Simulator study of conventional general aviation instrument displays in path-following tasks with emphasis on pilot-induced oscillations

NASA Technical Reports Server (NTRS)

Adams, J. J.

1980-01-01

A study of the use of conventional general aviation instruments by general aviation pilots in a six degree of freedom, fixed base simulator was conducted. The tasks performed were tracking a VOR radial and making an ILS approach to landing. A special feature of the tests was that the sensitivity of the displacement indicating instruments (the RMI, CDI, and HSI) was kept constant at values corresponding to 5 n. mi. and 1.25 n. mi. from the station. Both statistical and pilot model analyses of the data were made. The results show that performance in path following improved with increases in display sensitivity up to the highest sensitivity tested. At this maximum test sensitivity, which corresponds to the sensitivity existing at 1.25 n. mi. for the ILS glide slope transmitter, tracking accuracy was no better than it was at 5 n. mi. from the station and the pilot aircraft system exhibited a marked reduction in damping. In some cases, a pilot induced, long period unstable oscillation occurred.

Sense and sensitivity: responsiveness to offspring signals varies with the parents' potential to breed again

PubMed Central

Thorogood, Rose; Ewen, John G.; Kilner, Rebecca M.

2011-01-01

How sensitive should parents be to the demands of their young? Offspring are under selection to seek more investment than is optimal for parents to supply, which makes parents vulnerable to losing future fitness by responding to manipulative displays. Yet, parents cannot afford to ignore begging and risk allocating resources inefficiently. Here, we show that parents may solve this problem by adjusting their sensitivity to begging behaviour in relation to their own likelihood of breeding again, a factor largely neglected in previous analyses of parent–offspring interactions. In two carotenoid-supplementation experiments on a New Zealand passerine, the hihi Notiomystis cincta, we supplemented adults to enhance their propensity to breed again, and supplemented entire broods to increase their mouth colour, thus enhancing their solicitation display. We found that adults that attempted two breeding attempts a season were largely insensitive to the experimentally carotenoid-rich gapes of their brood, whereas those that bred just once responded by increasing their rate of provisioning at the nest. Our results show that parents can strategically vary their sensitivity to begging in relation to their future reproductive potential. By restricting opportunities for offspring to influence provisioning decisions, parents greatly limit the potential for offspring to win parent–offspring conflict. PMID:21270035

S-Glutathionylation of troponin I (fast) increases contractile apparatus Ca2+ sensitivity in fast-twitch muscle fibres of rats and humans

PubMed Central

Mollica, J P; Dutka, T L; Merry, T L; Lamboley, C R; McConell, G K; McKenna, M J; Murphy, R M; Lamb, G D

2012-01-01

Oxidation can decrease or increase the Ca2+ sensitivity of the contractile apparatus in rodent fast-twitch (type II) skeletal muscle fibres, but the reactions and molecular targets involved are unknown. This study examined whether increased Ca2+ sensitivity is due to S-glutathionylation of particular cysteine residues. Skinned muscle fibres were directly activated in heavily buffered Ca2+ solutions to assess contractile apparatus Ca2+ sensitivity. Rat type II fibres were subjected to S-glutathionylation by successive treatments with 2,2′-dithiodipyridine (DTDP) and glutathione (GSH), and displayed a maximal increase in pCa50 (−log10µCa2+½ at half-maximal force) of ∼0.24 pCa units, with little or no effect on maximum force or Hill coefficient. Partial similar effect was produced by exposure to oxidized gluthathione (GSSG, 10 mm) for 10 min at pH 7.1, and near-maximal effect by GSSG treatment at pH 8.5. None of these treatments significantly altered Ca2+ sensitivity in rat type I fibres. Western blotting showed that both the DTDP–GSH and GSSG–pH 8.5 treatments caused marked S-glutathionylation of the fast troponin I isoform (TnIf) present in type II fibres, but not of troponin C (TnC) or myosin light chain 2. Both the increased Ca2+ sensitivity and glutathionylation of TnIf were blocked by N-ethylmaleimide (NEM). S-Nitrosoglutathione (GSNO) also increased Ca2+ sensitivity, but only in conditions where it caused S-glutathionylation of TnIf. In human type II fibres from vastus lateralis muscle, DTDP–GSH treatment also caused similar increased Ca2+ sensitivity and S-glutathionylation of TnIf. When the slow isoform of TnI in type I fibres of rat was partially substituted (∼30%) with TnIf, DTDP–GSH treatment caused a significant increase in Ca2+ sensitivity (∼0.08 pCa units). TnIf in type II fibres from toad and chicken muscle lack Cys133 present in mammalian TnIf, and such fibres showed no change in Ca2+ sensitivity with DTDP–GSH nor any S-glutathionylation of TnIf (latter examined only in toad). Following 40 min of cycling exercise in human subjects (at ∼60% peak oxygen consumption), TnIf in vastus lateralis muscle displayed a marked increase in S-glutathionylation (∼4-fold). These findings show that S-glutathionylation of TnIf, most probably at Cys133, increases the Ca2+ sensitivity of the contractile apparatus, and that this occurs in exercising humans, with likely beneficial effects on performance. PMID:22250211

S-glutathionylation of troponin I (fast) increases contractile apparatus Ca2+ sensitivity in fast-twitch muscle fibres of rats and humans.

PubMed

Mollica, J P; Dutka, T L; Merry, T L; Lamboley, C R; McConell, G K; McKenna, M J; Murphy, R M; Lamb, G D

2012-03-15

Oxidation can decrease or increase the Ca2+ sensitivity of the contractile apparatus in rodent fast-twitch (type II) skeletal muscle fibres, but the reactions and molecular targets involved are unknown. This study examined whether increased Ca2+ sensitivity is due to S-glutathionylation of particular cysteine residues. Skinned muscle fibres were directly activated in heavily buffered Ca2+ solutions to assess contractile apparatus Ca2+ sensitivity. Rat type II fibres were subjected to S-glutathionylation by successive treatments with 2,2′-dithiodipyridine (DTDP) and glutathione (GSH), and displayed a maximal increase in pCa50 (−log10 [Ca2+] at half-maximal force) of ∼0.24 pCa units, with little or no effect on maximum force or Hill coefficient. Partial similar effect was produced by exposure to oxidized gluthathione (GSSG, 10 mM) for 10 min at pH 7.1, and near-maximal effect by GSSG treatment at pH 8.5. None of these treatments significantly altered Ca2+ sensitivity in rat type I fibres. Western blotting showed that both the DTDP–GSH and GSSG–pH 8.5 treatments caused marked S-glutathionylation of the fast troponin I isoform (TnI(f)) present in type II fibres, but not of troponin C (TnC) or myosin light chain 2. Both the increased Ca2+ sensitivity and glutathionylation of TnI(f) were blocked by N-ethylmaleimide (NEM). S-nitrosoglutathione (GSNO) also increased Ca2+ sensitivity, but only in conditions where it caused S-glutathionylation of TnI(f). In human type II fibres from vastus lateralis muscle, DTDP–GSH treatment also caused similar increased Ca2+ sensitivity and S-glutathionylation of TnI(f). When the slow isoform of TnI in type I fibres of rat was partially substituted (∼30%) with TnI(f), DTDP–GSH treatment caused a significant increase in Ca2+ sensitivity (∼0.08 pCa units). TnIf in type II fibres from toad and chicken muscle lack Cys133 present in mammalian TnIf, and such fibres showed no change in Ca2+ sensitivity with DTDP–GSH nor any S-glutathionylation of TnI(f) (latter examined only in toad). Following 40 min of cycling exercise in human subjects (at ∼60% peak oxygen consumption), TnI(f) in vastus lateralis muscle displayed a marked increase in S-glutathionylation (∼4-fold). These findings show that S-glutathionylation of TnI(f), most probably at Cys133, increases the Ca2+ sensitivity of the contractile apparatus, and that this occurs in exercising humans, with likely beneficial effects on performance.

Perception of biomechanical motions by infants: implementation of various processing constraints.

PubMed

Bertenthal, B I; Proffitt, D R; Kramer, S J

1987-11-01

Geometry informs us that there exist a large number of possible connectivity patterns consistent with a point-light display of a person walking. Yet there is only one pattern consistent with a "stick figure" representation of the human form, and that pattern is uniquely specified by those pairwise connections that remain locally rigid. In this study, sensitivity to local rigidity in biomechanical displays was investigated in 3- and 5-month-old infants. The results of Experiment 1 revealed that by 5 months of age, infants discriminate a locally rigid point-light walker display from one in which local rigidity is perturbed. In Experiment 2 we tested infants' sensitivity to the same stimuli when those stimuli were inverted. Contrary to the preceding experiment, the results revealed no evidence of discrimination. Taken together, these findings suggest that infants are sensitive to local rigidity in biomechanical displays but that this sensitivity is orientation specific. Possible mechanisms for this specificity are discussed in the context of additional constraints on the processing of biomechanical displays.

Novel Escherichia coli RF1 mutants with decreased translation termination activity and increased sensitivity to the cytotoxic effect of the bacterial toxins Kid and RelE.

PubMed

Diago-Navarro, Elizabeth; Mora, Liliana; Buckingham, Richard H; Díaz-Orejas, Ramón; Lemonnier, Marc

2009-01-01

Novel mutations in prfA, the gene for the polypeptide release factor RF1 of Escherichia coli, were isolated using a positive genetic screen based on the parD (kis, kid) toxin-antitoxin system. This original approach allowed the direct selection of mutants with altered translational termination efficiency at UAG codons. The isolated prfA mutants displayed a approximately 10-fold decrease in UAG termination efficiency with no significant changes in RF1 stability in vivo. All three mutations, G121S, G301S and R303H, were situated close to the nonsense codon recognition site in RF1:ribosome complexes. The prfA mutants displayed increased sensitivity to the RelE toxin encoded by the relBE system of E. coli, thus providing in vivo support for the functional interaction between RF1 and RelE. The prfA mutants also showed increased sensitivity to the Kid toxin. Since this toxin can cleave RNA in a ribosome-independent manner, this result was not anticipated and provided first evidence for the involvement of RF1 in the pathway of Kid toxicity. The sensitivity of the prfA mutants to RelE and Kid was restored to normal levels upon overproduction of the wild-type RF1 protein. We discuss these results and their utility for the design of novel antibacterial strategies in the light of the recently reported structure of ribosome-bound RF1.

Understanding the exposure-time effect on speckle contrast measurements for laser displays

NASA Astrophysics Data System (ADS)

Suzuki, Koji; Kubota, Shigeo

2018-02-01

To evaluate the influence of exposure time on speckle noise for laser displays, speckle contrast measurement method was developed observable at a human eye response time using a high-sensitivity camera which has a signal multiplying function. The nonlinearity of camera light sensitivity was calibrated to measure accurate speckle contrasts, and the measuring lower limit noise of speckle contrast was improved by applying spatial-frequency low pass filter to the captured images. Three commercially available laser displays were measured over a wide range of exposure times from tens of milliseconds to several seconds without adjusting the brightness of laser displays. The speckle contrast of raster-scanned mobile projector without any speckle-reduction device was nearly constant over various exposure times. On the contrary to this, in full-frame projection type laser displays equipped with a temporally-averaging speckle-reduction device, some of their speckle contrasts close to the lower limits noise were slightly increased at the shorter exposure time due to the noise. As a result, the exposure-time effect of speckle contrast could not be observed in our measurements, although it is more reasonable to think that the speckle contrasts of laser displays, which are equipped with the temporally-averaging speckle-reduction device, are dependent on the exposure time. This discrepancy may be attributed to the underestimation of temporal averaging factor. We expected that this method is useful for evaluating various laser displays and clarify the relationship between the speckle noise and the exposure time for a further verification of speckle reduction.

Evaluation of dietary soy sensitivity in snake river cutthroat trout

USDA-ARS?s Scientific Manuscript database

Hatchery-cultured cutthroat trout fed some commercially available rainbow trout feeds display slow growth and increased mortality. Feed characteristics such as buoyancy and texture alter feed acceptance in some fish species but their effects have not been adequately addressed in cutthroat trout. Th...

An Electrochemiluminescence Immunosensor Based on Gold-Magnetic Nanoparticles and Phage Displayed Antibodies

PubMed Central

Mu, Xihui; Tong, Zhaoyang; Huang, Qibin; Liu, Bing; Liu, Zhiwei; Hao, Lanqun; Dong, Hua; Zhang, Jinping; Gao, Chuan

2016-01-01

Using the multiple advantages of the ultra-highly sensitive electrochemiluminescence (ECL) technique, Staphylococcus protein A (SPA) functionalized gold-magnetic nanoparticles and phage displayed antibodies, and using gold-magnetic nanoparticles coated with SPA and coupled with a polyclonal antibody (pcAb) as magnetic capturing probes, and Ru(bpy)32+-labeled phage displayed antibody as a specific luminescence probe, this study reports a new way to detect ricin with a highly sensitive and specific ECL immunosensor and amplify specific detection signals. The linear detection range of the sensor was 0.0001~200 µg/L, and the limit of detection (LOD) was 0.0001 µg/L, which is 2500-fold lower than that of the conventional ELISA technique. The gold-magnetic nanoparticles, SPA and Ru(bpy)32+-labeled phage displayed antibody displayed different amplifying effects in the ECL immunosensor and can decrease LOD 3-fold, 3-fold and 20-fold, respectively, compared with the ECL immunosensors without one of the three effects. The integrated amplifying effect can decrease the LOD 180-fold. The immunosensor integrates the unique advantages of SPA-coated gold-magnetic nanoparticles that improve the activity of the functionalized capturing probe, and the amplifying effect of the Ru(bpy)32+-labeled phage displayed antibodies, so it increases specificity, interference-resistance and decreases LOD. It is proven to be well suited for the analysis of trace amounts of ricin in various environmental samples with high recovery ratios and reproducibility. PMID:26927130

Maltodextrin and sucrose preferences in sweet-sensitive (C57BL/6J) and subsensitive (129P3/J) mice revisited.

PubMed

Ackroff, Karen; Sclafani, Anthony

2016-10-15

Mice are attracted to the tastes of sugar and maltodextrin solutions. Sugar taste is mediated by the T1R2/T1R3 sweet taste receptor, while maltodextrin taste is dependent upon a different as yet unidentified receptor. In a prior study sweet-sensitive C57BL/6J (B6) mice displayed similar preferences for sucrose and maltodextrin solutions in 24-h saccharide vs. water choice tests that exceeded those of sweet-subsensitive 129P3/J (129) mice. In a subsequent experiment reported here, sucrose and maltodextrin (Polycose) preference and acceptance were compared in the two strains in saccharide vs. saccharide choice tests with isocaloric concentrations (0.5-32%). The 129 mice displayed significantly greater maltodextrin preferences than B6 mice at mid-range concentrations (2-8%), while the mice displayed an opposite preference profile at the highest concentration (32%). As in prior studies, 129 mice consumed less total saccharide than B6 mice at lower concentrations. These findings show that the conclusions reached from tastant vs. water tests may differ from those pitting one tastant against another. The increased sucrose preference and intake of B6 mice, relative to 129 mice, is consistent with their sweet-sensitive phenotype. Copyright © 2016 Elsevier Inc. All rights reserved.

Sex dimorphisms of crossbridge cycling kinetics in transgenic hypertrophic cardiomyopathy mice.

PubMed

Birch, Camille L; Behunin, Samantha M; Lopez-Pier, Marissa A; Danilo, Christiane; Lipovka, Yulia; Saripalli, Chandra; Granzier, Henk; Konhilas, John P

2016-07-01

Familial hypertrophic cardiomyopathy (HCM) is a disease of the sarcomere and may lead to hypertrophic, dilated, restrictive, and/or arrhythmogenic cardiomyopathy, congestive heart failure, or sudden cardiac death. We hypothesized that hearts from transgenic HCM mice harboring a mutant myosin heavy chain increase the energetic cost of contraction in a sex-specific manner. To do this, we assessed Ca(2+) sensitivity of tension and crossbridge kinetics in demembranated cardiac trabeculas from male and female wild-type (WT) and HCM hearts at an early time point (2 mo of age). We found a significant effect of sex on Ca(2+) sensitivity such that male, but not female, HCM mice displayed a decrease in Ca(2+) sensitivity compared with WT counterparts. The HCM transgene and sex significantly impacted the rate of force redevelopment by a rapid release-restretch protocol and tension cost by the ATPase-tension relationship. In each of these measures, HCM male trabeculas displayed a gain-of-function when compared with WT counterparts. In addition, cardiac remodeling measured by echocardiography, histology, morphometry, and posttranslational modifications demonstrated sex- and HCM-specific effects. In conclusion, female and male HCM mice display sex dimorphic crossbridge kinetics accompanied by sex- and HCM-dependent cardiac remodeling at the morphometric, histological, and cellular level. Copyright © 2016 the American Physiological Society.

The effects of display time and eccentricity on the detection of amplitude and phase degradations in textured stimuli.

PubMed

Clarke, Alasdair D F; Green, Patrick R; Chantler, Mike J

2012-03-08

The amplitude and phase spectra of an image contain important information for perception, and a large body of work has investigated the effects of manipulating these spectra on the recognition or classification of image content. Here, we use a novel means of investigating sensitivity to amplitude and phase spectra properties, testing the ability of observers to detect degradations of the spectral content of synthetic images of textured surfaces that are broadband in the frequency domain. The effects of display time and retinal eccentricity on sensitivity to these two manipulations are compared using stimuli matched for difficulty of detection. We find no difference between the time courses for the detection of degradation in the two spectra; in both cases, accuracy rises above chance when display times are greater than 80 ms. Increasing retinal eccentricity to 8.7°, however, has a significantly stronger effect on the accuracy of detecting degradations of the amplitude spectrum than of the phase spectrum. Further, sensitivity to phase randomization that is restricted to low spatial frequencies is greater in the periphery (at 8.7° eccentricity) than in the fovea. These last two results imply that the fovea and periphery are specialized for the processing of phase spectrum information in distinct spatial frequency bands.

Definition Of Touch-Sensitive Zones For Graphical Displays

NASA Technical Reports Server (NTRS)

Monroe, Burt L., III; Jones, Denise R.

1988-01-01

Touch zones defined simply by touching, while editing done automatically. Development of touch-screen interactive computing system, tedious task. Interactive Editor for Definition of Touch-Sensitive Zones computer program increases efficiency of human/machine communications by enabling user to define each zone interactively, minimizing redundancy in programming and eliminating need for manual computation of boundaries of touch areas. Information produced during editing process written to data file, to which access gained when needed by application program.

Stereotypes, Tolerance, and the Classroom.

ERIC Educational Resources Information Center

Brehm, Christine J.

This paper suggests that because higher education is instrumental in increasing awareness and sensitivity toward minority images and can influence levels of tolerance that students display and convey to public actors; therefore, many universities offer classes that challenge students to look beyond stereotypes and to appreciate the diversity of…

Effects of X-shaped reduction-sensitive amphiphilic block copolymer on drug delivery.

PubMed

Xiao, Haijun; Wang, Lu

2015-01-01

To study the effects of X-shaped amphiphilic block copolymers on delivery of docetaxel (DTX) and the reduction-sensitive property on drug release, a novel reduction-sensitive amphiphilic copolymer, (PLGA)2-SS-4-arm-PEG2000 with a Gemini-like X-shape, was successfully synthesized. The formation of nanomicelles was proved with respect to the blue shift of the emission fluorescence as well as the fluorescent intensity increase of coumarin 6-loaded particles. The X-shaped polymers exhibited a smaller critical micelle concentration value and possessed higher micellar stability in comparison with those of linear ones. The size of X-shaped (PLGA)2-SS-4-arm-PEG2000 polymer nanomicelles (XNMs) was much smaller than that of nanomicelles prepared with linear polymers. The reduction sensitivity of polymers was confirmed by the increase of micellar sizes as well as the in vitro drug release profile of DTX-loaded XNMs (DTX/XNMs). Cytotoxicity assays in vitro revealed that the blank XNMs were nontoxic against A2780 cells up to a concentration of 50 µg/mL, displaying good biocompatibility. DTX/XNMs were more toxic against A2780 cells than other formulations in both dose- and time-dependent manners. Cellular uptake assay displayed a higher intracellular drug delivery efficiency of XNMs than that of nanomicelles prepared with linear polymers. Besides, the promotion of tubulin polymerization induced by DTX was visualized by immunofluorescence analysis, and the acceleration of apoptotic process against A2780 cells was also imaged using a fluorescent staining method. Therefore, this X-shaped reduction-sensitive (PLGA)2-SS-4-arm-PEG2000 copolymer could effectively improve the micellar stability and significantly enhance the therapeutic efficacy of DTX by increasing the cellular uptake and selectively accelerating the drug release inside cancer cells.

Overexpression of heat shock protein 27 (HSP27) increases gemcitabine sensitivity in pancreatic cancer cells through S-phase arrest and apoptosis

PubMed Central

Guo, Yang; Ziesch, Andreas; Hocke, Sandra; Kampmann, Eric; Ochs, Stephanie; De Toni, Enrico N; Göke, Burkhard; Gallmeier, Eike

2015-01-01

We previously established a role for HSP27 as a predictive marker for therapeutic response towards gemcitabine in pancreatic cancer. Here, we investigate the underlying mechanisms of HSP27-mediated gemcitabine sensitivity. Utilizing a pancreatic cancer cell model with stable HSP27 overexpression, cell cycle arrest and apoptosis induction were analysed by flow cytometry, nuclear staining, immunoblotting and mitochondrial staining. Drug sensitivity studies were performed by proliferation assays. Hyperthermia was simulated using mild heat shock at 41.8°C. Upon gemcitabine treatment, HSP27-overexpressing cells displayed an early S-phase arrest subsequently followed by a strongly increased sub-G1 fraction. Apoptosis was characterized by PARP-, CASPASE 3-, CASPASE 8-, CASPASE 9- and BIM- activation along with a mitochondrial membrane potential loss. It was reversible through chemical caspase inhibition. Importantly, gemcitabine sensitivity and PARP cleavage were also elicited by heat shock-induced HSP27 overexpression, although to a smaller extent, in a panel of pancreatic cancer cell lines. Finally, HSP27-overexpressing pancreatic cancer cells displayed an increased sensitivity also towards death receptor-targeting agents, suggesting another pro-apoptotic role of HSP27 along the extrinsic apoptosis pathway. Taken together, in contrast to the well-established anti-apoptotic properties of HSP27 in cancer, our study reveals novel pro-apoptotic functions of HSP27—mediated through both the intrinsic and the extrinsic apoptotic pathways—at least in pancreatic cancer cells. HSP27 could represent a predictive marker of therapeutic response towards specific drug classes in pancreatic cancer and provides a novel molecular rationale for current clinical trials applying the combination of gemcitabine with regional hyperthermia in pancreatic cancer patients. PMID:25331547

Locomotor sensitization to intermittent ketamine administration is associated with nucleus accumbens plasticity in male and female rats.

PubMed

Strong, C E; Schoepfer, K J; Dossat, A M; Saland, S K; Wright, K N; Kabbaj, M

2017-07-15

Clinical evidence suggests superior antidepressant response over time with a repeated, intermittent ketamine treatment regimen as compared to a single infusion. However, the club drug ketamine is commonly abused. Therefore, the abuse potential of repeated ketamine injections at low doses needs to be investigated. In this study, we investigated the abuse potential of repeated exposure to either 0, 2.5, or 5 mg/kg ketamine administered once weekly for seven weeks. Locomotor activity and conditioned place preference (CPP) were assayed to evaluate behavioral sensitization to the locomotor activating effects of ketamine and its rewarding properties, respectively. Our results show that while neither males nor females developed CPP, males treated with 5 mg/kg and females treated with either 2.5 or 5 mg/kg ketamine behaviorally sensitized. Furthermore, dendritic spine density was increased in the NAc of both males and females administered 5 mg/kg ketamine, an effect specific to the NAc shell (NAcSh) in males but to both the NAc core (NAcC) and NAcSh in females. Additionally, males administered 5 mg/kg ketamine displayed increased protein expression of ΔfosB, calcium calmodulin kinase II alpha (CaMKIIα), and brain-derived neurotrophic factor (BDNF), an effect not observed in females administered either dose of ketamine. However, males and females administered 5 mg/kg ketamine displayed increased protein expression of AMPA receptors (GluA1). Taken together, low-dose ketamine, when administered intermittently, induces behavioral sensitization at a lower dose in females than males, accompanied by an increase in spine density in the NAc and protein expression changes in pathways commonly implicated in addiction. Copyright © 2017. Published by Elsevier Ltd.

Variations in the temperature sensitivity of spring leaf phenology from 1978 to 2014 in Mudanjiang, China

NASA Astrophysics Data System (ADS)

Dai, Junhu; Xu, Yunjia; Wang, Huanjiong; Alatalo, Juha; Tao, Zexing; Ge, Quansheng

2017-12-01

Continuous long-term temperature sensitivity (ST) of leaf unfolding date (LUD) and main impacting factors in spring in the period 1978-2014 for 40 plant species in Mudanjiang, Heilongjiang Province, Northeast China, were analyzed by using observation data from the China Phenological Observation Network (CPON), together with the corresponding meteorological data from the China Meteorological Data Service Center. Temperature sensitivities, slopes of the regression between LUD and mean temperature during the optimum preseason (OP), were analyzed using 15-year moving window to determine their temporal trends. Major factors impacting ST were then chosen and evaluated by applying a random sampling method. The results showed that LUD was sensitive to mean temperature in a defined period before phenophase onset for all plant species analyzed. Over the period 1978-2014, the mean ST of LUD for all plant species was - 3.2 ± 0.49 days °C-1. The moving window analysis revealed that 75% of species displayed increasing ST of LUD, with 55% showing significant increases (P < 0.05). ST for the other 25% exhibited a decreasing trend, with 17% showing significant decreases (P < 0.05). On average, ST increased by 16%, from - 2.8 ± 0.83 days °C-1 during 1980-1994 to - 3.30 ± 0.65 days °C-1 during 2000-2014. For species with later LUD and longer OP, ST tended to increase more, while species with earlier LUD and shorter OP tended to display a decreasing ST. The standard deviation of preseason temperature impacted the temporal variation in ST. Chilling conditions influenced ST for some species, but photoperiod limitation did not have significant or coherent effects on changes in ST.

Novel Escherichia coli RF1 mutants with decreased translation termination activity and increased sensitivity to the cytotoxic effect of the bacterial toxins Kid and RelE

PubMed Central

Diago-Navarro, Elizabeth; Mora, Liliana; Buckingham, Richard H; Díaz-Orejas, Ramón; Lemonnier, Marc

2008-01-01

Novel mutations in prfA, the gene for the polypeptide release factor RF1 of Escherichia coli, were isolated using a positive genetic screen based on the parD (kis, kid) toxin–antitoxin system. This original approach allowed the direct selection of mutants with altered translational termination efficiency at UAG codons. The isolated prfA mutants displayed a ∼10-fold decrease in UAG termination efficiency with no significant changes in RF1 stability in vivo. All three mutations, G121S, G301S and R303H, were situated close to the nonsense codon recognition site in RF1:ribosome complexes. The prfA mutants displayed increased sensitivity to the RelE toxin encoded by the relBE system of E. coli, thus providing in vivo support for the functional interaction between RF1 and RelE. The prfA mutants also showed increased sensitivity to the Kid toxin. Since this toxin can cleave RNA in a ribosome-independent manner, this result was not anticipated and provided first evidence for the involvement of RF1 in the pathway of Kid toxicity. The sensitivity of the prfA mutants to RelE and Kid was restored to normal levels upon overproduction of the wild-type RF1 protein. We discuss these results and their utility for the design of novel antibacterial strategies in the light of the recently reported structure of ribosome-bound RF1. PMID:19019162

Writing next-generation display photomasks

NASA Astrophysics Data System (ADS)

Sandstrom, Tor; Wahlsten, Mikael; Park, Youngjin

2016-10-01

Recent years have seen a fast technical development within the display area. Displays get ever higher pixel density and the pixels get smaller. Current displays have over 800 PPI and market forces will eventually drive for densities of 2000 PPI or higher. The transistor backplanes also get more complex. OLED displays require 4-7 transistors per pixel instead of the typical 1-2 transistors used for LCDs, and they are significantly more sensitive to errors. New large-area maskwriters have been developed for masks used in high volume production of screens for state-of-theart smartphones. Redesigned laser optics with higher NA and lower aberrations improve resolution and CD uniformity and reduce mura effects. The number of beams has been increased to maintain the throughput despite the higher writing resolution. OLED displays are highly sensitive to placement errors and registration in the writers has been improved. To verify the registration of produced masks a separate metrology system has been developed. The metrology system is self-calibrated to high accuracy. The calibration is repeatable across machines and sites using Z-correction. The repeatability of the coordinate system makes it possible to standardize the coordinate system across an entire supply chain or indeed across the entire industry. In-house metrology is a commercial necessity for high-end mask shop, but also the users of the masks, the panel makers, would benefit from having in-house metrology. It would act as the reference for their mask suppliers, give better predictive and post mortem diagnostic power for the panel process, and the metrology could be used to characterize and improve the entire production loop from data to panel.

Enhanced dopamine detection sensitivity by PEDOT/graphene oxide coating on in vivo carbon fiber electrodes.

PubMed

Taylor, I Mitch; Robbins, Elaine M; Catt, Kasey A; Cody, Patrick A; Happe, Cassandra L; Cui, Xinyan Tracy

2017-03-15

Dopamine (DA) is a monoamine neurotransmitter responsible for regulating a variety of vital life functions. In vivo detection of DA poses a challenge due to the low concentration and high speed of physiological signaling. Fast scan cyclic voltammetry at carbon fiber microelectrodes (CFEs) is an effective method to monitor real-time in vivo DA signaling, however the sensitivity is somewhat limited. Electrodeposition of poly(3,4-ethylene dioxythiophene) (PEDOT)/graphene oxide (GO) onto the CFE surface is shown to increase the sensitivity and lower the limit of detection for DA compared to bare CFEs. Thicker PEDOT/GO coatings demonstrate higher sensitivities for DA, but display the negative drawback of slow adsorption and electron transfer kinetics. The moderate thickness resulting from 25 s electrodeposition of PEDOT/GO produces the optimal electrode, exhibiting an 880% increase in sensitivity, a 50% decrease in limit of detection and minimally altered electrode kinetics. PEDOT/GO coated electrodes rapidly and robustly detect DA, both in solution and in the rat dorsal striatum. This increase in DA sensitivity is likely due to increasing the electrode surface area with a PEDOT/GO coating and improved adsorption of DA's oxidation product (DA-o-quinone). Increasing DA sensitivity without compromising electrode kinetics is expected to significantly improve our understanding of the DA function in vivo. Copyright © 2016 Elsevier B.V. All rights reserved.

Enhanced Dopamine Detection Sensitivity by PEDOT/Graphene Oxide Coating on in vivo Carbon Fiber Electrodes

PubMed Central

Taylor, I. Mitch; Robbins, Elaine M.; Catt, Kasey A.; Cody, Patrick A.; Weaver, Cassandra L.; Cui, Xinyan Tracy

2016-01-01

Dopamine (DA) is a monoamine neurotransmitter responsible for regulating a variety of vital life functions. In vivo detection of DA poses a challenge due to the low concentration and high speed of physiological signaling. Fast scan cyclic voltammetry at carbon fiber microelectrodes (CFEs) is an effective method to monitor real-time in vivo DA signaling, however the sensitivity is somewhat limited. Electrodeposition of poly(3,4-ethylene dioxythiophene) (PEDOT)/graphene oxide (GO) onto the CFE surface is shown to increase the sensitivity and lower the limit of detection for DA compared to bare CFEs. Thicker PEDOT/GO coatings demonstrate higher sensitivities for DA, but display the negative drawback of slow adsorption and electron transfer kinetics. The moderate thickness resulting from 25 s electrodeposition of PEDOT/GO produces the optimal electrode, exhibiting an 880% increase in sensitivity, a 50% decrease in limit of detection and minimally altered electrode kinetics. PEDOT/GO coated electrodes rapidly and robustly detect DA, both in solution and in the rat dorsal striatum. This increase in DA sensitivity is likely due to increasing the electrode surface area with a PEDOT/GO coating and improved adsorption of DA’s oxidation product (DA-o-quinone). Increasing DA sensitivity without compromising electrode kinetics is expected to significantly improve our understanding of the DA function in vivo. PMID:27268013

The Arabidopsis cax3 mutants display altered salt tolerance, pH sensitivity and reduced plasma membrane H+-ATPase activity.

PubMed

Zhao, Jian; Barkla, Bronwyn J; Marshall, Joy; Pittman, Jon K; Hirschi, Kendal D

2008-02-01

Perturbing CAX1, an Arabidopsis vacuolar H+/Ca2+ antiporter, and the related vacuolar transporter CAX3, has been previously shown to cause severe growth defects; however, the specific function of CAX3 has remained elusive. Here, we describe plant phenotypes that are shared among cax1 and cax3 including an increased sensitivity to both abscisic acid (ABA) and sugar during germination, and an increased tolerance to ethylene during early seedling development. We have also identified phenotypes unique to cax3, namely salt, lithium and low pH sensitivity. We used biochemical measurements to ascribe these cax3 sensitivities to a reduction in vacuolar H+/Ca2+ transport during salt stress and decreased plasma membrane H+-ATPase activity. These findings catalog an array of CAX phenotypes and assign a specific role for CAX3 in response to salt tolerance.

Alcohol effects on simulated driving performance and self-perceptions of impairment in DUI offenders

PubMed Central

Van Dyke, Nicholas; Fillmore, Mark T.

2014-01-01

Drivers with a history of driving under the influence (DUI) of alcohol self-report heightened impulsivity and display reckless driving behaviors as indicated by increased rates of vehicle crashes, moving violations, and traffic tickets. Such poor behavioral self-regulation could also increase sensitivity to the disruptive effects of alcohol on driving performance. The present study examined the degree to which DUI drivers display an increased sensitivity to the acute impairing effects of alcohol on simulated driving performance and overestimate their driving fitness following alcohol consumption. Adult drivers with a history of DUI and a demographically-matched group of drivers with no history of DUI (controls) were tested following a 0.65 g/kg alcohol and a placebo. Results indicated that alcohol impaired several measures of driving performance and there was no difference between DUI offenders and controls in these impairments. However, following alcohol DUI drivers self-reported a greater ability and willingness to drive compared with controls. These findings indicate that drivers with a history of DUI might perceive themselves as more fit to drive after drinking which could play an important role in their decisions to drink and drive. PMID:25347077

Alcohol effects on simulated driving performance and self-perceptions of impairment in DUI offenders.

PubMed

Van Dyke, Nicholas; Fillmore, Mark T

2014-12-01

Drivers with a history of driving under the influence (DUI) of alcohol self-report heightened impulsivity and display reckless driving behaviors as indicated by increased rates of vehicle crashes, moving violations, and traffic tickets. Such poor behavioral self-regulation could also increase sensitivity to the disruptive effects of alcohol on driving performance. The present study examined the degree to which DUI drivers display an increased sensitivity to the acute impairing effects of alcohol on simulated driving performance and overestimate their driving fitness following alcohol consumption. Adult drivers with a history of DUI and a demographically matched group of drivers with no history of DUI (controls) were tested following a 0.65 g/kg alcohol and a placebo. Results indicated that alcohol impaired several measures of driving performance, and there was no difference between DUI offenders and controls in these impairments. However, following alcohol, DUI drivers self-reported a greater ability and willingness to drive compared with controls. These findings indicate that drivers with a history of DUI might perceive themselves as more fit to drive after drinking, which could play an important role in their decisions to drink and drive. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Visual search and spatial attention: ERPs in focussed and divided attention conditions.

PubMed

Wijers, A A; Okita, T; Mulder, G; Mulder, L J; Lorist, M M; Poiesz, R; Scheffers, M K

1987-08-01

ERPs and performance were measured in divided and focussed attention visual search tasks. In focussed attention tasks, to-be-attended and to-be-ignored letters were presented simultaneously. We varied display load, mapping conditions and display size. RT, P3b-latency and negativity in the ERP associated with controlled search all increased with display load. Each of these measures showed selectivity of controlled search, in that they decreased with focussing of attention. An occipital N230, on the other hand, was not sensitive to focussing of attention, but was primarily affected by display load. ERPs to both attended and unattended targets in focussed attention conditions showed and N2 compared to nontargets, suggesting that both automatic and controlled letter classifications are possible. These effects were not affected by display size. Consistent mapping resulted in shorter RT and P3b-latency in divided attention conditions, compared to varied mapping conditions, but had no effect in focussed attention conditions.

Transverse section radionuclide scanning system

DOEpatents

Kuhl, David E.; Edwards, Roy Q.

1976-01-01

This invention provides a transverse section radionuclide scanning system for high-sensitivity quantification of brain radioactivity in cross-section picture format in order to permit accurate assessment of regional brain function localized in three-dimensions. High sensitivity crucially depends on overcoming the heretofore known raster type scanning, which requires back and forth detector movement involving dead-time or partial enclosure of the scan field. Accordingly, this invention provides a detector array having no back and forth movement by interlaced detectors that enclose the scan field and rotate as an integral unit around one axis of rotation in a slip ring that continuously transmits the detector data by means of laser emitting diodes, with the advantages that increased amounts of data can be continuously collected, processed and displayed with increased sensitivity according to a suitable computer program.

Economic Order Quantity (EOQ) Optimal Control Considering Selling Price and Salesman Initiative Cost

NASA Astrophysics Data System (ADS)

Hertini, Elis; Anggriani, Nursanti; Mianna, Winda; Supriatna, Asep K.

2018-03-01

Retailers usually offer several types of similar products. A larger number of available stock products in display space will lead consumer to buy more, as well as giving a negative impression on other types of less available products. However, the amount of display space is limited so capacity of carrying the products is limited. Competition among products to increase demand rate is influenced by stock levels available in display space, price and salesmen’s initiative in promoting the products. The Economic Order Quantity (EOQ) to replenish the stock of the product is dependent on the on-hand inventory. Salesman’s initiative also affects maximum profit obtained by the seller. In this paper, Potryagin’s Maximal Principle is used to determine the state of the inventory levels response to control prices of products. Sensitivity analysis of capacity allocation display space is also presented numerically.

Operant conditioning of facial displays of pain.

PubMed

Kunz, Miriam; Rainville, Pierre; Lautenbacher, Stefan

2011-06-01

The operant model of chronic pain posits that nonverbal pain behavior, such as facial expressions, is sensitive to reinforcement, but experimental evidence supporting this assumption is sparse. The aim of the present study was to investigate in a healthy population a) whether facial pain behavior can indeed be operantly conditioned using a discriminative reinforcement schedule to increase and decrease facial pain behavior and b) to what extent these changes affect pain experience indexed by self-ratings. In the experimental group (n = 29), the participants were reinforced every time that they showed pain-indicative facial behavior (up-conditioning) or a neutral expression (down-conditioning) in response to painful heat stimulation. Once facial pain behavior was successfully up- or down-conditioned, respectively (which occurred in 72% of participants), facial pain displays and self-report ratings were assessed. In addition, a control group (n = 11) was used that was yoked to the reinforcement plans of the experimental group. During the conditioning phases, reinforcement led to significant changes in facial pain behavior in the majority of the experimental group (p < .001) but not in the yoked control group (p > .136). Fine-grained analyses of facial muscle movements revealed a similar picture. Furthermore, the decline in facial pain displays (as observed during down-conditioning) strongly predicted changes in pain ratings (R(2) = 0.329). These results suggest that a) facial pain displays are sensitive to reinforcement and b) that changes in facial pain displays can affect self-report ratings.

Extracting Depth From Motion Parallax in Real-World and Synthetic Displays

NASA Technical Reports Server (NTRS)

Hecht, Heiko; Kaiser, Mary K.; Aiken, William; Null, Cynthia H. (Technical Monitor)

1994-01-01

In psychophysical studies on human sensitivity to visual motion parallax (MP), the use of computer displays is pervasive. However, a number of potential problems are associated with such displays: cue conflicts arise when observers accommodate to the screen surface, and observer head and body movements are often not reflected in the displays. We investigated observers' sensitivity to depth information in MP (slant, depth order, relative depth) using various real-world displays and their computer-generated analogs. Angle judgments of real-world stimuli were consistently superior to judgments that were based on computer-generated stimuli. Similar results were found for perceived depth order and relative depth. Perceptual competence of observers tends to be underestimated in research that is based on computer generated displays. Such findings cannot be generalized to more realistic viewing situations.

Interactive Whiteboards and Implications for Use in Education

ERIC Educational Resources Information Center

Gibson, Danita C.

2013-01-01

Interactive whiteboards (IWBs) have increasingly become a technology tool used in the educational field. IWBs are touch-sensitive screens that work in conjunction with a computer and a projector, and which are used to display information from a computer. As a qualitative case study, this study investigated the SMART Board-infused instructional…

Sensitization of salt appetite is associated with increased "wanting" but not "liking" of a salt reward in the sodium-deplete rat.

PubMed

Clark, Jeremy J; Bernstein, Ilene L

2006-02-01

To examine the role of incentive sensitization in the potentiation of salt appetite by prior depletions, the authors assessed the motivation to obtain salt ("wanting") and the palatability of salt ("liking") independently in salt-sensitized rats. Breakpoint on a progressive ratio reinforcement schedule was used to measure salt wanting and taste reactivity was used to measure salt liking in rats with and without a history of Na+ depletion. Salt-sensitized rats displayed higher breakpoints relative to controls. However, a history of Na+ depletion was not associated with a greater positive shift in taste reactivity measures. The data suggest that these components of reward are separable in this model and support the general proposition that sensitization may alter wanting but not liking.

THE REELIN RECEPTORS VLDLR AND ApoER2 REGULATE SENSORIMOTOR GATING IN MICE

PubMed Central

Barr, Alasdair M.; Fish, Kenneth N.; Markou, Athina

2007-01-01

Summary Postmortem brain loss of reelin is noted in schizophrenia patients. Accordingly, heterozygous reeler mutant mice have been proposed as a putative model of this disorder. Little is known, however, about the involvement of the two receptors for reelin, Very-Low-Density Lipoprotein Receptor (VLDLR) and Apolipoprotein E Receptor 2 (ApoER2), on pre-cognitive processes of relevance to deficits seen in schizophrenia. Thus, we evaluated sensorimotor gating in mutant mice heterozygous or homozygous for the two reelin receptors. Mutant mice lacking one of these reelin receptors were tested for prepulse inhibition (PPI) of the acoustic startle reflex prior to and following puberty, and on a crossmodal PPI task, involving the presentation of acoustic and tactile stimuli. Furthermore, because schizophrenia patients show increased sensitivity to N-methyl-D-aspartate (NMDA) receptor blockade, we assessed the sensitivity of these mice to the PPI-disruptive effects of the NMDA receptor antagonist phencyclidine. The results demonstrated that acoustic PPI did not differ between mutant and wildtype mice. However, VLDLR homozygous mice displayed significant deficits in crossmodal PPI, while ApoER2 heterozygous and homozygous mice displayed significantly increased crossmodal PPI. Both ApoER2 and VLDLR heterozygous and homozygous mice exhibited greater sensitivity to the PPI-disruptive effects of phencyclidine than wildtype mice. These results indicate that partial or complete loss of either one of the reelin receptors results in a complex pattern of alterations in PPI function that include alterations in crossmodal, but not acoustic, PPI and increased sensitivity to NMDA receptor blockade. Thus, reelin receptor function appears to be critically involved in crossmodal PPI and the modulation of the PPI response by NMDA receptors. These findings have relevance to a range of neuropsychiatric disorders that involve sensorimotor gating deficits, including schizophrenia.. PMID:17261317

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

Impact of speech presentation level on cognitive task performance: implications for auditory display design.

PubMed

Baldwin, Carryl L; Struckman-Johnson, David

2002-01-15

Speech displays and verbal response technologies are increasingly being used in complex, high workload environments that require the simultaneous performance of visual and manual tasks. Examples of such environments include the flight decks of modern aircraft, advanced transport telematics systems providing invehicle route guidance and navigational information and mobile communication equipment in emergency and public safety vehicles. Previous research has established an optimum range for speech intelligibility. However, the potential for variations in presentation levels within this range to affect attentional resources and cognitive processing of speech material has not been examined previously. Results of the current experimental investigation demonstrate that as presentation level increases within this 'optimum' range, participants in high workload situations make fewer sentence-processing errors and generally respond faster. Processing errors were more sensitive to changes in presentation level than were measures of reaction time. Implications of these findings are discussed in terms of their application for the design of speech communications displays in complex multi-task environments.

The mechanical microenvironment in cancer: How physics affects tumours.

PubMed

Nagelkerke, Anika; Bussink, Johan; Rowan, Alan E; Span, Paul N

2015-12-01

The tumour microenvironment contributes greatly to the response of tumour cells. It consists of chemical gradients, for example of oxygen and nutrients. However, a physical environment is also present. Apart from chemical input, cells also receive physical signals. Tumours display unique mechanical properties: they are a lot stiffer than normal tissue. This may be either a cause or a consequence of cancer, but literature suggests it has a major impact on tumour cells as will be described in this review. The mechanical microenvironment may cause malignant transformation, possibly through activation of oncogenic pathways and inhibition of tumour suppressor genes. In addition, the mechanical microenvironment may promote tumour progression by influencing processes such as epithelial-to-mesenchymal transition, enhancing cell survival through autophagy, but also affects sensitivity of tumour cells to therapeutics. Furthermore, multiple intracellular signalling pathways prove sensitive to the mechanical properties of the microenvironment. It appears the increased stiffness is unlikely to be caused by increased stiffness of the tumour cells themselves. However, there are indications that tumours display a higher cell density, making them more rigid. In addition, increased matrix deposition in the tumour, as well as increased interstitial fluid pressure may account for the increased stiffness of tumours. Overall, tumour mechanics are significantly different from normal tissue. Therefore, this feature should be further explored for use in cancer prevention, detection and treatment. Copyright © 2015 Elsevier Ltd. All rights reserved.

Value of shear wave arrival time contour display in shear wave elastography for breast masses diagnosis.

PubMed

Zhou, Bang-Guo; Wang, Dan; Ren, Wei-Wei; Li, Xiao-Long; He, Ya-Ping; Liu, Bo-Ji; Wang, Qiao; Chen, Shi-Gao; Alizad, Azra; Xu, Hui-Xiong

2017-08-01

To evaluate the diagnostic performance of shear wave arrival time contour (SWATC) display for the diagnosis of breast lesions and to identify factors associated with the quality of shear wave propagation (QSWP) in breast lesions. This study included 277 pathologically confirmed breast lesions. Conventional B-mode ultrasound characteristics and shear wave elastography parameters were computed. Using the SWATC display, the QSWP of each lesion was assigned to a two-point scale: score 1 (low quality) and score 2 (high quality). Binary logistic regression analysis was performed to identify factors associated with QSWP. The area under the receiver operating characteristic curve (AUROC) for QSWP to differentiate benign from malignant lesions was 0.913, with a sensitivity of 91.9%, a specificity of 90.7%, a positive predictive value (PPV) of 74.0%, and a negative predictive value (NPV) of 97.5%. Compared with using the standard deviation of shear wave speed (SWS SD ) alone, SWS SD combined with QSWP increased the sensitivity from 75.8% to 93.5%, but decreased the specificity from 95.8% to 89.3% (P < 0.05). SWS SD was identified to be the strongest factor associated with the QSWP, followed by tumor malignancy and the depth of the lesion. In conclusion, SWATC display may be useful for characterization of breast lesions.

Identification of Novel Glycosyltransferases Required for Assembly of the Pasteurella multocida A:1 Lipopolysaccharide and Their Involvement in Virulence▿ †

PubMed Central

Boyce, John D.; Harper, Marina; St. Michael, Frank; John, Marietta; Aubry, Annie; Parnas, Henrietta; Logan, Susan M.; Wilkie, Ian W.; Ford, Mark; Cox, Andrew D.; Adler, Ben

2009-01-01

We previously determined the structure of the Pasteurella multocida Heddleston type 1 lipopolysaccharide (LPS) molecule and characterized some of the transferases essential for LPS biosynthesis. We also showed that P. multocida strains expressing truncated LPS display reduced virulence. Here, we have identified all of the remaining glycosyltransferases required for synthesis of the oligosaccharide extension of the P. multocida Heddleston type 1 LPS, including a novel α-1,6 glucosyltransferase, a β-1,4 glucosyltransferase, a putative bifunctional galactosyltransferase, and two heptosyltransferases. In addition, we identified a novel oligosaccharide extension expressed only in a heptosyltransferase (hptE) mutant background. All of the analyzed mutants expressing LPS with a truncated main oligosaccharide extension displayed reduced virulence, but those expressing LPS with an intact heptose side chain were able to persist for long periods in muscle tissue. The hptC mutant, which expressed LPS with the shortest oligosaccharide extension and no heptose side chain, was unable to persist on the muscle or cause any disease. Furthermore, all of the mutants displayed increased sensitivity to the chicken antimicrobial peptide fowlicidin 1, with mutants expressing highly truncated LPS being the most sensitive. PMID:19168738

Insulin's acute effects on glomerular filtration rate correlate with insulin sensitivity whereas insulin's acute effects on proximal tubular sodium reabsorption correlation with salt sensitivity in normal subjects.

PubMed

ter Maaten, J C; Bakker, S J; Serné, E H; ter Wee, P M; Donker, A J; Gans, R O

1999-10-01

Insulin induces sodium retention by increasing distal tubular sodium reabsorption. Opposite effects of insulin to offset insulin-induced sodium retention are supposedly increases in glomerular filtration rate (GFR) and decreases in proximal tubular sodium reabsorption. Defects in these opposing effects could link insulin resistance to blood-pressure elevation and salt sensitivity. We assessed the relationship between the effects of sequential physiological and supraphysiological insulin dosages (50 and 150 mU/kg/h) on renal sodium handling, and insulin sensitivity and salt sensitivity using the euglycaemic clamp technique and clearances of [131I]hippuran, [125I]iothalamate, sodium, and lithium in 20 normal subjects displaying a wide range of insulin sensitivity. Time-control experiments were performed in the same subjects. Salt sensitivity was determined using a diet method. During the successive insulin infusions, GFR increased by 5.9% (P = 0.003) and 10.9% (P<0.001), while fractional sodium excretion decreased by 34 and 50% (both P<0.001). Distal tubular sodium reabsorption increased and proximal tubular sodium reabsorption decreased. Insulin sensitivity correlated with changes in GFR during physiological (r = 0.60, P = 0.005) and supraphysiological (r = 0.58, P = 0.007) hyperinsulinaemia, but not with changes in proximal tubular sodium reabsorption. Salt sensitivity correlated with changes in proximal tubular sodium reabsorption (r = 0.49, P = 0.028), but not in GFR, during physiological hyperinsulinaemia. Neither insulin sensitivity or salt sensitivity correlated with changes in overall fractional sodium excretion. Insulin sensitivity and salt sensitivity correlate with changes in different elements of renal sodium handling, but not with overall sodium excretion, during insulin infusion. The relevance for blood pressure regulation remains to be proved.

Overexpression of heat shock protein 27 (HSP27) increases gemcitabine sensitivity in pancreatic cancer cells through S-phase arrest and apoptosis.

PubMed

Guo, Yang; Ziesch, Andreas; Hocke, Sandra; Kampmann, Eric; Ochs, Stephanie; De Toni, Enrico N; Göke, Burkhard; Gallmeier, Eike

2015-02-01

We previously established a role for HSP27 as a predictive marker for therapeutic response towards gemcitabine in pancreatic cancer. Here, we investigate the underlying mechanisms of HSP27-mediated gemcitabine sensitivity. Utilizing a pancreatic cancer cell model with stable HSP27 overexpression, cell cycle arrest and apoptosis induction were analysed by flow cytometry, nuclear staining, immunoblotting and mitochondrial staining. Drug sensitivity studies were performed by proliferation assays. Hyperthermia was simulated using mild heat shock at 41.8°C. Upon gemcitabine treatment, HSP27-overexpressing cells displayed an early S-phase arrest subsequently followed by a strongly increased sub-G1 fraction. Apoptosis was characterized by PARP-, CASPASE 3-, CASPASE 8-, CASPASE 9- and BIM- activation along with a mitochondrial membrane potential loss. It was reversible through chemical caspase inhibition. Importantly, gemcitabine sensitivity and PARP cleavage were also elicited by heat shock-induced HSP27 overexpression, although to a smaller extent, in a panel of pancreatic cancer cell lines. Finally, HSP27-overexpressing pancreatic cancer cells displayed an increased sensitivity also towards death receptor-targeting agents, suggesting another pro-apoptotic role of HSP27 along the extrinsic apoptosis pathway. Taken together, in contrast to the well-established anti-apoptotic properties of HSP27 in cancer, our study reveals novel pro-apoptotic functions of HSP27-mediated through both the intrinsic and the extrinsic apoptotic pathways-at least in pancreatic cancer cells. HSP27 could represent a predictive marker of therapeutic response towards specific drug classes in pancreatic cancer and provides a novel molecular rationale for current clinical trials applying the combination of gemcitabine with regional hyperthermia in pancreatic cancer patients. © 2015 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Temperature shock, injury and transient sensitivity to nisin in Gram negatives.

PubMed

Boziaris, I S; Adams, M R

2001-10-01

The effect of thermal stresses on survival, injury and nisin sensitivity was investigated in Salmonella Enteritidis PT4, PT7 and Pseudomonas aeruginosa. Heating at 55 degrees C, rapid chilling to 0.5 degrees C or freezing at -20 degrees C produced transient sensitivity to nisin. Cells were only sensitive if nisin was present during stress. Resistance recovered rapidly afterwards, though some cells displayed residual injury. Injury was assessed by SDS sensitivity, hydrophobicity changes, lipopolysaccharide release and NPN uptake. LPS release and hydrophobicity were not always associated with transient nisin sensitivity. Uptake of NPN correlated better but persisted longer after treatment. Thermal shocks produce transient injury to the outer membrane, allowing nisin access. After treatment, the permeability barrier is rapidly restored by a process apparently involving reorganization rather than biosynthetic repair. Inclusion of nisin during food treatments that impose sub-lethal stress on Gram negatives could increase process lethality, enhancing microbiological safety and stability.

A Novel Yeast Surface Display Method for Large-Scale Screen Inhibitors of Sortase A.

PubMed

Wu, Lin; Li, Huijun; Tang, Tianle

2017-01-24

Fluorescence resonance energy transfer substrates of sortase A are too expensive to be used to roughly screen high-throughput sortase A inhibitors. This makes therapeutic strategies difficult to realize in a clinical therapeutic use. Instead, we design here an LPETG-EGFP (leucine, proline, glutamic, threonine and glycine-enhanced green fluorescence) protein displayed on a yeast surface as a substrate by adaptively reducing the cost. We do this by optimizing the induction conditions of sortase A expression in Escherichia coli DE3(BL21) and catalyzing LPETG proteins, which are displayed on surface of Pichia pastoris . Different expression conditions of sortase A include: induction temperature (22 °C, 28 °C, 37 °C and 40 °C), induction time (4 h, 5 h, 6 h and 7 h) and induction concentration of isopropyl β-d-thiogalactoside IPTG (0.25 mmol/L, 0.5 mmol/L, 1 mmol/L, and 2 mmol/L). The fluorescence change of the LPETG-EGFP protein on the surface of P. pastoris over time was detected by flow cytometry and fluorescence spectrophotometry, and then the sensitivities of the two methods were compared. Using berberine chloride as an inhibitor, the activity of sortase A was investigated with the substrates of LPETG-EGFP protein, and compared to Dabcyl-QALPETGEE-Edans. A high yield of sortase A was achieved by inducing 1.0 mmol/L IPTG at 28 °C for 6 h. The intensity of green fluorescence of substrates displayed on the yeast surface was increased over time, while the stability was decreased slightly. Both fluorescence spectrophotometery and flow cytometry were fit for detection because of their high sensitivity. We utilized two different substrates of sortase A to investigate sortase A activity, which resulted in the increase of fluorescence intensity with respect to the increased time of growth. However, the method with Dabcyl-QALPETGEE-Edans as its substrate was more robust. Thus, the method described in this paper is a simple and cheap method which is very suitable for high-throughput analysis, but the conventional method is much more sensitive. The method described in this paper is expected to lead to large-scale screening of sortase A inhibitors which can be used to decrease the risk of drug resistance development.

