentation of individual still images, which were frames extracted from the dynamic PLD. We found that the concentration of oxy-Hb increased in the right temporal area during the presentation of the upright PLD compared to that of the baseline period. This is the first study to demonstrate that infant's brain activity in face processing is induced only by the motion cue of facial movement depicted by dynamic PLD. (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Antioxidant activity and phenol content of extracts of bark, stems, and young and mature leaves from Blepharocalyx salicifolius (Kunth) O. Berg.

PubMed

Habermann, E; Imatomi, M; Pontes, F C; Gualtieri, S C J

2016-01-01

Phenolic compounds are a group of plant secondary metabolites known to have a variety of bioactivities, including the ability to function as antioxidants. Because of the side effects of the use of synthetic substances, the search for natural and less toxic compounds has increased significantly. This study was designed to evaluate the antioxidant activity and phenol content of hexane, ethyl acetate, and aqueous extracts of the bark (suber) and stems as well as the young and mature leaves of Blepharocalyx salicifolius. The extracts were obtained by extraction with organic solvents and subsequent fractionation by chromatographic partition coefficient. Preliminary tests for the presence of antioxidants were performed using bioautography in thin-layer chromatography. The antioxidant activity of the extracts was assessed using the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method, and the phenol content of the extracts was quantified using the Folin-Ciocalteu technique. The results showed that 9 of the 12 extracts evaluated displayed very strong antioxidant activity and three displayed moderate activity. Aqueous extracts of the young leaves and bark and the ethyl acetate extract of the young leaves showed the highest levels of antioxidant activity and total phenolic content (TPC). A correlation was observed between TPC and antioxidant activity index (AAI) with a correlation coefficient (r2) of 0.7999. Thus, the high phenol content of B. salicifolius extracts and its correlation with antioxidant activity provide substrates for further studies.

A Study of the Behavior of Children in a Preschool Equipped with Computers.

ERIC Educational Resources Information Center

Klinzing, Dene G.

A study was conducted: (1) to compare the popularity of computer stations with nine other activity stations; (2) to determine the differences in the type of play displayed by the children in preschool and note the type of play displayed at the computer stations versus the other activity stations; (3) to determine whether the preschool activities,…

ADST Software Design Document for the BDS-D VIDS-equipped M1

DTIC Science & Technology

1993-09-10

system responds to perceived threats in the following ways:I a. by displaying visual icons on the Commander’s Controls Display Panel (CCDP). b. by...also referred to as the Soldier Machine Interface (SMI) and the Commander’s Controls Display Panel (CCDP). 3.2.1. VIDS-GT CSC The VIDS-GT CSC handles...countermeasure will be activated first in Individual_CM_Simul. 4.1.3.4.3. IndividualCMSimul CSU IndividualCM-Simul controls the activation and deactivation of

Current Status Of Ergonomic Standards

NASA Astrophysics Data System (ADS)

Lynch, Gene

1984-05-01

The last five years have seen the development and adoption of new kinds of standards for the display industry. This standardization activity deals with the complex human computer interface. Here the concerns involve health, safety, productivity, and operator well-being. The standards attempt to specify the "proper" use of visual display units. There is a wide range of implications for the display industry - as manufacturers of displays, as employers, and as users of visual display units. In this paper we examine the development of these standards, their impact on the display industry and implications for the future.

Plasticity Beyond V1: Reinforcement of Motion Perception upon Binocular Central Retinal Lesions in Adulthood.

PubMed

Burnat, Kalina; Hu, Tjing-Tjing; Kossut, Małgorzata; Eysel, Ulf T; Arckens, Lutgarde

2017-09-13

Induction of a central retinal lesion in both eyes of adult mammals is a model for macular degeneration and leads to retinotopic map reorganization in the primary visual cortex (V1). Here we characterized the spatiotemporal dynamics of molecular activity levels in the central and peripheral representation of five higher-order visual areas, V2/18, V3/19, V4/21a,V5/PMLS, area 7, and V1/17, in adult cats with central 10° retinal lesions (both sexes), by means of real-time PCR for the neuronal activity reporter gene zif268. The lesions elicited a similar, permanent reduction in activity in the center of the lesion projection zone of area V1/17, V2/18, V3/19, and V4/21a, but not in the motion-driven V5/PMLS, which instead displayed an increase in molecular activity at 3 months postlesion, independent of visual field coordinates. Also area 7 only displayed decreased activity in its LPZ in the first weeks postlesion and increased activities in its periphery from 1 month onward. Therefore we examined the impact of central vision loss on motion perception using random dot kinematograms to test the capacity for form from motion detection based on direction and velocity cues. We revealed that the central retinal lesions either do not impair motion detection or even result in better performance, specifically when motion discrimination was based on velocity discrimination. In conclusion, we propose that central retinal damage leads to enhanced peripheral vision by sensitizing the visual system for motion processing relying on feedback from V5/PMLS and area 7. SIGNIFICANCE STATEMENT Central retinal lesions, a model for macular degeneration, result in functional reorganization of the primary visual cortex. Examining the level of cortical reactivation with the molecular activity marker zif268 revealed reorganization in visual areas outside V1. Retinotopic lesion projection zones typically display an initial depression in zif268 expression, followed by partial recovery with postlesion time. Only the motion-sensitive area V5/PMLS shows no decrease, and even a significant activity increase at 3 months post-retinal lesion. Behavioral tests of motion perception found no impairment and even better sensitivity to higher random dot stimulus velocities. We demonstrate that the loss of central vision induces functional mobilization of motion-sensitive visual cortex, resulting in enhanced perception of moving stimuli. Copyright © 2017 the authors 0270-6474/17/378989-11$15.00/0.

Attentional priorities and access to short-term memory: parietal interactions.

PubMed

Gillebert, Céline R; Dyrholm, Mads; Vangkilde, Signe; Kyllingsbæk, Søren; Peeters, Ronald; Vandenberghe, Rik

2012-09-01

The intraparietal sulcus (IPS) has been implicated in selective attention as well as visual short-term memory (VSTM). To contrast mechanisms of target selection, distracter filtering, and access to VSTM, we combined behavioral testing, computational modeling and functional magnetic resonance imaging. Sixteen healthy subjects participated in a change detection task in which we manipulated both target and distracter set sizes. We directly compared the IPS response as a function of the number of targets and distracters in the display and in VSTM. When distracters were not present, the posterior and middle segments of IPS showed the predicted asymptotic activity increase with an increasing target set size. When distracters were added to a single target, activity also increased as predicted. However, the addition of distracters to multiple targets suppressed both middle and posterior IPS activities, thereby displaying a significant interaction between the two factors. The interaction between target and distracter set size in IPS could not be accounted for by a simple explanation in terms of number of items accessing VSTM. Instead, it led us to a model where items accessing VSTM receive differential weights depending on their behavioral relevance, and secondly, a suppressive effect originates during the selection phase when multiple targets and multiple distracters are simultaneously present. The reverse interaction between target and distracter set size was significant in the right temporoparietal junction (TPJ), where activity was highest for a single target compared to any other condition. Our study reconciles the role of middle IPS in attentional selection and biased competition with its role in VSTM access. Copyright © 2012 Elsevier Inc. All rights reserved.

The sodium pump α1 sub-unit: a disease progression–related target for metastatic melanoma treatment

PubMed Central

Mathieu, Véronique; Pirker, Christine; Martin de Lassalle, Elisabeth; Vernier, Mathieu; Mijatovic, Tatjana; DeNeve, Nancy; Gaussin, Jean-François; Dehoux, Mischael; Lefranc, Florence; Berger, Walter; Kiss, Robert

2009-01-01

Melanomas remain associated with dismal prognosis because they are naturally resistant to apoptosis and they markedly metastasize. Up-regulated expression of sodium pump α sub-units has previously been demonstrated when comparing metastatic to non-metastatic melanomas. Our previous data revealed that impairing sodium pump α1 activity by means of selective ligands, that are cardiotonic steroids, markedly impairs cell migration and kills apoptosis-resistant cancer cells. The objective of this study was to determine the expression levels of sodium pump α sub-units in melanoma clinical samples and cell lines and also to characterize the role of α1 sub-units in melanoma cell biology. Quantitative RT-PCR, Western blotting and immunohistochemistry were used to determine the expression levels of sodium pump α sub-units. In vitro cytotoxicity of various cardenolides and of an anti-α1 siRNA was evaluated by means of MTT assay, quantitative videomicroscopy and through apoptosis assays. The in vivo activity of a novel cardenolide UNBS1450 was evaluated in a melanoma brain metastasis model. Our data show that all investigated human melanoma cell lines expressed high levels of the α1 sub-unit, and 33% of human melanomas displayed significant α1 sub-unit expression in correlation with the Breslow index. Furthermore, cardenolides (notably UNBS1450; currently in Phase I clinical trials) displayed marked anti-tumour effects against melanomas in vitro. This activity was closely paralleled by decreases in cMyc expression and by increases in apoptotic features. UNBS1450 also displayed marked anti-tumour activity in the aggressive human metastatic brain melanoma model in vivo. The α1 sodium pump sub-unit could represent a potential novel target for combating melanoma. PMID:19243476

Targeted overexpression of Tumor Necrosis Factor-α increases Cyclin-dependent kinase 5 activity and TRPV1-dependent Ca2+ influx in trigeminal neurons

PubMed Central

Rozas, Pablo; Lazcano, Pablo; Piña, Ricardo; Cho, Andrew; Terse, Anita; Pertusa, Maria; Madrid, Rodolfo; Gonzalez-Billault, Christian; Kulkarni, Ashok B.; Utreras, Elias

2016-01-01

We reported earlier that TNF-α, a proinflammatory cytokine implicated in many inflammatory disorders causing orofacial pain increases Cdk5 activity, a key kinase involved in brain development and function and recently in pain signaling. To investigate a potential mechanism underlying inflammatory pain in trigeminal ganglia (TG), we engineered a transgenic mouse model (TNFglo) that can conditionally overexpresses TNF-α upon genomic recombination by Cre recombinase. TNFglo mice were bred with Nav1.8-Cre mouse line that expresses the Cre recombinase in sensory neurons to obtain TNF-α:Nav1.8-Cre (TNF-α cTg) mice. Although TNF-α cTg mice appeared normal without any gross phenotype, they displayed a significant increase in TNF-α levels after activation of NFκB signaling in the TG. IL-6 and MCP-1 levels were also increased along with intense immunostaining for Iba1 and GFAP in TG, indicating the presence of infiltrating macrophages and the activation of satellite glial cells. TNF-α cTg mice displayed increased trigeminal Cdk5 activity, and this increase was associated with elevated levels of phospho-T407-TRPV1 and capsaicin-evocated Ca2+ influx in cultured trigeminal neurons. Remarkably, this effect was prevented by roscovitine, an inhibitor of Cdk5, suggesting that TNF-α overexpression induced sensitization of the TRPV1 channel. Furthermore, TNF-α cTg mice displayed more aversive behavior to noxious thermal stimulation (45°C) of the face in an operant pain assessment device as compared with control mice. In summary, TNF-α overexpression in the sensory neurons of TNF-α cTg mice results in inflammatory sensitization and increased Cdk5 activity, therefore this mouse model would be valuable for investigating mechanism involved TNF-α in orofacial pain. PMID:26894912

T cells in chronic lymphocytic leukemia display dysregulated expression of immune checkpoints and activation markers.

PubMed

Palma, Marzia; Gentilcore, Giusy; Heimersson, Kia; Mozaffari, Fariba; Näsman-Glaser, Barbro; Young, Emma; Rosenquist, Richard; Hansson, Lotta; Österborg, Anders; Mellstedt, Håkan

2017-03-01

Chronic lymphocytic leukemia is characterized by impaired immune functions largely due to profound T-cell defects. T-cell functions also depend on co-signaling receptors, inhibitory or stimulatory, known as immune checkpoints, including cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed death-1 (PD-1). Here we analyzed the T-cell phenotype focusing on immune checkpoints and activation markers in chronic lymphocytic leukemia patients (n=80) with different clinical characteristics and compared them to healthy controls. In general, patients had higher absolute numbers of CD3 + cells and the CD8 + subset was particularly expanded in previously treated patients. Progressive patients had higher numbers of CD4 + and CD8 + cells expressing PD-1 compared to healthy controls, which was more pronounced in previously treated patients ( P =0.0003 and P =0.001, respectively). A significant increase in antigen-experienced T cells was observed in patients within both the CD4 + and CD8 + subsets, with a significantly higher PD-1 expression. Higher numbers of CD4 + and CD8 + cells with intracellular CTLA-4 were observed in patients, as well as high numbers of proliferating (Ki67 + ) and activated (CD69 + ) CD4 + and CD8 + cells, more pronounced in patients with active disease. The numbers of Th1, Th2, Th17 and regulatory T cells were substantially increased in patients compared to controls ( P <0.05), albeit decreasing to low levels in pre-treated patients. In conclusion, chronic lymphocytic leukemia T cells display increased expression of immune checkpoints, abnormal subset distribution, and a higher proportion of proliferating cells compared to healthy T cells. Disease activity and previous treatment shape the T-cell profile of chronic lymphocytic leukemia patients in different ways. Copyright© Ferrata Storti Foundation.

Phage protein-targeted cancer nanomedicines

PubMed Central

Petrenko, V.A.; Jayanna, P.K.

2015-01-01

Nanoencapsulation of anticancer drugs improves their therapeutic indices by virtue of the enhanced permeation and retention effect which achieves passive targeting of nanoparticles in tumors. This effect can be significantly enhanced by active targeting of nanovehicles to tumors. Numerous ligands have been proposed and used in various studies with peptides being considered attractive alternatives to antibodies. This is further reinforced by the availability of peptide phage display libraries which offer an unlimited reservoir of target-specific probes. In particular landscape phages with multivalent display of target-specific peptides which enable the phage particle itself to become a nanoplatform creates a paradigm for high throughput selection of nanoprobes setting the stage for personalized cancer management. Despite its promise, this conjugate of combinatorial chemistry and nanotechnology has not made a significant clinical impact in cancer management due to a lack of using robust processes that facilitate scale-up and manufacturing. To this end we proposed the use of phage fusion protein as the navigating modules of novel targeted nanomedicine platforms which are described in this review. PMID:24269681

Functional display of family 11 endoxylanases on the surface of phage M13.

PubMed

Beliën, T; Hertveldt, K; Van den Brande, K; Robben, J; Van Campenhout, S; Volckaert, G

2005-02-09

Two family 11 endoxylanases (EC 3.2.1.8) were functionally displayed on the surface of bacteriophage M13. The genes encoding endo-1,4-xylanase I from Aspergillus niger (ExlA) and endo-1,4-xylanase A from Bacillus subtilis (XynA) were fused to the gene encoding the minor coat protein g3p in phagemid vector pHOS31. Phage rescue resulted in functional monovalent display of the enzymes as was demonstrated by three independent tests. Firstly, purified recombinant phage particles showed a clear hydrolytic activity in an activity assay based on insoluble, chromagenic arabinoxylan substrate. Secondly, specific binding of endoxylanase displaying phages to immobilized endoxylanase inhibitors was demonstrated by interaction ELISA. Finally, two rounds of selection and amplification in a biopanning procedure against immobilized endoxylanase inhibitor were performed. Phages displaying endoxylanases were strongly enriched from background phages displaying unrelated proteins. These results open perspectives to use phage display for analysing protein-protein interactions at the interface between endoxylanases and their inhibitors. In addition, this technology should enable engineering of endoxylanases into novel variants with altered binding properties towards endoxylanase inhibitors.

39 CFR 447.42 - Additional prohibited political activities.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Section 447.42 Postal Service UNITED STATES POSTAL SERVICE PERSONNEL RULES OF CONDUCT FOR POSTAL EMPLOYEES... restrictions on political activities mentioned in § 447.51, an employee may not: (1) Display a political... paragraph, however, from displaying a picture, including a personally autographed picture of a political...

Conflict and performance monitoring throughout the lifespan: An event-related potential (ERP) and temporospatial component analysis.

PubMed

Clawson, Ann; Clayson, Peter E; Keith, Cierra M; Catron, Christina; Larson, Michael J

2017-03-01

Cognitive control includes higher-level cognitive processes used to evaluate environmental conflict. Given the importance of cognitive control in regulating behavior, understanding the developmental course of these processes may contribute to a greater understanding of normal and abnormal development. We examined behavioral (response times [RTs], error rates) and event-related potential data (N2, error-related negativity [ERN], correct-response negativity [CRN], error positivity [Pe]) during a flanker task in cross-sectional groups of 45 youth (ages 8-18), 52 younger adults (ages 20-28), and 58 older adults (ages 56-91). Younger adults displayed the most efficient processing, including significantly reduced CRN and N2 amplitude, increased Pe amplitude, and significantly better task performance than youth or older adults (e.g., faster RTs, fewer errors). Youth displayed larger CRN and N2, attenuated Pe, and significantly worse task performance than younger adults. Older adults fell either between youth and younger adults (e.g., CRN amplitudes, N2 amplitudes) or displayed neural and behavioral performance that was similar to youth (e.g., Pe amplitudes, error rates). These findings point to underdeveloped neural and cognitive processes early in life and reduced efficiency in older adulthood, contributing to poor implementation and modulation of cognitive control in response to conflict. Thus, cognitive control processing appears to reach peak performance and efficiency in younger adulthood, marked by improved task performance with less neural activation. Copyright © 2017 Elsevier B.V. All rights reserved.

Proteasome inhibitory, antioxidant, and synergistic antibacterial and anticandidal activity of green biosynthesized magnetic Fe3O4 nanoparticles using the aqueous extract of corn (Zea mays L.) ear leaves.

PubMed

Patra, Jayanta Kumar; Ali, Md Sarafat; Oh, In-Gyung; Baek, Kwang-Hyun

2017-03-01

Herein, Fe 3 O 4 nanoparticles synthesized using aqueous extract of corn ear leaves were investigated for proteasome inhibitory activity, antioxidant activity, synergistic antibacterial, and anticandidal potential. The UV-Vis spectrum displayed an absorption band at 355 nm that indicated the formation of nano-sized Fe 3 O 4 particles. Vibrating sample magnetometer analysis revealed its superparamagnetic nature. Fe 3 O 4 nanoparticles exhibited strong proteasome inhibitory potential and antioxidant activity and exerted strong synergistic antibacterial and anticandidal activity. Its significant proteasome inhibitory potential could be useful in cancer treatment and drug delivery. Furthermore, strong antioxidant, antibacterial, and anticandidal activity make them a promising candidate for biomedical and pharmaceutical applications.

Pregnanolone Glutamate, a Novel Use-Dependent NMDA Receptor Inhibitor, Exerts Antidepressant-Like Properties in Animal Models.

PubMed

Holubova, Kristina; Nekovarova, Tereza; Pistovcakova, Jana; Sulcova, Alexandra; Stuchlík, Ales; Vales, Karel

2014-01-01

A number of studies demonstrated a rapid onset of an antidepressant effect of non-competitive N-methyl-d-aspartic acid receptor (NMDAR) antagonists. Nonetheless, its therapeutic potential is rather limited, due to a high coincidence of negative side-effects. Therefore, the challenge seems to be in the development of NMDAR antagonists displaying antidepressant properties, and at the same time maintaining regular physiological function of the NMDAR. Previous results demonstrated that naturally occurring neurosteroid 3α5β-pregnanolone sulfate shows pronounced inhibitory action by a use-dependent mechanism on the tonically active NMDAR. The aim of the present experiments is to find out whether the treatment with pregnanolone 3αC derivatives affects behavioral response to chronic and acute stress in an animal model of depression. Adult male mice were used throughout the study. Repeated social defeat and forced swimming tests were used as animal models of depression. The effect of the drugs on the locomotor/exploratory activity in the open-field test was also tested together with an effect on anxiety in the elevated plus maze. Results showed that pregnanolone glutamate (PG) did not induce hyperlocomotion, whereas both dizocilpine and ketamine significantly increased spontaneous locomotor activity in the open field. In the elevated plus maze, PG displayed anxiolytic-like properties. In forced swimming, PG prolonged time to the first floating. Acute treatment of PG disinhibited suppressed locomotor activity in the repeatedly defeated group-housed mice. Aggressive behavior of isolated mice was reduced after the chronic 30-day administration of PG. PG showed antidepressant-like and anxiolytic-like properties in the used tests, with minimal side-effects. Since PG combines GABAA receptor potentiation and use-dependent NMDAR inhibition, synthetic derivatives of neuroactive steroids present a promising strategy for the treatment of mood disorders. -3α5β-pregnanolone glutamate (PG) is a use-dependent antagonist of NMDA receptors.-We demonstrated that PG did not induce significant hyperlocomotion.-We showed that PG displayed anxiolytic-like and antidepressant-like properties.

Symmetrical choline-derived dications display strong anti-kinetoplastid activity

PubMed Central

Ibrahim, Hasan M. S.; Al-Salabi, Mohammed I.; El Sabbagh, Nasser; Quashie, Neils B.; Alkhaldi, Abdulsalam A. M.; Escale, Roger; Smith, Terry K.; Vial, Henri J.; de Koning, Harry P.

2011-01-01

Objectives To investigate the anti-kinetoplastid activity of choline-derived analogues with previously reported antimalarial efficacy. Methods From an existing choline analogue library, seven antimalarial compounds, representative of the first-, second- and third-generation analogues previously developed, were assessed for activity against Trypanosoma and Leishmania spp. Using a variety of techniques, the effects of choline analogue exposure on the parasites were documented and a preliminary investigation of their mode of action was performed. Results The activities of choline-derived compounds against Trypanosoma brucei and Leishmania mexicana were determined. The compounds displayed promising anti-kinetoplastid activity, particularly against T. brucei, to which 4/7 displayed submicromolar EC50 values for the wild-type strain. Low micromolar concentrations of most compounds cleared trypanosome cultures within 24–48 h. The compounds inhibit a choline transporter in Leishmania, but their entry may not depend only on this carrier; T. b. brucei lacks a choline carrier and the mode of uptake remains unclear. The compounds had no effect on the overall lipid composition of the cells, cell cycle progression or cyclic adenosine monophosphate production or short-term effects on intracellular calcium levels. However, several of the compounds, displayed pronounced effects on the mitochondrial membrane potential; this action was not associated with production of reactive oxygen species but rather with a slow rise of intracellular calcium levels and DNA fragmentation. Conclusions The choline analogues displayed strong activity against kinetoplastid parasites, particularly against T. b. brucei. In contrast to their antimalarial activity, they did not act on trypanosomes by disrupting choline salvage or phospholipid metabolism, instead disrupting mitochondrial function, leading to chromosomal fragmentation. PMID:21078603

Antioxidant responses to heat and light stress differ with habitat in a common reef coral

NASA Astrophysics Data System (ADS)

Hawkins, Thomas D.; Krueger, Thomas; Wilkinson, Shaun P.; Fisher, Paul L.; Davy, Simon K.

2015-12-01

Coral bleaching—the stress-induced collapse of the coral- Symbiodinium symbiosis—is a significant driver of worldwide coral reef degradation. Yet, not all corals are equally susceptible to bleaching, and we lack a clear understanding of the mechanisms underpinning their differential susceptibilities. Here, we focus on cellular redox regulation as a potential determinant of bleaching susceptibility in the reef coral Stylophora pistillata. Using slow heating (1 °C d-1) and altered irradiance, we induced bleaching in S. pistillata colonies sampled from two depths [5-8 m (shallow) and 15-18 m (deep)]. There was significant depth-dependent variability in the timing and extent of bleaching (loss of symbiont cells), as well as in host enzymatic antioxidant activity [specifically, superoxide dismutase and catalase (CAT)]. However, among the coral fragments that bleached, most did so without displaying any evidence of a host enzymatic antioxidant response. For example, both deep and shallow corals suffered significant symbiont loss at elevated temperature, but only deep colonies exposed to high temperature and high light displayed any up-regulation of host antioxidant enzyme activity (CAT). Surprisingly, this preceded the equivalent antioxidant responses of the symbiont, which raises questions about the source(s) of hydrogen peroxide in the symbiosis. Overall, changes in enzymatic antioxidant activity in the symbionts were driven primarily by irradiance rather than temperature, and responses were similar across depth groups. Taken together, our results suggest that in the absence of light stress, heating of 1 °C d-1 to 4 °C above ambient is not sufficient to induce a substantial oxidative challenge in S. pistillata. We provide some of the first evidence that regulation of coral enzymatic antioxidants can vary significantly depending on habitat, and, in terms of determining bleaching susceptibility, our results suggest a significant role for the host's differential regulation of cellular redox status.

Understanding the Role of MDSCs in Castration-Resistant Prostate Cancer and Metastasis

DTIC Science & Technology

2015-10-01

Ar+ cells down-regulate Ar expression in the CRPC tumors. Further, a significant amount of normal epithelium was identified in castrated Ptenpc... junction (consistent with their epithelial nature), stromal cells display activation of more diverse signaling pathways involved in chronic...will attend “Faculty Development Workshop and Seminar Series” of MDACC regularly to help me prepare the transition to independent PI. o How were the

Polymeric Smart Skin Materials: Concepts, Materials, and Devices

DTIC Science & Technology

2006-03-31

nanotube actuators for both sensing and active control of surfaces. State-of-the-art OLED and photovoltaic materials have been developed for display...format. 14. SUBJECT TERMS Multi-sensor paints; carbon nanotube materials and devices; OLED , 15. NUMBER OF PAGES nhntovnlthir ndni elp.trAn-nntjc ’vicn...Significant advances in organic light emitting device ( OLED ) materials has also been achieved as is evident from the publications and invention

Negative Symptoms and Avoidance of Social Interaction: A Study of Non-Verbal Behaviour.

PubMed

Worswick, Elizabeth; Dimic, Sara; Wildgrube, Christiane; Priebe, Stefan

2018-01-01

Non-verbal behaviour is fundamental to social interaction. Patients with schizophrenia display an expressivity deficit of non-verbal behaviour, exhibiting behaviour that differs from both healthy subjects and patients with different psychiatric diagnoses. The present study aimed to explore the association between non-verbal behaviour and symptom domains, overcoming methodological shortcomings of previous studies. Standardised interviews with 63 outpatients diagnosed with schizophrenia were videotaped. Symptoms were assessed using the Clinical Assessment Interview for Negative Symptoms (CAINS), the Positive and Negative Syndrome Scale (PANSS) and the Calgary Depression Scale. Independent raters later analysed the videos for non-verbal behaviour, using a modified version of the Ethological Coding System for Interviews (ECSI). Patients with a higher level of negative symptoms displayed significantly fewer prosocial (e.g., nodding and smiling), gesture, and displacement behaviours (e.g., fumbling), but significantly more flight behaviours (e.g., looking away, freezing). No gender differences were found, and these associations held true when adjusted for antipsychotic medication dosage. Negative symptoms are associated with both a lower level of actively engaging non-verbal behaviour and an increased active avoidance of social contact. Future research should aim to identify the mechanisms behind flight behaviour, with implications for the development of treatments to improve social functioning. © 2017 S. Karger AG, Basel.

Aberrant dopamine D2-like receptor function in a rodent model of schizophrenia.

PubMed

Perez, Stephanie M; Lodge, Daniel J

2012-11-01

Based on the observation that antipsychotic medications display antagonist properties at dopamine D2-like receptors, aberrant dopamine signaling has been proposed to underlie psychosis in patients with schizophrenia. Thus, it is not surprising that considerable research has been devoted to understanding the mechanisms involved in the antipsychotic action of these compounds. It is important to note that the majority of these studies have been performed in "normal" experimental animals. Given that these animals do not possess the aberrant neuronal information processing typically associated with schizophrenia, the aim of the current study was to examine the dopamine D2 receptor system in a rodent model of schizophrenia. Here, we demonstrate that methylazoxymethanol acetate (MAM)-treated rats display an enhanced effect of quinpirole on dopamine neuron activity and an aberrant locomotor response to D2-like receptor activation, suggesting changes in postsynaptic D2-like receptor function. To better understand the mechanisms underlying the enhanced response to D2-like ligands in MAM-treated rats, we examined the expression of D2, D3, and dopamine transporter mRNA in the nucleus accumbens and ventral tegmental area by quantitative reverse transcription-polymerase chain reaction. MAM-treated rats displayed a significant increase in dopamine D3 receptor mRNA expression in the nucleus accumbens with no significant changes in the expression of the D2 receptor. Taken together, these data demonstrate robust alterations in dopamine D2-like receptor function in a rodent model of schizophrenia and provide evidence that preclinical studies examining the mechanisms of antipsychotic drug action should be performed in animal models that mirror aspects of the abnormal neuronal transmission thought to underlie symptoms of schizophrenia.

The uniqueness of human milk. Psychological differences between breast and bottle feeding.

PubMed

Newton, N

1971-08-01

This paper examines the theory that breastfed and bottlefed infants are psychological equivalents. There are 2 patterns of breastfeeding most often encountered, unrestricted and token breastfeedings. There are maternal differences between those who breastfeed and those who do not. The initial experience of breastfeeding is culturally dependent. A mother who practices unretricted breastfeeding is receiving sustained stimulation to her nipples and experiences a generalized body response. Likewise such a breastfeeding mother experiences other long-term psychophysiologic reactions such as lactation amenorrhea and changes in hormonal balance. Breastfeeding women are often interested in a quick return to sexual intercourse and display a more general attitude towards men. A mother's personality and her ability to adjust to life situations often varies with the choice of feeding. 1 study found that mothers who breastfed displayed significantly less neuroticism than those who did not. Breastfeeding behavior appears to be sensitive to even minor variations in the social milieu. The type of breastfeeding practiced is likewise a significant variable for the infant. The initial feeding of an unrestricted breastfed infant is usually smooth unlike the situation for the token breastfed. Both feeding patterns involve assuagement of hunger needs but are dependent on social setting. For the breastfed infant, comfort as well as nourishment are presented with the mother as part of the package. These 2 experiences are often split in bottlefed and token breastfed infants. The 2 sucking patterns resemble each other superficially and the breastfed infant seems to develop more interest in sucking. Different activity levels manifest themselves by the 3rd day postpartum with the breastfed showing a greater propensity toward activity. Intelligence scores are also related to feeding patterns, with those exclusively breastfed for 4-9 months displaying the highest scores in relation to their age.

Characterization and Potential Environmental Risks of Leachate from Shredded Rubber Mulches

PubMed Central

Kanematsu, Masakazu; Hayashi, Ai; Denison, Michael S.; Young, Thomas M.

2009-01-01

In order to determine whether shredded rubber mulches (RM) posed water quality risks when used in stormwater best management practices (BMPs) such as bioretention basins, batch leaching tests were conducted to identify and quantify constituents in leachates from RM such as metal ions, nutrients, total organic carbon (TOC), and aryl hydrocarbon receptor (AhR) activity (determined by the chemically activated luciferase gene expression (CALUX) bioassay) at varied temperature and initial pH values. The results indicate that aqueous extracts of RM contain high concentrations of zinc (Zn) compared with wood mulches (WM), and its concentration increased at lower pH and higher temperature. Although methanol extracts of RM displayed high AhR activity, none of the aqueous extracts of RM had significant activity. Hence, while unknown constituents that have significant AhR activity are present in RM, they appear to be not measurably extracted by water under environmental conditions relevant for stormwater (5 < pH < 9, 10 < T < 40°C). Our results suggests that organic constituents in water extracts of RM which have AhR activity may not be of significant concern while leaching of Zn from RM appears to be a potentially larger water quality issue for RM. PMID:19450864

Method of fabrication of display pixels driven by silicon thin film transistors

DOEpatents

Carey, Paul G.; Smith, Patrick M.

1999-01-01

Display pixels driven by silicon thin film transistors are fabricated on plastic substrates for use in active matrix displays, such as flat panel displays. The process for forming the pixels involves a prior method for forming individual silicon thin film transistors on low-temperature plastic substrates. Low-temperature substrates are generally considered as being incapable of withstanding sustained processing temperatures greater than about 200.degree. C. The pixel formation process results in a complete pixel and active matrix pixel array. A pixel (or picture element) in an active matrix display consists of a silicon thin film transistor (TFT) and a large electrode, which may control a liquid crystal light valve, an emissive material (such as a light emitting diode or LED), or some other light emitting or attenuating material. The pixels can be connected in arrays wherein rows of pixels contain common gate electrodes and columns of pixels contain common drain electrodes. The source electrode of each pixel TFT is connected to its pixel electrode, and is electrically isolated from every other circuit element in the pixel array.

Poly-silicon TFT AM-OLED on thin flexible metal substrates

NASA Astrophysics Data System (ADS)

Afentakis, Themis; Hatalis, Miltiadis K.; Voutsas, Apostolos T.; Hartzell, John W.

2003-05-01

Thin metal foils present an excellent alternative to polymers for the fabrication of large area, flexible displays. Their main advantage spurs from their ability to withstand higher temperatures during processing; microelectronic fabrication at elevated temperatures offers the ability to utilize a variety of crystallization processes for the active layer of devices and thermally grown gate dielectrics. This can lead to high performance (high mobility, low threshold voltage) low cost and highly reliable thin film transistors. In some cases, the conductive substrate can also be used to provide power to the active devices, thus reducing layout complexity. This paper discusses the first successful attempt to design and fabricate a variety of active matrix organic light emitting diode displays on thin, flexible stainless steel foils. Different pixel architectures, such as two- and four-transistor implementations, and addressing modes, such as voltage- or current-driven schemese are examined. This work clearly demonstrates the advantages associated with the fabrication of OLED displays on thin metal foils, which - through roll-to-roll processing - can potentially result in revolutionizing today's display processing, leading to a new generation of low cost, high performance versatile display systems.

Flexible active-matrix organic light-emitting diode display enabled by MoS2 thin-film transistor.

PubMed

Choi, Minwoo; Park, Yong Ju; Sharma, Bhupendra K; Bae, Sa-Rang; Kim, Soo Young; Ahn, Jong-Hyun

2018-04-01

Atomically thin molybdenum disulfide (MoS 2 ) has been extensively investigated in semiconductor electronics but has not been applied in a backplane circuitry of organic light-emitting diode (OLED) display. Its applicability as an active drive element is hampered by the large contact resistance at the metal/MoS 2 interface, which hinders the transport of carriers at the dielectric surface, which in turn considerably deteriorates the mobility. Modified switching device architecture is proposed for efficiently exploiting the high- k dielectric Al 2 O 3 layer, which, when integrated in an active matrix, can drive the ultrathin OLED display even in dynamic folding states. The proposed architecture exhibits 28 times increase in mobility compared to a normal back-gated thin-film transistor, and its potential as a wearable display attached to a human wrist is demonstrated.