Adolescent and adult rat cortical protein kinase A display divergent responses to acute ethanol exposure

PubMed Central

Gigante, Eduardo D.; Santerre, Jessica L.; Carter, Jenna M.; Werner, David F.

2014-01-01

Adolescent rats display reduced sensitivity to many dysphoria-related effects of alcohol (ethanol) including motor ataxia and sedative hypnosis, but the underlying neurobiological factors that contribute to these differences remain unknown. The cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) pathway, particularly the type II regulatory subunit (RII), has been implicated in ethanol-induced molecular and behavioral responses in adults. Therefore, the current study examined cerebral cortical PKA in adolescent and adult ethanol responses. With the exception of early adolescence, PKA RIIα and RIIβ subunit levels largely did not differ from adult levels in either whole cell lysate or P2 synaptosomal expression. However, following acute ethanol exposure, PKA RIIβ P2 synaptosomal expression and activity were increased in adults, but not in adolescents. Behaviorally, intracerebroventricular administration of the PKA activator Sp-cAMP and inhibitor Rp-cAMP prior to ethanol administration increased adolescent sensitivity to the sedative-hypnotic effects of ethanol compared to controls. Sp-cAMP was ineffective in adults whereas Rp-cAMP suggestively reduced loss of righting reflex (LORR) with paralleled increases in blood ethanol concentrations. Overall, these data suggest that PKA activity modulates the sedative/hypnotic effects of ethanol and may potentially play a wider role in the differential ethanol responses observed between adolescents and adults. PMID:24874150

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:...

Color matrix display simulation based upon luminance and chromatic contrast sensitivity of early vision

NASA Technical Reports Server (NTRS)

Martin, Russel A.; Ahumada, Albert J., Jr.; Larimer, James O.

1992-01-01

This paper describes the design and operation of a new simulation model for color matrix display development. It models the physical structure, the signal processing, and the visual perception of static displays, to allow optimization of display design parameters through image quality measures. The model is simple, implemented in the Mathematica computer language, and highly modular. Signal processing modules operate on the original image. The hardware modules describe backlights and filters, the pixel shape, and the tiling of the pixels over the display. Small regions of the displayed image can be visualized on a CRT. Visual perception modules assume static foveal images. The image is converted into cone catches and then into luminance, red-green, and blue-yellow images. A Haar transform pyramid separates the three images into spatial frequency and direction-specific channels. The channels are scaled by weights taken from human contrast sensitivity measurements of chromatic and luminance mechanisms at similar frequencies and orientations. Each channel provides a detectability measure. These measures allow the comparison of images displayed on prospective devices and, by that, the optimization of display designs.

The effect of temperature during retail display on the colour stability of CO pretreated vacuum packaged beef steaks.

PubMed

Van Rooyen, Lauren Anne; Allen, Paul; Gallagher, Eimear I; O'Connor, David I

2018-05-24

The effect of CO pretreatments applied to beef striploin steaks (Longissimus thoracis et lumborum, LTL) prior to vacuum packaging and display temperature on colour stability, shelf life and tenderness was determined. Steaks were exposed to 5% CO, 60% CO 2 and 35% N 2 for 3 (CO3), 5 (CO5) or 7 (CO7) h, followed by 28 days display at 2 °C (good industry practice) or 6 °C (mild abuse). CO5 was the optimum exposure time as it induced the desirable colour while not retaining the bright colour, irrespective of display temperature. K/S ratios confirmed that CO pretreatment did not mask spoilage and could be more sensitive than colour parameters at monitoring discoloration as colour was not retained. Exposure to CO did not have any negative effect on meat quality attributes, while mild temperature abuse (6 °C) increased purge loss and decreased pH. Copyright © 2018 Elsevier Ltd. All rights reserved.

Application of a Noise Adaptive Contrast Sensitivity Function to Image Data Compression

NASA Astrophysics Data System (ADS)

Daly, Scott J.

1989-08-01

The visual contrast sensitivity function (CSF) has found increasing use in image compression as new algorithms optimize the display-observer interface in order to reduce the bit rate and increase the perceived image quality. In most compression algorithms, increasing the quantization intervals reduces the bit rate at the expense of introducing more quantization error, a potential image quality degradation. The CSF can be used to distribute this error as a function of spatial frequency such that it is undetectable by the human observer. Thus, instead of being mathematically lossless, the compression algorithm can be designed to be visually lossless, with the advantage of a significantly reduced bit rate. However, the CSF is strongly affected by image noise, changing in both shape and peak sensitivity. This work describes a model of the CSF that includes these changes as a function of image noise level by using the concepts of internal visual noise, and tests this model in the context of image compression with an observer study.

Ergonomic problems regarding the interactive touch input via screens in onboard and ground-based flight control

NASA Technical Reports Server (NTRS)

Holzhausen, K. P.; Gaertner, K. P.

1985-01-01

A significant problem concerning the integration of display and switching functions is related to the fact that numerous informative data which have to be processed by man must be read from only a few display devices. A satisfactory ergonomic design of integrated display devices and keyboards is in many cases difficult, because not all functions which can be displayed and selected are simultaneously available. A technical solution which provides an integration of display and functional elements on the basis of the highest flexibility is obtained by using a cathode ray tube with a touch-sensitive screen. The employment of an integrated data input/output system is demonstrated for the cases of onboard and ground-based flight control. Ergonomic studies conducted to investigate the suitability of an employment of touch-sensitive screens are also discussed.

Use of an Antecedent Analysis and a Force Sensitive Platform to Compare Stereotyped Movements and Motor Tics

ERIC Educational Resources Information Center

Crosland, Kimberly A.; Zarcone, Jennifer R.; Schroeder, Stephen; Zarcane, Troy; Fowler, Stephen

2005-01-01

Stereotyped movements displayed by 6 participants and tics displayed by 6 children were evaluated using an antecedent behavioral analysis and a force sensitive platform. We found that tics occurred more often in an alone condition when compared to high preference toy and play conditions, whereas stereotyped movements were more variable across…

Magnetostrictive GMR spin valves with composite FeGa/FeCo free layers

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

Liu, Luping; Institute of Materials Science, School of Materials Science and Engineering, Shanghai University, Shanghai 200072; Zhan, Qingfeng, E-mail: zhanqf@nimte.ac.cn, E-mail: runweili@nimte.ac.cn

2016-03-15

We have fabricated strain-sensitive spin valves on flexible substrates by utilizing the large magnetostrictive FeGa alloy to promote the strain sensitivity and the composite free layer of FeGa/FeCo to avoid the drastic reduction of giant magnetoresistance (GMR) ratio. This kind of spin valve (SV-FeGa/FeCo) displays a MR ratio about 5.9%, which is comparable to that of the conventional spin valve (SV-FeCo) with a single FeCo free layer. Different from the previously reported works on magnetostrictive spin valves, the SV-FeGa/FeCo displays an asymmetric strain dependent GMR behavior. Upon increasing the lateral strain, the MR ratio for the ascending branch decreases moremore » quickly than that for the descending branch, which is ascribed to the formation of a spiraling spin structure around the FeGa/FeCo interface under the combined influences of both magnetic field and mechanical strain. A strain sensitivity of GF = 7.2 was achieved at a magnetic bias field of -30 Oe in flexible SV-FeGa/FeCo, which is significantly larger than that of SV-FeCo.« less

Age-dependent differences in nicotine reward and withdrawal in female mice.

PubMed

Kota, D; Martin, B R; Damaj, M I

2008-06-01

Adolescent smoking is an increasing epidemic in the US. Research has shown that the commencement of smoking at a young age increases addiction and decreases the probability of successful cessation; however, limited work has focused on nicotine dependence in the female. The goal of the present study was to identify the biological and behavioral factors that may contribute to nicotine's increased abuse liability in female adolescents using animal models of nicotine dependence. Early adolescent (PND 28) and adult (PND 70) female mice were compared in various aspects of nicotine dependence using reward and withdrawal models following sub-chronic nicotine exposure. Furthermore, in vivo acute sensitivity and tolerance to nicotine were examined. In the conditioned place preference model, adolescents demonstrated a significant preference at 0.5 mg/kg nicotine, an inactive dose in adults. Adults found higher doses (0.7 and 1.0 mg/kg) of nicotine to elicit rewarding effects. Furthermore, adolescents displayed increased physical, but not affective, withdrawal signs in three models. Upon acute exposure to nicotine, adolescent mice showed increased sensitivity in an analgesic measure as well as hypothermia. After chronic nicotine exposure, both adults and adolescents displayed tolerance to nicotine with adolescents having a lower degree of tolerance to changes in body temperature. These data indicate that differences in nicotine's rewarding and aversive effects may contribute to variations in certain components of nicotine dependence between adult and adolescent female mice. Furthermore, this implies that smoking cessation therapies may not be equally effective across all ages.

Disgust Sensitivity and the Neurophysiology of Left-Right Political Orientations

PubMed Central

Smith, Kevin B.; Oxley, Douglas; Hibbing, Matthew V.; Alford, John R.; Hibbing, John R.

2011-01-01

Disgust has been described as the most primitive and central of emotions. Thus, it is not surprising that it shapes behaviors in a variety of organisms and in a variety of contexts—including homo sapien politics. People who believe they would be bothered by a range of hypothetical disgusting situations display an increased likelihood of displaying right-of-center rather than left-of-center political orientations. Given its primal nature and essential value in avoiding pathogens disgust likely has an effect even without registering in conscious beliefs. In this article, we demonstrate that individuals with marked involuntary physiological responses to disgusting images, such as of a man eating a large mouthful of writhing worms, are more likely to self-identify as conservative and, especially, to oppose gay marriage than are individuals with more muted physiological responses to the same images. This relationship holds even when controlling for the degree to which respondents believe themselves to be disgust sensitive and suggests that people's physiological predispositions help to shape their political orientations. PMID:22039415

Chronic mild stress facilitates melanoma tumor growth in mouse lines selected for high and low stress-induced analgesia.

PubMed

Ragan, Agnieszka R; Lesniak, Anna; Bochynska-Czyz, Marta; Kosson, Anna; Szymanska, Hanna; Pysniak, Kazimiera; Gajewska, Marta; Lipkowski, Andrzej W; Sacharczuk, Mariusz

2013-09-01

Both chronic stress conditions and hyperergic reaction to environmental stress are known to enhance cancer susceptibility. We described two mouse lines that displayed high (HA) and low (LA) swim stress-induced analgesia (SSIA) to investigate the relationship between inherited differences in sensitivity to stress and proneness to an increased growth rate of subcutaneously inoculated melanoma. These lines display several genetic and physiological differences, among which distinct sensitivity to mutagens and susceptibility to cancer are especially noticeable. High analgesic mice display high proneness both to stress and a rapid local spread of B16F0 melanoma. However, stress-resistant LA mice do not develop melanoma tumors after inoculation, or if so, tumors regress spontaneously. We found that the chronic mild stress (CMS) procedure leads to enhanced interlinear differences in melanoma susceptibility. Tumors developed faster in stress conditions in both lines. However, LA mice still displayed a tendency for spontaneous regression, and 50% of LA mice did not develop a tumor, even under stressed conditions. Moreover, we showed that chronic stress, but not tumor progression, induces depressive behavior, which may be an important clue in cancer therapy. Our results clearly indicate how the interaction between genetic susceptibility to stress and environmental stress determine the risk and progression of melanoma. To our knowledge, HA/LA mouse lines are the first animal models of distinct melanoma progression mediated by inherited differences in stress reactivity.

Development and evaluation of a method of calibrating medical displays based on fixed adaptation

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

Sund, Patrik, E-mail: patrik.sund@vgregion.se; Månsson, Lars Gunnar; Båth, Magnus

2015-04-15

Purpose: The purpose of this work was to develop and evaluate a new method for calibration of medical displays that includes the effect of fixed adaptation and by using equipment and luminance levels typical for a modern radiology department. Methods: Low contrast sinusoidal test patterns were derived at nine luminance levels from 2 to 600 cd/m{sup 2} and used in a two alternative forced choice observer study, where the adaptation level was fixed at the logarithmic average of 35 cd/m{sup 2}. The contrast sensitivity at each luminance level was derived by establishing a linear relationship between the ten pattern contrastmore » levels used at every luminance level and a detectability index (d′) calculated from the fraction of correct responses. A Gaussian function was fitted to the data and normalized to the adaptation level. The corresponding equation was used in a display calibration method that included the grayscale standard display function (GSDF) but compensated for fixed adaptation. In the evaluation study, the contrast of circular objects with a fixed pixel contrast was displayed using both calibration methods and was rated on a five-grade scale. Results were calculated using a visual grading characteristics method. Error estimations in both observer studies were derived using a bootstrap method. Results: The contrast sensitivities for the darkest and brightest patterns compared to the contrast sensitivity at the adaptation luminance were 37% and 56%, respectively. The obtained Gaussian fit corresponded well with similar studies. The evaluation study showed a higher degree of equally distributed contrast throughout the luminance range with the calibration method compensated for fixed adaptation than for the GSDF. The two lowest scores for the GSDF were obtained for the darkest and brightest patterns. These scores were significantly lower than the lowest score obtained for the compensated GSDF. For the GSDF, the scores for all luminance levels were statistically separated from the average value; three were lower and two were higher. For the compensated GSDF, three of the scores could not be separated from the average value. Conclusions: An observer study using clinically relevant displays and luminance settings has demonstrated that the calibration of displays according to the GSDF causes the perceived contrast to be unevenly distributed when using displays with a high luminance range. As the luminance range increases, the perceived contrast in the dark and bright regions will be significantly lower than the perceived contrast in the middle of the luminance range. A new calibration method that includes the effect of fixed adaptation was developed and evaluated in an observer study and was found to distribute the contrast of the display more evenly throughout the grayscale than the GSDF.« less

Dynamic Displays Enhance the Ability to Discriminate Genuine and Posed Facial Expressions of Emotion

PubMed Central

Namba, Shushi; Kabir, Russell S.; Miyatani, Makoto; Nakao, Takashi

2018-01-01

Accurately gauging the emotional experience of another person is important for navigating interpersonal interactions. This study investigated whether perceivers are capable of distinguishing between unintentionally expressed (genuine) and intentionally manipulated (posed) facial expressions attributed to four major emotions: amusement, disgust, sadness, and surprise. Sensitivity to this discrimination was explored by comparing unstaged dynamic and static facial stimuli and analyzing the results with signal detection theory. Participants indicated whether facial stimuli presented on a screen depicted a person showing a given emotion and whether that person was feeling a given emotion. The results showed that genuine displays were evaluated more as felt expressions than posed displays for all target emotions presented. In addition, sensitivity to the perception of emotional experience, or discriminability, was enhanced in dynamic facial displays, but was less pronounced in the case of static displays. This finding indicates that dynamic information in facial displays contributes to the ability to accurately infer the emotional experiences of another person. PMID:29896135

Loss-of-function mutations in the ethylene receptor ETR1 cause enhanced sensitivity and exaggerated response to ethylene in Arabidopsis.

PubMed

Cancel, Jesse D; Larsen, Paul B

2002-08-01

Ethylene signaling in Arabidopsis begins at a family of five ethylene receptors that regulate activity of a downstream mitogen-activated protein kinase kinase kinase, CTR1. Triple and quadruple loss-of-function ethylene receptor mutants display a constitutive ethylene response phenotype, indicating they function as negative regulators in this pathway. No ethylene-related phenotype has been described for single loss-of-function receptor mutants, although it was reported that etr1 loss-of-function mutants display a growth defect limiting plant size. In actuality, this apparent growth defect results from enhanced responsiveness to ethylene; a phenotype manifested in all tissues tested. The phenotype displayed by etr1 loss-of-function mutants was rescued by treatment with an inhibitor of ethylene perception, indicating that it is ethylene dependent. Identification of an ethylene-dependent phenotype for a loss-of-function receptor mutant gave a unique opportunity for genetic and biochemical analysis of upstream events in ethylene signaling, including demonstration that the dominant ethylene-insensitive phenotype of etr2-1 is partially dependent on ETR1. This work demonstrates that mutational loss of the ethylene receptor ETR1 alters responsiveness to ethylene in Arabidopsis and that enhanced ethylene response in Arabidopsis not only results in increased sensitivity but exaggeration of response.

Loss-of-Function Mutations in the Ethylene Receptor ETR1 Cause Enhanced Sensitivity and Exaggerated Response to Ethylene in Arabidopsis

PubMed Central

Cancel, Jesse D.; Larsen, Paul B.

2002-01-01

Ethylene signaling in Arabidopsis begins at a family of five ethylene receptors that regulate activity of a downstream mitogen-activated protein kinase kinase kinase, CTR1. Triple and quadruple loss-of-function ethylene receptor mutants display a constitutive ethylene response phenotype, indicating they function as negative regulators in this pathway. No ethylene-related phenotype has been described for single loss-of-function receptor mutants, although it was reported that etr1 loss-of-function mutants display a growth defect limiting plant size. In actuality, this apparent growth defect results from enhanced responsiveness to ethylene; a phenotype manifested in all tissues tested. The phenotype displayed by etr1 loss-of-function mutants was rescued by treatment with an inhibitor of ethylene perception, indicating that it is ethylene dependent. Identification of an ethylene-dependent phenotype for a loss-of-function receptor mutant gave a unique opportunity for genetic and biochemical analysis of upstream events in ethylene signaling, including demonstration that the dominant ethylene-insensitive phenotype of etr2-1 is partially dependent on ETR1. This work demonstrates that mutational loss of the ethylene receptor ETR1 alters responsiveness to ethylene in Arabidopsis and that enhanced ethylene response in Arabidopsis not only results in increased sensitivity but exaggeration of response. PMID:12177468

A generic approach to engineer antibody pH-switches using combinatorial histidine scanning libraries and yeast display.

PubMed

Schröter, Christian; Günther, Ralf; Rhiel, Laura; Becker, Stefan; Toleikis, Lars; Doerner, Achim; Becker, Janine; Schönemann, Andreas; Nasu, Daichi; Neuteboom, Berend; Kolmar, Harald; Hock, Björn

2015-01-01

There is growing interest in the fast and robust engineering of protein pH-sensitivity that aims to reduce binding at acidic pH, compared to neutral pH. Here, we describe a novel strategy for the incorporation of pH-sensitive antigen binding functions into antibody variable domains using combinatorial histidine scanning libraries and yeast surface display. The strategy allows simultaneous screening for both, high affinity binding at pH 7.4 and pH-sensitivity, and excludes conventional negative selection steps. As proof of concept, we applied this strategy to incorporate pH-dependent antigen binding into the complementary-determining regions of adalimumab. After 3 consecutive rounds of separate heavy and light chain library screening, pH-sensitive variants could be isolated. Heavy and light chain mutations were combined, resulting in 3 full-length antibody variants that revealed sharp, reversible pH-dependent binding profiles. Dissociation rate constants at pH 6.0 increased 230- to 780-fold, while high affinity binding at pH 7.4 in the sub-nanomolar range was retained. Furthermore, binding to huFcRn and thermal stability were not affected by histidine substitutions. Overall, this study emphasizes a generalizable strategy for engineering pH-switch functions potentially applicable to a variety of antibodies and further proteins-based therapeutics.

Deficits in acetylcholine homeostasis, receptors and behaviors in choline transporter heterozygous mice.

PubMed

Bazalakova, M H; Wright, J; Schneble, E J; McDonald, M P; Heilman, C J; Levey, A I; Blakely, R D

2007-07-01

Cholinergic neurons elaborate a hemicholinium-3 (HC-3) sensitive choline transporter (CHT) that mediates presynaptic, high-affinity choline uptake (HACU) in support of acetylcholine (ACh) synthesis and release. Homozygous deletion of CHT (-/-) is lethal shortly after birth (Ferguson et al. 2004), consistent with CHT as an essential component of cholinergic signaling, but precluding functional analyses of CHT contributions in adult animals. In contrast, CHT+/- mice are viable, fertile and display normal levels of synaptosomal HACU, yet demonstrate reduced CHT protein and increased sensitivity to HC-3, suggestive of underlying cholinergic hypofunction. We find that CHT+/- mice are equivalent to CHT+/+ siblings on measures of motor co-ordination (rotarod), general activity (open field), anxiety (elevated plus maze, light/dark paradigms) and spatial learning and memory (Morris water maze). However, CHT+/- mice display impaired performance as a result of physical challenge in the treadmill paradigm, as well as reduced sensitivity to challenge with the muscarinic receptor antagonist scopolamine in the open field paradigm. These behavioral alterations are accompanied by significantly reduced brain ACh levels, elevated choline levels and brain region-specific decreased expression of M1 and M2 muscarinic acetylcholine receptors. Our studies suggest that CHT hemizygosity results in adequate baseline ACh stores, sufficient to sustain many phenotypes, but normal sensitivities to physical and/or pharmacological challenge require full cholinergic signaling capacity.

How much crosstalk can be allowed in a stereoscopic system at various grey levels?

NASA Astrophysics Data System (ADS)

Shestak, Sergey; Kim, Daesik; Kim, Yongie

2012-03-01

We have calculated a perceptual threshold of stereoscopic crosstalk on the basis of mathematical model of human vision sensitivity. Instead of linear model of just noticeable difference (JND) known as Weber's law we applied nonlinear Barten's model. The predicted crosstalk threshold varies with the background luminance. The calculated values of threshold are in a reasonable agreement with known experimental data. We calculated perceptual threshold of crosstalk for various combinations of the applied grey level. This result can be applied for the assessment of grey-to-grey crosstalk compensation. Further computational analysis of the applied model predicts the increase of the displayable image contrast with reduction of the maximum displayable luminance.

Sensitization of human carcinoma cells to alkylating agents by small interfering RNA suppression of 3-alkyladenine-DNA glycosylase.

PubMed

Paik, Johanna; Duncan, Tod; Lindahl, Tomas; Sedgwick, Barbara

2005-11-15

One of the major cytotoxic lesions generated by alkylating agents is DNA 3-alkyladenine, which can be excised by 3-alkyladenine DNA glycosylase (AAG). Inhibition of AAG may therefore result in increased cellular sensitivity to chemotherapeutic alkylating agents. To investigate this possibility, we have examined the role of AAG in protecting human tumor cells against such agents. Plasmids that express small interfering RNAs targeted to two different regions of AAG mRNA were transfected into HeLa cervical carcinoma cells and A2780-SCA ovarian carcinoma cells. Stable derivatives of both cell types with low AAG protein levels were sensitized to alkylating agents. Two HeLa cell lines with AAG protein levels reduced by at least 80% to 90% displayed a 5- to 10-fold increase in sensitivity to methyl methanesulfonate, N-methyl-N-nitrosourea, and the chemotherapeutic drugs temozolomide and 1,3-bis(2-chloroethyl)-1-nitrosourea. These cells showed no increase in sensitivity to UV light or ionizing radiation. After treatment with methyl methanesulfonate, AAG knockdown HeLa cells were delayed in S phase but accumulated in G2-M. Our data support the hypothesis that ablation of AAG activity in human tumor cells may provide a useful strategy to enhance the efficacy of current chemotherapeutic regimens that include alkylating agents.

Altered sensitization patterns to sweet food stimuli in patients recovered from anorexia and bulimia nervosa.

PubMed

Wagner, Angela; Simmons, Alan N; Oberndorfer, Tyson A; Frank, Guido K W; McCurdy-McKinnon, Danyale; Fudge, Julie L; Yang, Tony T; Paulus, Martin P; Kaye, Walter H

2015-12-30

Recent studies show that higher-order appetitive neural circuitry may contribute to restricted eating in anorexia nervosa (AN) and overeating in bulimia nervosa (BN). The purpose of this study was to determine whether sensitization effects might underlie pathologic eating behavior when a taste stimulus is administered repeatedly. Recovered AN (RAN, n=14) and BN (RBN, n=15) subjects were studied in order to avoid the confounding effects of altered nutritional state. Functional magnetic resonance imaging (fMRI) measured higher-order brain response to repeated tastes of sucrose (caloric) and sucralose (non-caloric). To test sensitization, the neuronal response to the first and second administration was compared. RAN patients demonstrated a decreased sensitization to sucrose in contrast to RBN patients who displayed the opposite pattern, increased sensitization to sucrose. However, the latter was not as pronounced as in healthy control women (n=13). While both eating disorder subgroups showed increased sensitization to sucralose, the healthy controls revealed decreased sensitization. These findings could reflect on a neuronal level the high caloric intake of RBN during binges and the low energy intake for RAN. RAN seem to distinguish between high energy and low energy sweet stimuli while RBN do not. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Engineering an Anti-Transferrin Receptor ScFv for pH-Sensitive Binding Leads to Increased Intracellular Accumulation.

PubMed

Tillotson, Benjamin J; Goulatis, Loukas I; Parenti, Isabelle; Duxbury, Elizabeth; Shusta, Eric V

2015-01-01

The equilibrium binding affinity of receptor-ligand or antibody-antigen pairs may be modulated by protonation of histidine side-chains, and such pH-dependent mechanisms play important roles in biological systems, affecting molecular uptake and trafficking. Here, we aimed to manipulate cellular transport of single-chain antibodies (scFvs) against the transferrin receptor (TfR) by engineering pH-dependent antigen binding. An anti-TfR scFv was subjected to histidine saturation mutagenesis of a single CDR. By employing yeast surface display with a pH-dependent screening pressure, scFvs having markedly increased dissociation from TfR at pH 5.5 were identified. The pH-sensitivity generally resulted from a central cluster of histidine residues in CDRH1. When soluble, pH-sensitive, scFv clone M16 was dosed onto live cells, the internalized fraction was 2.6-fold greater than scFvs that lacked pH-sensitive binding and the increase was dependent on endosomal acidification. Differences in the intracellular distribution of M16 were also observed consistent with an intracellular decoupling of the scFv M16-TfR complex. Engineered pH-sensitive TfR binding could prove important for increasing the effectiveness of TfR-targeted antibodies seeking to exploit endocytosis or transcytosis for drug delivery purposes.

Engineering an Anti-Transferrin Receptor ScFv for pH-Sensitive Binding Leads to Increased Intracellular Accumulation

PubMed Central

Tillotson, Benjamin J.; Goulatis, Loukas I.; Parenti, Isabelle; Duxbury, Elizabeth; Shusta, Eric V.

2015-01-01

The equilibrium binding affinity of receptor-ligand or antibody-antigen pairs may be modulated by protonation of histidine side-chains, and such pH-dependent mechanisms play important roles in biological systems, affecting molecular uptake and trafficking. Here, we aimed to manipulate cellular transport of single-chain antibodies (scFvs) against the transferrin receptor (TfR) by engineering pH-dependent antigen binding. An anti-TfR scFv was subjected to histidine saturation mutagenesis of a single CDR. By employing yeast surface display with a pH-dependent screening pressure, scFvs having markedly increased dissociation from TfR at pH 5.5 were identified. The pH-sensitivity generally resulted from a central cluster of histidine residues in CDRH1. When soluble, pH-sensitive, scFv clone M16 was dosed onto live cells, the internalized fraction was 2.6-fold greater than scFvs that lacked pH-sensitive binding and the increase was dependent on endosomal acidification. Differences in the intracellular distribution of M16 were also observed consistent with an intracellular decoupling of the scFv M16-TfR complex. Engineered pH-sensitive TfR binding could prove important for increasing the effectiveness of TfR-targeted antibodies seeking to exploit endocytosis or transcytosis for drug delivery purposes. PMID:26713870

Young Children's Responses to Guilt Displays

ERIC Educational Resources Information Center

Vaish, Amrisha; Carpenter, Malinda; Tomasello, Michael

2011-01-01

Displaying guilt after a transgression serves to appease the victim and other group members, restore interpersonal relationships, and indicate the transgressors' awareness of and desire to conform to the group's norms. We investigated whether and when young children are sensitive to these functions of guilt displays. In Study 1, after 4- and…

Responses of Male C57BL/6N Mice to Observing the Euthanasia of Other Mice.

PubMed

Boivin, Gregory P; Bottomley, Michael A; Grobe, Nadja

2016-01-01

The AVMA Panel on Euthanasia recommends that sensitive animals should not be present during the euthanasia of others, especially of their own species, but does not provide guidelines on how to identify a sensitive species. To determine if mice are a sensitive species we reviewed literature on empathy in mice, and measured the cardiovascular and activity response of mice observing euthanasia of conspecifics. We studied male 16-wk-old C57BL/6N mice and found no increase in cardiovascular parameters or activity in the response of the mice to observing CO2 euthanasia. Mice observing decapitation had an increase in all values, but this was paralleled by a similar increase during mock decapitations in which no animals were handled or euthanized. We conclude that CO2 euthanasia of mice does not have an impact on other mice in the room, and that euthanasia by decapitation likely only has an effect due to the noise of the guillotine. We support the conceptual idea that mice are both a sensitive species and display empathy, but under the controlled circumstances of the euthanasia procedures used in this study there was no signaling of stress to witnessing inhabitants in the room.

Isolation of a pH-Sensitive IgNAR Variable Domain from a Yeast-Displayed, Histidine-Doped Master Library.

PubMed

Könning, Doreen; Zielonka, Stefan; Sellmann, Carolin; Schröter, Christian; Grzeschik, Julius; Becker, Stefan; Kolmar, Harald

2016-04-01

In recent years, engineering of pH-sensitivity into antibodies as well as antibody-derived fragments has become more and more attractive for biomedical and biotechnological applications. Herein, we report the isolation of the first pH-sensitive IgNAR variable domain (vNAR), which was isolated from a yeast-displayed, semi-synthetic master library. This strategy enables the direct identification of pH-dependent binders from a histidine-enriched CDR3 library. Displayed vNAR variants contained two histidine substitutions on average at random positions in their 12-residue CDR3 loop. Upon screening of seven rounds against the proof-of-concept target EpCAM (selection for binding at pH 7.4 and decreased binding at pH 6.0), a single clone was obtained that showed specific and pH-dependent binding as characterized by yeast surface display and biolayer interferometry. Potential applications for such pH-dependent vNAR domains include their employment in tailored affinity chromatography, enabling mild elution protocols. Moreover, utilizing a master library for the isolation of pH-sensitive vNAR variants may be a generic strategy to obtain binding entities with prescribed characteristics for applications in biotechnology, diagnostics, and therapy.

Cell type-specific hypersensitivity to oxidative damage in CSB and XPA mice.

PubMed

de Waard, Harm; de Wit, Jan; Gorgels, Theo G M F; van den Aardweg, Gerard; Andressoo, Jaan Olle; Vermeij, Marcel; van Steeg, Harry; Hoeijmakers, Jan H J; van der Horst, Gijsbertus T J

2003-01-02

Mutations in the CSB gene cause Cockayne syndrome (CS), a rare inherited disorder, characterized by UV-sensitivity, severe neurodevelopmental and progeroid symptoms. CSB functions in the transcription-coupled repair (TCR) sub-pathway of nucleotide excision repair (NER), responsible for the removal of UV-induced and other helix-distorting lesions from the transcribed strand of active genes. Several lines of evidence support the notion that the CSB TCR defect extends to other non-NER type transcription-blocking lesions, notably various kinds of oxidative damage, which may provide an explanation for part of the severe CS phenotype. We used genetically defined mouse models to examine the relationship between the CSB defect and sensitivity to oxidative damage in different cell types and at the level of the intact organism. The main conclusions are: (1) CSB(-/-) mouse embryo fibroblasts (MEFs) exhibit a clear hypersensitivity to ionizing radiation, extending the findings in genetically heterogeneous human CSB fibroblasts to another species. (2) CSB(-/-) MEFs are highly sensitive to paraquat, strongly indicating that the increased cytotoxicity is due to oxidative damage. (3) The hypersenstivity is independent of genetic background and directly related to the CSB defect and is not observed in totally NER-deficient XPA MEFs. (4) Wild type embryonic stem (ES) cells display an increased sensitivity to ionizing radiation compared to fibroblasts. Surprisingly, the CSB deficiency has only a very minor additional effect on ES cell sensitivity to oxidative damage and is comparable to that of an XPA defect, indicating cell type-specific differences in the contribution of TCR and NER to cellular survival. (5) Similar to ES cells, CSB and XPA mice both display a minor sensitivity to whole-body X-ray exposure. This suggests that the response of an intact organism to radiation is largely determined by the sensitivity of stem cells, rather than differentiated cells. These findings establish the role of transcription-coupled repair in resistance to oxidative damage and reveal a cell- and organ-specific impact of this repair pathway to the clinical phenotype of CS and XP.

Mental Imagery Training Increases Wanting of Rewards and Reward Sensitivity and Reduces Depressive Symptoms.

PubMed

Linke, Julia; Wessa, Michèle

2017-09-01

High reward sensitivity and wanting of rewarding stimuli help to identify and motivate repetition of pleasant activities. This behavioral activation is thought to increase positive emotions. Therefore, both mechanisms are highly relevant for resilience against depressive symptoms. Yet, these mechanisms have not been targeted by psychotherapeutic interventions. In the present study, we tested a mental imagery training comprising eight 10-minute sessions every second day and delivered via the Internet to healthy volunteers (N = 30, 21 female, mean age of 23.8 years, Caucasian) who were preselected for low reward sensitivity. Participants were paired according to age, sex, reward sensitivity, and mental imagery ability. Then, members of each pair were randomly assigned to either the intervention or wait condition. Ratings of wanting and response bias toward probabilistic reward cues (Probabilistic Reward Task) served as primary outcomes. We further tested whether training effects extended to approach behavior (Approach Avoidance Task) and depressive symptoms (Beck Depression Inventory). The intervention led to an increase in wanting (p < .001, η 2 p = .45) and reward sensitivity (p = .004, η 2 p = .27). Further, the training group displayed faster approach toward positive edibles and activities (p = .025, η 2 p = .18) and reductions in depressive symptoms (p = .028, η 2 p = .16). Results extend existing literature by showing that mental imagery training can increase wanting of rewarding stimuli and reward sensitivity. Further, the training appears to reduce depressive symptoms and thus may foster the successful implementation of exsiting treatments for depression such as behavioral activation and could also increase resilience against depressive symptoms. Copyright © 2017. Published by Elsevier Ltd.

Cocaine-Induced Behavioral Sensitization Is Associated With Changes in the Expression of Endocannabinoid and Glutamatergic Signaling Systems in the Mouse Prefrontal Cortex

PubMed Central

Blanco, Eduardo; Pavón, Francisco J.; Palomino, Ana; Luque-Rojas, María Jesús; Serrano, Antonia; Rivera, Patricia; Bilbao, Ainhoa; Alen, Francisco; Vida, Margarita; Suárez, Juan

2015-01-01

Background: Endocannabinoids modulate the glutamatergic excitatory transmission by acting as retrograde messengers. A growing body of studies has reported that both signaling systems in the mesocorticolimbic neural circuitry are involved in the neurobiological mechanisms underlying drug addiction. Methods: We investigated whether the expression of both endocannabinoid and glutamatergic systems in the prefrontal cortex (PFC) were altered by an acute and/or repeated cocaine administration schedule that resulted in behavioral sensitization. We measured the protein and mRNA expression of the main endocannabinoid metabolic enzymes and the cannabinoid receptor type 1 (CB1). We also analyzed the mRNA expression of relevant components of the glutamate-signaling system, including glutamate-synthesizing enzymes, metabotropic receptors, and ionotropic receptors. Results: Although acute cocaine (10mg/kg) produced no significant changes in the endocannabinoid-related proteins, repeated cocaine administration (20mg/kg daily) induced a pronounced increase in the CB1 receptor expression. In addition, acute cocaine administration (10mg/kg) in cocaine-sensitized mice (referred to as cocaine priming) induced a selective increase in the endocannabinoid-degrading enzymes fatty acid amide hydrolase (FAAH) and monoacylglycerol lipase (MAGL). These protein changes were accompanied by an overall decrease in the ratios of endocannabinoid synthesis/degradation, especially the N-acyl phosphatidylethanolamine phospholipase D/FAAH and diacylglycerol lipase alpha/MAGL ratios. Regarding mRNA expression, while acute cocaine administration produced a decrease in CB1 receptors and N-acyl phosphatidylethanolamine phospholipase D, repeated cocaine treatment enhanced CB1 receptor expression. Cocaine-sensitized mice that were administered priming injections of cocaine mainly displayed an increased FAAH expression. These endocannabinoid changes were associated with modifications in glutamatergic transmission-related genes. An overall decrease was observed in the mRNA expression of the glutamate-synthesizing gene kidney-type glutaminase (KGA), the metabotropic glutamate receptors (mGluR3 and GluR), and subunits of NMDA ionotropic receptors (NR1, NR2A, NR2B and NR2C) after acute cocaine administration, while mice repeatedly exposed to cocaine only displayed an increase in NR2C. However, in cocaine-sensitized mice primed with cocaine, this inhibition was reversed and a strong increase was detected in the mGluR5, NR2 subunits, and both GluR1 and GluR3. Conclusions: These findings indicate that cocaine sensitization is associated with an endocannabinoid downregulation and a hyperglutamatergic state in the PFC that, overall, contribute to an enhanced glutamatergic input into PFC-projecting areas. PMID:25539508

Task-dependent color discrimination

NASA Technical Reports Server (NTRS)

Poirson, Allen B.; Wandell, Brian A.

1990-01-01

When color video displays are used in time-critical applications (e.g., head-up displays, video control panels), the observer must discriminate among briefly presented targets seen within a complex spatial scene. Color-discrimination threshold are compared by using two tasks. In one task the observer makes color matches between two halves of a continuously displayed bipartite field. In a second task the observer detects a color target in a set of briefly presented objects. The data from both tasks are well summarized by ellipsoidal isosensitivity contours. The fitted ellipsoids differ both in their size, which indicates an absolute sensitivity difference, and orientation, which indicates a relative sensitivity difference.

Concomitant behavioral and PFC neuronal activity recorded following dose-response protocol of MPD in adult male rats.

PubMed

Venkataraman, Sidish S; Claussen, Catherine; Joseph, Michael; Dafny, Nachum

2017-04-01

The use of methylphenidate (MPD), a commonly prescribed drug to treat attention-deficit hyperactivity disorder (ADHD), has steadily increased over the past 25 years. This trend has been accompanied by more MPD abuse by ordinary individuals for its cognitive enhancing effects. Therefore, understanding the effects of MPD on the prefrontal cortex (PFC), a brain area involved in higher cortical processing such as executive function, language, planning, and attention regulation, is of particular importance. The goal of this study is to investigate the effects of acute and chronic dose-response characteristics following MPD exposure on both the PFC neuronal population and behavioral activity in freely behaving animals implanted previously with permanent electrodes within the PFC. Four groups of animals were used: saline (control), 0.6, 2.5, and 10.0mg/kg MPD. It was observed that the same dose of either 0.6, 2.5, or 10.0mg/kg repetitive (chronic) MPD exposure elicited behavioral sensitization in some animals and behavioral tolerance in others, and that the majority of PFC units recorded from animals expressing behavioral sensitization to chronic MPD exposure responded to MPD by increasing their neuronal firing rate, whereas the majority of PFC neurons recorded from animals expressing behavioral tolerance in response to chronic MPD responded by decreasing their neuronal firing rate. This data suggests that in animals that display behavioral sensitization, chronic MPD exposure causes an increase in the number of post-synaptic D1 dopamine receptors leading to an increase in behavioral and neuronal firing rate, while in animals that display behavioral tolerance, chronic MPD exposure causes an increase in the number of post-synaptic D2 dopamine receptors leading to a decrease in behavioral and neuronal firing rate. This dichotomy needs to be further investigated. Copyright © 2017 Elsevier Inc. All rights reserved.

[Different responses of DD/He and CC57BR/Mv mice to fasting].

PubMed

Baginskaia, N V; Vasil'eva, E D; Il'nitskaia, S I; Kaledin, V I

2004-03-01

Reaction to fasting of 2 mice strains differing in their sensitivity to spontaneous and induced hepatocarcinogenesis, has been investigated. It was shown that mice of both strains displayed similar stress reaction after 3-day fasting manifested in increase in blood corticosterone level; and decrease in testosterone level. At the same time, both strains demonstrated opposite changes at tissue- and enzyme levels in the liver. It was shown that DD/He mice, highly sensitive to induction of liver tumors, were characterized by significant increase in tyrosine aminotransferase (TAT) activity and reduction of lipid droplets in hepatocytes. CC57BR/Mv mice, demonstrating high frequency of spontaneous hepatomas and insensitive to induction of such tumors, were characterized by a decrease in the TAT activity and fatty infiltration of the liver.

IR sensitive photorefractive polymers, the first updateable holographic three-dimensional display

NASA Astrophysics Data System (ADS)

Tay, Savas

This work presents recent advances in the development of infra-red sensitive photorefractive polymers, and updateable near real-time holographic 3D displays based on photorefractive polymers. Theoretical and experimental techniques used for design, fabrication and characterization of photorefractive polymers are outlined. Materials development and technical advances that made possible the use of photorefractive polymers for infra-red free-space optical communications, and 3D holographic displays are presented. Photorefractive polymers are dynamic holographic materials that allow recording of highly efficient reversible holograms. The longest operation wavelength for a photorefractive polymer before this study has been 950nm, far shorter than 1550nm, the wavelength of choice for optical communications and medical imaging. The polymers shown here were sensitized using two-photon absorption, a third order nonlinear effect, beyond the linear absorption spectrum of organic dyes, and reach 40% diffraction efficiency with a 35ms response time at this wavelength. As a consequence of two-photon absorption sensitization they exhibit non-destructive readout, which is an important advantage for applications that require high signal-to-noise ratios. Holographic 3D displays provide highly realistic images without the need for special eyewear, making them valuable tools for applications that require "situational awareness" such as medical, industrial and military imaging. Current commercially available holographic 3D displays employ photopolymers that lack image updating capability, resulting in their restricted use and high cost per 3D image. The holographic 3D display shown here employs photorefractive polymers with nearly 100% diffraction efficiency and fast writing time, hours of image persistence, rapid erasure and large area, a combination of properties that has not been shown before. The 3D display is based on stereography and utilizes world's largest photorefractive devices (4x4 inch in size). It can be recorded within a few minutes, viewed for several hours without the need for refreshing and can be completely erased and updated with new images when desired, thusly comprising the first updateable holographic 3D display with memory, suitable for practical use.

Highly Sensitive and Long Term Stable Electrochemical Microelectrodes for Implantable Glucose Monitoring Devices

NASA Astrophysics Data System (ADS)

Qiang, Liangliang

A miniature wireless implantable electrochemical glucose system for continuous glucose monitoring with good selectivity, sensitivity, linearity and long term stability was developed. First, highly sensitive, long-term stable and reusable planar H2O2 microelectrodes have been fabricated by microlithography. These electrodes composed of a 300 nm Pt black layer situated on a 5 um thick Au layer, provide effective protection to the underlying chromium adhesion layer. Using repeated cyclic voltammetric sweeps in flowing buffer solution, highly sensitive Pt black working electrodes were realized with five-decade linear dynamic range and low detection limit (10 nM) for H2O2 at low oxidation potentials. Second, a highly sensitive, low cost and flexible microwire biosensor was described using 25-mum thick gold wire as working electrode together with 125-mum thick Pt/Ir and Ag wires as counter and reference electrode, embedded within a PDMS-filled polyethylene tube. Surface area and activity of sensor was enhanced by converting gold electrode to nanoporous configuration followed by electrodeposition of platinum black. Glucose oxidase based biosensors by electrodeposition of poly(o-phenylenediamine) and glucose oxidase on the working electrode, displayed a higher glucose sensitivity (1.2 mA mM-1 cm-2) than highest literature reported. In addition it exhibits wide detection range (up to 20 mM) and selectivity (>95%). Third, novel miniaturized and flexible microelectrode arrays with 8 of 25 mum electrodes displayed the much needed 3D diffusion profiles similar to a single 25 mum microelectrode, but with one order increase in current levels. These microelectrode arrays displayed a H2O2 sensitivity of 13 mA mM-1 cm-2, a wide dynamic range of 100 nM to 10 mM, limit of detection of 10 nM. These microwire based edge plane microsensors incorporated flexibility, miniaturization and low operation potential are an promising approach for continuous in vivo metabolic monitoring. Fourth, homemade miniature wireless potentisotat was fabricated based on low power consumption integrated circuits and surface mount parts. The miniature wireless potentisotat with up to two week life-time for continuous glucose sensing has a size less than 9x22x10 mm and weight ˜3.4 grams. Primary in vivo experiment showed homemade system has the exactly same respond and trend as commercial glucose meter.

Maternal Immune Activation Alters Nonspatial Information Processing in the Hippocampus of the Adult Offspring

PubMed Central

Ito, Hiroshi T.; Smith, Stephen E. P.; Hsiao, Elaine; Patterson, Paul H.

2010-01-01

The observation that maternal infection increases the risk for schizophrenia in the offspring suggests that the maternal immune system plays a key role in the etiology of schizophrenia. In a mouse model, maternal immune activation (MIA) by injection of poly(I:C) yields adult offspring that display abnormalities in a variety of behaviors relevant to schizophrenia. As abnormalities in the hippocampus are a consistent observation in schizophrenia patients, we examined synaptic properties in hippocampal slices prepared from the offspring of poly(I:C)- and saline-treated mothers. Compared to controls, CA1 pyramidal neurons from adult offspring of MIA mothers display reduced frequency and increased amplitude of miniature excitatory postsynaptic currents. In addition, the specific component of the temporoammonic pathway that mediates object-related information displays increased sensitivity to dopamine. To assess hippocampal network function in vivo, we used expression of the immediate early gene, c-Fos, as a surrogate measure of neuronal activity. Compared to controls, the offspring of poly(I:C)-treated mothers display a distinct c-Fos expression pattern in area CA1 following novel object, but not novel location, exposure. Thus, the offspring of MIA mothers may have an abnormality in modality-specific information processing. Indeed, the MIA offspring display enhanced discrimination in a novel object recognition, but not in an object location, task. Thus, analysis of object and spatial information processing at both synaptic and behavioral levels reveals a largely selective abnormality in object information processing in this mouse model. Our results suggest that altered processing of object-related information may be part of the pathogenesis of schizophrenia-like cognitive behaviors. PMID:20227486

Maternal immune activation alters nonspatial information processing in the hippocampus of the adult offspring.

PubMed

Ito, Hiroshi T; Smith, Stephen E P; Hsiao, Elaine; Patterson, Paul H

2010-08-01

The observation that maternal infection increases the risk for schizophrenia in the offspring suggests that the maternal immune system plays a key role in the etiology of schizophrenia. In a mouse model, maternal immune activation (MIA) by injection of poly(I:C) yields adult offspring that display abnormalities in a variety of behaviors relevant to schizophrenia. As abnormalities in the hippocampus are a consistent observation in schizophrenia patients, we examined synaptic properties in hippocampal slices prepared from the offspring of poly(I:C)- and saline-treated mothers. Compared to controls, CA1 pyramidal neurons from adult offspring of MIA mothers display reduced frequency and increased amplitude of miniature excitatory postsynaptic currents. In addition, the specific component of the temporoammonic pathway that mediates object-related information displays increased sensitivity to dopamine. To assess hippocampal network function in vivo, we used expression of the immediate-early gene, c-Fos, as a surrogate measure of neuronal activity. Compared to controls, the offspring of poly(I:C)-treated mothers display a distinct c-Fos expression pattern in area CA1 following novel object, but not novel location, exposure. Thus, the offspring of MIA mothers may have an abnormality in modality-specific information processing. Indeed, the MIA offspring display enhanced discrimination in a novel object recognition, but not in an object location, task. Thus, analysis of object and spatial information processing at both synaptic and behavioral levels reveals a largely selective abnormality in object information processing in this mouse model. Our results suggest that altered processing of object-related information may be part of the pathogenesis of schizophrenia-like cognitive behaviors. Copyright 2010 Elsevier Inc. All rights reserved.

Psychophysical contrast calibration

PubMed Central

To, Long; Woods, Russell L; Goldstein, Robert B; Peli, Eli

2013-01-01

Electronic displays and computer systems offer numerous advantages for clinical vision testing. Laboratory and clinical measurements of various functions and in particular of (letter) contrast sensitivity require accurately calibrated display contrast. In the laboratory this is achieved using expensive light meters. We developed and evaluated a novel method that uses only psychophysical responses of a person with normal vision to calibrate the luminance contrast of displays for experimental and clinical applications. Our method combines psychophysical techniques (1) for detection (and thus elimination or reduction) of display saturating nonlinearities; (2) for luminance (gamma function) estimation and linearization without use of a photometer; and (3) to measure without a photometer the luminance ratios of the display’s three color channels that are used in a bit-stealing procedure to expand the luminance resolution of the display. Using a photometer we verified that the calibration achieved with this procedure is accurate for both LCD and CRT displays enabling testing of letter contrast sensitivity to 0.5%. Our visual calibration procedure enables clinical, internet and home implementation and calibration verification of electronic contrast testing. PMID:23643843

Long-term alterations in vulnerability to addiction to drugs of abuse and in brain gene expression after early life ethanol exposure.

PubMed

Barbier, Estelle; Pierrefiche, Olivier; Vaudry, David; Vaudry, Hubert; Daoust, Martine; Naassila, Mickaël

2008-12-01

Exposure to ethanol early in life can have long-lasting implications on brain function and drug of abuse response later in life. The present study investigated in rats, the long-term consequences of pre- and postnatal (early life) ethanol exposure on drug consumption/reward and the molecular targets potentially associated with these behavioral alterations. Since a relationship has been demonstrated between heightened drugs intake and susceptibility to drugs-induced locomotor activity/sensitization, anxiolysis, we tested these behavioral responses, depending on the drug, in control and early life ethanol-exposed animals. Our results show that progeny exposed to early life ethanol displayed increased consumption of ethanol solutions and increased sensitivity to cocaine rewarding effects assessed in the conditioned place preference test. Offspring exposed to ethanol were more sensitive to the anxiolytic effect of ethanol and the increased sensitivity could, at least in part, explain the alteration in the consumption of ethanol for its anxiolytic effects. In addition, the sensitivity to hypothermic effects of ethanol and ethanol metabolism were not altered by early life ethanol exposure. The sensitization to cocaine (20 mg/kg) and to amphetamine (1.2 mg/kg) was increased after early life ethanol exposure and, could partly explain, an increase in the rewarding properties of psychostimulants. Gene expression analysis revealed that expression of a large number of genes was altered in brain regions involved in the reinforcing effects of drugs of abuse. Dopaminergic receptors and transporter binding sites were also down-regulated in the striatum of ethanol-exposed offspring. Such long-term neurochemical alterations in transmitter systems and in the behavioral responses to ethanol and other drugs of abuse may confer an increased liability for addiction in exposed offspring.

Targeted Overexpression of Inducible 6-Phosphofructo-2-kinase in Adipose Tissue Increases Fat Deposition but Protects against Diet-induced Insulin Resistance and Inflammatory Responses*

PubMed Central

Huo, Yuqing; Guo, Xin; Li, Honggui; Xu, Hang; Halim, Vera; Zhang, Weiyu; Wang, Huan; Fan, Yang-Yi; Ong, Kuok Teong; Woo, Shih-Lung; Chapkin, Robert S.; Mashek, Douglas G.; Chen, Yanming; Dong, Hui; Lu, Fuer; Wei, Lai; Wu, Chaodong

2012-01-01

Increasing evidence demonstrates the dissociation of fat deposition, the inflammatory response, and insulin resistance in the development of obesity-related metabolic diseases. As a regulatory enzyme of glycolysis, inducible 6-phosphofructo-2-kinase (iPFK2, encoded by PFKFB3) protects against diet-induced adipose tissue inflammatory response and systemic insulin resistance independently of adiposity. Using aP2-PFKFB3 transgenic (Tg) mice, we explored the ability of targeted adipocyte PFKFB3/iPFK2 overexpression to modulate diet-induced inflammatory responses and insulin resistance arising from fat deposition in both adipose and liver tissues. Compared with wild-type littermates (controls) on a high fat diet (HFD), Tg mice exhibited increased adiposity, decreased adipose inflammatory response, and improved insulin sensitivity. In a parallel pattern, HFD-fed Tg mice showed increased hepatic steatosis, decreased liver inflammatory response, and improved liver insulin sensitivity compared with controls. In both adipose and liver tissues, increased fat deposition was associated with lipid profile alterations characterized by an increase in palmitoleate. Additionally, plasma lipid profiles also displayed an increase in palmitoleate in HFD-Tg mice compared with controls. In cultured 3T3-L1 adipocytes, overexpression of PFKFB3/iPFK2 recapitulated metabolic and inflammatory changes observed in adipose tissue of Tg mice. Upon treatment with conditioned medium from iPFK2-overexpressing adipocytes, mouse primary hepatocytes displayed metabolic and inflammatory responses that were similar to those observed in livers of Tg mice. Together, these data demonstrate a unique role for PFKFB3/iPFK2 in adipocytes with regard to diet-induced inflammatory responses in both adipose and liver tissues. PMID:22556414

Fundamental Factors Impacting the Stability of Phosphonate-Derivatized Ruthenium Polypyridyl Sensitizers Adsorbed on Metal Oxide Surfaces.

PubMed

Raber, McKenzie; Brady, Matthew David; Troian-Gautier, Ludovic; Dickenson, John; Marquard, Seth L; Hyde, Jacob; Lopez, Santiago; Meyer, Gerald J; Meyer, Thomas J; Harrison, Daniel P

2018-06-08

A series of 18 ruthenium(II) polypyridyl complexes were synthesized and evaluated under electrochemically oxidative conditions, which generates the Ru(III) oxidation state and mimics the harsh conditions experienced during the kinetically-limited regime that can occur in dye-sensitized solar cells (DSSCs) and dye-sensitized photoelectrosynthesis cells (DSPECs), to further develop fundamental insights into the factors governing molecular sensitizer surface stability in aqueous 0.1 M HClO4 (aq). Both desorption and oxidatively induced ligand substitution were observed on planar fluorine doped tin oxide, FTO, electrodes, with a dependence on the E1/2 Ru(III/II) redox potential dictating the comparative ratios of the processes. Complexes such as RuP4OMe (E1/2 = 0.91 vs Ag/AgCl) displayed virtually only desorption, while complexes such as RuPbpz (E1/2 > 1.62 V vs Ag/AgCl) displayed only chemical decomposition. Comparing isomers of 4,4'- and 5,5-disubstituted-2,2'-bipyridine ancillary polypyridyl ligands, a dramatic increase in the rate of desorption of the Ru(III) complexes was observed for the 5,5'-ligands. Nanoscopic indium doped tin oxide thin films, nanoITO, were also sensitized and analyzed with cyclic voltammetry, UV-Vis absorption spectroscopy, and XPS, allowing for further distinction of desorption versus ligand substitution processes. Desorption loss to bulk solution associated with the planar surface of FTO is essentially non-existent on nanoITO, where both desorption and ligand substitution are shut down with RuP4OMe. These results revealed that minimizing time spent in the oxidized form, incorporating electron donating groups, maximizing hydrophobicity, and minimizing molecular bulk near the adsorbed ligand are critical to optimizing the performance of ruthenium(II) polypyridyl complexes in dye-sensitized solar cell devices.