Flexible active-matrix organic light-emitting diode display enabled by MoS2 thin-film transistor

PubMed Central

Park, Yong Ju

2018-01-01

Atomically thin molybdenum disulfide (MoS2) has been extensively investigated in semiconductor electronics but has not been applied in a backplane circuitry of organic light-emitting diode (OLED) display. Its applicability as an active drive element is hampered by the large contact resistance at the metal/MoS2 interface, which hinders the transport of carriers at the dielectric surface, which in turn considerably deteriorates the mobility. Modified switching device architecture is proposed for efficiently exploiting the high-k dielectric Al2O3 layer, which, when integrated in an active matrix, can drive the ultrathin OLED display even in dynamic folding states. The proposed architecture exhibits 28 times increase in mobility compared to a normal back-gated thin-film transistor, and its potential as a wearable display attached to a human wrist is demonstrated. PMID:29713686

Mobile Marine Museum.

ERIC Educational Resources Information Center

Bauer, R. D.; Schaadt, M. S.

1984-01-01

Calfiornia State University (Long Beach) purchased a motor home and converted it into a mobile marine science display unit, outfitting it with built-in display racks inside and an awning to provide shelter displays suited to outdoor use. School activities and programs using the mobile museum are described. (JN)

Combat vehicle crew helmet-mounted display: next generation high-resolution head-mounted display

NASA Astrophysics Data System (ADS)

Nelson, Scott A.

1994-06-01

The Combat Vehicle Crew Head-Mounted Display (CVC HMD) program is an ARPA-funded, US Army Natick Research, Development, and Engineering Center monitored effort to develop a high resolution, flat panel HMD for the M1 A2 Abrams main battle tank. CVC HMD is part of the ARPA High Definition Systems (HDS) thrust to develop and integrate small (24 micrometers square pels), high resolution (1280 X 1024 X 6-bit grey scale at 60 frame/sec) active matrix electroluminescent (AMEL) and active matrix liquid crystal displays (AMLCD) for head mounted and projection applications. The Honeywell designed CVC HMD is a next generation head-mounted display system that includes advanced flat panel image sources, advanced digital display driver electronics, high speed (> 1 Gbps) digital interconnect electronics, and light weight, high performance optical and mechanical designs. The resulting dramatic improvements in size, weight, power, and cost have already led to program spin offs for both military and commercial applications.

Applications of yeast surface display for protein engineering

PubMed Central

Cherf, Gerald M.; Cochran, Jennifer R.

2015-01-01

The method of displaying recombinant proteins on the surface of Saccharomyces cerevisiae via genetic fusion to an abundant cell wall protein, a technology known as yeast surface display, or simply, yeast display, has become a valuable protein engineering tool for a broad spectrum of biotechnology and biomedical applications. This review focuses on the use of yeast display for engineering protein affinity, stability, and enzymatic activity. Strategies and examples for each protein engineering goal are discussed. Additional applications of yeast display are also briefly presented, including protein epitope mapping, identification of protein-protein interactions, and uses of displayed proteins in industry and medicine. PMID:26060074

Activation of orexin/hypocretin neurons is associated with individual differences in cued fear extinction.

PubMed

Sharko, Amanda C; Fadel, Jim R; Kaigler, Kris F; Wilson, Marlene A

2017-09-01

Identifying the neurobiological mechanisms that underlie differential sensitivity to stress is critical for understanding the development and expression of stress-induced disorders, such as post-traumatic stress disorder (PTSD). Preclinical studies have suggested that rodents display different phenotypes associated with extinction of Pavlovian conditioned fear responses, with some rodent populations being resistant to extinction. An emerging literature also suggests a role for orexins in the consolidation processes associated with fear learning and extinction. To examine the possibility that the orexin system might be involved in individual differences in fear extinction, we used a Pavlovian conditioning paradigm in outbred Long-Evans rats. Rats showed significant variability in the extinction of cue-conditioned freezing and extinction recall, and animals were divided into groups based on their extinction profiles based on a median split of percent freezing behavior during repeated exposure to the conditioned cue. Animals resistant to extinction (high freezers) showed more freezing during repeated cue presentations during the within trial and between trial extinction sessions compared with the group showing significant extinction (low freezers), although there were no differences between these groups in freezing upon return to the conditioned context or during the conditioning session. Following the extinction recall session, activation of orexin neurons was determined using dual label immunohistochemistry for cFos in orexin positive neurons in the hypothalamus. Individual differences in the extinction of cue conditioned fear were associated with differential activation of hypothalamic orexin neurons. Animals showing poor extinction of cue-induced freezing (high freezers) had significantly greater percentage of orexin neurons with Fos in the medial hypothalamus than animals displaying significant extinction and good extinction recall (low freezers). Further, the freezing during extinction learning was positively correlated with the percentage of activated orexin neurons in both the lateral and medial hypothalamic regions. No differences in the overall density of orexin neurons or Fos activation were seen between extinction phenotypes. Although correlative, our results support other studies implicating a role of the orexinergic system in regulating extinction of conditioned responses to threat. Copyright © 2016 Elsevier Inc. All rights reserved.

Sulfation of 6-Gingerol by the Human Cytosolic Sulfotransferases: A Systematic Analysis.

PubMed

Luo, Lijun; Mei, Xue; Xi, Yuecheng; Zhou, Chunyang; Hui, Ying; Kurogi, Katsuhisa; Sakakibara, Yoichi; Suiko, Masahito; Liu, Ming-Cheh

2016-02-01

Previous studies have demonstrated the presence of the sulfated form of 6-gingerol, a major pharmacologically active component of ginger, in plasma samples of normal human subjects who were administered 6-gingerol. The current study was designed to systematically identify the major human cytosolic sulfotransferase enzyme(s) capable of mediating the sulfation of 6-gingerol. Of the 13 known human cytosolic sulfotransferases examined, six (SULT1A1, SULT1A2, SULT1A3, SULT1B1, SULT1C4, SULT1E1) displayed significant sulfating activity toward 6-gingerol. Kinetic parameters of SULT1A1, SULT1A3, SULT1C4, and SULT1E1 that showed stronger 6-gingerol-sulfating activity were determined. Of the four human organ samples tested, small intestine and liver cytosols displayed considerably higher 6-gingerol-sulfating activity than those of the lung and kidney. Moreover, sulfation of 6-gingerol was shown to occur in HepG2 human hepatoma cells and Caco-2 human colon adenocarcinoma cells under the metabolic setting. Collectively, these results provided useful information relevant to the metabolism of 6-gingerol through sulfation both in vitro and in vivo. Georg Thieme Verlag KG Stuttgart · New York.

Are One-to-One Computers Necessary? An Analysis of Collaborative Web Exploration Activities Supported by Shared Displays

ERIC Educational Resources Information Center

Chang, Chia-Jung; Liu, Chen-Chung; Shen, Yan-Jhih

2012-01-01

Collaborative web exploration, in which learners work together to explore the World Wide Web, has become a key learning activity in education contexts. Learners can use a shared computer with a shared display to explore the web together. However, such a shared-computer approach may limit active participation among learners. To address this issue,…

Family leadership styles and adolescent dietary and physical activity behaviors: a cross-sectional study

PubMed Central

2012-01-01

Background Transformational leadership is conceptualized as a set of behaviors designed to inspire, energize and motivate others to achieve higher levels of functioning, and is associated with salient health-related outcomes in organizational settings. Given (a) the similarities that exist between leadership within organizational settings and parenting within families, and (b) the importance of the family environment in the promotion of adolescent health-enhancing behaviors, the purpose of this exploratory study was to examine the cross-sectional relationships between parents’ transformational leadership behaviors and adolescent dietary and physical activity behaviors. Methods 857 adolescents (aged 13–15, mean age = 14.70 yrs) completed measures of transformational parenting behaviors, healthful dietary intake and leisure-time physical activity. Regression analyses were conducted to examine relationships between family transformational leadership and adolescent health outcomes. A further ‘extreme group analysis’ was conducted by clustering families based on quartile splits. A MANCOVA (controlling for child gender) was conducted to examine differences between families displaying (a) HIGH levels of transformational parenting (consistent HIGH TP), (b) LOW levels of transformational parenting (consistent LOW TP), and (c) inconsistent levels of transformational parenting (inconsistent HIGH-LOW TP). Results Results revealed that adolescents’ perceptions of family transformational parenting were associated with both healthy dietary intake and physical activity. Adolescents who perceived their families to display the highest levels of transformational parenting (HIGH TP group) displayed greater healthy eating and physical activity behaviors than adolescents who perceived their families to display the lowest levels of transformational parenting behaviors (LOW TP group). Adolescents who perceived their families to display inconsistent levels of transformational parenting behaviors (HIGH-LOW TP group) displayed the same levels of healthy eating behaviors as those adolescents from the LOW TP group. For physical activity behaviors, adolescents who perceived their families to display inconsistent levels of transformational parenting behaviors (HIGH-LOW TP group) did not differ in terms of physical activity than those in either the HIGH TP or LOW TP group. Conclusions Family transformational parenting behaviors were positively associated with both healthful dietary intake and leisure-time physical activity levels amongst adolescents. The findings suggest that transformational leadership theory is a useful framework for understanding the relationship between family leadership behaviors and adolescent health outcomes. PMID:22546151

Family leadership styles and adolescent dietary and physical activity behaviors: a cross-sectional study.

PubMed

Morton, Katie L; Wilson, Alexandra H; Perlmutter, Lisa S; Beauchamp, Mark R

2012-04-30

Transformational leadership is conceptualized as a set of behaviors designed to inspire, energize and motivate others to achieve higher levels of functioning, and is associated with salient health-related outcomes in organizational settings. Given (a) the similarities that exist between leadership within organizational settings and parenting within families, and (b) the importance of the family environment in the promotion of adolescent health-enhancing behaviors, the purpose of this exploratory study was to examine the cross-sectional relationships between parents' transformational leadership behaviors and adolescent dietary and physical activity behaviors. 857 adolescents (aged 13-15, mean age = 14.70 yrs) completed measures of transformational parenting behaviors, healthful dietary intake and leisure-time physical activity. Regression analyses were conducted to examine relationships between family transformational leadership and adolescent health outcomes. A further 'extreme group analysis' was conducted by clustering families based on quartile splits. A MANCOVA (controlling for child gender) was conducted to examine differences between families displaying (a) HIGH levels of transformational parenting (consistent HIGH TP), (b) LOW levels of transformational parenting (consistent LOW TP), and (c) inconsistent levels of transformational parenting (inconsistent HIGH-LOW TP). Results revealed that adolescents' perceptions of family transformational parenting were associated with both healthy dietary intake and physical activity. Adolescents who perceived their families to display the highest levels of transformational parenting (HIGH TP group) displayed greater healthy eating and physical activity behaviors than adolescents who perceived their families to display the lowest levels of transformational parenting behaviors (LOW TP group). Adolescents who perceived their families to display inconsistent levels of transformational parenting behaviors (HIGH-LOW TP group) displayed the same levels of healthy eating behaviors as those adolescents from the LOW TP group. For physical activity behaviors, adolescents who perceived their families to display inconsistent levels of transformational parenting behaviors (HIGH-LOW TP group) did not differ in terms of physical activity than those in either the HIGH TP or LOW TP group. Family transformational parenting behaviors were positively associated with both healthful dietary intake and leisure-time physical activity levels amongst adolescents. The findings suggest that transformational leadership theory is a useful framework for understanding the relationship between family leadership behaviors and adolescent health outcomes.

Depth Acuity Methodology for Electronic 3D Displays: eJames (eJ)

DTIC Science & Technology

2016-07-01

AFRL-RH-WP-TR-2016-0060 Depth Acuity Methodology for Electronic 3D Displays: eJames (eJ) Eric L. Heft, John McIntire...AND SUBTITLE Depth Acuity Methodology for Electronic 3D Displays: eJames (eJ) 5a. CONTRACT NUMBER FA8650-08-D-6801-0050 5b. GRANT NUMBER...of 3D electronic displays: one active-eyewear Stereo 3D (S3D) and two non-eyewear full parallax Field-of-Light Display (FoLD) systems. The two FoLD

The Impact of Different Degrees of Feedback on Physical Activity Levels: A 4-Week Intervention Study

PubMed Central

Van Hoye, Karen; Boen, Filip; Lefevre, Johan

2015-01-01

Assessing levels of physical activity (PA) and providing feedback about these levels might have an effect on participant’s PA behavior. This study discusses the effect of different levels of feedback—from minimal to use of a feedback display and coach—on PA over a 4-week intervention period. PA was measured at baseline, during and immediately after the intervention. Participants (n = 227) were randomly assigned to a Minimal Intervention Group (MIG-no feedback), Pedometer Group (PG-feedback on steps taken), Display Group (DG-feedback on steps, minutes of moderate to vigorous physical activity and energy expenditure) or Coaching Group (CoachG-same as DG with need-supportive coaching). Two-way ANCOVA showed no significant Group × Time interaction effect for the different PA variables between the MIG and PG. Also no differences emerged between PG and DG. As hypothesized, CoachG had higher PA values throughout the intervention compared with DG. Self-monitoring using a pedometer resulted in more steps compared with a no-feedback condition at the start of the intervention. However, adding individualized coaching seems necessary to increase the PA level until the end of the intervention. PMID:26067990

Construction of the yeast whole-cell Rhizopus oryzae lipase biocatalyst with high activity.

PubMed

Chen, Mei-ling; Guo, Qin; Wang, Rui-zhi; Xu, Juan; Zhou, Chen-wei; Ruan, Hui; He, Guo-qing

2011-07-01

Surface display is effectively utilized to construct a whole-cell biocatalyst. Codon optimization has been proven to be effective in maximizing production of heterologous proteins in yeast. Here, the cDNA sequence of Rhizopus oryzae lipase (ROL) was optimized and synthesized according to the codon bias of Saccharomyces cerevisiae, and based on the Saccharomyces cerevisiae cell surface display system with α-agglutinin as an anchor, recombinant yeast displaying fully codon-optimized ROL with high activity was successfully constructed. Compared with the wild-type ROL-displaying yeast, the activity of the codon-optimized ROL yeast whole-cell biocatalyst (25 U/g dried cells) was 12.8-fold higher in a hydrolysis reaction using p-nitrophenyl palmitate (pNPP) as the substrate. To our knowledge, this was the first attempt to combine the techniques of yeast surface display and codon optimization for whole-cell biocatalyst construction. Consequently, the yeast whole-cell ROL biocatalyst was constructed with high activity. The optimum pH and temperature for the yeast whole-cell ROL biocatalyst were pH 7.0 and 40 °C. Furthermore, this whole-cell biocatalyst was applied to the hydrolysis of tributyrin and the resulted conversion of butyric acid reached 96.91% after 144 h.

The Influence of Environmental Consequences and Internalizing Symptoms on Children's Tic Severity.

PubMed

Eaton, Cyd K; Jones, Anna M; Gutierrez-Colina, Ana M; Ivey, Emily K; Carlson, Olivia; Melville, Lauren; Kardon, Patricia; Blount, Ronald L

2017-04-01

Although there is evidence that environmental consequences for displaying tics and internalizing symptoms are related to tic severity in children with TS, less is known about the inter-relationships of these variables or how these factors jointly contribute to tic severity. This study included 45 children with Tourette syndrome. Caregivers reported on children's environmental consequences for displaying tics, internalizing symptoms, and tic severity. Results indicated that children with higher levels of internalizing symptoms experienced significantly more environmental consequences for displaying tics. Children with higher levels of separation anxiety symptoms demonstrated significantly greater tic severity. Environmental consequences for displaying tics accounted for significantly more variance in predicting tic severity than anxiety symptoms. This preliminary evidence suggests that environmental consequences for displaying tics, such as receiving accommodations or attention from others, have a greater influence on children's tic severity than emotional factors.

The impact of a highly visible display of cerebral perfusion pressure on outcome in individuals with cerebral aneurysms.

PubMed

Kirkness, Catherine J; Burr, Robert L; Cain, Kevin C; Newell, David W; Mitchell, Pamela H

2008-01-01

Nurses' ability to rapidly detect decreases in cerebral perfusion pressure (CPP), which may contribute to secondary brain injury, may be limited by poor visibility of CPP displays. To evaluate the impact of a highly visible CPP display on the functional outcome in individuals with cerebral aneurysms. Patients with cerebral aneurysms (n = 100) who underwent continuous CPP monitoring were enrolled and randomized to beds with or without the additional CPP display. Six-month outcome was assessed. Functional outcome was not significantly different between control and intervention groups after controlling for initial neurologic condition (odds ratio .904, 95% confidence interval 0.317 to 2.573). However, greater time below CPP thresholds (55 to 70 mm Hg) was significantly associated with poorer outcome (P = .005 to .010). Although the enhanced CPP display was not associated with significantly better outcome, longer periods of CPP below set levels were associated with poorer outcome.

Optically active red-emitting Cu nanoclusters originating from complexation and redox reaction between copper(ii) and d/l-penicillamine

NASA Astrophysics Data System (ADS)

Long, Tengfei; Guo, Yanjia; Lin, Min; Yuan, Mengke; Liu, Zhongde; Huang, Chengzhi

2016-05-01

Despite a significant surge in the number of investigations into both optically active Au and Ag nanostructures, there is currently only limited knowledge about optically active Cu nanoclusters (CuNCs) and their potential applications. Here, we have succeeded in preparing a pair of optically active red-emitting CuNCs on the basis of complexation and redox reaction between copper(ii) and penicillamine (Pen) enantiomers, in which Pen serves as both a reducing agent and a stabilizing ligand. Significantly, the CuNCs feature unique aggregation induced emission (AIE) characteristics and therefore can serve as pH stimuli-responsive functional materials. Impressively, the ligand chirality plays a dramatic role for the creation of brightly emissive CuNCs, attributed to the conformation of racemic Pen being unfavorable for the electrostatic interaction, and thus suppressing the formation of cluster aggregates. In addition, the clusters display potential toward cytoplasmic staining and labelling due to the high photoluminescence (PL) quantum yields (QYs) and remarkable cellular uptake, in spite that no chirality-dependent effects in autophagy and subcellular localization are observed in the application of chiral cluster enantiomer-based cell imaging.Despite a significant surge in the number of investigations into both optically active Au and Ag nanostructures, there is currently only limited knowledge about optically active Cu nanoclusters (CuNCs) and their potential applications. Here, we have succeeded in preparing a pair of optically active red-emitting CuNCs on the basis of complexation and redox reaction between copper(ii) and penicillamine (Pen) enantiomers, in which Pen serves as both a reducing agent and a stabilizing ligand. Significantly, the CuNCs feature unique aggregation induced emission (AIE) characteristics and therefore can serve as pH stimuli-responsive functional materials. Impressively, the ligand chirality plays a dramatic role for the creation of brightly emissive CuNCs, attributed to the conformation of racemic Pen being unfavorable for the electrostatic interaction, and thus suppressing the formation of cluster aggregates. In addition, the clusters display potential toward cytoplasmic staining and labelling due to the high photoluminescence (PL) quantum yields (QYs) and remarkable cellular uptake, in spite that no chirality-dependent effects in autophagy and subcellular localization are observed in the application of chiral cluster enantiomer-based cell imaging. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr01492e

“It Looks Like an Adult Sweetie Shop”: Point-of-Sale Tobacco Display Exposure and Brand Awareness in Scottish Secondary School Students

PubMed Central

van der Sluijs, Winfried; Miller, Martine; MacGregor, Andy; Sharp, Clare; Amos, Amanda; Best, Catherine; Stead, Martine; Eadie, Douglas; Pearce, Jamie; Frank, John; Haw, Sally

2016-01-01

Introduction: As further restrictions have been placed on tobacco advertising and promotions, point-of-sale (PoS) displays of cigarettes in shops have become an increasingly important source of young people’s exposure to tobacco products. This study explored the relationship between PoS displays of cigarettes and brand awareness among secondary school students in Scotland. Methods: Cross-sectional school surveys (n = 1406) and focus groups (n = 86) were conducted with S2 (13–14 years) and S4 (15–16 years) students in four schools of differing socioeconomic status in 2013, prior to the PoS display ban in large shops. Adjusted negative binomial regression analysis examined associations between brand awareness and exposure variables (visiting tobacco retailers, noticing displays of tobacco products). Results: Students visiting small shops more frequently (relative rate ratio [RRR] 1.19, 95% confidence interval [CI] 1.01–1.41) and those who noticed cigarette displays in small shops (RRR 1.24, 95% CI 1.03–1.51) and large supermarkets (RRR 1.15, 95% CI 1.01–1.30) had higher brand awareness. The focus groups supported these findings. Participants described PoS tobacco displays as being eye-catching, colorful and potentially attractive to young people. Conclusions: This mixed-methods study showed that higher cigarette brand awareness was significantly associated with regularly visiting small shops and noticing PoS displays in small and large shops, even when students’ smoking status, smoking in their social networks, leisure activities, and demographics were included as confounding variables. This highlights the importance of PoS displays of tobacco products in increasing brand awareness, which is known to increase youth smoking susceptibility, and thus the importance of implementing PoS display bans in all shops. Implications: As increasing restrictions have been placed on tobacco promotion in many countries, PoS displays of cigarettes in shops have become an important source of young people’s exposure to tobacco products and marketing. This mixed-methods study showed that prior to the PoS display ban in Scotland, and controlling for other factors, 13- and 15-year olds who regularly visited small shops and those who noticed PoS displays in small and large shops, had a higher awareness of cigarette brands. This highlights the importance of PoS displays in increasing youth brand awareness, which increases smoking susceptibility, and thus the need for comprehensive bans on PoS displays which cover all shops. PMID:26883750

"It Looks Like an Adult Sweetie Shop": Point-of-Sale Tobacco Display Exposure and Brand Awareness in Scottish Secondary School Students.

PubMed

van der Sluijs, Winfried; Haseen, Farhana; Miller, Martine; MacGregor, Andy; Sharp, Clare; Amos, Amanda; Best, Catherine; Stead, Martine; Eadie, Douglas; Pearce, Jamie; Frank, John; Haw, Sally

2016-10-01

As further restrictions have been placed on tobacco advertising and promotions, point-of-sale (PoS) displays of cigarettes in shops have become an increasingly important source of young people's exposure to tobacco products. This study explored the relationship between PoS displays of cigarettes and brand awareness among secondary school students in Scotland. Cross-sectional school surveys (n = 1406) and focus groups (n = 86) were conducted with S2 (13-14 years) and S4 (15-16 years) students in four schools of differing socioeconomic status in 2013, prior to the PoS display ban in large shops. Adjusted negative binomial regression analysis examined associations between brand awareness and exposure variables (visiting tobacco retailers, noticing displays of tobacco products). Students visiting small shops more frequently (relative rate ratio [RRR] 1.19, 95% confidence interval [CI] 1.01-1.41) and those who noticed cigarette displays in small shops (RRR 1.24, 95% CI 1.03-1.51) and large supermarkets (RRR 1.15, 95% CI 1.01-1.30) had higher brand awareness. The focus groups supported these findings. Participants described PoS tobacco displays as being eye-catching, colorful and potentially attractive to young people. This mixed-methods study showed that higher cigarette brand awareness was significantly associated with regularly visiting small shops and noticing PoS displays in small and large shops, even when students' smoking status, smoking in their social networks, leisure activities, and demographics were included as confounding variables. This highlights the importance of PoS displays of tobacco products in increasing brand awareness, which is known to increase youth smoking susceptibility, and thus the importance of implementing PoS display bans in all shops. As increasing restrictions have been placed on tobacco promotion in many countries, PoS displays of cigarettes in shops have become an important source of young people's exposure to tobacco products and marketing. This mixed-methods study showed that prior to the PoS display ban in Scotland, and controlling for other factors, 13- and 15-year olds who regularly visited small shops and those who noticed PoS displays in small and large shops, had a higher awareness of cigarette brands. This highlights the importance of PoS displays in increasing youth brand awareness, which increases smoking susceptibility, and thus the need for comprehensive bans on PoS displays which cover all shops. © The Author 2016. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.

Pheromone trailing behavior of the brown tree snake, Boiga irregularis.

PubMed

Greene, M J; Stark, S L; Mason, R T

2001-11-01

The ability of snakes to follow pheromone trails has significant consequences for survival and reproduction. Of particular importance is the ability of snakes to locate conspecifics during the breeding season via the detection of pheromone trails. In this study, the ability of male brown tree snakes (Boiga irregularis), a tropical, rear-fanged colubrid, to follow pheromone trails produced by reproductively active conspecifics was tested in the laboratory by using a Y maze. Males displayed a trailing response to both female and male pheromone trails over blank controls. As males of this species display ritualized combat behavior, these responses likely represent both direct and indirect mechanisms, respectively, for the location of potential mates in the wild. Males did not, however, discriminate between male and female trails when given a choice on the Y maze.

Muscle-specific AMPK β1β2-null mice display a myopathy due to loss of capillary density in nonpostural muscles

PubMed Central

Thomas, Melissa M.; Wang, David C.; D'Souza, Donna M.; Krause, Matthew P.; Layne, Andrew S.; Criswell, David S.; O'Neill, Hayley M.; Connor, Michael K.; Anderson, Judy E.; Kemp, Bruce E.; Steinberg, Gregory R.; Hawke, Thomas J.

2014-01-01

AMP-activated protein kinase (AMPK) is a master regulator of metabolism. While muscle-specific AMPK β1β2 double-knockout (β1β2M-KO) mice display alterations in metabolic and mitochondrial capacity, their severe exercise intolerance suggested a secondary contributor to the observed phenotype. We find that tibialis anterior (TA), but not soleus, muscles of sedentary β1β2M-KO mice display a significant myopathy (decreased myofiber areas, increased split and necrotic myofibers, and increased centrally nucleated myofibers. A mitochondrial- and fiber-type-specific etiology to the myopathy was ruled out. However, β1β2M-KO TA muscles displayed significant (P<0.05) increases in platelet aggregation and apoptosis within myofibers and surrounding interstitium (P<0.05). These changes correlated with a 45% decrease in capillary density (P<0.05). We hypothesized that the β1β2M-KO myopathy in resting muscle resulted from impaired AMPK-nNOSμ signaling, causing increased platelet aggregation, impaired vasodilation, and, ultimately, ischemic injury. Consistent with this hypothesis, AMPK-specific phosphorylation (Ser1446) of nNOSμ was decreased in β1β2M-KO compared to wild-type (WT) mice. The AMPK-nNOSμ relationship was further demonstrated by administration of 5-aminoimidazole-4-carboxamide 1-β-d-ribofuranoside (AICAR) to β1β2-MKO muscles and C2C12 myotubes. AICAR significantly increased nNOSμ phosphorylation and nitric oxide production (P<0.05) within minutes of administration in WT muscles and C2C12 myotubes but not in β1β2M-KO muscles. These findings highlight the importance of the AMPK-nNOSμ pathway in resting skeletal muscle.—Thomas, M. M., Wang, D. C., D'Souza, D. M., Krause, M. P., Layne, A. S., Criswell, D. S., O'Neill, H. M., Connor, M. K., Anderson, J. E., Kemp, B. E., Steinberg, G. R., and Hawke, T. J. Muscle-specific AMPK β1β2-null mice display a myopathy due to loss of capillary density in nonpostural muscles. PMID:24522207

Solar active region display system

NASA Astrophysics Data System (ADS)

Golightly, M.; Raben, V.; Weyland, M.

2003-04-01

The Solar Active Region Display System (SARDS) is a client-server application that automatically collects a wide range of solar data and displays it in a format easy for users to assimilate and interpret. Users can rapidly identify active regions of interest or concern from color-coded indicators that visually summarize each region's size, magnetic configuration, recent growth history, and recent flare and CME production. The active region information can be overlaid onto solar maps, multiple solar images, and solar difference images in orthographic, Mercator or cylindrical equidistant projections. Near real-time graphs display the GOES soft and hard x-ray flux, flare events, and daily F10.7 value as a function of time; color-coded indicators show current trends in soft x-ray flux, flare temperature, daily F10.7 flux, and x-ray flare occurrence. Through a separate window up to 4 real-time or static graphs can simultaneously display values of KP, AP, daily F10.7 flux, GOES soft and hard x-ray flux, GOES >10 and >100 MeV proton flux, and Thule neutron monitor count rate. Climatologic displays use color-valued cells to show F10.7 and AP values as a function of Carrington/Bartel's rotation sequences - this format allows users to detect recurrent patterns in solar and geomagnetic activity as well as variations in activity levels over multiple solar cycles. Users can customize many of the display and graph features; all displays can be printed or copied to the system's clipboard for "pasting" into other applications. The system obtains and stores space weather data and images from sources such as the NOAA Space Environment Center, NOAA National Geophysical Data Center, the joint ESA/NASA SOHO spacecraft, and the Kitt Peak National Solar Observatory, and can be extended to include other data series and image sources. Data and images retrieved from the system's database are converted to XML and transported from a central server using HTTP and SOAP protocols, allowing operation through network firewalls; data is compressed to enhance performance over limited bandwidth connections. All applications and services are written in the JAVA program language for platform independence. Several versions of SARDS have been in operational use by the NASA Space Radiation Analysis Group, NOAA Space Weather Operations, and U.S. Air Force Weather Agency since 1999.

The influence of lip form on incisal display with lips in repose on the esthetic preferences of dentists and lay people.

PubMed

Kim, Jee; Topolski, Richard; Dickinson, Douglas; Ramos, Van

2017-09-01

Information is lacking for viewer preferences for incisal display with lips in repose. The purpose of this online survey was to establish measurement parameters to classify and define a lip form and to evaluate the influence of lip form on dentists' and laypersons' preferences for the amount of incisal display with lips in repose. Computer-generated male and female models were created using 3 different lip forms each, straight, moderate, and high. Three images of these models (frontal full face, zoomed-in frontal around the mouth, and oblique zoomed-in image of the mouth) were arranged in an interactive survey that was disseminated on the Websites Facebook, Instagram, DentalTown and by word-of-mouth. Respondents manipulated the incisal display of all 3 images in unison, using a slide bar, and the resulting incisal display was measured in millimeters and served as the primary dependent measure. Survey demographic data were obtained from an online survey site. Data were assessed for skewness, kurtosis, and outliers and analyzed with 5-way ANOVA: 2 sex levels for model, 2 levels for sex of respondent, 3 levels for lip height, 3 levels for occupation, and 5 levels of ethnicity, with multiple comparisons corrected with Bonferroni adjustments and post hoc comparisons performed using the Scheffé test (α=.05 for all comparisons). A total of 1039 individuals consented to the study. A final sample size of 687 respondents was obtained after excluding 352 who failed to complete the survey. The results indicated that lip form affected the esthetic perception of incisal display significantly (P<.001), with a preference for a greater amount of incisal display corresponding with increasing lip forms. Sex of the model was also significant, with greater incisal display being preferred for female faces. A significant difference was found for respondents' ethnicity, with African Americans generally preferring smaller incisal displays than other ethnic groups. No other main effects were found to be statistically significant. Only 2 interactions were shown to be statistically significant. Post hoc tests examining the interaction between lip form and sex of model showed a preference for greater incisal displays for female faces with high lip forms. A 3-way interaction was observed between lip form, sex of respondent, and occupation. Significant differences were identified for the 3 different lip forms for both sexes of models. As the lip form changed from straight to moderate to high, there was a preference for increased incisal display. Incisal display preferences for male and female models were the same for all respondents, except for the high lip form, for which a greater amount of incisal display was preferred for the female model. Sex and occupation of respondent failed to produce main effects. Respondents' ethnicity was shown to be statistically significant, with African Americans generally preferring shorter incisal displays. Copyright © 2016 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.

Antibacterial and antioxidant activities of Vaccinium corymbosum L. leaf extract

PubMed Central

Pervin, Mehnaz; Hasnat, Md Abul; Lim, Beong Ou

2013-01-01

Objective To investigate antibacterial and antioxidant activity of the leaf extract of tropical medicinal herb and food plant Vaccinium corymbosum L. (V. corymbosum). Methods Free radical scavenging activity on DPPH, ABTS, and nitrites were used to analyse phenoic and flavonoid contents of leaf extract. Other focuses included the determination of antioxidant enzymatic activity (SOD, CAT and GPx), metal chelating activity, reduction power, lipid peroxidation inhibition and the prevention of oxidative DNA damage. Antibacterial activity was determined by using disc diffusion for seven strains of bacteria. Results Results found that V. corymbosum leaf extract had significant antibacterial activity. The tested extract displayed the highest activity (about 23.18 mm inhibition zone) against Salmonella typhymurium and the lowest antibacterial activity was observed against Enterococcus faecalis (about 14.08 mm inhibition zone) at 10 mg/ disc. The IC50 values for DPPH, ABTS and radical scavenging activity were 0.120, 0.049 and 1.160 mg/mL, respectively. V. corymbosum leaf extract also showed dose dependent reduction power, lipid peroxidation, DNA damage prevention and significant antioxidant enzymatic activity. Conclusions These findings demonstrate that leaf extract of V. corymbosum could be used as an alternative therapy for antibiotic-resistant bacteria and help prevent various free radical related diseases.

A biogeochemical and genetic survey of acetylene fermentation by environmental samples and bacterial isolates

USGS Publications Warehouse

Miller, Laurence G.; Baesman, Shaun M.; Kirshtein, Julie; Voytek, Mary A.; Oremland, Ronald S.

2013-01-01

Anoxic samples (sediment and groundwater) from 13 chemically diverse field sites were assayed for their ability to consume acetylene (C2H2). Over incubation periods ranging from ˜ 10 to 80 days, selected samples from 7 of the 13 tested sites displayed significant C2H2 removal. No significant formation of ethylene was noted in these incubations; therefore, C2H2 consumption could be attributed to acetylene hydratase (AH) rather than nitrogenase activity. This putative AH (PAH) activity was observed in only 21% of the total of assayed samples, while amplification of AH genes from extracted DNA using degenerate primers derived from Pelobacter acetylenicus occurred in even fewer (9.8%) samples. Acetylene-fermenting bacteria were isolated as a pure culture from the sediments of a tidal mudflat in San Francisco Bay (SFB93) and as an enrichment culture from freshwater Searsville Lake (SV7). Comparison of 16S rDNA clone libraries revealed that SFB93 was closely related to P. carbolinicus, while SV7 consisted of several unrelated bacteria. AH gene was amplified from SFB93 but not SV7. The inability of the primers to generate amplicons in the SV7 enrichment, as well as from several of the environmental samples that displayed PAH activity, implied that either the primers were too highly constrained in their specificity or that there was a different type of AH gene in these environmental samples than occurs in P. acetylenicus. The significance of this work with regard to the search for life in the outer Solar System, where C2HL2 is abundant, is discussed.

Evidence Supporting a Role for Constitutive Ghrelin Receptor Signaling in Fasting-Induced Hyperphagia in Male Mice.