Cellular Levels of Oxidative Stress Affect the Response of Cervical Cancer Cells to Chemotherapeutic Agents

PubMed Central

Williams, Vonetta M.; Kokoza, Anatolii; Bashkirova, Svetlana; Duerksen-Hughes, Penelope

2014-01-01

Treatment of advanced and relapsed cervical cancer is frequently ineffective, due in large part to chemoresistance. To examine the pathways responsible, we employed the cervical carcinoma-derived SiHa and CaSki cells as cellular models of resistance and sensitivity, respectively, to treatment with chemotherapeutic agents, doxorubicin, and cisplatin. We compared the proteomic profiles of SiHa and CaSki cells and identified pathways with the potential to contribute to the differential response. We then extended these findings by comparing the expression level of genes involved in reactive oxygen species (ROS) metabolism through the use of a RT-PCR array. The analyses demonstrated that the resistant SiHa cells expressed higher levels of antioxidant enzymes. Decreasing or increasing oxidative stress led to protection or sensitization, respectively, in both cell lines, supporting the idea that cellular levels of oxidative stress affect responsiveness to treatment. Interestingly, doxorubicin and cisplatin induced different profiles of ROS, and these differences appear to contribute to the sensitivity to treatment displayed by cervical cancer cells. Overall, our findings demonstrate that cervical cancer cells display variable profiles with respect to their redox-generating and -adaptive systems, and that these different profiles have the potential to contribute to their responses to treatments with chemotherapy. PMID:25478571

Development of sensitivity versus specificity for print in the visual word form area.

PubMed

Centanni, Tracy M; King, Livia W; Eddy, Marianna D; Whitfield-Gabrieli, Susan; Gabrieli, John D E

2017-07-01

An area near the left lateral occipito-temporal sulcus that responds preferentially to print has been designated as the visual word form area (VWFA). Research suggests that specialization in this brain region increases as reading expertise is achieved. Here we aimed to characterize that development in terms of sensitivity (response to printed words relative to non-linguistic faces) versus specificity (response to printed words versus line drawings of nameable objects) in typically reading children ages 7-14 versus young adults as measured by functional magnetic resonance imaging (fMRI). Relative to adults, children displayed equivalent sensitivity but reduced specificity. These findings suggest that sensitivity for print relative to non-linguistic stimuli develops relatively early in the VWFA in the course of reading development, but that specificity for printed words in VWFA is still developing through at least age 14. Copyright © 2017 Elsevier Inc. All rights reserved.

An ultrasensitive quartz crystal microbalance-micropillars based sensor for humidity detection

NASA Astrophysics Data System (ADS)

Wang, Pengtao; Su, Junwei; Su, Che-Fu; Dai, Wen; Cernigliaro, George; Sun, Hongwei

2014-06-01

A unique sensing device, which couples microscale pillars with quartz crystal microbalance (QCM) substrate to form a resonant system, is developed to achieve several orders of magnitude enhancement in sensitivity compared to conventional QCM sensors. In this research, Polymethyl Methacrylate (PMMA) micropillars are fabricated on a QCM substrate using nanoimprinting lithography. The effects of pillar geometry and physical properties, tuned by molecular weight (MW) of PMMA, on the resonant characteristics of QCM-micropillars device are systematically investigated. It is found that the resonant frequency shift increases with increasing MW. The coupled QCM-micropillars device displays nonlinear frequency response, which is opposite to the linear response of conventional QCM devices. In addition, a positive resonant frequency shift is captured near the resonant point of the coupled QCM-micropillars system. Humidity detection experiments show that compared to current nanoscale feature based QCM sensors, QCM-micropillars devices offer higher sensitivity and moderate response time. This research points to a novel way of improving sensitivity of acoustic wave sensors without the need for fabricating surface nanostructures.

Real-time analysis of dual-display phage immobilization and autoantibody screening using quartz crystal microbalance with dissipation monitoring.

PubMed

Rajaram, Kaushik; Losada-Pérez, Patricia; Vermeeren, Veronique; Hosseinkhani, Baharak; Wagner, Patrick; Somers, Veerle; Michiels, Luc

2015-01-01

Over the last three decades, phage display technology has been used for the display of target-specific biomarkers, peptides, antibodies, etc. Phage display-based assays are mostly limited to the phage ELISA, which is notorious for its high background signal and laborious methodology. These problems have been recently overcome by designing a dual-display phage with two different end functionalities, namely, streptavidin (STV)-binding protein at one end and a rheumatoid arthritis-specific autoantigenic target at the other end. Using this dual-display phage, a much higher sensitivity in screening specificities of autoantibodies in complex serum sample has been detected compared to single-display phage system on phage ELISA. Herein, we aimed to develop a novel, rapid, and sensitive dual-display phage to detect autoantibodies presence in serum samples using quartz crystal microbalance with dissipation monitoring as a sensing platform. The vertical functionalization of the phage over the STV-modified surfaces resulted in clear frequency and dissipation shifts revealing a well-defined viscoelastic signature. Screening for autoantibodies using antihuman IgG-modified surfaces and the dual-display phage with STV magnetic bead complexes allowed to isolate the target entities from complex mixtures and to achieve a large response as compared to negative control samples. This novel dual-display strategy can be a potential alternative to the time consuming phage ELISA protocols for the qualitative analysis of serum autoantibodies and can be taken as a departure point to ultimately achieve a point of care diagnostic system.

Efficient iodine-free dye-sensitized solar cells employing truxene-based organic dyes.

PubMed

Zong, Xueping; Liang, Mao; Chen, Tao; Jia, Jiangnan; Wang, Lina; Sun, Zhe; Xue, Song

2012-07-07

Two new truxene-based organic sensitizers (M15 and M16) featuring high extinction coefficients were synthesized for dye-sensitized solar cells employing cobalt electrolyte. The M16-sensitized device displays a 7.6% efficiency at an irradiation of AM1.5 full sunlight.

Cytotoxicity of bacterial-derived toxins to immortal lung epithelial and macrophage cells.

PubMed

Peterson, Dianne E; Collier, Jayne M; Katterman, Matthew E; Turner, Rachael A; Riley, Mark R

2010-03-01

Health risks associated with inhalation and deposition of biological materials have been a topic of great concern due to highly publicized cases of inhalation anthrax, of new regulations on the release of particulate matter, and to increased concerns on the hazards of indoor air pollution. Here, we present an evaluation of the sensitivity of two immortal cell lines (A549, human lung carcinoma epithelia) and NR8383 (rat alveolar macrophages) to a variety of bacterial-derived inhalation hazards and simulants including etoposide, gliotoxin, streptolysin O, and warfarin. The cell response is evaluated through quantification of changes in mitochondrial succinate dehydrogenase activity, release of lactate dehydrogenase, initiation of apoptosis, and through changes in morphology as determined by visible light microscopy and scanning electron microscopy. These cells display dose-response relations to each toxin, except for triton which has a step change response. The first observable responses of the epithelial cells to these compounds are changes in metabolism for one toxin (warfarin) and alterations in membrane permeability for another (gliotoxin). The other four toxins display a similar time course in response as gauged by changes in metabolism and loss of membrane integrity. Macrophages are more sensitive to most toxins; however, they display a lower level of stability. This information can be used in the design of cell-based sensors responding to these and similar hazards.

Directed evolution of PDZ variants to generate high-affinity detection reagents.

PubMed

Ferrer, Marc; Maiolo, Jim; Kratz, Patricia; Jackowski, Jessica L; Murphy, Dennis J; Delagrave, Simon; Inglese, James

2005-04-01

High-throughput protease assays are used to identify new protease inhibitors which have the potential to become valuable therapeutic products. Antibodies are of great utility as affinity reagents to detect proteolysis products in protease assays, but isolating and producing such antibodies is unreliable, slow and costly. It has been shown previously that PDZ domains can also be used to detect proteolysis products in high-throughput homogeneous assays but their limited natural repertoire restricts their use to only a few peptides. Here we show that directed evolution is an efficient way to create new PDZ domains for detection of protease activity. We report the first use of phage display to alter the specificity of a PDZ domain, yielding three variants with up to 25-fold increased affinity for a peptide cleavage product of HIV protease. Three distinct roles are assigned to the amino acid substitutions found in the selected variants of the NHERF PDZ domain: specific 'beta1-beta3' interaction with ligand residue -1, interactions with ligand residues -4 to -7 and improvement in phage display efficiency. The variants, having affinities as high as 620 nM, display improvements in assay sensitivity of over 5-fold while requiring smaller amounts of reagents. The approach demonstrated here leads the way to highly sensitive reagents for drug discovery that can be isolated more reliably and produced less expensively.

An interactive editor for definition of touch-sensitive zones for a graphic display

NASA Technical Reports Server (NTRS)

Monroe, Burt L., III; Jones, Denise R.

1987-01-01

In the continuing effort to develop more efficient man-machine communications methods, touch displays have shown potential as straightforward input systems. The development of software necessary to handle such systems, however, can become tedious. In order to reduce the need for redundant programming, a touch editor has been developed which allows a programmer to interactively define touch-sensitive areas for a graphic display. The information produced during the editing process is written to a data file, which can be accessed easily when needed by an application program. This paper outlines the structure, logic, and use of the editor, as well as the hardware with which it is presently compatible.

How Interactive Is the Interactive Whiteboard?

ERIC Educational Resources Information Center

Quashie, Valerie

2009-01-01

An interactive whiteboard (IWB) is simply a surface onto which a computer screen can be displayed, via a projector. It is touch-sensitive and lets one use a pen like a mouse, controlling the computer from the board itself. Everything that can be displayed on a computer can be displayed onto the whiteboard and, if the computer is linked to speakers…

Infants Perceive Human Point-Light Displays as Solid Forms

ERIC Educational Resources Information Center

Moore, Derek G.; Goodwin, Julia E.; George, Rachel; Axelsson, Emma L.; Braddick, Fleur M. B.

2007-01-01

While five-month-old infants show orientation-specific sensitivity to changes in the motion and occlusion patterns of human point-light displays, it is not known whether infants are capable of binding a human representation to these displays. Furthermore, it has been suggested that infants do not encode the same physical properties for humans and…

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.

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.

Biguanides sensitize leukemia cells to ABT-737-induced apoptosis by inhibiting mitochondrial electron transport

PubMed Central

Velez, Juliana; Pan, Rongqing; Lee, Jason T.C.; Enciso, Leonardo; Suarez, Marta; Duque, Jorge Eduardo; Jaramillo, Daniel; Lopez, Catalina; Morales, Ludis; Bornmann, William; Konopleva, Marina; Krystal, Gerald; Andreeff, Michael; Samudio, Ismael

2016-01-01

Metformin displays antileukemic effects partly due to activation of AMPK and subsequent inhibition of mTOR signaling. Nevertheless, Metformin also inhibits mitochondrial electron transport at complex I in an AMPK-independent manner, Here we report that Metformin and rotenone inhibit mitochondrial electron transport and increase triglyceride levels in leukemia cell lines, suggesting impairment of fatty acid oxidation (FAO). We also report that, like other FAO inhibitors, both agents and the related biguanide, Phenformin, increase sensitivity to apoptosis induction by the bcl-2 inhibitor ABT-737 supporting the notion that electron transport antagonizes activation of the intrinsic apoptosis pathway in leukemia cells. Both biguanides and rotenone induce superoxide generation in leukemia cells, indicating that oxidative damage may sensitize toABT-737 induced apoptosis. In addition, we demonstrate that Metformin sensitizes leukemia cells to the oligomerization of Bak, suggesting that the observed synergy with ABT-737 is mediated, at least in part, by enhanced outer mitochondrial membrane permeabilization. Notably, Phenformin was at least 10-fold more potent than Metformin in abrogating electron transport and increasing sensitivity to ABT-737, suggesting that this agent may be better suited for targeting hematological malignancies. Taken together, our results suggest that inhibition of mitochondrial metabolism by Metformin or Phenformin is associated with increased leukemia cell susceptibility to induction of intrinsic apoptosis, and provide a rationale for clinical studies exploring the efficacy of combining biguanides with the orally bioavailable derivative of ABT-737, Venetoclax. PMID:27283492

Biguanides sensitize leukemia cells to ABT-737-induced apoptosis by inhibiting mitochondrial electron transport.

PubMed

Velez, Juliana; Pan, Rongqing; Lee, Jason T C; Enciso, Leonardo; Suarez, Marta; Duque, Jorge Eduardo; Jaramillo, Daniel; Lopez, Catalina; Morales, Ludis; Bornmann, William; Konopleva, Marina; Krystal, Gerald; Andreeff, Michael; Samudio, Ismael

2016-08-09

Metformin displays antileukemic effects partly due to activation of AMPK and subsequent inhibition of mTOR signaling. Nevertheless, Metformin also inhibits mitochondrial electron transport at complex I in an AMPK-independent manner, Here we report that Metformin and rotenone inhibit mitochondrial electron transport and increase triglyceride levels in leukemia cell lines, suggesting impairment of fatty acid oxidation (FAO). We also report that, like other FAO inhibitors, both agents and the related biguanide, Phenformin, increase sensitivity to apoptosis induction by the bcl-2 inhibitor ABT-737 supporting the notion that electron transport antagonizes activation of the intrinsic apoptosis pathway in leukemia cells. Both biguanides and rotenone induce superoxide generation in leukemia cells, indicating that oxidative damage may sensitize toABT-737 induced apoptosis. In addition, we demonstrate that Metformin sensitizes leukemia cells to the oligomerization of Bak, suggesting that the observed synergy with ABT-737 is mediated, at least in part, by enhanced outer mitochondrial membrane permeabilization. Notably, Phenformin was at least 10-fold more potent than Metformin in abrogating electron transport and increasing sensitivity to ABT-737, suggesting that this agent may be better suited for targeting hematological malignancies. Taken together, our results suggest that inhibition of mitochondrial metabolism by Metformin or Phenformin is associated with increased leukemia cell susceptibility to induction of intrinsic apoptosis, and provide a rationale for clinical studies exploring the efficacy of combining biguanides with the orally bioavailable derivative of ABT-737, Venetoclax.

Contribution of impaired myofibril and ryanodine receptor function to prolonged low-frequency force depression after in situ stimulation in rat skeletal muscle.

PubMed

Watanabe, Daiki; Kanzaki, Keita; Kuratani, Mai; Matsunaga, Satoshi; Yanaka, Noriyuki; Wada, Masanobu

2015-06-01

The aim of this study was to examine whether prolonged low-frequency force depression (PLFFD) that occurs in situ is the result of decreased myofibrillar Ca(2+) sensitivity and/or reduced sarcoplasmic reticulum (SR) Ca(2+) release. Intact rat gastrocnemius muscles were electrically stimulated via the sciatic nerve until force was reduced to ~50% of the initial and dissected 30 min following the cessation of stimulation. Skinned fibre and whole muscle analyses were performed in the superficial region composed exclusively of type IIB fibres. Fatiguing stimulation significantly reduced the ratio of force at low frequency to that at high frequency to 65% in skinned fibres (1 vs. 50 Hz) and 73% in whole muscles (20 vs. 100 Hz). In order to evaluate changes in myofibrillar Ca(2+) sensitivity and ryanodine receptor caffeine sensitivity, skinned fibres were activated in Ca(2+)- and caffeine-containing solutions, respectively. Skinned fibres from fatigued muscles displayed decreased caffeine sensitivity together with increased myofibrillar Ca(2+) sensitivity. Treatment with 2,2'-dithiodipyridine and reduced glutathione induced a smaller increase in myofibrillar Ca(2+)sensitivity in fatigued than in rested fibres. In fatigued muscles, S-glutathionylation of troponin I was increased and submaximal SR Ca(2+) release, induced by 4-chloro-m-cresol, was decreased. These findings suggest that in the early stage of PLFFD that occurs in fast-twitch muscles of exercising animals and humans, S-glutathionylation of troponin I may attenuate PLFFD by increasing myofibrillar Ca(2+) sensitivity and that under such a circumstance, PLFFD may be ascribable to failure of SR Ca(2+) release.

Radio-sensitization by Piper longumine of human breast adenoma MDA-MB-231 cells in vitro.

PubMed

Yao, Jian-Xin; Yao, Zhi-Feng; Li, Zhan-Feng; Liu, Yong-Biao

2014-01-01

The current study investigated the effects of Piper longumine on radio-sensitization of human breast cancer MDA-MB-231 cells and underlying mechanisms. Human breast cancer MDA-MB-231 cells were cultured in vitro and those in logarithmic growth phase were selected for experiments divided into four groups: control, X-ray exposed, Piper longumine, and Piper longumine combined with X-rays. Conogenic assays were performed to determine the radio-sensitizing effects. Cell survival curves were fitted by single-hit multi-target model and then the survival fraction (SF), average lethal dose (D0), quasi-threshold dose (Dq) and sensitive enhancement ratio (SER) were calculated. Cell apoptosis was analyzed by flow cytometry (FCM).Western blot assays were employed for expression of apoptosis-related proteins (Bc1-2 and Bax) after treatment with Piper longumine and/or X-ray radiation. The intracellular reactive oxygen species (ROS) level was detected by FCM with a DCFH-DA probe. The cloning formation capacity was decreased in the group of piperlongumine plus radiation, which displayed the values of SF2, D0, Dq significantly lower than those of radiation alone group and the sensitive enhancement ratio (SER) of D0 was1.22 and 1.29, respectively. The cell apoptosis rate was increased by the combination treatment of Piper longumine and radiation. Piper longumine increased the radiation-induced intracellular levels of ROS. Compared with the control group and individual group, the combination group demonstrated significantly decreased expression of Bcl-2 with increased Bax. Piper longumine at a non-cytotoxic concentration can enhance the radio-sensitivity of MDA- MB-231cells, which may be related to its regulation of apoptosis-related protein expression and the increase of intracellular ROS level, thus increasing radiation-induced apoptosis.

Enhanced GABAergic transmission in the central nucleus of the amygdala of genetically selected Marchigian Sardinian rats: alcohol and CRF effects

PubMed Central

Herman, Melissa; Kallupi, Marsida; Luu, George; Oleata, Christopher; Heilig, Markus; Koob, George F.; Ciccocioppo, Roberto; Roberto, Marisa

2012-01-01

The GABAergic system in the central amygdala (CeA) plays a major role in ethanol dependence and the anxiogenic-like response to ethanol withdrawal. Alcohol dependence is associated with increased corticotropin releasing factor (CRF) influence on CeA GABA release and CRF type 1 receptor (CRF1) antagonists prevent the excessive alcohol consumption associated with dependence. Genetically-selected Marchigian Sardinian (msP) rats have an overactive extrahypothalamic CRF1 system, are highly sensitive to stress, and display an innate preference for alcohol. The present study examined differences in CeA GABAergic transmission and the effects of ethanol, CRF and a CRF1 antagonist in msP, Sprague-Dawley, and Wistar rats using an electrophysiological approach. We found no significant differences in membrane properties or mean amplitude of evoked GABAA-inhibitory postsynaptic potentials (IPSPs). However, paired-pulse facilitation (PPF) ratios of evoked IPSPs were significantly lower and spontaneous miniature inhibitory postsynaptic current (mIPSC) frequencies were higher in msP rats, suggesting increased CeA GABA release in msP as compared to Sprague-Dawley and Wistar rats. The sensitivity of spontaneous GABAergic transmission to ethanol (44 mM), CRF (200 nM) and CRF1 antagonist (R121919, 1 μM) was comparable in msP, Sprague Dawley, and Wistar rats. However, a history of ethanol drinking significantly increased the baseline mIPSC frequency and decreased the effects of a CRF1 antagonist in msP rats, suggesting increased GABA release and decreased CRF1 sensitivity. These results provide electrophysiological evidence that msP rats display distinct CeA GABAergic activity as compared to Sprague Dawley and Wistar rats. The elevated GABAergic transmission observed in naïve mSP rats is consistent with the neuroadaptations reported in Sprague Dawley rats after the development of ethanol dependence. PMID:23220399

Concepts of Interface Usability and the Enhancement of Design through Eye Tracking and Psychophysiology

DTIC Science & Technology

2008-09-01

attention. Heart rate (HR) and heart rate variability ( HRV ) are biometrics that can be used to identify periods of high mental effort and high stress...HR is known to increase when a person is exposed to mental stressors; HRV will decrease in the same situation. HRV is a much more sensitive measure...mistakes, the display is cluttered, meaningfulness. Measuring specific attitudes Annoyance, anxiety , complexity control, engagement, flexibility, fun

Dissociation of performance and subjective measures of workload

NASA Technical Reports Server (NTRS)

Yeh, Yei-Yu; Wickens, Christopher D.

1988-01-01

A theory is presented to identify sources that produce dissociations between performance and subjective measures of workload. The theory states that performance is determined by (1) amount of resources invested, (2) resource efficiency, and (3) degree of competition for common resources in a multidimensional space described in the multiple-resources model. Subjective perception of workload, multidimensional in nature, increases with greater amounts of resource investment and with greater demands on working memory. Performance and subjective workload measures dissociate when greater resources are invested to improve performance of a resource-limited task; when demands on working memory are increased by time-sharing between concurrent tasks or between display elements; and when performance is sensitive to resource competition and subjective measures are more sensitive to total investment. These dissociation findings and their implications are discussed and directions for future research are suggested.

Responses of Male C57BL/6N Mice to Observing the Euthanasia of Other Mice

PubMed Central

Boivin, Gregory P; Bottomley, Michael A; Grobe, Nadja

2016-01-01

The AVMA Panel on Euthanasia recommends that sensitive animals should not be present during the euthanasia of others, especially of their own species, but does not provide guidelines on how to identify a sensitive species. To determine if mice are a sensitive species we reviewed literature on empathy in mice, and measured the cardiovascular and activity response of mice observing euthanasia of conspecifics. We studied male 16-wk-old C57BL/6N mice and found no increase in cardiovascular parameters or activity in the response of the mice to observing CO2 euthanasia. Mice observing decapitation had an increase in all values, but this was paralleled by a similar increase during mock decapitations in which no animals were handled or euthanized. We conclude that CO2 euthanasia of mice does not have an impact on other mice in the room, and that euthanasia by decapitation likely only has an effect due to the noise of the guillotine. We support the conceptual idea that mice are both a sensitive species and display empathy, but under the controlled circumstances of the euthanasia procedures used in this study there was no signaling of stress to witnessing inhabitants in the room. PMID:27423146

Visual and ocular effects from the use of flat-panel displays.

PubMed

Porcar, Esteban; Pons, Alvaro M; Lorente, Amalia

2016-01-01

To evaluate the prevalence of eye symptoms in a non-presbyopic population of video display unit (VDU) users with flat-panel displays. One hundred and sixteen VDU users with flat-panel display from an urban population participated in the study; their ages ranging from 20 to 34y. There were 60 females and 56 males. An eye examination to rule out the presence of significant uncorrected refractive errors, general binocular dysfunctions and eye conditions was carried out. In order to determine and quantify the type and nature of eye symptoms, participants were asked to answer written questionnaire and the results were grouped by gender, age and number of hours a day spent using a VDU. Seventy-two percent of participants reported eye symptoms related to VDU use. Eye symptoms from moderate-to-severe were found in 23% of participants. The main symptom was moderate-to-severe tired eyes (14%); followed by sensitivity to bright lights (12%), blurred vision at far distances (10%), eyestrain or dry eye or irritated or burning eyes (9%), difficulty in refocusing from one distance to another or headache (8%) and blurred vision at near or intermediate distances (<4%). Eye symptoms were greater among females (P=0.005) and increased with VDU use, markedly above 6h spent using a VDU in a typical day (P=0.01). Significant eye symptoms relate to VDU use often occur and should not be underestimated. The increasing use of electronic devices with flat-panel display should prompt users to take appropriate measures to prevent or to relieve the eye symptoms arising from their use.

Selective skin sensitivity changes and sensory reweighting following short-duration space flight.

PubMed

Lowrey, Catherine R; Perry, Stephen D; Strzalkowski, Nicholas D J; Williams, David R; Wood, Scott J; Bent, Leah R

2014-03-15

Skin sensory input from the foot soles is coupled with vestibular input to facilitate body orientation in a gravitational environment. Anecdotal observations suggest that foot sole skin becomes hypersensitive following space flight. The veritable level of skin sensitivity and its impact on postural disequilibrium observed post space flight have not been documented. Skin sensitivity of astronauts (n = 11) was measured as vibration perception at the great toe, fifth metatarsal and heel. Frequencies targeted four classes of receptors: 3 and 25 Hz for slow-adapting (SA) receptors and 60 and 250 Hz for fast-adapting (FA) receptors. Data were collected pre- and post-space flight. We hypothesized that skin sensitivity would increase post-space flight and correlate to balance measures. Decreased skin sensitivity was found on landing day at 3 and 25 Hz on the great toe. Hypersensitivity was found for a subset of astronauts (n = 6) with significantly increased sensitivity to 250 Hz at the heel. This subset displayed a greater reduction in computerized dynamic posturography (CDP) equilibrium (EQ) scores (-54%) on landing vs. non-hypersensitive participants (-11%). Observed hyposensitivity of SA (pressure) receptors may indicate a strategy to reduce pressure input during periods of unloading. Hypersensitivity of FAs coupled with reduced EQ scores may reflect targeted sensory reweighting. Altered gravito-inertial environments reduce vestibular function in balance control which may trigger increased weighting of FAs (that signal foot contact, slips). Understanding modulations to skin sensitivity has translational implications for mitigating postural disequilibrium following space flight and for on-Earth preventative strategies for imbalance in older adults.

Protective laser beam viewing device

DOEpatents

Neil, George R.; Jordan, Kevin Carl

2012-12-18

A protective laser beam viewing system or device including a camera selectively sensitive to laser light wavelengths and a viewing screen receiving images from the laser sensitive camera. According to a preferred embodiment of the invention, the camera is worn on the head of the user or incorporated into a goggle-type viewing display so that it is always aimed at the area of viewing interest to the user and the viewing screen is incorporated into a video display worn as goggles over the eyes of the user.

Touchscreen everywhere: on transferring a normal planar surface to a touch-sensitive display.

PubMed

Dai, Jingwen; Chung, Chi-Kit Ronald

2014-08-01

We address how a human-computer interface with small device size, large display, and touch-input facility can be made possible by a mere projector and camera. The realization is through the use of a properly embedded structured light sensing scheme that enables a regular light-colored table surface to serve the dual roles of both a projection screen and a touch-sensitive display surface. A random binary pattern is employed to code structured light in pixel accuracy, which is embedded into the regular projection display in a way that the user perceives only regular display but not the structured pattern hidden in the display. With the projection display on the table surface being imaged by a camera, the observed image data, plus the known projection content, can work together to probe the 3-D workspace immediately above the table surface, like deciding if there is a finger present and if the finger touches the table surface, and if so, at what position on the table surface the contact is made. All the decisions hinge upon a careful calibration of the projector-camera-table surface system, intelligent segmentation of the hand in the image data, and exploitation of the homography mapping existing between the projector's display panel and the camera's image plane. Extensive experimentation including evaluation of the display quality, hand segmentation accuracy, touch detection accuracy, trajectory tracking accuracy, multitouch capability and system efficiency are shown to illustrate the feasibility of the proposed realization.

Design and synthesis of theranostic antibiotic nanodrugs that display enhanced antibacterial activity and luminescence

PubMed Central

Xie, Sheng; Manuguri, Sesha; Proietti, Giampiero; Romson, Joakim; Fu, Ying; Inge, A. Ken; Wu, Bin; Zhang, Yang; Häll, Daniel; Ramström, Olof; Yan, Mingdi

2017-01-01

We report the modular formulation of ciprofloxacin-based pure theranostic nanodrugs that display enhanced antibacterial activities, as well as aggregation-induced emission (AIE) enhancement that was successfully used to image bacteria. The drug derivatives, consisting of ciprofloxacin, a perfluoroaryl ring, and a phenyl ring linked by an amidine bond, were efficiently synthesized by a straightforward protocol from a perfluoroaryl azide, ciprofloxacin, and an aldehyde in acetone at room temperature. These compounds are propeller-shaped, and upon precipitation into water, readily assembled into stable nanoaggregates that transformed ciprofloxacin derivatives into AIE-active luminogens. The nanoaggregates displayed increased luminescence and were successfully used to image bacteria. In addition, these nanodrugs showed enhanced antibacterial activities, lowering the minimum inhibitory concentration (MIC) by more than one order of magnitude against both sensitive and resistant Escherichia coli. The study represents a strategy in the design and development of pure theranostic nanodrugs for combating drug-resistant bacterial infections. PMID:28743748

Influence of Lake Stratification Onset on Summer Surface Water Temperature

NASA Astrophysics Data System (ADS)

Woolway, R. I.; Merchant, C. J.

2016-12-01

Summer lake surface water temperatures (LSSWT) are sensitive to climatic warming and have previously been shown to increase at a faster rate than surface air temperatures in some lakes, as a response to thermal stratification occurring earlier in spring. We explore this relationship using a combination of in situ, satellite derived, and simulated temperatures from 144 lakes. Our results demonstrate that LSSWTs of high-latitude and large deep lakes are particularly sensitive to changes in stratification onset and can be expected to display an amplified response to climatic changes in summer air temperature. Climatic modification of LSSWT has numerous consequences for water quality and lake ecosystems, so quantifying this amplified response is important.

The effects of insulin sensitizers on the cardiovascular risk factors in women with polycystic ovary syndrome.

PubMed

Kassi, E; Diamanti-Kandarakis, E

2008-12-01

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in pre-menopausal women characterized by menstrual cycle disturbances, chronic anovulation, and clinical and/or biochemical hyperandrogenism. Although, the primary etiology of PCOS remains unknown, insulin resistance/hyperinsulinemia plays a pivotal role in the pathogenesis of the syndrome. A growing body of recent data support that women with PCOS have displayed an increased prevelance of cardiovascular disease (CVD) risk factors putting potentially at a hight risk for heart disease. Most of these CVD risk factors are etiologically correlated with insulin resistance/hyperinsulinemia, highlighting the role of insulin sensitizers in the therapeutic quiver for the chronic treatment of PCOS. In this review, we discuss the current literature on the CVD risk factors in PCOS and the influence of insulin sensitizers upon these risk factors.

Functional Association of Arabidopsis CAX1 and CAX3 Is Required for Normal Growth and Ion Homeostasis1

PubMed Central

Cheng, Ning-Hui; Pittman, Jon K.; Shigaki, Toshiro; Lachmansingh, Jinesh; LeClere, Sherry; Lahner, Brett; Salt, David E.; Hirschi, Kendal D.

2005-01-01

Cation levels within the cytosol are coordinated by a network of transporters. Here, we examine the functional roles of calcium exchanger 1 (CAX1), a vacuolar H+/Ca2+ transporter, and the closely related transporter CAX3. We demonstrate that like CAX1, CAX3 is also localized to the tonoplast. We show that CAX1 is predominately expressed in leaves, while CAX3 is highly expressed in roots. Previously, using a yeast assay, we demonstrated that an N-terminal truncation of CAX1 functions as an H+/Ca2+ transporter. Here, we use the same yeast assay to show that full-length CAX1 and full-length CAX3 can partially, but not fully, suppress the Ca2+ hypersensitive yeast phenotype and coexpression of full-length CAX1 and CAX3 conferred phenotypes not produced when either transporter was expressed individually. In planta, CAX3 null alleles were modestly sensitive to exogenous Ca2+ and also displayed a 22% reduction in vacuolar H+-ATPase activity. cax1/cax3 double mutants displayed a severe reduction in growth, including leaf tip and flower necrosis and pronounced sensitivity to exogenous Ca2+ and other ions. These growth defects were partially suppressed by addition of exogenous Mg2+. The double mutant displayed a 42% decrease in vacuolar H+/Ca2+ transport, and a 47% decrease in H+-ATPase activity. While the ionome of cax1 and cax3 lines were modestly perturbed, the cax1/cax3 lines displayed increased PO43−, Mn2+, and Zn2+ and decreased Ca2+ and Mg2+ in shoot tissue. These findings suggest synergistic function of CAX1 and CAX3 in plant growth and nutrient acquisition. PMID:16055687

Monosodium glutamate-sensitive hypothalamic neurons contribute to the control of bone mass

NASA Technical Reports Server (NTRS)

Elefteriou, Florent; Takeda, Shu; Liu, Xiuyun; Armstrong, Dawna; Karsenty, Gerard

2003-01-01

Using chemical lesioning we previously identified hypothalamic neurons that are required for leptin antiosteogenic function. In the course of these studies we observed that destruction of neurons sensitive to monosodium glutamate (MSG) in arcuate nuclei did not affect bone mass. However MSG treatment leads to hypogonadism, a condition inducing bone loss. Therefore the normal bone mass of MSG-treated mice suggested that MSG-sensitive neurons may be implicated in the control of bone mass. To test this hypothesis we assessed bone resorption and bone formation parameters in MSG-treated mice. We show here that MSG-treated mice display the expected increase in bone resorption and that their normal bone mass is due to a concomitant increase in bone formation. Correction of MSG-induced hypogonadism by physiological doses of estradiol corrected the abnormal bone resorptive activity in MSG-treated mice and uncovered their high bone mass phenotype. Because neuropeptide Y (NPY) is highly expressed in MSG-sensitive neurons we tested whether NPY regulates bone formation. Surprisingly, NPY-deficient mice had a normal bone mass. This study reveals that distinct populations of hypothalamic neurons are involved in the control of bone mass and demonstrates that MSG-sensitive neurons control bone formation in a leptin-independent manner. It also indicates that NPY deficiency does not affect bone mass.

Endogenous peripheral neuromodulators of the mammalian taste bud.

PubMed

Dando, Robin

2010-10-01

The sensitivity of the mammalian taste system displays a degree of plasticity based on short-term nutritional requirements. Deficiency in a particular substance may lead to a perceived increase in palatability of this substance, providing an additional drive to redress this nutritional imbalance through modification of intake. This alteration occurs not only in the brain but also, before any higher level processing has occurred, in the taste buds themselves. A brief review of recent advances is offered.

Interplay between mast cells, enterochromaffin cells, and sensory signaling in the aging human bowel.

PubMed

Yu, Y; Daly, D M; Adam, I J; Kitsanta, P; Hill, C J; Wild, J; Shorthouse, A; Grundy, D; Jiang, W

2016-10-01

Advanced age is associated with a reduction in clinical visceral pain perception. However, the underlying mechanisms remain largely unknown. Previous studies have suggested that an abnormal interplay between mast cells, enterochromaffin (EC) cells, and afferent nerves contribute to nociception in gastrointestinal disorders. The aim of this study was to investigate how aging affects afferent sensitivity and neuro-immune association in the human bowel. Mechanical and chemical sensitivity of human bowel afferents were examined by ex vivo afferent nerve recordings. Age-related changes in the density of mast cells, EC cells, sensory nerve terminals, and mast cell-nerve micro-anatomical association were investigated by histological and immune staining. Human afferents could be broadly classified into subpopulations displaying mechanical and chemical sensitivity, adaptation, chemo-sensitization, and recruitment. Interestingly human bowel afferent nerve sensitivity was attenuated with age. The density of substance P-immunoreactive (SP-IR) nerve varicosities was also reduced with age. In contrast, the density of ileal and colonic mucosal mast cells was increased with age, as was ileal EC cell number. An increased proportion of mast cells was found in close apposition to SP-IR nerves. Afferent sensitivity in human bowel was reduced with advancing age. Augmentation of mast cells and EC cell numbers and the mast cell-nerve association suggest a compensatory mechanism for sensory neurodegeneration. © 2016 The Authors. Neurogastroenterology & Motility Published by John Wiley & Sons Ltd.

Sulfhydryl oxidation modifies the calcium dependence of ryanodine-sensitive calcium channels of excitable cells.

PubMed Central

Marengo, J J; Hidalgo, C; Bull, R

1998-01-01

The calcium dependence of ryanodine-sensitive single calcium channels was studied after fusing with planar lipid bilayers sarcoendoplasmic reticulum vesicles isolated from excitable tissues. Native channels from mammalian or amphibian skeletal muscle displayed three different calcium dependencies, cardiac (C), mammalian skeletal (MS), and low fractional open times (low Po), as reported for channels from brain cortex. Native channels from cardiac muscle presented only the MS and C dependencies. Channels with the MS or low Po behaviors showed bell-shaped calcium dependencies, but the latter had fractional open times of <0.1 at all [Ca2+]. Channels with C calcium dependence were activated by [Ca2+] < 10 microM and were not inhibited by increasing cis [Ca2+] up to 0.5 mM. After oxidation with 2,2'-dithiodipyridine or thimerosal, channels with low Po or MS dependencies increased their activity. These channels modified their calcium dependencies sequentially, from low Po to MS and C, or from MS to C. Reduction with glutathione of channels with C dependence (native or oxidized) decreased their fractional open times in 0.5 mM cis [Ca2+], from near unity to 0.1-0.3. These results show that all native channels displayed at least two calcium dependencies regardless of their origin, and that these changed after treatment with redox reagents. PMID:9512024

Comparison of the antidepressant sertraline on differential depression-like behaviors elicited by restraint stress and repeated corticosterone administration.

PubMed

Ulloa, J L; Castañeda, P; Berríos, C; Díaz-Veliz, G; Mora, S; Bravo, J A; Araneda, K; Menares, C; Morales, P; Fiedler, J L

2010-12-01

Depressive disorder involves emotional, cognitive, autonomic and endocrine alterations and also evidences support the role of stress in the development of this disorder. Because the hypothalamic-pituitary-adrenal axis is involved in the stress response with a concomitant rise in plasma corticoids, the present study compares the antidepressant effects of sertraline (10mg/kg, i.p.) on behavioral changes elicited by (i) restraint stress (2.5h/day for 13days) and (ii) corticosterone injections (30mg/kg, s.c., for 13days). Stressed animals, but not corticosterone-treated animals displayed anxiety behavior and a reduction in the acquisition of a conditioned avoidance response to 25% of control levels (8.0±2.2 vs. 31.7±3.2), being this effect partly sensitive to sertraline. Stressed, but not corticosterone-treated, animals displayed an increased escape failure compared with the control group (24.6%±3.5 vs. 1.6±0.7), an effect partly prevented by sertraline treatment (7.3%±2.0). Both stressed rats and corticosterone-treated rats showed an increase in immobility in the forced swim test, an effect prevented by sertraline. These results suggest that the altered behaviors elicited by stress and corticosterone can be explained by neural modifications that are sensitive to the sertraline antidepressant. Copyright © 2010 Elsevier Inc. All rights reserved.

Long-term exposure to abnormal glucose levels alters drug metabolism pathways and insulin sensitivity in primary human hepatocytes

NASA Astrophysics Data System (ADS)

Davidson, Matthew D.; Ballinger, Kimberly R.; Khetani, Salman R.

2016-06-01

Hyperglycemia in type 2 diabetes mellitus has been linked to non-alcoholic fatty liver disease, which can progress to inflammation, fibrosis/cirrhosis, and hepatocellular carcinoma. Understanding how chronic hyperglycemia affects primary human hepatocytes (PHHs) can facilitate the development of therapeutics for these diseases. Conversely, elucidating the effects of hypoglycemia on PHHs may provide insights into how the liver adapts to fasting, adverse diabetes drug reactions, and cancer. In contrast to declining PHH monocultures, micropatterned co-cultures (MPCCs) of PHHs and 3T3-J2 murine embryonic fibroblasts maintain insulin-sensitive glucose metabolism for several weeks. Here, we exposed MPCCs to hypo-, normo- and hyperglycemic culture media for ~3 weeks. While albumin and urea secretion were not affected by glucose level, hypoglycemic MPCCs upregulated CYP3A4 enzyme activity as compared to other glycemic states. In contrast, hyperglycemic MPCCs displayed significant hepatic lipid accumulation in the presence of insulin, while also showing decreased sensitivity to insulin-mediated inhibition of glucose output relative to a normoglycemic control. In conclusion, we show for the first time that PHHs exposed to hypo- and hyperglycemia can remain highly functional, but display increased CYP3A4 activity and selective insulin resistance, respectively. In the future, MPCCs under glycemic states can aid in novel drug discovery and mechanistic investigations.

Frequency organization and responses to complex sounds in the medial geniculate body of the mustached bat.

PubMed

Wenstrup, J J

1999-11-01

The auditory cortex of the mustached bat (Pteronotus parnellii) displays some of the most highly developed physiological and organizational features described in mammalian auditory cortex. This study examines response properties and organization in the medial geniculate body (MGB) that may contribute to these features of auditory cortex. About 25% of 427 auditory responses had simple frequency tuning with single excitatory tuning curves. The remainder displayed more complex frequency tuning using two-tone or noise stimuli. Most of these were combination-sensitive, responsive to combinations of different frequency bands within sonar or social vocalizations. They included FM-FM neurons, responsive to different harmonic elements of the frequency modulated (FM) sweep in the sonar signal, and H1-CF neurons, responsive to combinations of the bat's first sonar harmonic (H1) and a higher harmonic of the constant frequency (CF) sonar signal. Most combination-sensitive neurons (86%) showed facilitatory interactions. Neurons tuned to frequencies outside the biosonar range also displayed combination-sensitive responses, perhaps related to analyses of social vocalizations. Complex spectral responses were distributed throughout dorsal and ventral divisions of the MGB, forming a major feature of this bat's analysis of complex sounds. The auditory sector of the thalamic reticular nucleus also was dominated by complex spectral responses to sounds. The ventral division was organized tonotopically, based on best frequencies of singly tuned neurons and higher best frequencies of combination-sensitive neurons. Best frequencies were lowest ventrolaterally, increasing dorsally and then ventromedially. However, representations of frequencies associated with higher harmonics of the FM sonar signal were reduced greatly. Frequency organization in the dorsal division was not tonotopic; within the middle one-third of MGB, combination-sensitive responses to second and third harmonic CF sonar signals (60-63 and 90-94 kHz) occurred in adjacent regions. In the rostral one-third, combination-sensitive responses to second, third, and fourth harmonic FM frequency bands predominated. These FM-FM neurons, thought to be selective for delay between an emitted pulse and echo, showed some organization of delay selectivity. The organization of frequency sensitivity in the MGB suggests a major rewiring of the output of the central nucleus of the inferior colliculus, by which collicular neurons tuned to the bat's FM sonar signals mostly project to the dorsal, not the ventral, division. Because physiological differences between collicular and MGB neurons are minor, a major role of the tecto-thalamic projection in the mustached bat may be the reorganization of responses to provide for cortical representations of sonar target features.

Exercise differentially affects metabolic functions and white adipose tissue in female letrozole- and dihydrotestosterone-induced mouse models of polycystic ovary syndrome.

PubMed

Marcondes, Rodrigo R; Maliqueo, Manuel; Fornes, Romina; Benrick, Anna; Hu, Min; Ivarsson, Niklas; Carlström, Mattias; Cushman, Samuel W; Stenkula, Karin G; Maciel, Gustavo A R; Stener-Victorin, Elisabet

2017-06-15

Here we hypothesized that exercise in dihydrotestosterone (DHT) or letrozole (LET)-induced polycystic ovary syndrome mouse models improves impaired insulin and glucose metabolism, adipose tissue morphology, and expression of genes related to adipogenesis, lipid metabolism, Notch pathway and browning in inguinal and mesenteric fat. DHT-exposed mice had increased body weight, increased number of large mesenteric adipocytes. LET-exposed mice displayed increased body weight and fat mass, decreased insulin sensitivity, increased frequency of small adipocytes and increased expression of genes related to lipolysis in mesenteric fat. In both models, exercise decreased fat mass and inguinal and mesenteric adipose tissue expression of Notch pathway genes, and restored altered mesenteric adipocytes morphology. In conclusion, exercise restored mesenteric adipocytes morphology in DHT- and LET-exposed mice, and insulin sensitivity and mesenteric expression of lipolysis-related genes in LET-exposed mice. Benefits could be explained by downregulation of Notch, and modulation of browning and lipolysis pathways in the adipose tissue. Copyright © 2017 Elsevier B.V. All rights reserved.

Intramyocellular Lipid Droplet Size Rather Than Total Lipid Content is Related to Insulin Sensitivity After 8 Weeks of Overfeeding.

PubMed

Covington, Jeffrey D; Johannsen, Darcy L; Coen, Paul M; Burk, David H; Obanda, Diana N; Ebenezer, Philip J; Tam, Charmaine S; Goodpaster, Bret H; Ravussin, Eric; Bajpeyi, Sudip

2017-12-01

Intramyocellular lipid (IMCL) is inversely related to insulin sensitivity in sedentary populations, yet no prospective studies in humans have examined IMCL accumulation with overfeeding. Twenty-nine males were overfed a high-fat diet (140% caloric intake, 44% from fat) for 8 weeks. Measures of IMCL, whole-body fat oxidation from a 24-hour metabolic chamber, muscle protein extracts, and muscle ceramide measures were obtained before and after the intervention. Eight weeks of overfeeding did not increase overall IMCL. The content of smaller lipid droplets peripherally located in the myofiber decreased, while increases in larger droplets correlated inversely with glucose disposal rate. Overfeeding resulted in inhibition of Akt activity, which correlated with the reductions in smaller, peripherally located lipid droplets and drastic increases in ceramide content. Additionally, peripherally located lipid droplets were associated with more efficient lipid oxidation. Finally, participants who maintained a greater number of smaller, peripherally located lipid droplets displayed a better resistance to weight gain with overfeeding. These results show that lipid droplet size and location rather than mere IMCL content are important to understanding insulin sensitivity. © 2017 The Obesity Society.

Food odors trigger an endocrine response that affects food ingestion and metabolism.

PubMed

Lushchak, Oleh V; Carlsson, Mikael A; Nässel, Dick R

2015-08-01

Food odors stimulate appetite and innate food-seeking behavior in hungry animals. The smell of food also induces salivation and release of gastric acid and insulin. Conversely, sustained odor exposure may induce satiation. We demonstrate novel effects of food odors on food ingestion, metabolism and endocrine signaling in Drosophila melanogaster. Acute exposure to attractive vinegar odor triggers a rapid and transient increase in circulating glucose, and a rapid upregulation of genes encoding the glucagon-like hormone adipokinetic hormone (AKH), four insulin-like peptides (DILPs) and some target genes in peripheral tissues. Sustained exposure to food odors, however, decreases food intake. Hunger-induced strengthening of synaptic signaling from olfactory sensory neurons (OSNs) to brain neurons increases food-seeking behavior, and conversely fed flies display reduced food odor sensitivity and feeding. We show that increasing the strength of OSN signaling chronically by genetic manipulation of local peptide neuromodulation reduces feeding, elevates carbohydrates and diminishes lipids. Furthermore, constitutively strengthened odor sensitivity altered gene transcripts for AKH, DILPs and some of their targets. Thus, we show that food odor can induce a transient anticipatory endocrine response, and that boosted sensitivity to this odor affects food intake, as well as metabolism and hormonal signaling.

Social Stress Increases Cortisol and Hampers Attention in Adolescents with Excess Weight

PubMed Central

Verdejo-Garcia, Antonio; Moreno-Padilla, Maria; Garcia-Rios, M. Carmen; Lopez-Torrecillas, Francisca; Delgado-Rico, Elena; Schmidt-Rio-Valle, Jacqueline; Fernandez-Serrano, Maria J.

2015-01-01

Objective To experimentally examine if adolescents with excess weight are more sensitive to social stress and hence more sensitive to harmful effects of stress in cognition. Design and Methods We conducted an experimental study in 84 adolescents aged 12 to 18 years old classified in two groups based on age adjusted Body Mass Index percentile: Normal weight (n=42) and Excess weight (n=42). Both groups were exposed to social stress as induced by the virtual reality version of the Trier Social Stress Task --participants were requested to give a public speech about positive and negative aspects of their personalities in front of a virtual audience. The outcome measures were salivary cortisol levels and performance in cognitive tests before and after the social stressor. Cognitive tests included the CANTAB Rapid Visual Processing Test (measuring attention response latency and discriminability) and the Iowa Gambling Task (measuring decision-making). Results Adolescents with excess weight compared to healthy weight controls displayed increased cortisol response and less improvement of attentional performance after the social stressor. Decision-making performance decreased after the social stressor in both groups. Conclusion Adolescents who are overweight or obese have increased sensitivity to social stress, which detrimentally impacts attentional skills. PMID:25898204

Time course of the response of carbohydrate metabolism to unloading of the soleus

NASA Technical Reports Server (NTRS)

Henriksen, Erik J.; Tischler, Marc E.

1988-01-01

The time course of the response of carbohydrate metabolism to unloading was studied in the soleus muscle of rats subjected to tail-cast suspension. In the fresh soleus, 12 hours of unloading led to higher concentrations of glycogen and lower activity ratios of both glycogen synthase and glycogen phosphorylase. These changes were still evident on day three. Thereafter, the increased glycogen concentration apparently diminished the activity ratio of glycogen synthase, leading to a subsequent fall in the total glycogen content after day one. After 24 hours of unloading, when no significant atrophy was detectable, there was no differential response to insulin for in vitro glucose metabolism. On day three, the soleus atrophied significantly and displayed a greater sensitivity to insulin for most of these parameters compared to the weight-bearing control muscle. However, insulin sensitivity for glycogen synthesis was unchanged. These results showed that the increased sensitivity to insulin of the unloaded soleus is associated with the degree of muscle atrophy, likely due to an increased insulin binding capacity relative to muscle mass. This study also showed that insulin regulation of glucose uptake and of glycogen synthesis is affected differentially in the unloaded soleus muscle.

Fatty acid composition modulates sensitivity of Legionella pneumophila to warnericin RK, an antimicrobial peptide.

PubMed

Verdon, Julien; Labanowski, Jérome; Sahr, Tobias; Ferreira, Thierry; Lacombe, Christian; Buchrieser, Carmen; Berjeaud, Jean-Marc; Héchard, Yann

2011-04-01

Warnericin RK is an antimicrobial peptide, produced by a Staphyloccocus warneri strain, described to be specifically active against Legionella, the pathogenic bacteria responsible for Legionnaires' disease. Warnericin RK is an amphiphilic alpha-helical peptide, which possesses a detergent-like mode of action. Two others peptides, δ-hemolysin I and II, produced by the same S. warneri strain, are highly similar to S. aureus δ-hemolysin and also display anti-Legionella activity. It has been recently reported that S. aureus δ-hemolysin activity on vesicles is likewise related to phospholipid acyl-chain structure, such as chain length and saturation. As staphylococcal δ-hemolysins were highly similar, we thus hypothesized that fatty acid composition of Legionella's membrane might influence the sensitivity of the bacteria to warnericin RK. Relationship between sensitivity to the peptide and fatty acid composition was then followed in various conditions. Cells in stationary phase, which were already described as less resistant than cells in exponential phase, displayed higher amounts of branched-chain fatty acids (BCFA) and short chain fatty acids. An adapted strain, able to grow at a concentration 33 fold higher than minimal inhibitory concentration of the wild type (i.e. 1μM), was isolated after repeated transfers of L. pneumophila in the presence of increased concentrations of warnericin RK. The amount of BCFA was significantly higher in the adapted strain than in the wild type strain. Also, a transcriptomic analysis of the wild type and adapted strains showed that two genes involved in fatty acid biosynthesis were repressed in the adapted strain. These genes encode enzymes involved in desaturation and elongation of fatty acids respectively. Their repression was in agreement with the decrease of unsaturated fatty acids and fatty acid chain length in the adapted strain. Conclusively, our results indicate that the increase of BCFA and the decrease of fatty acid chain length in membrane were correlated with the increase in resistance to warnericin RK. Therefore, fatty acid profile seems to play a critical role in the sensitivity of L. pneumophila to warnericin RK. Copyright © 2010 Elsevier B.V. All rights reserved.

Biocular image misalignment tolerance

NASA Astrophysics Data System (ADS)

Kalich, Melvyn E.; Rash, Clarence E.; van de Pol, Corina; Rowe, Terri L.; Lont, Lisa M.; Peterson, R. David

2003-09-01

Biocular helmet-mounted display (HMD) design flexibility and cost are directly related to image misalignment tolerance standards. Currently recommended tolerance levels are based on highly variable data from a number of studies. This paper presents progress of an ongoing study to evaluate optometric measures sensitive to misalignment in partial-overlap biocular optical systems like that proposed for the Comanche RAH-66 helicopter helmet integrated display sighting system (HIDSS). Horizontal divergent and relative vertical misalignments (offsets) of see-through biocular symbology viewed against a simulated daytime background were chosen for this study. Misalignments within and just beyond current tolerance recommendations were evaluated using pre, pre and post, and during measures of visual performance. Data were obtained from seven experimental and four control subjects. The diplopia responses from experimental and control subjects were essentially the same. However, accommodative facility showed a rate decrement following exposure to both types of misalignment. Horizontal heterophorias showed definite post-misalignment increases. Subject responses to questionnaires universally indicated increased adaptation to (ease with) visual tasks over the testing period.

Detection of hepatitis B virus core antigen by phage display mediated TaqMan real-time immuno-PCR.

PubMed

Monjezi, Razieh; Tan, Sheau Wei; Tey, Beng Ti; Sieo, Chin Chin; Tan, Wen Siang

2013-01-01

The core antigen (HBcAg) of hepatitis B virus (HBV) is one of the markers for the identification of the viral infection. The main purpose of this study was to develop a TaqMan real-time detection assay based on the concept of phage display mediated immuno-PCR (PD-IPCR) for the detection of HBcAg. PD-IPCR combines the advantages of immuno-PCR (IPCR) and phage display technology. IPCR integrates the versatility of enzyme-linked immunosorbent assay (ELISA) with the sensitivity and signal generation power of PCR. Whereas, phage display technology exploits the physical association between the displayed peptide and the encoding DNA within the same phage particle. In this study, a constrained peptide displayed on the surface of an M13 recombinant bacteriophage that interacts tightly with HBcAg was applied as a diagnostic reagent in IPCR. The phage displayed peptide and its encoding DNA can be used to replace monoclonal antibody (mAb) and chemically bound DNA, respectively. This method is able to detect as low as 10ng of HBcAg with 10(8)pfu/ml of the recombinant phage which is about 10,000 times more sensitive than the phage-ELISA. The PD-IPCR provides an alternative means for the detection of HBcAg in human serum samples. Copyright © 2012 Elsevier B.V. All rights reserved.

Spinal Changes of a Newly Isolated Neuropeptide Endomorphin-2 Concomitant with Vincristine-Induced Allodynia

PubMed Central

Huang, Ben-Qing; Liu, Ji-Dong; Liu, Hui; Zhang, Nan; Li, Li; Chen, Jian-Hua

2014-01-01

Chemotherapy-induced neuropathic pain (CNP) is the major dose-limiting factor in cancer chemotherapy. However, the neural mechanisms underlying CNP remain unclear. There is increasing evidence implicating the involvement of spinal endomorphin-2 (EM2) in neuropathic pain. In this study, we used a vincristine-evoked rat CNP model displaying mechanical allodynia and central sensitization, and observed a significant decrease in the expression of spinal EM2 in CNP. Also, while intrathecal administration of exogenous EM2 attenuated allodynia and central sensitization, the mu-opioid receptor antagonist β-funaltrexamine facilitated these events. We found that the reduction in spinal EM2 was mediated by increased activity of dipeptidylpeptidase IV, possibly as a consequence of chemotherapy-induced oxidative stress. Taken together, our findings suggest that a decrease in spinal EM2 expression causes the loss of endogenous analgesia and leads to enhanced pain sensation in CNP. PMID:24586889

Characterization of Anodic Aluminum Oxide Membrane with Variation of Crystallizing Temperature for pH Sensor.

PubMed

Yeo, Jin-Ho; Lee, Sung-Gap; Jo, Ye-Won; Jung, Hye-Rin

2015-11-01

We fabricated electrolyte-dielectric-metal (EDM) device incorporating a high-k Al2O3 sensing membrane from a porous anodic aluminum oxide (AAO) using a two step anodizing process for pH sensors. In order to change the properties of the AAO template, the crystallizing temperature was varied from 400 degrees C to 700 degrees C over 2 hours. The structural properties were observed by field emission scanning electron microscopy (FE-SEM). The pH sensitivity increased with an increase in the crystallizing temperature from 400 degrees C to 600 degrees C. However at 700 degrees C, deformation occurred. The porous AAO sensor with a crystallizing temperature of 600 degrees C displayed the good sensitivity and long-term stability and the values were 55.7 mV/pH and 0.16 mV/h, respectively.