PubMed

Fernandez, Gimena; Cabral, Agustina; Andreoli, María F; Labarthe, Alexandra; M'Kadmi, Céline; Ramos, Jorge G; Marie, Jacky; Fehrentz, Jean-Alain; Epelbaum, Jacques; Tolle, Virginie; Perello, Mario

2018-02-01

Ghrelin is a potent orexigenic peptide hormone that acts through the growth hormone secretagogue receptor (GHSR), a G protein-coupled receptor highly expressed in the hypothalamus. In vitro studies have shown that GHSR displays a high constitutive activity, whose physiological relevance is uncertain. As GHSR gene expression in the hypothalamus is known to increase in fasting conditions, we tested the hypothesis that constitutive GHSR activity at the hypothalamic level drives the fasting-induced hyperphagia. We found that refed wild-type (WT) mice displayed a robust hyperphagia that continued for 5 days after refeeding and changed their food intake daily pattern. Fasted WT mice showed an increase in plasma ghrelin levels, as well as in GHSR expression levels and ghrelin binding sites in the hypothalamic arcuate nucleus. When fasting-refeeding responses were evaluated in ghrelin- or GHSR-deficient mice, only the latter displayed an ∼15% smaller hyperphagia, compared with WT mice. Finally, fasting-induced hyperphagia of WT mice was significantly smaller in mice centrally treated with the GHSR inverse agonist K-(D-1-Nal)-FwLL-NH2, compared with mice treated with vehicle, whereas it was unaffected in mice centrally treated with the GHSR antagonists D-Lys3-growth hormone-releasing peptide 6 or JMV2959. Taken together, genetic models and pharmacological results support the notion that constitutive GHSR activity modulates the magnitude of the compensatory hyperphagia triggered by fasting. Thus, the hypothalamic GHSR signaling system could affect the set point of daily food intake, independently of plasma ghrelin levels, in situations of negative energy balance. Copyright © 2018 Endocrine Society.

Seasonal variation in Internet searches for vitamin D.

PubMed

Moon, Rebecca J; Curtis, Elizabeth M; Davies, Justin H; Cooper, Cyrus; Harvey, Nicholas C

2017-12-01

Internet search rates for "vitamin D" were explored using Google Trends. Search rates increased from 2004 until 2010 and thereafter displayed a seasonal pattern peaking in late winter. This knowledge could help guide the timing of public health interventions aimed at managing vitamin D deficiency. The Internet is an important source of health information. Analysis of Internet search activity rates can provide information on disease epidemiology, health related behaviors and public interest. We explored Internet search rates for vitamin D to determine whether this reflects the increasing scientific interest in this topic. Google Trends is a publically available tool that provides data on Internet searches using Google. Search activity for the term "vitamin D" from 1st January 2004 until 31st October 2016 was obtained. Comparison was made to other bone and nutrition related terms. Worldwide, searches for "vitamin D" increased from 2004 until 2010 and thereafter a statistically significant (p < 0.001) seasonal pattern with a peak in February and nadir in August was observed. This seasonal pattern was evident for searches originating from both the USA (peak in February) and Australia (peak in August); p < 0.001 for both. Searches for the terms "osteoporosis", "rickets", "back pain" or "folic acid" did not display the increase observed for vitamin D or evidence of seasonal variation. Public interest in vitamin D, as assessed by Internet search activity, did increase from 2004 to 2010, likely reflecting the growing scientific interest, but now displays a seasonal pattern with peak interest during late winter. This information could be used to guide public health approaches to managing vitamin D deficiency.

Controlling motion sickness and spatial disorientation and enhancing vestibular rehabilitation with a user-worn see-through display.

PubMed

Krueger, Wesley W O

2011-01-01

An eyewear mounted visual display ("User-worn see-through display") projecting an artificial horizon aligned with the user's head and body position in space can prevent or lessen motion sickness in susceptible individuals when in a motion provocative environment as well as aid patients undergoing vestibular rehabilitation. In this project, a wearable display device, including software technology and hardware, was developed and a phase I feasibility study and phase II clinical trial for safety and efficacy were performed. Both phase I and phase II were prospective studies funded by the NIH. The phase II study used repeated measures for motion intolerant subjects and a randomized control group (display device/no display device) pre-posttest design for patients in vestibular rehabilitation. Following technology and display device development, 75 patients were evaluated by test and rating scales in the phase II study; 25 subjects with motion intolerance used the technology in the display device in provocative environments and completed subjective rating scales, whereas 50 patients were evaluated before and after vestibular rehabilitation (25 using the display device and 25 in a control group) using established test measures. All patients with motion intolerance rated the technology as helpful for nine symptoms assessed, and 96% rated the display device as simple and easy to use. Duration of symptoms significantly decreased with use of the technology displayed. In patients undergoing vestibular rehabilitation, there were no significant differences in amount of change from pre- to posttherapy on objective balance tests between display device users and controls. However, those using the technology required significantly fewer rehabilitation sessions to achieve those outcomes than the control group. A user-worn see-through display, utilizing a visual fixation target coupled with a stable artificial horizon and aligned with user movement, has demonstrated substantial benefit for individuals susceptible to motion intolerance and spatial disorientation and those undergoing vestibular rehabilitation. The technology developed has applications in any environment where motion sensitivity affects human performance.

Lipophilic stinging nettle extracts possess potent anti-inflammatory activity, are not cytotoxic and may be superior to traditional tinctures for treating inflammatory disorders

PubMed Central

Johnson, Tyler A.; Sohn, Johann; Inman, Wayne D.; Bjeldanes, Leonard F.; Rayburn, Keith

2012-01-01

Extracts of four plant portions (roots, stems, leaves and flowers) of Urtica dioica, (the stinging nettle) were prepared using accelerated solvent extraction (ASE) involving water, hexanes, methanol and dichloromethane. The extracts were evaluated for their anti-inflammatory and cytotoxic activity in an NF-κB luciferase and MTT assay using macrophage immune (RAW264.7) cells. A standardized commercial ethanol extract of nettle leaves were also evaluated. The methanolic extract of the flowering portions displayed significant anti-inflammatory activity on par with the standard anti-inflammatory agent celastrol (1) but was moderately cytotoxic. Alternatively, the polar extracts (water, methanol, ethanol) of the roots, stems and leaves plant portions displayed moderate to weak anti-inflammatory activity, while the methanol and especially the water soluble extracts exhibited noticeable cytotoxicity. In contrast, the lipophilic dichloromethane extracts of the roots, stems and leaves exhibited potent anti-inflammatory effects ≥ 1 with minimal cytotoxicity to RAW264.7 cells. Collectively these results suggest that using lipophilic extracts of the roots, stems or leaves of stinging nettle may be more effective then traditional tinctures (water, methanol, ethanol) to undergo clinical evaluations for the treatment of inflammatory disorders including arthritis. A chemical investigation into the lipophillic extracts of stinging nettle to identify the bioactive compound(s) responsible for their observed anti-inflammatory activity is further warranted. PMID:23092723

Lipophilic stinging nettle extracts possess potent anti-inflammatory activity, are not cytotoxic and may be superior to traditional tinctures for treating inflammatory disorders.

PubMed

Johnson, Tyler A; Sohn, Johann; Inman, Wayne D; Bjeldanes, Leonard F; Rayburn, Keith

2013-01-15

Extracts of four plant portions (roots, stems, leaves and flowers) of Urtica dioica (the stinging nettle) were prepared using accelerated solvent extraction (ASE) involving water, hexanes, methanol and dichloromethane. The extracts were evaluated for their anti-inflammatory and cytotoxic activities in an NF-κB luciferase and MTT assay using macrophage immune (RAW264.7) cells. A standardized commercial ethanol extract of nettle leaves was also evaluated. The methanolic extract of the flowering portions displayed significant anti-inflammatory activity on par with a standard compound celastrol (1) but were moderately cytotoxic. Alternatively, the polar extracts (water, methanol, ethanol) of the roots, stems and leaves displayed moderate to weak anti-inflammatory activity, while the methanol and especially the water soluble extracts exhibited noticeable cytotoxicity. In contrast, the lipophilic dichloromethane extracts of the roots, stems and leaves exhibited potent anti-inflammatory effects greater than or equal to 1 with minimal cytotoxicity to RAW264.7 cells. Collectively these results suggest that using lipophilic extracts of stinging nettle may be more effective than traditional tinctures (water, methanol, ethanol) in clinical evaluations for the treatment of inflammatory disorders especially arthritis. A chemical investigation into the lipophilic extracts of stinging nettle to identify the bioactive compound(s) responsible for their observed anti-inflammatory activity is further warranted. Published by Elsevier GmbH.

Antibacterial activity of 2-alkynoic fatty acids against multidrug-resistant bacteria.

PubMed

Sanabria-Ríos, David J; Rivera-Torres, Yaritza; Maldonado-Domínguez, Gamalier; Domínguez, Idializ; Ríos, Camille; Díaz, Damarith; Rodríguez, José W; Altieri-Rivera, Joanne S; Ríos-Olivares, Eddy; Cintrón, Gabriel; Montano, Nashbly; Carballeira, Néstor M

2014-02-01

The first study aimed at determining the structural characteristics needed to prepare antibacterial 2-alkynoic fatty acids (2-AFAs) was accomplished by synthesizing several 2-AFAs and other analogs in 18-76% overall yields. Among all the compounds tested, the 2-hexadecynoic acid (2-HDA) displayed the best overall antibacterial activity against Gram-positive Staphylococcus aureus (MIC=15.6 μg/mL), Staphylococcus saprophyticus (MIC=15.5 μg/mL), and Bacillus cereus (MIC=31.3 μg/mL), as well as against the Gram-negative Klebsiella pneumoniae (7.8 μg/mL) and Pseudomonas aeruginosa (MIC=125 μg/mL). In addition, 2-HDA displayed significant antibacterial activity against methicillin-resistant S. aureus (MRSA) ATCC 43300 (MIC=15.6 μg/mL) and clinical isolates of MRSA (MIC=3.9 μg/mL). No direct relationship was found between the antibacterial activity of 2-AFAs and their critical micelle concentration (CMC) suggesting that the antibacterial properties of these fatty acids are not mediated by micelle formation. It was demonstrated that the presence of a triple bond at C-2 and the carboxylic acid moiety in 2-AFAs are important for their antibacterial activity. 2-HDA has the potential to be further evaluated for use in antibacterial formulations. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

NOTCH1 Is Aberrantly Activated in Chronic Lymphocytic Leukemia Hematopoietic Stem Cells.

PubMed

Di Ianni, Mauro; Baldoni, Stefano; Del Papa, Beatrice; Aureli, Patrizia; Dorillo, Erica; De Falco, Filomena; Albi, Elisa; Varasano, Emanuela; Di Tommaso, Ambra; Giancola, Raffaella; Accorsi, Patrizia; Rotta, Gianluca; Rompietti, Chiara; Silva Barcelos, Estevão Carlos; Campese, Antonio Francesco; Di Bartolomeo, Paolo; Screpanti, Isabella; Rosati, Emanuela; Falzetti, Franca; Sportoletti, Paolo

2018-01-01

To investigate chronic lymphocytic leukemia (CLL)-initiating cells, we assessed NOTCH1 mutation/expression in hematopoietic stem cells (HSCs). In NOTCH1- mutated CLL, we detected subclonal mutations in 57% CD34+/CD38- HSCs. NOTCH1 mutation was present in 66% CD34+/CD38+ progenitor cells displaying an increased mutational burden compared to HSCs. Flow cytometric analysis revealed significantly higher NOTCH1 activation in CD34+/CD38- and CD34+/CD38+ cells from CLL patients, regardless NOTCH1 mutation compared to healthy donors. Activated NOTCH1 resulted in overexpression of the NOTCH1 target c-MYC. We conclude that activated NOTCH1 is an early event in CLL that may contribute to aberrant HSCs in this disease.

Placotylene A, an Inhibitor of the Receptor Activator of Nuclear Factor-κB Ligand-Induced Osteoclast Differentiation, from a Korean Sponge Placospongia sp.

PubMed Central

Kim, Hiyoung; Kim, Kwang-Jin; Yeon, Jeong-Tae; Kim, Seong Hwan; Won, Dong Hwan; Choi, Hyukjae; Nam, Sang-Jip; Son, Young-Jin; Kang, Heonjoong

2014-01-01

A new inhibitor, placotylene A (1), of the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation, and a regioisomer of placotylene A, placotylene B (2), were isolated from a Korean marine sponge Placospongia sp. The chemical structures of placotylenes A and B were elucidated on the basis of 1D and 2D NMR, along with MS spectral analysis and revealed as an iodinated polyacetylene class of natural products. Placotylene A (1) displayed inhibitory activity against RANKL-induced osteoclast differentiation at 10 μM while placotylene B (2) did not show any significant activity up to 100 μM, respectively. PMID:24705502

Human platelet lysate improves human cord blood derived ECFC survival and vasculogenesis in three dimensional (3D) collagen matrices

PubMed Central

Kim, Hyojin; Prasain, Nutan; Vemula, Sasidhar; Ferkowicz, Michael J.; Yoshimoto, Momoko; Voytik-Harbin, Sherry L.; Yoder, Mervin C.

2015-01-01

Human cord blood (CB) is enriched in circulating endothelial colony forming cells (ECFC) that display high proliferative potential and in vivo vessel forming ability. Since diminished ECFC survival is known to dampen the vasculogenic response in vivo, we tested how long implanted ECFC survive and generate vessels in three-dimensional (3D) type I collagen matrices in vitro and in vivo. We hypothesized that human platelet lysate (HPL) would promote cell survival and enhance vasculogenesis in the 3D collagen matrices. We report that the percentage of ECFC co-cultured with HPL that were alive was significantly enhanced on days 1 and 3 post- matrix formation, compared to ECFC alone containing matrices. Also, co-culture of ECFC with HPL displayed significantly more vasculogenic activity compared to ECFC alone and expressed significantly more pro-survival molecules (pAkt, p-Bad and Bcl-xL) in the 3D collagen matrices in vitro. Treatment with Akt1 inhibitor (A-674563), Akt2 inhibitor (CCT128930) and Bcl-xL inhibitor (ABT-263/Navitoclax) significantly decreased the cell survival and vasculogenesis of ECFC co-cultured with or without HPL and implicated activation of the Akt1 pathway as the critical mediator of the HPL effect on ECFC in vitro. A significantly greater average vessel number and total vascular area of human CD31+ vessels were present in implants containing ECFC and HPL, compared to the ECFC alone implants in vivo. We conclude that implantation of ECFC with HPL in vivo promotes vasculogenesis and augments blood vessel formation via diminishing apoptosis of the implanted ECFC. PMID:26122935

Human platelet lysate improves human cord blood derived ECFC survival and vasculogenesis in three dimensional (3D) collagen matrices.

PubMed

Kim, Hyojin; Prasain, Nutan; Vemula, Sasidhar; Ferkowicz, Michael J; Yoshimoto, Momoko; Voytik-Harbin, Sherry L; Yoder, Mervin C

2015-09-01

Human cord blood (CB) is enriched in circulating endothelial colony forming cells (ECFCs) that display high proliferative potential and in vivo vessel forming ability. Since diminished ECFC survival is known to dampen the vasculogenic response in vivo, we tested how long implanted ECFC survive and generate vessels in three-dimensional (3D) type I collagen matrices in vitro and in vivo. We hypothesized that human platelet lysate (HPL) would promote cell survival and enhance vasculogenesis in the 3D collagen matrices. We report that the percentage of ECFC co-cultured with HPL that were alive was significantly enhanced on days 1 and 3 post-matrix formation, compared to ECFC alone containing matrices. Also, co-culture of ECFC with HPL displayed significantly more vasculogenic activity compared to ECFC alone and expressed significantly more pro-survival molecules (pAkt, p-Bad and Bcl-xL) in the 3D collagen matrices in vitro. Treatment with Akt1 inhibitor (A-674563), Akt2 inhibitor (CCT128930) and Bcl-xL inhibitor (ABT-263/Navitoclax) significantly decreased the cell survival and vasculogenesis of ECFC co-cultured with or without HPL and implicated activation of the Akt1 pathway as the critical mediator of the HPL effect on ECFC in vitro. A significantly greater average vessel number and total vascular area of human CD31(+) vessels were present in implants containing ECFC and HPL, compared to the ECFC alone implants in vivo. We conclude that implantation of ECFC with HPL in vivo promotes vasculogenesis and augments blood vessel formation via diminishing apoptosis of the implanted ECFC. Copyright © 2015 Elsevier Inc. All rights reserved.

A novel series of enoyl reductase inhibitors targeting the ESKAPE pathogens, Staphylococcus aureus and Acinetobacter baumannii.

PubMed

Kwon, Jieun; Mistry, Tina; Ren, Jinhong; Johnson, Michael E; Mehboob, Shahila

2018-01-01

S. aureus and A. baumannii are among the ESKAPE pathogens that are increasingly difficult to treat due to the rise in the number of drug resistant strains. Novel therapeutics targeting these pathogens are much needed. The bacterial enoyl reductase (FabI) is as potentially significant drug target for developing pathogen-specific antibiotics due to the presence of alternate FabI isoforms in many other bacterial species. We report the identification and development of a novel N-carboxy pyrrolidine scaffold targeting FabI in S. aureus and A. baumannii, two pathogens for which FabI essentiality has been established. This scaffold is unrelated to other known antibiotic families, and FabI is not targeted by any currently approved antibiotic. Our data shows that this scaffold displays promising enzyme inhibitory activity against FabI from both S. aureus and A. baumannii, as well as encouraging antibacterial activity in S. aureus. Compounds also display excellent synergy when combined with colistin and tested against A. baumannii. In this combination the MIC of colistin is reduced by 10-fold. Our first generation compound displays promising enzyme inhibition, targets FabI in S. aureus with a favorable selectivity index (ratio of cytotoxicity to MIC), and has excellent synergy with colistin against A. baumannii, including a multidrug resistant strain. Copyright © 2017 Elsevier Ltd. All rights reserved.

Pyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H)-dione derivatives as novel small molecule chaperone amplifiers.

PubMed

Zhou, Yuefen; Wei, Linyi; Brady, Thomas P; Murali Mohan Redddy, P S; Nguyen, Tram; Chen, Jinhua; Au, Qingyan; Yoon, Il Sang; Yip, Gary; Zhang, Bin; Barber, Jack R; Ng, Shi Chung

2009-08-01

Pyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H)-dione derivatives were investigated as novel small molecule amplifiers of heat shock factor 1 transcriptional activity. Lead optimization led to the discovery of compound 4A-13, which displayed potent HSF1 activity under mild heat stress (EC(50)=2.5microM) and significant cytoprotection in both rotenone (EC(50)=0.23microM) and oxygen-glucose deprivation cell toxicity models (80% protection at 2.5microM).

Synthesis and Biological Evaluation of Neopeltolide and Analogs

PubMed Central

Cui, Yubo; Balachandran, Raghavan

2012-01-01

The synthesis of neopeltolide analogs that contain variations in the oxazole-containing side chain and in the macrolide core are reported along with the GI50 values for these compounds against MCF7, HCT-116, and p53 knockout HCT-116 cell lines. Although biological activity is sensitive to changes in the macrocycle and the side chain, several analogs displayed GI50 values of <25 nM. Neopeltolide and several of the more potent analogs were significantly less potent against p53 knockout cells, suggesting that p53 plays an auxiliary role in the activity of these compounds. PMID:22329423

Synthesis, structure and in vitro cytostatic activity of ferrocene-Cinchona hybrids.

PubMed

Kocsis, László; Szabó, Ildikó; Bősze, Szilvia; Jernei, Tamás; Hudecz, Ferenc; Csámpai, Antal

2016-02-01

Exploring copper(I)- and ruthenium(II)-catalyzed azide-alkyne cycloadditions and a Sonogashira protocol, novel cytostatic ferrocene-cinchona hybrids were synthetized displaying significant in vitro activity on HepG-2 and HT-29 cells. Preliminary SAR studies disclosed that compounds incorporating linkers with 1,2,3-triazole and chalchone residues can be considered as promising lead structures. According to the best of our knowledge this is the first letter on the incorporation of ferrocene nucleus in the reputed cinchona family via triazole and chalcone linkers with established pharmaceutical profile. Copyright © 2015 Elsevier Ltd. All rights reserved.

A comparative study on the antinociceptive and anti-inflammatory activities of five Juniperus taxa.

PubMed

Akkol, Esra Küpeli; Güvenç, Ayşegül; Yesilada, Erdem

2009-09-07

Juniperus L. (Cupressaceae) species have been used to various inflammatory and infectious diseases such as bronchitis, colds, cough, fungal infections, hemorrhoids, gynecological diseases, and wounds in Turkish folk medicine. To evaluate this traditional information, anti-inflammatory and antinociceptive activities of the methanolic and aqueous extracts prepared from different parts (stem, fruit and leaves) of the five Turkish taxa under Juniperus section of the gender; J. drupacea, J. communis var. communis, J. communis var. saxatilis, J. oxycedrus subsp. oxycedrus, and J. oxycedrus subsp. macrocarpa growing were investigated. For the anti-inflammatory activity, carrageenan-induced and PGE(2)-induced hind paw edema models, and for the antinociceptive activity p-benzoquinone-induced writhing and hot plate tests in mice were employed. The methanolic extracts of fruit and leaves from J. oxycedrus subsp. oxycedrus and J. communis var. saxatilis exhibited notable inhibition in carrageenan-induced edema model at a dose of 100mg/kg. The same extracts also displayed significant activity against PGE(2)-induced edema model. While, the remaining extracts were found inactive against these edema models. A similar activity pattern was observed against p-benzoquinone-induced abdominal constriction test without inducing any gastric damage or apparent acute toxicity, whereas all extracts were inactive in hot plate test. The experimental data demonstrated that J. oxycedrus subsp. oxycedrus and J. communis var. saxatilis displayed remarkable anti-inflammatory and antinociceptive activities; however, further studies are warranted to define and isolate the active anti-inflammatory and antinociceptive components from these active species which may yield safe and effective agents to be used in the treatment of inflammatory disorders.

Camera calibration: active versus passive targets

NASA Astrophysics Data System (ADS)

Schmalz, Christoph; Forster, Frank; Angelopoulou, Elli

2011-11-01

Traditionally, most camera calibrations rely on a planar target with well-known marks. However, the localization error of the marks in the image is a source of inaccuracy. We propose the use of high-resolution digital displays as active calibration targets to obtain more accurate calibration results for all types of cameras. The display shows a series of coded patterns to generate correspondences between world points and image points. This has several advantages. No special calibration hardware is necessary because suitable displays are practically ubiquitious. The method is fully automatic, and no identification of marks is necessary. For a coding scheme based on phase shifting, the localization accuracy is approximately independent of the camera's focus settings. Most importantly, higher accuracy can be achieved compared to passive targets, such as printed checkerboards. A rigorous evaluation is performed to substantiate this claim. Our active target method is compared to standard calibrations using a checkerboard target. We perform camera, calibrations with different combinations of displays, cameras, and lenses, as well as with simulated images and find markedly lower reprojection errors when using active targets. For example, in a stereo reconstruction task, the accuracy of a system calibrated with an active target is five times better.

The impact of occlusal plane cant along with gingival display on smile attractiveness.

PubMed

Kaya, B; Uyar, R

2016-05-01

To evaluate the influence of occlusal plane cant in conjunction with maxillary gingival display on perception of smile attractiveness by orthodontists, dentists, and laypersons. Faculty of Dentistry at Baskent University. A total of 204 raters for smile attractiveness. A frontal intra-oral photograph of aligned teeth was modified using image processing software. Six different occlusal lines representing 0° to 5° cants were obtained by tilting the photographs. Each occlusal cant was adjusted in five manners resulting in five different gingival display amounts. Attractiveness of the 30 different smiles was evaluated by 204 raters divided into three groups (n = 68 in each group). Both occlusal cant (p < 0.001) and gingival display amount (p < 0.001) had a statistically significant influence on smile attractiveness. Smile attractiveness scores with reference to amount of gingival display showed a significant difference between rater groups (p < 0.001). Orthodontists preferred 1-mm coverage of upper central incisors by the upper lip, whereas dentists and laypersons preferred 2 mm. Significant (p < 0.001) interaction was observed between occlusal cant and gingival display amount, which influenced smile attractiveness. Increase in both occlusal plane cant and gingival display negatively influences smile attractiveness. The influence of occlusal plane cant becomes less when gingival display increases, whereas the influence of gingival display decreases when occlusal cant increases. Dentists are more generous than orthodontists, while laypersons are the most generous regarding smile attractiveness scores. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Respiratory muscle stretch gymnastics in patients with post coronary artery bypass grafting pain: impact on respiratory muscle function, activity, mood and exercise capacity.

PubMed

Aida, Nobuko; Shibuya, Masako; Yoshino, Katsuki; Komoda, Masaji; Inoue, Tomoko

2002-12-01

A new rehabilitation (New-RH) program including respiratory muscle stretch gymnastics (RMSG) was developed to alleviate post-coronary artery bypass grafting pain (PCP). Effects on respiratory muscle function, pain, activities of daily living (ADL), mood and exercise capacity were investigated. Subjects were 16 consecutive patients undergoing median full sternotomy coronary artery bypass grafting (CABG), and were randomly divided into equal New-RH (S-group) and conventional therapy (C-group) groups. Rib cage dominant breathing was observed postoperatively in both groups. With preoperative tan deltaVrc/deltaVab, increases at 1-week postoperatively and decreases at discharge for S-group tended to exceed those of C-group (p > .05). Decreased maximum inspiratory and expiratory pressure status for functional residual capacity and percent forced expiratory volume in one second at discharge again only tended to be smaller for S-group (p > .05). S-group displayed significantly reduced pain around both scapulas at discharge (p = .049), and increased mean overall ADL and profile of mood states (POMS)/Vigor scores (p = .031 and p = .018, respectively). POMS/Tension-Anxiety scores at discharge for S-group were significantly smaller than those preoperatively (p = .025), and S-group displayed significantly increased distance walked over 6-minutes at discharge than C-group (p = .029). New-RH improves patient participation in exercise therapy and increases exercise capacity by reducing PCP, relieving anxiety and tension, and improving ADL.

Characteristic Markers of the WNT Signaling Pathways Are Differentially Expressed in Osteoarthritic Cartilage

PubMed Central

Dehne, T.; Lindahl, A.; Brittberg, M.; Pruss, A.; Ringe, J.; Sittinger, M.; Karlsson, C.

2012-01-01

Objective: It is well known that expression of markers for WNT signaling is dysregulated in osteoarthritic (OA) bone. However, it is still not fully known if the expression of these markers also is affected in OA cartilage. The aim of this study was therefore to examine this issue. Methods: Human cartilage biopsies from OA and control donors were subjected to genome-wide oligonucleotide microarrays. Genes involved in WNT signaling were selected using the BioRetis database, KEGG pathway analysis was searched using DAVID software tools, and cluster analysis was performed using Genesis software. Results from the microarray analysis were verified using quantitative real-time PCR and immunohistochemistry. In order to study the impact of cytokines for the dysregulated WNT signaling, OA and control chondrocytes were stimulated with interleukin-1 and analyzed with real-time PCR for their expression of WNT-related genes. Results: Several WNT markers displayed a significantly altered expression in OA compared to normal cartilage. Interestingly, inhibitors of the canonical and planar cell polarity WNT signaling pathways displayed significantly increased expression in OA cartilage, while the Ca2+/WNT signaling pathway was activated. Both real-time PCR and immunohistochemistry verified the microarray results. Real-time PCR analysis demonstrated that interleukin-1 upregulated expression of important WNT markers. Conclusions: WNT signaling is significantly affected in OA cartilage. The result suggests that both the canonical and planar cell polarity WNT signaling pathways were partly inhibited while the Ca2+/WNT pathway was activated in OA cartilage. PMID:26069618

Yeast cell surface display for lipase whole cell catalyst and its applications

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

Liu, Yun; Zhang, Rui; Lian, Zhongshuai

The cell surface display technique allows for the expression of target proteins or peptides on the microbial cell surface by fusing an appropriate protein as an anchoring motif. Yeast display systems, such as Pichia pastoris, Yarowia lipolytica and Saccharomyces cerevisiae, are ideal, alternative and extensive display systems with the advantage of simple genetic manipulation and post-translational modification of expressed heterologous proteins. Engineered yeasts show high performance characteristics and variant utilizations. Herein, we comprehensively summarize the variant factors affecting lipase whole cell catalyst activity and display efficiency, including the structure and size of target proteins, screening anchor proteins, type and chainmore » length of linkers, and the appropriate matching rules among the above-mentioned display units. Furthermore, we also address novel approaches to enhance stability and activity of recombinant lipases, such as VHb gene co-expression, multi-enzyme co-display technique, and the micro-environmental interference and self-assembly techniques. Finally, we represent the variety of applications of whole cell surface displayed lipases on yeast cells in non-aqueous phases, including synthesis of esters, PUFA enrichment, resolution of chiral drugs, organic synthesis and biofuels. We demonstrate that the lipase surface display technique is a powerful tool for functionalizing yeasts to serve as whole cell catalysts, and increasing interest is providing an impetus for broad application of this technique.« less

Solving bezel reliability and CRT obsolescence

NASA Astrophysics Data System (ADS)

Schwartz, Richard J.; Bowen, Arlen R.; Knowles, Terry

2003-09-01

Scientific Research Corporation designed a Smart Multi-Function Color Display with Positive Pilot Feedback under the funding of an U. S. Navy Small Business Innovative Research program. The Smart Multi-Function Color Display can replace the obsolete monochrome Cathode Ray Tube display currently on the T-45C aircraft built by Boeing. The design utilizes a flat panel color Active Matrix Liquid Crystal Display and TexZec's patented Touch Thru Metal bezel technology providing both visual and biomechanical feedback to the pilot in a form, fit, and function replacement to the current T-45C display. Use of an existing color AMLCD, requires the least adaptation to fill the requirements of this application, thereby minimizing risk associated with developing a new display technology and maximizing the investment in improved user interface technology. The improved user interface uses TexZec's Touch Thru Metal technology to eliminate all of the moving parts that traditionally have limited Mean-Time-Between-Failure. The touch detection circuit consists of Commercial-Off-The-Shelf components, creating touch detection circuitry, which is simple and durable. This technology provides robust switch activation and a high level of environmental immunity, both mechanical and electrical. Replacement of all the T-45C multi-function displays with this design will improve the Mean-Time-Between-Failure and drastically reduce display life cycle costs. The design methodology described in this paper can be adapted to any new or replacement display.

Reversion of the P-glycoprotein-mediated multidrug resistance of cancer cells by FK-506 derivatives.

PubMed

Jachez, B; Boesch, D; Grassberger, M A; Loor, F

1993-04-01

FK-506 is a resistance-modulating agent (RMA) for tumor cells whose multidrug resistance (MDR) involves a P-glycoprotein (Pgp)-mediated anti-cancer drug efflux. The family of FK-506 relatives and derivatives includes analogs which display a whole range of chemosensitizing strengths, from no detectable RMA activity to a complete reversion of the MDR phenotype. Similarly, FK-506 analogs display a whole range of immunosuppressive activities, including inactive ones. FK-506 was compared for RMA activity with 11 FK-506 analogs which were at least 20-fold less active than FK-506 for the inhibition of the bi-directional mixed lymphocyte reaction displayed the whole range of RMA activity. One such strong RMA derivative of FK-506 (SDZ 280-629) was further shown able to restore completely daunomycin retention by highly resistant MDR P388 tumor cells.

Protein kinase D displays intrinsic Tyr autophosphorylation activity: insights into mechanism and regulation.

PubMed

Cobbaut, Mathias; Derua, Rita; Parker, Peter J; Waelkens, Etienne; Janssens, Veerle; Van Lint, Johan

2018-06-22

The protein kinase D (PKD) family is regulated through multi-site phosphorylation, including autophosphorylation. For example, PKD displays in vivo autophosphorylation on Ser-742 (and Ser-738 in vitro) in the activation loop and Ser-910 in the C-tail (hPKD1 numbering). In this paper, we describe the surprising observation that PKD also displays in vitro autocatalytic activity towards a Tyr residue in the P+1 loop of the activation segment. We define the molecular determinants for this unusual activity and identify a Cys residue (C705 in PKD1) in the catalytic loop as of utmost importance. In cells, PKD Tyr autophosphorylation is suppressed through the association of an inhibitory factor. Our findings provide important novel insights into PKD (auto)regulation. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Photocatalytic activity of PANI loaded coordination polymer composite materials: Photoresponse region extension and quantum yields enhancement via the loading of PANI nanofibers on surface of coordination polymer

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

Cui, Zhongping; Qi, Ji; Xu, Xinxin, E-mail: xuxx@mail.neu.edu.cn

2013-09-15

To enhance photocatalytic property of coordination polymer in visible light region, polyaniline (PANI) loaded coordination polymer photocatalyst was synthesized through in-situ chemical oxidation of aniline on the surface of coordination polymer. The photocatalytic activity of PANI loaded coordination polymer composite material for degradation of Rhodamine B (RhB) was investigated. Compared with pure coordination polymer photocatalyst, which can decompose RhB merely under UV light irradiation, PANI loaded coordination polymer photocatalyst displays more excellent photocatalytic activity in visible light region. Furthermore, PANI loaded coordination polymer photocatalyst exhibits outstanding stability during the degradation of RhB. - Graphical abstract: PANI loaded coordination polymer compositemore » material, which displays excellent photocatalytic activity under visible light was firstly synthesized through in-situ chemical oxidation of aniline on surface of coordination polymer. Display Omitted - Highlights: • This PANI loaded coordination polymer composite material represents the first conductive polymer loaded coordination polymer composite material. • PANI/coordination polymer composite material displays more excellent photocatalytic activity for the degradation of MO in visible light region. • The “combination” of coordination polymer and PANI will enable us to design high-activity, high-stability and visible light driven photocatalyst in the future.« less

Differential Processing of Isolated Object and Multi-item Pop-Out Displays in LIP and PFC.