Abnormal social reward processing in autism as indexed by pupillary responses to happy faces

PubMed Central

2012-01-01

Background Individuals with Autism Spectrum Disorders (ASD) typically show impaired eye contact during social interactions. From a young age, they look less at faces than typically developing (TD) children and tend to avoid direct gaze. However, the reason for this behavior remains controversial; ASD children might avoid eye contact because they perceive the eyes as aversive or because they do not find social engagement through mutual gaze rewarding. Methods We monitored pupillary diameter as a measure of autonomic response in children with ASD (n = 20, mean age = 12.4) and TD controls (n = 18, mean age = 13.7) while they looked at faces displaying different emotions. Each face displayed happy, fearful, angry or neutral emotions with the gaze either directed to or averted from the subjects. Results Overall, children with ASD and TD controls showed similar pupillary responses; however, they differed significantly in their sensitivity to gaze direction for happy faces. Specifically, pupillary diameter increased among TD children when viewing happy faces with direct gaze as compared to those with averted gaze, whereas children with ASD did not show such sensitivity to gaze direction. We found no group differences in fixation that could explain the differential pupillary responses. There was no effect of gaze direction on pupil diameter for negative affect or neutral faces among either the TD or ASD group. Conclusions We interpret the increased pupillary diameter to happy faces with direct gaze in TD children to reflect the intrinsic reward value of a smiling face looking directly at an individual. The lack of this effect in children with ASD is consistent with the hypothesis that individuals with ASD may have reduced sensitivity to the reward value of social stimuli. PMID:22958650

Cumulative and antagonistic effects of a mixture of the antiandrogens vinclozolin and iprodione in the pubertal male rat.

PubMed

Blystone, Chad R; Lambright, Christy S; Cardon, Mary C; Furr, Johnathan; Rider, Cynthia V; Hartig, Phillip C; Wilson, Vickie S; Gray, Leon E

2009-09-01

Vinclozolin and iprodione are dicarboximide fungicides that display antiandrogenic effects in the male rat, which suggests that a mixture would lead to cumulative effects on androgen-sensitive end points. Iprodione is a steroid synthesis inhibitor, but androgen receptor antagonist activity, which is displayed by vinclozolin, has not been fully evaluated. Here, we demonstrate that iprodione binds to the human androgen receptor (IC(50) = 86.0 microM), reduces androgen-dependent gene expression, and reduces androgen-sensitive tissue weights in castrated male rats (Hershberger assay). Since vinclozolin and iprodione affect common targets in the pubertal male rat, we tested the hypothesis that a mixture would have cumulative antiandrogenic effects. An iprodione dose, that does not significantly affect androgen-dependent morphological end points, was combined with vinclozolin doses (2 x 5 factorial design). Sprague-Dawley rats were dosed by gavage with vinclozolin at 0, 10, 30, 60, and 100 mg/kg/day with and without 50 mg iprodione/kg/day from postnatal day (PND) 23 to 55-57 (n = 8 per group). The age at puberty (preputial separation [PPS]), organ weights, serum hormones, and ex vivo testis steroid hormone production were measured. Vinclozolin delayed PPS, reduced androgen-sensitive organ weights, and increased serum testosterone. The addition of iprodione enhanced the vinclozolin inhibition of PPS (PND 47.5 vs.49.1; two-way ANOVA: iprodione main effect p = 0.0002). The dose response for several reproductive and nonreproductive organ weights was affected in a cumulative manner. In contrast, iprodione antagonized the vinclozolin-induced increase in serum testosterone. These results demonstrate that these fungicides interact on common targets in a tissue-specific manner when coadministered to the pubertal male rat.

Industrial femtosecond lasers for machining of heat-sensitive polymers (Conference Presentation)

NASA Astrophysics Data System (ADS)

Hendricks, Frank; Bernard, Benjamin; Matylitsky, Victor V.

2017-03-01

Heat-sensitive materials, such as polymers, are used increasingly in various industrial sectors such as medical device manufacturing and organic electronics. Medical applications include implantable devices like stents, catheters and wires, which need to be structured and cut with minimum heat damage. Also the flat panel display market moves from LCD displays to organic LED (OLED) solutions, which utilize heat-sensitive polymer substrates. In both areas, the substrates often consist of multilayer stacks with different types of materials, such as metals, dielectric layers and polymers with different physical characteristic. The different thermal behavior and laser absorption properties of the materials used makes these stacks difficult to machine using conventional laser sources. Femtosecond lasers are an enabling technology for micromachining of these materials since it is possible to machine ultrafine structures with minimum thermal impact and very precise control over material removed. An industrial femtosecond Spirit HE laser system from Spectra-Physics with pulse duration <400 fs, pulse energies of >120 μJ and average output powers of >16 W is an ideal tool for industrial micromachining of a wide range of materials with highest quality and efficiency. The laser offers process flexibility with programmable pulse energy, repetition rate, and pulse width. In this paper, we provide an overview of machining heat-sensitive materials using Spirit HE laser. In particular, we show how the laser parameters (e.g. laser wavelength, pulse duration, applied energy and repetition rate) and the processing strategy (gas assisted single pass cut vs. multi-scan process) influence the efficiency and quality of laser processing.

Radio Frequency Identification and Motion-sensitive Video Efficiently Automate Recording of Unrewarded Choice Behavior by Bumblebees

PubMed Central

Orbán, Levente L.; Plowright, Catherine M.S.

2014-01-01

We present two methods for observing bumblebee choice behavior in an enclosed testing space. The first method consists of Radio Frequency Identification (RFID) readers built into artificial flowers that display various visual cues, and RFID tags (i.e., passive transponders) glued to the thorax of bumblebee workers. The novelty in our implementation is that RFID readers are built directly into artificial flowers that are capable of displaying several distinct visual properties such as color, pattern type, spatial frequency (i.e., “busyness” of the pattern), and symmetry (spatial frequency and symmetry were not manipulated in this experiment). Additionally, these visual displays in conjunction with the automated systems are capable of recording unrewarded and untrained choice behavior. The second method consists of recording choice behavior at artificial flowers using motion-sensitive high-definition camcorders. Bumblebees have number tags glued to their thoraces for unique identification. The advantage in this implementation over RFID is that in addition to observing landing behavior, alternate measures of preference such as hovering and antennation may also be observed. Both automation methods increase experimental control, and internal validity by allowing larger scale studies that take into account individual differences. External validity is also improved because bees can freely enter and exit the testing environment without constraints such as the availability of a research assistant on-site. Compared to human observation in real time, the automated methods are more cost-effective and possibly less error-prone. PMID:25489677

Radio Frequency Identification and motion-sensitive video efficiently automate recording of unrewarded choice behavior by bumblebees.

PubMed

Orbán, Levente L; Plowright, Catherine M S

2014-11-15

We present two methods for observing bumblebee choice behavior in an enclosed testing space. The first method consists of Radio Frequency Identification (RFID) readers built into artificial flowers that display various visual cues, and RFID tags (i.e., passive transponders) glued to the thorax of bumblebee workers. The novelty in our implementation is that RFID readers are built directly into artificial flowers that are capable of displaying several distinct visual properties such as color, pattern type, spatial frequency (i.e., "busyness" of the pattern), and symmetry (spatial frequency and symmetry were not manipulated in this experiment). Additionally, these visual displays in conjunction with the automated systems are capable of recording unrewarded and untrained choice behavior. The second method consists of recording choice behavior at artificial flowers using motion-sensitive high-definition camcorders. Bumblebees have number tags glued to their thoraces for unique identification. The advantage in this implementation over RFID is that in addition to observing landing behavior, alternate measures of preference such as hovering and antennation may also be observed. Both automation methods increase experimental control, and internal validity by allowing larger scale studies that take into account individual differences. External validity is also improved because bees can freely enter and exit the testing environment without constraints such as the availability of a research assistant on-site. Compared to human observation in real time, the automated methods are more cost-effective and possibly less error-prone.

Toxicity of oil sands acid-extractable organic fractions to freshwater fish: Pimephales promelas (fathead minnow) and Oryzias latipes (Japanese medaka).

PubMed

Bauer, Anthony E; Frank, Richard A; Headley, John V; Peru, Kerry M; Farwell, Andrea J; Dixon, D George

2017-03-01

The Alberta oil sands are one of the largest global petroleum deposits and, due to non-release practices for oil sands process-affected waters, produced tailings are stored in large ponds. The acid extractable organic (AEO) compounds in oil sands process-affected water are of greatest concern due to their persistence and toxicity to a variety of aquatic biota. The present study evaluated the toxicity of the five AEO fractions to two fish species: Oryzias latipes (Japanese medaka) and Pimephales promelas (fathead minnow). The fractions (F1-F5) were comprised of AEO with increasing mean molecular weight and subsequent increases in cyclicity, aromaticity, degree of oxygenation, and heteroatom content. The lowest molecular weight fraction, F1, displayed the lowest acute toxicity to both fish species. For fathead minnow, F5 displayed the greatest toxic potency, while F2 to F4 displayed intermediate toxicities. For Japanese medaka, F2 and F3 displayed the greatest acute toxicities and F1, F4 and F5 were significantly less potent. Overall, fathead minnow were more acutely sensitive to AEO than Japanese medaka. The present study indicates that AEO toxicity may not be solely driven by a narcotic mode of action, but chemical composition such as aromaticity and heteroatom content and their relation to toxicity suggest other drivers indicative of additional modes of toxic action. Copyright © 2016 Elsevier Ltd. All rights reserved.

Hypothalamic PKA regulates leptin sensitivity and adiposity

PubMed Central

Yang, Linghai; McKnight, G. Stanley

2015-01-01

Mice lacking the RIIβ regulatory subunit of cyclic AMP-dependent protein kinase A (PKA) display reduced adiposity and resistance to diet-induced obesity. Here we show that RIIβ knockout (KO) mice have enhanced sensitivity to leptin's effects on both feeding and energy metabolism. After administration of a low dose of leptin, the duration of hypothalamic JAK/STAT3 signalling is increased, resulting in enhanced POMC mRNA induction. Consistent with the extended JAK/STAT3 activation, we find that the negative feedback regulator of leptin receptor signalling, Socs3, is inhibited in the hypothalamus of RIIβ KO mice. During fasting, RIIβ–PKA is activated and this correlates with an increase in CREB phosphorylation. The increase in CREB phosphorylation is absent in the fasted RIIβ KO hypothalamus. Selective inhibition of PKA activity in AgRP neurons partially recapitulates the leanness and resistance to diet-induced obesity of RIIβ KO mice. Our findings suggest that RIIβ–PKA modulates the duration of leptin receptor signalling and therefore the magnitude of the catabolic response to leptin. PMID:26381935

Protein-Tyrosine Phosphatase-1B Mediates Sleep Fragmentation-Induced Insulin Resistance and Visceral Adipose Tissue Inflammation in Mice.

PubMed

Gozal, David; Khalyfa, Abdelnaby; Qiao, Zhuanghong; Akbarpour, Mahzad; Maccari, Rosanna; Ottanà, Rosaria

2017-09-01

Sleep fragmentation (SF) is highly prevalent and has emerged as an important contributing factor to obesity and metabolic syndrome. We hypothesized that SF-induced increases in protein tyrosine phosphatase-1B (PTP-1B) expression and activity underlie increased food intake, inflammation, and leptin and insulin resistance. Wild-type (WT) and ObR-PTP-1b-/- mice (Tg) were exposed to SF and control sleep (SC), and food intake was monitored. WT mice received a PTP-1B inhibitor (RO-7d; Tx) or vehicle (Veh). Upon completion of exposures, systemic insulin and leptin sensitivity tests were performed as well as assessment of visceral white adipose tissue (vWAT) insulin receptor sensitivity and macrophages (ATM) polarity. SF increased food intake in either untreated or Veh-treated WT mice. Leptin-induced hypothalamic STAT3 phosphorylation was decreased, PTP-1B activity was increased, and reduced insulin sensitivity emerged both systemic and in vWAT, with the latter displaying proinflammatory ATM polarity changes. All of the SF-induced effects were abrogated following PTP-1B inhibitor treatment and in Tg mice. SF induces increased food intake, reduced leptin signaling in hypothalamus, systemic insulin resistance, and reduced vWAT insulin sensitivity and inflammation that are mediated by increased PTP-1B activity. Thus, PTP-1B may represent a viable therapeutic target in the context of SF-induced weight gain and metabolic dysfunction. © Sleep Research Society 2017. Published by Oxford University Press on behalf of the Sleep Research Society. All rights reserved. For permissions, please e-mail journals.permissions@oup.com.

Methyltestosterone-induced changes in electro-olfactogram responses and courtship behaviors of cyprinids.

PubMed

Belanger, Rachelle M; Pachkowski, Melanie D; Stacey, Norm E

2010-01-01

In the tinfoil barb (Barbonymus schwanenfeldii; family Cyprinidae), we previously found that increased olfactory sensitivity to a female prostaglandin pheromone could induce sexual behavior display in juvenile fish treated with androgens. Here, we determined if this phenomenon is widespread among cyprinid fishes by adding 17alpha-methyltestosterone (MT) to aquaria containing juveniles of 4 cyprinid species (tinfoil barbs; redtail sharkminnows, Epalzeorhynchos bicolor; goldfish, Carassius auratus; zebrafish, Danio rerio) and then using electro-olfactogram (EOG) recordings and behavioral assays to determine if androgen treatment enhances pheromone detection and male sex behaviors. In all 4 cyprinids, MT treatment increased the magnitudes and sensitivities of EOG response to prostaglandins and, consistent with our initial study on tinfoil barbs, did not affect EOG responses to the free and conjugated steroid to which each species is most sensitive. In zebrafish, EOG responses to prostaglandins were similar in MT-treated juveniles and adult males, whereas responses of control (ethanol exposed) fish were similar to those of adult females. Finally, as previously observed in tinfoil barbs, MT treatment of juvenile redtail sharkminnows increased courtship behaviors (nuzzling and quivering) with a stimulus fish. We conclude that androgen-induced increase in olfactory responsiveness to pheromonal prostaglandins is common among the family Cyprinidae. This phenomenon will help us unravel the development of sexually dimorphic olfactory-mediated behavior.

Training for Night Operations - Research Challenges and Opportunities

DTIC Science & Technology

2012-08-08

Training and Simulation Conference Exhibits and Visuals by Type ……………..……... 1 Figure 2: Radiant Sensitivity of Intensifiers Currently Used in Night Vision...wavelengths across Figure 2. Radiant Sensitivity of Intensifiers the entire radiant sensitivity band. In either case, in order to be Currently...the projector/display technology and NVGs used. NVGs are very sensitive to any light within their band of radiant sensitivity . The intensifier

EWS-FLI1 increases transcription to cause R-loops and block BRCA1 repair in Ewing sarcoma.

PubMed

Gorthi, Aparna; Romero, July Carolina; Loranc, Eva; Cao, Lin; Lawrence, Liesl A; Goodale, Elicia; Iniguez, Amanda Balboni; Bernard, Xavier; Masamsetti, V Pragathi; Roston, Sydney; Lawlor, Elizabeth R; Toretsky, Jeffrey A; Stegmaier, Kimberly; Lessnick, Stephen L; Chen, Yidong; Bishop, Alexander J R

2018-03-15

Ewing sarcoma is an aggressive paediatric cancer of the bone and soft tissue. It results from a chromosomal translocation, predominantly t(11;22)(q24:q12), that fuses the N-terminal transactivation domain of the constitutively expressed EWSR1 protein with the C-terminal DNA binding domain of the rarely expressed FLI1 protein. Ewing sarcoma is highly sensitive to genotoxic agents such as etoposide, but the underlying molecular basis of this sensitivity is unclear. Here we show that Ewing sarcoma cells display alterations in regulation of damage-induced transcription, accumulation of R-loops and increased replication stress. In addition, homologous recombination is impaired in Ewing sarcoma owing to an enriched interaction between BRCA1 and the elongating transcription machinery. Finally, we uncover a role for EWSR1 in the transcriptional response to damage, suppressing R-loops and promoting homologous recombination. Our findings improve the current understanding of EWSR1 function, elucidate the mechanistic basis of the sensitivity of Ewing sarcoma to chemotherapy (including PARP1 inhibitors) and highlight a class of BRCA-deficient-like tumours.

Protein disulfide isomerases: Impact of thapsigargin treatment on their expression in melanoma cell lines.

PubMed

Silva, Zélia; Veríssimo, Teresa; Videira, Paula A; Novo, Carlos

2015-08-01

Anti-cancer treatments usually elevate the content of unfolded or misfolded proteins in the endoplasmic reticulum (ER). Here we aimed to get insights into the relation between sensitivity of melanoma cell lines to the ER stress inducer thapsigargin (THG) and the genetic expression of protein disulfide isomerase family members (PDIs). The expression of PDIs was analysed by flow cytometry and real-time PCR. The results showed that SK-MEL-30, the less THG sensitive cell line, displays higher basal PDIs' expression levels and the sensitivity is increased by the PDIs inhibitor bacitracin. While SK-MEL-30 PDIs' expression is not THG dose-dependent, an increase in glucose related protein 78 (GRP78), PDIA5, PDIA6, and thioredoxin-related-transmembrane proteins' (TMX3 and TMX4) expression, in response to higher drug concentrations, was observed in MNT-1. The differences in PDIs' gene expression in MNT-1 suggest a different response to ER stress compared to the other cell lines and highlight the importance of understanding the diversity among cancer cells. Copyright © 2015 Elsevier B.V. All rights reserved.

Red wine polyphenols increase calcium in bovine aortic endothelial cells: a basis to elucidate signalling pathways leading to nitric oxide production

PubMed Central

Martin, Sophie; Andriambeloson, Emile; Takeda, Ken; Andriantsitohaina, Ramaroson

2002-01-01

The present study investigates the mechanisms by which polyphenolic compounds from red wine elicit Ca2+ mobilization in bovine aortic endothelial cells (BAECs). Two polyphenol-containing red wine extracts, red wine polyphenolic compounds (RWPC) and Provinols™, and delphinidin, an anthocyanin were used. RWPC stimulated a Ca2+-dependent release of nitric oxide (NO) from BAECs accounting for the relaxation of endothelium-denuded rat aortic rings as shown by cascade bioassay. RWPC, Provinols™ and delphinidin increased cytosolic free calcium ([Ca2+]i), by releasing Ca2+ from intracellular stores and by increasing Ca2+ entry. The RWPC-induced increase in [Ca2+]i was decreased by exposure to ryanodine (30 μM), whereas Provinols™ and delphinidin-induced increases in [Ca2+]i were decreased by bradykinin (0.1 μM) and thapsigargin (1 μM) pre-treatment. RWPC, Provinols™ and delphinidin-induced increases in [Ca2+]i were sensitive to inhibitors of phospholipase C (neomycin, 3 mM; U73122, 3 μM) and tyrosine kinase (herbimycin A, 1 μM). RWPC, Provinols™ and delphinidin induced herbimycin A (1 μM)-sensitive tyrosine phosphorylation of several intracellular proteins. Provinols™ released Ca2+ via both a cholera (CTX) and pertussis toxins (PTX)-sensitive pathway, whereas delphinidin released Ca2+ only via a PTX-sensitive mechanism. Our data contribute in defining the mechanisms of endothelial NO production caused by wine polyphenols including the increase in [Ca2+]i and the activation of tyrosine kinases. Furthermore, RWPC, Provinols™ and delphinidin display differences in the process leading to [Ca2+]i increases in endothelial cells illustrating multiple cellular targets of natural dietary polyphenolic compounds. PMID:11906973

A Rationally Designed, General Strategy for Membrane Orientation of Photoinduced Electron Transfer-Based Voltage-Sensitive Dyes.

PubMed

Kulkarni, Rishikesh U; Yin, Hang; Pourmandi, Narges; James, Feroz; Adil, Maroof M; Schaffer, David V; Wang, Yi; Miller, Evan W

2017-02-17

Voltage imaging with fluorescent dyes offers promise for interrogating the complex roles of membrane potential in coordinating the activity of neurons in the brain. Yet, low sensitivity often limits the broad applicability of optical voltage indicators. In this paper, we use molecular dynamics (MD) simulations to guide the design of new, ultrasensitive fluorescent voltage indicators that use photoinduced electron transfer (PeT) as a voltage-sensing switch. MD simulations predict an approximately 16% increase in voltage sensitivity resulting purely from improved alignment of dye with the membrane. We confirm this theoretical finding by synthesizing 9 new voltage-sensitive (VoltageFluor, or VF) dyes and establishing that all of them display the expected improvement of approximately 19%. This synergistic outworking of theory and experiment enabled computational and theoretical estimation of VF dye orientation in lipid bilayers and has yielded the most sensitive PeT-based VF dye to date. We use this new voltage indicator to monitor voltage spikes in neurons from rat hippocampus and human pluripotent-stem-cell-derived dopaminergic neurons.

Carbon nanotube modified probes for stable and high sensitivity conductive atomic force microscopy

NASA Astrophysics Data System (ADS)

Slattery, Ashley D.; Shearer, Cameron J.; Gibson, Christopher T.; Shapter, Joseph G.; Lewis, David A.; Stapleton, Andrew J.

2016-11-01

Conductive atomic force microscopy (C-AFM) is used to characterise the nanoscale electrical properties of many conducting and semiconducting materials. We investigate the effect of single walled carbon nanotube (SWCNT) modification of commercial Pt/Ir cantilevers on the sensitivity and image stability during C-AFM imaging. Pt/Ir cantilevers were modified with small bundles of SWCNTs via a manual attachment procedure and secured with a conductive platinum pad. AFM images of topography and current were collected from heterogeneous polymer and nanomaterial samples using both standard and SWCNT modified cantilevers. Typically, achieving a good current image comes at the cost of reduced feedback stability. In part, this is due to electrostatic interaction and increased tip wear upon applying a bias between the tip and the sample. The SWCNT modified tips displayed superior current sensitivity and feedback stability which, combined with superior wear resistance of SWCNTs, is a significant advancement for C-AFM.

Effect of fibril shape on adhesive properties

NASA Astrophysics Data System (ADS)

Soto, Daniel; Hill, Ginel; Parness, Aaron; Esparza, Noé; Cutkosky, Mark; Kenny, Tom

2010-08-01

Research into the gecko's adhesive system revealed a unique architecture for adhesives using tiny hairs. By using a stiff material (β-keratin) to create a highly structured adhesive, the gecko's system demonstrates properties not seen in traditional pressure-sensitive adhesives which use a soft, unstructured planar layer. In contrast to pressure sensitive adhesives, the gecko adhesive displays frictional adhesion, in which increased shear force allows it to withstand higher normal loads. Synthetic fibrillar adhesives have been fabricated but not all demonstrate this frictional adhesion property. Here we report the dual-axis force testing of single silicone rubber pillars from synthetic adhesive arrays. We find that the shape of the adhesive pillar dictates whether frictional adhesion or pressure-sensitive behavior is observed. This work suggests that both types of behavior can be achieved with structures much larger than gecko terminal structures. It also indicates that subtle differences in the shape of these pillars can significantly influence their properties.

Fiber-optic three axis magnetometer prototype development

NASA Technical Reports Server (NTRS)

Wang, Thomas D.; Mccomb, David G.; Kingston, Bradley R.; Dube, C. Michael; Poehls, Kenneth A.; Wanser, Keith

1989-01-01

The goal of this research program was to develop a high sensitivity, fiber optic, interferometric, three-axis magnetometer for interplanetary spacecraft applications. Dynamics Technology, Inc. (DTI) has successfully integrated a low noise, high bandwidth interferometer with high sensitivity metallic glass transducers. Also, DTI has developed sophisticated signal processing electronics and complete data acquisition, filtering, and display software. The sensor was packaged in a compact, low power and weight unit which facilitates deployment. The magnetic field sensor had subgamma sensitivity and a dynamic range of 10(exp 5) gamma in a 10 Hz bandwidth. Furthermore, the vector instrument exhibited the lowest noise level when only one axis was in operation. A system noise level of 1 gamma rms was observed in a 1 Hz bandwidth. However, with the other two channels operating, the noise level increased by about one order of magnitude. Higher system noise was attributed to cross-channel interference among the dither fields.

Deficient expression of aldehyde dehydrogenase 1A1 is consistent with increased sensitivity of Gorlin syndrome patients to radiation carcinogenesis.

PubMed

Wright, Aaron T; Magnaldo, Thierry; Sontag, Ryan L; Anderson, Lindsey N; Sadler, Natalie C; Piehowski, Paul D; Gache, Yannick; Weber, Thomas J

2015-06-01

Human phenotypes that are highly susceptible to radiation carcinogenesis have been identified. Sensitive phenotypes often display robust regulation of molecular features that modify biological response, which can facilitate identification of the pathways/networks that contribute to pathophysiological outcomes. Here we interrogate primary dermal fibroblasts isolated from Gorlin syndrome patients (GDFs), who display a pronounced inducible tumorigenic response to radiation, in comparison to normal human dermal fibroblasts (NHDFs). Our approach exploits newly developed thiol reactive probes to define changes in protein thiol profiles in live cell studies, which minimizes artifacts associated with cell lysis. Redox probes revealed deficient expression of an apparent 55 kDa protein thiol in GDFs from independent Gorlin syndrome patients, compared with NHDFs. Proteomics tentatively identified this protein as aldehyde dehydrogenase 1A1 (ALDH1A1), a key enzyme regulating retinoic acid synthesis, and ALDH1A1 protein deficiency in GDFs was confirmed by Western blot. A number of additional protein thiol differences in GDFs were identified, including radiation responsive annexin family members and lamin A/C. Collectively, candidates identified in our study have plausible implications for radiation health effects and cancer susceptibility. © 2013 Wiley Periodicals, Inc.

A Study on Attention Guidance to Driver by Subliminal Visual Information

NASA Astrophysics Data System (ADS)

Takahashi, Hiroshi; Honda, Hirohiko

This paper presents a new warning method for increasing drivers' sensitivity for recognizing hazardous factors in the driving environment. The method is based on a subliminal effect. The results of many experiments performed by three dimensional head-mounted display shows that the response time for detecting a flashing mark tended to decrease when a subliminal mark was shown in advance. Priming effects are observed in subliminal visual information. This paper also proposes a scenario for implementing this method in real vehicles.

Analgesia for early-life pain prevents deficits in adult anxiety and stress in rats.

PubMed

Victoria, Nicole C; Karom, Mary C; Murphy, Anne Z

2015-01-01

Previous studies in rats have established that inflammatory pain experienced on the day of birth (P0) decreases sensitivity to acute noxious, anxiety- and stress-provoking stimuli. However, to date, the impact of early-life pain on adult responses to chronic stress is not known. Further, the ability of morphine, administered at the time of injury, to mitigate changes in adult behavioral and hormonal responses to acute or chronic stressors has not been examined. P0 male and female Sprague-Dawley rat pups were given an intraplantar injection of 1% carrageenan or handled in an identical manner in the presence or absence of morphine. As adults, rats that experienced early-life pain displayed decreased sensitivity to acute stressors, as indicated by increased time in the inner area of the Open Field, and increased latency to immobility and decreased time immobile in the Forced Swim Test (FST). An accelerated return of corticosterone to baseline was also observed. Morphine administration at the time of injury completely reversed this 'hyporesponsive' phenotype. By contrast, following 7 days of chronic variable stress, injured animals displayed a 'hyperresponsive' phenotype in that they initiated immobility and spent significantly more time immobile in the FST than controls. Responses to chronic stress were also rescued in animals that received morphine at the time of injury. These data suggest that analgesia for early-life pain prevents adult hyposensitivity to acute anxiety- and stress-provoking stimuli and increased vulnerability to chronic stress, and have important clinical implications for the management of pain in infants. © 2014 S. Karger AG, Basel.

76 FR 35910 - Notice of Receipt of Complaint; Solicitation of Comments Relating to the Public Interest

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-20

... Motion-Sensitive Sound Effects Devices and Image Display Devices and Components and Products Containing... sale within the United States after importation of certain motion- sensitive sound devices and image...

NR2B Expression in Rat DRG Is Differentially Regulated Following Peripheral Nerve Injuries That Lead to Transient or Sustained Stimuli-Evoked Hypersensitivity

PubMed Central

Norcini, Monica; Sideris, Alexandra; Adler, Samantha M.; Hernandez, Lourdes A. M.; Zhang, Jin; Blanck, Thomas J. J.; Recio-Pinto, Esperanza

2016-01-01

Following injury, primary sensory neurons undergo changes that drive central sensitization and contribute to the maintenance of persistent hypersensitivity. NR2B expression in the dorsal root ganglia (DRG) has not been previously examined in neuropathic pain models. Here, we investigated if changes in NR2B expression within the DRG are associated with hypersensitivities that result from peripheral nerve injuries. This was done by comparing the NR2B expression in the DRG derived from two modalities of the spared nerve injury (SNI) model, since each variant produces different neuropathic pain phenotypes. Using the electronic von Frey to stimulate the spared and non-spared regions of the hindpaws, we demonstrated that sural-SNI animals develop sustained neuropathic pain in both regions while the tibial-SNI animals recover. NR2B expression was measured at Day 23 and Day 86 post-injury. At Day 23 and 86 post-injury, sural-SNI animals display strong hypersensitivity, whereas tibial-SNI animals display 50 and 100% recovery from post-injury-induced hypersensitivity, respectively. In tibial-SNI at Day 86, but not at Day 23 the perinuclear region of the neuronal somata displayed an increase in NR2B protein. This retention of NR2B protein within the perinuclear region, which will render them non-functional, correlates with the recovery observed in tibial-SNI. In sural-SNI at Day 86, DRG displayed an increase in NR2B mRNA which correlates with the development of sustained hypersensitivity in this model. The increase in NR2B mRNA was not associated with an increase in NR2B protein within the neuronal somata. The latter may result from a decrease in kinesin Kif17, since Kif17 mediates NR2B transport to the soma’s plasma membrane. In both SNIs, microglia/macrophages showed a transient increase in NR2B protein detected at Day 23 but not at Day 86, which correlates with the initial post-injury induced hypersensitivity in both SNIs. In tibial-SNI at Day 86, but not at Day 23, satellite glia cells (SGCs) displayed an increase in NR2B protein. This study is the first to characterize of cell-specific changes in NR2B expression within the DRG following peripheral nerve injury. We discuss how the observed NR2B changes in DRG can contribute to the different neuropathic pain phenotypes displayed by each SNI variant. PMID:27803647

NR2B Expression in Rat DRG Is Differentially Regulated Following Peripheral Nerve Injuries That Lead to Transient or Sustained Stimuli-Evoked Hypersensitivity.

PubMed

Norcini, Monica; Sideris, Alexandra; Adler, Samantha M; Hernandez, Lourdes A M; Zhang, Jin; Blanck, Thomas J J; Recio-Pinto, Esperanza

2016-01-01

Following injury, primary sensory neurons undergo changes that drive central sensitization and contribute to the maintenance of persistent hypersensitivity. NR2B expression in the dorsal root ganglia (DRG) has not been previously examined in neuropathic pain models. Here, we investigated if changes in NR2B expression within the DRG are associated with hypersensitivities that result from peripheral nerve injuries. This was done by comparing the NR2B expression in the DRG derived from two modalities of the spared nerve injury (SNI) model, since each variant produces different neuropathic pain phenotypes. Using the electronic von Frey to stimulate the spared and non-spared regions of the hindpaws, we demonstrated that sural-SNI animals develop sustained neuropathic pain in both regions while the tibial-SNI animals recover. NR2B expression was measured at Day 23 and Day 86 post-injury. At Day 23 and 86 post-injury, sural-SNI animals display strong hypersensitivity, whereas tibial-SNI animals display 50 and 100% recovery from post-injury-induced hypersensitivity, respectively. In tibial-SNI at Day 86, but not at Day 23 the perinuclear region of the neuronal somata displayed an increase in NR2B protein. This retention of NR2B protein within the perinuclear region, which will render them non-functional, correlates with the recovery observed in tibial-SNI. In sural-SNI at Day 86, DRG displayed an increase in NR2B mRNA which correlates with the development of sustained hypersensitivity in this model. The increase in NR2B mRNA was not associated with an increase in NR2B protein within the neuronal somata. The latter may result from a decrease in kinesin Kif17, since Kif17 mediates NR2B transport to the soma's plasma membrane. In both SNIs, microglia/macrophages showed a transient increase in NR2B protein detected at Day 23 but not at Day 86, which correlates with the initial post-injury induced hypersensitivity in both SNIs. In tibial-SNI at Day 86, but not at Day 23, satellite glia cells (SGCs) displayed an increase in NR2B protein. This study is the first to characterize of cell-specific changes in NR2B expression within the DRG following peripheral nerve injury. We discuss how the observed NR2B changes in DRG can contribute to the different neuropathic pain phenotypes displayed by each SNI variant.

Does prenatal methamphetamine exposure affect the drug-seeking behavior of adult male rats?

PubMed

Slamberová, Romana; Schutová, Barbora; Hrubá, Lenka; Pometlová, Marie

2011-10-10

Methamphetamine (MA) is one of the most frequently used illicit drugs worldwide and also one of the most common drugs abused by pregnant women. Repeated administration of psychostimulants induces behavioral sensitization in response to treatment of the same or related drugs in rodents. The effect of prenatal MA exposure on sensitivity to drugs in adulthood is not yet fully determined. Because our most recent studies demonstrated that prenatal MA (5mg/kg) exposure makes adult rats more sensitive to acute injection of the same drug, we were interested whether the increased sensitivity corresponds with the increased drug-seeking behavior. The aim of the present study was to examine the effect of prenatal MA exposure on drug-seeking behavior of adult male rats tested in the conditioned place preference (CPP). The following psychostimulant drugs were used as a challenge in adulthood: MA (5mg/kg), amphetamine (5mg/kg) and cocaine (10mg/kg). All psychostimulant drugs induced increased drug-seeking behavior in adult male rats. However, while MA and amphetamine-induced increase in drug-seeking behavior did not differ based on the prenatal drug exposure, prenatally MA-exposed rats displayed tolerance effect to cocaine in adulthood. In addition, prenatally MA-exposed rats had decreased weight gain after administration of MA or amphetamine, while the weight of prenatally MA-exposed rats stayed unchanged after cocaine administration. Defecation was increased by all the drugs (MA, amphetamine and cocaine), while only amphetamine increased the tail temperature. In conclusion, our results did not confirm our hypothesis that prenatal MA exposure increases drug-seeking behavior in adulthood in the CPP test. Copyright © 2011 Elsevier B.V. All rights reserved.

Aortic Baroreceptors Display Higher Mechanosensitivity than Carotid Baroreceptors.

PubMed

Lau, Eva On-Chai; Lo, Chun-Yin; Yao, Yifei; Mak, Arthur Fuk-Tat; Jiang, Liwen; Huang, Yu; Yao, Xiaoqiang

2016-01-01

Arterial baroreceptors are mechanical sensors that detect blood pressure changes. It has long been suggested that the two arterial baroreceptors, aortic and carotid baroreceptors, have different pressure sensitivities. However, there is no consensus as to which of the arterial baroreceptors are more sensitive to changes in blood pressure. In the present study, we employed independent methods to compare the pressure sensitivity of the two arterial baroreceptors. Firstly, pressure-activated action potential firing was measured by whole-cell current clamp with a high-speed pressure clamp system in primary cultured baroreceptor neurons. The results show that aortic depressor neurons possessed a higher percentage of mechano-sensitive neurons. Furthermore, aortic baroreceptor neurons show a lower pressure threshold than that of carotid baroreceptor neurons. Secondly, uniaxial stretching of baroreceptor neurons, that mimics the forces exerted on blood vessels, elicited a larger increase in intracellular Ca(2+) rise in aortic baroreceptor neurons than in carotid baroreceptor neurons. Thirdly, the pressure-induced action potential firing in the aortic depressor nerve recorded in vivo was also higher. The present study therefore provides for a basic physiological understanding on the pressure sensitivity of the two baroreceptor neurons and suggests that aortic baroreceptors have a higher pressure sensitivity than carotid baroreceptors.

Thiopurine S-methyltransferase testing for averting drug toxicity: a meta-analysis of diagnostic test accuracy

PubMed Central

Zur, RM; Roy, LM; Ito, S; Beyene, J; Carew, C; Ungar, WJ

2016-01-01

Thiopurine S-methyltransferase (TPMT) deficiency increases the risk of serious adverse events in persons receiving thiopurines. The objective was to synthesize reported sensitivity and specificity of TPMT phenotyping and genotyping using a latent class hierarchical summary receiver operating characteristic meta-analysis. In 27 studies, pooled sensitivity and specificity of phenotyping for deficient individuals was 75.9% (95% credible interval (CrI), 58.3–87.0%) and 98.9% (96.3–100%), respectively. For genotype tests evaluating TPMT*2 and TPMT*3, sensitivity and specificity was 90.4% (79.1–99.4%) and 100.0% (99.9–100%), respectively. For individuals with deficient or intermediate activity, phenotype sensitivity and specificity was 91.3% (86.4–95.5%) and 92.6% (86.5–96.6%), respectively. For genotype tests evaluating TPMT*2 and TPMT*3, sensitivity and specificity was 88.9% (81.6–97.5%) and 99.2% (98.4–99.9%), respectively. Genotyping has higher sensitivity as long as TPMT*2 and TPMT*3 are tested. Both approaches display high specificity. Latent class meta-analysis is a useful method for synthesizing diagnostic test performance data for clinical practice guidelines. PMID:27217052

Non-binary Colour Modulation for Display Device Based on Phase Change Materials.

PubMed

Ji, Hong-Kai; Tong, Hao; Qian, Hang; Hui, Ya-Juan; Liu, Nian; Yan, Peng; Miao, Xiang-Shui

2016-12-19

A reflective-type display device based on phase change materials is attractive because of its ultrafast response time and high resolution compared with a conventional display device. This paper proposes and demonstrates a unique display device in which multicolour changing can be achieved on a single device by the selective crystallization of double layer phase change materials. The optical contrast is optimized by the availability of a variety of film thicknesses of two phase change layers. The device exhibits a low sensitivity to the angle of incidence, which is important for display and colour consistency. The non-binary colour rendering on a single device is demonstrated for the first time using optical excitation. The device shows the potential for ultrafast display applications.

A DsbA-Deficient Periplasm Enables Functional Display of a Protein with Redox-Sensitive Folding on M13 Phage.

PubMed

Chen, Minyong; Samuelson, James C

2016-06-14

The requirements for target protein folding in M13 phage display are largely underappreciated. Here we chose Fbs1, a carbohydrate binding protein, as a model to address this issue. Importantly, folding of Fbs1 is impaired in an oxidative environment. Fbs1 can be displayed on M13 phage using the SRP or Sec pathway. However, the displayed Fbs1 protein is properly folded only when Fbs1 is translocated via the SRP pathway and displayed using Escherichia coli cells with a DsbA-negative periplasm. This study indicates M13 phage display may be improved using a system specifically designed according to the folding requirements of each target protein.

Quantification of color vision using a tablet display.

PubMed

Chacon, Alicia; Rabin, Jeff; Yu, Dennis; Johnston, Shawn; Bradshaw, Timothy

2015-01-01

Accurate color vision is essential for optimal performance in aviation and space environments using nonredundant color coding to convey critical information. Most color tests detect color vision deficiency (CVD) but fail to diagnose type or severity of CVD, which are important to link performance to occupational demands. The computer-based Cone Contrast Test (CCT) diagnoses type and severity of CVD. It is displayed on a netbook computer for clinical application, but a more portable version may prove useful for deployments, space and aviation cockpits, as well as accident and sports medicine settings. Our purpose was to determine if the CCT can be conducted on a tablet display (Windows 8, Microsoft, Seattle, WA) using touch-screen response input. The CCT presents colored letters visible only to red (R), green (G), and blue (B) sensitive retinal cones to determine the lowest R, G, and B cone contrast visible to the observer. The CCT was measured in 16 color vision normals (CVN) and 16 CVDs using the standard netbook computer and a Windows 8 tablet display calibrated to produce equal color contrasts. Both displays showed 100% specificity for confirming CVN and 100% sensitivity for detecting CVD. In CVNs there was no difference between scores on netbook vs. tablet displays. G cone CVDs showed slightly lower G cone CCT scores on the tablet. CVD can be diagnosed with a tablet display. Ease-of-use, portability, and complete computer capabilities make tablets ideal for multiple settings, including aviation, space, military deployments, accidents and rescue missions, and sports vision. Chacon A, Rabin J, Yu D, Johnston S, Bradshaw T. Quantification of color vision using a tablet display.

How to reinforce perception of depth in single two-dimensional pictures

NASA Technical Reports Server (NTRS)

Nagata, S.

1989-01-01

The physical conditions of the display of single 2-D pictures, which produce images realistically, were studied by using the characteristics of the intake of the information for visual depth perception. Depth sensitivity, which is defined as the ratio of viewing distance to depth discrimination threshold, was introduced in order to evaluate the availability of various cues for depth perception: binocular parallax, motion parallax, accommodation, convergence, size, texture, brightness, and air-perspective contrast. The effects of binocular parallax in different conditions, the depth sensitivity of which is greatest at a distance of up to about 10 m, were studied with the new versatile stereoscopic display. From these results, four conditions to reinforce the perception of depth in single pictures were proposed, and these conditions are met by the old viewing devices and the new high-definition and wide television displays.

Stress Sensitivity Is Associated with Differential Accumulation of Reactive Oxygen and Nitrogen Species in Maize Genotypes with Contrasting Levels of Drought Tolerance

PubMed Central

Yang, Liming; Fountain, Jake C.; Wang, Hui; Ni, Xinzhi; Ji, Pingsheng; Lee, Robert D.; Kemerait, Robert C.; Scully, Brian T.; Guo, Baozhu

2015-01-01

Drought stress decreases crop growth, yield, and can further exacerbate pre-harvest aflatoxin contamination. Tolerance and adaptation to drought stress is an important trait of agricultural crops like maize. However, maize genotypes with contrasting drought tolerances have been shown to possess both common and genotype-specific adaptations to cope with drought stress. In this research, the physiological and metabolic response patterns in the leaves of maize seedlings subjected to drought stress were investigated using six maize genotypes including: A638, B73, Grace-E5, Lo964, Lo1016, and Va35. During drought treatments, drought-sensitive maize seedlings displayed more severe symptoms such as chlorosis and wilting, exhibited significant decreases in photosynthetic parameters, and accumulated significantly more reactive oxygen species (ROS) and reactive nitrogen species (RNS) than tolerant genotypes. Sensitive genotypes also showed rapid increases in enzyme activities involved in ROS and RNS metabolism. However, the measured antioxidant enzyme activities were higher in the tolerant genotypes than in the sensitive genotypes in which increased rapidly following drought stress. The results suggest that drought stress causes differential responses to oxidative and nitrosative stress in maize genotypes with tolerant genotypes with slower reaction and less ROS and RNS production than sensitive ones. These differential patterns may be utilized as potential biological markers for use in marker assisted breeding. PMID:26492235

Using genome-wide CRISPR library screening with library resistant DCK to find new sources of Ara-C drug resistance in AML.

PubMed

Kurata, Morito; Rathe, Susan K; Bailey, Natashay J; Aumann, Natalie K; Jones, Justine M; Veldhuijzen, G Willemijn; Moriarity, Branden S; Largaespada, David A

2016-11-03

Acute myeloid leukemia (AML) can display de novo or acquired resistance to cytosine arabinoside (Ara-C), a primary component of induction chemotherapy. To identify genes capable of independently imposing Ara-C resistance, we applied a genome-wide CRISPR library to human U937 cells and exposed to them to Ara-C. Interestingly, all drug resistant clones contained guide RNAs for DCK. To avoid DCK gene modification, gRNA resistant DCK cDNA was created by the introduction of silent mutations. The CRISPR screening was repeated using the gRNA resistant DCK, and loss of SLC29A was identified as also being capable of conveying Ara-C drug resistance. To determine if loss of Dck results in increased sensitivity to other drugs, we conducted a screen of 446 FDA approved drugs using two Dck-defective BXH-2 derived murine AML cell lines and their Ara-C sensitive parental lines. Both cell lines showed an increase in sensitivity to prednisolone. Guide RNA resistant cDNA rescue was a legitimate strategy and multiple DCK or SLC29A deficient human cell clones were established with one clone becoming prednisolone sensitive. Dck-defective leukemic cells may become prednisolone sensitive indicating prednisolone may be an effective adjuvant therapy in some cases of DCK-negative AML.

Improving the color fidelity of cameras for advanced television systems

NASA Astrophysics Data System (ADS)

Kollarits, Richard V.; Gibbon, David C.

1992-08-01

In this paper we compare the accuracy of the color information obtained from television cameras using three and five wavelength bands. This comparison is based on real digital camera data. The cameras are treated as colorimeters whose characteristics are not linked to that of the display. The color matrices for both cameras were obtained by identical optimization procedures that minimized the color error The color error for the five band camera is 2. 5 times smaller than that obtained from the three band camera. Visual comparison of color matches on a characterized color monitor indicate that the five band camera is capable of color measurements that produce no significant visual error on the display. Because the outputs from the five band camera are reduced to the normal three channels conventionally used for display there need be no increase in signal handling complexity outside the camera. Likewise it is possible to construct a five band camera using only three sensors as in conventional cameras. The principal drawback of the five band camera is the reduction in effective camera sensitivity by about 3/4 of an I stop. 1.

Pain sensitivity and tactile spatial acuity are altered in healthy musicians as in chronic pain patients

PubMed Central

Zamorano, Anna M.; Riquelme, Inmaculada; Kleber, Boris; Altenmüller, Eckart; Hatem, Samar M.; Montoya, Pedro

2015-01-01

Extensive training of repetitive and highly skilled movements, as it occurs in professional classical musicians, may lead to changes in tactile sensitivity and corresponding cortical reorganization of somatosensory cortices. It is also known that professional musicians frequently experience musculoskeletal pain and pain-related symptoms during their careers. The present study aimed at understanding the complex interaction between chronic pain and music training with respect to somatosensory processing. For this purpose, tactile thresholds (mechanical detection, grating orientation, two-point discrimination) and subjective ratings to thermal and pressure pain stimuli were assessed in 17 professional musicians with chronic pain, 30 pain-free musicians, 20 non-musicians with chronic pain, and 18 pain-free non-musicians. We found that pain-free musicians displayed greater touch sensitivity (i.e., lower mechanical detection thresholds), lower tactile spatial acuity (i.e., higher grating orientation thresholds) and increased pain sensitivity to pressure and heat compared to pain-free non-musicians. Moreover, we also found that musicians and non-musicians with chronic pain presented lower tactile spatial acuity and increased pain sensitivity to pressure and heat compared to pain-free non-musicians. The significant increment of pain sensitivity together with decreased spatial discrimination in pain-free musicians and the similarity of results found in chronic pain patients, suggests that the extensive training of repetitive and highly skilled movements in classical musicians could be considered as a risk factor for developing chronic pain, probably due to use-dependent plastic changes elicited in somatosensory pathways. PMID:25610384

Countermovement Jump Performance with Increased Training Loads in Elite Female Rugby Athletes.

PubMed

Gathercole, R; Sporer, B; Stellingwerff, T

2015-08-01

Countermovement jump (CMJ) performance is typically analyzed through single-point concentric-based variables (e. g., peak power or force and height). However, methodological approaches examining movement strategies may be more sensitive to neuromuscular fatigue. 12 elite female rugby sevens athletes undertook weekly CMJ testing throughout a 6-week training block involving progressively increased training loads. Athletes self-reported training load (TRIMP) and wellness daily. 22 CMJ variables were assessed, incorporating analyses of force, velocity, power and time measured during eccentric and concentric jump phases. Differences over time were examined using the magnitude of change (effect sizes; ES) compared to baseline. Pearson correlations examined relationships between CMJ variables, wellness and TRIMP. TRIMP displayed large increases (mean ES; weeks 2-6: 2.47). Wellness decreased in week 3 (-0.41), with small reductions following (weeks 4-6: -0.34). Flight time (weeks 3-6: -1.84), peak displacement (weeks 2-6: -2.24), time to peak force (weeks 3-6: 2.58), force at zero velocity (F@0V) (weeks 5-6: -1.28) displayed multiple changes indicative of diminished neuromuscular function. Wellness scores and max rate of force development (mean; r=0.32), F@0V (r=0.28) and flight time (r=0.34) displayed positive correlations. Intensified training decreased CMJ output and altered CMJ mechanics. Longitudinal neuromuscular fatigue monitoring of team-sport athletes appears improved through CMJ mechanics analysis. © Georg Thieme Verlag KG Stuttgart · New York.

Sensitivity to Lateral Information on a Perceptual Word Identification Task in French Third and Fifth Graders

ERIC Educational Resources Information Center

Khelifi, Rachid; Sparrow, Laurent; Casalis, Severine

2012-01-01

This study aimed at examining sensitivity to lateral linguistic and nonlinguistic information in third and fifth grade readers. A word identification task with a threshold was used, and targets were displayed foveally with or without distractors. Sensitivity to lateral information was inferred from the deterioration of the rate of correct word…

The Sensitivity of Precocious Child Writers: More Evidence of the Double-Edged Sword

ERIC Educational Resources Information Center

Edmunds, Alan L.; Edmunds, Gail

2014-01-01

This article provides further evidence of the often observed sensitive nature displayed by children who are gifted. It also addresses the positive and negative effects that this sensitivity can have on these individuals. Earlier, the authors explored this concept through an analysis of the works and life experiences of Geoffrey, aged 9, a prolific…

Differential sensitivity of melanoma cell lines with BRAFV600E mutation to the specific Raf inhibitor PLX4032

PubMed Central

2010-01-01

Blocking oncogenic signaling induced by the BRAFV600E mutation is a promising approach for melanoma treatment. We tested the anti-tumor effects of a specific inhibitor of Raf protein kinases, PLX4032/RG7204, in melanoma cell lines. PLX4032 decreased signaling through the MAPK pathway only in cell lines with the BRAFV600E mutation. Seven out of 10 BRAFV600E mutant cell lines displayed sensitivity based on cell viability assays and three were resistant at concentrations up to 10 μM. Among the sensitive cell lines, four were highly sensitive with IC50 values below 1 μM, and three were moderately sensitive with IC50 values between 1 and 10 μM. There was evidence of MAPK pathway inhibition and cell cycle arrest in both sensitive and resistant cell lines. Genomic analysis by sequencing, genotyping of close to 400 oncogeninc mutations by mass spectrometry, and SNP arrays demonstrated no major differences in BRAF locus amplification or in other oncogenic events between sensitive and resistant cell lines. However, metabolic tracer uptake studies demonstrated that sensitive cell lines had a more profound inhibition of FDG uptake upon exposure to PLX4032 than resistant cell lines. In conclusion, BRAFV600E mutant melanoma cell lines displayed a range of sensitivities to PLX4032 and metabolic imaging using PET probes can be used to assess sensitivity. PMID:20406486

Deficient expression of aldehyde dehydrogenase 1A1 is consistent with increased sensitivity of Gorlin syndrome patients to radiation carcinogenesis

DOE PAGES

Wright, Aaron T.; Magnaldo, Thierry; Sontag, Ryan L.; ...

2013-11-27

Human phenotypes that are highly susceptible to radiation carcinogenesis have been identified. Sensitive phenotypes often display robust regulation of molecular features that modify biological response, which can facilitate identification of relevant pathways/networks. Here we interrogate primary dermal fibroblasts isolated from Gorlin syndrome patients (GDFs), who display a pronounced tumorigenic response to radiation, in comparison to normal human dermal fibroblasts (NHDFs). Our approach exploits newly developed thiol-reactive probes with a flexible click chemistry functional group to define changes in protein thiol profiles in live cell studies, which minimizes artifacts associated with cell lysis. We observe qualitative differences in protein thiol profilesmore » by SDS-PAGE analysis when detection by iodoacetamide vs maleimide probe chemistries are compared, and pretreatment of cells with hydrogen peroxide eliminates detection of the majority of SDS-PAGE bands. Redox probes revealed deficient expression of an apparent 55 kDa protein thiol in GDFs from independent donors, compared with NHDFs. Proteomics tentatively identified this protein as aldehyde dehydrogenase 1A1 (ALDH1A1), a key enzyme regulating retinoic acid synthesis, and this deficiency was confirmed by Western blot. Redox probes revealed additional protein thiol differences between GDFs and NHDFs, including radiation responsive annexin family members. Our results indicate a multifactorial basis for the unusual sensitivity of Gorlin syndrome to radiation carcinogenesis, and the pathways identified have plausible implications for radiation health effects.« less

Deficient expression of aldehyde dehydrogenase 1A1 is consistent with increased sensitivity of Gorlin syndrome patients to radiation carcinogenesis

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

Wright, Aaron T.; Magnaldo, Thierry; Sontag, Ryan L.

Human phenotypes that are highly susceptible to radiation carcinogenesis have been identified. Sensitive phenotypes often display robust regulation of molecular features that modify biological response, which can facilitate identification of relevant pathways/networks. Here we interrogate primary dermal fibroblasts isolated from Gorlin syndrome patients (GDFs), who display a pronounced tumorigenic response to radiation, in comparison to normal human dermal fibroblasts (NHDFs). Our approach exploits newly developed thiol-reactive probes with a flexible click chemistry functional group to define changes in protein thiol profiles in live cell studies, which minimizes artifacts associated with cell lysis. We observe qualitative differences in protein thiol profilesmore » by SDS-PAGE analysis when detection by iodoacetamide vs maleimide probe chemistries are compared, and pretreatment of cells with hydrogen peroxide eliminates detection of the majority of SDS-PAGE bands. Redox probes revealed deficient expression of an apparent 55 kDa protein thiol in GDFs from independent donors, compared with NHDFs. Proteomics tentatively identified this protein as aldehyde dehydrogenase 1A1 (ALDH1A1), a key enzyme regulating retinoic acid synthesis, and this deficiency was confirmed by Western blot. Redox probes revealed additional protein thiol differences between GDFs and NHDFs, including radiation responsive annexin family members. Our results indicate a multifactorial basis for the unusual sensitivity of Gorlin syndrome to radiation carcinogenesis, and the pathways identified have plausible implications for radiation health effects.« less

The hyperthermia mediated by 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy) is sensitive to sex differences

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

Wyeth, Richard P.; Division of Physiology, Virginia College of Osteopathic Medicine, Blacksburg, VA 24060; Mills, Edward M.

Female subjects have been reported to be less sensitive to the hyperthermic effects of 3,4-methylenedioxymethamine (MDMA) than males. Studies were designed to examine the cellular mechanisms involved in these sex sensitive differences. Gonadectomized female and male rats were treated with a 200 {mu}g 100 {mu}L{sup -1} of estrogen or 100 {mu}g 100 {mu}L{sup -1} of testosterone respectively every 5 days for a total of three doses. Rats were then challenged with either saline or MDMA (20 mg kg{sup -1}, sc). Rats were then euthanized and aortas were constricted, in vitro, by serial phenylephrine (Phe) addition with or without the inhibitormore » of nitric oxide (NO) synthase, g-nitro-L-Arginine-Methyl Ester (L-NAME). Skeletal muscle uncoupling protein-3 (UCP3) expression was measured as well as plasma norepinephrine (NE) levels. All males but no females developed hyperthermia following MDMA treatment. The EC{sub 50} for Phe dose response curves increased only in the females treated with MDMA and T{sub max} for Phe increased following L-NAME only in the females. Both males and females demonstrated an increase in plasma NE following MDMA treatment; however, males displayed a significantly greater NE concentration. Skeletal muscle UCP3 expression was 80% less in females than in males. These results suggest that the inability of MDMA to induce a thermogenic response in the female subjects may be due to four sex-specific mechanisms: 1) Female subjects have reduced sympathetic activation following MDMA challenge; 2) Female vasculature is less sensitive to {alpha}{sub 1}-AR stimulation following MDMA challenge; 3) Female vasculature has an increased sensitivity to NO; 4) UCP3 expression in skeletal muscle is less in females.« less

Systemic morphine treatment induces changes in firing patterns and responses of nociceptive afferent fibers in mouse glabrous skin

PubMed Central

Hogan, Dale; Baker, Alyssa L.; Morón, Jose A.; Carlton, Susan M.

2013-01-01

Patients receiving opioids for pain may experience decreased effectiveness of the drug and even abnormal pain sensitivity – either hyperalgesia and/or allodynia. We hypothesize that peripheral nociceptor hyperexcitability contributes to opioid-induced hyperalgesia and test this using an in vitro mouse glabrous skin-nerve preparation. Mice were injected i.p. with escalating doses of morphine (5, 8, 10, 15 mg/kg) or saline every 12 h for 48 h and sacrificed ~12 h following the last injection. Receptive fields of nociceptors were tested for mechanical, heat, and cold sensitivity. Activity was also measured during an initial 2 min period and during 5 min periods between stimuli. Aberrant activity was common in fibers from morphine-treated mice but rare in salinetreated mice. Resting background activity was elevated in C-fibers from morphinetreated mice. Both C- and Aδ -fibers had afterdischarge in response to mechanical, heat and/or cold stimulation of the skin as well as spontaneous, unevoked activity. Compared to saline, morphine treatment increased the proportion of fibers displaying polymodal rather than mechanical-only responses. A significant increase in Aδ-mechanoreceptive fibers responding to cold accounted for most of this change. In agreement with this, morphine-treated mice showed increased sensitivity in the cold tail flick test. In morphine-treated mice, aberrant activity and hyperexcitability of nociceptors could contribute to increased pain sensitivity. Importantly, this activity is likely driving central sensitization, a phenomenon contributing to abnormal sensory processing and chronic pain. If similar changes occur in human patients, aberrant nociceptor activity is likely to be interpreted as pain, and could contribute to opioid-induced hyperalgesia. PMID:23711478

Contrast sensitivity function in stereoscopic viewing of Gabor patches on a medical polarized three-dimensional stereoscopic display

NASA Astrophysics Data System (ADS)

Rousson, Johanna; Haar, Jérémy; Santal, Sarah; Kumcu, Asli; Platiša, Ljiljana; Piepers, Bastian; Kimpe, Tom; Philips, Wilfried

2016-03-01

While three-dimensional (3-D) imaging systems are entering hospitals, no study to date has explored the luminance calibration needs of 3-D stereoscopic diagnostic displays and if they differ from two-dimensional (2-D) displays. Since medical display calibration incorporates the human contrast sensitivity function (CSF), we first assessed the 2-D CSF for benchmarking and then examined the impact of two image parameters on the 3-D stereoscopic CSF: (1) five depth plane (DP) positions (between DP: -171 and DP: 2853 mm), and (2) three 3-D inclinations (0 deg, 45 deg, and 60 deg around the horizontal axis of a DP). Stimuli were stereoscopic images of a vertically oriented 2-D Gabor patch at one of seven frequencies ranging from 0.4 to 10 cycles/deg. CSFs were measured for seven to nine human observers with a staircase procedure. The results indicate that the 2-D CSF model remains valid for a 3-D stereoscopic display regardless of the amount of disparity between the stereo images. We also found that the 3-D CSF at DP≠0 does not differ from the 3-D CSF at DP=0 for DPs and disparities which allow effortless binocular fusion. Therefore, the existing 2-D medical luminance calibration algorithm remains an appropriate tool for calibrating polarized stereoscopic medical displays.

Mismatched summation mechanisms in older adults for the perception of small moving stimuli.

PubMed

McDougall, Thomas J; Nguyen, Bao N; McKendrick, Allison M; Badcock, David R

2018-01-01

Previous studies have found evidence for reduced cortical inhibition in aging visual cortex. Reduced inhibition could plausibly increase the spatial area of excitation in receptive fields of older observers, as weaker inhibitory processes would allow the excitatory receptive field to dominate and be psychophysically measureable over larger areas. Here, we investigated aging effects on spatial summation of motion direction using the Battenberg summation method, which aims to control the influence of locally generated internal noise changes by holding overall display size constant. This method produces more accurate estimates of summation area than conventional methods that simply increase overall stimulus dimensions. Battenberg stimuli have a checkerboard arrangement, where check size (luminance-modulated drifting gratings alternating with mean luminance areas), but not display size, is varied and compared with performance for a full field stimulus to provide a measure of summation. Motion direction discrimination thresholds, where contrast was the dependent variable, were measured in 14 younger (24-34 years) and 14 older (62-76 years) adults. Older observers were less sensitive for all check sizes, but the relative sensitivity across sizes, also differed between groups. In the older adults, the full field stimulus offered smaller performance improvements compared to that for younger adults, specifically for the small checked Battenberg stimuli. This suggests aging impacts on short-range summation mechanisms, potentially underpinned by larger summation areas for the perception of small moving stimuli. Copyright © 2017 Elsevier Ltd. All rights reserved.

A comparison of kinesthetic-tactual and visual displays via a critical tracking task. [for aircraft control

NASA Technical Reports Server (NTRS)

Jagacinski, R. J.; Miller, D. P.; Gilson, R. D.

1979-01-01

The feasibility of using the critical tracking task to evaluate kinesthetic-tactual displays was examined. The test subjects were asked to control a first-order unstable system with a continuously decreasing time constant by using either visual or tactual unidimensional displays. The results indicate that the critical tracking task is both a feasible and a reliable methodology for assessing tactual tracking. Further, that the critical tracking methodology is as sensitive and valid a measure of tactual tracking as visual tracking is demonstrated by the approximately equal effects of quickening for the tactual and visual displays.

Reward sensitivity predicts ice cream-related attentional bias assessed by inattentional blindness.

PubMed

Li, Xiaoming; Tao, Qian; Fang, Ya; Cheng, Chen; Hao, Yangyang; Qi, Jianjun; Li, Yu; Zhang, Wei; Wang, Ying; Zhang, Xiaochu

2015-06-01

The cognitive mechanism underlying the association between individual differences in reward sensitivity and food craving is unknown. The present study explored the mechanism by examining the role of reward sensitivity in attentional bias toward ice cream cues. Forty-nine college students who displayed high level of ice cream craving (HICs) and 46 who displayed low level of ice cream craving (LICs) performed an inattentional blindness (IB) task which was used to assess attentional bias for ice cream. In addition, reward sensitivity and coping style were assessed by the Behavior Inhibition System/Behavior Activation System Scales and Simplified Coping Style Questionnaire. Results showed significant higher identification rate of the critical stimulus in the HICs than LICs, suggesting greater attentional bias for ice cream in the HICs. It was indicated that attentional bias for food cues persisted even under inattentional condition. Furthermore, a significant correlation was found between the attentional bias and reward sensitivity after controlling for coping style, and reward sensitivity predicted attentional bias for food cues. The mediation analyses showed that attentional bias mediated the relationship between reward sensitivity and food craving. Those findings suggest that the association between individual differences in reward sensitivity and food craving may be attributed to attentional bias for food-related cues. Copyright © 2015 Elsevier Ltd. All rights reserved.

Cold hypersensitivity increases with age in mice with sickle cell disease.

PubMed

Zappia, Katherine J; Garrison, Sheldon R; Hillery, Cheryl A; Stucky, Cheryl L

2014-12-01

Sickle cell disease (SCD) is associated with acute vaso-occlusive crises that trigger painful episodes and frequently involves ongoing, chronic pain. In addition, both humans and mice with SCD experience heightened cold sensitivity. However, studies have not addressed the mechanism(s) underlying the cold sensitization or its progression with age. Here we measured thermotaxis behavior in young and aged mice with severe SCD. Sickle mice had a marked increase in cold sensitivity measured by a cold preference test. Furthermore, cold hypersensitivity worsened with advanced age. We assessed whether enhanced peripheral input contributes to the chronic cold pain behavior by recording from C fibers, many of which are cold sensitive, in skin-nerve preparations. We observed that C fibers from sickle mice displayed a shift to warmer (more sensitive) cold detection thresholds. To address mechanisms underlying the cold sensitization in primary afferent neurons, we quantified mRNA expression levels for ion channels thought to be involved in cold detection. These included the transient receptor potential melastatin 8 (Trpm8) and transient receptor potential ankyrin 1 (Trpa1) channels, as well as the 2-pore domain potassium channels, TREK-1 (Kcnk2), TREK-2 (Kcnk10), and TRAAK (Kcnk4). Surprisingly, transcript expression levels of all of these channels were comparable between sickle and control mice. We further examined transcript expression of 83 additional pain-related genes, and found increased mRNA levels for endothelin 1 and tachykinin receptor 1. These factors may contribute to hypersensitivity in sickle mice at both the afferent and behavioral levels. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

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.

Added value of Virtual Touch IQ shear wave elastography in the ultrasound assessment of breast lesions.

PubMed

Ianculescu, Victor; Ciolovan, Laura Maria; Dunant, Ariane; Vielh, Philippe; Mazouni, Chafika; Delaloge, Suzette; Dromain, Clarisse; Blidaru, Alexandru; Balleyguier, Corinne

2014-05-01

To determine the diagnostic performance of Acoustic Radiation Force Impulse (ARFI) Virtual Touch IQ shear wave elastography in the discrimination of benign and malignant breast lesions. Conventional B-mode and elasticity imaging were used to evaluate 110 breast lesions. Elastographic assessment of breast tissue abnormalities was done using a shear wave based technique, Virtual Touch IQ (VTIQ), implemented on a Siemens Acuson S3000 ultrasound machine. Tissue mechanical properties were interpreted as two-dimensional qualitative and quantitative colour maps displaying relative shear wave velocity. Wave speed measurements in m/s were possible at operator defined regions of interest. The pathologic diagnosis was established on samples obtained by ultrasound guided core biopsy or fine needle aspiration. BIRADS based B-mode evaluation of the 48 benign and 62 malignant lesions achieved 92% sensitivity and 62.5% specificity. Subsequently performed VTIQ elastography relying on visual interpretation of the colour overlay displaying relative shear wave velocities managed similar standalone diagnostic performance with 92% sensitivity and 64.6% specificity. Lesion and surrounding tissue shear wave speed values were calculated and a significant difference was found between the benign and malignant populations (Mann-Whitney U test, p<0.0001). By selecting a lesion cut-off value of 3.31m/s we achieved 80.4% sensitivity and 73% specificity. Applying this threshold only to BIRADS 4a masses, we reached overall levels of 92% sensitivity and 72.9% specificity. VTIQ qualitative and quantitative elastography has the potential to further characterise B-mode detected breast lesions, increasing specificity and reducing the number of unnecessary biopsies. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

High expression of TROP2 characterizes different cell subpopulations in androgen-sensitive and androgen-independent prostate cancer cells.

PubMed

Xie, Jinhan; Mølck, Christina; Paquet-Fifield, Sophie; Butler, Lisa; Sloan, Erica; Ventura, Sabatino; Hollande, Frédéric

2016-07-12

Progression of castration-resistant tumors is frequent in prostate cancer. Current systemic treatments for castration-resistant prostate cancer only produce modest increases in survival time and self-renewing Tumor-Initiating Cells (TICs) are suspected to play an important role in resistance to these treatments. However it remains unclear whether the same TICs display both chemo-resistance and self-renewing abilities throughout progression from early stage lesions to late, castration resistant tumors. Here, we found that treatment of mice bearing LNCaP-derived xenograft tumors with cytotoxic (docetaxel) and anti-androgen (flutamide) compounds enriched for cells that express TROP2, a putative TIC marker. Consistent with a tumor-initiating role, TROP2high cells from androgen-sensitive prostate cancer cell lines displayed an enhanced ability to re-grow in culture following treatment with taxane-based chemotherapy with or without androgen blockade. TROP2 down-regulation in these cells reduced their ability to recur after treatment with docetaxel, in the presence or absence of flutamide. Accordingly, in silico analysis of published clinical data revealed that prostate cancer patients with poor prognosis exhibit significantly elevated TROP2 expression level compared to low-risk patients, particularly in the case of patients diagnosed with early stage tumors. In contrast, in androgen-independent prostate cancer cell lines, TROP2high cells did not exhibit a differential treatment response but were characterized by their high self-renewal ability. Based on these findings we propose that high TROP2 expression identifies distinct cell sub-populations in androgen-sensitive and androgen-independent prostate tumors and that it may be a predictive biomarker for prostate cancer treatment response in androgen-sensitive tumors.

Increased thermal pain sensitivity in animals exposed to chronic high dose Vicodin but not pure hydrocodone.

PubMed

O'Connell, Thomas F; Carpenter, Patrick S; Caballero, Nadia; Putnam, Andrew J; Steere, Joshua T; Matz, Gregory J; Foecking, Eileen M

2014-01-01

Vicodin, the combination drug of acetaminophen and the opioid hydrocodone, is one of the most prescribed drugs on the market today. Opioids have demonstrated the ability to paradoxically cause increased pain sensitivity to users in a phenomena called opioid-induced hyperalgesia (OIH). While selected opioids have been shown to produce OIH symptoms in an animal model, hydrocodone and the combination drug Vicodin have yet to be studied. The purpose of this study was to explore the effect of exposure to chronic high dose Vicodin or its components on the sensitivity to both thermal and mechanical pain. Animals were randomly divided into 4 groups, Vicodin, acetaminophen, hydrocodone, or vehicle control, and administered the drug daily for 120 days. Rats were subsequently tested for thermal and mechanical sensitivity. The rats in the Vicodin group displayed a significant decrease in withdrawal time to thermal pain. The rats receiving acetaminophen, hydrocodone, and vehicle showed no statistically significant hypersensitivity in thermal testing. None of the groups demonstrated statistically significant hypersensitivity to mechanical testing. The data suggests Vicodin produces signs of OIH in a rodent model. However, increased pain sensitivity was only noted in the thermal pathway and the hypersensitivity was only seen with the opioid combination drug, not the opioid alone. The results of this study both support the results of previous rodent opioid studies while generating further questions about the specific properties of Vicodin that contribute to pain hypersensitivity. The growing use of Vicodin to treat chronic pain necessitates further research looking into this paradoxical pain response.

Susceptibility of vancomycin-resistant and -sensitive Enterococcus faecium obtained from Danish hospitals to benzalkonium chloride, chlorhexidine and hydrogen peroxide biocides.

PubMed

Alotaibi, Sulaiman M I; Ayibiekea, Alafate; Pedersen, Annemette Frøling; Jakobsen, Lotte; Pinholt, Mette; Gumpert, Heidi; Hammerum, Anette M; Westh, Henrik; Ingmer, Hanne

2017-12-01

In Danish hospitals, the number of infections caused by vancomycin-resistant Enterococcus faecium (VRE faecium) has dramatically increased in recent years. Hospital disinfectants are essential in eliminating pathogenic microorganisms, and reduced susceptibility may contribute to hospital-associated infections. We have addressed whether clinical VRE faecium display decreased biocide susceptibility when compared to vancomycin-sensitive Enterococcus faecium (VSE faecium) isolates. In total 12 VSE faecium and 37 VRE faecium isolates obtained from Danish hospitals over an extended time period were tested for susceptibility towards three commonly applied biocides, namely benzalkonium chloride, chlorhexidine and hydrogen peroxide. For benzalkonium chloride, 89 % of VRE faecium strains had a minimal inhibitory concentration (MIC) of 8 mg l -1 , whereas for VSE faecium, only 25 % of the strains had an MIC of 8 mg l -1 . For chlorhexidine, the MIC of 95 % of VRE faecium strains was 4 mg l -1 or higher, while only 33 % of VSE faecium strains displayed MIC values at the same level. In contrast, both VRE and VSE faecium displayed equal susceptibility to hydrogen peroxide, but a higher minimal bactericidal concentration (MBC) was found for the former. The efflux activity was also assessed, and this was generally higher for the VRE faecium strains compared to VSE faecium. VRE faecium from Danish hospitals demonstrated decreased susceptibility towards benzalkonium chloride and chlorhexidine compared to VSE faecium, where the use of chlorhexidine is particularly heavy in the hospital environment. These findings suggest that biocide tolerance may characterize VRE faecium isolated in Danish hospitals.

Effects of Iron Depletion on CALM-AF10 Leukemias

PubMed Central

Heath, Jessica L.; Weiss, Joshua M.

2014-01-01

Iron, an essential nutrient for cellular growth and proliferation, enters cells via clathrin-mediated endocytosis (CME). The clathrin assembly lymphoid myeloid (CALM) protein plays an essential role in the cellular import of iron by CME. CALM-AF10 leukemias harbor a single copy of the normal CALM gene, and may therefore be more sensitive to the growth inhibitory effect of iron restriction compared with normal hematopoietic cells. We found that Calm heterozygous (CalmHET) murine fibroblasts exhibit signs of iron deficiency, with increased surface transferrin receptor (sTfR) levels and reduced growth rates. CalmHET hematopoietic cells are more sensitive in vitro to iron chelators than their wild type counterparts. Iron chelation also displayed toxicity towards cultured CalmHET CALM-AF10 leukemia cells and this effect was additive to that of chemotherapy. In mice transplanted with CalmHET CALM-AF10 leukemia, we found that dietary iron restriction reduces tumor burden in the spleen. However, dietary iron restriction, used alone or in conjunction with chemotherapy, did not increase survival of mice with CalmHET CALM-AF10 leukemia. In summary, while Calm heterozygosity results in iron deficiency and increased sensitivity to iron chelation in vitro, our data in mice do not suggest that iron depletion strategies would be beneficial for the therapy of CALM-AF10 leukemia patients. PMID:25193880

Development of high sensitivity and high speed large size blank inspection system LBIS

NASA Astrophysics Data System (ADS)

Ohara, Shinobu; Yoshida, Akinori; Hirai, Mitsuo; Kato, Takenori; Moriizumi, Koichi; Kusunose, Haruhiko

2017-07-01

The production of high-resolution flat panel displays (FPDs) for mobile phones today requires the use of high-quality large-size photomasks (LSPMs). Organic light emitting diode (OLED) displays use several transistors on each pixel for precise current control and, as such, the mask patterns for OLED displays are denser and finer than the patterns for the previous generation displays throughout the entire mask surface. It is therefore strongly demanded that mask patterns be produced with high fidelity and free of defect. To enable the production of a high quality LSPM in a short lead time, the manufacturers need a high-sensitivity high-speed mask blank inspection system that meets the requirement of advanced LSPMs. Lasertec has developed a large-size blank inspection system called LBIS, which achieves high sensitivity based on a laser-scattering technique. LBIS employs a high power laser as its inspection light source. LBIS's delivery optics, including a scanner and F-Theta scan lens, focus the light from the source linearly on the surface of the blank. Its specially-designed optics collect the light scattered by particles and defects generated during the manufacturing process, such as scratches, on the surface and guide it to photo multiplier tubes (PMTs) with high efficiency. Multiple PMTs are used on LBIS for the stable detection of scattered light, which may be distributed at various angles due to irregular shapes of defects. LBIS captures 0.3mμ PSL at a detection rate of over 99.5% with uniform sensitivity. Its inspection time is 20 minutes for a G8 blank and 35 minutes for G10. The differential interference contrast (DIC) microscope on the inspection head of LBIS captures high-contrast review images after inspection. The images are classified automatically.

A novel helper phage enabling construction of genome-scale ORF-enriched phage display libraries.

PubMed

Gupta, Amita; Shrivastava, Nimisha; Grover, Payal; Singh, Ajay; Mathur, Kapil; Verma, Vaishali; Kaur, Charanpreet; Chaudhary, Vijay K

2013-01-01

Phagemid-based expression of cloned genes fused to the gIIIP coding sequence and rescue using helper phages, such as VCSM13, has been used extensively for constructing large antibody phage display libraries. However, for randomly primed cDNA and gene fragment libraries, this system encounters reading frame problems wherein only one of 18 phages display the translated foreign peptide/protein fused to phagemid-encoded gIIIP. The elimination of phages carrying out-of-frame inserts is vital in order to improve the quality of phage display libraries. In this study, we designed a novel helper phage, AGM13, which carries trypsin-sensitive sites within the linker regions of gIIIP. This renders the phage highly sensitive to trypsin digestion, which abolishes its infectivity. For open reading frame (ORF) selection, the phagemid-borne phages are rescued using AGM13, so that clones with in-frame inserts express fusion proteins with phagemid-encoded trypsin-resistant gIIIP, which becomes incorporated into the phages along with a few copies of AGM13-encoded trypsin-sensitive gIIIP. In contrast, clones with out-of-frame inserts produce phages carrying only AGM13-encoded trypsin-sensitive gIIIP. Trypsin treatment of the phage population renders the phages with out-of-frame inserts non-infectious, whereas phages carrying in-frame inserts remain fully infectious and can hence be enriched by infection. This strategy was applied efficiently at a genome scale to generate an ORF-enriched whole genome fragment library from Mycobacterium tuberculosis, in which nearly 100% of the clones carried in-frame inserts after selection. The ORF-enriched libraries were successfully used for identification of linear and conformational epitopes for monoclonal antibodies specific to mycobacterial proteins.

OVA-induced airway hyperresponsiveness alters murine heart rate variability and body temperature.

PubMed

Domnik, N J; Seaborn, G; Vincent, S G; Akl, S G; Redfearn, D P; Fisher, J T

2012-01-01

Altered autonomic (ANS) tone in chronic respiratory disease is implicated as a factor in cardiovascular co-morbidities, yet no studies address its impact on cardiovascular function in the presence of murine allergic airway (AW) hyperresponsiveness (AHR). Since antigen (Ag)-induced AHR is used to model allergic asthma (in which ANS alterations have been reported), we performed a pilot study to assess measurement feasibility of, as well as the impact of allergic sensitization to ovalbumin (OVA) on, heart rate variability (HRV) in a murine model. Heart rate (HR), body temperature (T(B)), and time- and frequency-domain HRV analyses, a reflection of ANS control, were obtained in chronically instrumented mice (telemetry) before, during and for 22 h after OVA or saline aerosolization in sensitized (OVA) or Alum adjuvant control exposed animals. OVA mice diverged significantly from Alum mice with respect to change in HR during aerosol challenge (P < 0.001, Two-Way ANOVA; HR max change Ctrl = +80 ± 10 bpm vs. OVA = +1 ± 23 bpm, mean ± SEM), and displayed elevated HR during the subsequent dark cycle (P = 0.006). Sensitization decreased the T(B) during aerosol challenge (P < 0.001). Sensitized mice had decreased HRV prior to challenge (SDNN: P = 0.038; Low frequency (LF) power: P = 0.021; Low/high Frequency (HF) power: P = 0.042), and increased HRV during Ag challenge (RMSSD: P = 0.047; pNN6: P = 0.039). Sensitized mice displayed decreased HRV subsequent to OVA challenge, primarily in the dark cycle (RMSSD: P = 0.018; pNN6: P ≤ 0.001; LF: P ≤ 0.001; HF: P = 0.040; LF/HF: P ≤ 0.001). We conclude that implanted telemetry technology is an effective method to assess the ANS impact of allergic sensitization. Preliminary results show mild sensitization is associated with reduced HRV and a suppression of the acute T(B)-response to OVA challenge. This approach to assess altered ANS control in the acute OVA model may also be beneficial in chronic AHR models.

THE PRODUCTION OF ERYTHROCYTE AUTOANTIBODIES IN CHIMPANZEES

PubMed Central

Zmijewski, Chester M.

1965-01-01

Young adult chimpanzees immunized with human blood products produced circulating antibodies which reacted with human red cells of a certain proportion of chimpanzees. In addition, agglutinins were formed which reacted with the animals' own erythrocytes. That these agglutinins were true autoantibodies was demonstrated by: (a) their ability to sensitize the animals' own erythrocytes at 37°C both in vivo and in intro; (b) the iso-specificity which they displayed toward other chimpanzee red cells; and (c) the fact that they belonged to the γG-class of immunoglobulins. Complement appeared to be bound to the in vivo sensitized cells but no evidence of increased cell destruction was observed. It seemed most likely that these autoagglutinins were produced as a result of active immunization with closely related antigens. PMID:14278223

Reduced dopamine and glutamate neurotransmission in the nucleus accumbens of quinpirole-sensitized rats hints at inhibitory D2 autoreceptor function.

PubMed

Escobar, Angélica P; Cornejo, Francisca A; Olivares-Costa, Montserrat; González, Marcela; Fuentealba, José A; Gysling, Katia; España, Rodrigo A; Andrés, María E

2015-09-01

Dopamine from the ventral tegmental area and glutamate from several brain nuclei converge in the nucleus accumbens (NAc) to drive motivated behaviors. Repeated activation of D2 receptors with quinpirole (QNP) induces locomotor sensitization and compulsive behaviors, but the mechanisms are unknown. In this study, in vivo microdialysis and fast scan cyclic voltammetry in adult anesthetized rats were used to investigate the effect of repeated QNP on dopamine and glutamate neurotransmission within the NAc. Following eight injections of QNP, a significant decrease in phasic and tonic dopamine release was observed in rats that displayed locomotor sensitization. Either a systemic injection or the infusion of QNP into the NAc decreased dopamine release, and the extent of this effect was similar in QNP-sensitized and control rats, indicating that inhibitory D2 autoreceptor function is maintained despite repeated activation of D2 receptors and decreased dopamine extracellular levels. Basal extracellular levels of glutamate in the NAc were also significantly lower in QNP-treated rats than in controls. Moreover, the increase in NAc glutamate release induced by direct stimulation of medial prefrontal cortex was significantly lower in QNP-sensitized rats. Together, these results indicate that repeated activation of D2 receptors disconnects NAc from medial prefrontal cortex and ventral tegmental area. Repeated administration of the dopamine D2 receptor agonist quinpirole (QNP) induces locomotor sensitization. We found that the NAc of QNP-sensitized rats has reduced glutamate levels coming from prefrontal cortex together with a decreased phasic and tonic dopamine neurotransmission but a conserved presynaptic D2 receptor function. We suggest that locomotor sensitization is because of increased affinity state of D2 post-synaptic receptors. © 2015 International Society for Neurochemistry.

Ethical sensitivity in obsessive-compulsive disorder and generalized anxiety disorder: the role of reversal learning.

PubMed

Szabó, Csilla; Németh, Attila; Kéri, Szabolcs

2013-12-01

In obsessive-compulsive disorder (OCD), amplified moral sensitivity may be related to the orbitofrontal-striatal circuit, which is also critical in reversal learning. This study examined three questions: (1) What aspects of ethical sensitivity is altered in OCD?; (2) What is the relationship between ethical sensitivity and reversal learning?; (3) Are potential alterations in ethical sensitivity and reversal learning present in generalized anxiety disorder (GAD)? Participants were 28 outpatients with OCD, 21 individuals with GAD, and 30 matched healthy controls. Participants received the ethical sensitivity scale questionnaire (ESSQ), rating scales for clinical symptoms, a reversal learning task, and the Wisconsin Card Sorting Test (WCST). We found higher ethical sensitivity scores in OCD compared with healthy controls in the case of generating interpretations and options and identifying the consequences of actions. Individuals with OCD displayed prolonged reaction times on probabilistic errors without shift and final reversal errors. Participants with GAD did not differ from healthy controls on the ESSQ, but they were slower on reversal learning relative to nonpatients. In OCD, reaction time on final reversal errors mediated the relationship between ethical sensitivity and compulsions. WCST performance was intact in OCD and GAD. Small sample size, limited neuropsychological assessment, self-rating scale for ethical sensitivity. Prolonged reaction time at switching reinforcement contingencies is related to increased ethical sensitivity in OCD. Slow affective switching may link ethical sensitivity and compulsions. Copyright © 2013 Elsevier Ltd. All rights reserved.

Child and parent predictors of picky eating from preschool to school age.

PubMed

Steinsbekk, Silje; Bonneville-Roussy, Arielle; Fildes, Alison; Llewellyn, Clare H; Wichstrøm, Lars

2017-07-06

Picky eating is prevalent in childhood. Because pickiness concerns parents and is associated with nutrient deficiency and psychological problems, the antecedents of pickiness need to be identified. We propose an etiological model of picky eating involving child temperament, sensory sensitivity and parent-child interaction. Two cohorts of 4-year olds (born 2003 or 2004) in Trondheim, Norway were invited to participate (97.2% attendance; 82.0% consent rate, n = 2475) and a screen-stratified subsample of 1250 children was recruited. We interviewed 997 parents about their child's pickiness and sensory sensitivity using the Preschool Age Psychiatric Assessment (PAPA). Two years later, 795 of the parents completed the interview. The Children's Behavior Questionnaire (CBQ) was used to assess children's temperament. Parent- child interactions were videotaped and parental sensitivity (i.e., parental awareness and appropriate responsiveness to children's verbal and nonverbal cues) and structuring were rated using the Emotional Availability Scales (EAS). At both measurement times, 26% of the children were categorized as picky eaters. Pickiness was moderately stable from preschool to school age (OR = 5.92, CI = 3.95, 8.86), and about half of those who displayed pickiness at age 4 were also picky eaters two years later. While accounting for pickiness at age 4, sensory sensitivity at age 4 predicted pickiness at age 6 (OR = 1.25, CI = 1.08, 2.23), whereas temperamental surgency (OR = 0.88, CI = 0.64, 1.22) and negative affectivity (OR = 1.17, CI = 0.75, 1.84) did not. Parental structuring was found to reduce the risk of children's picky eating two years later (OR = 0.90, CI = 0.82, 0.99), whereas parental sensitivity increased the odds for pickiness (OR = 1.10, CI = 1.00, 1.21). Although pickiness is stable from preschool to school age, children who are more sensory sensitive are at higher risk for pickiness two years later, as are children whose parents display relatively higher levels of sensitivity and lower levels of structuring. Our findings suggest that interventions targeting children's sensory sensitivity, as well as parental sensitivity and structuring, might reduce the risk of childhood pickiness. Health care providers should support parents of picky eaters in repeatedly offering unfamiliar and rejected foods to their children without pressure and acknowledging child autonomy.

Fluorescent Microscopy Enhancement Using Imaging

NASA Astrophysics Data System (ADS)

Conrad, Morgan P.; Reck tenwald, Diether J.; Woodhouse, Bryan S.

1986-06-01

To enhance our capabilities for observing fluorescent stains in biological systems, we are developing a low cost imaging system based around an IBM AT microcomputer and a commercial image capture board compatible with a standard RS-170 format video camera. The image is digitized in real time with 256 grey levels, while being displayed and also stored in memory. The software allows for interactive processing of the data, such as histogram equalization or pseudocolor enhancement of the display. The entire image, or a quadrant thereof, can be averaged over time to improve the signal to noise ratio. Images may be stored to disk for later use or comparison. The camera may be selected for better response in the UV or near IR. Combined with signal averaging, this increases the sensitivity relative to that of the human eye, while still allowing for the fluorescence distribution on either the surface or internal cytoskeletal structure to be observed.

Ratiometric near infrared luminescent thermometer based on lanthanide metal-organic frameworks

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

Yue, Dan; Zhang, Jun; Zhao, Dian

2016-09-15

A near infrared luminescent MOFs thermometer (Nd{sub 0.676}Yb{sub 0.324}BTC) was prepared via a simple solvothermal method using Ln{sup 3+} (Ln=Nd, Yb) ions and 1, 3, 5-benznenetricarboxylic acid (H{sub 3}BTC), and characterized by PXRD, TGA, ICP, and photoluminescence (PL) spectrum. These results indicate that the Nd{sub 0.676}Yb{sub 0.324}BTC displays high relative sensitivity and excellent repeatability in the physiological temperature range (288–323 K), and the maximum relative sensitivity is determined to be 1.187% K{sup −1} at 323 K. These NIR luminescent MOFs may have potential applications in physiological temperature sensing. - Graphical abstract: A near infrared luminescent MOFs thermometer (Nd{sub 0.054}Yb{sub 0.946}BTCmore » ) displays high relative sensitivity and excellent repeatability in the physiological temperature range (288–323 K). Display Omitted - Highlights: • A ratiometric near infrared luminescent MOFs thermometer (Nd{sub 0.676}Yb{sub 0.324}BTC) was prepared via a simple solvothermal method. • The maximum relative sensitivity of Nd{sub 0.676}Yb{sub 0.324}BTC is determined to be 1.187% K{sup −1} at 323 K. • Nd{sub 0.676}Yb{sub 0.324}BTC showed excellent repeatability in the physiological temperature range (288–323 K).« less

Parent ratings of executive functioning in children with shunted hydrocephalus.

PubMed

Lacy, Maureen; Baldassarre, Megan; Nader, Todd; Frim, David

2012-01-01

The present study examined the executive functioning of a group of children with a history of communicating hydrocephalus and how their level of functioning was correlated with parent ratings of executive functioning. The study examined the executive functioning of 39 shunted children with a history of hydrocephalus and 20 healthy peers. Additionally, parents of both groups of children completed the Behavior Rating Inventory of Executive Function (BRIEF) to assess the parents' perceptions of their children's executive functioning. Finally, the study investigated the relationship between the shunted hydrocephalus children's executive functioning and the parent ratings of their executive functioning. Overall, the children with a history of shunted hydrocephalus displayed more executive dysfunction than their healthy peers. These children were rated by their parents as having more executive dysfunction than their healthy peers and displaying working memory, initiation, mental flexibility and self-monitoring difficulties, which appear to increase with age among the shunted hydrocephalus group. While parent ratings as measured by the BRIEF indices did not correlate with all executive tasks within the shunted hydrocephalus group, the cognitive tests assessing mental flexibility may be sensitive to the problems noted by parents at home. The children with a history of shunted hydrocephalus displayed executive functioning deficits on formal examination. The parents of children with a history of shunted hydrocephalus report ongoing executive difficulties which may increase with age. Copyright © 2012 S. Karger AG, Basel.

Effect of varying displays and room illuminance on caries diagnostic accuracy in digital dental radiographs.

PubMed

Pakkala, T; Kuusela, L; Ekholm, M; Wenzel, A; Haiter-Neto, F; Kortesniemi, M

2012-01-01

In clinical practice, digital radiographs taken for caries diagnostics are viewed on varying types of displays and usually in relatively high ambient lighting (room illuminance) conditions. Our purpose was to assess the effect of room illuminance and varying display types on caries diagnostic accuracy in digital dental radiographs. Previous studies have shown that the diagnostic accuracy of caries detection is significantly better in reduced lighting conditions. Our hypothesis was that higher display luminance could compensate for this in higher ambient lighting conditions. Extracted human teeth with approximal surfaces clinically ranging from sound to demineralized were radiographed and evaluated by 3 observers who detected carious lesions on 3 different types of displays in 3 different room illuminance settings ranging from low illumination, i.e. what is recommended for diagnostic viewing, to higher illumination levels corresponding to those found in an average dental office. Sectioning and microscopy of the teeth validated the presence or absence of a carious lesion. Sensitivity, specificity and accuracy were calculated for each modality and observer. Differences were estimated by analyzing the binary data assuming the added effects of observer and modality in a generalized linear model. The observers obtained higher sensitivities in lower illuminance settings than in higher illuminance settings. However, this was related to a reduction in specificity, which meant that there was no significant difference in overall accuracy. Contrary to our hypothesis, there were no significant differences between the accuracy of different display types. Therefore, different displays and room illuminance levels did not affect the overall accuracy of radiographic caries detection. Copyright © 2012 S. Karger AG, Basel.

Interactions among aging, gender, and gonadectomy effects upon naloxone hypophagia in rats.

PubMed

Islam, A K; Beczkowska, I W; Bodnar, R J

1993-11-01

The present study examined the dose-dependent (0.25-5 mg/kg) effects of systemic naloxone upon deprivation-induced intake and high-fat intake as functions of age (4, 8, 14, and 20 months), gender, and gonadectomy in rats. Significant increases in body weight were observed as functions of age and gonadectomy. Whereas aging significantly reduced basal deprivation-induced intake, it generally failed to alter basal high-fat intake. Whereas age, gender, and gonadectomy failed to alter the decreases in deprivation-induced intake following low (0.25-2.5 mg/kg) naloxone doses, sham males displayed significantly greater age-related and gender-related inhibition following the 5 mg/kg dose of naloxone. Young gonadectomized rats displayed significant increases in naloxone's inhibition of deprivation-induced intake as well. More dramatic changes occurred in naloxone's inhibition of high-fat intake. Naloxone's potency increased in sham female rats as a function of age, and decreased in sham males and ovariectomized females as a function of age. Whereas sham males and ovariectomized females were most sensitive to naloxone's inhibition of high-fat intake at young ages, sham females were most sensitive at older ages. These data indicate that effects of age, gender, and gonadectomy upon naloxone-induced hypophagia dissociate as a function of the type of intake. Because selective opioid antagonist studies demonstrate that deprivation-induced intake is mediated by the mu1 receptor and high-fat intake is mediated by kappa and mu2 receptors, it is postulated that the differential effects of aging, gender, and gonadectomy variables upon opioid mediation of the two forms of intake may reflect their interaction with different opioid receptor subtypes.

DRP1 Suppresses Leptin and Glucose Sensing of POMC Neurons.

PubMed

Santoro, Anna; Campolo, Michela; Liu, Chen; Sesaki, Hiromi; Meli, Rosaria; Liu, Zhong-Wu; Kim, Jung Dae; Diano, Sabrina

2017-03-07

Hypothalamic pro-opiomelanocortin (POMC) neurons regulate energy and glucose metabolism. Intracellular mechanisms that enable these neurons to respond to changes in metabolic environment are ill defined. Here we show reduced expression of activated dynamin-related protein (pDRP1), a mitochondrial fission regulator, in POMC neurons of fed mice. These POMC neurons displayed increased mitochondrial size and aspect ratio compared to POMC neurons of fasted animals. Inducible deletion of DRP1 of mature POMC neurons (Drp1 fl/fl -POMC-cre:ER T2 ) resulted in improved leptin sensitivity and glucose responsiveness. In Drp1 fl/fl -POMC-cre:ER T2 mice, POMC neurons showed increased mitochondrial size, ROS production, and neuronal activation with increased expression of Kcnj11 mRNA regulated by peroxisome proliferator-activated receptor (PPAR). Furthermore, deletion of DRP1 enhanced the glucoprivic stimulus in these neurons, causing their stronger inhibition and a greater activation of counter-regulatory responses to hypoglycemia that were PPAR dependent. Together, these data unmasked a role for mitochondrial fission in leptin sensitivity and glucose sensing of POMC neurons. Copyright © 2017 Elsevier Inc. All rights reserved.

Teleoperated robotic sorting system

DOEpatents

Roos, Charles E.; Sommer, Jr., Edward J.; Parrish, Robert H.; Russell, James R.

2008-06-24

A method and apparatus are disclosed for classifying materials utilizing a computerized touch sensitive screen or other computerized pointing device for operator identification and electronic marking of spatial coordinates of materials to be extracted. An operator positioned at a computerized touch sensitive screen views electronic images of the mixture of materials to be sorted as they are conveyed past a sensor array which transmits sequences of images of the mixture either directly or through a computer to the touch sensitive display screen. The operator manually "touches" objects displayed on the screen to be extracted from the mixture thereby registering the spatial coordinates of the objects within the computer. The computer then tracks the registered objects as they are conveyed and directs automated devices including mechanical means such as air jets, robotic arms, or other mechanical diverters to extract the registered objects.

Teleoperated robotic sorting system

DOEpatents

Roos, Charles E.; Sommer, Edward J.; Parrish, Robert H.; Russell, James R.

2000-01-01

A method and apparatus are disclosed for classifying materials utilizing a computerized touch sensitive screen or other computerized pointing device for operator identification and electronic marking of spatial coordinates of materials to be extracted. An operator positioned at a computerized touch sensitive screen views electronic images of the mixture of materials to be sorted as they are conveyed past a sensor array which transmits sequences of images of the mixture either directly or through a computer to the touch sensitive display screen. The operator manually "touches" objects displayed on the screen to be extracted from the mixture thereby registering the spatial coordinates of the objects within the computer. The computer then tracks the registered objects as they are conveyed and directs automated devices including mechanical means such as air jets, robotic arms, or other mechanical diverters to extract the registered objects.

Renal tubular angiotensin converting enzyme is responsible for nitro-L-arginine methyl ester (L-NAME)-induced salt sensitivity

PubMed Central

Giani, Jorge F.; Eriguchi, Masahiro; Bernstein, Ellen A.; Katsumata, Makoto; Shen, Xiao Z.; Li, Liang; McDonough, Alicia A.; Fuchs, Sebastien; Bernstein, Kenneth E.; Gonzalez-Villalobos, Romer A.

2017-01-01

Renal parenchymal injury predisposes to salt-sensitive hypertension, but how this occurs is not known. Here we tested whether renal tubular angiotensin converting enzyme (ACE), the main site of kidney ACE expression, is central to the development of salt sensitivity in this setting. Two mouse models were used: it-ACE mice in which ACE expression is selectively eliminated from renal tubular epithelial cells; and ACE 3/9 mice, a compound heterozygous mouse model that makes ACE only in renal tubular epithelium from the ACE 9 allele, and in liver hepatocytes from the ACE 3 allele. Salt sensitivity was induced using a post L-NAME salt challenge. While both wild-type and ACE 3/9 mice developed arterial hypertension following three weeks of high salt administration, it-ACE mice remained normotensive with low levels of renal angiotensin II. These mice displayed increased sodium excretion, lower sodium accumulation, and an exaggerated reduction in distal sodium transporters. Thus, in mice with renal injury induced by L-NAME pretreatment, renal tubular epithelial ACE, and not ACE expression by renal endothelium, lung, brain, or plasma, is essential for renal angiotensin II accumulation and salt-sensitive hypertension. PMID:27988209

P21-activated kinase 2 (PAK2) regulates glucose uptake and insulin sensitivity in neuronal cells.

PubMed

Varshney, Pallavi; Dey, Chinmoy Sankar

2016-07-05

P21-activated kinases (PAKs) are recently reported as important players of insulin signaling and glucose homeostasis in tissues like muscle, pancreas and liver. However, their role in neuronal insulin signaling is still unknown. Present study reports the involvement of PAK2 in neuronal insulin signaling, glucose uptake and insulin resistance. Irrespective of insulin sensitivity, insulin stimulation decreased PAK2 activity. PAK2 downregulation displayed marked enhancement of GLUT4 translocation with increase in glucose uptake whereas PAK2 over-expression showed its reduction. Treatment with Akti-1/2 and wortmannin suggested that Akt and PI3K are mediators of insulin effect on PAK2 and glucose uptake. Rac1 inhibition demonstrated decreased PAK2 activity while inhibition of PP2A resulted in increased PAK2 activity, with corresponding changes in glucose uptake. Taken together, present study demonstrates an inhibitory role of insulin signaling (via PI3K-Akt) and PP2A on PAK2 activity and establishes PAK2 as a Rac1-dependent negative regulator of neuronal glucose uptake and insulin sensitivity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Lizards fail to plastically adjust nesting behavior or thermal tolerance as needed to buffer populations from climate warming.

PubMed

Telemeco, Rory S; Fletcher, Brooke; Levy, Ofir; Riley, Angela; Rodriguez-Sanchez, Yesenia; Smith, Colton; Teague, Collin; Waters, Amanda; Angilletta, Michael J; Buckley, Lauren B

2017-03-01

Although observations suggest the potential for phenotypic plasticity to allow adaptive responses to climate change, few experiments have assessed that potential. Modeling suggests that Sceloporus tristichus lizards will need increased nest depth, shade cover, or embryonic thermal tolerance to avoid reproductive failure resulting from climate change. To test for such plasticity, we experimentally examined how maternal temperatures affect nesting behavior and embryonic thermal sensitivity. The temperature regime that females experienced while gravid did not affect nesting behavior, but warmer temperatures at the time of nesting reduced nest depth. Additionally, embryos from heat-stressed mothers displayed increased sensitivity to high-temperature exposure. Simulations suggest that critically low temperatures, rather than high temperatures, historically limit development of our study population. Thus, the plasticity needed to buffer this population has not been under selection. Plasticity will likely fail to compensate for ongoing climate change when such change results in novel stressors. © 2016 John Wiley & Sons Ltd.

Prenatal Stress as a Risk-and an Opportunity-Factor.

PubMed

Hartman, Sarah; Freeman, Sara M; Bales, Karen L; Belsky, Jay

2018-04-01

Two separate lines of research indicate (a) that prenatal stress is associated with heightened behavioral and physiological reactivity and (b) that these postnatal phenotypes are associated with increased susceptibility to both positive and negative developmental experiences. Therefore, prenatal stress may increase sensitivity to the rearing environment. We tested this hypothesis by manipulating prenatal stress and rearing-environment quality, using a cross-fostering paradigm, in prairie voles. Results showed that prenatally stressed voles, as adults, displayed the highest behavioral and physiological reactivity when cross-fostered to low-contact (i.e., low-quality) rearing but the lowest behavioral and physiological reactivity when cross-fostered to high-contact (i.e., high-quality) rearing; non-prenatally stressed voles showed no effect of rearing condition. Additionally, while neither prenatal stress nor rearing condition affected oxytocin receptor binding, prenatally stressed voles cross-fostered to high-contact rearing showed the highest vasopressin-1a receptor binding in the amygdala. Results indicate that prenatal stress induces greater environmental sensitivity, making it both a risk and an opportunity factor.

Rolling blackout is required for synaptic vesicle exocytosis.

PubMed

Huang, Fu-De; Woodruff, Elvin; Mohrmann, Ralf; Broadie, Kendal

2006-03-01

Rolling blackout (RBO) is a putative transmembrane lipase required for phospholipase C-dependent phosphatidylinositol 4,5-bisphosphate-diacylglycerol signaling in Drosophila neurons. Conditional temperature-sensitive (TS) rbo mutants display complete, reversible paralysis within minutes, demonstrating that RBO is acutely required for movement. RBO protein is localized predominantly in presynaptic boutons at neuromuscular junction (NMJ) synapses and throughout central synaptic neuropil, and rbo TS mutants display a complete, reversible block of both central and peripheral synaptic transmission within minutes. This phenotype appears limited to adults, because larval NMJs do not manifest the acute blockade. Electron microscopy of adult rbo TS mutant boutons reveals an increase in total synaptic vesicle (SV) content, with a concomitant shrinkage of presynaptic bouton size and an accumulation of docked SVs at presynaptic active zones within minutes. Genetic tests reveal a synergistic interaction between rbo and syntaxin1A TS mutants, suggesting that RBO is required in the mechanism of N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-mediated SV exocytosis, or in a parallel pathway necessary for SV fusion. The rbo TS mutation does not detectably alter SNARE complex assembly, suggesting a downstream requirement in SV fusion. We conclude that RBO plays an essential role in neurotransmitter release, downstream of SV docking, likely mediating SV fusion.

Research Methods

DTIC Science & Technology

1992-01-01

cognitive function. For example. physiological methods allow for visual sensitivity measurements in infants and children with about the same level of...potential (ERP), the event-related magnetic field (ERF), and pupillometry . Where possible, we cite specific experiments that deal with display or stimulus...technical barrier preventing the application of these methods to the analysis of human performance with color displays. Pupillometry . The pupillary

Insulin sensitivity in relation to fat distribution and plasma adipocytokines among abusers of anabolic androgenic steroids.

PubMed

Rasmussen, Jon Jarløv; Schou, Morten; Selmer, Christian; Johansen, Marie Louise; Gustafsson, Finn; Frystyk, Jan; Dela, Flemming; Faber, Jens; Kistorp, Caroline

2017-09-01

Abuse of anabolic androgenic steroids (AAS) is prevalent among young men, but information regarding effects on insulin sensitivity and fat distribution is limited. The objective was to investigate insulin sensitivity in relation to fat distribution and adipocytokines among current and former AAS abusers compared with controls. Cross-sectional study among men involved in recreational strength training. Current and former AAS abusers (n=37 and n=33) and controls (n=30) volunteered from the community. We assessed insulin sensitivity by Matsuda index (oral glucose tolerance test). Using overnight fasting blood samples, adiponectin and leptin were measured. Body composition and fat distribution, including visceral adipose tissue (VAT), were assessed by dual energy X-ray absorptiometry. Current and former AAS abusers displayed lower Matsuda index than controls (%-difference (95%CI) from controls, -26% (-45; -1) and -39% (-55; -18)). Testosterone was markedly higher among current AAS abusers and subnormal among former AAS abusers compared with controls. Current AAS abusers displayed higher mean VAT than controls (388 (17) vs 293 (12) cm 3 , P<.001) whereas body fat %, adiponectin and leptin concentrations were lower. In contrast, former AAS abusers showed highest leptin concentrations and body fat %. Multivariate linear regressions identified VAT as independent predictor of lower Matsuda index among current AAS abusers compared with controls; while body fat % independently predicted lower Matsuda index among former AAS abusers. Both current and former AAS abusers displayed lower insulin sensitivity which could be mediated by higher VAT and total body fat %, respectively. © 2017 John Wiley & Sons Ltd.

Evaluating stereoscopic displays: both efficiency measures and perceived workload sensitive to manipulations in binocular disparity

NASA Astrophysics Data System (ADS)

van Beurden, Maurice H. P. H.; Ijsselsteijn, Wijnand A.; de Kort, Yvonne A. W.

2011-03-01

Stereoscopic displays are known to offer a number of key advantages in visualizing complex 3D structures or datasets. The large majority of studies that focus on evaluating stereoscopic displays for professional applications use completion time and/or the percentage of correct answers to measure potential performance advantages. However, completion time and accuracy may not fully reflect all the benefits of stereoscopic displays. In this paper, we argue that perceived workload is an additional valuable indicator reflecting the extent to which users can benefit from using stereoscopic displays. We performed an experiment in which participants were asked to perform a visual path-tracing task within a convoluted 3D wireframe structure, varying in level of complexity of the visualised structure and level of disparity of the visualisation. The results showed that an optimal performance (completion time, accuracy and workload), depend both on task difficulty and disparity level. Stereoscopic disparity revealed a faster and more accurate task performance, whereas we observed a trend that performance on difficult tasks stands to benefit more from higher levels of disparity than performance on easy tasks. Perceived workload (as measured using the NASA-TLX) showed a similar response pattern, providing evidence that perceived workload is sensitive to variations in disparity as well as task difficulty. This suggests that perceived workload could be a useful concept, in addition to standard performance indicators, in characterising and measuring human performance advantages when using stereoscopic displays.

ER-mitochondria contacts control surface glycan expression and sensitivity to killer lymphocytes in glioma stem-like cells.

PubMed

Bassoy, Esen Yonca; Kasahara, Atsuko; Chiusolo, Valentina; Jacquemin, Guillaume; Boydell, Emma; Zamorano, Sebastian; Riccadonna, Cristina; Pellegatta, Serena; Hulo, Nicolas; Dutoit, Valérie; Derouazi, Madiha; Dietrich, Pierre Yves; Walker, Paul R; Martinvalet, Denis

2017-06-01

Glioblastoma is a highly heterogeneous aggressive primary brain tumor, with the glioma stem-like cells (GSC) being more sensitive to cytotoxic lymphocyte-mediated killing than glioma differentiated cells (GDC). However, the mechanism behind this higher sensitivity is unclear. Here, we found that the mitochondrial morphology of GSCs modulates the ER-mitochondria contacts that regulate the surface expression of sialylated glycans and their recognition by cytotoxic T lymphocytes and natural killer cells. GSCs displayed diminished ER-mitochondria contacts compared to GDCs. Forced ER-mitochondria contacts in GSCs increased their cell surface expression of sialylated glycans and reduced their susceptibility to cytotoxic lymphocytes. Therefore, mitochondrial morphology and dynamism dictate the ER-mitochondria contacts in order to regulate the surface expression of certain glycans and thus play a role in GSC recognition and elimination by immune effector cells. Targeting the mitochondrial morphology, dynamism, and contacts with the ER could be an innovative strategy to deplete the cancer stem cell compartment to successfully treat glioblastoma. © 2017 The Authors.

Explaining Discrepancies in Arrest Rates Between Black and White Male Juveniles

PubMed Central

Fite, Paula J.; Wynn, Porche’; Pardini, Dustin A.

2010-01-01

The authors investigated discrepancies in arrest rates between Black and White male juveniles by examining the role of early risk factors for arrest. Two hypotheses were evaluated: (a) Disproportionate minority arrest is due to increased exposure to early risk factors, and (b) a differential sensitivity to early risk factors contributes to disproportionate minority arrest. The study included 481 Black and White boys who were followed from childhood to early adulthood. A higher incidence of early risk factors accounted for racial differences related to any juvenile arrest, as well as differences in violence- and theft-related arrests. However, increased exposure to early risk factors did not explain race differences in drug-related arrests. Minimal support was found for the hypothesis that a differential sensitivity to risk factors accounts for disproportionate rate of minority male arrests. In sum, most racial discrepancies in juvenile male arrests were accounted for by an increased exposure to childhood risk factors. Specifically, Black boys were more likely to display early conduct problems and low academic achievement and experience poor parent–child communication, peer delinquency, and neighborhood problems, which increased their risk for juvenile arrest. PMID:19803571

A selective and sensitive D-xylose electrochemical biosensor based on xylose dehydrogenase displayed on the surface of bacteria and multi-walled carbon nanotubes modified electrode.

PubMed

Li, Liang; Liang, Bo; Shi, Jianguo; Li, Feng; Mascini, Marco; Liu, Aihua

2012-03-15

A novel Nafion/bacteria-displaying xylose dehydrogenase (XDH)/multi-walled carbon nanotubes (MWNTs) composite film-modified electrode was fabricated and applied for the sensitive and selective determination of d-xylose (INS 967), where the XDH-displayed bacteria (XDH-bacteria) was prepared using a newly identified ice nucleation protein from Pseudomonas borealis DL7 as an anchoring motif. The XDH-displayed bacteria can be used directly, eliminating further enzyme-extraction and purification, thus greatly improved the stability of the enzyme. The optimal conditions for the construction of biosensor were established: homogeneous Nafion-MWNTs composite dispersion (10 μL) was cast onto the inverted glassy carbon electrode, followed by casting 10-μL of XDH-bacteria aqueous solution to stand overnight to dry, then a 5-μL of Nafion solution (0.05 wt%) is syringed to the electrode surface. The bacteria-displaying XDH could catalyze the oxidization of xylose to xylonolactone with coenzyme NAD(+) in 0.1M PBS buffer (pH7.4), where NAD(+) (nicotinamide adenine dinucleotide) is reduced to NADH (the reduced form of nicotinamide adenine dinucleotide). The resultant NADH is further electrocatalytically oxidized by MWNTs on the electrode, resulting in an obvious oxidation peak around 0.50 V (vs. Ag/AgCl). In contrast, the bacteria-XDH-only modified electrode showed oxidation peak at higher potential of 0.7 V and less sensitivity. Therefore, the electrode/MWNTs/bacteria-XDH/Nafion exhibited good analytical performance such as long-term stability, a wide dynamic range of 0.6-100 μM and a low detection limit of 0.5 μM D-xylose (S/N=3). No interference was observed in the presence of 300-fold excess of other saccharides including D-glucose, D-fructose, D-maltose, D-galactose, D-mannose, D-sucrose, and D-cellbiose as well as 60-fold excess of L-arabinose. The proposed microbial biosensor is stable, specific, sensitive, reproducible, simple, rapid and cost-effective, which holds great potential in real applications. Copyright © 2012 Elsevier B.V. All rights reserved.

p16INK4a deficiency promotes IL-4-induced polarization and inhibits proinflammatory signaling in macrophages

PubMed Central

Cudejko, Céline; Wouters, Kristiaan; Fuentes, Lucía; Hannou, Sarah Anissa; Paquet, Charlotte; Bantubungi, Kadiombo; Bouchaert, Emmanuel; Vanhoutte, Jonathan; Fleury, Sébastien; Remy, Patrick; Tailleux, Anne; Chinetti, Giulia; Dombrowicz, David; Staels, Bart; Paumelle, Réjane

2011-01-01

The CDKN2A locus, which contains the tumor suppressor gene p16INK4a, is associated with an increased risk of age-related inflammatory diseases, such as cardiovascular disease and type 2 diabetes, in which macrophages play a crucial role. Monocytes can polarize towards classically (CAMφ) or alternatively (AAMφ) activated macrophages. However, the molecular mechanisms underlying the acquisition of these phenotypes are not well defined. Here, we show that p16INK4a-deficiency (p16−/−) modulates the macrophage phenotype. Transcriptome analysis revealed that p16−/− bone marrow-derived macrophages (BMDM) exhibit a phenotype resembling interleukin (IL)-4-induced macrophage polarization. In line with this observation, p16−/− BMDM displayed a decreased response to classically polarizing IFNγ and LPS and an increased sensitivity to alternative polarization by IL-4. Furthermore, mice transplanted with p16−/− bone marrow displayed higher hepatic AAMφ marker expression levels upon Schistosoma mansoni infection, an in vivo model of AAMφ phenotype-skewing. Surprisingly, p16−/− BMDM did not display increased IL-4-induced STAT6 signaling, but decreased IFNγ-induced STAT1 and LPS-induced IKKα,β phosphorylation. This decrease correlated with decreased JAK2 phosphorylation and with higher levels of inhibitory acetylation of STAT1 and IKKα,β. These findings identify p16INK4a as a modulator of macrophage activation and polarization via the JAK2-STAT1 pathway with possible roles in inflammatory diseases. PMID:21636855

Experience, Context, and the Visual Perception of Human Movement

ERIC Educational Resources Information Center

Jacobs, Alissa; Pinto, Jeannine; Shiffrar, Maggie

2004-01-01

Why are human observers particularly sensitive to human movement? Seven experiments examined the roles of visual experience and motor processes in human movement perception by comparing visual sensitivities to point-light displays of familiar, unusual, and impossible gaits across gait-speed and identity discrimination tasks. In both tasks, visual…

Involvement of alternative oxidase in the regulation of sensitivity of Sclerotinia sclerotiorum to the fungicides azoxystrobin and procymidone.