PubMed

Meyers, Ethan M; Liang, Andy; Katsuki, Fumi; Constantinidis, Christos

2017-10-11

Objects that are highly distinct from their surroundings appear to visually "pop-out." This effect is present for displays in which: (1) a single cue object is shown on a blank background, and (2) a single cue object is highly distinct from surrounding objects; it is generally assumed that these 2 display types are processed in the same way. To directly examine this, we applied a decoding analysis to neural activity recorded from the lateral intraparietal (LIP) area and the dorsolateral prefrontal cortex (dlPFC). Our analyses showed that for the single-object displays, cue location information appeared earlier in LIP than in dlPFC. However, for the display with distractors, location information was substantially delayed in both brain regions, and information first appeared in dlPFC. Additionally, we see that pattern of neural activity is similar for both types of displays and across different color transformations of the stimuli, indicating that location information is being coded in the same way regardless of display type. These results lead us to hypothesize that 2 different pathways are involved processing these 2 types of pop-out displays. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Re-Mediating Classroom Activity with a Non-Linear, Multi-Display Presentation Tool

ERIC Educational Resources Information Center

Bligh, Brett; Coyle, Do

2013-01-01

This paper uses an Activity Theory framework to evaluate the use of a novel, multi-screen, non-linear presentation tool. The Thunder tool allows presenters to manipulate and annotate multiple digital slides and to concurrently display a selection of juxtaposed resources across a wall-sized projection area. Conventional, single screen presentation…

One-pot wet-chemical co-reduction synthesis of bimetallic gold-platinum nanochains supported on reduced graphene oxide with enhanced electrocatalytic activity

NASA Astrophysics Data System (ADS)

Chen, De-Jun; Zhang, Qian-Li; Feng, Jin-Xia; Ju, Ke-Jian; Wang, Ai-Jun; Wei, Jie; Feng, Jiu-Ju

2015-08-01

In this work, a simple, rapid and facile one-pot wet-chemical co-reduction method is developed for synthesis of bimetallic Au-Pt alloyed nanochains supported on reduced graphene oxide (Au-Pt NCs/RGO), in which caffeine is acted as a capping agent and a structure-directing agent, while no any seed, template, surfactant or polymer involved. The as-prepared nanocomposites display enlarged electrochemical active surface area, significantly enhanced catalytic activity and better stability for methanol and ethylene glycol oxidation, compared with commercial Pt-C (Pt 50 wt%), PtRu-C (Pt 30 wt% and Ru 15 wt%) and Pt black.

Comparative Analysis of Conventional Electronic and OZ Concept Displays for Aircraft Energy Management

NASA Astrophysics Data System (ADS)

Baker, Erik Reese

A repeated-measures, within-subjects design was conducted on 58 participant pilots to assess mean differences on energy management situation awareness response time and response accuracy between a conventional electronic aircraft display, a primary flight display (PFD), and an ecological interface design aircraft display, the OZ concept display. Participants were associated with a small Midwestern aviation university, including student pilots, flight instructors, and faculty with piloting experience. Testing consisted of observing 15 static screenshots of each cockpit display type and then selecting applicable responses from 27 standardized responses for each screen. A paired samples t-test was computed comparing accuracy and response time for the two displays. There was no significant difference in means between PFD Response Time and OZ Response Time. On average, mean PFD Accuracy was significantly higher than mean OZ Accuracy (MDiff = 13.17, SDDiff = 20.96), t(57) = 4.78, p < .001, d = 0.63. This finding showed operational potential for the OZ display, since even without first training to proficiency on the previously unseen OZ display, participant performance differences were not operationally remarkable. There was no significant correlation between PFD Response Time and PFD Accuracy, but there was a significant correlation between OZ Response Time and OZ Accuracy, r (58) = .353, p < .01. These findings suggest the participant familiarity of the PFD resulted in accuracy scores unrelated to response time, compared to the participants unaccustomed with the OZ display where longer response times manifested in greater understanding of the OZ display. PFD Response Time and PFD Accuracy were not correlated with pilot flight hours, which was not expected. It was thought that increased experience would translate into faster and more accurate assessment of the aircraft stimuli. OZ Response Time and OZ Accuracy were also not correlated with pilot flight hours, but this was expected. This was consistent with previous research that observed novice operators performing as well as experienced professional pilots on dynamic flight tasks with the OZ display. A demographic questionnaire and a feedback survey were included in the trial. An equivalent three-quarters majority of participants rated the PFD as "easy" and the OZ as "confusing", yet performance accuracy and response times between the two displays were not operationally different.

Spatial characterization of proteolytic enzyme activity in the foregut region of the adult necrophagous fly, Protophormia terraenovae.

PubMed

Rivers, David B; Acca, Gillian; Fink, Marc; Brogan, Rebecca; Schoeffield, Andrew

2014-08-01

The spatial distribution of proteolytic enzymes in the adult foregut of Protophormia terraenovae was studied in the context of protein digestion and regurgitation. Based on substrate specificity, pH optima, and use of specific protease inhibitors, all adults tested displayed enzyme activity in the foregut consistent with pepsin, trypsin and chymotrypsin. Chymotrypsin-like and trypsin-like enzyme activity were detected in all gut fluids and tissues tested, with chymotrypsin displaying the highest activity in saliva and salivary gland tissue, whereas maximal trypsin activity was evident in the crop. Pepsin-like activity was only evident in crop fluids and tissues. The activity of all three enzymes was low or undetectable (pepsin) in the fluids and tissue homogenates derived from the esophagus and cardia of any of the adults assayed. Fed adult females displayed higher enzyme activities than fed males, and the activity of all three enzymes were much more prevalent in fed adults than starved. The pH optimum of the trypsin-like enzyme was between pH 7.0 and 8.0; chymotrypsin was near pH 8.0; and maximal pepsin-like activity occurred between pH 1.0 and 2.0. Regurgitate from fed adult females displayed enzyme activity consistent with the proteolytic enzymes detected in crop gut fluids. Enzymes in regurgitate were not derived from food sources based on assays of bovine liver samples. These latter observations suggest that adult flies release fluids from foregut when encountering dry foods, potentially as a means to initiate extra-oral digestion. Copyright © 2014 Elsevier Ltd. All rights reserved.

Evaluation of Equivalent Vision Technologies for Supersonic Aircraft Operations

NASA Technical Reports Server (NTRS)

Kramer, Lynda J.; Williams, Steven P.; Wilz, Susan P.; Arthur, Jarvis J., III; Bailey, Randall E.

2009-01-01

Twenty-four air transport-rated pilots participated as subjects in a fixed-based simulation experiment to evaluate the use of Synthetic/Enhanced Vision (S/EV) and eXternal Vision System (XVS) technologies as enabling technologies for future all-weather operations. Three head-up flight display concepts were evaluated a monochromatic, collimated Head-up Display (HUD) and a color, non-collimated XVS display with a field-of-view (FOV) equal to and also, one significantly larger than the collimated HUD. Approach, landing, departure, and surface operations were conducted. Additionally, the apparent angle-of-attack (AOA) was varied (high/low) to investigate the vertical field-of-view display requirements and peripheral, side window visibility was experimentally varied. The data showed that lateral approach tracking performance and lateral landing position were excellent regardless of the display type and AOA condition being evaluated or whether or not there were peripheral cues in the side windows. Longitudinal touchdown and glideslope tracking were affected by the display concepts. Larger FOV display concepts showed improved longitudinal touchdown control, superior glideslope tracking, significant situation awareness improvements and workload reductions compared to smaller FOV display concepts.

A minimal peptide scaffold for beta-turn display: optimizing a strand position in disulfide-cyclized beta-hairpins.

PubMed

Cochran, A G; Tong, R T; Starovasnik, M A; Park, E J; McDowell, R S; Theaker, J E; Skelton, N J

2001-01-31

Phage display of peptide libraries has become a powerful tool for the evolution of novel ligands that bind virtually any protein target. However, the rules governing conformational preferences in natural peptides are poorly understood, and consequently, structure-activity relationships in these molecules can be difficult to define. In an effort to simplify this process, we have investigated the structural stability of 10-residue, disulfide-constrained beta-hairpins and assessed their suitability as scaffolds for beta-turn display. Using disulfide formation as a probe, relative free energies of folding were measured for 19 peptides that differ at a one strand position. A tryptophan substitution promotes folding to a remarkable degree. NMR analysis confirms that the measured energies correlate well with the degree of beta-hairpin structure in the disulfide-cyclized peptides. Reexamination of a subset of the strand substitutions in peptides with different turn sequences reveals linear free energy relationships, indicating that turns and strand-strand interactions make independent, additive contributions to hairpin stability. Significantly, the tryptophan strand substitution is highly stabilizing with all turns tested, and peptides that display model turns or the less stable C'-C' ' turn of CD4 on this tryptophan "stem" are highly structured beta-hairpins in water. Thus, we have developed a small, structured beta-turn scaffold, containing only natural L-amino acids, that may be used to display peptide libraries of limited conformational diversity on phage.

Effects of supplementation with two sources and two levels of copper on meat lipid oxidation, meat colour and superoxide dismutase and glutathione peroxidase enzyme activities in Nellore beef cattle.

PubMed

Correa, Lísia Bertonha; Zanetti, Marcus Antonio; Del Claro, Gustavo Ribeiro; de Paiva, Fernanda Alves; da Luz e Silva, Saulo; Netto, Arlindo Saran

2014-10-28

In the present study, thirty-five Nellore bulls were used to determine the effects of two levels and two sources (organic and inorganic) of Cu supplementation on the oxidative stability of lipids, measured by the thiobarbituric acid-reactive substance (TBARS) test, meat colour and superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) enzyme activities. The following treatments were used: (1) control (C) - basal diet without supplementation of Cu (7 mg Cu/kg DM); (2) I10 - basal diet supplemented with 10 mg Cu/kg DM in the form of copper sulphate (inorganic form); (3) I40 - basal diet supplemented with 40 mg Cu/kg DM in the form of copper sulphate; (4) O10 - basal diet supplemented with 10 mg Cu/kg DM in the form of copper proteinate (organic form); (5) O40 - basal diet supplemented with 40 mg Cu/kg DM in the form of copper proteinate. Lipid oxidation was determined in meat samples exposed to display, modified atmosphere (MA) and vacuum packaging (VC) conditions and in liver samples using the TBARS test. These samples were also evaluated for meat discolouration after exposure to air. The activities of SOD and GSH-Px enzymes were determined in liver samples. In display, MA and VC conditions, the TBARS values of samples from animals supplemented with 40 mg Cu/kg DM were lower than those of samples from control animals. There was no effect of treatment on the colour variables (L*, a*, b*). There was also no significant effect of treatment on hepatic TBARS concentrations and GSH-Px activity. Supplementation with Cu at 40 mg/kg, regardless of the source, induced higher hepatic SOD activity compared with the control treatment. In conclusion, Cu supplementation improved the oxidative stability of lipids in samples exposed to display, MA and VC conditions, demonstrating the antioxidant effect of this mineral.

PEGylated DX-1000: pharmacokinetics and antineoplastic activity of a specific plasmin inhibitor.

PubMed

Devy, Laetitia; Rabbani, Shafaat A; Stochl, Mark; Ruskowski, Mary; Mackie, Ian; Naa, Laurent; Toews, Mark; van Gool, Reinoud; Chen, Jie; Ley, Art; Ladner, Robert C; Dransfield, Daniel T; Henderikx, Paula

2007-11-01

Novel inhibitors of the urokinase-mediated plasminogen (plg) activation system are potentially of great clinical benefit as anticancer treatments. Using phage display, we identified DX-1000 a tissue factor pathway inhibitor-derived Kunitz domain protein which is a specific high-affinity inhibitor of plasmin (pln) (K(i) = 99 pM). When tested in vitro, DX-1000 blocks plasmin-mediated pro-matrix metalloproteinase-9 (proMMP-9) activation on cells and dose-dependently inhibits tube formation, while not significantly affecting hemostasis and coagulation. However, this low-molecular weight protein inhibitor ( approximately 7 kDa) exhibits rapid plasma clearance in mice and rabbits, limiting its potential clinical use in chronic diseases. After site-specific PEGylation, DX-1000 retains its activity and exhibits a decreased plasma clearance. This PEGylated derivative is effective in vitro, as well as potent in inhibiting tumor growth of green fluorescent protein (GFP)-labeled MDA-MB-231 cells. 4PEG-DX-1000 treatment causes a significant reduction of urokinase-type plasminogen activator (uPA) and plasminogen expressions, a reduction of tumor proliferation, and vascularization. 4PEG-DX-1000 treatment significantly decreases the level of active mitogen-activated protein kinase (MAPK) in the primary tumors and reduces metastasis incidence. Together, our results demonstrate the potential value of plasmin inhibitors as therapeutic agents for blocking breast cancer growth and metastasis.

The impact of gender and age on the nutritional parameters of alpaca (Vicugna pacos) meat, colour stability and fat traits.

PubMed

Smith, M A; Bush, R D; van de Ven, R J; Hall, E J S; Greenwood, P L; Hopkins, D L

2017-01-01

Meat quality parameters for 50 huacaya alpacas, representing three age groups (18, 24 and 36months) and two genders (females and castrated males) were studied. Prior to chilling, samples of m. longissimus thoracis et lumborum (LL) were taken to determine isocitrate dehydrogenase activity and glycogen concentration, and further meat quality samples were taken after 24h. Alpaca meat has low levels (<1%) of intramuscular fat in the LL, m. semimembranosus and m. biceps femoris, but the level in the LL increases with animal age, with levels of desirable polyunsaturated fatty acids (PUFA) ranging from 96.3 to 136.4mg/100g. Lipid oxidisation post retail display ranged from 1.27 to 1.96MDA/kg meat. Colour stability testing indicated alpaca meat was relatively stable during retail display with day of display having no significant effect on lightness (L*), or the 630nm/580nm ratio. These results may relate to the high proportion (76%) of glycolytic and type IIX muscle fibres in LL. Copyright © 2016 Elsevier Ltd. All rights reserved.

Age- or stage-appropriate? Recreation and the relevance of Piaget's theory in dementia care.

PubMed

Mahoney, Alison E J

2003-01-01

In this study, the immediate effects (within 10 minutes) of age- and stage-appropriate activities and two control activities were observed in 56 dementia sufferers. Compared with the control activities, the two experimental treatment conditions elicited greater reductions in agitation and negative emotion and increases in positive emotion and duration of activity. Stage-appropriate activity was superior to age-appropriate activity in increasing positive emotion and had about the same effect in reducing negative emotion and agitation. The study also addressed the idea that people with Alzheimer's disease may regress through Piaget's stages of cognitive development and thus display the play interests associated with each stage. There was a significant relationship between cognitive level and type of Piagetian play observed; however, Piaget's descriptions of play were not entirely appropriate for persons with with Alzheimer's disease.

In vitro 5-lipoxygenase and anti-oxidant activities of South African medicinal plants commonly used topically for skin diseases.

PubMed

Frum, Y; Viljoen, A M

2006-01-01

An investigation was undertaken to determine the possible mechanisms of action of medicinal plants used for dermatological pathologies. A total of 14 plant species were selected from the readily available ethnobotanical literature. 5-Lipoxygenase and DPPH (2,2-diphenyl-1-picrylhydrazyl) assays were used to determine the anti-inflammatory activity and the anti-oxidant activity of selected medicinal plants, respectively. Both aqueous and methanol extracts were tested. Among the plants screened, four species (Croton sylvaticus, Warburgia salutaris, Pentanisia prunelloides, and Melianthus comosus) displayed promising 5-lipoxygenase inhibitory activity with IC(50) values <61 ppm. A large number of plants exhibited significant anti-oxidant activities with IC(50) values between 5.27 and 83.36 ppm. Aqueous extracts of M. comosus exhibited the most potent anti-inflammatory and anti-oxidant activity.

Multimission helicopter information display technology

NASA Astrophysics Data System (ADS)

Terry, William S.

1995-06-01

A new Operator display subsystem is being incorporated as part of the next generation United States Navy (USN) helicopter avionics system to be integrated into the Multi-Mission Helicopter (MMH) which will replace both the SH-60B and the SH- 60F in 2001. This subsystem exploits state-of-the-art technology for the display hardware, the display driver hardware, information presentation methodologies, and software architecture. The technologies to be base technologies have evolved during the development period and the solution has been modified to include current elements including high resolution AMLCD color displays that are sunlight readable, highly reliable, and significantly lighter that CRT technology, as well as Reduced Instruction Set Computer (RISC) based high-performance display generators that have only recently become feasible to implement in a military aircraft. This paper describes the overall subsystem architecture, some detail on the individual elements along with supporting rationale, the manner in which the display subsystem provides the necessary tools to significantly enhance the performance of the weapon system through the vital Operator-System Interface. Also addressed is a summary of the evolution of design leading to the current approach to MMH Operator displays and display processing as well as the growth path that the MMH display subsystem will most likely follow as additional technology evolution occurs.

Altered CD19/CD22 balance in Egyptian children and adolescents with systemic lupus erythematosus.

PubMed

El-Sayed, Zeinab A; Ragab, Seham M; Khalifa, Khaled A; El Ashmawy, Ramy A

2009-01-01

B cells from systemic lupus erythematosus (SLE) patients display signalling defects that may underlie disease pathogenesis activity.CD19 and CD22 play a major role as regulators of B-cell response. The aim of this study was to clarify the relationship between B cell surface markers namely CD19, CD20 and CD22 expression and clinical and laboratory indices of SLE activity. The study included 33 SLE patients and 20 healthy children and adolescents as controls. Flowcytometric assay of dual markers, CD19/CD20, and CD20/CD22 was done. SLE disease activity was assessed by SLEDAI score. CD22% was significantly higher while CD20% was significantly lower in the study compared to the control group. No significant difference was observed in both groups with respect to CD19% or CD19/CD22% ratio. The level of CD22 expression was significantly lower in high and very high active cases than in mild and moderate cases and negatively correlated with SLDEAI score and ESR. Results obtained showed that, B cell surface receptors CD20 and CD22 are significantly affected in patients with SLE, pointing to their possible involvement in the aetiopathogenesis of the disease and in the regulatory mechanisms in response to the immune disturbance.

JIP1-Mediated JNK Activation Negatively Regulates Synaptic Plasticity and Spatial Memory.

PubMed

Morel, Caroline; Sherrin, Tessi; Kennedy, Norman J; Forest, Kelly H; Avcioglu Barutcu, Seda; Robles, Michael; Carpenter-Hyland, Ezekiel; Alfulaij, Naghum; Standen, Claire L; Nichols, Robert A; Benveniste, Morris; Davis, Roger J; Todorovic, Cedomir

2018-04-11

The c-Jun N-terminal kinase (JNK) signal transduction pathway is implicated in learning and memory. Here, we examined the role of JNK activation mediated by the JNK-interacting protein 1 (JIP1) scaffold protein. We compared male wild-type mice with a mouse model harboring a point mutation in the Jip1 gene that selectively blocks JIP1-mediated JNK activation. These male mutant mice exhibited increased NMDAR currents, increased NMDAR-mediated gene expression, and a lower threshold for induction of hippocampal long-term potentiation. The JIP1 mutant mice also displayed improved hippocampus-dependent spatial memory and enhanced associative fear conditioning. These results were confirmed using a second JIP1 mutant mouse model that suppresses JNK activity. Together, these observations establish that JIP1-mediated JNK activation contributes to the regulation of hippocampus-dependent, NMDAR-mediated synaptic plasticity and learning. SIGNIFICANCE STATEMENT The results of this study demonstrate that c-Jun N-terminal kinase (JNK) activation induced by the JNK-interacting protein 1 (JIP1) scaffold protein negatively regulates the threshold for induction of long-term synaptic plasticity through the NMDA-type glutamate receptor. This change in plasticity threshold influences learning. Indeed, mice with defects in JIP1-mediated JNK activation display enhanced memory in hippocampus-dependent tasks, such as contextual fear conditioning and Morris water maze, indicating that JIP1-JNK constrains spatial memory. This study identifies JIP1-mediated JNK activation as a novel molecular pathway that negatively regulates NMDAR-dependent synaptic plasticity and memory. Copyright © 2018 the authors 0270-6474/18/383708-21$15.00/0.

Mesenchymal stem cells display hepato-protective activity in lymphoma bearing xenografts.

PubMed

Secchiero, Paola; Corallini, Federica; Zavan, Barbara; Tripodo, Claudio; Vindigni, Vincenzo; Zauli, Giorgio

2012-04-01

A disseminated model of non-Hodgkin's lymphoma with prevalent liver metastasis was generated by intraperitoneal (i.p.) injection of EBV(+) B lymphoblastoid SKW6.4 in nude-SCID mice. The survival of SKW6.4 xenografts (median survival = 27 days) was significantly improved when hyaluronan scaffolds embedded with mesenchimal stem cells (MSC) were implanted in the abdominal area 4 days after SKW6.4 injection (median survival = 39.5 days). Mice implanted with MSC showed a significant improvement of hepatic functionality in lymphoma xenografts, as demonstrated by measurement of serum ALT/AST levels. Co-culture of MSC with lymphoma cells enhanced the release of hepatocyte growth factor (HGF) by MSC. These data suggest that hyaluronan-embedded MSC exert anti-lymphoma activity by ameliorating hepatic functionality.

Design, Synthesis and Inhibitory Activity of Photoswitchable RET Kinase Inhibitors

NASA Astrophysics Data System (ADS)

Ferreira, Rubén; Nilsson, Jesper R.; Solano, Carlos; Andréasson, Joakim; Grøtli, Morten

2015-05-01

REarranged during Transfection (RET) is a transmembrane receptor tyrosine kinase required for normal development and maintenance of neurons of the central and peripheral nervous systems. Deregulation of RET and hyperactivity of the RET kinase is intimately connected to several types of human cancers, most notably thyroid cancers, making it an attractive therapeutic target for small-molecule kinase inhibitors. Novel approaches, allowing external control of the activity of RET, would be key additions to the signal transduction toolbox. In this work, photoswitchable RET kinase inhibitors based on azo-functionalized pyrazolopyrimidines were developed, enabling photonic control of RET activity. The most promising compound displays excellent switching properties and stability with good inhibitory effect towards RET in cell-free as well as live-cell assays and a significant difference in inhibitory activity between its two photoisomeric forms. As the first reported photoswitchable small-molecule kinase inhibitor, we consider the herein presented effector to be a significant step forward in the development of tools for kinase signal transduction studies with spatiotemporal control over inhibitor concentration in situ.

Part A: Assessing the performance of the COMFA outdoor thermal comfort model on subjects performing physical activity

NASA Astrophysics Data System (ADS)

Kenny, Natasha A.; Warland, Jon S.; Brown, Robert D.; Gillespie, Terry G.

2009-09-01

This study assessed the performance of the COMFA outdoor thermal comfort model on subjects performing moderate to vigorous physical activity. Field tests were conducted on 27 subjects performing 30 min of steady-state activity (walking, running, and cycling) in an outdoor environment. The predicted COMFA budgets were compared to the actual thermal sensation (ATS) votes provided by participants during each 5-min interval. The results revealed a normal distribution in the subjects’ ATS votes, with 82% of votes received in categories 0 (neutral) to +2 (warm). The ATS votes were significantly dependent upon sex, air temperature, short and long-wave radiation, wind speed, and metabolic activity rate. There was a significant positive correlation between the ATS and predicted budgets (Spearman’s rho = 0.574, P < 0.01). However, the predicted budgets did not display a normal distribution, and the model produced erroneous estimates of the heat and moisture exchange between the human body and the ambient environment in 6% of the cases.

Chronic baclofen desensitizes GABA(B)-mediated G-protein activation and stimulates phosphorylation of kinases in mesocorticolimbic rat brain.

PubMed

Keegan, Bradley M T; Beveridge, Thomas J R; Pezor, Jeffrey J; Xiao, Ruoyu; Sexton, Tammy; Childers, Steven R; Howlett, Allyn C

2015-08-01

The GABAB receptor is a therapeutic target for CNS and neuropathic disorders; however, few preclinical studies have explored effects of chronic stimulation. This study evaluated acute and chronic baclofen treatments on GABAB-activated G-proteins and signaling protein phosphorylation as indicators of GABAB signaling capacity. Brain sections from rats acutely administered baclofen (5 mg/kg, i.p.) showed no significant differences from controls in GABAB-stimulated GTPγS binding in any brain region, but displayed significantly greater phosphorylation/activation of focal adhesion kinase (pFAK(Tyr397)) in mesocorticolimbic regions (caudate putamen, cortex, hippocampus, thalamus) and elevated phosphorylated/activated glycogen synthase kinase 3-β (pGSK3β(Tyr216)) in the prefrontal cortex, cerebral cortex, caudate putamen, nucleus accumbens, thalamus, septum, and globus pallidus. In rats administered chronic baclofen (5 mg/kg, t.i.d. for five days), GABAB-stimulated GTPγS binding was significantly diminished in the prefrontal cortex, septum, amygdala, and parabrachial nucleus compared to controls. This effect was specific to GABAB receptors: there was no effect of chronic baclofen treatment on adenosine A1-stimulated GTPγS binding in any region. Chronically-treated rats also exhibited increases in pFAK(Tyr397) and pGSK3β(Tyr216) compared to controls, and displayed wide-spread elevations in phosphorylated dopamine- and cAMP-regulated phosphoprotein-32 (pDARPP-32(Thr34)) compared to acutely-treated or control rats. We postulate that those neuroadaptive effects of GABAB stimulation mediated by G-proteins and their sequelae correlate with tolerance to several of baclofen's effects, whereas sustained signaling via kinase cascades points to cross-talk between GABAB receptors and alternative mechanisms that are resistant to desensitization. Both desensitized and sustained signaling pathways should be considered in the development of pharmacotherapies targeting the GABA system. Copyright © 2015 Elsevier Ltd. All rights reserved.

Toughening and healing of continuous fibre reinforced composites with bis-maleimide based pre-pregs

NASA Astrophysics Data System (ADS)

Kostopoulos, V.; Kotrotsos, A.; Tsantzalis, S.; Tsokanas, P.; Christopoulos, A. C.; Loutas, T.

2016-08-01

Unidirectional (UD) pre-pregs containing self-healing materials based on Diels-Alder reaction bis-maleimide (BMI) polymers were successfully incorporated on the mid-plane of UD carbon fibre reinforced polymers. The fracture toughness of these composites and the introduced healing capability were measured under mode I loading. The interlaminar fracture toughness was enhanced considerably, since the maximum load (P max) of the modified composite increased approximately 1.5 times and the mode I fracture energy (G IC) displayed a significant increase of almost 3.5 times when compared to the reference composites. Furthermore the modified composites displayed a healing efficiency (HE) value of about 30% for P max and 20% for G IC after the first healing, appearing to be an almost stable behaviour after the third healing cycle. The HE displayed a decrease of 20% and 15% for P max and G IC values, respectively, after the fifth healing cycle. During the tests, the monitored acoustic emission (AE) activity of the samples showed that there is no significant difference due to the presence of BMI polymer in terms of AE hits. Moreover, optical microscopy not only showed that the epoxy matrix at the interface is partly infiltrated by the BMI polymer, but it also revealed the presence of pulled out fibres at the fractured surface, indicating ductile behaviour.

Behavioural abnormalities of the hyposulphataemic Nas1 knock-out mouse.

PubMed

Dawson, Paul Anthony; Steane, Sarah Elizabeth; Markovich, Daniel

2004-10-05

We recently generated a sodium sulphate cotransporter knock-out mouse (Nas1-/-) which has increased urinary sulphate excretion and hyposulphataemia. To examine the consequences of disturbed sulphate homeostasis in the modulation of mouse behavioural characteristics, Nas1-/- mice were compared with Nas1+/- and Nas1+/+ littermates in a series of behavioural tests. The Nas1-/- mice displayed significantly (P < 0.001) decreased marble burying behaviour (4.33 +/- 0.82 buried) when compared to Nas1+/+ (7.86 +/- 0.44) and Nas1+/- (8.40 +/- 0.37) animals, suggesting that Nas1-/- mice may have decreased object-induced anxiety. The Nas1-/- mice also displayed decreased locomotor activity by moving less distance (1.53 +/- 0.27 m, P < 0.05) in an open-field test when compared to Nas1+/+ (2.31 +/- 0.24 m) and Nas1+/- (2.15 +/- 0.19 m) mice. The three genotypes displayed similar spatiotemporal and ethological behaviours in the elevated-plus maze and open-field test, with the exception of a decreased defecation frequency by the Nas1-/- mice (40% reduction, P < 0.01). There were no significant differences between Nas1-/- and Nas1+/+ mice in a rotarod performance test of motor coordination and in the forced swim test assessing (anti-)depressant-like behaviours. This is the first study to demonstrate behavioural abnormalities in the hyposulphataemic Nas1-/- mice.

Identification of antibiotics using small molecule variable ligand display on gold nanoparticles.

PubMed

Bresee, Jamee; Maier, Keith E; Melander, Christian; Feldheim, Daniel L

2010-10-28

Here we describe the use of simple 1-pot thiol exchange reactions to generate a library of mixed ligand-coated gold nanoparticles that was screened for antibiotic activity. A library of 120 nanoparticle conjugates was assembled and antibiotic activity toward E. coli was determined and found to depend upon the combination of thiols assembled onto the nanoparticles. The most active conjugate displayed 99.9% growth inhibition at 0.5 μM.

The integrated manual and automatic control of complex flight systems

NASA Technical Reports Server (NTRS)

Schmidt, D. K.

1986-01-01

The topics of research in this program include pilot/vehicle analysis techniques, identification of pilot dynamics, and control and display synthesis techniques for optimizing aircraft handling qualities. The project activities are discussed. The current technical activity is directed at extending and validating the active display synthesis procedure, and the pilot/vehicle analysis of the NLR rate-command flight configurations in the landing task. Two papers published by the researchers are attached as appendices.

Thin glass substrates for mobile applications

NASA Astrophysics Data System (ADS)

Mauch, Reiner H.; Wegener, Holger; Kruse, Anke; Hildebrand, Norbert

2000-10-01

Flat panel displays play an important role as the visual interface for today's electronic devices (Notebook computers, PDA's, pagers, mobile phones, etc.). Liquid Crystal Display's are dominating the market. While for higher resolution displays active matrix displays like Thin Film Transistor LCD's are used, portable devices are mainly using Super Twisted Nematic (STN) displays. Based on the application, STN displays for mobile applications require thinner glass substrates with improved surface quality at a lower cost. The requirements and trends for STN glass substrates are identified and discussed. Different glass manufacturing processes are used today for the manufacture of these substrates. Advantages and disadvantages of the different glass substrate types are presented and discussed.

Undifferentiated Facial Electromyography Responses to Dynamic, Audio-Visual Emotion Displays in Individuals with Autism Spectrum Disorders

ERIC Educational Resources Information Center

Rozga, Agata; King, Tricia Z.; Vuduc, Richard W.; Robins, Diana L.

2013-01-01

We examined facial electromyography (fEMG) activity to dynamic, audio-visual emotional displays in individuals with autism spectrum disorders (ASD) and typically developing (TD) individuals. Participants viewed clips of happy, angry, and fearful displays that contained both facial expression and affective prosody while surface electrodes measured…

Development and Evaluation of an Educational Display for Older Adults: Journey through Health

ERIC Educational Resources Information Center

Jung, Seung Eun; Hermann, Janice; Parker, Stephany; Smith, Brenda J.

2015-01-01

The Journey Through Health educational display was developed using the Health Belief Model and provided information on how the Dietary Guidelines Consumer Brochure messages can positively influence nutrition and physical activity choices to prevent or delay age-related changes throughout the body. The display consisted of 12 posters, educational…

Electrical Stimulation Frequency and Skeletal Muscle Characteristics: Effects on Force and Fatigue.

PubMed

Vromans, Maria; Faghri, Pouran

2017-12-05

This investigation aimed to determine the force and muscle surface electromyography (EMG) responses to different frequencies of electrical stimulation (ES) in two groups of muscles with different size and fiber composition (fast- and slow-twitch fiber proportions) during a fatigue-inducing protocol. Progression towards fatigue was evaluated in the abductor pollicis brevis (APB) and vastus lateralis (VL) when activated by ES at three frequencies (10, 35, and 50Hz). Ten healthy adults (mean age: 23.2 ± 3.0 years) were recruited; participants signed an IRB approved consent form prior to participation. Protocols were developed to 1) identify initial ES current intensity required to generate the 25% maximal voluntary contraction (MVC) at each ES frequency and 2) evaluate changes in force and EMG activity during ES-induced contraction at each frequency while progressing towards fatigue. For both muscles, stimulation at 10Hz required higher current intensity of ES to generate the initial force. There was a significant decline in force in response to ES-induced fatigue for all frequencies and for both muscles (p<0.05). However, the EMG response was not consistent between muscles. During the progression towards fatigue, the APB displayed an initial drop in force followed by an increase in EMG activity and the VL displayed a decrease in EMG activity for all frequencies. Overall, it appeared that there were some significant interactions between muscle size and fiber composition during progression towards fatigue for different ES frequencies. It could be postulated that muscle characteristics (size and fiber composition) should be considered when evaluating progression towards fatigue as EMG and force responses are not consistent between muscles.

Changes in matrix metalloproteinase network in a spontaneous autoimmune uveitis model.

PubMed

Hofmaier, Florian; Hauck, Stefanie M; Amann, Barbara; Degroote, Roxane L; Deeg, Cornelia A

2011-04-08

Autoimmune uveitis is a sight-threatening disease in which autoreactive T cells cross the blood-retinal barrier. Molecular mechanisms contributing to the loss of eye immune privilege in this autoimmune disease are not well understood. In this study, the authors investigated the changes in the matrix metalloproteinase network in spontaneous uveitis. Matrix metalloproteinase (MMP) MMP2, MMP9, and MMP14 expression and tissue inhibitor of metalloproteinase (TIMP)-2 and lipocalin 2 (LCN2) expression were analyzed using Western blot quantification. Enzyme activities were examined with zymography. Expression patterns of network candidates were revealed with immunohistochemistry, comparing physiological appearance and changes in a spontaneous recurrent uveitis model. TIMP2 protein expression was found to be decreased in both the vitreous and the retina of a spontaneous model for autoimmune uveitis (equine recurrent uveitis [ERU]), and TIMP2 activity was significantly reduced in ERU vitreous. Functionally associated MMPs such as MMP2, MMP14, and MMP9 were found to show altered or shifted expression and activity. Although MMP2 decreased in ERU vitreous, MMP9 expression and activity were found to be increased. These changes were reflected by profound changes within uveitic target tissue, where TIMP2, MMP9, and MMP14 decreased in expression, whereas MMP2 displayed a shifted expression pattern. LCN2, a potential stabilizer of MMP9, was found prominently expressed in equine healthy retina and displayed notable changes in expression patterns accompanied by significant upregulation in autoimmune conditions. Invading cells expressed MMP9 and LCN2. This study implicates a dysregulation or a change in functional protein-protein interactions in this TIMP2-associated protein network, together with altered expression of functionally related MMPs.

Evaluations of the removal of Varroa destructor in Russian honey bee colonies that display different levels of Varroa Sensitive Hygienic activities

USDA-ARS?s Scientific Manuscript database

The removal of Varroa destructor was assessed in Russian honey bee (RHB) colonies with known levels of Varroa Sensitive Hygienic (VSH) and brood removal activities. The expression of grooming behaviour using individual bees was also measured using three groups of RHB displaying different VSH levels:...

Heat tolerance and expression of protein synthesis elongation factors, EF-Tu and EF-1a, in spring wheat

USDA-ARS?s Scientific Manuscript database

Protein elongation factors, EF-Tu and EF-1a, have been implicated in cell response to heat stress. In spring wheat, EF-Tu displays chaperone activity and reduces thermal aggregation of Rubisco activase. Similarly, in mammalian cells, EF-1a displays chaperone-like activity and regulates the expressio...