PubMed

Xu, Ting; Wang, Ya-Ting; Liang, Wu-Sheng; Yao, Fei; Li, Yong-Hong; Li, Dian-Rong; Wang, Hao; Wang, Zheng-Yi

2013-06-01

Sclerotinia sclerotiorum is a filamentous fungal pathogen that can infect many economically important crops and vegetables. Alternative oxidase is the terminal oxidase of the alternative respiratory pathway in fungal mitochondria. The function of alternative oxidase was investigated in the regulation of sensitivity of S. sclerotiorum to two commercial fungicides, azoxystrobin and procymidone which have different fungitoxic mechanisms. Two isolates of S. sclerotiorum were sensitive to both fungicides. Application of salicylhydroxamic acid, a specific inhibitor of alternative oxidase, significantly increased the values of effective concentration causing 50% mycelial growth inhibition (EC50) of azoxystrobin to both S. sclerotiorum isolates, whereas notably decreased the EC50 values of procymidone. In mycelial respiration assay azoxystrobin displayed immediate inhibitory effect on cytochrome pathway capacity, but had no immediate effect on alternative pathway capacity. In contrast, procymidone showed no immediate impact on capacities of both cytochrome and alternative pathways in the mycelia. However, alternative oxidase encoding gene (aox) transcript and protein levels, alternative respiration pathway capacity of the mycelia were obviously increased by pre-treatment for 24 h with both azoxystrobin and procymidone. These results indicate that alternative oxidase was involved in the regulation of sensitivity of S. sclerotiorum to the fungicides azoxystrobin and procymidone, and that both fungicides could affect aox gene expression and the alternative respiration pathway capacity development in mycelia of this fungal pathogen.

ATM inhibition induces synthetic lethality and enhances sensitivity of PTEN-deficient breast cancer cells to cisplatin.

PubMed

Li, Ke; Yan, Huaying; Guo, Wenhao; Tang, Mei; Zhao, Xinyu; Tong, Aiping; Peng, Yong; Li, Qintong; Yuan, Zhu

2018-05-01

PTEN deficiency often causes defects in DNA damage repair. Currently, effective therapies for breast cancer are lacking. ATM is an attractive target for cancer treatment. Previous studies suggested a synthetic lethality between PTEN and PARP. However, the synthetically lethal interaction between PTEN and ATM in breast cancer has not been reported. Moreover, the mechanism remains elusive. Here, using KU-60019, an ATM kinase inhibitor, we investigated ATM inhibition as a synthetically lethal strategy to target breast cancer cells with PTEN defects. We found that KU-60019 preferentially sensitizes PTEN-deficient MDA-MB-468 breast cancer cells to cisplatin, though it also slightly enhances sensitivity of PTEN wild-type breast cancer cells. The increased cytotoxic sensitivity is associated with apoptosis, as evidenced by flow cytometry and PARP cleavage. Additionally, the increase of DNA damage accumulation due to the decreased capability of DNA repair, as indicated by γ-H2AX and Rad51 foci, also contributed to this selective cytotoxicity. Mechanistically, compared with PTEN wild-type MDA-MB-231 cells, PTEN-deficient MDA-MB-468 cells have lower level of Rad51, higher ATM kinase activity, and display the elevated level of DNA damage. Moreover, these differences could be further enlarged by cisplatin. Our findings suggest that ATM is a promising target for PTEN-defective breast cancer. Copyright © 2018 Elsevier Inc. All rights reserved.

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.

Electrophoresis Gel Quantification with a Flatbed Scanner and Versatile Lighting from a Screen Scavenged from a Liquid Crystal Display (LCD) Monitor

ERIC Educational Resources Information Center

Yeung, Brendan; Ng, Tuck Wah; Tan, Han Yen; Liew, Oi Wah

2012-01-01

The use of different types of stains in the quantification of proteins separated on gels using electrophoresis offers the capability of deriving good outcomes in terms of linear dynamic range, sensitivity, and compatibility with specific proteins. An inexpensive, simple, and versatile lighting system based on liquid crystal display backlighting is…

Unpleasant odors increase aversion to monetary losses.

PubMed

Stancak, Andrej; Xie, Yuxin; Fallon, Nicholas; Bulsing, Patricia; Giesbrecht, Timo; Thomas, Anna; Pantelous, Athanasios A

2015-04-01

Loss aversion is the tendency to prefer avoiding losses over acquiring gains of equal nominal values. Unpleasant odors not only influence affective state but have also been shown to activate brain regions similar to those mediating loss aversion. Therefore, we hypothesized a stronger loss aversion in a monetary gamble task if gambles were associated with an unpleasant as opposed to pleasant odor. In thirty human subjects, unpleasant (methylmercaptan), pleasant (jasmine), and neutral (clean air) odors were presented for 4 s. At the same time, uncertain gambles offering an equal chance of gain or loss of a variable amount of money, or a prospect of an assured win were displayed. One hundred different gambles were presented three times, each time paired with a different odor. Loss aversion, risk aversion, and logit sensitivity were evaluated using non-linear fitting of individual gamble decisions. Loss aversion was larger when prospects were displayed in the presence of methylmercaptan compared to jasmine or clean air. Moreover, individual differences in changes in loss aversion to the unpleasant as compared to pleasant odor correlated with odor pleasantness but not with odor intensity. Skin conductance responses to losses during the outcome period were larger when gambles were associated with methylmercaptan compared to jasmine. Increased loss aversion while perceiving an unpleasant odor suggests a dynamic adjustment of loss aversion toward greater sensitivity to losses. Given that odors are biological signals of hazards, such adjustment of loss aversion may have adaptive value in situations entailing threat or danger. Copyright © 2015 Elsevier B.V. All rights reserved.

Psychophysical Calibration of Mobile Touch-Screens for Vision Testing in the Field

NASA Technical Reports Server (NTRS)

Mulligan, Jeffrey B.

2015-01-01

The now ubiquitous nature of touch-screen displays in cell phones and tablet computers makes them an attractive option for vision testing outside of the laboratory or clinic. Accurate measurement of parameters such as contrast sensitivity, however, requires precise control of absolute and relative screen luminances. The nonlinearity of the display response (gamma) can be measured or checked using a minimum motion technique similar to that developed by Anstis and Cavanagh (1983) for the determination of isoluminance. While the relative luminances of the color primaries vary between subjects (due to factors such as individual differences in pre-retinal pigment densities), the gamma nonlinearity can be checked in the lab using a photometer. Here we compare results obtained using the psychophysical method with physical measurements for a number of different devices. In addition, we present a novel physical method using the device's built-in front-facing camera in conjunction with a mirror to jointly calibrate the camera and display. A high degree of consistency between devices is found, but some departures from ideal performance are observed. In spite of this, the effects of calibration errors and display artifacts on estimates of contrast sensitivity are found to be small.

Sociability modifies dogs' sensitivity to biological motion of different social relevance.

PubMed

Ishikawa, Yuko; Mills, Daniel; Willmott, Alexander; Mullineaux, David; Guo, Kun

2018-03-01

Preferential attention to living creatures is believed to be an intrinsic capacity of the visual system of several species, with perception of biological motion often studied and, in humans, it correlates with social cognitive performance. Although domestic dogs are exceptionally attentive to human social cues, it is unknown whether their sociability is associated with sensitivity to conspecific and heterospecific biological motion cues of different social relevance. We recorded video clips of point-light displays depicting a human or dog walking in either frontal or lateral view. In a preferential looking paradigm, dogs spontaneously viewed 16 paired point-light displays showing combinations of normal/inverted (control condition), human/dog and frontal/lateral views. Overall, dogs looked significantly longer at frontal human point-light display versus the inverted control, probably due to its clearer social/biological relevance. Dogs' sociability, assessed through owner-completed questionnaires, further revealed that low-sociability dogs preferred the lateral point-light display view, whereas high-sociability dogs preferred the frontal view. Clearly, dogs can recognize biological motion, but their preference is influenced by their sociability and the stimulus salience, implying biological motion perception may reflect aspects of dogs' social cognition.

Genotype Modulates Age-Related Alterations in Sensitivity to the Aversive Effects of Ethanol: An 8 Inbred Strain Analysis of Conditioned Taste Aversion

PubMed Central

Moore, Eileen M.; Forrest, Robert D.; Boehm, Stephen L.

2012-01-01

Adolescent individuals display altered behavioral sensitivity to ethanol, which may contribute to the increased ethanol consumption seen in this age-group. However, genetics also exert considerable influence on both ethanol intake and sensitivity. Thus far there is little research assessing the combined influence of developmental and genetic alcohol sensitivities. Sensitivity to the aversive effects of ethanol using a conditioned taste aversion (CTA) procedure was measured during both adolescence (P30) and adulthood (P75) in 8 inbred mouse strains (C57BL/6J, DBA/2J, 129S1/SvImJ, A/J, BALB/cByJ, BTBR T+tf/J, C3H/HeJ, and FVB/NJ). Adolescent and adult mice were water deprived, and subsequently provided with access to 0.9% (v/v) NaCl solution for 1h. Immediately following access mice were administered ethanol (0, 1.5, 2.25, 3g/kg, ip). This procedure was repeated in 72h intervals for a total of 5 CTA trials. Sensitivity to the aversive effects of ethanol was highly dependent upon both strain and age. Within an inbred strain, adolescent animals were consistently less sensitive to the aversive effects of ethanol than their adult counterparts. However, the dose of ethanol required to produce an aversion response differed as a function of both age and strain. PMID:23171343

Light sensitivity of a one transistor-one capacitor memory cell when used as a micromirror actuator in projector applications

NASA Astrophysics Data System (ADS)

Huffman, James Douglas

2001-11-01

The most important issue facing the future business success of the Digital Micromirror Device or DMD™ produced by Texas Instruments is the cost of the actual device. As the business and consumer markets call for higher resolution displays, the array size will have to be increased to incorporate more pixels. The manufacturing costs associated with building these higher resolution displays follow an exponential relation with the number of pixels due to yield loss and reduced number of chips per silicon wafer. Each pixel is actuated by electrostatics that are provided by a memory cell that is built in the underlying silicon substrate. One way to decrease cost of the wafer is to change the memory cell architecture from a static random access configuration or SRAM to a dynamic random access configuration or DRAM. This change has the benefits of having fewer components per area and a lower metal density. This reduction in the component count and metal density has a dramatic effect on the yield of the memory array by reducing the particle sensitivity of the underlying cell. The main drawback to using a DRAM configuration in a display application is the light sensitivity of a charge storage device built in the silicon substrate. As the photons pass through the mechanical micromirrors and illuminate the DRAM cell, the effective electrostatic potential of the memory element used for the mirror actuation is reduced. This dissertation outlines the issues associated with the light sensitivity of a DRAM memory cell as the actuation element for a micromirror. The concept of charge depletion on a silicon capacitor due to recombination of photogenerated carriers is explored and experimentally verified. The effects of the reduced potential on the capacitor on the micromirror are also explored. Optical modeling is used to determine the incoming photon flux to determine the benefits of adding a charge recombination region as part of the DRAM memory cell. Several options are explored to reduce the effect of the incoming photons on the potential of the memory cell. The results will show that a 1T1C memory cell with N-type recombination regions and maximum light shielding is sufficient for a projector application.

GDC-0941 sensitizes breast cancer to ABT-737 in vitro and in vivo through promoting the degradation of Mcl-1.

PubMed

Zheng, Lin; Yang, Wei; Zhang, Chong; Ding, Wan-jing; Zhu, Hong; Lin, Neng-ming; Wu, Hong-hai; He, Qiao-jun; Yang, Bo

2011-10-01

The present study showed that GDC-0941 potently sensitized breast cancer to ABT-737 in vitro and in vivo. ABT-737 exhibited limited lethality in breast cancer cells; however, when combined with GDC-0941, it displayed strong synergistic cytotoxicity and enhanced caspase-mediated apoptosis. GDC-0941 promoted proteasomal degradation of Mcl-1, of which the overexpression has been validated to confer ABT-737 resistance, thereby enhanced the anticancer efficacy of ABT-737. Furthermore, the combination of GDC-0941 and ABT-737 exerted increased anti-tumor efficacy on MDA-MB-231 xenograft models. Overall, our data described unprecedentedly the promising therapeutic potential and underlying mechanisms of combining GDC-0941 with ABT-737 in treating breast cancer. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Interoceptive sensitivity as a proxy for emotional intensity and its relationship with perseverative cognition

PubMed Central

Lugo, Ricardo G; Helkala, Kirsi; Knox, Benjamin J; Jøsok, Øyvind; Lande, Natalie M; Sütterlin, Stefan

2018-01-01

Background Technical advancement in military cyber defense poses increased cognitive demands on cyber officers. In the cyber domain, the influence of emotion on decision-making is rarely investigated. The purpose of this study was to assess psychophysiological correlation with perseverative cognitions during emotionally intensive/stressful situations in cyber military personnel. In line with parallel research on clinical samples high on perseverative cognition, we expected a decreased interoceptive sensitivity in officers with high levels of perseverative cognition. Method We investigated this association in a sample of 27 cyber officer cadets. Results Contrary to our hypothesis, there was no relationship between the factors. Discussion Cyber officers might display characteristics not otherwise found in general populations. The cyber domain may lead to a selection process that attracts different profiles of cognitive and emotional processing. PMID:29296103

The moderating role of food cue sensitivity in the behavioral response of children to their neighborhood food environment: a cross-sectional study.

PubMed

Paquet, Catherine; de Montigny, Luc; Labban, Alice; Buckeridge, David; Ma, Yu; Arora, Narendra; Dubé, Laurette

2017-07-05

Neighborhood food cues have been inconsistently related to residents' health, possibly due to variations in residents' sensitivity to such cues. This study sought to investigate the degree to which children's predisposition to eat upon exposure to food environment and food cues (external eating), could explain differences in strength of associations between their food consumption and the type of food outlets and marketing strategies present in their neighborhood. Data were obtained from 616 6-12 y.o. children recruited into a population-based cross-sectional study in which food consumption was measured through a 24-h food recall and responsiveness to food cues measured using the external eating scale. The proportion of food retailers within 3 km of residence considered as "healthful" was calculated using a Geographical Information System. Neighborhood exposure to food marketing strategies (displays, discount frequency, variety, and price) for vegetables and soft drinks were derived from a geocoded digital marketing database. Adjusted mixed models with spatial covariance tested interaction effects of food environment indicators and external eating on food consumption. In children with higher external eating scores, healthful food consumption was more positively related to vegetable displays, and more negatively to the display and variety of soft drinks. No interactions were observed for unhealthful food consumption and no main effects of food environment indicators were found on food consumption. Children differ in their responsiveness to marketing-related visual food cues on the basis of their external eating phenotype. Strategies aiming to increase the promotion of healthful relative to unhealthful food products in stores may be particularly beneficial for children identified as being more responsive to food cues.

High Fat Diet Augments Amphetamine Sensitization in Mice: Role of Feeding Pattern, Obesity, and Dopamine Terminal Changes

PubMed Central

Fordahl, Steve C.; Locke, Jason L.; Jones, Sara R.

2016-01-01

High fat (HF) diet-induced obesity has been shown to augment behavioral responses to psychostimulants that target the dopamine system. The purpose of this study was to characterize dopamine terminal changes induced by a HF diet that correspond with enhanced locomotor sensitization to amphetamine. C57BL/6J mice had limited (2hr 3d/week) or extended (24h 7d/week) access to a HF diet or standard chow for six weeks. Mice were then repeatedly exposed to amphetamine (AMPH), and their locomotor responses to an amphetamine challenge were measured. Fast scan cyclic voltammetry was used to identify changes in dopamine terminal function after AMPH exposure. Exposure to a HF diet reduced dopamine uptake and increased locomotor responses to acute, high-dose AMPH administration compared to chow fed mice. Microdialysis showed elevated extracellular dopamine in the nucleus accumbens (NAc) coincided with enhanced locomotion after acute AMPH in HF-fed mice. All mice exhibited locomotor sensitization to amphetamine, but both extended and limited access to a HF diet augmented this response. Neither HF-fed group showed the robust amphetamine sensitization-induced increases in dopamine release, reuptake, and amphetamine potency observed in chow fed animals. However, the potency of amphetamine as an uptake inhibitor was significantly elevated after sensitization in mice with extended (but not limited) access to HF. Conversely, after amphetamine sensitization, mice with limited (but not extended) access to HF displayed reduced autoreceptor sensitivity to the D2/D3 agonist quinpirole. Additionally, we observed reduced membrane dopamine transporter (DAT) levels after HF, and a shift in DAT localization to the cytosol was detected with limited access to HF. This study showed that different patterns of HF exposure produced distinct dopamine terminal adaptations to repeated AMPH, which differed from chow fed mice, and enhanced sensitization to AMPH. Locomotor sensitization in chow fed mice coincided with elevated DAT function and increased AMPH potency; however, the enhanced behavioral response to AMPH after HF exposure was unique in that it coincided with reduced DAT function and diet pattern-specific adaptations. PMID:27267686

Magnetic sensor technology based on giant magneto-impedance effect in amorphous wires

NASA Astrophysics Data System (ADS)

Wang, X.; Teng, Y.; Wang, C.; Li, Q.

2012-12-01

This project focuses on giant magneto-impedance (GMI) effect that found in the soft magnetic amorphous wires in recent years, when AC current through the amorphous wire, induced voltage in the wires would change sensitively with a small external magnetic field along the wire vertical imposed changes. GMI magnetic sensor could compensate for the shortcomings of the traditional magnetic sensors and detect weak magnetic field, meanwhile the characteristics of high stability, high sensitivity, high resolution, fast response and low power consumption, which makes it becoming the focus of extensive research at home and abroad and being new mode of the next age of the physical geography observation. The emphasis of the project is the research on the high sensitivity amorphous wire detector and the low noise capability circuit design. In this paper, it is analyzed the theory of the Amorphous Wire Giant-Magneto-Impedance (AWGMI) effect and its influence factors in details, and expatiated the sensor principle based on AWGMI. On the basis of AWGMI, the experimental system of the micro-magnetic sensor is designed, which is composed of the detecting signals, processing and collecting data, display and transmitting data circuit and corresponding functional software etc. The properties of this kind of micro-magnetic sensor are studied by experiments, such as its linearity, sensitivity, frequency response, noise, stability and temperature properties and so on, especially analyzed the relation of the drive signals with all kinds of characteristics. The results show that there is no direct relationship between the frequency of the drive signals and linear property of the sensor. But with the increase of its frequency, some fluctuation appears on the characteristic curves; the direct relation is found between the frequency of the drive signal and sensitivity, with the increase of the frequency, AWGMI effect increases monotonously. It leads to the amplitude of the output voltage increase with the change of the outer magnetic field and results in the increase of the sensor sensitivity; it can be enhanced the corresponding rate of the sensor to the low frequency magnetic field by increasing the drive signal frequency. By experiments, the best sensitivity and noise valves is 0.5225 mV/nT, 1.566nT respectively.

Increased mitochondrial calcium sensitivity and abnormal expression of innate immunity genes precede dopaminergic defects in Pink1-deficient mice.

PubMed

Akundi, Ravi S; Huang, Zhenyu; Eason, Joshua; Pandya, Jignesh D; Zhi, Lianteng; Cass, Wayne A; Sullivan, Patrick G; Büeler, Hansruedi

2011-01-13

PTEN-induced kinase 1 (PINK1) is linked to recessive Parkinsonism (EOPD). Pink1 deletion results in impaired dopamine (DA) release and decreased mitochondrial respiration in the striatum of mice. To reveal additional mechanisms of Pink1-related dopaminergic dysfunction, we studied Ca²+ vulnerability of purified brain mitochondria, DA levels and metabolism and whether signaling pathways implicated in Parkinson's disease (PD) display altered activity in the nigrostriatal system of Pink1⁻/⁻ mice. Purified brain mitochondria of Pink1⁻/⁻ mice showed impaired Ca²+ storage capacity, resulting in increased Ca²+ induced mitochondrial permeability transition (mPT) that was rescued by cyclosporine A. A subpopulation of neurons in the substantia nigra of Pink1⁻/⁻ mice accumulated phospho-c-Jun, showing that Jun N-terminal kinase (JNK) activity is increased. Pink1⁻/⁻ mice 6 months and older displayed reduced DA levels associated with increased DA turnover. Moreover, Pink1⁻/⁻ mice had increased levels of IL-1β, IL-12 and IL-10 in the striatum after peripheral challenge with lipopolysaccharide (LPS), and Pink1⁻/⁻ embryonic fibroblasts showed decreased basal and inflammatory cytokine-induced nuclear factor kappa-β (NF-κB) activity. Quantitative transcriptional profiling in the striatum revealed that Pink1⁻/⁻ mice differentially express genes that (i) are upregulated in animals with experimentally induced dopaminergic lesions, (ii) regulate innate immune responses and/or apoptosis and (iii) promote axonal regeneration and sprouting. Increased mitochondrial Ca²+ sensitivity and JNK activity are early defects in Pink1⁻/⁻ mice that precede reduced DA levels and abnormal DA homeostasis and may contribute to neuronal dysfunction in familial PD. Differential gene expression in the nigrostriatal system of Pink1⁻/⁻ mice supports early dopaminergic dysfunction and shows that Pink1 deletion causes aberrant expression of genes that regulate innate immune responses. While some differentially expressed genes may mitigate neurodegeneration, increased LPS-induced brain cytokine expression and impaired cytokine-induced NF-κB activation may predispose neurons of Pink1⁻/⁻ mice to inflammation and injury-induced cell death.

Human-scale interaction for virtual model displays: a clear case for real tools

NASA Astrophysics Data System (ADS)

Williams, George C.; McDowall, Ian E.; Bolas, Mark T.

1998-04-01

We describe a hand-held user interface for interacting with virtual environments displayed on a Virtual Model Display. The tool, constructed entirely of transparent materials, is see-through. We render a graphical counterpart of the tool on the display and map it one-to-one with the real tool. This feature, combined with a capability for touch- sensitive, discrete input, results in a useful spatial input device that is visually versatile. We discuss the tool's design and interaction techniques it supports. Briefly, we look at the human factors issues and engineering challenges presented by this tool and, in general, by the class of hand-held user interfaces that are see-through.

Spin-dependent limits from the DRIFT-IId directional dark matter detector

NASA Astrophysics Data System (ADS)

Daw, E.; Fox, J. R.; Gauvreau, J.-L.; Ghag, C.; Harmon, L. J.; Gold, M.; Lee, E. R.; Loomba, D.; Miller, E. H.; Murphy, A. Stj.; Paling, S. M.; Landers, J. M.; Pipe, M.; Pushkin, K.; Robinson, M.; Snowden-Ifft, D. P.; Spooner, N. J. C.; Walker, D.

2012-02-01

Data are presented from the DRIFT-IId detector operated in the Boulby Underground Science Facility in England. A 0.8 m3 fiducial volume, containing partial pressures of 30 Torr CS2 and 10 Torr CF4, was exposed for a duration of 47.4 live-time days with sufficient passive shielding to provide a neutron free environment within the detector. The nuclear recoil events seen are consistent with a remaining low-level background from the decay of radon daughters attached to the central cathode of the detector. However, charge from such events must drift across the entire width of the detector, and thus display large diffusion upon reaching the readout planes of the device. Exploiting this feature, it is shown to be possible to reject energy depositions from these Radon Progeny Recoil events while still retaining sensitivity to fiducial-volume nuclear recoil events. The response of the detector is then interpreted, using the F nuclei content of the gas, in terms of sensitivity to proton spin-dependent WIMP-nucleon interactions, displaying a minimum in sensitivity cross section at 1.8 pb for a WIMP mass of 100 GeV/c2. This sensitivity was achieved without compromising the direction sensitivity of DRIFT.

Infants’ sensitivity to emotion in music and emotion-action understanding

PubMed Central

Siu, Tik-Sze Carrey; Cheung, Him

2017-01-01

Emerging evidence has indicated infants’ early sensitivity to acoustic cues in music. Do they interpret these cues in emotional terms to represent others’ affective states? The present study examined infants’ development of emotional understanding of music with a violation-of-expectation paradigm. Twelve- and 20-month-olds were presented with emotionally concordant and discordant music-face displays on alternate trials. The 20-month-olds, but not the 12-month-olds, were surprised by emotional incongruence between musical and facial expressions, suggesting their sensitivity to musical emotion. In a separate non-music task, only the 20-month-olds were able to use an actress’s affective facial displays to predict her subsequent action. Interestingly, for the 20-month-olds, such emotion-action understanding correlated with sensitivity to musical expressions measured in the first task. These two abilities however did not correlate with family income, parental estimation of language and communicative skills, and quality of parent-child interaction. The findings suggest that sensitivity to musical emotion and emotion-action understanding may be supported by a generalised common capacity to represent emotion from social cues, which lays a foundation for later social-communicative development. PMID:28152081

Behavioral profiles of feline breeds in Japan.

PubMed

Takeuchi, Yukari; Mori, Yuji

2009-08-01

To clarify the behavioral profiles of 9 feline purebreds, 2 Persian subbreeds and the Japanese domestic cat, a questionnaire survey was distributed to 67 small-animal veterinarians. We found significant differences among breeds in all behavioral traits examined except for "inappropriate elimination". In addition, sexual differences were observed in certain behaviors, including "aggression toward cats", "general activity", "novelty-seeking", and "excitability". These behaviors were more common in males than females, whereas "nervousness" and "inappropriate elimination" were rated higher in females. When all breeds were categorized into four groups on the basis of a cluster analysis using the scores of two behavioral trait factors called "aggressiveness/sensitivity" and "vivaciousness", the group including Abyssinian, Russian Blue, Somali, Siamese, and Chinchilla breeds showed high aggressiveness/sensitivity and low vivaciousness. In contrast, the group including the American Shorthair and Japanese domestic cat displayed low aggressiveness/sensitivity and high vivaciousness, and the Himalayan and Persian group showed mild aggressiveness/sensitivity and very low vivaciousness. Finally, the group containing Maine Coon, Ragdoll, and Scottish Fold breeds displayed very low aggressiveness/sensitivity and low vivaciousness. The present results demonstrate that some feline behavioral traits vary by breed and/or sex.

Oxytocin and Social Sensitivity: Gene Polymorphisms in Relation to Depressive Symptoms and Suicidal Ideation

PubMed Central

McQuaid, Robyn J.; McInnis, Opal A.; Matheson, Kimberly; Anisman, Hymie

2016-01-01

Although the neuropeptide oxytocin has been associated with enhanced prosocial behaviors, it has also been linked to aggression and mental health disorders. Thus, it was suggested that oxytocin might act by increasing the salience of social stimuli, irrespective of whether these are positive or negative, thus increasing vulnerability to negative mental health outcomes. The current study (N = 243), conducted among white university students, examined the relation of trauma, depressive symptoms including suicidal ideation in relation to a single nucleotide polymorphism (SNP) within the oxytocin receptor gene (OXTR), rs53576, and a SNP on the CD38 gene that controls oxytocin release, rs3796863. Individuals with the polymorphism on both alleles (AA genotype) of the CD38 SNP had previously been linked to elevated plasma oxytocin levels. Consistent with the social sensitivity perspective, however, in the current study, individuals carrying the AA genotype displayed elevated feelings of alienation from parents and peers as well as increased levels of suicidal ideation. Moreover, they tended to report elevated depressive symptoms compared to CC homozygotes. It was also observed that the CD38 genotype moderated the relation between trauma and suicidal ideation scores, such that high levels of trauma were associated with elevated suicidal ideation among all CD38 genotypes, but this relationship was stronger among individuals with the AA genotype. In contrast, there was no relationship between the OXTR SNP, rs53576, depression or suicidal ideation. These findings support a social sensitivity hypothesis of oxytocin, wherein the AA genotype of the CD38 SNP, which has been considered the “protective allele” was associated with increased sensitivity and susceptibility to disturbed social relations and suicidal ideation. PMID:27486392

Is contextual cueing more than the guidance of visual-spatial attention?

PubMed

Schankin, Andrea; Hagemann, Dirk; Schubö, Anna

2011-04-01

When search displays are repeatedly presented, participants become faster in finding the target (contextual cueing, CC). It has been debated whether a more liberal response criterion might contribute to CC. In the current experiment, participants had to search through target-absent and target-present trials to compute d-prime as the measurement of sensitivity and beta as the measurement of response bias. Results showed that participants' sensitivity was not affected by the repetition of search displays. Although repeated displays led to both faster RTs and a more liberal response criterion, these effects were uncorrelated. In the event-related potential, RT effects were reflected by a late positive activity, which reflects response-related processes, but not by differences in the N2pc as electrophysiological correlate of focused attention. These results indicate that a more liberal response criterion is not the cause for CC effects in RTs but that other response-related processes might still contribute to the effect. Copyright © 2011 Elsevier B.V. All rights reserved.

Detection and quantification of microcystins (cyanobacterial hepatotoxins) with recombinant antibody fragments isolated from a naïve human phage display library.

PubMed

McElhiney, J; Lawton, L A; Porter, A J

2000-12-01

Single-chain antibody fragments against the cyanobacterial hepatotoxin microcystin-LR were isolated from a naive human phage display library and expressed in Escherichia coli. In competition enzyme-linked immunosorbent assay (ELISA), the most sensitive antibody clone selected from the library detected free microcystin-LR with an IC(50) value of 4 microM. It was found to cross react with three other microcystin variants - microcystin-RR, microcystin-LW and microcystin-LF - and detected microcystins in extracts of the cyanobacterium Microcystis aeruginosa, found to contain the toxins by high-performance liquid chromatography (HPLC). The quantification of microcystins in these extracts by ELISA and HPLC showed good correlation. Although the antibody isolated in this study was considerably less sensitive than the polyclonal and monoclonal antibodies already available for microcystin detection, phage display technology represents a cheaper, more rapid alternative for the production of anti-microcystin antibodies than the methods currently in use.

Ferrocene-cinchona hybrids with triazolyl-chalcone linkers act as pro-oxidants and sensitize human cancer cell lines to paclitaxel.

PubMed

Podolski-Renić, Ana; Bősze, Szilvia; Dinić, Jelena; Kocsis, László; Hudecz, Ferenc; Csámpai, Antal; Pešić, Milica

2017-08-16

Recently, we demonstrated that ferrocene-containing compounds with a cinchona moiety displayed marked anticancer activity. Here we report on the effects of the most promising isomers encompassing quinine- (compounds 4 and 5) and quinidine-epimers (compounds 6 and 7) - synthesized using improved methods providing controlled diastereoselectivity - in three different human multidrug resistant (MDR) cancer cell lines and their sensitive counterparts (non-small cell lung carcinoma NCI-H460/R/NCI-H460, colorectal carcinoma DLD1-TxR/DLD1 and glioblastoma U87-TxR/U87). We observed that the presence of the MDR phenotype did not diminish the activity of the compounds suggesting that ferrocene quinine- and quinidine-epimers are not substrates for P-glycoprotein, which has been indicated as a major mechanism of MDR in the cell lines used. Considering that metal-based anticancer agents mainly act by increasing ROS production, we investigated the potential of ferrocene-quinidine epimers to generate ROS. We found that 6 and 7 more readily increased ROS production and induced mitochondrial damage in MDR cancer cells. According to cell death analysis, 6 and 7 were more active against MDR cancer cells showing collateral sensitivity. In addition, our data suggest that these compounds could act as inhibitors of autophagy. Importantly, simultaneous treatments of 6 and 7 with paclitaxel (PTX) increased the sensitivity of MDR cancer cells to PTX. In conclusion, the ferrocene-quinidine epimers, besides being selective towards MDR cancer cells, could also possess potential to overcome PTX resistance.

LRRK2 phosphorylates pre-synaptic N-ethylmaleimide sensitive fusion (NSF) protein enhancing its ATPase activity and SNARE complex disassembling rate.

PubMed

Belluzzi, Elisa; Gonnelli, Adriano; Cirnaru, Maria-Daniela; Marte, Antonella; Plotegher, Nicoletta; Russo, Isabella; Civiero, Laura; Cogo, Susanna; Carrion, Maria Perèz; Franchin, Cinzia; Arrigoni, Giorgio; Beltramini, Mariano; Bubacco, Luigi; Onofri, Franco; Piccoli, Giovanni; Greggio, Elisa

2016-01-13

Lrrk2, a gene linked to Parkinson's disease, encodes a large scaffolding protein with kinase and GTPase activities implicated in vesicle and cytoskeletal-related processes. At the presynaptic site, LRRK2 associates with synaptic vesicles through interaction with a panel of presynaptic proteins. Here, we show that LRRK2 kinase activity influences the dynamics of synaptic vesicle fusion. We therefore investigated whether LRRK2 phosphorylates component(s) of the exo/endocytosis machinery. We have previously observed that LRRK2 interacts with NSF, a hexameric AAA+ ATPase that couples ATP hydrolysis to the disassembling of SNARE proteins allowing them to enter another fusion cycle during synaptic exocytosis. Here, we demonstrate that NSF is a substrate of LRRK2 kinase activity. LRRK2 phosphorylates full-length NSF at threonine 645 in the ATP binding pocket of D2 domain. Functionally, NSF phosphorylated by LRRK2 displays enhanced ATPase activity and increased rate of SNARE complex disassembling. Substitution of threonine 645 with alanine abrogates LRRK2-mediated increased ATPase activity. Given that the most common Parkinson's disease LRRK2 G2019S mutation displays increased kinase activity, our results suggest that mutant LRRK2 may impair synaptic vesicle dynamics via aberrant phosphorylation of NSF.

aroA-Deficient Salmonella enterica Serovar Typhimurium Is More Than a Metabolically Attenuated Mutant

PubMed Central

Frahm, Michael; Kocijancic, Dino; Rohde, Manfred; Eckweiler, Denitsa; Bielecka, Agata; Bueno, Emilio; Cava, Felipe; Abraham, Wolf-Rainer; Curtiss, Roy; Häussler, Susanne; Erhardt, Marc; Weiss, Siegfried

2016-01-01

ABSTRACT Recombinant attenuated Salmonella enterica serovar Typhimurium strains are believed to act as powerful live vaccine carriers that are able to elicit protection against various pathogens. Auxotrophic mutations, such as a deletion of aroA, are commonly introduced into such bacteria for attenuation without incapacitating immunostimulation. In this study, we describe the surprising finding that deletion of aroA dramatically increased the virulence of attenuated Salmonella in mouse models. Mutant bacteria lacking aroA elicited increased levels of the proinflammatory cytokine tumor necrosis factor alpha (TNF-α) after systemic application. A detailed genetic and phenotypic characterization in combination with transcriptomic and metabolic profiling demonstrated that ΔaroA mutants display pleiotropic alterations in cellular physiology and lipid and amino acid metabolism, as well as increased sensitivity to penicillin, complement, and phagocytic uptake. In concert with other immunomodulating mutations, deletion of aroA affected flagellin phase variation and gene expression of the virulence-associated genes arnT and ansB. Finally, ΔaroA strains displayed significantly improved tumor therapeutic activity. These results highlight the importance of a functional shikimate pathway to control homeostatic bacterial physiology. They further highlight the great potential of ΔaroA-attenuated Salmonella for the development of vaccines and cancer therapies with important implications for host-pathogen interactions and translational medicine. PMID:27601574

Metformin directly acts on mitochondria to alter cellular bioenergetics

PubMed Central

2014-01-01

Background Metformin is widely used in the treatment of diabetes, and there is interest in ‘repurposing’ the drug for cancer prevention or treatment. However, the mechanism underlying the metabolic effects of metformin remains poorly understood. Methods We performed respirometry and stable isotope tracer analyses on cells and isolated mitochondria to investigate the impact of metformin on mitochondrial functions. Results We show that metformin decreases mitochondrial respiration, causing an increase in the fraction of mitochondrial respiration devoted to uncoupling reactions. Thus, cells treated with metformin become energetically inefficient, and display increased aerobic glycolysis and reduced glucose metabolism through the citric acid cycle. Conflicting prior studies proposed mitochondrial complex I or various cytosolic targets for metformin action, but we show that the compound limits respiration and citric acid cycle activity in isolated mitochondria, indicating that at least for these effects, the mitochondrion is the primary target. Finally, we demonstrate that cancer cells exposed to metformin display a greater compensatory increase in aerobic glycolysis than nontransformed cells, highlighting their metabolic vulnerability. Prevention of this compensatory metabolic event in cancer cells significantly impairs survival. Conclusions Together, these results demonstrate that metformin directly acts on mitochondria to limit respiration and that the sensitivity of cells to metformin is dependent on their ability to cope with energetic stress. PMID:25184038

Dual-sensing porphyrin-containing copolymer nanosensor as full-spectrum colorimeter and ultra-sensitive thermometer.

PubMed

Yan, Qiang; Yuan, Jinying; Kang, Yan; Cai, Zhinan; Zhou, Lilin; Yin, Yingwu

2010-04-28

A porphyrin-containing copolymer has dual-sensing in response to metal ions and temperature as a novel nanosensor. Triggered by ions, the sensor exhibits full-color tunable behavior as a cationic detector and colorimeter. Responding to temperature, the sensor displays an "isothermal" thermochromic point as an ultra-sensitive thermometer.

Perceiving Group Behavior: Sensitive Ensemble Coding Mechanisms for Biological Motion of Human Crowds

ERIC Educational Resources Information Center

Sweeny, Timothy D.; Haroz, Steve; Whitney, David

2013-01-01

Many species, including humans, display group behavior. Thus, perceiving crowds may be important for social interaction and survival. Here, we provide the first evidence that humans use ensemble-coding mechanisms to perceive the behavior of a crowd of people with surprisingly high sensitivity. Observers estimated the headings of briefly presented…

Anxiety sensitivity and negative urgency: a pathway to negative reinforcement-related smoking expectancies.

PubMed

Guillot, Casey R; Pang, Raina D; Leventhal, Adam M

2014-01-01

Anxiety sensitivity--fear of anxiety symptoms--may increase motivation to smoke by influencing the development of cognitive expectations regarding smoking's negative reinforcing effects; yet, the nature and mechanisms of this pathway are unclear. We hypothesized that relations between anxiety sensitivity and negative reinforcement-related smoking expectancies would be mediated by negative urgency, that is, a trait tendency to act impulsively during negative affect. In a cross-sectional design, we administered self-report measures of anxiety sensitivity, negative urgency, and negative reinforcement-related smoking outcome and abstinence expectancies to 205 smokers (≥10 cigarettes/d, 34% female, M age = 44.4 years). Anxiety sensitivity was associated with stronger expectancies that smoking alleviates negative affect (β = 0.30; P < 0.0001) and smoking abstinence exacerbates aversive withdrawal symptoms (β = 0.24; P = 0.0004). Negative urgency partially mediated the relation between anxiety sensitivity and both types of negative reinforcement-related smoking expectancies (βs ≥ 0.057; Ps ≤ 0.007). Results remained significant after statistically controlling for anxiety and nicotine dependence symptoms. Smokers high in anxiety sensitivity tend to display negative urgency, which in turn is related to greater expectations of negative reinforcement consequences of smoking and smoking abstinence. Treatments that mitigate fear of anxiety symptoms and the tendency to act impulsively in response to negative affect (eg, interoceptive exposure, distress tolerance skills training, and mindfulness training) may be particularly useful in assisting with smoking cessation for high-anxiety sensitivity smokers.

Use of the stereoscopic virtual reality display system for the detection and characterization of intracranial aneurysms: A Icomparison with conventional computed tomography workstation and 3D rotational angiography.

PubMed

Liu, Xiujuan; Tao, Haiquan; Xiao, Xigang; Guo, Binbin; Xu, Shangcai; Sun, Na; Li, Maotong; Xie, Li; Wu, Changjun

2018-07-01

This study aimed to compare the diagnostic performance of the stereoscopic virtual reality display system with the conventional computed tomography (CT) workstation and three-dimensional rotational angiography (3DRA) for intracranial aneurysm detection and characterization, with a focus on small aneurysms and those near the bone. First, 42 patients with suspected intracranial aneurysms underwent both 256-row CT angiography (CTA) and 3DRA. Volume rendering (VR) images were captured using the conventional CT workstation. Next, VR images were transferred to the stereoscopic virtual reality display system. Two radiologists independently assessed the results that were obtained using the conventional CT workstation and stereoscopic virtual reality display system. The 3DRA results were considered as the ultimate reference standard. Based on 3DRA images, 38 aneurysms were confirmed in 42 patients. Two cases were misdiagnosed and 1 was missed when the traditional CT workstation was used. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the conventional CT workstation were 94.7%, 85.7%, 97.3%, 75%, and99.3%, respectively, on a per-aneurysm basis. The stereoscopic virtual reality display system missed a case. The sensitivity, specificity, PPV, NPV, and accuracy of the stereoscopic virtual reality display system were 100%, 85.7%, 97.4%, 100%, and 97.8%, respectively. No difference was observed in the accuracy of the traditional CT workstation, stereoscopic virtual reality display system, and 3DRA in detecting aneurysms. The stereoscopic virtual reality display system has some advantages in detecting small aneurysms and those near the bone. The virtual reality stereoscopic vision obtained through the system was found as a useful tool in intracranial aneurysm diagnosis and pre-operative 3D imaging. Copyright © 2018 Elsevier B.V. All rights reserved.

Sampling-Based Stochastic Sensitivity Analysis Using Score Functions for RBDO Problems with Correlated Random Variables

DTIC Science & Technology

2010-08-01

a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. a ...SECURITY CLASSIFICATION OF: This study presents a methodology for computing stochastic sensitivities with respect to the design variables, which are the...Random Variables Report Title ABSTRACT This study presents a methodology for computing stochastic sensitivities with respect to the design variables

Detection capability of a pulsed Ground Penetrating Radar utilizing an oscilloscope and Radargram Fusion Approach for optimal signal quality

NASA Astrophysics Data System (ADS)

Seyfried, Daniel; Schoebel, Joerg

2015-07-01

In scientific research pulsed radars often employ a digital oscilloscope as sampling unit. The sensitivity of an oscilloscope is determined in general by means of the number of digits of its analog-to-digital converter and the selected full scale vertical setting, i.e., the maximal voltage range displayed. Furthermore oversampling or averaging of the input signal may increase the effective number of digits, hence the sensitivity. Especially for Ground Penetrating Radar applications high sensitivity of the radar system is demanded since reflection amplitudes of buried objects are strongly attenuated in ground. Hence, in order to achieve high detection capability this parameter is one of the most crucial ones. In this paper we analyze the detection capability of our pulsed radar system utilizing a Rohde & Schwarz RTO 1024 oscilloscope as sampling unit for Ground Penetrating Radar applications, such as detection of pipes and cables in the ground. Also effects of averaging and low-noise amplification of the received signal prior to sampling are investigated by means of an appropriate laboratory setup. To underline our findings we then present real-world radar measurements performed on our GPR test site, where we have buried pipes and cables of different types and materials in different depths. The results illustrate the requirement for proper choice of the settings of the oscilloscope for optimal data recording. However, as we show, displaying both strong signal contributions due to e.g., antenna cross-talk and direct ground bounce reflection as well as weak reflections from objects buried deeper in ground requires opposing trends for the oscilloscope's settings. We therefore present our Radargram Fusion Approach. By means of this approach multiple radargrams recorded in parallel, each with an individual optimized setting for a certain type of contribution, can be fused in an appropriate way in order to finally achieve a single radargram which displays all contributions occurring originally at different strengths in an equalized and normalized way by means of appropriate digital signal post-processing.

Touch displays: the effects of palm rejection technology on productivity, comfort, biomechanics and positioning.

PubMed

Camilleri, Matt J; Malige, Ajith; Fujimoto, Jeffrey; Rempel, David M

2013-01-01

Direct touch displays can improve the human-computer experience and productivity; however, the higher hand locations may increase shoulder fatigue. Palm rejection (PR) technology may reduce shoulder loads by allowing the palms to rest on the display and increase productivity by registering the touched content and fingertips through the palms rather than shoulders. The effects of PR were evaluated by having participants perform touch tasks while posture and reaction force on the display were measured. Enabling PR, during which the subjects could place the palms on the display (but were not required to), resulted in increased wrist extension, force applied to the display and productivity, and less discomfort, but had no effect on the self-selected positioning of the display. Participants did not deliberately place their palms on the display; therefore, there was no reduction in shoulder load and the increased productivity was not due to improved hand registration. The increased productivity may have been due to reduced interruptions from palm contacts or reduced motor control demands.

The Role of Sea Ice in 2 x CO2 Climate Model Sensitivity. Part 2; Hemispheric Dependencies

NASA Technical Reports Server (NTRS)

Rind, D.; Healy, R.; Parkinson, C.; Martinson, D.

1997-01-01

How sensitive are doubled CO2 simulations to GCM control-run sea ice thickness and extent? This issue is examined in a series of 10 control-run simulations with different sea ice and corresponding doubled CO2 simulations. Results show that with increased control-run sea ice coverage in the Southern Hemisphere, temperature sensitivity with climate change is enhanced, while there is little effect on temperature sensitivity of (reasonable) variations in control-run sea ice thickness. In the Northern Hemisphere the situation is reversed: sea ice thickness is the key parameter, while (reasonable) variations in control-run sea ice coverage are of less importance. In both cases, the quantity of sea ice that can be removed in the warmer climate is the determining factor. Overall, the Southern Hemisphere sea ice coverage change had a larger impact on global temperature, because Northern Hemisphere sea ice was sufficiently thick to limit its response to doubled CO2, and sea ice changes generally occurred at higher latitudes, reducing the sea ice-albedo feedback. In both these experiments and earlier ones in which sea ice was not allowed to change, the model displayed a sensitivity of -0.02 C global warming per percent change in Southern Hemisphere sea ice coverage.

Evaluation of touch-sensitive screen tablet terminal button size and spacing accounting for effect of fingertip contact angle.

PubMed

Nishimura, T; Doi, K; Fujimoto, H

2015-08-01

Touch-sensitive screen terminals enabling intuitive operation are used as input interfaces in a wide range of fields. Tablet terminals are one of the most common devices with a touch-sensitive screen. They have a feature of good portability, enabling use under various conditions. On the other hand, they require a GUI designed to prevent decrease of usability under various conditions. For example, the angle of fingertip contact with the display changes according to finger posture during operation and how the case is held. When a human fingertip makes contact with an object, the contact area between the fingertip and contact object increases or decreases as the contact angle changes. A touch-sensitive screen detects positions using the change in capacitance of the area touched by the fingertip; hence, differences in contact area between the touch-sensitive screen and fingertip resulting from different forefinger angles during operation could possibly affect operability. However, this effect has never been studied. We therefore conducted an experiment to investigate the relationship between size/spacing and operability, while taking the effect of fingertip contact angle into account. As a result, we have been able to specify the button size and spacing conditions that enable accurate and fast operation regardless of the forefinger contact angle.

Blood pressure responses to dietary sodium: Association with autonomic cardiovascular function in normotensive adults.

PubMed

Matthews, Evan L; Brian, Michael S; Edwards, David G; Stocker, Sean D; Wenner, Megan M; Farquhar, William B

2017-12-01

Blood pressure responses to dietary sodium vary widely person-to-person. Salt sensitive rodent models display altered autonomic function, a trait thought to contribute to poor cardiovascular health. Thus, we hypothesized that increased salt sensitivity (SS) in normotensive humans would be associated with increased muscle sympathetic nerve activity (MSNA), decreased high frequency heart rate variability (HF-HRV), and decreased baroreflex sensitivity. Healthy normotensive men and women completed 1week of high (300mmol·day -1 ) and 1week of low (20mmol·day -1 ) dietary sodium (random order) with 24h mean arterial pressure (MAP) assessed on the last day of each diet to assess SS. Participants returned to the lab under habitual sodium conditions for testing. Forty-two participants are presented in this analysis, 19 of which successful MSNA recordings were obtained (n=42: age 39±2yrs., BMI 24.3±0.5kg·(m 2 ) -1 , MAP 83±1mmHg, habitual urine sodium 93±7mmol·24h -1 ; n=19: MSNA burst frequency 20±2 bursts·min -1 ). The variables of interest were linearly regressed over the magnitude of SS. Higher SS was associated with increased MSNA (burst frequency: r=0.469, p=0.041), decreased HF-HRV (r=-0.349, p=0.046), and increased LF/HF-HRV (r=0.363, p=0.034). SS was not associated with sympathetic or cardiac baroreflex sensitivity (p>0.05). Multiple regression analysis accounting for age found that age, not SS, independently predicted HF-HRV (age adjusted no longer significant; p=0.369) and LF/HF-HRV (age adjusted p=0.273). These data suggest that age-related salt sensitivity of blood pressure in response to dietary sodium is associated with altered resting autonomic cardiovascular function. Copyright © 2017 Elsevier B.V. All rights reserved.

Deoxycytidine Deaminase-Deficient Escherichia coli Strains Display Acute Sensitivity to Cytidine, Adenosine, and Guanosine and Increased Sensitivity to a Range of Antibiotics, Including Vancomycin

PubMed Central

Kang, Tina Manzhu; Yuan, Jessica; Zhou, Alice; Beppler, Casey

2014-01-01

We show here that deoxycytidine deaminase (DCD)-deficient mutants of Escherichia coli are hypersensitive to killing by exogenous cytidine, adenosine, or guanosine, whereas wild-type cells are not. This hypersensitivity is reversed by exogenous thymidine. The mechanism likely involves the allosteric regulation of ribonucleotide reductase and severe limitations of the dTTP pools, resulting in thymineless death, the phenomenon of cell death due to thymidine starvation. We also report here that DCD-deficient mutants of E. coli are more sensitive to a series of different antibiotics, including vancomycin, and we show synergistic killing with the combination of vancomycin and cytidine. One possibility is that a very low, subinhibitory concentration of vancomycin enters Gram-negative cells and that this concentration is potentiated by chromosomal lesions resulting from the thymineless state. A second possibility is that the metabolic imbalance resulting from DCD deficiency affects the assembly of the outer membrane, which normally presents a barrier to drugs such as vancomycin. We consider these findings with regard to ideas of rendering Gram-negative bacteria sensitive to drugs such as vancomycin. PMID:24633874

The Effects of Maternal Exposure to Bisphenol A on Allergic Lung Inflammation into Adulthood

PubMed Central

Lawrence, B. Paige

2012-01-01

Bisphenol A (BPA) is a high–production volume chemical classified as an environmental estrogen and used primarily in the plastics industry. BPA’s increased usage correlates with rising BPA levels in people and a corresponding increase in the incidence of asthma. Due to limited studies, the contribution of maternal BPA exposure to allergic asthma pathogenesis is unclear. Using two established mouse models of allergic asthma, we examined whether developmental exposure to BPA alters hallmarks of allergic lung inflammation in adult offspring. Pregnant C57BL/6 dams were gavaged with 0, 0.5, 5, 50, or 500 μg BPA/kg/day from gestational day 6 until postnatal day 21. To induce allergic inflammation, adult offspring were mucosally sensitized with inhaled ovalbumin containing low-dose lipopolysaccharide or ip sensitized using ovalbumin with alum followed by ovalbumin aerosol challenge. In the mucosal sensitization model, female offspring that were maternally exposed to ≥ 50 μg BPA/kg/day displayed enhanced airway lymphocytic and lung inflammation, compared with offspring of control dams. Peritoneally sensitized, female offspring exposed to ≤ 50 μg BPA/kg/day presented dampened lung eosinophilia, compared with vehicle controls. Male offspring did not exhibit these differences in either sensitization model. Our data demonstrate that maternal exposure to BPA has subtle and qualitatively different effects on allergic inflammation, which are critically dependent upon route of allergen sensitization and sex. However, these subtle, yet persistent changes due to developmental exposure to BPA did not lead to significant differences in overall airway responsiveness, suggesting that early life exposure to BPA does not exacerbate allergic inflammation into adulthood. PMID:22821851

Aldosterone acting through the central nervous system sensitizes angiotensin II-induced hypertension.

PubMed

Xue, Baojian; Zhang, Zhongming; Roncari, Camila F; Guo, Fang; Johnson, Alan Kim

2012-10-01

Previous studies have shown that preconditioning rats with a nonpressor dose of angiotensin II (Ang II) sensitizes the pressor response produced by later treatment with a higher dose of Ang II and that Ang II and aldosterone (Aldo) can modulate each other's pressor effects through actions involving the central nervous system. The current studies tested whether Aldo can cross-sensitize the pressor actions of Ang II to enhance hypertension by employing an induction-delay-expression experimental design. Male rats were implanted for telemetered blood pressure recording. During induction, subpressor doses of either subcutaneous or intracerebroventricular Aldo were delivered for 1 week. Rats were then rested for 1 week (delay) to assure that any exogenous Aldo was metabolized. After this, Ang II was given subcutaneously for 2 weeks (expression). During induction and delay, Aldo had no sustained effect on blood pressure. However, during expression, Ang II-induced hypertension was greater in the groups receiving subcutaneous or intracerebroventricular Aldo during induction in comparison with those groups receiving vehicle. Central administration of mineralocorticoid receptor antagonist blocked sensitization. Brain tissue collected at the end of delay and expression showed increased mRNA expression of several renin-angiotensin-aldosterone system components in cardiovascular-related forebrain regions of cross-sensitized rats. Cultured subfornical organ neurons preincubated with Aldo displayed greater increases in [Ca2+]i after Ang II treatment, and there was a greater Fra-like immunoreactivity present at the end of expression in cardiovascular-related forebrain structures. Taken together, these results indicate that Aldo pretreatment cross-sensitizes the development of Ang II-induced hypertension probably by mechanisms that involve the central nervous system.