Coupling Binding to Catalysis: Using Yeast Cell Surface Display to Select Enzymatic Activities.

PubMed

Zhang, Keya; Bhuripanyo, Karan; Wang, Yiyang; Yin, Jun

2015-01-01

We find yeast cell surface display can be used to engineer enzymes by selecting the enzyme library for high affinity binding to reaction intermediates. Here we cover key steps of enzyme engineering on the yeast cell surface including library design, construction, and selection based on magnetic and fluorescence-activated cell sorting.

Peptides of the Constant Region of Antibodies Display Fungicidal Activity

PubMed Central

Polonelli, Luciano; Ciociola, Tecla; Magliani, Walter; Zanello, Pier Paolo; D'Adda, Tiziana; Galati, Serena; De Bernardis, Flavia; Arancia, Silvia; Gabrielli, Elena; Pericolini, Eva; Vecchiarelli, Anna; Arruda, Denise C.; Pinto, Marcia R.; Travassos, Luiz R.; Pertinhez, Thelma A.; Spisni, Alberto; Conti, Stefania

2012-01-01

Synthetic peptides with sequences identical to fragments of the constant region of different classes (IgG, IgM, IgA) of antibodies (Fc-peptides) exerted a fungicidal activity in vitro against pathogenic yeasts, such as Candida albicans, Candida glabrata, Cryptococcus neoformans, and Malassezia furfur, including caspofungin and triazole resistant strains. Alanine-substituted derivatives of fungicidal Fc-peptides, tested to evaluate the critical role of each residue, displayed unaltered, increased or decreased candidacidal activity in vitro. An Fc-peptide, included in all human IgGs, displayed a therapeutic effect against experimental mucosal and systemic candidiasis in mouse models. It is intriguing to hypothesize that some Fc-peptides may influence the antifungal immune response and constitute the basis for devising new antifungal agents. PMID:22470523

Evaluation of an integrated graphical display to promote acute change detection in ICU patients

PubMed Central

Anders, Shilo; Albert, Robert; Miller, Anne; Weinger, Matthew B.; Doig, Alexa K.; Behrens, Michael; Agutter, Jim

2012-01-01

Objective The purpose of this study was to evaluate ICU nurses’ ability to detect patient change using an integrated graphical information display (IGID) versus a conventional tabular ICU patient information display (i.e. electronic chart). Design Using participants from two different sites, we conducted a repeated measures simulator-based experiment to assess ICU nurses’ ability to detect abnormal patient variables using a novel IGID versus a conventional tabular information display. Patient scenarios and display presentations were fully counterbalanced. Measurements We measured percent correct detection of abnormal patient variables, nurses’ perceived workload (NASA-TLX), and display usability ratings. Results 32 ICU nurses (87% female, median age of 29 years, and median ICU experience of 2.5 years) using the IGID detected more abnormal variables compared to the tabular display [F (1,119)=13.0, p < 0.05]. There was a significant main effect of site [F (1, 119)=14.2], with development site participants doing better. There were no significant differences in nurses’ perceived workload. The IGID display was rated as more usable than the conventional display, [F (1, 60)=31.7]. Conclusion Overall, nurses reported more important physiological information with the novel IGID than tabular display. Moreover, the finding of site differences may reflect local influences in work practice and involvement in iterative display design methodology. Information displays developed using user-centered design should accommodate the full diversity of the intended user population across use sites. PMID:22534099

Asymmetric triplex metallohelices with high and selective activity against cancer cells

NASA Astrophysics Data System (ADS)

Faulkner, Alan D.; Kaner, Rebecca A.; Abdallah, Qasem M. A.; Clarkson, Guy; Fox, David J.; Gurnani, Pratik; Howson, Suzanne E.; Phillips, Roger M.; Roper, David I.; Simpson, Daniel H.; Scott, Peter

2014-09-01

Small cationic amphiphilic α-helical peptides are emerging as agents for the treatment of cancer and infection, but they are costly and display unfavourable pharmacokinetics. Helical coordination complexes may offer a three-dimensional scaffold for the synthesis of mimetic architectures. However, the high symmetry and modest functionality of current systems offer little scope to tailor the structure to interact with specific biomolecular targets, or to create libraries for phenotypic screens. Here, we report the highly stereoselective asymmetric self-assembly of very stable, functionalized metallohelices. Their anti-parallel head-to-head-to-tail ‘triplex’ strand arrangement creates an amphipathic functional topology akin to that of the active sub-units of, for example, host-defence peptides and p53. The metallohelices display high, structure-dependent toxicity to the human colon carcinoma cell-line HCT116 p53++, causing dramatic changes in the cell cycle without DNA damage. They have lower toxicity to human breast adenocarcinoma cells (MDA-MB-468) and, most remarkably, they show no significant toxicity to the bacteria methicillin-resistant Staphylococcus aureus and Escherichia coli.

Secondary visual workload capability with primary visual and kinesthetic-tactual displays

NASA Technical Reports Server (NTRS)

Gilson, R. D.; Burke, M. W.; Jagacinski, R. J.

1978-01-01

Subjects performed a cross-adaptive tracking task with a visual secondary display and either a visual or a quickened kinesthetic-tactual (K-T) primary display. The quickened K-T display resulted in superior secondary task performance. Comparisons of secondary workload capability with integrated and separated visual displays indicated that the superiority of the quickened K-T display was not simply due to the elimination of visual scanning. When subjects did not have to perform a secondary task, there was no significant difference between visual and quickened K-T displays in performing a critical tracking task.

Investigating the Relationship between Instructors’ Use of Active-Learning Strategies and Students’ Conceptual Understanding and Affective Changes in Introductory Biology: A Comparison of Two Active-Learning Environments

PubMed Central

Cleveland, Lacy M.; Olimpo, Jeffrey T.; DeChenne-Peters, Sue Ellen

2017-01-01

In response to calls for reform in undergraduate biology education, we conducted research examining how varying active-learning strategies impacted students’ conceptual understanding, attitudes, and motivation in two sections of a large-lecture introductory cell and molecular biology course. Using a quasi-experimental design, we collected quantitative data to compare participants’ conceptual understanding, attitudes, and motivation in the biological sciences across two contexts that employed different active-learning strategies and that were facilitated by unique instructors. Students participated in either graphic organizer/worksheet activities or clicker-based case studies. After controlling for demographic and presemester affective differences, we found that students in both active-learning environments displayed similar and significant learning gains. In terms of attitudinal and motivational data, significant differences were observed for two attitudinal measures. Specifically, those students who had participated in graphic organizer/worksheet activities demonstrated more expert-like attitudes related to their enjoyment of biology and ability to make real-world connections. However, all motivational and most attitudinal data were not significantly different between the students in the two learning environments. These data reinforce the notion that active learning is associated with conceptual change and suggests that more research is needed to examine the differential effects of varying active-learning strategies on students’ attitudes and motivation in the domain. PMID:28389428

A Mammalian Conserved Element Derived from SINE Displays Enhancer Properties Recapitulating Satb2 Expression in Early-Born Callosal Projection Neurons

PubMed Central

Nakanishi, Akiko; Sasaki, Takeshi; Yan, Kuo; Tarabykin, Victor; Vigier, Lisa; Sumiyama, Kenta; Hirakawa, Mika; Nishihara, Hidenori; Pierani, Alessandra; Okada, Norihiro

2011-01-01

Short interspersed repetitive elements (SINEs) are highly repeated sequences that account for a significant proportion of many eukaryotic genomes and are usually considered “junk DNA”. However, we previously discovered that many AmnSINE1 loci are evolutionarily conserved across mammalian genomes, suggesting that they may have acquired significant functions involved in controlling mammalian-specific traits. Notably, we identified the AS021 SINE locus, located 390 kbp upstream of Satb2. Using transgenic mice, we showed that this SINE displays specific enhancer activity in the developing cerebral cortex. The transcription factor Satb2 is expressed by cortical neurons extending axons through the corpus callosum and is a determinant of callosal versus subcortical projection. Mouse mutants reveal a crucial function for Sabt2 in corpus callosum formation. In this study, we compared the enhancer activity of the AS021 locus with Satb2 expression during telencephalic development in the mouse. First, we showed that the AS021 enhancer is specifically activated in early-born Satb2+ neurons. Second, we demonstrated that the activity of the AS021 enhancer recapitulates the expression of Satb2 at later embryonic and postnatal stages in deep-layer but not superficial-layer neurons, suggesting the possibility that the expression of Satb2 in these two subpopulations of cortical neurons is under genetically distinct transcriptional control. Third, we showed that the AS021 enhancer is activated in neurons projecting through the corpus callosum, as described for Satb2+ neurons. Notably, AS021 drives specific expression in axons crossing through the ventral (TAG1−/NPY+) portion of the corpus callosum, confirming that it is active in a subpopulation of callosal neurons. These data suggest that exaptation of the AS021 SINE locus might be involved in enhancement of Satb2 expression, leading to the establishment of interhemispheric communication via the corpus callosum, a eutherian-specific brain structure. PMID:22174821

Identification of antimutagenic properties of anthocyanins and other polyphenols from rose (Rosa centifolia) petals and tea.

PubMed

Kumar, Sanjeev; Gautam, Satyendra; Sharma, Arun

2013-06-01

Petals from different rose (Rosa centifolia) cultivars ("passion," "pink noblesse," and "sphinx") were assessed for antimutagenicity using Escherichia coli RNA polymerase B (rpoB)-based Rif (S) →Rif (R) (rifampicin sensitive to resistant) forward mutation assay against ethyl methanesulfonate (EMS)-induced mutagenesis. The aqueous extracts of rose petals from different cultivars exhibited a wide variation in their antimutagenicity. Among these, cv. "passion" was found to display maximum antimutagenicity. Upon further fractionation, the anthocyanin extract of cv. "passion" displayed significantly higher antimutagenicity than its phenolic extract. During thin-layer chromatography (TLC) analysis, the anthocyanin extract got resolved into 3 spots: yellow (Rf : 0.14), blue (Rf : 0.30), and pink (Rf : 0.49). Among these spots, the blue one displayed significantly higher antimutagenicity than the other 2. Upon high-performance liquid chromatography analysis, this blue spot further got resolved into 2 peaks (Rt : 2.7 and 3.8 min). The 2nd peak (Rt : 3.8 min) displaying high antimutagenicity was identified by ESI-IT-MS/MS analysis as peonidin 3-glucoside, whereas less antimutagenic peak 1 (Rt : 2.7) was identified as cyanidin 3, 5-diglucoside. The other TLC bands were also characterized by ESI-IT-MS/MS analysis. The least antimutagenic pink band (Rf : 0.49) was identified as malvidin 3-acetylglucoside-4-vinylcatechol, whereas non-antimutagenic yellow band (Rf : 0.14) was identified as luteolinidin anthocyanin derivative. Interestingly, the anthocyanin extracted from rose tea of cv. "passion" exhibited a similar antimutagenicity as that of the raw rose petal indicating the thermal stability of the contributing bioactive(s). The findings thus indicated the health protective property of differently colored rose cultivars and the nature of their active bioingredients. © 2013 Institute of Food Technologists®

CNS Schwann cells display oligodendrocyte precursor-like potassium channel activation and antigenic expression in vitro.

PubMed

Kegler, Kristel; Imbschweiler, Ilka; Ulrich, Reiner; Kovermann, Peter; Fahlke, Christoph; Deschl, Ulrich; Kalkuhl, Arno; Baumgärnter, Wolfgang; Wewetzer, Konstantin

2014-06-01

Central nervous system (CNS) injury triggers production of myelinating Schwann cells from endogenous oligodendrocyte precursors (OLPs). These CNS Schwann cells may be attractive candidates for novel therapeutic strategies aiming to promote endogenous CNS repair. However, CNS Schwann cells have been so far mainly characterized in situ regarding morphology and marker expression, and it has remained enigmatic whether they display functional properties distinct from peripheral nervous system (PNS) Schwann cells. Potassium channels (K+) have been implicated in progenitor and glial cell proliferation after injury and may, therefore, represent a suitable pharmacological target. In the present study, we focused on the function and expression of voltage-gated K+ channels Kv(1-12) and accessory β-subunits in purified adult canine CNS and PNS Schwann cell cultures using electrophysiology and microarray analysis and characterized their antigenic phenotype. We show here that K+ channels differed significantly in both cell types. While CNS Schwann cells displayed prominent K D-mediated K+ currents, PNS Schwann cells elicited K(D-) and K(A-type) K+ currents. Inhibition of K+ currents by TEA and Ba2+ was more effective in CNS Schwann cells. These functional differences were not paralleled by differential mRNA expression of Kv(1-12) and accessory β-subunits. However, O4/A2B5 and GFAP expressions were significantly higher and lower, respectively, in CNS than in PNS Schwann cells. Taken together, this is the first evidence that CNS Schwann cells display specific properties not shared by their peripheral counterpart. Both Kv currents and increased O4/A2B5 expression were reminiscent of OLPs suggesting that CNS Schwann cells retain OLP features during maturation.

High-performance large-area AMLCD avionic display module

NASA Astrophysics Data System (ADS)

Syroid, Daniel D.; Hansen, Glenn A.

1995-06-01

There is a need for a reliable source of high performance large area sunlight readable active matrix liquid crystal displays (AMLCDs) for avionic and military land vehicle applications. Image Quest has developed an avionic display module (ADM) to demonstrate the capability to produce high performance avionic displays to satisfy this need. The ADM is a large area (6.24 X 8.32 inch) display with VGA compatible interface, 640 X 480 color pixels and 64 gray shades per primary color. The display features excellent color discrimination in full sunlight due to a saturated color gamut, very low specular reflectance (< 1%) and high output white luminance (200 fL). The ADM is designed from the glass up to fully meet the avionic and military application and environment. Control over all the display performance parameters including contrast, transmission, chroma, resolution, active size and packaging configuration is ensured because Image Quest produces all of the critical elements of the display. These elements include the a-Si TFT AMLCD glass, RGB color filter matrix, bonding of folded back driver TABs, anti-reflective cover glass, LC heater and integration of high luminance hot cathode backlight with thermal controls. The display features rugged compact packaging, 2000:1 luminance dimming range and wide operating temperature range (-40 to +71 $DRGC). In the immediate future Image Quest plans to expand the development efforts to other similar custom high resolution and high performance avionic display module configurations including 4 X 4 inch delta triad, 6.7 X 6.7 inch delta triad and 16.5 inch diagonal with 1280 X 1024 pixels. Image Quest can deliver up to 10,000 displays per year on a timely basis at a reasonable cost.

Image Quality Characteristics of Handheld Display Devices for Medical Imaging

PubMed Central

Yamazaki, Asumi; Liu, Peter; Cheng, Wei-Chung; Badano, Aldo

2013-01-01

Handheld devices such as mobile phones and tablet computers have become widespread with thousands of available software applications. Recently, handhelds are being proposed as part of medical imaging solutions, especially in emergency medicine, where immediate consultation is required. However, handheld devices differ significantly from medical workstation displays in terms of display characteristics. Moreover, the characteristics vary significantly among device types. We investigate the image quality characteristics of various handheld devices with respect to luminance response, spatial resolution, spatial noise, and reflectance. We show that the luminance characteristics of the handheld displays are different from those of workstation displays complying with grayscale standard target response suggesting that luminance calibration might be needed. Our results also demonstrate that the spatial characteristics of handhelds can surpass those of medical workstation displays particularly for recent generation devices. While a 5 mega-pixel monochrome workstation display has horizontal and vertical modulation transfer factors of 0.52 and 0.47 at the Nyquist frequency, the handheld displays released after 2011 can have values higher than 0.63 at the respective Nyquist frequencies. The noise power spectra for workstation displays are higher than 1.2×10−5 mm2 at 1 mm−1, while handheld displays have values lower than 3.7×10−6 mm2. Reflectance measurements on some of the handheld displays are consistent with measurements for workstation displays with, in some cases, low specular and diffuse reflectance coefficients. The variability of the characterization results among devices due to the different technological features indicates that image quality varies greatly among handheld display devices. PMID:24236113

Pyrazolo[1,5-a]-1,3,5-triazine as a purine bioisostere: access to potent cyclin-dependent kinase inhibitor (R)-roscovitine analogue.

PubMed

Popowycz, Florence; Fournet, Guy; Schneider, Cédric; Bettayeb, Karima; Ferandin, Yoan; Lamigeon, Cyrile; Tirado, Oscar M; Mateo-Lozano, Silvia; Notario, Vicente; Colas, Pierre; Bernard, Philippe; Meijer, Laurent; Joseph, Benoît

2009-02-12

Pharmacological inhibitors of cyclin-dependent kinases (CDKs) have a wide therapeutic potential. Among the CDK inhibitors currently under clinical trials, the 2,6,9-trisubstituted purine (R)-roscovitine displays rather high selectivity, low toxicity, and promising antitumor activity. In an effort to improve this structure, we synthesized several bioisosteres of roscovitine. Surprisingly, one of them, pyrazolo[1,5-a]-1,3,5-triazine 7a (N-&-N1, GP0210), displayed significantly higher potency, compared to (R)-roscovitine and imidazo[2,1-f]-1,2,4-triazine 13 (N-&-N2, GP0212), at inhibiting various CDKs and at inducing cell death in a wide variety of human tumor cell lines. This approach may thus provide second generation analogues with enhanced biomedical potential.

Novel ZnO-binding peptides obtained by the screening of a phage display peptide library

NASA Astrophysics Data System (ADS)

Golec, Piotr; Karczewska-Golec, Joanna; Łoś, Marcin; Węgrzyn, Grzegorz

2012-11-01

Zinc oxide (ZnO) is a semiconductor compound with a potential for wide use in various applications, including biomaterials and biosensors, particularly as nanoparticles (the size range of ZnO nanoparticles is from 2 to 100 nm, with an average of about 35 nm). Here, we report isolation of novel ZnO-binding peptides, by screening of a phage display library. Interestingly, amino acid sequences of the ZnO-binding peptides reported in this paper and those described previously are significantly different. This suggests that there is a high variability in sequences of peptides which can bind particular inorganic molecules, indicating that different approaches may lead to discovery of different peptides of generally the same activity (e.g., binding of ZnO) but having various detailed properties, perhaps crucial under specific conditions of different applications.

Effects of translational and rotational motions and display polarity on visual performance.

PubMed

Feng, Wen-Yang; Tseng, Feng-Yi; Chao, Chin-Jung; Lin, Chiuhsiang Joe

2008-10-01

This study investigated effects of both translational and rotational motion and display polarity on a visual identification task. Three different motion types--heave, roll, and pitch--were compared with the static (no motion) condition. The visual task was presented on two display polarities, black-on-white and white-on-black. The experiment was a 4 (motion conditions) x 2 (display polarities) within-subjects design with eight subjects (six men and two women; M age = 25.6 yr., SD = 3.2). The dependent variables used to assess the performance on the visual task were accuracy and reaction time. Motion environments, especially the roll condition, had statistically significant effects on the decrement of accuracy and reaction time. The display polarity was significant only in the static condition.

Context based configuration management system

NASA Technical Reports Server (NTRS)

Gurram, Mohana M. (Inventor); Maluf, David A. (Inventor); Mederos, Luis A. (Inventor); Gawdiak, Yuri O. (Inventor)

2010-01-01

A computer-based system for configuring and displaying information on changes in, and present status of, a collection of events associated with a project. Classes of icons for decision events, configurations and feedback mechanisms, and time lines (sequential and/or simultaneous) for related events are displayed. Metadata for each icon in each class is displayed by choosing and activating the corresponding icon. Access control (viewing, reading, writing, editing, deleting, etc.) is optionally imposed for metadata and other displayed information.

Space Station Displays and Controls Technology Evolution

NASA Technical Reports Server (NTRS)

Blackburn, Greg C.

1990-01-01

Viewgraphs on space station displays and controls technology evolution are presented. Topics covered include: a historical perspective; major development objectives; current development activities; key technology areas; and technology evolution issues.

A study on aircraft map display location and orientation. [effects of map display location on manual piloting performance

NASA Technical Reports Server (NTRS)

Baty, D. L.; Wempe, T. E.; Huff, E. M.

1973-01-01

Six airline pilots participated in a fixed-base simulator study to determine the effects of two Horizontal Situation Display (HSD/map) panel locations relative to the Vertical Situation Display (VSD), and of three map orientations on manual piloting performance. Pilot comments and opinions were formally obtained. Significant performance differences were found between wind conditions, and among pilots, but not between map locations and orientations. The results also illustrate the potential tracking accuracy of such a display. Recommendations concerning display location and map orientation are made.

New perspectives for natural antimicrobial peptides: application as antinflammatory drugs in a murine model.

PubMed

Capparelli, Rosanna; De Chiara, Francesco; Nocerino, Nunzia; Montella, Rosa Chiara; Iannaccone, Marco; Fulgione, Andrea; Romanelli, Alessandra; Avitabile, Concetta; Blaiotta, Giuseppe; Capuano, Federico

2012-11-17

Antimicrobial peptides (AMPs) are an ancient group of defense molecules. AMPs are widely distributed in nature (being present in mammals, birds, amphibians, insects, plants, and microorganisms). They display bactericidal as well as immunomodulatory properties. The aim of this study was to investigate the antimicrobial and anti-inflammatory activities of a combination of two AMPs (temporin B and the royal jellein I) against Staphylococcus epidermidis. The temporin B (TB-KK) and the royal jelleins I, II, III chemically modified at the C terminal (RJI-C, RJII-C, RJIII-C), were tested for their activity against 10 different Staphylococcus epidermidis strains, alone and in combination. Of the three royal jelleins, RJI-C showed the highest activity. Moreover, the combination of RJI-C and TB-KK (MIX) displayed synergistic activity. In vitro, the MIX displayed low hemolytic activity, no NO2- production and the ability to curb the synthesis of the pro-inflammatory cytokines TNF-α and IFN-γ to the same extent as acetylsalicylic acid. In vivo, the MIX sterilized mice infected with Staphylococcus epidermidis in eleven days and inhibited the expression of genes encoding the prostaglandin-endoperoxide synthase 2 (COX-2) and CD64, two important parameters of inflammation. The study shows that the MIX - a combination of two naturally occurring peptides - displays both antimicrobial and anti-inflammatory activities.

Cardiovascular and metabolic activity at rest and during psychological and physical challenge in normotensives and subjects with mildly elevated blood pressure.

PubMed

Sims, J; Carroll, D

1990-03-01

Heart rate, systolic and diastolic blood pressure, and respiratory and metabolic activity were recorded prior to and during mental arithmetic and a video game task in 20 young men with mildly elevated casual systolic blood pressures. Twenty-five unambiguously normotensive young men were tested under the same protocol. For pretask baseline physiological activity, group differences emerged for all cardiovascular and metabolic variables; thus the elevated blood pressure group displayed not only higher resting cardiovascular levels than normotensive subjects, but higher levels of metabolic activity too. With regard to change in physiological activity from rest to task, the group with mildly elevated blood pressure showed reliably larger increases in heart rate to the mental arithmetic task than the normotensive subjects. These effects, however, were not paralleled by group differences in metabolic activity increase. Physiological measures were also taken prior to and during graded dynamic exercise. The subsequent calculation of individual heart rate-oxygen consumption exercise regression lines allowed the comparison of actual and predicted heart rates during psychological challenge. The subjects with mildly elevated blood pressure displayed significantly greater discrepancies between actual and predicted heart rate values than normotensives during the psychological tasks in general and mental arithmetic in particular. Group differences in physiological activity during exercise largely reflected the pattern seen at rest. A possible exception here was systolic blood pressure. Not only were systolic blood pressure levels higher throughout the exercise phase for mildly elevated blood pressure subjects, but this group evidenced more of an increase from rest to exercise than the normotensives.

Complexation of carbendazim with hydroxypropyl-β-cyclodextrin to improve solubility and fungicidal activity.

PubMed

Ge, Xia; Huang, Zheng; Tian, Shilong; Huang, Yulong; Zeng, Chaozhen

2012-06-05

The effect of hydroxypropyl-β-cyclodextrin (HPβCD) on the improvement of the solubility and fungicidal activity of carbendazim (MBC) has been investigated. The inclusion complexation of HPβCD with MBC has been prepared and characterized by phase solubility diagram, fluorescence, (1)H NMR, ROESY and FT-IR spectra. The stoichiometric ratio and stability constant were determined by Job's plot and phase solubility studies, respectively. The inclusion complex MBC·HPβCD has exhibited different properties from MBC. The obtained inclusion complex was found to significantly improve the water solubility of MBC. In addition, the biological activity indicated that the complex displayed the better fungicidal activity than MBC. The present study provided useful information for a more rational application of MBC. Copyright © 2012 Elsevier Ltd. All rights reserved.

Antibacterial activity of Pinus elliottii against anaerobic bacteria present in primary endodontic infections.

PubMed

Caetano da Silva, Sandro Donizete; Mendes de Souza, Maria Gorete; Oliveira Cardoso, Miguel Jorge; da Silva Moraes, Thais; Ambrósio, Sérgio Ricardo; Sola Veneziani, Rodrigo Cássio; Martins, Carlos Henrique G

2014-12-01

Endodontic infections have a polymicrobial nature, but anaerobic bacteria prevail among the infectious microbes. Considering that it is easy to eliminate planktonic bacteria, biofilm-forming bacteria still challenge clinicians during the fight against endodontic diseases. The chemical constituents of the oleoresin of Pinus elliottii, a plant belonging to the family Pinaceae, stand out in the search for biologically active compounds based on natural products with potential application in the treatment of endodontic infections. Indeed, plant oleoresins are an abundant natural source of diterpenes that display significant and well-defined biological activities as well as potential antimicrobial action. In this context, this study aimed to (1) evaluate the in vitro antibacterial activity of the oleoresin, fractions, and subfractions of P. elliottii as well as the action of dehydroabietic acid against 11 anaerobic bacteria that cause endodontic infection in both their planktonic and biofilm forms and (2) assess the in vitro antibiofilm activity of dehydroabietic acid against the same group of bacteria. The broth microdilution technique helped to determine the minimum inhibitory concentration (MIC) of the oleoresin and fractions. This same technique aided determination of the MIC values of nine subfractions of Fraction 1, the most active fraction. The MIC, minimum bactericidal concentration, and antibiofilm activity of dehydroabietic acid against the tested anaerobic bacteria were also examined. The oleoresin and fractions, especially fraction PE1, afforded promising MIC values, which ranged from 0.4 to 50 μg/mL. Concerning the nine evaluated subfractions, PE1.3 and PE1.4 furnished the most noteworthy MIC values, between 6.2 and 100 μg/mL. Dehydroabietic acid displayed antibacterial activity, with MIC values lying from 6.2 to 50 μg/mL, as well as bactericidal effect for all the investigated bacteria, except for Prevotella nigrescens. Assessment of the antibiofilm activity revealed significant results--MICB50 lay between 7.8 and 62.5 μg/mL, and dehydroabietic acid prevented all the evaluated bacteria from forming a biofilm. Hence, the chemical constituents of P. elliottii are promising biomolecules to develop novel therapeutic strategies to fight against endodontic infections. Copyright © 2014 Elsevier Ltd. All rights reserved.

Cytotoxic arylnaphthalene lignans from a Vietnamese acanthaceae, Justicia patentiflora.

PubMed

Susplugas, Sophie; Hung, Nguyen Van; Bignon, Jérôme; Thoison, Odile; Kruczynski, Anna; Sévenet, Thierry; Guéritte, Françoise

2005-05-01

One new norlignan (1) and five new lignans (2-6) were isolated from the leaves and stems of Justicia patentiflora by a bioassay-guided purification. Five known compounds, carinatone, diphyllin, justicidin A, taiwanin E, and tuberculatin, were also found in J. patentiflora. Most of the new compounds display significant activity in in vitro cytotoxic assays against KB, HCT116, and MCF-7 cancer cell lines and arrest the cell cycle in the G0/G1 phase.

Mitochondria-localized phospholipase A2, AoPlaA, in Aspergillus oryzae displays phosphatidylethanolamine-specific activity and is involved in the maintenance of mitochondrial phospholipid composition.

PubMed

Kotani, Shohei; Izawa, Sho; Komai, Noriyuki; Takayanagi, Ayumi; Arioka, Manabu

2016-11-01

In mammals, cytosolic phospholipases A 2 (cPLA 2 s) play important physiological roles by releasing arachidonic acid, a precursor for bioactive lipid mediators, from the biological membranes. In contrast, fungal cPLA 2 -like proteins are much less characterized and their roles have remained elusive. AoPlaA is a cPLA 2 -like protein in the filamentous fungus Aspergillus oryzae which, unlike mammalian cPLA 2 , localizes to mitochondria. In this study, we investigated the biochemical and physiological functions of AoPlaA. Recombinant AoPlaA produced in E. coli displayed Ca 2+ -independent lipolytic activity. Mass spectrometry analysis demonstrated that AoPlaA displayed PLA 2 activity to phosphatidylethanolamine (PE), but not to other phospholipids, and generated 1-acylated lysoPE. Catalytic site mutants of AoPlaA displayed almost no or largely reduced activity to PE. Consistent with PE-specific activity of AoPlaA, AoplaA-overexpressing strain showed decreased PE content in the mitochondrial fraction. In contrast, AoplaA-disruption strain displayed increased content of cardiolipin. AoplaA-overexpressing strain, but not its counterparts overexpressing the catalytic site mutants, exhibited retarded growth at low temperature, possibly because of the impairment of the mitochondrial function caused by excess degradation of PE. These results suggest that AoPlaA is a novel PE-specific PLA 2 that plays a regulatory role in the maintenance of mitochondrial phospholipid composition. Copyright © 2016 Elsevier Inc. All rights reserved.

EV20-Sap, a novel anti-HER-3 antibody-drug conjugate, displays promising antitumor activity in melanoma

PubMed Central

Ponziani, Sara; Lamolinara, Alessia; Iezzi, Manuela; Cimini, Annamaria; Angelucci, Francesco; Sorda, Rossana La; Laurenzi, Vincenzo De; Natali, Pier Giorgio; Ippoliti, Rodolfo; Iacobelli, Stefano; Sala, Gianluca

2017-01-01

Melanoma is the most biologically aggressive skin cancer of well established constitutive and induced resistance to pharmacological treatment. Despite the recent progresses in immunotherapies, many advanced metastatic melanoma patients still face a significant mortality risk. The aggressive nature of this disease sustains an urgent need for more successful, effective drugs. HER-3 - one of the four member of the tyrosin kinase epidermal growth factor receptors (EGFRs) family- is frequently overexpressed in solid tumors, including melanoma. Moreover, up-regulation of HER-3 and its ligand NRGβ-1 are associated with poor prognosis, thus suggesting this receptor as a suitable target for cancer therapy. Several monoclonal antibodies targeting HER-3 are currently available, but preliminary results from clinical testing of these agents reveal a modest efficacy. Thus, a substantial improvement over this immunotherapeutic approach could be offered by an anti-HER-3 based Antibody-Drug Conjugate (ADC). In the present paper, we describe the generation of an ADC obtained by coupling the HER-3 targeting antibody EV20 linked to the plant toxin Saporin (Sap). In vitro, this ADC displays a powerful, specific and target-dependent cytotoxic activity which correlates with the degree of expression and internalization of HER-3 on tumor cells. Furthermore, in a murine melanoma model, EV20-Sap treatment leads to a significant reduction of the number of pulmonary metastasis. PMID:29221137

A phosphodiesterase 4B-dependent interplay between tumor cells and the microenvironment regulates angiogenesis in B-cell lymphoma

PubMed Central

Suhasini, Avvaru N.; Lin, An-Ping; Bhatnagar, Harshita; Kim, Sang-Woo; Moritz, August W.; Aguiar, Ricardo C. T.

2015-01-01

Angiogenesis associates with poor outcome in diffuse large B-cell lymphoma (DLBCL), but the contribution of the lymphoma cells to this process remains unclear. Addressing this knowledge gap may uncover unsuspecting proangiogenic signaling nodes and highlight alternative antiangiogenic therapies. Here we identify the second messenger cyclic-AMP (cAMP) and the enzyme that terminates its activity, phosphodiesterase 4B (PDE4B), as regulators of B-cell lymphoma angiogenesis. We first show that cAMP, in a PDE4B-dependent manner, suppresses PI3K/AKT signals to down-modulate VEGF secretion and vessel formation in vitro. Next, we create a novel mouse model that combines the lymphomagenic Myc transgene with germline deletion of Pde4b. We show that lymphomas developing in a Pde4b-null background display significantly lower microvessel density in association with lower VEGF levels and PI3K/AKT activity. We recapitulate these observations by treating lymphoma-bearing mice with the FDA-approved PDE4 inhibitor Roflumilast. Lastly, we show that primary human DLBCLs with high PDE4B expression display significantly higher microvessel density. Here, we defined an unsuspected signaling circuitry in which the cAMP generated in lymphoma cells downmodulates PI3K/AKT and VEGF secretion to negatively influence vessel development in the microenvironment. These data identify PDE4 as an actionable antiangiogenic target in DLBCL. PMID:26503641

The GPI transamidase complex subunit PbGPI16 of Plasmodium berghei is important for inducing experimental cerebral malaria.

PubMed

Liu, Qingyang; Zhao, Yan; Zheng, Li; Zhu, Xiaotong; Cui, Liwang; Cao, Yaming

2018-05-21

In animal models of experimental cerebral malaria (ECM), the glycosylphosphatidylinositols (GPIs) and GPI anchors are the major factors that induce nuclear factor kappa B (NF-κB) activation and proinflammatory responses, which contribute to malaria pathogenesis. GPIs and GPI anchors are transported to the cell surface via a process called GPI transamidation, which involves the GPI transamidase (GPI-T) complex. In this study, we showed that GPI16, one of the GPI-T subunits, is highly conserved among Plasmodium species. Genetic knockout of pbgpi16 ( Δpbgpi16 ) in the rodent malaria parasite Plasmodium berghei ANKA strain led to a significant reduction of the amount of GPIs in the membranes of merozoites as well as surface display of several GPI-anchored merozoite surface proteins. Compared with the wild-type parasites, Δpbgpi16 parasites in C57BL/6 mice caused much less NF-κB activation and elicited a substantially attenuated T helper type 1 response. As a result, Δpbgpi16 -infected mice displayed much less severe brain pathology and considerably fewer Δpbgpi16 -infected mice died from ECM. This study corroborated the GPI toxin as a significant inducer of ECM and further suggested that vaccines against parasite GPIs may be a promising strategy to limit the severity of malaria. Copyright © 2018 American Society for Microbiology.

Synthesis and pharmacological evaluation of pyrazolo[4,3-c]cinnoline derivatives as potential anti-inflammatory and antibacterial agents.

PubMed

Tonk, Rajiv Kumar; Bawa, Sandhya; Chawla, Gita; Deora, Girdhar Singh; Kumar, Suresh; Rathore, Vandana; Mulakayala, Naveen; Rajaram, Azad; Kalle, Arunasree M; Afzal, Obaid

2012-11-01

A series of pyrazolo[4,3-c]cinnoline derivatives was synthesized, characterized and evaluated for anti-inflammatory and antibacterial activity. Test compounds that exhibited good anti-inflammatory activity were further screened for their ulcerogenic and lipid peroxidation activity. Compounds 4d and 4l showed promising anti-inflammatory activity with reduced ulcerogenic and lipid peroxidation activity when compared to naproxen. Docking results of these two compounds with COX-2 (PDB ID: 1CX2) also exhibited a strong binding profile. Among the test derivatives, compound 4i displayed significant antibacterial property against gram-negative (Escherichia coli and Pseudomonas aeruginosa) and gram-positive (Staphylococcus aureus) bacteria. However, compound 4b emerged as the best dual anti-inflammatory-antibacterial agent in the present study. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Hormones and the neuromuscular control of courtship in the golden-collared manakin (Manacus vitellinus)

PubMed Central

Schlinger, Barney A.; Barske, Julia; Day, Lainy; Fusani, Leonida; Fuxjager, Matthew J.

2014-01-01

Many animals engage in spectacular courtship displays, likely recruiting specialized neural, hormonal and muscular systems to facilitate these performances. Male golden-collared manakins (Manacus vitellinus) of Panamanian rainforests perform physically elaborate courtship displays that include novel forms of visual and acoustic signaling. We study the behavioral neuroendocrinology of this male’s courtship, combining field behavioral observations with anatomical, biochemical and molecular laboratory-based studies. Seasonally, male courtship is activated by testosterone with little correspondence between testosterone levels and display intensity. Females prefer males whose displays are exceptionally frequent, fast and accurate. The activation of androgen receptors (AR) is crucial for optimal display performance, with AR expressed at elevated levels in several neuromuscular tissues. Apparently, courtship enlists an elaborate androgen-dependent network that includes spinal motoneurons, skeletal muscles and somatosensory systems. This work highlights the value of studying non-traditional species to illuminate physiological adaptations and, hopefully, stimulates future research on other species with complex behaviors. PMID:23624091

Signal enhancement, not active suppression, follows the contingent capture of visual attention.

PubMed

Livingstone, Ashley C; Christie, Gregory J; Wright, Richard D; McDonald, John J

2017-02-01

Irrelevant visual cues capture attention when they possess a task-relevant feature. Electrophysiologically, this contingent capture of attention is evidenced by the N2pc component of the visual event-related potential (ERP) and an enlarged ERP positivity over the occipital hemisphere contralateral to the cued location. The N2pc reflects an early stage of attentional selection, but presently it is unclear what the contralateral ERP positivity reflects. One hypothesis is that it reflects the perceptual enhancement of the cued search-array item; another hypothesis is that it is time-locked to the preceding cue display and reflects active suppression of the cue itself. Here, we varied the time interval between a cue display and a subsequent target display to evaluate these competing hypotheses. The results demonstrated that the contralateral ERP positivity is tightly time-locked to the appearance of the search display rather than the cue display, thereby supporting the perceptual enhancement hypothesis and disconfirming the cue-suppression hypothesis. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Separated carbon nanotube macroelectronics for active matrix organic light-emitting diode displays.

PubMed

Zhang, Jialu; Fu, Yue; Wang, Chuan; Chen, Po-Chiang; Liu, Zhiwei; Wei, Wei; Wu, Chao; Thompson, Mark E; Zhou, Chongwu

2011-11-09

Active matrix organic light-emitting diode (AMOLED) display holds great potential for the next generation visual technologies due to its high light efficiency, flexibility, lightweight, and low-temperature processing. However, suitable thin-film transistors (TFTs) are required to realize the advantages of AMOLED. Preseparated, semiconducting enriched carbon nanotubes are excellent candidates for this purpose because of their excellent mobility, high percentage of semiconducting nanotubes, and room-temperature processing compatibility. Here we report, for the first time, the demonstration of AMOLED displays driven by separated nanotube thin-film transistors (SN-TFTs) including key technology components, such as large-scale high-yield fabrication of devices with superior performance, carbon nanotube film density optimization, bilayer gate dielectric for improved substrate adhesion to the deposited nanotube film, and the demonstration of monolithically integrated AMOLED display elements with 500 pixels driven by 1000 SN-TFTs. Our approach can serve as the critical foundation for future nanotube-based thin-film display electronics.

Separated Carbon Nanotube Macroelectronics for Active Matrix Organic Light-Emitting Diode Displays

NASA Astrophysics Data System (ADS)

Fu, Yue; Zhang, Jialu; Wang, Chuan; Chen, Pochiang; Zhou, Chongwu

2012-02-01

Active matrix organic light-emitting diode (AMOLED) display holds great potential for the next generation visual technologies due to its high light efficiency, flexibility, lightweight, and low-temperature processing. However, suitable thin-film transistors (TFTs) are required to realize the advantages of AMOLED. Pre-separated, semiconducting enriched carbon nanotubes are excellent candidates for this purpose because of their excellent mobility, high percentage of semiconducting nanotubes, and room-temperature processing compatibility. Here we report, for the first time, the demonstration of AMOLED displays driven by separated nanotube thin-film transistors (SN-TFTs) including key technology components such as large-scale high-yield fabrication of devices with superior performance, carbon nanotube film density optimization, bilayer gate dielectric for improved substrate adhesion to the deposited nanotube film, and the demonstration of monolithically integrated AMOLED display elements with 500 pixels driven by 1000 SN-TFTs. Our approach can serve as the critical foundation for future nanotube-based thin-film display electronics.

Maraviroc as intensification strategy in HIV-1 positive patients with deficient immunological response: an Italian randomized clinical trial.

PubMed

Rusconi, Stefano; Vitiello, Paola; Adorni, Fulvio; Colella, Elisa; Focà, Emanuele; Capetti, Amedeo; Meraviglia, Paola; Abeli, Clara; Bonora, Stefano; D'Annunzio, Marco; Di Biagio, Antonio; Di Pietro, Massimo; Butini, Luca; Orofino, Giancarlo; Colafigli, Manuela; d'Ettorre, Gabriella; Francisci, Daniela; Parruti, Giustino; Soria, Alessandro; Buonomini, Anna Rita; Tommasi, Chiara; Mosti, Silvia; Bai, Francesca; Di Nardo Stuppino, Silvia; Morosi, Manuela; Montano, Marco; Tau, Pamela; Merlini, Esther; Marchetti, Giulia

2013-01-01

Immunological non-responders (INRs) lacked CD4 increase despite HIV-viremia suppression on HAART and had an increased risk of disease progression. We assessed immune reconstitution profile upon intensification with maraviroc in INRs. We designed a multi-centric, randomized, parallel, open label, phase 4 superiority trial. We enrolled 97 patients on HAART with CD4+<200/µL and/or CD4+ recovery ≤ 25% and HIV-RNA<50 cp/mL. Patients were randomized 1:1 to HAART+maraviroc or continued HAART. CD4+ and CD8+ CD45+RA/RO, Ki67 expression and plasma IL-7 were quantified at W0, W12 and W48. By W48 both groups displayed a CD4 increase without a significant inter-group difference. A statistically significant change in CD8 favored patients in arm HAART+maraviroc versus HAART at W12 (p=.009) and W48 (p=.025). The CD4>200/µL and CD4>200/µL + CD4 gain ≥ 25% end-points were not satisfied at W12 (p=.24 and p=.619) nor at W48 (p=.076 and p=.236). Patients continuing HAART displayed no major changes in parameters of T-cell homeostasis and activation. Maraviroc-receiving patients experienced a significant rise in circulating IL-7 by W48 (p=.01), and a trend in temporary reduction in activated HLA-DR+CD38+CD4+ by W12 (p=.06) that was not maintained at W48. Maraviroc intensification in INRs did not have a significant advantage in reconstituting CD4 T-cell pool, but did substantially expand CD8. It resulted in a low rate of treatment discontinuations. ClinicalTrials.gov NCT00884858 http://clinicaltrials.gov/show/NCT00884858.

Sex- and Disease-Specific Inflammasome Signatures in Circulating Blood Leukocytes of Patients with Abdominal Aortic Aneurysm

PubMed Central

Wu, Xiaoyu; Cakmak, Sinan; Wortmann, Markus; Hakimi, Maani; Zhang, Jian; Böckler, Dittmar; Dihlmann, Susanne

2016-01-01

Male sex is a risk factor for abdominal aortic aneurysm (AAA). Within the AAA adventitia, infiltrating leukocytes express high levels of inflammasome components. To further elucidate the role of inflammatory cells in the pathogenesis of AAA, we here addressed expression and functionality of inflammasome components in peripheral blood mononuclear cells (PBMC) of AAA patients in association with sex. PBMC and plasma were isolated from 100 vascular patients, including 34 pairs of AAA patients and age/sex-matched non-AAA patients. Male PBMC were found to express significantly higher mRNA levels of AIM2, NLRP3, ASC (PYCARD), CASP1, CASP5, and IL1B (all P < 0.0001) than female PBMC. Within the male patients, PBMC of AAA patients displayed increased mRNA levels of NLRP3 (P = 0.044), CASP1 (P = 0.032) and IL1B (P = 0.0004) compared with matched non-AAA PBMC, whereas there was no difference between female AAA and non-AAA patients. The relative protein level of NLRP3 was significantly lower in PBMC lysates from all AAA patients than in matched controls (P = 0.038), whereas AIM2 and active Caspase-1 (p10) protein levels were significantly increased (P = 0.014 and P = 0.049). ELISA revealed significantly increased IL-1α (mean = 6.34 versus 0.01 pg/mL) and IL-1β plasma levels (mean = 12.07 versus 0.04 pg/mL) in AAA patients. The data indicate that male PBMC display a systemic proinflammatory state with primed inflammasomes that may contribute to AAA-pathogenesis. The AAA-specific inflammasome activation pattern suggests differential regulation of the sensors AIM2 and NLRP3 in inflammatory cells of AAA patients. PMID:27474483

Soya bean Gα proteins with distinct biochemical properties exhibit differential ability to complement Saccharomyces cerevisiae gpa1 mutant.

PubMed

Roy Choudhury, Swarup; Wang, Yuqi; Pandey, Sona

2014-07-01

Signalling pathways mediated by heterotrimeric G-proteins are common to all eukaryotes. Plants have a limited number of each of the G-protein subunits, with the most elaborate G-protein network discovered so far in soya bean (Glycine max, also known as soybean) which has four Gα, four Gβ and ten Gγ proteins. Biochemical characterization of Gα proteins from plants suggests significant variation in their properties compared with the well-characterized non-plant proteins. Furthermore, the four soya bean Gα (GmGα) proteins exhibit distinct biochemical activities among themselves, but the extent to which such biochemical differences contribute to their in vivo function is also not known. We used the yeast gpa1 mutant which displays constitutive signalling and growth arrest in the pheromone-response pathway as an in vivo model to evaluate the effect of distinct biochemical activities of GmGα proteins. We showed that specific GmGα proteins can be activated during pheromone-dependent receptor-mediated signalling in yeast and they display different strengths towards complementation of yeast gpa1 phenotypes. We also identified amino acids that are responsible for differential complementation abilities of specific Gα proteins. These data establish that specific plant Gα proteins are functional in the receptor-mediated pheromone-response pathway in yeast and that the subtle biochemical differences in their activity are physiologically relevant.

Killing of Mycobacterium avium by Lactoferricin Peptides: Improved Activity of Arginine- and d-Amino-Acid-Containing Molecules

PubMed Central

Silva, Tânia; Magalhães, Bárbara; Maia, Sílvia; Gomes, Paula; Nazmi, Kamran; Bolscher, Jan G. M.; Rodrigues, Pedro N.; Bastos, Margarida

2014-01-01

Mycobacterium avium causes respiratory disease in susceptible individuals, as well as disseminated infections in immunocompromised hosts, being an important cause of morbidity and mortality among these populations. Current therapies consist of a combination of antibiotics taken for at least 6 months, with no more than 60% overall clinical success. Furthermore, mycobacterial antibiotic resistance is increasing worldwide, urging the need to develop novel classes of antimicrobial drugs. One potential and interesting alternative strategy is the use of antimicrobial peptides (AMP). These are present in almost all living organisms as part of their immune system, acting as a first barrier against invading pathogens. In this context, we investigated the effect of several lactoferrin-derived AMP against M. avium. Short peptide sequences from both human and bovine lactoferricins, namely, hLFcin1-11 and LFcin17-30, as well as variants obtained by specific amino acid substitutions, were evaluated. All tested peptides significantly inhibited the axenic growth of M. avium, the bovine peptides being more active than the human. Arginine residues were found to be crucial for the display of antimycobacterial activity, whereas the all-d-amino-acid analogue of the bovine sequence displayed the highest mycobactericidal activity. These findings reveal the promising potential of lactoferricins against mycobacteria, thus opening the way for further research on their development and use as a new weapon against mycobacterial infections. PMID:24709266

Biologically active perspective synthesis of heteroannulated 8-nitroquinolines with green chemistry approach.

PubMed

Arasakumar, Thangaraj; Mathusalini, Sadasivam; Gopalan, Subashini; Shyamsivappan, Selvaraj; Ata, Athar; Mohan, Palathurai Subramaniam

2017-04-01

A new class of pyrazolo[4,3-c]quinoline (5a-i, 7a-b) and pyrano[3,2-c]quinoline (9a-i) derivatives were designed and synthesized in moderate to good yields by microwave conditions. To enhance the yield of pyrano[3,2-c]quinoline derivatives, multicomponent one-pot synthesis has been developed. The synthesized compounds were identified by spectral and elemental analyses. Compounds 9a and 9i showed good antibacterial activity against Gram-positive and Gram-negative bacterial strains. All of the new compounds exhibited weak to moderate antioxidant activity, compound 9d exerted significant antioxidant power. The cytotoxicity of these compounds were also evaluated against MCF-7 (breast) and A549 (Lung) cancer cell lines. Most of the compounds displayed moderate to good cytotoxic activity against these cell lines. Compound 9i was found to be significantly active in this assay and also induced cell death by apoptosis. Molecular docking studies were carried out using EGFR inhibitor in order to determine the molecular interactions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Association of hair iron levels with creativity and psychological variables related to creativity

PubMed Central

Takeuchi, Hikaru; Taki, Yasuyuki; Sekiguchi, Atsushi; Nouchi, Rui; Kotozaki, Yuka; Nakagawa, Seishu; Miyauchi, Carlos M.; Iizuka, Kunio; Yokoyama, Ryoichi; Shinada, Takamitsu; Yamamoto, Yuki; Hanawa, Sugiko; Araki, Tsuyoshi; Hashizume, Hiroshi; Kunitoki, Keiko; Sassa, Yuko; Kawashima, Ryuta

2013-01-01

Creativity generally involves the conception of original and valuable ideas. Previous studies have suggested an association between creativity and the dopaminergic system, and that physical activity facilitates creativity. Iron plays a key role in the dopaminergic system and physical activity. Here, we newly investigated the associations between hair iron levels and creativity, dopamine-related traits and states [novelty seeking, extraversion, and vigor (motivational state)], as well as the physical activity level. In the present study, we addressed this issue by performing a hair mineral analysis to determine iron levels and a behavioral creativity test of divergent thinking and related psychological measures among young adults (254 men, 88 women; mean age 20.79 ± 2.03 years). Iron levels did not show any significant association with creativity but displayed significant positive associations with novelty seeking, extraversion, and physical activity level. These results may be partly congruent with the notion that iron plays a key role in the dopaminergic system and imply that iron is important for traits and physical activity, which facilitate creativity. Future interventional or longitudinal studies are warranted to identify any causal effects. PMID:24385960

Sulforaphane and Other Nutrigenomic Nrf2 Activators: Can the Clinician's Expectation Be Matched by the Reality?

PubMed

Houghton, Christine A; Fassett, Robert G; Coombes, Jeff S

2016-01-01

The recognition that food-derived nonnutrient molecules can modulate gene expression to influence intracellular molecular mechanisms has seen the emergence of the fields of nutrigenomics and nutrigenetics. The aim of this review is to describe the properties of nutrigenomic activators of transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2), comparing the potential for sulforaphane and other phytochemicals to demonstrate clinical efficacy as complementary medicines. Broccoli-derived sulforaphane emerges as a phytochemical with this capability, with oral doses capable of favourably modifying genes associated with chemoprevention. Compared with widely used phytochemical-based supplements like curcumin, silymarin, and resveratrol, sulforaphane more potently activates Nrf2 to induce the expression of a battery of cytoprotective genes. By virtue of its lipophilic nature and low molecular weight, sulforaphane displays significantly higher bioavailability than the polyphenol-based dietary supplements that also activate Nrf2. Nrf2 activation induces cytoprotective genes such as those playing key roles in cellular defense mechanisms including redox status and detoxification. Both its high bioavailability and significant Nrf2 inducer capacity contribute to the therapeutic potential of sulforaphane-yielding supplements.

Aniracetam improves contextual fear conditioning and increases hippocampal gamma-PKC activation in DBA/2J mice.

PubMed

Smith, Amy M; Wehner, Jeanne M

2002-01-01

DBA/2J (D2) mice display poor contextual learning and have less membrane-bound hippocampal protein kinase C (PKC) compared with C57BL/6 (B6) mice. Aniracetam and oxiracetam were previously shown to improve contextual learning in D2 mice and increase PKC activity. This study investigated a possible mechanism for learning enhancement by examining the effects of aniracetam on contextual fear conditioning and activation of the y isoform of PKC (gamma-PKC) in male D2 mice. In comparison to animals treated with vehicle only (10% 2-hydroxypropyl-beta-cyclodextrin), mice treated with aniracetam (100 mg/kg) 30 min prior to fear conditioning training demonstrated significantly improved contextual learning when tested 30 min and 24 h after training. This corresponded with a significant increase in activated, membrane-bound hippocampal gamma-PKC 30 min after training. No increase in learning or gamma-PKC was found 5 min after training. These results suggest an altered time course of activation of gamma-PKC in response to treatment with aniracetam, which improves learning in D2 mice.

Cross-resistance of bisultap resistant strain of Nilaparvata lugens and its biochemical mechanism.

PubMed

Ling, Shanfeng; Zhang, Runjie

2011-02-01

The resistant (R) strain of the planthopper Nilaparvata lugens (Stål) selected for bisultap resistance displayed 7.7-fold resistance to bisultap and also had cross-resistance to nereistoxin (monosultap, thiocyclam, and cartap), chlorpyrifos, dimethoate, and malathion but no cross-resistance to buprofezin, imidacloprid, and fipronil. To find out the biochemical mechanism of resistance to bisultap, biochemical assay was done. The results showed that cytochrome P450 monooxygenases (P450) activity in R strain was 2.71-fold that in susceptible strain (S strain), in which the changed activity for general esterase (EST) was 1.91 and for glutathione S-transferases only 1.32. Piperonyl butoxide (PBO) could significantly inhibit P450 activity (percentage of inhibition [PI]: 37.31%) in the R strain, with ESTs PI = 16.04% by triphenyl phosphate (TPP). The results also demonstrated that diethyl maleate had no synergism with bisultap. However, PBO displayed significant synergism in three different strains, and the synergism increased with resistance (S strain 1.42, Lab strain, 2.24 and R strain, 3.23). TPP also showed synergism for three strains, especially in R strain (synergistic ratio = 2.47). An in vitro biochemical study and in vivo synergistic study indicated that P450 might be play important role in the biochemical mechanism of bisultap resistance and that esterase might be the important factor of bisultap resistance. Acetylcholinesterase (AChE) insensitivity play important role in bisultap resistance. We suggest that buprofezin, imidacloprid, and fipronil could be used in resistance management programs for N. lugens via alternation and rotation with bisultap.

Microgap flat panel display

DOEpatents

Wuest, C.R.

1998-12-08

A microgap flat panel display is disclosed which includes a thin gas-filled display tube that utilizes switched X-Y ``pixel`` strips to trigger electron avalanches and activate a phosphor at a given location on a display screen. The panel utilizes the principal of electron multiplication in a gas subjected to a high electric field to provide sufficient electron current to activate standard luminescent phosphors located on an anode. The X-Y conductive strips of a few micron widths may for example, be deposited on opposite sides of a thin insulating substrate, or on one side of the adjacent substrates and function as a cathode. The X-Y strips are separated from the anode by a gap filled with a suitable gas. Electrical bias is selectively switched onto X and Y strips to activate a ``pixel`` in the region where these strips overlap. A small amount of a long-lived radioisotope is used to initiate an electron avalanche in the overlap region when bias is applied. The avalanche travels through the gas filled gap and activates a luminescent phosphor of a selected color. The bias is adjusted to give a proportional electron multiplication to control brightness for given pixel. 6 figs.

Chiral Thioxanthones as Modulators of P-glycoprotein: Synthesis and Enantioselectivity Studies.

PubMed

Lopes, Ana; Martins, Eva; Silva, Renata; Pinto, Madalena M M; Remião, Fernando; Sousa, Emília; Fernandes, Carla

2018-03-10

Recently, thioxanthone derivatives were found to protect cells against toxic P-glycoprotein (P-gp) substrates, acting as potent inducers/activators of this efflux pump. The study of new P-gp chiral modulators produced from thioxanthone derivatives could clarify the enantioselectivity of this ABC transporter towards this new class of modulators. The aim of this study was to evaluate the P-gp modulatory ability of four enantiomeric pairs of new synthesized chiral aminated thioxanthones (ATxs) 1 - 8 , studying the influence of the stereochemistry on P-gp induction/ activation in cultured Caco-2 cells. The data displayed that all the tested compounds (at 20 μM) significantly decreased the intracellular accumulation of a P-gp fluorescent substrate (rhodamine 123) when incubated simultaneously for 60 min, demonstrating an increased activity of the efflux, when compared to control cells. Additionally, all of them except ATx 3 (+), caused similar results when the accumulation of the P-gp fluorescent substrate was evaluated after pre-incubating cells with the test compounds for 24 h, significantly reducing the rhodamine 123 intracellular accumulation as a result of a significant increase in P-gp activity. However, ATx 2 (-) was the only derivative that, after 24 h of incubation, significantly increased P-gp expression. These results demonstrated a significantly increased P-gp activity, even without an increase in P-gp expression. Therefore, ATxs 1 - 8 were shown to behave as P-gp activators. Furthermore, no significant differences were detected in the activity of the protein when comparing the enantiomeric pairs. Nevertheless, ATx 2 (-) modulates P-gp expression differently from its enantiomer, ATx 1 (+). These results disclosed new activators and inducers of P-gp and highlight the existence of enantioselectivity in the induction mechanism.

Software Displays Data on Active Regions of the Sun

NASA Technical Reports Server (NTRS)

Golightly, Mike; Weyland, Mark; Raben, Vern

2011-01-01

The Solar Active Region Display System is a computer program that generates, in near real time, a graphical display of parameters indicative of the spatial and temporal variations of activity on the Sun. These parameters include histories and distributions of solar flares, active region growth, coronal mass ejections, size, and magnetic configuration. By presenting solar-activity data in graphical form, this program accelerates, facilitates, and partly automates what had previously been a time-consuming mental process of interpretation of solar-activity data presented in tabular and textual formats. Intended for original use in predicting space weather in order to minimize the exposure of astronauts to ionizing radiation, the program might also be useful on Earth for predicting solar-wind-induced ionospheric effects, electric currents, and potentials that could affect radio-communication systems, navigation systems, pipelines, and long electric-power lines. Raw data for the display are obtained automatically from the Space Environment Center (SEC) of the National Oceanic and Atmospheric Administration (NOAA). Other data must be obtained from the NOAA SEC by verbal communication and entered manually. The Solar Active Region Display System automatically accounts for the latitude dependence of the rate of rotation of the Sun, by use of a mathematical model that is corrected with NOAA SEC active-region position data once every 24 hours. The display includes the date, time, and an image of the Sun in H light overlaid with latitude and longitude coordinate lines, dots that mark locations of active regions identified by NOAA, identifying numbers assigned by NOAA to such regions, and solar-region visual summary (SRVS) indicators associated with some of the active regions. Each SRVS indicator is a small pie chart containing five equal sectors, each of which is color-coded to provide a semiquantitative indication of the degree of hazard posed by one aspect of the activity at the indicated location. The five aspects in question are the history of solar flares, the history of coronal mass ejections, the growth or decay of activity, the overall size, and the magnetic configuration. Mouse-clicking on an active-region-marking dot, SRVS indicator, or NOAA region number causes the program to generate a solar-region summary table (SRT) for the active region in question. The SRT contains additional quantitative and qualitative data, beyond those contained in the SRVS: These data include the solar coordinates of the region, the area of the region and its change in area during the past 24 hours, the change in the number of sunspots in the region during the past 24 hours, the magnetic configuration, and the types, dates, and times of the most recent flare and coronal mass ejection.

Enhanced tissue factor pathway activity and fibrin turnover in the alveolar compartment of patients with interstitial lung disease.

PubMed

Günther, A; Mosavi, P; Ruppert, C; Heinemann, S; Temmesfeld, B; Velcovsky, H G; Morr, H; Grimminger, F; Walmrath, D; Seeger, W

2000-06-01

Bronchoalveolar lavage fluids (BALF) from patients with hypersensitivity pneumonitis (HP; n = 35), idiopathic pulmonary fibrosis (IPF, n = 41) and sarcoidosis (SARC, n = 48) were investigated for alterations in the alveolar hemostatic balance. Healthy individuals (n = 21) served as Controls. Procoagulant activity (PCA), tissue factor (TF) activity and F VII activity were assessed by means of specific recalcification assays. The overall fibrinolytic activity (FA) was measured using the (125)I-labeled fibrin plate assay. Fibrinopeptide A (FP-A), D-Dimer, plasminogen activators (PA) of the urokinase (u-PA) or tissue type (t-PA), PA-inhibitor I (PAI-1) and alpha2-antiplasmin (alpha2-AP) were determined by ELISA technique. As compared to Controls, all groups with interstitial lung disease (ILD) displayed an increase in BALF PCA by approximately one order of magnitude, and this was ascribed to enhanced TF activity by >98%. Accordingly, F VII-activity was increased in all ILD groups, and elevated FP-A levels were noted. There was no significant difference in procoagulant activities between the different ILD entities, but the increase in TF was significantly correlated with deterioration of lung compliance. Overall fibrinolytic activity did not significantly differ between ILD entities and Controls, although some reduction in IPF subjects was observed. Nevertheless, changes in the profile of the different pro- and antifibrinolytic compounds were noted. U-PA, but not t-PA levels were significantly reduced in all ILD groups. alpha2-AP was markedly elevated throughout, whereas PAI-1 levels were lowered. As a balance of

Frequency encoded auditory display of the critical tracking task

NASA Technical Reports Server (NTRS)

Stevenson, J.

1984-01-01

The use of auditory displays for selected cockpit instruments was examined. In auditory, visual, and combined auditory-visual compensatory displays of a vertical axis, critical tracking task were studied. The visual display encoded vertical error as the position of a dot on a 17.78 cm, center marked CRT. The auditory display encoded vertical error as log frequency with a six octave range; the center point at 1 kHz was marked by a 20-dB amplitude notch, one-third octave wide. Asymptotic performance on the critical tracking task was significantly better when using combined displays rather than the visual only mode. At asymptote, the combined display was slightly, but significantly, better than the visual only mode. The maximum controllable bandwidth using the auditory mode was only 60% of the maximum controllable bandwidth using the visual mode. Redundant cueing increased the rate of improvement of tracking performance, and the asymptotic performance level. This enhancement increases with the amount of redundant cueing used. This effect appears most prominent when the bandwidth of the forcing function is substantially less than the upper limit of controllability frequency.

Synthesis and antitumor activity of quinonoid derivatives of cannabinoids.

PubMed

Kogan, Natalya M; Rabinowitz, Ruth; Levi, Paloma; Gibson, Dan; Sandor, Peter; Schlesinger, Michael; Mechoulam, Raphael

2004-07-15

Three cannabis constituents, cannabidiol (1), Delta(8)-tetrahydrocannabinol (3), and cannabinol (5), were oxidized to their respective para-quinones 2, 4, and 6. In the 1960s, the oxidized product 4 had been assigned a para-quinone structure, which was later modified to an ortho-quinone. To distinguish between the two possible quinone structures, a detailed NMR investigation was undertaken. The original para-quinone structure was confirmed. X-ray crystallography elucidated the structures of the crystalline 2 and 6. All three compounds displayed antiproliferative activity in several human cancer cell lines in vitro, and quinone 2 significantly reduced cancer growth of HT-29 cancer in nude mice.

Impact of Storage Conditions on the Stability of Predominant Phenolic Constituents and Antioxidant Activity of Dried Piper betle Extracts.

PubMed

Ali, Ameena; Chong, Chien Hwa; Mah, Siau Hui; Abdullah, Luqman Chuah; Choong, Thomas Shean Yaw; Chua, Bee Lin

2018-02-23

The phenolic constituents in Piper betle are well known for their antioxidant potential; however, current literature has very little information on their stability under the influence of storage factors. Present study evaluated the stability of total phenolic content (TPC) and antioxidant activity together with individual phenolic constituents (hydroxychavicol, eugenol, isoeugenol and allylpyrocatechol 3,4-diacetate) present in dried Piper betle 's extract under different storage temperature of 5 and 25 °C with and without light for a period of six months. Both light and temperature significantly influenced TPC and its corresponding antioxidant activity over time. More than 95% TPC and antioxidant activity was retained at 5 °C in dark condition after 180 days of storage. Hydroxychavicol demonstrated the best stability with no degradation while eugenol and isoeugenol displayed moderate stability in low temperature (5 °C) and dark conditions. 4-allyl-1,2-diacetoxybenzene was the only compound that underwent complete degradation. A new compound, 2,4-di- tert -butylphenol, was detected after five weeks of storage only in the extracts exposed to light. Both zero-order and first-order kinetic models were adopted to describe the degradation kinetics of the extract's antioxidant activity. Zero-order displayed better fit with higher correlation coefficients ( R ² = 0.9046) and the half-life was determined as 62 days for the optimised storage conditions (5 °C in dark conditions).

Re-engineering of CYP2C9 to probe acid-base substrate selectivity.

PubMed

Tai, Guoying; Dickmann, Leslie J; Matovic, Nicholas; DeVoss, James J; Gillam, Elizabeth M J; Rettie, Allan E

2008-10-01

A common feature of many CYP2C9 ligands is their weak acidity. As revealed by crystallography, the structural basis for this behavior involves a charge-pairing interaction between an anionic moiety on the substrate and an active site R108 residue. In the present study we attempted to re-engineer CYP2C9 to better accept basic ligands by charge reversal at this key residue. We expressed and purified the R108E and R108E/D293N mutants and compared their ability with that of native CYP2C9 to interact with (S)-warfarin, diclofenac, pyrene, propranolol, and ibuprofen amine. As expected, the R108E mutant maintained all the native enzyme's pyrene 1-hydroxylation activity, but catalytic activity toward diclofenac and (S)-warfarin was abrogated. In contrast, the double mutant displayed much less selectivity in its behavior toward these control ligands. Neither of the mutants displayed significant enhancement of propranolol metabolism, and all three preparations exhibited a type II (inhibitor) rather than type I (substrate) spectrum with ibuprofen amine, although binding became progressively weaker with the single and double mutants. Collectively, these data underscore the importance of the amino acid at position 108 in the acid substrate selectivity of CYP2C9, highlight the accommodating nature of the CYP2C9 active site, and provide a cautionary note regarding facile re-engineering of these complex cytochrome P450 active sites.

Re-engineering of CYP2C9 to Probe Acid-Base Substrate Selectivity

PubMed Central

Tai, Guoying; Dickmann, Leslie J.; Matovic, Nicholas; DeVoss, James J.; Gillam, Elizabeth M. J.; Rettie, Allan E.

2009-01-01

A common feature of many CYP2C9 ligands is their weak acidity. As revealed by crystallography, the structural basis for this behavior involves a charge-pairing interaction between an anionic moiety on the substrate and an active site R108 residue. In the present study we attempted to re-engineer CYP2C9 to better accept basic ligands by charge reversal at this key residue. We expressed and purified the R108E and R108E/D293N mutants and compared their ability with that of native CYP2C9 to interact with (S)-warfarin, diclofenac, pyrene, propranolol, and ibuprofen amine. As expected, the R108E mutant maintained all the native enzyme's pyrene 1-hydroxylation activity, but catalytic activity toward diclofenac and (S)-warfarin was abrogated. In contrast, the double mutant displayed much less selectivity in its behavior toward these control ligands. Neither of the mutants displayed significant enhancement of propranolol metabolism, and all three preparations exhibited a type II (inhibitor) rather than type I (substrate) spectrum with ibuprofen amine, although binding became progressively weaker with the single and double mutants. Collectively, these data underscore the importance of the amino acid at position 108 in the acid substrate selectivity of CYP2C9, highlight the accommodating nature of the CYP2C9 active site, and provide a cautionary note regarding facile re-engineering of these complex cytochrome P450 active sites. PMID:18606741

Secretory phospholipase A2 in dromedary tears: a host defense against staphylococci and other gram-positive bacteria.

PubMed

Ben Bacha, Abir; Abid, Islem

2013-03-01

The best known physiologic function of secreted phospholipase A2 (sPLA2) group IIA (sPLA2-IIA) is defense against bacterial infection through hydrolytic degradation of bacterial membrane phospholipids. In fact, sPLA2-IIA effectively kills Gram-positive bacteria and to a lesser extent Gram-negative bacteria and is considered a major component of the eye's innate immune defense system. The antibacterial properties of sPLA2 have been demonstrated in rabbit and human tears. In this report, we have analyzed the bactericidal activity of dromedary tears and the subsequently purified sPLA2 on several Gram-positive bacteria. Our results showed that the sPLA2 displays a potent bactericidal activity against all the tested bacteria particularly against the Staphylococcus strains when tested in the ionic environment of tears. There is a synergic action of the sPLA2 with lysozyme when added to the bacteria culture prior to sPLA2. Interestingly, lysozyme purified from dromedary tears showed a significant bactericidal activity against Listeria monocytogene and Staphylococcus epidermidis, whereas the one purified from human tears displayed no activity against these two strains. We have also demonstrated that Ca(2+) is crucial for the activity of dromedary tear sPLA2 and to a less extent Mg(2+) ions. Given the presence of sPLA2 in tears and intestinal secretions, this enzyme may play a substantial role in innate mucosal and systemic bactericidal defenses against Gram-positive bacteria.