Germline missense pathogenic variants in the BRCA1 BRCT domain, p.Gly1706Glu and p.Ala1708Glu, increase cellular sensitivity to PARP inhibitor olaparib by a dominant negative effect

PubMed Central

Vaclová, Tereza; Woods, Nicholas T.; Megías, Diego; Gomez-Lopez, Sergio; Setién, Fernando; García Bueno, José María; Macías, José Antonio; Barroso, Alicia; Urioste, Miguel; Esteller, Manel; Monteiro, Alvaro N.A.; Benítez, Javier; Osorio, Ana

2016-01-01

Abstract BRCA1-deficient cells show defects in DNA repair and rely on other members of the DNA repair machinery, which makes them sensitive to PARP inhibitors (PARPi). Although carrying a germline pathogenic variant in BRCA1/2 is the best determinant of response to PARPi, a significant percentage of the patients do not show sensitivity and/or display increased toxicity to the agent. Considering previously suggested mutation-specific BRCA1 haploinsufficiency, we aimed to investigate whether there are any differences in cellular response to PARPi olaparib depending on the BRCA1 mutation type. Lymphoblastoid cell lines derived from carriers of missense pathogenic variants in the BRCA1 BRCT domain (c.5117G > A, p.Gly1706Glu and c.5123C > A, p.Ala1708Glu) showed higher sensitivity to olaparib than cells with truncating variants or wild types (WT). Response to olaparib depended on a basal PARP enzymatic activity, but did not correlate with PARP1 expression. Interestingly, cellular sensitivity to the agent was associated with the level of BRCA1 recruitment into γH2AX foci, being the lowest in cells with missense variants. Since these variants lead to partially stable protein mutants, we propose a model in which the mutant protein acts in a dominant negative manner on the WT BRCA1, impairing the recruitment of BRCA1 into DNA damage sites and, consequently, increasing cellular sensitivity to PARPi. Taken together, our results indicate that carriers of different BRCA1 mutations could benefit from olaparib in a distinct way and show different toxicities to the agent, which could be especially relevant for a potential future use of PARPi as prophylactic agents in BRCA1 mutation carriers. PMID:27742776

Fabrication of amorphous InGaZnO thin-film transistor-driven flexible thermal and pressure sensors

NASA Astrophysics Data System (ADS)

Park, Ick-Joon; Jeong, Chan-Yong; Cho, In-Tak; Lee, Jong-Ho; Cho, Eou-Sik; Kwon, Sang Jik; Kim, Bosul; Cheong, Woo-Seok; Song, Sang-Hun; Kwon, Hyuck-In

2012-10-01

In this work, we present the results concerning the use of amorphous indium-gallium-zinc-oxide (a-IGZO) thin-film transistor (TFT) as a driving transistor of the flexible thermal and pressure sensors which are applicable to artificial skin systems. Although the a-IGZO TFT has been attracting much attention as a driving transistor of the next-generation flat panel displays, no study has been performed about the application of this new device to the driving transistor of the flexible sensors yet. The proposed thermal sensor pixel is composed of the series-connected a-IGZO TFT and ZnO-based thermistor fabricated on a polished metal foil, and the ZnO-based thermistor is replaced by the pressure sensitive rubber in the pressure sensor pixel. In both sensor pixels, the a-IGZO TFT acts as the driving transistor and the temperature/pressure-dependent resistance of the ZnO-based thermistor/pressure-sensitive rubber mainly determines the magnitude of the output currents. The fabricated a-IGZO TFT-driven flexible thermal sensor shows around a seven times increase in the output current as the temperature increases from 20 °C to 100 °C, and the a-IGZO TFT-driven flexible pressure sensors also exhibit high sensitivity under various pressure environments.

The influence of Adh function on ethanol preference and tolerance in adult Drosophila melanogaster.

PubMed

Ogueta, Maite; Cibik, Osman; Eltrop, Rouven; Schneider, Andrea; Scholz, Henrike

2010-11-01

Preference determines behavioral choices such as choosing among food sources and mates. One preference-affecting chemical is ethanol, which guides insects to fermenting fruits or leaves. Here, we show that adult Drosophila melanogaster prefer food containing up to 5% ethanol over food without ethanol and avoid food with high levels (23%) of ethanol. Although female and male flies behaved differently at ethanol-containing food sources, there was no sexual dimorphism in the preference for food containing modest ethanol levels. We also investigated whether Drosophila preference, sensitivity and tolerance to ethanol was related to the activity of alcohol dehydrogenase (Adh), the primary ethanol-metabolizing enzyme in D. melanogaster. Impaired Adh function reduced ethanol preference in both D. melanogaster and a related species, D. sechellia. Adh-impaired flies also displayed reduced aversion to high ethanol concentrations, increased sensitivity to the effects of ethanol on postural control, and negative tolerance/sensitization (i.e., a reduction of the increased resistance to ethanol's effects that normally occurs upon repeated exposure). These data strongly indicate a linkage between ethanol-induced behavior and ethanol metabolism in adult fruit flies: Adh deficiency resulted in reduced preference to low ethanol concentrations and reduced aversion to high ones, despite recovery from ethanol being strongly impaired.

Amyloid-β Deposits Target Efficient Near-Infrared Fluorescent Probes: Synthesis, in Vitro Evaluation, and in Vivo Imaging.

PubMed

Fu, Hualong; Tu, Peiyu; Zhao, Liu; Dai, Jiapei; Liu, Boli; Cui, Mengchao

2016-02-02

The formation of extracellular amyloid-β (Aβ) plaques is a common molecular change that underlies several debilitating human conditions, including Alzheimer's disease (AD); however, the existing near-infrared (NIR) fluorescent probes for the in vivo detection of Aβ plaques are limited by undesirable fluorescent properties and poor brain kinetics. In this work, we designed, synthesized, and evaluated a new family of efficient NIR probes that target Aβ plaques by incorporating hydroxyethyl groups into the ligand structure. Among these probes, DANIR 8c showed excellent fluorescent properties with an emission maximum above 670 nm upon binding to Aβ aggregates and also displayed a high sensitivity (a 629-fold increase in fluorescence intensity) and affinity (Kd = 14.5 nM). Because of the improved hydrophilicity that was induced by hydroxyls, 8c displayed increased initial brain uptake and a fast washout from the brain, as well as an acceptable biostability in the brain. In vivo NIR fluorescent imaging revealed that 8c could efficiently distinguish between AD transgenic model mice and normal controls. Overall, 8c is an efficient and veritable NIR fluorescent probe for the in vivo detection of Aβ plaques in the brain.

Mitochondrial remodeling in adipose tissue associated with obesity and treatment with rosiglitazone

PubMed Central

Wilson-Fritch, Leanne; Nicoloro, Sarah; Chouinard, My; Lazar, Mitchell A.; Chui, Patricia C.; Leszyk, John; Straubhaar, Juerg; Czech, Michael P.; Corvera, Silvia

2004-01-01

Adipose tissue plays a central role in the control of energy homeostasis through the storage and turnover of triglycerides and through the secretion of factors that affect satiety and fuel utilization. Agents that enhance insulin sensitivity, such as rosiglitazone, appear to exert their therapeutic effect through adipose tissue, but the precise mechanisms of their actions are unclear. Rosiglitazone changes the morphological features and protein profiles of mitochondria in 3T3-L1 adipocytes. To examine the relevance of these effects in vivo, we studied white adipocytes from ob/ob mice during the development of obesity and after treatment with rosiglitazone. The levels of approximately 50% of gene transcripts encoding mitochondrial proteins were decreased with the onset of obesity. About half of those genes were upregulated after treatment with rosiglitazone, and this was accompanied by an increase in mitochondrial mass and changes in mitochondrial structure. Functionally, adipocytes from rosiglitazone-treated mice displayed markedly enhanced oxygen consumption and significantly increased palmitate oxidation. These data reveal mitochondrial remodeling and increased energy expenditure in white fat in response to rosiglitazone treatment in vivo and suggest that enhanced lipid utilization in this tissue may affect whole-body energy homeostasis and insulin sensitivity. PMID:15520860

Allyl isothiocyanate induces replication-associated DNA damage response in NSCLC cells and sensitizes to ionizing radiation.

PubMed

Tripathi, Kaushlendra; Hussein, Usama K; Anupalli, Roja; Barnett, Reagan; Bachaboina, Lavanya; Scalici, Jennifer; Rocconi, Rodney P; Owen, Laurie B; Piazza, Gary A; Palle, Komaraiah

2015-03-10

Allyl isothiocyanate (AITC), a constituent of many cruciferous vegetables exhibits significant anticancer activities in many cancer models. Our studies provide novel insights into AITC-induced anticancer mechanisms in human A549 and H1299 non-small cell lung cancer (NSCLC) cells. AITC exposure induced replication stress in NSCLC cells as evidenced by γH2AX and FANCD2 foci, ATM/ATR-mediated checkpoint responses and S and G2/M cell cycle arrest. Furthermore, AITC-induced FANCD2 foci displayed co-localization with BrdU foci, indicating stalled or collapsed replication forks in these cells. Although PITC (phenyl isothiocyanate) exhibited concentration-dependent cytotoxic effects, treatment was less effective compared to AITC. Previously, agents that induce cell cycle arrest in S and G2/M phases were shown to sensitize tumor cells to radiation. Similar to these observations, combination therapy involving AITC followed by radiation treatment exhibited increased DDR and cell killing in NSCLC cells compared to single agent treatment. Combination index (CI) analysis revealed synergistic effects at multiple doses of AITC and radiation, resulting in CI values of less than 0.7 at Fa of 0.5 (50% reduction in survival). Collectively, these studies identify an important anticancer mechanism displayed by AITC, and suggest that the combination of AITC and radiation could be an effective therapy for NSCLC.

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.

Past and future challenges from a display mask writer perspective

NASA Astrophysics Data System (ADS)

Ekberg, Peter; von Sydow, Axel

2012-06-01

Since its breakthrough, the liquid crystal technology has continued to gain momentum and the LCD is today the dominating display type used in desktop monitors, television sets, mobile phones as well as other mobile devices. To improve production efficiency and enable larger screen sizes, the LCD industry has step by step increased the size of the mother glass used in the LCD manufacturing process. Initially the mother glass was only around 0.1 m2 large, but with each generation the size has increased and with generation 10 the area reaches close to 10 m2. The increase in mother glass size has in turn led to an increase in the size of the photomasks used - currently the largest masks are around 1.6 × 1.8 meters. A key mask performance criterion is the absence of "mura" - small systematic errors captured only by the very sensitive human eye. To eliminate such systematic errors, special techniques have been developed by Micronic Mydata. Some mura suppressing techniques are described in this paper. Today, the race towards larger glass sizes has come to a halt and a new race - towards higher resolution and better image quality - is ongoing. The display mask is therefore going through a change that resembles what the semiconductor mask went through some time ago: OPC features are introduced, CD requirements are increasing sharply and multi tone masks (MTMs) are widely used. Supporting this development, Micronic Mydata has introduced a number of compensation methods in the writer, such as Z-correction, CD map and distortion control. In addition, Micronic Mydata MMS15000, the world's most precise large area metrology tool, has played an important role in improving mask placement quality and is briefly described in this paper. Furthermore, proposed specifications and system architecture concept for a new generation mask writers - able to fulfill future image quality requirements - is presented in this paper. This new system would use an AOD/AOM writing engine and be capable of resolving 0.6 micron features.

Low-intensity interval exercise training attenuates coronary vascular dysfunction and preserves Ca²⁺-sensitive K⁺ current in miniature swine with LV hypertrophy.

PubMed

Emter, Craig A; Tharp, Darla L; Ivey, Jan R; Ganjam, Venkataseshu K; Bowles, Douglas K

2011-10-01

Coronary vascular dysfunction has been observed in several models of heart failure (HF). Recent evidence indicates that exercise training is beneficial for patients with HF, but the precise intensity and underlying mechanisms are unknown. Left ventricular (LV) hypertrophy can play a significant role in the development of HF; therefore, the purpose of this study was to assess the effects of low-intensity interval exercise training on coronary vascular function in sedentary (HF) and exercise trained (HF-TR) aortic-banded miniature swine displaying LV hypertrophy. Six months postsurgery, in vivo coronary vascular responses to endothelin-1 (ET-1) and adenosine were measured in the left anterior descending coronary artery. Baseline and maximal coronary vascular conductance were similar between all groups. ET-1-induced reductions in coronary vascular conductance (P < 0.05) were greater in HF vs. sedentary control and HF-TR groups. Pretreatment with the ET type A (ET(A)) receptor blocker BQ-123 prevented ET-1 hypersensitivity in HF animals. Whole cell voltage clamp was used to characterize composite K(+) currents (I(K(+))) in coronary smooth muscle cells. Raising internal Ca(2+) from 200 to 500 nM increased Ca(2+)-sensitive K(+) current in HF-TR and control, but not HF animals. In conclusion, an ET(A)-receptor-mediated hypersensitivity to ET-1, elevated resting LV wall tension, and decreased coronary smooth muscle cell Ca(2+)-sensitive I(K(+)) was found in sedentary animals with LV hypertrophy. Low-intensity interval exercise training preserved normal coronary vascular function and smooth muscle cell Ca(2+)-sensitive I(K(+)), illustrating a potential mechanism underlying coronary vascular dysfunction in a large-animal model of LV hypertrophy. Our results demonstrate the potential clinical impact of exercise on coronary vascular function in HF patients displaying pathological LV hypertrophy.

Low-intensity interval exercise training attenuates coronary vascular dysfunction and preserves Ca2+-sensitive K+ current in miniature swine with LV hypertrophy

PubMed Central

Tharp, Darla L.; Ivey, Jan R.; Ganjam, Venkataseshu K.; Bowles, Douglas K.

2011-01-01

Coronary vascular dysfunction has been observed in several models of heart failure (HF). Recent evidence indicates that exercise training is beneficial for patients with HF, but the precise intensity and underlying mechanisms are unknown. Left ventricular (LV) hypertrophy can play a significant role in the development of HF; therefore, the purpose of this study was to assess the effects of low-intensity interval exercise training on coronary vascular function in sedentary (HF) and exercise trained (HF-TR) aortic-banded miniature swine displaying LV hypertrophy. Six months postsurgery, in vivo coronary vascular responses to endothelin-1 (ET-1) and adenosine were measured in the left anterior descending coronary artery. Baseline and maximal coronary vascular conductance were similar between all groups. ET-1-induced reductions in coronary vascular conductance (P < 0.05) were greater in HF vs. sedentary control and HF-TR groups. Pretreatment with the ET type A (ETA) receptor blocker BQ-123 prevented ET-1 hypersensitivity in HF animals. Whole cell voltage clamp was used to characterize composite K+ currents (IK+) in coronary smooth muscle cells. Raising internal Ca2+ from 200 to 500 nM increased Ca2+-sensitive K+ current in HF-TR and control, but not HF animals. In conclusion, an ETA-receptor-mediated hypersensitivity to ET-1, elevated resting LV wall tension, and decreased coronary smooth muscle cell Ca2+-sensitive IK+ was found in sedentary animals with LV hypertrophy. Low-intensity interval exercise training preserved normal coronary vascular function and smooth muscle cell Ca2+-sensitive IK+, illustrating a potential mechanism underlying coronary vascular dysfunction in a large-animal model of LV hypertrophy. Our results demonstrate the potential clinical impact of exercise on coronary vascular function in HF patients displaying pathological LV hypertrophy. PMID:21841018

Quantification of M13 and T7 bacteriophages by TaqMan and SYBR green qPCR.

PubMed

Peng, Xiujuan; Nguyen, Alex; Ghosh, Debadyuti

2018-02-01

TaqMan and SYBR Green quantitative PCR (qPCR) methods were developed as DNA-based approaches to reproducibly enumerate M13 and T7 phages from phage display selection experiments individually and simultaneously. The genome copies of M13 and T7 phages were quantified by TaqMan or SYBR Green qPCR referenced against M13 and T7 DNA standard curves of known concentrations. TaqMan qPCR was capable of quantifying M13 and T7 phage DNA simultaneously with a detection range of 2.75*10 1 -2.75*10 8 genome copies(gc)/μL and 2.66*10 1 -2.66*10 8 genome copies(gc)/μL respectively. TaqMan qPCR demonstrated an efficient amplification efficiency (E s ) of 0.97 and 0.90 for M13 and T7 phage DNA, respectively. SYBR Green qPCR was ten-fold more sensitive than TaqMan qPCR, able to quantify 2.75-2.75*10 7 gc/μL and 2.66*10 1 -2.66*10 7 gc/μL of M13 and T7 phage DNA, with an amplification efficiency E s of 1.06 and 0.78, respectively. Due to its superior sensitivity, SYBR Green qPCR was used to enumerate M13 and T7 phage display clones selected against a cell line, and quantified titers demonstrated accuracy comparable to titers from traditional double-layer plaque assay. Compared to enzyme linked immunosorbent assay, both qPCR methods exhibited increased detection sensitivity and reproducibility. These qPCR methods are reproducible, sensitive, and time-saving to determine their titers and to quantify a large number of phage samples individually or simultaneously, thus avoiding the need for time-intensive double-layer plaque assay. These findings highlight the attractiveness of qPCR for phage enumeration for applications ranging from selection to next-generation sequencing (NGS). Copyright © 2017 Elsevier B.V. All rights reserved.

New Saccharomyces cerevisiae baker's yeast displaying enhanced resistance to freezing.

PubMed

Codón, Antonio C; Rincón, Ana M; Moreno-Mateos, Miguel A; Delgado-Jarana, Jesús; Rey, Manuel; Limón, Carmen; Rosado, Ivan V; Cubero, Beatriz; Peñate, Xenia; Castrejón, Francisco; Benítez, Tahía

2003-01-15

Three procedures were used to obtain new Saccharomyces cerevisiae baker's yeasts with increased storage stability at -20, 4, 22, and 30 degrees C. The first used mitochondria from highly ethanol-tolerant wine yeast, which were transferred to baker's strains. Viability of the heteroplasmons was improved shortly after freezing. However, after prolonged storage, viability dramatically decreased and was accompanied by an increase in the frequency of respiratory-deficient (petite) mutant formation. This indicated that mitochondria were not stable and were incompatible with the nucleus. The strains tested regained their original resistance to freezing after recovering their own mitochondria. The second procedure used hybrid formation after protoplast fusion and isolation on selective media of fusants from baker's yeast meiotic products resistant to parafluorphenylalanine and cycloheximide, respectively. No hybrids were obtained when using the parentals, probably due to the high ploidy of the baker's strains. Hybrids obtained from nonisogenic strains manifested in all cases a resistance to freezing intermediate between those of their parental strains. Hybrids from crosses between meiotic products of the same strain were always more sensitive than their parentals. The third method was used to develop baker's yeast mutants resistant to 2-deoxy-d-glucose (DOG) and deregulated for maltose and sucrose metabolism. Mutant DOG21 displayed a slight increase in trehalose content and viability both in frozen doughs and during storage at 4 and 22 degrees C. This mutant also displayed a capacity to ferment, under laboratory conditions, both lean and sweet fresh and frozen doughs. For industrial uses, fermented lean and sweet bakery products, both from fresh and frozen doughs obtained with mutant DOG21, were of better quality with regard to volume, texture, and organoleptic properties than those produced by the wild type.

Motivated social categorization: fundamental motives enhance people's sensitivity to basic social categories.

PubMed

Maner, Jon K; Miller, Saul L; Moss, Justin H; Leo, Jennifer L; Plant, E Ashby

2012-07-01

This article presents an evolutionary framework for identifying the characteristics people use to categorize members of their social world. Findings suggest that fundamental social motives lead people to implicitly categorize social targets based on whether those targets display goal-relevant phenotypic traits. A mate-search prime caused participants to categorize opposite-sex targets (but not same-sex targets) based on their level of physical attractiveness (Experiment 1). A mate-guarding prime interacted with relationship investment, causing participants to categorize same-sex targets (but not opposite-sex targets) based on their physical attractiveness (Experiment 2). A self-protection prime interacted with chronic beliefs about danger, increasing participants' tendency to categorize targets based on their racial group membership (Black or White; Experiment 3). This work demonstrates that people categorize others based on whether they display goal-relevant characteristics reflecting high levels of perceived desirability or threat. Social categorization is guided by fundamental evolved motives designed to enhance adaptive social outcomes. PsycINFO Database Record (c) 2012 APA, all rights reserved

Immunohistochemical expression study of proapoptotic BH3-only protein bad in canine nonneoplastic tissues and canine lymphomas.

PubMed

Dettwiler, M; Croci, M; Vaughan, L; Guscetti, F

2013-09-01

The BH3-only protein Bad is a proapoptotic Bcl-2 family member that acts as a sensitizer in intrinsic apoptosis by inactivating antiapoptotic members through heterodimer formation. Bad has been shown to contribute to tumorigenesis, including lymphoma formation in humans and mice, through alteration in expression or functional status. Here, its immunohistochemical expression was analyzed in canine nonneoplastic and lymphoma tissues using tissue microarrays. Bad was expressed in the cytoplasm of a wide range of nonneoplastic tissues, especially epithelial cells. Nonneoplastic lymph nodes displayed weak immunostaining in the follicular germinal centers only. Immunoblotting supported these observations but also revealed presence of nonspecific labeling in some organs. Of 81 lymphomas, 29 (35.8%) displayed moderate to strong immunohistochemical Bad labeling, and a significant expression increase was found in lymphomas (especially B cell and double negative) compared to nonneoplastic lymph nodes. These findings warrant further investigations of the functional status, the involvement of partner proteins, and a possible impact of Bad on prognosis in canine lymphoma.

CD14 Deficiency Impacts Glucose Homeostasis in Mice through Altered Adrenal Tone

PubMed Central

Young, James L.; Mora, Alfonso; Cerny, Anna; Czech, Michael P.; Woda, Bruce; Kurt-Jones, Evelyn A.; Finberg, Robert W.; Corvera, Silvia

2012-01-01

The toll-like receptors comprise one of the most conserved components of the innate immune system, signaling the presence of molecules of microbial origin. It has been proposed that signaling through TLR4, which requires CD14 to recognize bacterial lipopolysaccharide (LPS), may generate low-grade inflammation and thereby affect insulin sensitivity and glucose metabolism. To examine the long-term influence of partial innate immune signaling disruption on glucose homeostasis, we analyzed knockout mice deficient in CD14 backcrossed into the diabetes-prone C57BL6 background at 6 or 12 months of age. CD14-ko mice, fed either normal or high-fat diets, displayed significant glucose intolerance compared to wild type controls. They also displayed elevated norepinephrine urinary excretion and increased adrenal medullary volume, as well as an enhanced norepinephrine secretory response to insulin-induced hypoglycemia. These results point out a previously unappreciated crosstalk between innate immune- and sympathoadrenal- systems, which exerts a major long-term effect on glucose homeostasis. PMID:22253759

Feasibility of dynamic cardiac ultrasound transmission via mobile phone for basic emergency teleconsultation.

PubMed

Lim, Tae Ho; Choi, Hyuk Joong; Kang, Bo Seung

2010-01-01

We assessed the feasibility of using a camcorder mobile phone for teleconsulting about cardiac echocardiography. The diagnostic performance of evaluating left ventricle (LV) systolic function was measured by three emergency medicine physicians. A total of 138 short echocardiography video sequences (from 70 subjects) was selected from previous emergency room ultrasound examinations. The measurement of LV ejection fraction based on the transmitted video displayed on a mobile phone was compared with the original video displayed on the LCD monitor of the ultrasound machine. The image quality was evaluated using the double stimulation impairment scale (DSIS). All observers showed high sensitivity. There was an improvement in specificity with the observer's increasing experience of cardiac ultrasound. Although the image quality of video on the mobile phone was lower than that of the original, a receiver operating characteristic (ROC) analysis indicated that there was no significant difference in diagnostic performance. Immediate basic teleconsulting of echocardiography movies is possible using current commercially-available mobile phone systems.

FAK-heterozygous mice display enhanced tumour angiogenesis.

PubMed

Kostourou, Vassiliki; Lechertier, Tanguy; Reynolds, Louise E; Lees, Delphine M; Baker, Marianne; Jones, Dylan T; Tavora, Bernardo; Ramjaun, Antoine R; Birdsey, Graeme M; Robinson, Stephen D; Parsons, Maddy; Randi, Anna M; Hart, Ian R; Hodivala-Dilke, Kairbaan

2013-01-01

Genetic ablation of endothelial focal adhesion kinase (FAK) can inhibit pathological angiogenesis, suggesting that loss of endothelial FAK is sufficient to reduce neovascularization. Here we show that reduced stromal FAK expression in FAK-heterozygous mice unexpectedly enhances both B16F0 and CMT19T tumour growth and angiogenesis. We further demonstrate that cell proliferation and microvessel sprouting, but not migration, are increased in serum-stimulated FAK-heterozygous endothelial cells. FAK-heterozygous endothelial cells display an imbalance in FAK phosphorylation at pY397 and pY861 without changes in Pyk2 or Erk1/2 activity. By contrast, serum-stimulated phosphorylation of Akt is enhanced in FAK-heterozygous endothelial cells and these cells are more sensitive to Akt inhibition. Additionally, low doses of a pharmacological FAK inhibitor, although too low to affect FAK autophosphorylation in vitro, can enhance angiogenesis ex vivo and tumour growth in vivo. Our results highlight a potential novel role for FAK as a nonlinear, dose-dependent regulator of angiogenesis where heterozygous levels of FAK enhance angiogenesis.

FAK-heterozygous mice display enhanced tumour angiogenesis

PubMed Central

Kostourou, Vassiliki; Lechertier, Tanguy; Reynolds, Louise E.; Lees, Delphine M.; Baker, Marianne; Jones, Dylan T.; Tavora, Bernardo; Ramjaun, Antoine R.; Birdsey, Graeme M.; Robinson, Stephen D.; Parsons, Maddy; Randi, Anna M.; Hart, Ian R; Hodivala-Dilke, Kairbaan

2013-01-01

Genetic ablation of endothelial Focal Adhesion Kinase (FAK) can inhibit pathological angiogenesis, suggesting that loss of endothelial FAK is sufficient to reduce neovascularisation. Here we show that reduced stromal-FAK expression in FAK-heterozygous mice unexpectedly enhances both B16F0 and CMT19T tumour growth and angiogenesis. We further demonstrate that cell proliferation and microvessel sprouting, but not migration, are increased in serum-stimulated FAK-heterozygous endothelial cells. FAK-heterozygous endothelial cells display an imbalance in FAK phosphorylation at pY397 and pY861 without changes in Pyk2 or Erk1/2 activity. By contrast, serum-stimulated phosphorylation of Akt is enhanced in FAK-heterozygous endothelial cells and these cells are more sensitive to Akt inhibition. Additionally, low doses of a pharmacological FAK inhibitor, although too low to affect FAK autophosphorylation in vitro, can enhance angiogenesis ex vivo and tumor growth in vivo. Our results highlight a potential novel role for FAK as a non-linear, dose-dependent regulator of angiogenesis where heterozygous levels of FAK enhance angiogenesis. PMID:23799510

Gender differences in the motivational processing of facial beauty☆

PubMed Central

Levy, Boaz; Ariely, Dan; Mazar, Nina; Chi, Won; Lukas, Scott; Elman, Igor

2013-01-01

Gender may be involved in the motivational processing of facial beauty. This study applied a behavioral probe, known to activate brain motivational regions, to healthy heterosexual subjects. Matched samples of men and women were administered two tasks: (a) key pressing to change the viewing time of average or beautiful female or male facial images, and (b) rating the attractiveness of these images. Men expended more effort (via the key-press task) to extend the viewing time of the beautiful female faces. Women displayed similarly increased effort for beautiful male and female images, but the magnitude of this effort was substantially lower than that of men for beautiful females. Heterosexual facial attractiveness ratings were comparable in both groups. These findings demonstrate heterosexual specificity of facial motivational targets for men, but not for women. Moreover, heightened drive for the pursuit of heterosexual beauty in the face of regular valuational assessments, displayed by men, suggests a gender-specific incentive sensitization phenomenon. PMID:24282336

Rapid Assessment of Contrast Sensitivity with Mobile Touch-screens

NASA Technical Reports Server (NTRS)

Mulligan, Jeffrey B.

2013-01-01

The availability of low-cost high-quality touch-screen displays in modern mobile devices has created opportunities for new approaches to routine visual measurements. Here we describe a novel method in which subjects use a finger swipe to indicate the transition from visible to invisible on a grating which is swept in both contrast and frequency. Because a single image can be swiped in about a second, it is practical to use a series of images to zoom in on particular ranges of contrast or frequency, both to increase the accuracy of the measurements and to obtain an estimate of the reliability of the subject. Sensitivities to chromatic and spatio-temporal modulations are easily measured using the same method. We will demonstrate a prototype for Apple Computer's iPad-iPod-iPhone family of devices, implemented using an open-source scripting environment known as QuIP (QUick Image Processing,

A Magnetic Tracking System based on Highly Sensitive Integrated Hall Sensors

NASA Astrophysics Data System (ADS)

Schlageter, Vincent; Drljaca, Predrag; Popovic, Radivoje S.; KuČERA, Pavel

A tracking system with five degrees of freedom based on a 2D-array of 16 Hall sensors and a permanent magnet is presented in this paper. The sensitivity of the Hall sensors is increased by integrated micro- and external macro-flux-concentrators. Detection distance larger than 20cm (during one hour without calibration) is achieved using a magnet of 0.2cm3. This corresponds to a resolution of the sensors of 0.05µTrms. The position and orientation of the marker is displayed in real time at least 20 times per second. The sensing system is small enough to be hand-held and can be used in a normal environment. This presented tracking system has been successfully applied to follow a small swallowed magnet through the entire human digestive tube. This approach is extremely promising as a new non-invasive diagnostic technique in gastro-enterology.

Misophonia: incidence, phenomenology, and clinical correlates in an undergraduate student sample.

PubMed

Wu, Monica S; Lewin, Adam B; Murphy, Tanya K; Storch, Eric A

2014-10-01

Individuals with misophonia display extreme sensitivities to selective sounds, often resulting in negative emotions and subsequent maladaptive behaviors, such as avoidance and anger outbursts. While there has been increasing interest in misophonia, few data have been published to date. This study investigated the incidence, phenomenology, correlates, and impairment associated with misophonia symptoms in 483 undergraduate students through self-report measures. Misophonia was a relatively common phenomenon, with nearly 20% of the sample reporting clinically significant misophonia symptoms. Furthermore, misophonia symptoms demonstrated strong associations with measures of impairment and general sensory sensitivities, and moderate associations with obsessive-compulsive, anxiety, and depressive symptoms. Anxiety mediated the relationship between misophonia and anger outbursts. This investigation contributes to a better understanding of misophonia and indicates potential factors that may co-occur and influence the clinical presentation of a person with misophonia symptoms. © 2014 Wiley Periodicals, Inc.

Infants' Sensitivity to the Congruence of Others' Emotions and Actions

ERIC Educational Resources Information Center

Hepach, Robert; Westermann, Gert

2013-01-01

As humans, we are attuned to the moods and emotions of others. This understanding of emotions enables us to interpret other people's actions on the basis of their emotional displays. However, the development of this capacity is not well understood. Here we show a developmental pattern in 10- and 14-month-old infants' sensitivity to others'…

The Effect of Script on Poor Readers' Sensitivity to Dynamic Visual Stimuli

ERIC Educational Resources Information Center

Kim, Jeesun; Davis, Chris; Burnham, Denis; Luksaneeyanawin, Sudaporn

2004-01-01

The current research examined performance of good and poor readers of Thai on two tasks that assess sensitivity to dynamic visual displays. Readers of Thai, a complex alphabetic script that nonetheless has a regular orthography, were chosen in order to contrast patterns of performance with readers of Korean Hangul (a similarly regular language but…

On a "Level-Sensitive" Headcount Ratio: Revisiting Shorrocks' Poverty Index

ERIC Educational Resources Information Center

Subramanian, Sreenivasan

2008-01-01

It is often argued that indicators of achievement or deprivation should be measured such that they display a property of "level-sensitivity", whereby a given change in the indicator acquires a greater significance the higher (lower) the level of achievement (deprivation) at which the change occurs. In this note, it is shown that a level-sensitive…

Molecular dissection of the interactions of an antitumor interleukin-2-derived mutein on a phage display-based platform.

PubMed

Rojas, Gertrudis; Carmenate, Tania; Leon, Kalet

2015-04-01

A mutein with stronger antitumor activity and lower toxicity than wild-type human interleukin-2 (IL-2) has been recently described. The rationale behind its design was to reinforce the immunostimulatory potential through the introduction of four mutations that would selectively disrupt the interaction with the IL-2 receptor alpha chain (thought to be critical for both IL-2-driven expansion of T regulatory cells and IL-2-mediated toxic effects). Despite the successful results of the mutein in several tumor models, characterization of its interactions was still to be performed. The current work, based on phage display of IL-2-derived variants, showed the individual contribution of each mutation to the impairment of alpha chain binding. A more sensitive assay, based on the ability of phage-displayed IL-2 variants to induce proliferation of the IL-2-dependent CTLL-2 cell line, revealed differences between the mutated variants. The results validated the mutein design, highlighting the importance of the combined effects of the four mutations. The developed phage display-based platform is robust and sensitive, allows a fast comparative evaluation of multiple variants, and could be broadly used to engineer IL-2 and related cytokines, accelerating the development of cytokine-derived therapeutics. Copyright © 2015 John Wiley & Sons, Ltd.

The Role of Hypothalamic Estrogen Receptors in Metabolic Regulation

PubMed Central

Frank, Aaron; Brown, Lynda M.; Clegg, Deborah J.

2014-01-01

Estrogens regulate key features of metabolism, including food intake, body weight, energy expenditure, insulin sensitivity, leptin sensitivity, and body fat distribution. There are two ”classical“ estrogen receptors (ERs): estrogen receptor alpha (ERS1) and estrogen receptor beta (ERS2). Human and murine data indicate ERS1 contributes to metabolic regulation more so than ESR2. For example, there are human inactivating mutations of ERS1 which recapitulate aspects of the metabolic syndrome in both men and women. Much of our understanding of the metabolic roles of ERS1 was initially uncovered in estrogen receptor α-null mice (ERS1−/−); these mice display aspects of the metabolic syndrome, including increased body weight, increased visceral fat deposition and dysregulated glucose intolerance. Recent data further implicate ERS1 in specific tissues and neuronal populations as being critical for regulating food intake, energy expenditure, body fat distribution and adipose tissue function. This review will focus predominantly on the role of hypothalamic ERs and their critical role in regulating all aspects of energy homeostasis and metabolism. PMID:24882636

The role of hypothalamic estrogen receptors in metabolic regulation.

PubMed

Frank, Aaron; Brown, Lynda M; Clegg, Deborah J

2014-10-01

Estrogens regulate key features of metabolism, including food intake, body weight, energy expenditure, insulin sensitivity, leptin sensitivity, and body fat distribution. There are two 'classical' estrogen receptors (ERs): estrogen receptor alpha (ERS1) and estrogen receptor beta (ERS2). Human and murine data indicate ERS1 contributes to metabolic regulation more so than ESR2. For example, there are human inactivating mutations of ERS1 which recapitulate aspects of the metabolic syndrome in both men and women. Much of our understanding of the metabolic roles of ERS1 was initially uncovered in estrogen receptor α-null mice (ERS1(-/-)); these mice display aspects of the metabolic syndrome, including increased body weight, increased visceral fat deposition and dysregulated glucose intolerance. Recent data further implicate ERS1 in specific tissues and neuronal populations as being critical for regulating food intake, energy expenditure, body fat distribution and adipose tissue function. This review will focus predominantly on the role of hypothalamic ERs and their critical role in regulating all aspects of energy homeostasis and metabolism. Copyright © 2014 Elsevier Inc. All rights reserved.

C-reactive protein in relation to early atherosclerosis and periodontitis.

PubMed

Yakob, Maha; Meurman, Jukka H; Jogestrand, Tomas; Nowak, Jacek; Söder, Per-Östen; Söder, Birgitta

2012-02-01

Periodontitis may affect atherosclerosis via the chronic inflammation. We investigated high-sensitivity C-reactive protein (hsCRP) in relation to early vascular atherosclerotic changes in non-symptomatic subjects with and without long-term periodontitis. Carotid ultrasonography with calculation of common carotid artery intima-media area (cIMA) was performed, and hsCRP and atherosclerosis risk factors were analysed in randomly chosen 93 patients with periodontitis and 41 controls. The relationship between hsCRP, cIMA and atherosclerosis risk factors was evaluated with multiple logistic regression analysis. Women displayed lower hsCRP (p < 0.05) and higher serum HDL (p < 0.001) than men. In all patients with periodontitis, cIMA values were higher than in controls. Periodontitis appeared to be a major predictor for increased cIMA (odds ratio, 3.82; 95% confidence interval, 1.19-12.26). Neither of these factors was significantly associated with hsCRP which thus appeared not sensitive enough to be a marker for periodontitis or atherosclerosis. Hence, irrespective of low hsCRP levels, periodontitis appeared to increase the risk for atherosclerosis.

Plant response to solar ultraviolet radiation

NASA Technical Reports Server (NTRS)

Caldwell, M. M.

1981-01-01

Plant reactions and mechanisms of reaction to solar UV radiation are reviewed, along with characteristics of plants which enhance UV tolerance. Wavelength regions to which proteins are particularly sensitive are examined and the possibility of synergistic effects from photoreactions to multiple wavelengths is considered, along with available evidence of nonadditive plant spectral responses to UV radiation. Decreases in atmospheric ozone content are explored in terms of UV wavelengths which would increase with the ozone decreases, particularly for UV-B, which depresses photosynthesis and would increase 1% with a 16% reduction of stratospheric ozone. Higher elevations are projected to display effects of increased UV incident flux first, and global distributions of UV increases due to atmospheric inhomogeneity and water surface clarity are examined. Finally, the response of plant nucleic acids, DNA, chlorophyll to enhanced UV are described, along with repair, avoidance, and optical mechanisms which aid plant survival

A three-dimensional microelectrode array composed of vertically aligned ultra-dense carbon nanotube networks

NASA Astrophysics Data System (ADS)

Nick, C.; Yadav, S.; Joshi, R.; Schneider, J. J.; Thielemann, C.

2015-07-01

Electrodes based on carbon nanotubes are a promising approach to manufacture highly sensitive sensors with a low limit of signal detection and a high signal-to-noise ratio. This is achieved by dramatically increasing the electrochemical active surface area without increasing the overall geometrical dimensions. Typically, carbon nanotube electrodes are nearly planar and composed of randomly distributed carbon nanotube networks having a limited surface gain for a specific geometrical surface area. To overcome this limitation, we have introduced vertically aligned carbon nanotube (VACNT) networks as electrodes, which are arranged in a microelectrode pattern of 60 single electrodes. Each microelectrode features a very high aspect ratio of more than 300 and thus a dramatically increased surface area. These microelectrodes composed of VACNT networks display dramatically decreased impedance over the entire frequency range compared to planar microelectrodes caused by the enormous capacity increase. This is experimentally verified by electrochemical impedance spectroscopy and cyclic voltammetry.

3D culture of Her2+ breast cancer cells promotes AKT to MAPK switching and a loss of therapeutic response.

PubMed

Gangadhara, Sharath; Smith, Chris; Barrett-Lee, Peter; Hiscox, Stephen

2016-06-01

The Her2 receptor is overexpressed in up to 25 % of breast cancers and is associated with a poor prognosis. Around half of Her2+ breast cancers also express the estrogen receptor and treatment for such tumours can involve both endocrine and Her2-targeted therapies. However, despite preclinical data supporting the effectiveness of these agents, responses can vary widely in the clinical setting. In light of the increasing evidence pointing to the interplay between the tumour and its extracellular microenvironment as a significant determinant of therapeutic sensitivity and response here we investigated the impact of 3D matrix culture of breast cancer cells on their therapeutic sensitivity. A 3D Matrigel-based culture system was established and optimized for the growth of ER+/Her2+ breast cancer cell models. Growth of cells in response to trastuzumab and endocrine agents in 3D culture versus routine monolayer culture were assessed using cell counting and Ki67 staining. Endogenous and trastuzumab-modulated signalling pathway activity in 2D and 3D cultures were assessed using Western blotting. Breast cancer cells in 3D culture displayed an attenuated response to both endocrine agents and trastuzumab compared with cells cultured in traditional 2D monolayers. Underlying this phenomenon was an apparent matrix-induced shift from AKT to MAPK signalling; consequently, suppression of MAPK in 3D cultures restores therapeutic response. These data suggest that breast cancer cells in 3D culture display a reduced sensitivity to therapeutic agents which may be mediated by internal MAPK-mediated signalling. Targeting of adaptive pathways that maintain growth in 3D culture may represent an effective strategy to improve therapeutic response clinically.

Enhanced visualization of inner ear structures

NASA Astrophysics Data System (ADS)

Niemczyk, Kazimierz; Kucharski, Tomasz; Kujawinska, Malgorzata; Bruzgielewicz, Antoni

2004-07-01

Recently surgery requires extensive support from imaging technologies in order to increase effectiveness and safety of operations. One of important tasks is to enhance visualisation of quasi-phase (transparent) 3d structures. Those structures are characterized by very low contrast. It makes differentiation of tissues in field of view very difficult. For that reason the surgeon may be extremly uncertain during operation. This problem is connected with supporting operations of inner ear during which physician has to perform cuts at specific places of quasi-transparent velums. Conventionally during such operations medical doctor views the operating field through stereoscopic microscope. In the paper we propose a 3D visualisation system based on Helmet Mounted Display. Two CCD cameras placed at the output of microscope perform acquisition of stereo pairs of images. The images are processed in real-time with the goal of enhancement of quasi-phased structures. The main task is to create algorithm that is not sensitive to changes in intensity distribution. The disadvantages of existing algorithms is their lack of adaptation to occuring reflexes and shadows in field of view. The processed images from both left and right channels are overlaid on the actual images exported and displayed at LCD's of Helmet Mounted Display. A physician observes by HMD (Helmet Mounted Display) a stereoscopic operating scene with indication of the places of special interest. The authors present the hardware ,procedures applied and initial results of inner ear structure visualisation. Several problems connected with processing of stereo-pair images are discussed.

Characteristics of gradient-interface-structured ZnCdSSe quantum dots with modified interface and its application to quantum-dot-sensitized solar cells

NASA Astrophysics Data System (ADS)

Jeong, Da-Woon; Kim, Jae-Yup; Seo, Han Wook; Lim, Kyoung-Mook; Ko, Min Jae; Seong, Tae-Yeon; Kim, Bum Sung

2018-01-01

Colloidal quantum dots (QDs) are attractive materials for application in photovoltaics, LEDs, displays, and bio devices owing to their unique properties. In this study, we synthesized gradient-interface-structured ZnCdSSe QDs and modified the interface based on a thermodynamic simulation to investigate its optical and physical properties. In addition, the interface was modified by increasing the molar concentration of Se. QDs at the modified interface were applied to QD-sensitized solar cells, which showed a 25.5% increase in photoelectric conversion efficiency owing to the reduced electron confinement effect. The increase seems to be caused by the excited electrons being relatively easily transferred to the level of TiO2 owing to the reduced electron confinement effect. Consequently, the electron confinement effect was observed to be reduced by increasing the ZnSe (or Zn1-xCdxSe)-rich phase at the interface. This means that, based on the thermodynamic simulation, the interface between the core QDs and the surface of the QDs can be controlled. The improvement of optical and electronic properties by controlling interfaces and surfaces during the synthesis of QDs, as reported in this work, can be useful for many applications beyond solar cells.

A reinforcement sensitivity model of affective and behavioral dysregulation in marijuana use and associated problems.

PubMed

Emery, Noah N; Simons, Jeffrey S

2017-08-01

This study tested a model linking sensitivity to punishment (SP) and reward (SR) to marijuana use and problems via affect lability and poor control. A 6-month prospective design was used in a sample of 2,270 young-adults (64% female). The hypothesized SP × SR interaction did not predict affect lability or poor control, but did predict use likelihood at baseline. At low levels of SR, SP was associated with an increased likelihood of abstaining, which was attenuated as SR increased. SP and SR displayed positive main effects on both affect lability and poor control. Affect lability and poor control, in turn, mediated effects on the marijuana outcomes. Poor control predicted both increased marijuana use and, controlling for use level, greater intensity of problems. Affect lability predicted greater intensity of problems, but was not associated with use level. There were few prospective effects. SR consistently predicted greater marijuana use and problems. SP however, exhibited both risk and protective pathways. Results indicate that SP is associated with a decreased likelihood of marijuana use. However, once use is initiated SP is associated with increased risk of problems, in part, due to its effects on both affect and behavioral dysregulation. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Genotype modulates age-related alterations in sensitivity to the aversive effects of ethanol: an eight inbred strain analysis of conditioned taste aversion.

PubMed

Moore, E M; Forrest, R D; Boehm, S L

2013-02-01

Adolescent individuals display altered behavioral sensitivity to ethanol, which may contribute to the increased ethanol consumption seen in this age-group. However, genetics also exert considerable influence on both ethanol intake and sensitivity. Currently there is little research assessing the combined influence of developmental and genetic alcohol sensitivities. Sensitivity to the aversive effects of ethanol using a conditioned taste aversion (CTA) procedure was measured during both adolescence (P30) and adulthood (P75) in eight inbred mouse strains (C57BL/6J, DBA/2J, 129S1/SvImJ, A/J, BALB/cByJ, BTBR T(+) tf/J, C3H/HeJ and FVB/NJ). Adolescent and adult mice were water deprived, and subsequently provided with access to 0.9% (v/v) NaCl solution for 1 h. Immediately following access mice were administered ethanol (0, 1.5, 2.25 and 3 g/kg, ip). This procedure was repeated in 72 h intervals for a total of five CTA trials. Sensitivity to the aversive effects of ethanol was highly dependent upon both strain and age. Within an inbred strain, adolescent animals were consistently less sensitive to the aversive effects of ethanol than their adult counterparts. However, the dose of ethanol required to produce an aversion response differed as a function of both age and strain. © 2012 Blackwell Publishing Ltd and International Behavioural and Neural Genetics Society.

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.

Response of amphipod assemblages to desalination brine discharge: Impact and recovery

NASA Astrophysics Data System (ADS)

de-la-Ossa-Carretero, J. A.; Del-Pilar-Ruso, Y.; Loya-Fernández, A.; Ferrero-Vicente, L. M.; Marco-Méndez, C.; Martinez-Garcia, E.; Sánchez-Lizaso, J. L.

2016-04-01

Desalination has become an important industry whose dense, high-salinity effluent has an impact on marine communities. Without adequate dilution, brine remains on the bottom increasing bottom salinity and affecting benthic communities. Amphipods showed high sensitivity to increased salinity produced by desalination brine discharge. A decrease in abundance and diversity of amphipods was detected at the station closest to the outfall, where salinity values reached 53. This salinity was later reduced by including a diffuser at the end of the pipeline. Six months after diffuser installation, amphipod abundance increased. During the first stage of this recovery, species such as Photis longipes recovered their abundance, others such as Microdeutopus versiculatus displayed opportunistic patterns, while others needed more time for recovery, e.g. Harpinia pectinata. These differences may be dependent on the organism living habits.

Renal tubular NEDD4-2 deficiency causes NCC-mediated salt-dependent hypertension.

PubMed

Ronzaud, Caroline; Loffing-Cueni, Dominique; Hausel, Pierrette; Debonneville, Anne; Malsure, Sumedha Ram; Fowler-Jaeger, Nicole; Boase, Natasha A; Perrier, Romain; Maillard, Marc; Yang, Baoli; Stokes, John B; Koesters, Robert; Kumar, Sharad; Hummler, Edith; Loffing, Johannes; Staub, Olivier

2013-02-01

The E3 ubiquitin ligase NEDD4-2 (encoded by the Nedd4L gene) regulates the amiloride-sensitive epithelial Na+ channel (ENaC/SCNN1) to mediate Na+ homeostasis. Mutations in the human β/γENaC subunits that block NEDD4-2 binding or constitutive ablation of exons 6-8 of Nedd4L in mice both result in salt-sensitive hypertension and elevated ENaC activity (Liddle syndrome). To determine the role of renal tubular NEDD4-2 in adult mice, we generated tetracycline-inducible, nephron-specific Nedd4L KO mice. Under standard and high-Na+ diets, conditional KO mice displayed decreased plasma aldosterone but normal Na+/K+ balance. Under a high-Na+ diet, KO mice exhibited hypercalciuria and increased blood pressure, which were reversed by thiazide treatment. Protein expression of βENaC, γENaC, the renal outer medullary K+ channel (ROMK), and total and phosphorylated thiazide-sensitive Na+Cl- cotransporter (NCC) levels were increased in KO kidneys. Unexpectedly, Scnn1a mRNA, which encodes the αENaC subunit, was reduced and proteolytic cleavage of αENaC decreased. Taken together, these results demonstrate that loss of NEDD4-2 in adult renal tubules causes a new form of mild, salt-sensitive hypertension without hyperkalemia that is characterized by upregulation of NCC, elevation of β/γENaC, but not αENaC, and a normal Na+/K+ balance maintained by downregulation of ENaC activity and upregulation of ROMK.

Characterization of ibrutinib-sensitive and -resistant mantle lymphoma cells.

PubMed

Ma, Jiao; Lu, Pin; Guo, Ailin; Cheng, Shuhua; Zong, Hongliang; Martin, Peter; Coleman, Morton; Wang, Y Lynn

2014-09-01

Ibrutinib inhibits Bruton tyrosine kinase (BTK), a key component of early B-cell receptor (BCR) signalling pathways. A multicentre phase 2 trial of ibrutinib in patients with relapsed/refractory mantle cell lymphoma (MCL) demonstrated a remarkable response rate. However, approximately one-third of patients have primary resistance to the drug while other patients appear to lose response and develop secondary resistance. Understanding the molecular mechanisms underlying ibrutinib sensitivity is of paramount importance. In this study, we investigated cell lines and primary MCL cells that display differential sensitivity to ibrutinib. We found that the primary cells display a higher BTK activity than normal B cells and MCL cells show differential sensitivity to BTK inhibition. Genetic knockdown of BTK inhibits the growth, survival and proliferation of ibrutinib-sensitive but not resistant MCL cell lines, suggesting that ibrutinib acts through BTK to produce its anti-tumour activities. Interestingly, inhibition of ERK1/2 and AKT, but not BTK phosphorylation per se, correlates well with cellular response to BTK inhibition in cell lines as well as in primary tumours. Our study suggests that, to prevent primary resistance or to overcome secondary resistance to BTK inhibition, a combinatory strategy that targets multiple components or multiple pathways may represent the most effective approach. © 2014 John Wiley & Sons Ltd.

Association between frontal plane knee control and lower extremity injuries: a prospective study on young team sport athletes

PubMed Central

Pasanen, Kati; Krosshaug, Tron; Vasankari, Tommi; Kannus, Pekka; Heinonen, Ari; Kujala, Urho M; Avela, Janne; Perttunen, Jarmo; Parkkari, Jari

2018-01-01

Background/aim Poor frontal plane knee control can manifest as increased dynamic knee valgus during athletic tasks. The purpose of this study was to investigate the association between frontal plane knee control and the risk of acute lower extremity injuries. In addition, we wanted to study if the single-leg squat (SLS) test can be used as a screening tool to identify athletes with an increased injury risk. Methods A total of 306 basketball and floorball players participated in the baseline SLS test and a 12-month injury registration follow-up. Acute lower extremity time-loss injuries were registered. Frontal plane knee projection angles (FPKPA) during the SLS were calculated using a two-dimensional video analysis. Results Athletes displaying a high FPKPA were 2.7 times more likely to sustain a lower extremity injury (adjusted OR 2.67, 95% CI 1.23 to 5.83) and 2.4 times more likely to sustain an ankle injury (OR 2.37, 95% CI 1.13 to 4.98). There was no statistically significant association between FPKPA and knee injury (OR 1.49, 95% CI 0.56 to 3.98). The receiver operating characteristic curve analyses indicated poor combined sensitivity and specificity when FPKPA was used as a screening test for lower extremity injuries (area under the curve of 0.59) and ankle injuries (area under the curve of 0.58). Conclusions Athletes displaying a large FPKPA in the SLS test had an elevated risk of acute lower extremity and ankle injuries. However, the SLS test is not sensitive and specific enough to be used as a screening tool for future injury risk. PMID:29387448

Genetic variance contributes to ingestive processes: a survey of eleven inbred mouse strains for fat (Intralipid) intake.

PubMed

Lewis, Sarah R; Dym, Cheryl; Chai, Christina; Singh, Amreeta; Kest, Benjamin; Bodnar, Richard J

2007-01-30

Genetic variation across inbred and outbred mouse strains have been observed for intake of sweet solutions, salts, bitter tastants and a high-fat diet. Our laboratory recently reported marked strain differences in the amounts and/or percentages of kilocalories of sucrose consumed among 11 inbred and one outbred mouse strains exposed to a wide range of nine sucrose concentrations (0.0001-5%) in two-bottle 24-h preference tests. To assess whether differences in fat intake were similarly associated with genetic variation, the present study examined intake of chow, water and an emulsified fat source (Intralipid) across nine different concentrations (0.00001-5%) in the same 11 inbred and 1 outbred mouse strains using two-bottle 24-h preference tests, which controlled for Intralipid concentration presentation effects, Intralipid and water bottle positions, and measurement of kilocalorie intake consumed as Intralipid or chow. Strains displayed differential increases in Intralipid intake relative to corresponding water with significant effects observed at the seven (BALB/cJ: 0.001% threshold sensitivity), four (AKR/J, C57BL/6J, DBA/2J, SWR/J: 0.5% threshold sensitivity), three (CD-1, C57BL/10J, SJL/J: 1% threshold sensitivity) and two (A/J, CBA/J, C3H/HeJ, 129P3/J: 2% threshold sensitivity) highest concentrations. In assessing the percentage of kilocalories consumed as Intralipid, SWR/J mice consumed significantly more at the three highest concentrations to a greater degree than BALB/cJ, C57BL/6J, CD-1, C3H/HeJ, DBA/J and 129P3/J strains which in turn consumed more than A/J, AKR/J, CBA/J, C57BL/10J and SJL/J mice. Relatively strong (h2 = 0.73-0.79) heritability estimates were obtained for weight-adjusted Intralipid intake at those concentrations (0.001-1%) that displayed the largest strain-specific effects in sensitivity to Intralipid. The identification of strains with diverging abilities to regulate kilocalorie intake when presented with high Intralipid concentrations may lead to the successful mapping of genes related to hedonics and obesity.

Complex multifractal nature in Mycobacterium tuberculosis genome

PubMed Central

Mandal, Saurav; Roychowdhury, Tanmoy; Chirom, Keilash; Bhattacharya, Alok; Brojen Singh, R. K.

2017-01-01

The mutifractal and long range correlation (C(r)) properties of strings, such as nucleotide sequence can be a useful parameter for identification of underlying patterns and variations. In this study C(r) and multifractal singularity function f(α) have been used to study variations in the genomes of a pathogenic bacteria Mycobacterium tuberculosis. Genomic sequences of M. tuberculosis isolates displayed significant variations in C(r) and f(α) reflecting inherent differences in sequences among isolates. M. tuberculosis isolates can be categorised into different subgroups based on sensitivity to drugs, these are DS (drug sensitive isolates), MDR (multi-drug resistant isolates) and XDR (extremely drug resistant isolates). C(r) follows significantly different scaling rules in different subgroups of isolates, but all the isolates follow one parameter scaling law. The richness in complexity of each subgroup can be quantified by the measures of multifractal parameters displaying a pattern in which XDR isolates have highest value and lowest for drug sensitive isolates. Therefore C(r) and multifractal functions can be useful parameters for analysis of genomic sequences. PMID:28440326

Complex multifractal nature in Mycobacterium tuberculosis genome

NASA Astrophysics Data System (ADS)

Mandal, Saurav; Roychowdhury, Tanmoy; Chirom, Keilash; Bhattacharya, Alok; Brojen Singh, R. K.

2017-04-01

The mutifractal and long range correlation (C(r)) properties of strings, such as nucleotide sequence can be a useful parameter for identification of underlying patterns and variations. In this study C(r) and multifractal singularity function f(α) have been used to study variations in the genomes of a pathogenic bacteria Mycobacterium tuberculosis. Genomic sequences of M. tuberculosis isolates displayed significant variations in C(r) and f(α) reflecting inherent differences in sequences among isolates. M. tuberculosis isolates can be categorised into different subgroups based on sensitivity to drugs, these are DS (drug sensitive isolates), MDR (multi-drug resistant isolates) and XDR (extremely drug resistant isolates). C(r) follows significantly different scaling rules in different subgroups of isolates, but all the isolates follow one parameter scaling law. The richness in complexity of each subgroup can be quantified by the measures of multifractal parameters displaying a pattern in which XDR isolates have highest value and lowest for drug sensitive isolates. Therefore C(r) and multifractal functions can be useful parameters for analysis of genomic sequences.