Novel Broad Spectrum Inhibitors Targeting the Flavivirus Methyltransferase

PubMed Central

Liu, Binbin; Banavali, Nilesh K.; Jones, Susan A.; Zhang, Jing; Li, Zhong; Kramer, Laura D.; Li, Hongmin

2015-01-01

The flavivirus methyltransferase (MTase) is an essential enzyme that sequentially methylates the N7 and 2’-O positions of the viral RNA cap, using S-adenosyl-L-methionine (SAM) as a methyl donor. We report here that small molecule compounds, which putatively bind to the SAM-binding site of flavivirus MTase and inhibit its function, were identified by using virtual screening. In vitro methylation experiments demonstrated significant MTase inhibition by 13 of these compounds, with the most potent compound displaying sub-micromolar inhibitory activity. The most active compounds showed broad spectrum activity against the MTase proteins of multiple flaviviruses. Two of these compounds also exhibited low cytotoxicity and effectively inhibited viral replication in cell-based assays, providing further structural insight into flavivirus MTase inhibition. PMID:26098995

Design, synthesis and inhibitory activities of 8-(substituted styrol-formamido)phenyl-xanthine derivatives on monoamine oxidase B.

PubMed

Hu, Suwen; Nian, Siyun; Qin, Kuiyou; Xiao, Tong; Li, Lingna; Qi, Xiaolu; Ye, Faqing; Liang, Guang; Hu, Guoxin; He, Jincai; Yu, Yinfei; Song, Bo

2012-01-01

The design and synthesis of two series of 8-(substituted styrol-formamido)phenyl-xanthine derivatives are described. Their in vitro monoamine oxidase B (MAO-B) inhibition were tested and the effect of substituents on the N-7, phenyl and the substituted positions are discussed. It was observed that compound 9b displayed significant MAO-B inhibition activity and selectivity, fluorine substitution plays a key role in the selectivity of MAO-B inhibition, and the styrol-formamido group at position-3' may enhance the activity and selectivity of 8-phenyl-xanthine analogues. These results suggest that such compounds may be utilized for the development of new candidate MAO-B inhibitors for treatment of Parkinson's disease.

Decoding emotional valence from electroencephalographic rhythmic activity.

PubMed

Celikkanat, Hande; Moriya, Hiroki; Ogawa, Takeshi; Kauppi, Jukka-Pekka; Kawanabe, Motoaki; Hyvarinen, Aapo

2017-07-01

We attempt to decode emotional valence from electroencephalographic rhythmic activity in a naturalistic setting. We employ a data-driven method developed in a previous study, Spectral Linear Discriminant Analysis, to discover the relationships between the classification task and independent neuronal sources, optimally utilizing multiple frequency bands. A detailed investigation of the classifier provides insight into the neuronal sources related with emotional valence, and the individual differences of the subjects in processing emotions. Our findings show: (1) sources whose locations are similar across subjects are consistently involved in emotional responses, with the involvement of parietal sources being especially significant, and (2) even though the locations of the involved neuronal sources are consistent, subjects can display highly varying degrees of valence-related EEG activity in the sources.

Homoisoflavonoids from Caesalpinia sappan displaying viral neuraminidases inhibition.

PubMed

Jeong, Hyung Jae; Kim, Young Min; Kim, Jang Hoon; Kim, Ji Young; Park, Ji-Young; Park, Su-Jin; Ryu, Young Bae; Lee, Woo Song

2012-01-01

In this study, twelve neuraminidase (NA) inhibitory compounds 1-12 were isolated from heartwood of Caesalpinia sappan on the basis of their biological activities against three types of viral NAs. Of isolated homoisoflavonoids, sappanone A (2) showed the most potent NAs inhibitory activities with IC(50) values of 0.7 µM [H1N1], 1.1 µM [H3N2], and 1.0 µM [H9N2], respectively, whereas saturated homoisoflavonoid (3) did not show significantly inhibition. This result revealed that α,β-unsaturated carbonyl group in A-ring was the key requirements for viral NAs inhibitory activity. In our enzyme kinetic study, all NA inhibitors screened were found to be reversible noncompetitive types.

The crystal structure of dihydrodipicolinate synthase from Escherichia coli with bound pyruvate and succinic acid semialdehyde: unambiguous resolution of the stereochemistry of the condensation product.

PubMed

Boughton, Berin A; Dobson, Renwick C J; Hutton, Craig A

2012-08-01

The crystal structure of Escherichia coli dihydrodipicolinate synthase with pyruvate and substrate analogue succinic acid semialdehyde condensed with the active site lysine-161 was solved to a resolution of 2.3 Å. Comparative analysis to a previously reported structure both resolves the configuration at the aldol addition center, where the final addition product clearly displays the (S)-configuration, and the final conformation of the adduct within the active site. Direct comparison to two other crystal structures found in the Protein Data Bank, 1YXC, and 3DU0, demonstrates significant similarity between the active site residues of these structures. Copyright © 2012 Wiley Periodicals, Inc.

Synthesis and antifungal activity of the derivatives of novel pyrazole carboxamide and isoxazolol pyrazole carboxylate.

PubMed

Sun, Jialong; Zhou, Yuanming

2015-03-09

A series of pyrazole carboxamide and isoxazolol pyrazole carboxylate derivatives were designed and synthesized in this study. The structures of the compounds were elucidated based on spectral data (infrared, proton nuclear magnetic resonance and mass spectroscopy). Then, all of the compounds were bioassayed in vitro against four types of phytopathogenic fungi (Alternaria porri, Marssonina coronaria, Cercospora petroselini and Rhizoctonia solani) using the mycelium growth inhibition method. The results showed that some of the synthesized pyrazole carboxamides displayed notable antifungal activity. The isoxazole pyrazole carboxylate 7ai exhibited significant antifungal activity against R. solani, with an EC50 value of 0.37 μg/mL. Nonetheless, this value was lower than that of the commercial fungicide, carbendazol.

Active glass-type human augmented cognition system considering attention and intention

NASA Astrophysics Data System (ADS)

Kim, Bumhwi; Ojha, Amitash; Lee, Minho

2015-10-01

Human cognition is the result of an interaction of several complex cognitive processes with limited capabilities. Therefore, the primary objective of human cognitive augmentation is to assist and expand these limited human cognitive capabilities independently or together. In this study, we propose a glass-type human augmented cognition system, which attempts to actively assist human memory functions by providing relevant, necessary and intended information by constantly assessing intention of the user. To achieve this, we exploit selective attention and intention processes. Although the system can be used in various real-life scenarios, we test the performance of the system in a person identity scenario. To detect the intended face, the system analyses the gaze points and change in pupil size to determine the intention of the user. An assessment of the gaze points and change in pupil size together indicates that the user intends to know the identity and information about the person in question. Then, the system retrieves several clues through speech recognition system and retrieves relevant information about the face, which is finally displayed through head-mounted display. We present the performance of several components of the system. Our results show that the active and relevant assistance based on users' intention significantly helps the enhancement of memory functions.

Fronto-parietal regulation of media violence exposure in adolescents: a multi-method study

PubMed Central

Strenziok, Maren; Krueger, Frank; Deshpande, Gopikrishna; Lenroot, Rhoshel K.; van der Meer, Elke

2011-01-01

Adolescents spend a significant part of their leisure time watching TV programs and movies that portray violence. It is unknown, however, how the extent of violent media use and the severity of aggression displayed affect adolescents’ brain function. We investigated skin conductance responses, brain activation and functional brain connectivity to media violence in healthy adolescents. In an event-related functional magnetic resonance imaging experiment, subjects repeatedly viewed normed videos that displayed different degrees of aggressive behavior. We found a downward linear adaptation in skin conductance responses with increasing aggression and desensitization towards more aggressive videos. Our results further revealed adaptation in a fronto-parietal network including the left lateral orbitofrontal cortex (lOFC), right precuneus and bilateral inferior parietal lobules, again showing downward linear adaptations and desensitization towards more aggressive videos. Granger causality mapping analyses revealed attenuation in the left lOFC, indicating that activation during viewing aggressive media is driven by input from parietal regions that decreased over time, for more aggressive videos. We conclude that aggressive media activates an emotion–attention network that has the capability to blunt emotional responses through reduced attention with repeated viewing of aggressive media contents, which may restrict the linking of the consequences of aggression with an emotional response, and therefore potentially promotes aggressive attitudes and behavior. PMID:20934985

Identification of highly potent BTK and JAK3 dual inhibitors with improved activity for the treatment of B-cell lymphoma.

PubMed

Ge, Yang; Wang, Changyuan; Song, Shijie; Huang, Jiaxin; Liu, Zhihao; Li, Yongming; Meng, Qiang; Zhang, Jianbin; Yao, Jihong; Liu, Kexin; Ma, Xiaodong; Sun, Xiuli

2018-01-01

The BTK and JAK3 receptor tyrosine kinases are two validated and therapeutically amenable targets in the treatment of B-cell lymphomas. Here we report the identification of several classes of pyrimidine derivatives as potent BTK and JAK3 dual inhibitors. Among these molecules, approximately two thirds displayed strong inhibitory capacity at less than 10 nM concentration, and four compounds (7e, 7g, 7m and 7n) could significantly inhibit the phosphorylation of BTK and JAK3 enzymes at concentrations lower than 1 nM. Additionally, these pyrimidine derivatives also exhibited enhanced activity to block the proliferation of B-cell lymphoma cells compared with the representative BTK inhibitor ibrutinib. In particular, two structure-specific compounds 7b and 7e displayed stronger activity than reference agents in cell-based evaluation, with IC 50 values lower than 10 μM. Further biological studies, including flow cytometric analysis, and a xenograft model for in vivo evaluation, also indicated their efficacy and low toxicity in the treatment of B-cell lymphoma. These findings provide a new insight for the development of novel anti-B-cell lymphoma drugs with multi-target actions. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Comparison of the anti-proliferation and apoptosis-induction activities of sulindac, celecoxib, curcumin, and nifedipine in mismatch repair-deficient cell lines.

PubMed

Wei, Shu-Chen; Lin, Young-Sun; Tsao, Po-Nien; Wu-Tsai, Jyy-Ji; Wu, C H Herbert; Wong, Jau-Min

2004-08-01

The adenomatous polyposis coli (APC) and mismatch repair (MMR) pathways are both involved in the tumorigenesis of hereditary colorectal cancers. Chemoprevention focuses on the APC pathway in the absence of information concerning MMR targets. This study compared the anticancer effects of sulindac, celecoxib, curcumin, and nifedipine in MMR-deficient cell lines, in order to determine the most appropriate chemopreventive agent for long-term use in patients with hereditary colorectal cancer. Five human colorectal cell lines (SW480, HCT116, LoVo, SW48, and HCT15) and an endometrial cancer cell line (HEC-1-A) were used for susceptibility testing. Tests included assays for growth inhibition, cell-cycle arrest, and apoptosis. Sulindac, celecoxib, curcumin, and nifedipine all displayed dose- and time-dependent anti-proliferation activities. Celecoxib was the most effective anti-proliferative agent, and increased the G0/G1 phase proportion in the cell cycle after treatment more significantly than the other agents in all cell lines. Curcumin displayed a more potent apoptosis-inducing activity than the other agents in treated cells. The tested drugs were effective against colorectal and endometrial cancer cell lines. Celecoxib is more potent with fewer side effects than sulindac. Nifedipine's observed chemopreventive efficacy may complement its known therapeutic application in patients with hypertension.

Formononetin promotes angiogenesis through the estrogen receptor alpha-enhanced ROCK pathway

PubMed Central

Li, Shang; Dang, Yuanye; Zhou, Xuelin; Huang, Bin; Huang, Xiaohui; Zhang, Zherui; Kwan, Yiu Wa; Chan, Shun Wan; Leung, George Pak Heng; Lee, Simon Ming Yuen; Hoi, Maggie Pui Man

2015-01-01

Formononetin is an isoflavone that has been shown to display estrogenic properties and induce angiogenesis activities. However, the interrelationship between the estrogenic properties and angiogenesis activities of formononetin are not well defined. In the present study, docking and enzymatic assay demonstrated that formononetin displayed direct binding to the ligand-binding domain (LBD) of estrogen receptor alpha (ERα) with an agonistic property. Results from Human Umbilical Vein Endothelial Cells (HUVEC) by using real-time migration xCELLigence system, immunofluorescence and western blotting provided strong evidences of formononetin induced endothelial cell migration and dramatic actin cytoskeleton spatial modification through ERα-enhanced-ROCK-II/MMP2/9 signaling pathways. In addition, results from co-immunoprecipitation suggested formononetin induced cell migration via recruiting of ERα/ROCK-II activated complex formation. More interestingly, in zebrafish embryo we observed that formononetin significantly promoted angiogenic sproutings in the subintestinal vessels (SIVs) that could be completely abolished by ROCK inhibitor. In this study, we elucidated the underlying mechanisms that formononetin produced proangiogenesis effects through an ERα-enhanced ROCK-II signaling pathways. Results from the present study also expand our knowledge about the enigmatic underlying mechanisms of phytoestrogenic compounds in the promotion of angiogenesis in relation to ERα and ROCK interaction in endothelial cells and their relationship with actin assembly and cell migration. PMID:26568398

Formononetin promotes angiogenesis through the estrogen receptor alpha-enhanced ROCK pathway.

PubMed

Li, Shang; Dang, Yuanye; Zhou, Xuelin; Huang, Bin; Huang, Xiaohui; Zhang, Zherui; Kwan, Yiu Wa; Chan, Shun Wan; Leung, George Pak Heng; Lee, Simon Ming Yuen; Hoi, Maggie Pui Man

2015-11-16

Formononetin is an isoflavone that has been shown to display estrogenic properties and induce angiogenesis activities. However, the interrelationship between the estrogenic properties and angiogenesis activities of formononetin are not well defined. In the present study, docking and enzymatic assay demonstrated that formononetin displayed direct binding to the ligand-binding domain (LBD) of estrogen receptor alpha (ERα) with an agonistic property. Results from Human Umbilical Vein Endothelial Cells (HUVEC) by using real-time migration xCELLigence system, immunofluorescence and western blotting provided strong evidences of formononetin induced endothelial cell migration and dramatic actin cytoskeleton spatial modification through ERα-enhanced-ROCK-II/MMP2/9 signaling pathways. In addition, results from co-immunoprecipitation suggested formononetin induced cell migration via recruiting of ERα/ROCK-II activated complex formation. More interestingly, in zebrafish embryo we observed that formononetin significantly promoted angiogenic sproutings in the subintestinal vessels (SIVs) that could be completely abolished by ROCK inhibitor. In this study, we elucidated the underlying mechanisms that formononetin produced proangiogenesis effects through an ERα-enhanced ROCK-II signaling pathways. Results from the present study also expand our knowledge about the enigmatic underlying mechanisms of phytoestrogenic compounds in the promotion of angiogenesis in relation to ERα and ROCK interaction in endothelial cells and their relationship with actin assembly and cell migration.

CARbodies: Human Antibodies Against Cell Surface Tumor Antigens Selected From Repertoires Displayed on T Cell Chimeric Antigen Receptors

PubMed Central

Alonso-Camino, Vanesa; Sánchez-Martín, David; Compte, Marta; Nuñez-Prado, Natalia; Diaz, Rosa M; Vile, Richard; Alvarez-Vallina, Luis

2013-01-01

A human single-chain variable fragment (scFv) antibody library was expressed on the surface of human T cells after transduction with lentiviral vectors (LVs). The repertoire was fused to a first-generation T cell receptor ζ (TCRζ)-based chimeric antigen receptor (CAR). We used this library to isolate antibodies termed CARbodies that recognize antigens expressed on the tumor cell surface in a proof-of-principle system. After three rounds of activation-selection there was a clear repertoire restriction, with the emergence dominant clones. The CARbodies were purified from bacterial cultures as soluble and active proteins. Furthermore, to validate its potential application for adoptive cell therapy, human T cells were transduced with a LV encoding a second-generation costimulatory CAR (CARv2) bearing the selected CARbodies. Transduced human primary T cells expressed significant levels of the CARbodies-based CARv2 fusion protein on the cell surface, and importantly could be specifically activated, after stimulation with tumor cells. This approach is a promising tool for the generation of antibodies fully adapted to the display format (CAR) and the selection context (cell synapse), which could extend the scope of current adoptive cell therapy strategies with CAR-redirected T cells. PMID:23695536

Immunomodulatory activity of purified arabinoxylans from finger millet (Eleusine coracana, v. Indaf 15) bran.

PubMed

Savitha Prashanth, M R; Shruthi, R R; Muralikrishna, G

2015-09-01

Biological activities of alkali extracted (Barium hydroxide: BE-480 kDa, Potassium hydroxide: KE1-1080 and KE2-40 kDa), purified arabinoxylans (AX) from the finger millet bran varying in their molecular weight, phenolic acid content, arabinose to xylose ratios were evaluated for their immune-stimulatory activities using murine lymphocytes and peritoneal exudate macrophages. All three purified AX displayed significant (p < 0.001) mitogenic activity and activation of macrophages including phagocytosis. Among these BE has shown higher enhancing lymphocyte proliferation (>2 fold) and macrophage phagocytosis than KE1 and KE2. The above results clearly documented that the immunostimulatory activity of arabinoxylans is directly proportional to the amount of ferulic acid content (0.11 mg/100 g), whereas molecular weight as well as arabinose/xylose ratio, did not have any bearing. Purified AX from the finger millet bran can be explored as a potent natural immunomodulator.

Antiarrhythmic and antioxidant activity of novel pyrrolidin-2-one derivatives with adrenolytic properties

PubMed Central

Nowaczyk, Alicja; Kulig, Katarzyna

2010-01-01

A series of novel pyrrolidin-2-one derivatives (17 compounds) with adrenolytic properties was evaluated for antiarrhythmic, electrocardiographic and antioxidant activity. Some of them displayed antiarrhythmic activity in barium chloride-induced arrhythmia and in the rat coronary artery ligation-reperfusion model, and slightly decreased the heart rate, prolonged P–Q, Q–T intervals and QRS complex. Among them, compound EP-40 (1-[2-hydroxy-3-[4-[(2-hydroxyphenyl)piperazin-1-yl]propyl]pyrrolidin-2-one showed excellent antiarrhythmic activity. This compound had significantly antioxidant effect, too. The present results suggest that the antiarrhythmic effect of compound EP-40 is related to their adrenolytic and antioxidant properties. A biological activity prediction using the PASS software shows that compound EP-35 and EP-40 can be characterized by antiischemic activity; whereas, compound EP-68, EP-70, EP-71 could be good tachycardia agents. PMID:20949258

Antiarrhythmic and antioxidant activity of novel pyrrolidin-2-one derivatives with adrenolytic properties.

PubMed

Sapa, Jacek; Nowaczyk, Alicja; Kulig, Katarzyna

2011-01-01

A series of novel pyrrolidin-2-one derivatives (17 compounds) with adrenolytic properties was evaluated for antiarrhythmic, electrocardiographic and antioxidant activity. Some of them displayed antiarrhythmic activity in barium chloride-induced arrhythmia and in the rat coronary artery ligation-reperfusion model, and slightly decreased the heart rate, prolonged P-Q, Q-T intervals and QRS complex. Among them, compound EP-40 (1-[2-hydroxy-3-[4-[(2-hydroxyphenyl)piperazin-1-yl]propyl]pyrrolidin-2-one showed excellent antiarrhythmic activity. This compound had significantly antioxidant effect, too. The present results suggest that the antiarrhythmic effect of compound EP-40 is related to their adrenolytic and antioxidant properties. A biological activity prediction using the PASS software shows that compound EP-35 and EP-40 can be characterized by antiischemic activity; whereas, compound EP-68, EP-70, EP-71 could be good tachycardia agents.

Cortisol Patterns for Young Children Displaying Disruptive Behavior: Links to a Teacher-Child, Relationship-Focused Intervention.

PubMed

Hatfield, Bridget E; Williford, Amanda P

2017-01-01

Supportive and close relationships that young children have with teachers have lasting effects on children's behavior and academic success, and this is particularly true for children with challenging behaviors. These relationships are also important for children's developing stress response system, and children in child care may be more likely to display atypical cortisol patterns at child care. However, warm, supportive relationships with teachers may buffer these negative effects of child care. While many relationship-focused early childhood interventions demonstrate changes in child behavior, associations with children's stress response system are unknown. This study assessed children's activity in the hypothalamic-pituitary-adrenal axis via salivary cortisol as a function of their participation in a dyadic intervention intended to improve a teacher's interaction quality with a particular child. Seventy teachers and 113 preschool children participated who were part of a larger study of teachers and children were randomly assigned at the classroom level across three intervention conditions: Banking Time, Time-Control Comparison (Child Time), and Business-as-Usual. At the end of the school year, children in the Banking Time condition displayed a significantly greater decline in cortisol across the morning during preschool compared to children in Business-as-Usual condition. These pilot results are among the first to provide preliminary evidence that school-based interventions that promote sensitive and responsive interactions may improve young children's activity in the stress response system within the child care/early education context.

The Evaluation of a Pulmonary Display to Detect Adverse Respiratory Events Using High Resolution Human Simulator

PubMed Central

Wachter, S. Blake; Johnson, Ken; Albert, Robert; Syroid, Noah; Drews, Frank; Westenskow, Dwayne

2006-01-01

Objective Authors developed a picture-graphics display for pulmonary function to present typical respiratory data used in perioperative and intensive care environments. The display utilizes color, shape and emergent alerting to highlight abnormal pulmonary physiology. The display serves as an adjunct to traditional operating room displays and monitors. Design To evaluate the prototype, nineteen clinician volunteers each managed four adverse respiratory events and one normal event using a high-resolution patient simulator which included the new displays (intervention subjects) and traditional displays (control subjects). Between-group comparisons included (i) time to diagnosis and treatment for each adverse respiratory event; (ii) the number of unnecessary treatments during the normal scenario; and (iii) self-reported workload estimates while managing study events. Measurements Two expert anesthesiologists reviewed video-taped transcriptions of the volunteers to determine time to treat and time to diagnosis. Time values were then compared between groups using a Mann-Whitney-U Test. Estimated workload for both groups was assessed using the NASA-TLX and compared between groups using an ANOVA. P-values < 0.05 were considered significant. Results Clinician volunteers detected and treated obstructed endotracheal tubes and intrinsic PEEP problems faster with graphical rather than conventional displays (p < 0.05). During the normal scenario simulation, 3 clinicians using the graphical display, and 5 clinicians using the conventional display gave unnecessary treatments. Clinician-volunteers reported significantly lower subjective workloads using the graphical display for the obstructed endotracheal tube scenario (p < 0.001) and the intrinsic PEEP scenario (p < 0.03). Conclusion Authors conclude that the graphical pulmonary display may serve as a useful adjunct to traditional displays in identifying adverse respiratory events. PMID:16929038

Thermal ecology and activity patterns of the short-horned lizard (Phrynosoma douglassi) and the sage brush lizard (Sceloporus graciosus) in southeastern Idaho

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

Guyer, C.; Linder, A.D.

1985-10-31

A mark-recapture study of the short-horned lizard (Phyrnosoma douglassi) and the sagebrush lizard (Sceloporus graciosus) was performed from 1976 to 1977 in southeastern Idaho. Both species had mean cloacal temperatures of approximately 33 C. However, P. douglassi had more variable cloacal temperatures, particularly during morning and evening periods. This was caused by differences in sleeping sites chosen by the two species. Adults of both species were active from mid-April through late August, with peak activity in June. Juvenile P. douglassi displayed a seasonal activity pattern similar to that of adults. Juvenile S. graciosus were most active later in the yearmore » (August), when adults were disappearing. In both species, young-of-the-year appeared in early to mid-August. Adult and juvenile P. douglassi were active during all daylight hours and displayed no activity peaks, whereas young-of-the-year displayed a bimodal activity pattern. Adult and juvenile S. graciosus were active over all daylight hours but had peak activity between 1200 and 1500 h. Ants (Pogonomyrmex) were the lizard's principle prey. However, only young-of-the-year P. douglassi had activity patterns that paralleled that of ants on their mounds. 22 references, 4 figures.« less

Effects of the histone-like protein HU on cellulose degradation and biofilm formation of Cytophaga hutchinsonii.

PubMed

Guan, Zhiwei; Wang, Ying; Gao, Lijuan; Zhang, Weican; Lu, Xuemei

2018-06-06

Cytophaga hutchinsonii, belonging to Bacteroidetes, is speculated to use a novel cell-contact mode to digest cellulose. In this study, we identified a histone-like protein HU, CHU_2750, in C. hutchinsonii, whose transcription could be induced by crystalline but not amorphous cellulose. We constructed a CHU_2750-deleted mutant and expressed CHU_2750 in Escherichia coli to study the gene's functions. Our results showed that although the deletion of CHU_2750 was not lethal to C. hutchinsonii, the mutant displayed an abnormal filamentous morphology, loose nucleoid, and obvious defects in the degradation of crystalline cellulose and cell motility. Further study indicated that the mutant displayed significantly decreased cell surface and intracellular endoglucanase activities but with β-glucosidase activities similar to the wild-type strain. Analyses by real-time quantitative PCR revealed that the transcription levels of many genes involved in cellulose degradation and/or cell motility were significantly downregulated in the mutant. In addition, we found that CHU_2750 was important for biofilm formation of C. hutchinsonii. The main extracellular components of the biofilm were analyzed, and the results showed that the mutant yielded significantly less exopolysaccharide but more extracellular DNA and protein than the wild-type strain. Collectively, our findings demonstrated that CHU_2750 is important for cellulose degradation, cell motility, and biofilm formation of C. hutchinsonii by modulating transcription of certain related genes, and it is the first identified transcriptional regulator in these processes of C. hutchinsonii. Our study shed more light on the mechanisms of cellulose degradation, cell motility, and biofilm formation by C. hutchinsonii.

Trade-off between thermal tolerance and insecticide resistance in Plutella xylostella.

PubMed

Zhang, Lin Jie; Wu, Zhao Li; Wang, Kuan Fu; Liu, Qun; Zhuang, Hua Mei; Wu, Gang

2015-01-01

Fitness costs associated with resistance to insecticides have been well documented, usually at normal temperature conditions, in many insect species. In this study, using chlorpyrifos-resistant homozygote (RR) and chlorpyrifos-susceptible homozygote (SS) of resistance ace1 allele of Plutella xylostella (DBM), we confirmed firstly that high temperature experience in pupal stage influenced phenotype of wing venation in insecticide-resistant and insecticide-susceptible Plutella xylostella, and SS DBM showed significantly higher thermal tolerance and lower damages of wing veins under heat stress than RR DBM. As compared to SS DBM, RR DBM displayed significantly lower AChE sensitivity to chlorpyrifos, higher basal GSTs activity and P450 production at 25°C, but higher inhibitions on the enzyme activities and P450 production as well as reduced resistance to chlorpyrifos under heat stress. Furthermore, RR DBM displayed significantly higher basal expressions of hsp69s, hsp72s, hsp20,hsp90,Apaf-1, and caspase-7 at 25°C, but lower induced expressions of hsps and higher induced expressions of Apaf-1,caspase-9, and caspase-7 under heat stress. These results suggest that fitness costs of chlorpyrifos resistance in DBM may partly attribute to excess consumption of energy caused by over production of detoxification enzymes and hsps when the proteins are less demanded at conducive environments but reduced expressions when they are highly demanded by the insects to combat environmental stresses, or to excess expressions of apoptotic genes under heat stress, which results in higher apoptosis. The evolutionary and ecological implications of these findings at global warming are discussed.

Demonstration of arbitrary views based on autostereoscopic three-dimensional display system

NASA Astrophysics Data System (ADS)

Liu, Boyang; Sang, Xinzhu; Yu, Xunbo; Li, Liu; Yang, Le; Yan, Binbin; Wang, Kuiru; Yu, Chongxiu

2017-10-01

A method to realize arbitrary views for the lenticular lens array based on autostereoscopic three-dimensional display system is demonstrated. Normally, the number of views is proportional to pitch of the lenticular lens array. Increasing the number of views will result in reducing resolution and enhancing of granular sensation. 32 dense views can be achieved with one lenticular lens pitch covering 5.333 sub-pixels, which does significantly increases the number of views without affecting the resolution. But the structure of pitch and the number of views are fixed. Here, the 3D display method that the number of views can be changed artificially for most structures of lenticular lens is presented. Compared with the previous 32 views display method, the smoothness of motion parallex and the display depth of field are significantly improved.

Display activity and seasonality of faecal sexual steroids in male great bustard (Otis tarda L.).

PubMed

Biczó, A; Péczely, P

2007-03-01

The non-invasive faecal sampling and RIA was used to measure faecal equivalents of testosterone (T), dehydroepiandrosterone (DHEA), oestradiol-17beta (E2) and progesterone (P4) in juvenile and adult great bustard males. Possible connections of diurnal and seasonal changes of sexual steroid levels and display activity were studied. Correlations were found between sexual steroid equivalent levels of faeces and display activity and agonistic behaviour in the different phases of annual cycle of adult males. In early display period increasing levels of androgens were measured, during main display period very high androgen dominance was observable against E2 and P4. During postnuptial moult strong T decrease and DHEA and P4 increase were detected. Elevation of E2 was measured during wintering. In juveniles level of DHEA was higher than level of T suggesting its importance in immature males. Decrease of T was detected between reproductive period and postnuptial moult and DHEA between reproduction and wintering, accompanying with E2 elevation. The inhibiting effect of inclement weather on gonad functions also was detected in our study. We suppose that the unexpected cold weather with strong wind depressed the levels of androgens both in juveniles and adults and the increase of faecal E2 was also detected.

Operator modeling in commerical aviation: Cognitive models, intelligent displays, and pilot's assistants

NASA Technical Reports Server (NTRS)

Govindaraj, T.; Mitchell, C. M.

1994-01-01

One of the goals of the National Aviation Safety/Automation program is to address the issue of human-centered automation in the cockpit. Human-centered automation is automation that, in the cockpit, enhances or assists the crew rather than replacing them. The Georgia Tech research program focused on this general theme, with emphasis on designing a computer-based pilot's assistant, intelligent (i.e, context-sensitive) displays, and an intelligent tutoring system for understanding and operating the autoflight system. In particular, the aids and displays were designed to enhance the crew's situational awareness of the current state of the automated flight systems and to assist the crew's situational awareness of the current state of the automated flight systems and to assist the crew in coordinating the autoflight system resources. The activities of this grant included: (1) an OFMspert to understand pilot navigation activities in a 727 class aircraft; (2) an extension of OFMspert to understand mode control in a glass cockpit, Georgia Tech Crew Activity Tracking System (GT-CATS); (3) the design of a training system to teach pilots about the vertical navigation portion of the flight management system -VNAV Tutor; and (4) a proof-of-concept display, using existing display technology, to facilitate mode awareness, particularly in situations in which controlled flight into terrain (CFIT) is a potential.

A study on aircraft map display location and orientation

NASA Technical Reports Server (NTRS)

Baty, D. L.; Wempe, T.; Huff, E.

1973-01-01

Six airline pilots participated in a fixed-based simulator study to determine the effects of two horizontal situation display (HSD/map) panel locations relative to the vertical situation display (VSD), and of three map orientations on manual piloting performance. Pilot comments and opinions were formally obtained. Significant performance differences were found between wind conditions and among pilots but not between map locations and orientations. The results also illustrate the potential tracking accuracy of such a display. Recommendations concerning display location and map orientation are made.

A study on aircraft map display location and orientation

NASA Technical Reports Server (NTRS)

Baty, D. L.; Wempe, T. E.; Huff, E. M.

1974-01-01

Six airline pilots participated in a fixed-base simulator study to determine the effects of two horizontal situation display (HSD/map) panel locations relative to the vertical situation display (VSD), and of three map orientations on manual piloting performance. Pilot comments and opinions were formally obtained. Significant performance differences were found between wind conditions and among pilots, but not between map locations and orientations. The results also illustrate the potential tracking accuracy of such a display. Recommendations concerning display location and map orientation are made.

The music of your emotions: neural substrates involved in detection of emotional correspondence between auditory and visual music actions.

PubMed

Petrini, Karin; Crabbe, Frances; Sheridan, Carol; Pollick, Frank E

2011-04-29

In humans, emotions from music serve important communicative roles. Despite a growing interest in the neural basis of music perception, action and emotion, the majority of previous studies in this area have focused on the auditory aspects of music performances. Here we investigate how the brain processes the emotions elicited by audiovisual music performances. We used event-related functional magnetic resonance imaging, and in Experiment 1 we defined the areas responding to audiovisual (musician's movements with music), visual (musician's movements only), and auditory emotional (music only) displays. Subsequently a region of interest analysis was performed to examine if any of the areas detected in Experiment 1 showed greater activation for emotionally mismatching performances (combining the musician's movements with mismatching emotional sound) than for emotionally matching music performances (combining the musician's movements with matching emotional sound) as presented in Experiment 2 to the same participants. The insula and the left thalamus were found to respond consistently to visual, auditory and audiovisual emotional information and to have increased activation for emotionally mismatching displays in comparison with emotionally matching displays. In contrast, the right thalamus was found to respond to audiovisual emotional displays and to have similar activation for emotionally matching and mismatching displays. These results suggest that the insula and left thalamus have an active role in detecting emotional correspondence between auditory and visual information during music performances, whereas the right thalamus has a different role.

A dual host vector for Fab phage display and expression of native IgG in mammalian cells.

PubMed

Tesar, Devin; Hötzel, Isidro

2013-10-01

A significant bottleneck in antibody discovery by phage display is the transfer of immunoglobulin variable regions from phage clones to vectors that express immunoglobulin G (IgG) in mammalian cells for screening. Here, we describe a novel phagemid vector for Fab phage display that allows expression of native IgG in mammalian cells without sub-cloning. The vector uses an optimized mammalian signal sequence that drives robust expression of Fab fragments fused to an M13 phage coat protein in Escherichia coli and IgG expression in mammalian cells. To allow the expression of Fab fragments fused to a phage coat protein in E.coli and full-length IgG in mammalian cells from the same vector without sub-cloning, the sequence encoding the phage coat protein was embedded in an optimized synthetic intron within the immunoglobulin heavy chain gene. This intron is removed from transcripts in mammalian cells by RNA splicing. Using this vector, we constructed a synthetic Fab phage display library with diversity in the heavy chain only and selected for clones binding different antigens. Co-transfection of mammalian cells with DNA from individual phage clones and a plasmid expressing the invariant light chain resulted in the expression of native IgG that was used to assay affinity, ligand blocking activity and specificity.

Rolling blackout is required for bulk endocytosis in non-neuronal cells and neuronal synapses

PubMed Central

Vijayakrishnan, Niranjana; Woodruff, Elvin A.; Broadie, Kendal

2009-01-01

Summary Rolling blackout (RBO) is a Drosophila EFR3 integral membrane lipase. A conditional temperature-sensitive (TS) mutant (rbots) displays paralysis within minutes following a temperature shift from 25°C to 37°C, an impairment previously attributed solely to blocked synaptic-vesicle exocytosis. However, we found that rbots displays a strong synergistic interaction with the Syntaxin-1A TS allele syx3-69, recently shown to be a dominant positive mutant that increases Syntaxin-1A function. At neuromuscular synapses, rbots showed a strong defect in styryl-FM-dye (FM) endocytosis, and rbots;syx3-69 double mutants displayed a synergistic, more severe, endocytosis impairment. Similarly, central rbots synapses in primary brain culture showed severely defective FM endocytosis. Non-neuronal nephrocyte Garland cells showed the same endocytosis defect in tracer-uptake assays. Ultrastructurally, rbots displayed a specific defect in tracer uptake into endosomes in both neuronal and non-neuronal cells. At the rbots synapse, there was a total blockade of endosome formation via activity-dependent bulk endocytosis. Clathrin-mediated endocytosis was not affected; indeed, there was a significant increase in direct vesicle formation. Together, these results demonstrate that RBO is required for constitutive and/or bulk endocytosis and/or macropinocytosis in both neuronal and non-neuronal cells, and that, at the synapse, this mechanism is responsive to the rate of Syntaxin-1A-dependent exocytosis. PMID:19066280

Rolling blackout is required for bulk endocytosis in non-neuronal cells and neuronal synapses.

PubMed

Vijayakrishnan, Niranjana; Woodruff, Elvin A; Broadie, Kendal

2009-01-01

Rolling blackout (RBO) is a Drosophila EFR3 integral membrane lipase. A conditional temperature-sensitive (TS) mutant (rbo(ts)) displays paralysis within minutes following a temperature shift from 25 degrees C to 37 degrees C, an impairment previously attributed solely to blocked synaptic-vesicle exocytosis. However, we found that rbo(ts) displays a strong synergistic interaction with the Syntaxin-1A TS allele syx(3-69), recently shown to be a dominant positive mutant that increases Syntaxin-1A function. At neuromuscular synapses, rbo(ts) showed a strong defect in styryl-FM-dye (FM) endocytosis, and rbo(ts);syx(3-69) double mutants displayed a synergistic, more severe, endocytosis impairment. Similarly, central rbo(ts) synapses in primary brain culture showed severely defective FM endocytosis. Non-neuronal nephrocyte Garland cells showed the same endocytosis defect in tracer-uptake assays. Ultrastructurally, rbo(ts) displayed a specific defect in tracer uptake into endosomes in both neuronal and non-neuronal cells. At the rbo(ts) synapse, there was a total blockade of endosome formation via activity-dependent bulk endocytosis. Clathrin-mediated endocytosis was not affected; indeed, there was a significant increase in direct vesicle formation. Together, these results demonstrate that RBO is required for constitutive and/or bulk endocytosis and/or macropinocytosis in both neuronal and non-neuronal cells, and that, at the synapse, this mechanism is responsive to the rate of Syntaxin-1A-dependent exocytosis.

Controlling Motion Sickness and Spatial Disorientation and Enhancing Vestibular Rehabilitation with a User-Worn See-Through Display

PubMed Central

Krueger, Wesley W.O.

2010-01-01

Objectives/Hypotheses An eyewear mounted visual display (“User-worn see-through display”) projecting an artificial horizon aligned with the user's head and body position in space can prevent or lessen motion sickness in susceptible individuals when in a motion provocative environment as well as aid patients undergoing vestibular rehabilitation. In this project, a wearable display device, including software technology and hardware, was developed and a phase I feasibility study and phase II clinical trial for safety and efficacy were performed. Study Design Both phase I and phase II were prospective studies funded by the NIH. The phase II study used repeated measures for motion intolerant subjects and a randomized control group (display device/no display device) pre-post test design for patients in vestibular rehabilitation. Methods Following technology and display device development, 75 patients were evaluated by test and rating scales in the phase II study; 25 subjects with motion intolerance used the technology in the display device in provocative environments and completed subjective rating scales while 50 patients were evaluated before and after vestibular rehabilitation (25 using the display device and 25 in a control group) using established test measures. Results All patients with motion intolerance rated the technology as helpful for nine symptoms assessed, and 96% rated the display device as simple and easy to use. Duration of symptoms significantly decreased with use of the technology displayed. In patients undergoing vestibular rehabilitation, there were no significant differences in amount of change from pre- to post-therapy on objective balance tests between display device users and controls. However, those using the technology required significantly fewer rehabilitation sessions to achieve those outcomes than the control group. Conclusions A user-worn see-through display, utilizing a visual fixation target coupled with a stable artificial horizon and aligned with user movement, has demonstrated substantial benefit for individuals susceptible to motion intolerance and spatial disorientation and those undergoing vestibular rehabilitation. The technology developed has applications in any environment where motion sensitivity affects human performance. PMID:21181963

Low-density lipoprotein (LDL)-antioxidant biflavonoids from Garcinia madruno.

PubMed

Osorio, Edison; Londoño, Julián; Bastida, Jaume

2013-05-22

Six biflavonoids were isolated from G. madruno, one of which, 7''-O-(6''''-acetyl)-glucoside of morelloflavone, is a new compound identified on the basis of 1D, 2D NMR (HMQC and HMBC) spectroscopic methods and chemical evidence. The antioxidant activity of the biflavonoids against low-density lipoprotein (LDL) peroxidation induced with Cu²⁺, was studied by means of a TBARS assay. The antioxidant potential of a biflavonoid fraction (BF) was also evaluated and correlated with its biflavonoid content. The flavanone-(3→8'')-flavone biflavonoids displayed antioxidant activity, particularly morelloflavone, which was significantly more potent than quercetin, with a CE₅₀ of 12.36 μg/mL. Lipid peroxidation, was also significantly reduced in the presence of the BF (EC₅₀ = 11.85 μg/mL). These results suggest that the BF is an excellent antioxidant.

Solution-Processed Organic Thin-Film Transistor Array for Active-Matrix Organic Light-Emitting Diode

NASA Astrophysics Data System (ADS)

Harada, Chihiro; Hata, Takuya; Chuman, Takashi; Ishizuka, Shinichi; Yoshizawa, Atsushi

2013-05-01

We developed a 3-in. organic thin-film transistor (OTFT) array with an ink-jetted organic semiconductor. All layers except electrodes were fabricated by solution processes. The OTFT performed well without hysteresis, and the field-effect mobility in the saturation region was 0.45 cm2 V-1 s-1, the threshold voltage was 3.3 V, and the on/off current ratio was more than 106. We demonstrated a 3-in. active-matrix organic light-emitting diode (AMOLED) display driven by the OTFT array. The display could provide clear moving images. The peak luminance of the display was 170 cd/m2.

Mimtags: the use of phage display technology to produce novel protein-specific probes.

PubMed

Ahmed, Nayyar; Dhanapala, Pathum; Sadli, Nadia; Barrow, Colin J; Suphioglu, Cenk

2014-03-01

In recent times the use of protein-specific probes in the field of proteomics has undergone evolutionary changes leading to the discovery of new probing techniques. Protein-specific probes serve two main purposes: epitope mapping and detection assays. One such technique is the use of phage display in the random selection of peptide mimotopes (mimtags) that can tag epitopes of proteins, replacing the use of monoclonal antibodies in detection systems. In this study, phage display technology was used to screen a random peptide library with a biologically active purified human interleukin-4 receptor (IL-4R) and interleukin-13 (IL-13) to identify mimtag candidates that interacted with these proteins. Once identified, the mimtags were commercially synthesised, biotinylated and used for in vitro immunoassays. We have used phage display to identify M13 phage clones that demonstrated specific binding to IL-4R and IL-13 cytokine. A consensus in binding sequences was observed and phage clones characterised had identical peptide sequence motifs. Only one was synthesised for use in further immunoassays, demonstrating significant binding to either IL-4R or IL-13. We have successfully shown the use of phage display to identify and characterise mimtags that specifically bind to their target epitope. Thus, this new method of probing proteins can be used in the future as a novel tool for immunoassay and detection technique, which is cheaper and more rapidly produced and therefore a better alternative to the use of monoclonal antibodies. Copyright © 2014 Elsevier B.V. All rights reserved.

Streaming Seismograms into Earth-Science Classrooms

NASA Astrophysics Data System (ADS)

Ammon, C. J.

2011-12-01

Seismograms are the fundamental observations upon which seismology is based; they are central to any course in seismology and important for any discussion of earthquake-related phenomena based on seismic observations. Advances in the collection and distribution of seismic data have made the use of research-quality seismograms in any network capable classroom feasible. The development of large, deep seismogram archives place an unprecedented quantity of high-quality data within reach of the modern classroom environment. I describe and discuss several computer tools and classroom activities that I use in introductory (general education) and advanced undergraduate courses that present near real-time research-quality seismic observations in the classroom. The Earth Motion Monitor Application (EMMA), is a MacOS application that presents a visually clear seismogram display that can be projected in classrooms with internet access. Seismic signals from thousands of station are available from the IRIS data center and the bandwidth can be tailored to the particular type of signal of interest (large event, low frequencies; small event, high frequencies). In introductory classes for non-science students, the near realtime display routinely shows magnitude 4.0-5.0 earthquake-generated signals, demonstrating to students the frequency of earthquake occurrence. Over the next few minutes as the waves travel through and across the planet, their arrival on the seismogram display provides some basic data for a qualitative estimate of the event's general location. When a major or great earthquake occurs, a broad-band display of signals from nearby stations can dramatically and dynamically illuminate the frequent activity associated with the aftershock sequence. Routine use of the display (while continuing the traditional classroom activities) provides students with a significant dose of seismogram study. Students generally find all the signals, including variations in seismic background motions, interesting and formulate good questions related to the signal details. A few minutes at the beginning of class reviewing the activity between classes and a few minutes when an earthquake occurs provide valuable discussion points related to earthquake science and seismic-wave propagation. Other tools discussed are related to global earthquake geography, with self-updating global maps of earthquakes (Epicentral, a MacOS and iOS application). When a signal first shows up on the EMMA seismogram display, students can invest a few minutes estimating the event's general location (and checking the signal character - relative arrival times, dispersion, etc). When a location is posted by an appropriate authority (e.g. the U. S. Geological Survey) the student's estimates can be checked and discussed. Additionally, Epicentral for MacOS presents a self-updated Twitter stream that can light up substantially when a felt earthquake occurs. Although the language of many of the tweeters can be colorful, the results are interesting and instant. The inclusion of these tools takes some time away from traditional lectures, but helps produce a dynamic, thought-provoking classroom experience.

Neuromuscular Characteristics of Individuals Displaying Excessive Medial Knee Displacement

PubMed Central

Padua, Darin A.; Bell, David R.; Clark, Micheal A.

2012-01-01

Context Knee-valgus motion is a potential risk factor for certain lower extremity injuries, including anterior cruciate ligament injury and patellofemoral pain. Identifying neuromuscular characteristics associated with knee-valgus motion, such as hip and lower leg muscle activation, may improve our ability to prevent lower extremity injuries. Objective We hypothesized that hip and lower leg muscle-activation amplitude would differ among individuals displaying knee valgus (medial knee displacement) during a double-legged squat compared with those who did not display knee valgus. We further suggested that the use of a heel lift would alter lower leg muscle activation and frontal-plane knee motion in those demonstrating medial knee displacement. Design Descriptive laboratory study. Setting Research laboratory. Patients or Other Participants A total of 37 healthy participants were assigned to the control (n = 19) or medial-knee-displacement (n = 18) group based on their double-legged squat performance. Main Outcome Measure(s) Muscle-activation amplitude for the gluteus maximus, gluteus medius, adductor magnus, medial and lateral gastrocnemius, and tibialis anterior was measured during 2 double-legged squat tasks. The first task consisted of performing a double-legged squat without a heel lift; the second consisted of performing a double-legged squat task with a 2-in (5.08-cm) lift under the heels. Results Muscle-activation amplitude for the hip adductor, gastrocnemius, and tibialis anterior was greater in those who displayed knee valgus than in those who did not (P < .05). Also, use of heel lifts resulted in decreased activation of the gluteus maximus, hip adductor, gastrocnemius, and tibialis anterior muscles (P < .05). Use of heel lifts also eliminated medially directed frontal-plane knee motion in those displaying medial knee displacement. Conclusions Medial knee displacement during squatting tasks appears to be associated with increased hip-adductor activation and increased coactivation of the gastrocnemius and tibialis anterior muscles. PMID:23068590

SPAK and OSR1 play essential roles in potassium homeostasis through actions on the distal convoluted tubule

PubMed Central

Ferdaus, Mohammed Z.; Barber, Karl W.; López‐Cayuqueo, Karen I.; Terker, Andrew S.; Argaiz, Eduardo R.; Gassaway, Brandon M.; Chambrey, Régine; Gamba, Gerardo; Rinehart, Jesse

2016-01-01

Key points STE20 (Sterile 20)/SPS‐1 related proline/alanine‐rich kinase (SPAK) and oxidative stress‐response kinase‐1 (OSR1) phosphorylate and activate the renal Na+–K+–2Cl− cotransporter 2 (NKCC2) and Na+Cl− cotransporter (NCC).Mouse models suggest that OSR1 mainly activates NKCC2‐mediated sodium transport along the thick ascending limb, while SPAK mainly activates NCC along the distal convoluted tubule, but the kinases may compensate for each other. We hypothesized that disruption of both kinases would lead to polyuria and severe salt‐wasting, and generated SPAK/OSR1 double knockout mice to test this.Despite a lack of SPAK and OSR1, phosphorylated NKCC2 abundance was still high, suggesting the existence of an alternative activating kinase.Compensatory changes in SPAK/OSR1‐independent phosphorylation sites on both NKCC2 and NCC and changes in sodium transport along the collecting duct were also observed.Potassium restriction revealed that SPAK and OSR1 play essential roles in the emerging model that NCC activation is central to sensing changes in plasma [K+]. Abstract STE20 (Sterile 20)/SPS‐1 related proline/alanine‐rich kinase (SPAK) and oxidative stress‐response kinase‐1 (OSR1) activate the renal cation cotransporters Na+–K+–2Cl− cotransporter (NKCC2) and Na+–Cl− cotransporter (NCC) via phosphorylation. Knockout mouse models suggest that OSR1 mainly activates NKCC2, while SPAK mainly activates NCC, with possible cross‐compensation. We tested the hypothesis that disrupting both kinases causes severe polyuria and salt‐wasting by generating SPAK/OSR1 double knockout (DKO) mice. DKO mice displayed lower systolic blood pressure compared with SPAK knockout (SPAK‐KO) mice, but displayed no severe phenotype even after dietary salt restriction. Phosphorylation of NKCC2 at SPAK/OSR1‐dependent sites was lower than in SPAK‐KO mice, but still significantly greater than in wild type mice. In the renal medulla, there was significant phosphorylation of NKCC2 at SPAK/OSR1‐dependent sites despite a complete absence of SPAK and OSR1, suggesting the existence of an alternative activating kinase. The distal convoluted tubule has been proposed to sense plasma [K+], with NCC activation serving as the primary effector pathway that modulates K+ secretion, by metering sodium delivery to the collecting duct. Abundance of phosphorylated NCC (pNCC) is dramatically lower in SPAK‐KO mice than in wild type mice, and the additional disruption of OSR1 further reduced pNCC. SPAK‐KO and kidney‐specific OSR1 single knockout mice maintained plasma [K+] following dietary potassium restriction, but DKO mice developed severe hypokalaemia. Unlike mice lacking SPAK or OSR1 alone, DKO mice displayed an inability to phosphorylate NCC under these conditions. These data suggest that SPAK and OSR1 are essential components of the effector pathway that maintains plasma [K+]. PMID:27068441

Younger and older adults' perception of the Wundt-Hering illusion as a function of display illumination and reflectance contrast.

PubMed

Astor-Stetson, E; Lane, S

1991-08-01

Reflectance contrast (i.e., black as compared to grey figures on white ground) and display illumination were manipulated to vary the brightness contrast of Wundt-Hering figures. 16 college students and 16 older adults were presented with high, medium, and low reflectance contrast figures. For half the participants, display illumination was manipulated by covering the figures with a .5 yellow neutral density filter. Magnitude of the illusion increased significantly with increased reflectance contrast for college students, and college students were significantly more susceptible to the high contrast figures than were older adults. Display illumination had no effect on the performance of either group.

Novel Tacrine-Benzofuran Hybrids as Potent Multitarget-Directed Ligands for the Treatment of Alzheimer's Disease: Design, Synthesis, Biological Evaluation, and X-ray Crystallography.

PubMed

Zha, Xiaoming; Lamba, Doriano; Zhang, Lili; Lou, Yinghan; Xu, Changxu; Kang, Di; Chen, Li; Xu, Yungen; Zhang, Luyong; De Simone, Angela; Samez, Sarah; Pesaresi, Alessandro; Stojan, Jure; Lopez, Manuela G; Egea, Javier; Andrisano, Vincenza; Bartolini, Manuela

2016-01-14

Twenty-six new tacrine-benzofuran hybrids were designed, synthesized, and evaluated in vitro on key molecular targets for Alzheimer's disease. Most hybrids exhibited good inhibitory activities on cholinesterases and β-amyloid self-aggregation. Selected compounds displayed significant inhibition of human β-secretase-1 (hBACE-1). Among the 26 hybrids, 2e showed the most interesting profile as a subnanomolar selective inhibitor of human acetylcholinesterase (hAChE) (IC50 = 0.86 nM) and a good inhibitor of both β-amyloid aggregation (hAChE- and self-induced, 61.3% and 58.4%, respectively) and hBACE-1 activity (IC50 = 1.35 μM). Kinetic studies showed that 2e acted as a slow, tight-binding, mixed-type inhibitor, while X-ray crystallographic studies highlighted the ability of 2e to induce large-scale structural changes in the active-site gorge of Torpedo californica AChE (TcAChE), with significant implications for structure-based drug design. In vivo studies confirmed that 2e significantly ameliorates performances of scopolamine-treated ICR mice. Finally, 2e administration did not exhibit significant hepatotoxicity.

N-terminal acylation of somatostatin analog with long chain fatty acids enhances its stability and anti-proliferative activity in human breast adenocarcinoma cells.

PubMed

Dasgupta, Piyali; Singh, Anu; Mukherjee, Rama

2002-01-01

The anti-proliferative activity of the somatostatin analog RC-160 is limited by its short serum half life. To circumvent this limitation, fatty acids of chain lengths ranging from 4 to 18 were individually conjugated to the N-terminal residue of RC-160. The lipophilized derivatives of RC-160 were synthesized, purified and characterized. The anti-proliferative activity of lipophilized-RC-160 on the human breast carcinoma cell line MCF-7, was evaluated in vitro. The long chain lipopeptides like pamitoyl-RC-160 exhibited significantly higher anti-proliferative activity on MCF-7 cells (p<0.001), relative to RC-160. The affinity of RC-160 towards somatostatin receptors remained unaltered by pamitoylation. However, the observed increase in bioactivity was manifested within an optimum range of chain length of the lipoppetide. Increasing the peptide hydrophobicity beyond this range reduced the bioactivity of lipophilized-RC-160. Accordingly, stearoyl-RC-160, manifested lower anti-neoplastic activity and receptor affinity relative to pamitoyl-RC-160 and RC-160 itself. The signaling pathways underlying the antineoplastic activity of these lipopeptides were found to be similar to RC-160. Pamitoyl-RC-160 displayed enhanced inhibition of protein tyrosine kinase activity and intracellular cAMP levels in MCF-7 cells, relative to butanoyl-RC-160 or RC-160 itself. Pamitoyl-RC-160 also displayed greater resistance towards trypsin and serum degradation than RC-160. Lipophilization of RC-160 with long chain fatty acids like pamitic acid improves its stability and anti-proliferative activity, thereby improving the scope of enhancing its therapeutic index. However, the optimization of peptide hydrophobicity seems to be a crucial factor governing the efficacy of bioactive lipopeptides.

Schistosomiasis Control Using Piplartine against Biomphalaria glabrata at Different Developmental Stages

PubMed Central

Rapado, Ludmila Nakamura; Pinheiro, Alessandro de Sá; Lopes, Priscila Orechio de Moraes Victor; Fokoue, Harold Hilarion; Scotti, Marcus Tullius; Marques, Joaquim Vogt; Ohlweiler, Fernanda Pires; Borrely, Sueli Ivone; Pereira, Carlos Alberto de Bragança; Kato, Massuo Jorge; Nakano, Eliana; Yamaguchi, Lydia Fumiko

2013-01-01

Background Schistosomiasis is one of the most significant diseases in tropical countries and affects almost 200 million people worldwide. The application of molluscicides to eliminate the parasite's intermediate host, Biomphalaria glabrata, from infected water supplies is one strategy currently being used to control the disease. Previous studies have shown a potent molluscicidal activity of crude extracts from Piper species, with extracts from Piper tuberculatum being among the most active. Methods and Findings The molluscicidal activity of P. tuberculatum was monitored on methanolic extracts from different organs (roots, leaves, fruit and stems). The compounds responsible for the molluscicidal activity were identified using 1H NMR and ESIMS data and multivariate analyses, including principal component analysis and partial least squares. These results indicated that the high molluscicidal activity displayed by root extracts (LC50 20.28 µg/ml) was due to the presence of piplartine, a well-known biologically-active amide. Piplartine was isolated from P. tuberculatum root extracts, and the molluscicidal activity of this compound on adults and embryos of B. glabrata was determined. The compound displayed potent activity against all developmental stages of B. glabrata. Next, the environmental toxicity of piplartine was evaluated using the microcrustacean Daphnia similis (LC50 7.32 µg/ml) and the fish Danio rerio (1.69 µg/ml). The toxicity to these organisms was less compared with the toxicity of niclosamide, a commercial molluscicide. Conclusions The development of a new, natural molluscicide is highly desirable, particularly because the commercially available molluscicide niclosamide is highly toxic to some organisms in the environment (LC50 0.25 µg/ml to D. similis and 0.12 µg/ml to D. rerio). Thus, piplartine is a potential candidate for a natural molluscicide that has been extracted from a tropical plant species and showed less toxic to environment. PMID:23755312

Recent advances in AM OLED technologies for application to aerospace and military systems

NASA Astrophysics Data System (ADS)

Sarma, Kalluri R.; Roush, Jerry; Chanley, Charles

2012-06-01

While initial AM OLED products have been introduced in the market about a decade ago, truly successful commercialization of OLEDs has started only a couple of years ago, by Samsung Mobile Display (SMD), with small high performance displays for smart phone applications. This success by Samsung has catalyzed significant interest in AM OLED technology advancement and commercialization by other display manufacturers. Currently, significant manufacturing capacity for AM OLED displays is being established by the industry to serve the growing demand for these displays. The current development in the AM OLED industry are now focused on the development and commercialization of medium size (~10") AM OLED panels for Tablet PC applications and large size (~55") panels for TV applications. This significant progress in commercialization of AM OLED technology is enabled by major advances in various enabling technologies that include TFT backplanes, OLED materials and device structures and manufacturing know-how. In this paper we will discuss these recent advances, particularly as they relate to supporting high performance applications such as aerospace and military systems, and then discuss the results of the OLED testing for aerospace applications.

Lectin activity in mycelial extracts of Fusarium species.

PubMed

Bhari, Ranjeeta; Kaur, Bhawanpreet; Singh, Ram S

2016-01-01

Lectins are non-immunogenic carbohydrate-recognizing proteins that bind to glycoproteins, glycolipids, or polysaccharides with high affinity and exhibit remarkable ability to agglutinate erythrocytes and other cells. In the present study, ten Fusarium species previously not explored for lectins were screened for the presence of lectin activity. Mycelial extracts of F. fujikuroi, F. beomiformii, F. begoniae, F. nisikadoi, F. anthophilum, F. incarnatum, and F. tabacinum manifested agglutination of rabbit erythrocytes. Neuraminidase treatment of rabbit erythrocytes increased lectin titers of F. nisikadoi and F. tabacinum extracts, whereas the protease treatment resulted in a significant decline in agglutination by most of the lectins. Results of hapten inhibition studies demonstrated unique carbohydrate specificity of Fusarium lectins toward O-acetyl sialic acids. Activity of the majority of Fusarium lectins exhibited binding affinity to d-ribose, l-fucose, d-glucose, l-arabinose, d-mannitol, d-galactosamine hydrochloride, d-galacturonic acid, N-acetyl-d-galactosamine, N-acetyl-neuraminic acid, 2-deoxy-d-ribose, fetuin, asialofetuin, and bovine submaxillary mucin. Melibiose and N-glycolyl neuraminic acid did not inhibit the activity of any of the Fusarium lectins. Mycelial extracts of F. begoniae, F. nisikadoi, F. anthophilum, and F. incarnatum interacted with most of the carbohydrates tested. F. fujikuroi and F. anthophilum extracts displayed strong interaction with starch. The expression of lectin activity as a function of culture age was investigated. Most species displayed lectin activity on the 7th day of cultivation, and it varied with progressing of culture age. Copyright © 2016 Sociedade Brasileira de Microbiologia. Published by Elsevier Editora Ltda. All rights reserved.

Purification and characterization of halophilic lipase of Chromohalobacter sp. from ancient salt well.

PubMed

Ai, Li; Huang, Yaping; Wang, Chuan

2018-06-04

A halophilic lipase (LipS2) was produced by Chromohalobacter canadensis strain which was isolated from ancient salt well of Zigong, China. LipS2 was purified to homogeneity and showed a single band with molecular mass of 58 kDa by SDS-PAGE. LipS2 preferred middle-to-long acyl chain esters with C14 triglycerides as optimum substrate. It was noteworthy that LipS2 displayed efficient hydrolysis activity to some vegetable oils which were composed of polyunsaturated fatty acid. LipS2 showed high activity in range of 2.5-3.5 M NaCl, no activity without salt. Optimum temperature and pH were 55 °C and pH 8.5, respectively. Notably, the thermostability and pH stability of LipS2, varying with salt concentration, reached optimum in the presence of 3.0 M NaCl. LipS2 was stimulated by Ca 2+ and Mg 2+ , inhibited by Zn 2+ , Cu 2+ , Mn 2+ , Fe 2+ , and Hg 2+ . Moreover, LipS2 displayed significant tolerance to organic solvents including methanol, ethanol, ethyl acetate and acetone, especially, LipS2 activity was enhanced markedly by the hexane and benzene. Non-ionic surfactants increased LipS2 activity, while ionic surfactants decreased activity. This was the first report on halophilic lipase of Chromohalobacter from ancient salt well. The results suggested that LipS2 may have considerable potential for biotechnological applications. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

In vivo imaging of zebrafish digestive organ function using multiple quenched fluorescent reporters.

PubMed

Hama, Kotaro; Provost, Elayne; Baranowski, Timothy C; Rubinstein, Amy L; Anderson, Jennifer L; Leach, Steven D; Farber, Steven A

2009-02-01

Optical clarity of larvae makes the zebrafish ideal for real-time analyses of vertebrate organ function through the use of fluorescent reporters of enzymatic activities. A key function of digestive organs is to couple the generation of enzymes with mechanical processes that enable nutrient availability and absorption. However, it has been extremely difficult, and in many cases not possible, to directly observe digestive processes in a live vertebrate. Here we describe a new method to visualize intestinal protein and lipid processing simultaneously in live zebrafish larvae using a quenched fluorescent protein (EnzChek) and phospholipid (PED6). By employing these reagents, we found that wild-type larvae exhibit significant variation in intestinal phospholipase and protease activities within a group but display a strong correlation between the activities within individuals. Furthermore, we found that pancreas function is essential for larval digestive protease activity but not for larval intestinal phospholipase activity. Although fat-free (ffr) mutant larvae were previously described to exhibit impaired lipid processes, we found they also had significantly reduced protease activity. Finally, we selected and evaluated compounds that were previously suggested to have altered phospholipase activity and are known or suspected to have inflammatory effects in the intestinal tract including nonsteroidal anti-inflammatory drugs, and identified a compound that significantly increases intestinal phospholipid processing. Thus the multiple fluorescent reporter-based methodology facilitates the rapid analysis of digestive organ function in live zebrafish larvae.

Associations of office workers' objectively assessed occupational sitting, standing and stepping time with musculoskeletal symptoms.

PubMed

Coenen, Pieter; Healy, Genevieve N; Winkler, Elisabeth A H; Dunstan, David W; Owen, Neville; Moodie, Marj; LaMontagne, Anthony D; Eakin, Elizabeth A; O'Sullivan, Peter B; Straker, Leon M

2018-04-22

We examined the association of musculoskeletal symptoms (MSS) with workplace sitting, standing and stepping time, as well as sitting and standing time accumulation (i.e. usual bout duration of these activities), measured objectively with the activPAL3 monitor. Using baseline data from the Stand Up Victoria trial (216 office workers, 14 workplaces), cross-sectional associations of occupational activities with self-reported MSS (low-back, upper and lower extremity symptoms in the last three months) were examined using probit regression, correcting for clustering and adjusting for confounders. Sitting bout duration was significantly (p < 0.05) associated, non-linearly, with MSS, such that those in the middle tertile displayed the highest prevalence of upper extremity symptoms. Other associations were non-significant but sometimes involved large differences in symptom prevalence (e.g. 38%) by activity. Though causation is unclear, these non-linear associations suggest that sitting and its alternatives (i.e. standing and stepping) interact with MSS and this should be considered when designing safe work systems. Practitioner summary: We studied associations of objectively assessed occupational activities with musculoskeletal symptoms in office workers. Workers who accumulated longer sitting bouts reported fewer upper extremity symptoms. Total activity duration was not significantly associated with musculoskeletal symptoms. We underline the importance of considering total volumes and patterns of activity time in musculoskeletal research.

In vivo activity assessment of a "honey-bee pollen mix" formulation.

PubMed

Küpeli Akkol, Esra; Orhan, Didem Deliorman; Gürbüz, Ilhan; Yesilada, Erdem

2010-03-01

Honey-bee pollen mix (HBM) formulation is claimed to be effective for the treatment of asthma, bronchitis, cancers, peptic ulcers, colitis, various types of infections including hepatitis B, and rheumatism by the herb dealers in northeast Turkey. In the present study, in vivo antinociceptive, anti-inflammatory, gastroprotective and antioxidant effects of pure honey and HBM formulation were evaluated comparatively. HBM did not show any significant gastroprotective activity in a single administration at 250 mg/kg dose, whereas a weak activity was observed after three days of successive administration at 500 mg/kg dose. On the other hand, HBM displayed significant antinociceptive (p <0.01) and anti-inflammatory (p <0.01) activities at 500 mg/kg dose orally without inducing any apparent acute toxicity or gastric damage. HBM was also shown to possess potent antilipidperoxidant activity (p <0.01) at 500 mg/kg dose against acetaminophen-induced liver necrosis model in mice. On the other hand, pure honey did not exert any remarkable antinociceptive, anti-inflammatory and gastroprotective activity, but a potent antilipidperoxidant activity (p <0.01) was determined. Results have clearly proved that mixing pure honey with bee pollen significantly increased the healing potential of honey and provided additional support for its traditional use. Total phenolic and flavonoid contents of HBM were found to be 145 and 59.3 mg/100 g of honey, which were estimated as gallic acid and quercetin equivalents, respectively.

Effects of in-vehicle warning information displays with or without spatial compatibility on driving behaviors and response performance.

PubMed

Liu, Yung-Ching; Jhuang, Jing-Wun

2012-07-01

A driving simulator study was conducted to evaluate the effects of five in-vehicle warning information displays upon drivers' emergent response and decision performance. These displays include visual display, auditory displays with and without spatial compatibility, hybrid displays in both visual and auditory format with and without spatial compatibility. Thirty volunteer drivers were recruited to perform various tasks that involved driving, stimulus-response, divided attention and stress rating. Results show that for displays of single-modality, drivers benefited more when coping with visual display of warning information than auditory display with or without spatial compatibility. However, auditory display with spatial compatibility significantly improved drivers' performance in reacting to the divided attention task and making accurate S-R task decision. Drivers' best performance results were obtained for hybrid display with spatial compatibility. Hybrid displays enabled drivers to respond the fastest and achieve the best accuracy in both S-R and divided attention tasks. Copyright © 2011 Elsevier Ltd and The Ergonomics Society. All rights reserved.

Novel green synthesis of gold nanoparticles using Citrullus lanatus rind and investigation of proteasome inhibitory activity, antibacterial, and antioxidant potential

PubMed Central

Patra, Jayanta Kumar; Baek, Kwang-Hyun

2015-01-01

Biological synthesis of nanoparticles using nontoxic, eco-friendly approaches is gaining importance owing to their fascinating biocompatibility and environmentally benign nature. This study describes the green synthesis approach for synthesis of gold nanoparticles (ANPs) using aqueous extract of the rind of watermelon as a fruit waste and evaluate its biopotential in terms of proteasome inhibitory activity, antibacterial, and antioxidant potential. The synthesized ANPs were characterized using UV–vis spectroscopy, scanning electron microscopy, X-ray diffraction, Fourier-transform infrared spectroscopy, and thermogravimetric analysis. The surface plasmon resonance spectra of ANPs were obtained at 560 nm. Scanning electron microscopy image revealed that particles had a spherical shape and have a size distribution of 20–140 nm, followed by the elemental analysis by energy-dispersive X-ray spectroscopy. X-ray diffraction analysis confirmed the crystallite nature of the ANPs and Fourier-transform infrared spectroscopy revealed the involvement of bioactive compounds from watermelon rind in the synthesis, capping, and stabilization of ANPs. ANPs exhibited potential antibacterial activity against five different foodborne pathogenic bacteria with diameter of inhibition zones ranged between 9.23 and 11.58 mm. They also displayed strong synergistic antibacterial activity together with kanamycin (11.93–21.08 mm inhibition zones) and rifampicin (10.32–24.84 mm inhibition zones). ANPs displayed strong antioxidant activity in terms of DPPH radical scavenging (24.69%), nitric oxide scavenging (25.62%), ABTS scavenging (29.42%), and reducing power. Significantly high proteasome inhibitory potential of the ANPs (28.16%) could be highly useful for cancer treatment and targeted cancer drug delivery. Overall, results highlight a potential low-cost green method of synthesizing ANPs from food waste materials. Significant biopotentials of synthesized ANPs could make it a potential candidate for its application in the biomedical, pharmaceutical, cosmetics, and food sectors. PMID:26664116

System Engineering Concept Demonstration, Technology Assessments. Volume 5

DTIC Science & Technology

1992-12-01

MacUser Editor’s Choice Award for the most significant hardware/software product for the Macintosh for the year. Ivan Mimica, founder and CEO of...industry has typed for decades, the devices that are really, to borrow the phrase Apple computer founder Steve Jobs, "the computer for the rest of us.ŕ...43. 3 Ibid. 4 Ibid. 76 android is also displayed, indicating to the group that Liza is participating."’ Liza represents a set of rules that are active