The High Strain Rate Deformation Behavior of High Purity Magnesium and AZ31B Magnesium Alloy

NASA Astrophysics Data System (ADS)

Livescu, Veronica; Cady, Carl M.; Cerreta, Ellen K.; Henrie, Benjamin L.; Gray, George T.

The deformation in compression of pure magnesium and AZ31B magnesium alloy, both with a strong basal pole texture, has been investigated as a function of temperature, strain rate, and specimen orientation. The mechanical response of both metals is highly dependent upon the orientation of loading direction with respect to the basal pole. Specimens compressed along the basal pole direction have a high sensitivity to strain rate and temperature and display a concave down work hardening behavior. Specimens loaded perpendicularly to the basal pole have a yield stress that is relatively insensitive to strain rate and temperature and a work hardening behavior that is parabolic and then linearly upwards. Both specimen orientations display a mechanical response that is sensitive to temperature and strain rate. Post mortem characterization of the pure magnesium was conducted on a subset of specimens to determine the microstructural and textural evolution during deformation and these results are correlated with the observed work hardening behavior and strain rate sensitivities were calculated.

Patients with premenstrual syndrome have reduced sensitivity to midazolam compared to control subjects.

PubMed

Sundström, I; Nyberg, S; Bäckström, T

1997-12-01

Premenstrual syndrome (PMS) depends on gonadal hormones produced by the corpus luteum. Given the facilitory actions on GABAergic inhibitory neurotransmission exerted by certain progesterone metabolites, further studies on the GABAA receptor system in premenstrual syndrome are warranted. This study evaluated the benzodiazepine sensitivity in PMS patients and control subjects, using saccadic eye velocity (SEV) and visual analogue ratings of sedation as dependent measures. PMS patients displayed a significantly reduced SEV responsiveness to benzodiazepines compared to control subjects in the follicular phase, whereas there was no difference between groups in the luteal phase. In the luteal phase, the sedation response to benzodiazepines was significantly reduced in PMS patients compared to control subjects. There was also an influence of PMS symptom severity on these measures, as high-severity PMS patients displayed blunted SEV and sedation responses to benzodiazepines compared to low-severity patients. These results indicate that PMS patients have a reduced functional sensitivity at the GABAA/benzodiazepine receptor complex throughout the menstrual cycle.

Resistance to BET Inhibitor Leads to Alternative Therapeutic Vulnerabilities in Castration-Resistant Prostate Cancer.

PubMed

Pawar, Aishwarya; Gollavilli, Paradesi Naidu; Wang, Shaomeng; Asangani, Irfan A

2018-02-27

BRD4 plays a major role in the transcription networks orchestrated by androgen receptor (AR) in castration-resistant prostate cancer (CRPC). Several BET inhibitors (BETi) that displace BRD4 from chromatin are being evaluated in clinical trials for CRPC. Here, we describe mechanisms of acquired resistance to BETi that are amenable to targeted therapies in CRPC. BETi-resistant CRPC cells displayed cross-resistance to a variety of BETi in the absence of gatekeeper mutations, exhibited reduced chromatin-bound BRD4, and were less sensitive to BRD4 degraders/knockdown, suggesting a BRD4-independent transcription program. Transcriptomic analysis revealed reactivation of AR signaling due to CDK9-mediated phosphorylation of AR, resulting in sensitivity to CDK9 inhibitors and enzalutamide. Additionally, increased DNA damage associated with PRC2-mediated transcriptional silencing of DDR genes was observed, leading to PARP inhibitor sensitivity. Collectively, our results identify the therapeutic limitation of BETi as a monotherapy; however, our BETi resistance data suggest unique opportunities for combination therapies in treating CRPC. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Influence of long-term gravity vector changes on mesenchymal stem cells in vitro

NASA Astrophysics Data System (ADS)

Buravkova, L. B.; Merzlikina, N. V.; Romanov, Yu. A.; Buravkov, S. V.

2005-08-01

In vivo and in vitro studies have identified the bone marrow as the primary source of a multipotential mesenchymal stem cells (MSC) that give rise to progenitors for several mesenchymal tissues, including bone, cartilage, tendon, adipose, muscle and hematopoietic-supporting stroma. It is known that MSC are sensitive to chemical signals and mechanical stimuli. It was also suggested that microgravity may influence on progenitor cells and induce abnormalities in cellular differentiation in muscle and skeletal components leading to the changes in physiological regeneration of these tissues. To prove gravitational sensitivity of MSC, we studied the effects of prolonged clinorotation on cultured human MSC (hMSC) morphology, actin cytoskeleton organization and phenotype. It was found that the proliferation rate was significantly decreased during clinorotation but augmented during recovery. The cell cytoskeleton displayed actin filament thinning and altered morphology at clinorotation. The production of interleukin-6 was increased and expression of surface molecules was modified by simulated microgravity. Observed changes of cultured hMSC behavior suggest the gravitational sensitivity of human stromal progenitor cells.

Enhanced Ultraviolet Photon Capture in Ligand-Sensitized Nanocrystals

DOE PAGES

Agbo, Peter; Xu, Tao; Sturzbecher-Hoehne, Manuel; ...

2016-04-06

The small absorption cross sections (ϵ < 10 M -1 cm -1 ) characteristic of Laporte-forbidden transitions in the f-elements have limited the practical implementation of lanthanide nanoparticles in solar capture devices. And while various strategies designed to circumvent the problems of low f-f oscillator strengths have been investigated, comparatively little work has explored the utility of organic ligands with high absorption coefficients (ϵ ≈ 10 3 -10 5 M -1 cm -1 ) in sensitizing excited states in lanthanide nanocrystals. Here, we detail the photophysics of NaGd 1-x Eu x F 4 nanoparticles featuring surface display of the ligandmore » 3,4,3-LI(1,2-HOPO), an aromatic antenna functioning as the terminal light absorber in this system. The result is a ligand-nanocrystal hybrid that converts UV (250-360 nm) light into red Eu(III) luminescence with an external quantum yield of 3.3%. Here, we analyze this sensitization process, responsible for a 10 4 -fold increase in luminescence relative to metal-centered excitation, through a quantitative treatment of energy transfer between ligand and metal states.« less

Measurement of luminance and color uniformity of displays using the large-format scanner

NASA Astrophysics Data System (ADS)

Mazikowski, Adam

2017-08-01

Uniformity of display luminance and color is important for comfort and good perception of the information presented on the display. Although display technology has developed and improved a lot over the past years, different types of displays still present a challenge in selected applications, e.g. in medical use or in case of multi-screen installations. A simplified 9-point method of determining uniformity does not always produce satisfactory results, so a different solution is proposed in the paper. The developed system consists of the large-format X-Y-Z ISEL scanner (isel Germany AG), Konica Minolta high sensitivity spot photometer-colorimeter (e.g. CS-200, Konica Minolta, Inc.) and PC computer. Dedicated software in LabView environment for control of the scanner, transfer the measured data to the computer, and visualization of measurement results was also prepared. Based on the developed setup measurements of plasma display and LCD-LED display were performed. A heavily wornout plasma TV unit, with several artifacts visible was selected. These tests show the advantages and drawbacks of described scanning method with comparison with 9-point simplified uniformity determining method.

M13 bacteriophage coat proteins engineered for improved phage display.

PubMed

Sidhu, Sachdev S; Feld, Birte K; Weiss, Gregory A

2007-01-01

This chapter describes a method for increasing levels of protein fusions displayed on the surfaces of M13 bacteriophage particles. By introducing mutations into the anchoring M13 coat protein, protein display levels can be increased by up to two orders of magnitude. Experimental methods are presented for the design, construction, and screening of phage-displayed libraries for improved protein display.

Mimicking emotions: how 3-12-month-old infants use the facial expressions and eyes of a model.

PubMed

Soussignan, Robert; Dollion, Nicolas; Schaal, Benoist; Durand, Karine; Reissland, Nadja; Baudouin, Jean-Yves

2018-06-01

While there is an extensive literature on the tendency to mimic emotional expressions in adults, it is unclear how this skill emerges and develops over time. Specifically, it is unclear whether infants mimic discrete emotion-related facial actions, whether their facial displays are moderated by contextual cues and whether infants' emotional mimicry is constrained by developmental changes in the ability to discriminate emotions. We therefore investigate these questions using Baby-FACS to code infants' facial displays and eye-movement tracking to examine infants' looking times at facial expressions. Three-, 7-, and 12-month-old participants were exposed to dynamic facial expressions (joy, anger, fear, disgust, sadness) of a virtual model which either looked at the infant or had an averted gaze. Infants did not match emotion-specific facial actions shown by the model, but they produced valence-congruent facial responses to the distinct expressions. Furthermore, only the 7- and 12-month-olds displayed negative responses to the model's negative expressions and they looked more at areas of the face recruiting facial actions involved in specific expressions. Our results suggest that valence-congruent expressions emerge in infancy during a period where the decoding of facial expressions becomes increasingly sensitive to the social signal value of emotions.

Inherited macular degeneration-associated mutations in CNGB3 increase the ligand sensitivity and spontaneous open probability of cone cyclic nucleotide-gated channels

PubMed Central

Meighan, Peter C.; Peng, Changhong; Varnum, Michael D.

2015-01-01

Cyclic nucleotide gated (CNG) channels are a critical component of the visual transduction cascade in the vertebrate retina. Mutations in the genes encoding these channels have been associated with a spectrum of inherited retinal disorders. To gain insight into their pathophysiological mechanisms, we have investigated the functional consequences of several CNGB3 mutations, previously associated with macular degeneration (Y469D and L595F) or complete achromatopsia (S156F, P309L, and G558C), by expressing these subunits in combination with wild-type CNGA3 in Xenopus oocytes and characterizing them using patch-clamp recordings in the inside-out configuration. These mutations did not prevent the formation of functional heteromeric channels, as indicated by sensitivity to block by L-cis-diltiazem. With the exception of S156F, each of the mutant channels displayed electrophysiological properties reflecting enhanced channel activity at physiological concentrations of cGMP (i.e., a gain-of-function phenotype). The increased channel activity produced by these mutations resulted from either increased functional expression levels, or increased sensitivity to cyclic nucleotides. Furthermore, L595F increased the spontaneous open probability in the absence of activating ligand, signifying a ligand independent gain-of-function change. In addition to the CNGB3 disease-associate mutations, we characterized the effects of several common CNGB3 and CNGA3 single-nucleotide polymorphisms (SNPs) on heteromeric CNGA3+CNGB3 channel function. Two of the SNPs examined (A3-T153M, and B3-W234C) produced decreased ligand sensitivity for heteromeric CNG channels. These changes may contribute to background disease susceptibility when combined with other genetic or non-genetic factors. Together, these studies help to define the underlying molecular phenotype for mutations relating to CNG channel disease pathogenesis. PMID:26106334

Dissociation of thirst and sodium appetite in the furo/cap model of extracellular dehydration and a role for N-methyl-D-aspartate receptors in the sensitization of sodium appetite

PubMed Central

Hurley, Seth. W.; Johnson, Alan Kim

2015-01-01

Depletion of extracellular fluids motivates many animals to seek out and ingest water and sodium. Animals with a history of extracellular dehydration display enhanced sodium appetite and in some cases thirst. The progressive increase in sodium intake induced by repeated sodium depletions is known as sensitization of sodium appetite. Administration of the diuretic and natriuretic drug, furosemide, along with a low dose of captopril (furo/cap), elicits thirst and a rapid onset of sodium appetite. In the present studies the furo/cap model was used to explore the physiological mechanisms of sensitization of sodium appetite. However, when thirst and sodium appetite were measured concurrently in the furo/cap model, individual rats exhibited sensitization of either thirst or sodium appetite. In subsequent studies, thirst and sodium appetite were dissociated by offering either water prior to sodium or sodium before water. When water and sodium intake were dissociated in time, the furo/cap model reliably produced sensitization of sodium appetite. It is likely that neuroplasticity mediates this sensitization. Glutamatergic N-methyl-d-aspartate receptor (NMDA-R) activation is critical for the development of most forms of neuroplasticity. Therefore, we hypothesized that integrity of NMDA-R function is necessary for the sensitization of sodium appetite. Pharmacological blockade of NMDA-Rs with systemic administration of MK-801 (0.15mg/kg) prevented the sensitization of fluid intake in general when water and sodium were offered concurrently, and prevented sensitization of sodium intake specifically when water and sodium intake were dissociated. The involvement of NMDA-Rs provides support for the possibility that sensitization of sodium appetite is mediated by neuroplasticity. PMID:24341713

Characterization of the insulin sensitivity of ghrelin receptor KO mice using glycemic clamps

PubMed Central

2011-01-01

Background We and others have demonstrated previously that ghrelin receptor (GhrR) knock out (KO) mice fed a high fat diet (HFD) have increased insulin sensitivity and metabolic flexibility relative to WT littermates. A striking feature of the HFD-fed GhrR KO mouse is the dramatic decrease in hepatic steatosis. To characterize further the underlying mechanisms of glucose homeostasis in GhrR KO mice, we conducted both hyperglycemic (HG) and hyperinsulinemic-euglycemic (HI-E) clamps. Additionally, we investigated tissue glucose uptake and specifically examined liver insulin sensitivity. Results Consistent with glucose tolerance-test data, in HG clamp experiments, GhrR KO mice showed a reduction in glucose-stimulated insulin release relative to WT littermates. Nevertheless, a robust 1st phase insulin secretion was still achieved, indicating that a healthy β-cell response is maintained. Additionally, GhrR KO mice demonstrated both a significantly increased glucose infusion rate and significantly reduced insulin requirement for maintenance of the HG clamp, consistent with their relative insulin sensitivity. In HI-E clamps, both LFD-fed and HFD-fed GhrR KO mice showed higher peripheral insulin sensitivity relative to WT littermates as indicated by a significant increase in insulin-stimulated glucose disposal (Rd), and decreased hepatic glucose production (HGP). HFD-fed GhrR KO mice showed a marked increase in peripheral tissue glucose uptake in a variety of tissues, including skeletal muscle, brown adipose tissue and white adipose tissue. GhrR KO mice fed a HFD also showed a modest, but significant decrease in conversion of pyruvate to glucose, as would be anticipated if these mice displayed increased liver insulin sensitivity. Additionally, the levels of UCP2 and UCP1 were reduced in the liver and BAT, respectively, in GhrR KO mice relative to WT mice. Conclusions These results indicate that improved glucose homeostasis of GhrR KO mice is characterized by robust improvements of glucose disposal in both normal and metabolically challenged states, relative to WT controls. GhrR KO mice have an intact 1st phase insulin response but require significantly less insulin for glucose disposal. Our experiments reveal that the insulin sensitivity of GhrR KO mice is due to both BW independent and dependent factors. We also provide several lines of evidence that a key feature of the GhrR KO mouse is maintenance of hepatic insulin sensitivity during metabolic challenge. PMID:21211044

Development of an Inventory for Health-Care Office Staff to Self-Assess Their Patient-Centered Cultural Sensitivity.

PubMed

Tucker, Carolyn M; Wall, Whitney A; Wippold, Guillermo; Roncoroni, Julia; Marsiske, Michael; Linn, Gabriel S

2016-04-27

Patient-centered culturally sensitive health care (PC-CSHC) is a best practice approach for improving health-care delivery to culturally diverse populations and reducing health disparities. Despite patients' report that cultural sensitivity by health-care office staff is an important aspect of PC-CSHC, the majority of available research on PC-CSHC focuses exclusively on health-care providers. This may be due in part to the paucity of instruments available to assess the cultural sensitivity of health-care office staff. The objective of the present study is to determine the psychometric properties of the Tucker-Culturally Sensitive Health Care Office Staff Inventory-Self-Assessment Form (T-CSHCOSI-SAF). This instrument is designed to enable health-care office staff to self-assess their level of agreement that they display behaviors and attitudes that culturally diverse patients have identified as office staff cultural sensitivity indicators. A sample of 510 health-care office staff were recruited at 67 health-care sites across the United States. These health-care office staff anonymously completed the T-CSHCOSI-SAF and a demographic data questionnaire. Confirmatory factor analyses of the T-CSHCOSI-SAF revealed that this inventory has 2 factors with high internal consistency reliability (Cronbach's αs= .916 and .912). The T-CSHCOSI-SAF is a useful inventory for health-care office staff to assess their own level of patient-centered cultural sensitivity. Such self-assessment data can be used in the development and implementation of trainings to promote patient-centered cultural sensitivity of health-care office staff and to help draw the attention of these staff to displaying patient-centered cultural sensitivity.

Large Screen Display Technology Survey.

DTIC Science & Technology

1984-07-01

gadolinium gallium garnet ). The film is etched to form small light sensitive cells. The area between the cells is covered with a metal film to block the light...Failures MTTR - Mean-Time-To-Repair Nd:YAG - Noedymium: Yttrium Aluminum Garnet Nematic - A term used to describe one of the states of certain liquid...valve within a display, projection or optical processing system. It uses garnet films grown on non-magnetic substrates (Figure 10). The garnet films can

Electrochemical Glucose Biosensor Based on Glucose Oxidase Displayed on Yeast Surface.

PubMed

Wang, Hongwei; Lang, Qiaolin; Liang, Bo; Liu, Aihua

2015-01-01

The conventional enzyme-based biosensor requires chemical or physical immobilization of purified enzymes on electrode surface, which often results in loss of enzyme activity and/or fractions immobilized over time. It is also costly. A major advantage of yeast surface display is that it enables the direct utilization of whole cell catalysts with eukaryote-produced proteins being displayed on the cell surface, providing an economic alternative to traditional production of purified enzymes. Herein, we describe the details of the display of glucose oxidase (GOx) on yeast cell surface and its application in the development of electrochemical glucose sensor. In order to achieve a direct electrochemistry of GOx, the entire cell catalyst (yeast-GOx) was immobilized together with multiwalled carbon nanotubes on the electrode, which allowed sensitive and selective glucose detection.

Isotopic diversity indices: how sensitive to food web structure?

PubMed

Brind'Amour, Anik; Dubois, Stanislas F

2013-01-01

Recently revisited, the concept of niche ecology has lead to the formalisation of functional and trophic niches using stable isotope ratios. Isotopic diversity indices (IDI) derived from a set of measures assessing the dispersion/distribution of points in the δ-space were recently suggested and increasingly used in the literature. However, three main critics emerge from the use of these IDI: 1) they fail to account for the isotopic sources overlap, 2) some indices are highly sensitive to the number of species and/or the presence of rare species, and 3) the lack of standardization prevents any spatial and temporal comparisons. Using simulations we investigated the ability of six commonly used IDI to discriminate among different trophic food web structures, with a focus on the first two critics. We tested the sensitivity of the IDI to five food web structures along a gradient of sources overlap, varying from two distinct food chains with differentiated sources to two superimposed food chains sharing two sources. For each of the food web structure we varied the number of species (from 10 to 100 species) and the type of species feeding behaviour (i.e. random or selective feeding). Values of IDI were generally larger in food webs with distinct basal sources and tended to decrease as the superimposition of the food chains increased. This was more pronounced when species displayed food preferences in comparison to food webs where species fed randomly on any prey. The number of species composing the food web also had strong effects on the metrics, including those that were supposedly less sensitive to small sample size. In all cases, computing IDI on food webs with low numbers of species always increases the uncertainty of the metrics. A threshold of ~20 species was detected above which several metrics can be safely used.

DHA-fluorescent probe is sensitive to membrane order and reveals molecular adaptation of DHA in ordered lipid microdomains☆

PubMed Central

Teague, Heather; Ross, Ron; Harris, Mitchel; Mitchell, Drake C.; Shaikh, Saame Raza

2012-01-01

Docosahexaenoic acid (DHA) disrupts the size and order of plasma membrane lipid microdomains in vitro and in vivo. However, it is unknown how the highly disordered structure of DHA mechanistically adapts to increase the order of tightly packed lipid microdomains. Therefore, we studied a novel DHA-Bodipy fluorescent probe to address this issue. We first determined if the DHA-Bodipy probe localized to the plasma membrane of primary B and immortal EL4 cells. Image analysis revealed that DHA-Bodipy localized into the plasma membrane of primary B cells more efficiently than EL4 cells. We then determined if the probe detected changes in plasma membrane order. Quantitative analysis of time-lapse movies established that DHA-Bodipy was sensitive to membrane molecular order. This allowed us to investigate how DHA-Bodipy physically adapted to ordered lipid microdomains. To accomplish this, we employed steady-state and time-resolved fluorescence anisotropy measurements in lipid vesicles of varying composition. Similar to cell culture studies, the probe was highly sensitive to membrane order in lipid vesicles. Moreover, these experiments revealed, relative to controls, that upon incorporation into highly ordered microdomains, DHA-Bodipy underwent an increase in its fluorescence lifetime and molecular order. In addition, the probe displayed a significant reduction in its rotational diffusion compared to controls. Altogether, DHA-Bodipy was highly sensitive to membrane order and revealed for the first time that DHA, despite its flexibility, could become ordered with less rotational motion inside ordered lipid microdomains. Mechanistically, this explains how DHA acyl chains can increase order upon formation of lipid microdomains in vivo. PMID:22841541

Early life stress sensitizes the renal and systemic sympathetic system in rats.

PubMed

Loria, Analia S; Brands, Michael W; Pollock, David M; Pollock, Jennifer S

2013-08-01

We hypothesized that maternal separation (MS), an early life stress model, induces a sensitization of the sympathetic system. To test this hypothesis, we evaluated the renal and systemic sympathetic system in 12- to 14-wk-old male control or MS rats with the following parameters: 1) effect of renal denervation on conscious renal filtration capacity, 2) norepinephrine (NE) content in key organs involved in blood pressure control, and 3) acute systemic pressor responses to adrenergic stimulation or ganglion blockade. MS was performed by separating pups from their mothers for 3 h/day from day 2 to 14; controls were nonhandled littermates. Glomerular filtration rate (GFR) was examined in renal denervated (DnX; within 2 wk) or sham rats using I¹²⁵-iothalamate plasma clearance. MS-DnX rats showed significantly increased GFR compared with MS-SHAM rats (3.8 ± 0.4 vs. 2.4 ± 0.2 ml/min, respectively, P < 0.05), whereas DnX had no effect in controls, indicating that renal nerves regulate GFR in MS rats. NE content was significantly increased in organ tissues from MS rats (P < 0.05, n = 6-8), suggesting a sensitization of the renal and systemic sympathetic system. Conscious MS rats displayed a significantly greater increase in mean arterial pressure (MAP) in response to NE (2 μg/kg ip) and a greater reduction in MAP in response to mecamylamine (2 mg/kg ip, P < 0.05, n = 4) monitored by telemetry, indicating that MS rats exhibit exaggerated responses to sympathetic stimulation. In conclusion, these data indicate that MS sensitizes the renal and systemic sympathetic system ultimately impairing blood pressure regulation.

Use of sonification in the detection of anomalous events

NASA Astrophysics Data System (ADS)

Ballora, Mark; Cole, Robert J.; Kruesi, Heidi; Greene, Herbert; Monahan, Ganesh; Hall, David L.

2012-06-01

In this paper, we describe the construction of a soundtrack that fuses stock market data with information taken from tweets. This soundtrack, or auditory display, presents the numerical and text data in such a way that anomalous events may be readily detected, even by untrained listeners. The soundtrack generation is flexible, allowing an individual listener to create a unique audio mix from the available information sources. Properly constructed, the display exploits the auditory system's sensitivities to periodicities, to dynamic changes, and to patterns. This type of display could be valuable in environments that demand high levels of situational awareness based on multiple sources of incoming information.

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

Quam, W.; Del Duca, T.; Plake, W.

This paper describes a pocket-calculator-sized, neutron-sensitive, REM-responding personnel dosimeter that uses three tissue-equivalent cylindrical proportional counters as neutron-sensitive detectors. These are conventionally called Linear Energy Transfer (LET) counters. Miniaturized hybrid circuits are used for the linear pulse handling electronics, followed by a 256-channel ADC. A CMOS microprocessor is used to calculate REM exposure from the basic rads-tissue data supplied by the LET counters and also to provide timing and display functions. The instrument is used to continuously accumulate time in hours since reset, total counts accumulated, rads-tissue, and REM. The user can display any one of these items or amore » channel number (an aid in calibration) at any time. Such data are provided with a precision of +- 3% for a total exposure of 1 mREM over eight hours.« less

Construction and Evaluation of an Ultra Low Latency Frameless Renderer for VR.

PubMed

Friston, Sebastian; Steed, Anthony; Tilbury, Simon; Gaydadjiev, Georgi

2016-04-01

Latency - the delay between a user's action and the response to this action - is known to be detrimental to virtual reality. Latency is typically considered to be a discrete value characterising a delay, constant in time and space - but this characterisation is incomplete. Latency changes across the display during scan-out, and how it does so is dependent on the rendering approach used. In this study, we present an ultra-low latency real-time ray-casting renderer for virtual reality, implemented on an FPGA. Our renderer has a latency of ~1 ms from 'tracker to pixel'. Its frameless nature means that the region of the display with the lowest latency immediately follows the scan-beam. This is in contrast to frame-based systems such as those using typical GPUs, for which the latency increases as scan-out proceeds. Using a series of high and low speed videos of our system in use, we confirm its latency of ~1 ms. We examine how the renderer performs when driving a traditional sequential scan-out display on a readily available HMO, the Oculus Rift OK2. We contrast this with an equivalent apparatus built using a GPU. Using captured human head motion and a set of image quality measures, we assess the ability of these systems to faithfully recreate the stimuli of an ideal virtual reality system - one with a zero latency tracker, renderer and display running at 1 kHz. Finally, we examine the results of these quality measures, and how each rendering approach is affected by velocity of movement and display persistence. We find that our system, with a lower average latency, can more faithfully draw what the ideal virtual reality system would. Further, we find that with low display persistence, the sensitivity to velocity of both systems is lowered, but that it is much lower for ours.

Neonatal vaginal irritation results in long-term visceral and somatic hypersensitivity and increased hypothalamic–pituitary–adrenal axis output in female mice

PubMed Central

Pierce, Angela N.; Zhang, Zhen; Fuentes, Isabella M.; Wang, Ruipeng; Ryals, Janelle M.; Christianson, Julie A.

2015-01-01

Abstract Experiencing early life stress or injury increases a woman's likelihood of developing vulvodynia and concomitant dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis. To investigate the outcome of neonatal vaginal irritation (NVI), female mouse pups were administered intravaginal zymosan on postnatal days 8 and 10 and were assessed as adults for vaginal hypersensitivity by measuring the visceromotor response to vaginal balloon distension (VBD). Western blotting and calcium imaging were performed to measure transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) in the vagina and innervating primary sensory neurons. Serum corticosterone (CORT), mast cell degranulation, and corticotropin-releasing factor receptor 1 (CRF1) expression were measured as indicators of peripheral HPA axis activation. Colorectal and hind paw sensitivity were measured to determine cross-sensitization resulting from NVI. Adult NVI mice had significantly larger visceromotor response during VBD than naive mice. TRPA1 protein expression was significantly elevated in the vagina, and calcium transients evoked by mustard oil (TRPA1 ligand) or capsaicin (TRPV1 ligand) were significantly decreased in dorsal root ganglion from NVI mice, despite displaying increased depolarization-evoked calcium transients. Serum CORT, vaginal mast cell degranulation, and CRF1 protein expression were all significantly increased in NVI mice, as were colorectal and hind paw mechanical and thermal sensitivity. Neonatal treatment with a CRF1 antagonist, NBI 35965, immediately before zymosan administration largely attenuated many of the effects of NVI. These results suggest that NVI produces chronic hypersensitivity of the vagina, as well as of adjacent visceral and distant somatic structures, driven in part by increased HPA axis activation. PMID:26098441

The effect of the temperature on the bandgaps based on the chiral liquid crystal polymer

NASA Astrophysics Data System (ADS)

Wang, Jianhua; Shi, Shuhui; Wang, Bainian

2015-10-01

Chiral side-chain liquid crystal polymer is synthesized from polysiloxanes and liqud crystal monomer 4-(Undecenoic-1- yloxybenzoyloxy)-4'-benzonitrile and 6-[4-(4- Undecenoic -1-yloxybenzoyloxy)- hydroxyphenyl] cholesteryl hexanedioate. The optical and thermal property of the monomer and polymer are shown by POM and DSC. As the unique optical property of the polymer, the bandgaps are shifted for heating temperature. The reflection bandgaps is shifted from 546nm to 429nm with temperature increase. As a photonic material, the chiral polymer which sensitive responses under the outfield is widely studied for reflection display, smart switchable reflective windows and defect model CLC laser etc.

IL-10 administration reduces PGE-2 levels and promotes CR3-mediated clearance of Escherichia coli K1 by phagocytes in meningitis.

PubMed

Mittal, Rahul; Gonzalez-Gomez, Ignacio; Panigrahy, Ashok; Goth, Kerstin; Bonnet, Richard; Prasadarao, Nemani V

2010-06-07

Ineffectiveness of antibiotics in treating neonatal Escherichia coli K1 meningitis and the emergence of antibiotic-resistant strains evidently warrants new prevention strategies. We observed that administration of interleukin (IL)-10 during high-grade bacteremia clears antibiotic-sensitive and -resistant E. coli from blood of infected mice. Micro-CT studies of brains from infected animals displayed gross morphological changes similar to those observed in infected human neonates. In mice, IL-10, but not antibiotic or anti-TNF antibody treatment prevented brain damage caused by E. coli. IL-10 administration elevated CR3 expression in neutrophils and macrophages of infected mice, whereas infected and untreated mice displayed increased expression of FcgammaRI and TLR2. Neutrophils or macrophages pretreated with IL-10 ex vivo exhibited a significantly greater microbicidal activity against E. coli compared with cells isolated from wild-type or IL-10-/- mice. The protective effect of IL-10 was abrogated when CR3 was knocked-down in vivo by siRNA. The increased expression of CR3 in phagocytes was caused by inhibition of prostaglandin E-2 (PGE-2) levels, which were significantly increased in neutrophils and macrophages upon E. coli infection. These findings describe a novel modality of IL-10-mediated E. coli clearance by diverting the entry of bacteria via CR3 and preventing PGE-2 formation in neonatal meningitis.

Citrulline-modified phage display: a novel high-throughput discovery approach for the identification of citrulline-containing ligands.

PubMed

Somers, Klaartje; Stinissen, Piet; Somers, Veerle

2011-06-01

Phage display is a high-throughput technology used to identify ligands for a given target. A drawback of the approach is the absence of PTMs in phage-displayed peptides. The applicability of phage display could be broadened considerably by the implementation of PTMs in this system. The aim of this study was to investigate the possible application of citrullination, a PTM of an arginine into a citrulline amino acid, in filamentous (M13) and lytic (T7) phage display. After in vitro citrullination of T7 and M13 phages, citrullination was confirmed and the infectivity of both citrullinated and non-citrullinated phage was compared by titer determination. We demonstrated the successful in vitro citrullination of T7 and M13 phage-displayed peptides. This in vitro modification did not affect the viability or infectivity of the T7 virions, a necessary prerequisite for the implementation of this approach in T7 phage display. For M13 phage, however, the infecting phage titer decreased five-fold upon citrullination, limiting the use of this modification in M13 phage display. In conclusion, in vitro citrullination can be applied in T7 phage display giving rise to a high-throughput and sensitive approach to identify citrulline-containing ligands by the use of the strengths of phage display technology. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Validation of tablet-based evaluation of color fundus images

PubMed Central

Christopher, Mark; Moga, Daniela C.; Russell, Stephen R.; Folk, James C.; Scheetz, Todd; Abràmoff, Michael D.

2012-01-01

Purpose To compare diabetic retinopathy (DR) referral recommendations made by viewing fundus images using a tablet computer to recommendations made using a standard desktop display. Methods A tablet computer (iPad) and a desktop PC with a high-definition color display were compared. For each platform, two retinal specialists independently rated 1200 color fundus images from patients at risk for DR using an annotation program, Truthseeker. The specialists determined whether each image had referable DR, and also how urgently each patient should be referred for medical examination. Graders viewed and rated the randomly presented images independently and were masked to their ratings on the alternative platform. Tablet- and desktop display-based referral ratings were compared using cross-platform, intra-observer kappa as the primary outcome measure. Additionally, inter-observer kappa, sensitivity, specificity, and area under ROC (AUC) were determined. Results A high level of cross-platform, intra-observer agreement was found for the DR referral ratings between the platforms (κ=0.778), and for the two graders, (κ=0.812). Inter-observer agreement was similar for the two platforms (κ=0.544 and κ=0.625 for tablet and desktop, respectively). The tablet-based ratings achieved a sensitivity of 0.848, a specificity of 0.987, and an AUC of 0.950 compared to desktop display-based ratings. Conclusions In this pilot study, tablet-based rating of color fundus images for subjects at risk for DR was consistent with desktop display-based rating. These results indicate that tablet computers can be reliably used for clinical evaluation of fundus images for DR. PMID:22495326

Evaluation of SYBR green I based visual loop-mediated isothermal amplification (LAMP) assay for genus and species-specific diagnosis of malaria in P. vivax and P. falciparum endemic regions.

PubMed

Singh, Ruchi; Singh, Dhirendra Pratap; Savargaonkar, Deepali; Singh, Om P; Bhatt, Rajendra M; Valecha, Neena

2017-01-01

Loop-mediated isothermal amplification (LAMP) is an emerging nucleic acid based diag- nostic approach that is easily adaptable to the field settings with limited technical resources. This study was aimed to evaluate the LAMP assay for the detection and identification of Plasmodium falciparum and P. vivax infection in malaria suspected cases using genus and species-specific assay. The 18S rRNA-based LAMP assay was evaluated for diagnosis of genus Plasmodium, and species- specific diagnosis of P. falciparum and P. vivax, infection employing 317 malaria suspected cases, and the results were compared with those obtained by 18S nested PCR (n-PCR). All the samples were confirmed by microscopy for the presence of Plasmodium parasite. The n-PCR was positive in all Plasmodium-infected cases (n=257; P. falciparum=133; P. vivax=124) and negative in microscopy negative cases (n=58) except for two cases which were positive for P. vivax, giving a sen- sitivity of 100% (95% CI: 97.04-100%) and a specificity of 100% (95% CI: 88.45-99.5%). Genus-specific LAMP assay missed 11 (3.2%) microscopy and n-PCR confirmed vivax malaria cases. Considering PCR results as a refer- ence, LAMP was 100% sensitive and specific for P. falciparum, whereas it exhibited 95.16% sensitivity and 96.7% specificity for P. vivax. The n-PCR assay detected 10 mixed infection cases while species-specific LAMP detected five mixed infection cases of P. vivax and P. falciparum, which were not detected by microscopy. Genus-specific LAMP assay displayed low sensitivity. Falciparum specific LAMP assay displayed high sensitivity whereas vivax specific LAMP assay displayed low sensitivity. Failed detection of vivax cases otherwise confirmed by the n-PCR assay indicates exploitation of new targets and improved detection methods to attain 100% results for P. vivax detection.

Heat processing of peanut seed enhances the sensitization potential of the major peanut allergen Ara h 6.

PubMed

Guillon, Blanche; Bernard, Hervé; Drumare, Marie-Françoise; Hazebrouck, Stéphane; Adel-Patient, Karine

2016-12-01

Processing of food has been shown to impact IgE binding and functionality of food allergens. In the present study, we investigated the impact of heat processing on the sensitization capacity of Ara h 6, a major peanut allergen and one of the most potent elicitors of the allergic reaction. Peanut extracts obtained from raw or heat-processed peanut and some fractions thereof were biochemically and immunochemically characterized. These extracts/fractions, purified Ara h 6, or recombinant Ara h 6 including Ara h 6 mutants lacking disulfide bridges were used in in vitro digestion tests and mouse models of experimental sensitization. Peanut roasting led to the formation of complexes of high molecular weight, notably between Ara h 6 and Ara h 1, which supported the induction of IgE specific to native Ara h 6. On the contrary, a fraction containing free monomeric 2S albumins or purified native Ara h 6 displayed no intrinsic allergenicity. In addition to complex formation, heat denaturation and/or partial destabilization enhanced Ara h 6 immunogenicity and increased its sensitivity to digestion. These results suggest that sensitization potency and IgE binding capacity can be supported by different structures, modified and/or produced during food processing in interaction with other food constituents. © 2016 The Authors. Molecular Nutrition & Food Research published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Age and experience shape developmental changes in the neural basis of language-related learning.

PubMed

McNealy, Kristin; Mazziotta, John C; Dapretto, Mirella

2011-11-01

Very little is known about the neural underpinnings of language learning across the lifespan and how these might be modified by maturational and experiential factors. Building on behavioral research highlighting the importance of early word segmentation (i.e. the detection of word boundaries in continuous speech) for subsequent language learning, here we characterize developmental changes in brain activity as this process occurs online, using data collected in a mixed cross-sectional and longitudinal design. One hundred and fifty-six participants, ranging from age 5 to adulthood, underwent functional magnetic resonance imaging (fMRI) while listening to three novel streams of continuous speech, which contained either strong statistical regularities, strong statistical regularities and speech cues, or weak statistical regularities providing minimal cues to word boundaries. All age groups displayed significant signal increases over time in temporal cortices for the streams with high statistical regularities; however, we observed a significant right-to-left shift in the laterality of these learning-related increases with age. Interestingly, only the 5- to 10-year-old children displayed significant signal increases for the stream with low statistical regularities, suggesting an age-related decrease in sensitivity to more subtle statistical cues. Further, in a sample of 78 10-year-olds, we examined the impact of proficiency in a second language and level of pubertal development on learning-related signal increases, showing that the brain regions involved in language learning are influenced by both experiential and maturational factors. 2011 Blackwell Publishing Ltd.

Comparison of sensitivity and reading time for the use of computer aided detection (CAD) of pulmonary nodules at MDCT as concurrent or second reader

NASA Astrophysics Data System (ADS)

Beyer, F.; Zierott, L.; Fallenberg, E. M.; Juergens, K.; Stoeckel, J.; Heindel, W.; Wormanns, D.

2006-03-01

Purpose: To compare sensitivity and reading time when using CAD as second reader resp. concurrent reader. Materials and Methods: Fifty chest MDCT scans due to clinical indication were analysed independently by four radiologists two times: First with CAD as concurrent reader (display of CAD results simultaneously to the primary reading by the radiologist); then after a median of 14 weeks with CAD as second reader (CAD results were shown after completion of a reading session without CAD). A prototype version of Siemens LungCAD (Siemens,Malvern,USA) was used. Sensitivities and reading times for detecting nodules >=4mm of concurrent reading, reading without CAD and second reading were recorded. In a consensus conference false positive findings were eliminated. Student's T-Test was used to compare sensitivities and reading times. Results: 108 true positive nodules were found. Mean sensitivity was .68 for reading without CAD, .68 for concurrent reading and .75 for second reading. Differences of sensitivities were significant between concurrent and second reading (p<.001) resp. reading without CAD and second reading (p=.001). Mean reading time for concurrent reading was significant shorter (274s) compared to reading without CAD (294s;p=.04) and second reading (337sp<.001). New work to be presented: To our knowledge this is the first study that compares sensitivities and reading times between use of CAD as concurrent resp. second reader. Conclusion: CAD can either be used to speed up reading of chest CT cases for pulmonary nodules without loss of sensitivity as concurrent reader -OR (and not AND) to increase sensitivity and reading time as second reader.

Regime Shifts and Weakened Environmental Gradients in Open Oak and Pine Ecosystems

PubMed Central

Hanberry, Brice B.; Dey, Dan C.; He, Hong S.

2012-01-01

Fire suppression allows tree species that are intolerant of fire stress to increase their distribution, potentially resulting in disruption of historical species-environmental relationships. To measure changes between historical General Land Office surveys (1815 to 1850) and current USDA Forest Inventory and Assessment surveys (2004 to 2008), we compared composition, distribution, and site factors of 21 tree species or species groups in the Missouri Ozarks. We used 24 environmental variables and random forests as a classification method to model distributions. Eastern redcedar, elms, maples, and other fire-sensitive species have increased in dominance in oak forests, with concurrent reductions by oak species; specific changes varied by ecological subsection. Ordinations displayed loss of separation between formerly distinctive oak and fire-sensitive tree species groups. Distribution maps showed decreased presence of disturbance-dependent oak and pine species and increased presence of fire-sensitive species that generally expanded from subsections protected from fire along rivers to upland areas, except for eastern redcedar, which expanded into these subsections. Large scale differences in spatial gradients between past and present communities paralleled reduced influence of local topographic gradients in the varied relief of the Missouri Ozarks, as fire-sensitive species have moved to higher, drier, and sunnier sites away from riverine corridors. Due to changes in land use, landscapes in the Missouri Ozarks, eastern United States, and world-wide are changing from open oak and pine-dominated ecosystems to novel oak-mixed species forests, although at fine scales, forests are becoming more diverse in tree species today. Fire suppression weakened the influence by environmental gradients over species dominance, allowing succession from disturbance-dependent oaks to an alternative state of fire-sensitive species. Current and future research and conservation that rely on historical relationships and ecological principles based on disturbance across the landscape will need to incorporate modern interactions among species for resources into management plans and projections. PMID:22848467

Locomotor conditioning by amphetamine requires cyclin-dependent kinase 5 signaling in the nucleus accumbens

PubMed Central

Singer, Bryan F; Neugebauer, Nichole M; Forneris, Justin; Rodvelt, Kelli R; Li, Dongdong; Bubula, Nancy; Vezina, Paul

2014-01-01

Intermittent systemic exposure to psychostimulants such as amphetamine leads to several forms of long-lasting behavioral plasticity including nonassociative sensitization and associative conditioning. In the nucleus accumbens (NAcc), the protein serine/threonine kinase cyclin-dependent kinase 5 (Cdk5) and its phosphorylation target, the guanine-nucleotide exchange factor kalirin-7 (Kal7), may contribute to the neuroadaptations underlying each of these forms of plasticity. Pharmacological inhibition of Cdk5 in the NAcc prevents the increases in dendritic spine density in this site and enhances the locomotor sensitization normally observed following repeated cocaine. Mice lacking the Kal7 gene display similar phenotypes suggesting that locomotor sensitization and increased NAcc spine density need not be positively correlated. As increases in spine density may relate to the formation of associative memories and both Cdk5 and Kal7 regulate the generation of spines following repeated drug exposure, we hypothesized that either inhibiting Cdk5 or preventing its phosphorylation of Kal7 in the NAcc may prevent the induction of drug conditioning. In the present experiments, blockade in rats of NAcc Cdk5 activity with roscovitine (40 nmol/0.5μl/side) prior to each of 4 injections of amphetamine (1.5 mg/kg; i.p.) prevented the accrual of contextual locomotor conditioning but spared the induction of locomotor sensitization as revealed on tests conducted one week later. Similarly, transient viral expression in the NAcc exclusively during amphetamine exposure of a threoninealanine mutant form of Kal7 [mKal7(T1590A)] that is not phosphorylated by Cdk5 also prevented the accrual of contextual conditioning and spared the induction of sensitization. These results indicate that signaling via Cdk5 and Kal7 in the NAcc is necessary for the formation of context-drug associations, potentially through the modulation of dendritic spine dynamics in this site. PMID:24939858

Regime shifts and weakened environmental gradients in open oak and pine ecosystems.

PubMed

Hanberry, Brice B; Dey, Dan C; He, Hong S

2012-01-01

Fire suppression allows tree species that are intolerant of fire stress to increase their distribution, potentially resulting in disruption of historical species-environmental relationships. To measure changes between historical General Land Office surveys (1815 to 1850) and current USDA Forest Inventory and Assessment surveys (2004 to 2008), we compared composition, distribution, and site factors of 21 tree species or species groups in the Missouri Ozarks. We used 24 environmental variables and random forests as a classification method to model distributions. Eastern redcedar, elms, maples, and other fire-sensitive species have increased in dominance in oak forests, with concurrent reductions by oak species; specific changes varied by ecological subsection. Ordinations displayed loss of separation between formerly distinctive oak and fire-sensitive tree species groups. Distribution maps showed decreased presence of disturbance-dependent oak and pine species and increased presence of fire-sensitive species that generally expanded from subsections protected from fire along rivers to upland areas, except for eastern redcedar, which expanded into these subsections. Large scale differences in spatial gradients between past and present communities paralleled reduced influence of local topographic gradients in the varied relief of the Missouri Ozarks, as fire-sensitive species have moved to higher, drier, and sunnier sites away from riverine corridors. Due to changes in land use, landscapes in the Missouri Ozarks, eastern United States, and world-wide are changing from open oak and pine-dominated ecosystems to novel oak-mixed species forests, although at fine scales, forests are becoming more diverse in tree species today. Fire suppression weakened the influence by environmental gradients over species dominance, allowing succession from disturbance-dependent oaks to an alternative state of fire-sensitive species. Current and future research and conservation that rely on historical relationships and ecological principles based on disturbance across the landscape will need to incorporate modern interactions among species for resources into management plans and projections.

Amphetamine-induced incentive sensitization of sign-tracking behavior in adolescent and adult female rats

PubMed Central

Doremus-Fitzwater, Tamara L.; Spear, Linda P.

2010-01-01

Age-specific behavioral and neural characteristics may predispose adolescents to initiate and escalate use of alcohol and drugs. Adolescents may avidly seek novel experiences, including drugs of abuse, because of enhanced incentive motivation for drugs and natural rewards, perhaps especially when that incentive motivation is sensitized by prior drug exposure. Using a Pavlovian conditioned approach (PCA) procedure, sign-tracking (ST) and goal-tracking (GT) behavior was examined in amphetamine-sensitized and control adolescent and adult female Sprague-Dawley rats, with expression of elevated ST behavior used to index enhanced incentive motivation for reward-associated cues. Rats were first exposed to a sensitizing regimen of amphetamine injections (3.0 mg/kg/ml d-amphetamine per day) or given saline (0.9% w/v) once daily for 4 days. Expression of ST and GT was then examined over 8 days of PCA training consisting of 25 pairings of an 8-sec presentation of an illuminated lever immediately followed by response-independent delivery of a banana-flavored food pellet. Results showed that adults clearly displayed more ST behavior than adolescents, reflected via both more contacts with, and shorter latencies to approach, the lever. Prior amphetamine sensitization increased ST (but not GT) behaviors regardless of age. Thus, when indexed via ST, incentive motivation was found to be greater in adults than adolescents, with a prior history of amphetamine exposure generally sensitizing incentive motivation for cues predicting a food reward regardless of age. PMID:21534648

Increased Mitochondrial Calcium Sensitivity and Abnormal Expression of Innate Immunity Genes Precede Dopaminergic Defects in Pink1-Deficient Mice

PubMed Central

Akundi, Ravi S.; Huang, Zhenyu; Eason, Joshua; Pandya, Jignesh D.; Zhi, Lianteng; Cass, Wayne A.; Sullivan, Patrick G.; Büeler, Hansruedi

2011-01-01

Background PTEN-induced kinase 1 (PINK1) is linked to recessive Parkinsonism (EOPD). Pink1 deletion results in impaired dopamine (DA) release and decreased mitochondrial respiration in the striatum of mice. To reveal additional mechanisms of Pink1-related dopaminergic dysfunction, we studied Ca2+ vulnerability of purified brain mitochondria, DA levels and metabolism and whether signaling pathways implicated in Parkinson's disease (PD) display altered activity in the nigrostriatal system of Pink1−/− mice. Methods and Findings Purified brain mitochondria of Pink1−/− mice showed impaired Ca2+ storage capacity, resulting in increased Ca2+ induced mitochondrial permeability transition (mPT) that was rescued by cyclosporine A. A subpopulation of neurons in the substantia nigra of Pink1−/− mice accumulated phospho-c-Jun, showing that Jun N-terminal kinase (JNK) activity is increased. Pink1−/− mice 6 months and older displayed reduced DA levels associated with increased DA turnover. Moreover, Pink1−/− mice had increased levels of IL-1β, IL-12 and IL-10 in the striatum after peripheral challenge with lipopolysaccharide (LPS), and Pink1−/− embryonic fibroblasts showed decreased basal and inflammatory cytokine-induced nuclear factor kappa-β (NF-κB) activity. Quantitative transcriptional profiling in the striatum revealed that Pink1−/− mice differentially express genes that (i) are upregulated in animals with experimentally induced dopaminergic lesions, (ii) regulate innate immune responses and/or apoptosis and (iii) promote axonal regeneration and sprouting. Conclusions Increased mitochondrial Ca2+ sensitivity and JNK activity are early defects in Pink1−/− mice that precede reduced DA levels and abnormal DA homeostasis and may contribute to neuronal dysfunction in familial PD. Differential gene expression in the nigrostriatal system of Pink1−/− mice supports early dopaminergic dysfunction and shows that Pink1 deletion causes aberrant expression of genes that regulate innate immune responses. While some differentially expressed genes may mitigate neurodegeneration, increased LPS-induced brain cytokine expression and impaired cytokine-induced NF-κB activation may predispose neurons of Pink1−/− mice to inflammation and injury-induced cell death. PMID:21249202

Determination of depth-viewing volumes for stereo three-dimensional graphic displays

NASA Technical Reports Server (NTRS)

Parrish, Russell V.; Williams, Steven P.

1990-01-01

Real-world, 3-D, pictorial displays incorporating true depth cues via stereopsis techniques offer a potential means of displaying complex information in a natural way to prevent loss of situational awareness and provide increases in pilot/vehicle performance in advanced flight display concepts. Optimal use of stereopsis requires an understanding of the depth viewing volume available to the display designer. Suggested guidelines are presented for the depth viewing volume from an empirical determination of the effective region of stereopsis cueing (at several viewer-CRT screen distances) for a time multiplexed stereopsis display system. The results provide the display designer with information that will allow more effective placement of depth information to enable the full exploitation of stereopsis cueing. Increasing viewer-CRT screen distances provides increasing amounts of usable depth, but with decreasing fields-of-view. A stereopsis hardware system that permits an increased viewer-screen distance by incorporating larger screen sizes or collimation optics to maintain the field-of-view at required levels would provide a much larger stereo depth-viewing volume.

Surface Coatings for Gas Detection via Porous Silicon

NASA Astrophysics Data System (ADS)

Ozdemir, Serdar; Li, Ji-Guang; Gole, James

2009-03-01

Nanopore covered microporous silicon interfaces have been formed via an electrochemical etch for gas sensor applications. Rapid reversible and sensitive gas sensors have been fabricated. The fabricated porous silicon (PS) gas sensors display the advantages of operation at room temperature as well as at a single, readily accessible temperature with an insensitivity to temperature drift; operation in a heat-sunk configuration, ease of coating with gas-selective materials; low cost of fabrication and operation, and the ability to rapidly assess false positives by operating the sensor in a pulsed mode. The PS surface has been modified with unique coatings on the basis of a general theory in order to achieve maximum sensitivity and selectivity. Sensing of NH3, NOx and PH3 at or below the ppm level have been observed. A typical PS nanostructure coated microstructured hybrid configuration when coated with tin oxide (NOx, CO) and gold nanostructures (NH3) provides a greatly increased sensitivity to the indicated gases. Al2O3 coating of the porous silicon using atomic layer deposition and its effect on PH3 sensing has been investigated. 20-100 nm TiO2 nanoparticles have been produced using sol-gel methods to coat PS surfaces and the effects on the selectivity and the sensitivity have been studied.

Utilization of a Response-Surface Technique in the Study of Plant Responses to Ozone and Sulfur Dioxide Mixtures 1

PubMed Central

Ormrod, Douglas P.; Tingey, David T.; Gumpertz, Marcia L.; Olszyk, David M.

1984-01-01

A second order rotatable design was used to obtain polynomial equations describing the effects of combinations of sulfur dioxide (SO2) and ozone (O3) on foliar injury and plant growth. The response surfaces derived from these equations were displayed as contour or isometric (3-dimensional) plots. The contour plots aided in the interpretation of the pollutant interactions and were judged easier to use than the isometric plots. Plants of `Grand Rapids' lettuce (Lactuca sativa L.), `Cherry Belle' radish (Raphanus sativus L.), and `Alsweet' pea (Pisum sativum L.) were grown in a controlled environment chamber and exposed to seven combinations of SO2 and O3. Injury was evaluated based on visible chlorosis and necrosis and growth was evaluated as leaf area and dry weight. Covariate measurements were used to increase precision. Radish and pea had greater injury, in general, that did lettuce; all three species were sensitive to O3, and pea was most sensitive and radish least sensitive to SO2. Leaf injury responses were relatively more affected by the pollutants than were plant growth responses in radish and pea but not in lettuce. In radish, hypocotyl growth was more sensitive to the pollutants than was leaf growth. PMID:16663598

Utilization of a response-surface technique in the study of plant responses to ozone and sulfur dioxide mixtures.

PubMed

Ormrod, D P; Tingey, D T; Gumpertz, M L; Olszyk, D M

1984-05-01

A second order rotatable design was used to obtain polynomial equations describing the effects of combinations of sulfur dioxide (SO(2)) and ozone (O(3)) on foliar injury and plant growth. The response surfaces derived from these equations were displayed as contour or isometric (3-dimensional) plots. The contour plots aided in the interpretation of the pollutant interactions and were judged easier to use than the isometric plots. Plants of ;Grand Rapids' lettuce (Lactuca sativa L.), ;Cherry Belle' radish (Raphanus sativus L.), and ;Alsweet' pea (Pisum sativum L.) were grown in a controlled environment chamber and exposed to seven combinations of SO(2) and O(3). Injury was evaluated based on visible chlorosis and necrosis and growth was evaluated as leaf area and dry weight. Covariate measurements were used to increase precision. Radish and pea had greater injury, in general, that did lettuce; all three species were sensitive to O(3), and pea was most sensitive and radish least sensitive to SO(2). Leaf injury responses were relatively more affected by the pollutants than were plant growth responses in radish and pea but not in lettuce. In radish, hypocotyl growth was more sensitive to the pollutants than was leaf growth.

d-PET-controlled “off-on” Polarity-sensitive Probes for Reporting Local Hydrophilicity within Lysosomes

NASA Astrophysics Data System (ADS)

Zhu, Hao; Fan, Jiangli; Mu, Huiying; Zhu, Tao; Zhang, Zhen; Du, Jianjun; Peng, Xiaojun

2016-10-01

Polarity-sensitive fluorescent probes are powerful chemical tools for studying biomolecular structures and activities both in vitro and in vivo. However, the lack of “off-on” polarity-sensing probes has limited the accurate monitoring of biological processes that involve an increase in local hydrophilicity. Here, we design and synthesize a series of “off-on” polarity-sensitive fluorescent probes BP series consisting of the difluoroboron dippyomethene (BODIPY) fluorophore connected to a quaternary ammonium moiety via different carbon linkers. All these probes showed low fluorescence quantum yields in nonpolar solution but became highly fluorescent in polar media. BP-2, which contains a two-carbon linker and a trimethyl quaternary ammonium, displayed a fluorescence intensity and quantum yield that were both linearly correlated with solvent polarity. In addition, BP-2 exhibited high sensitivity and selectivity for polarity over other environmental factors and a variety of biologically relevant species. BP-2 can be synthesized readily via an unusual Mannich reaction followed by methylation. Using electrochemistry combined with theoretical calculations, we demonstrated that the “off-on” sensing behavior of BP-2 is primarily due to the polarity-dependent donor-excited photoinduced electron transfer (d-PET) effect. Live-cell imaging established that BP-2 enables the detection of local hydrophilicity within lysosomes under conditions of lysosomal dysfunction.

Beauty and the beholder: the role of visual sensitivity in visual preference

PubMed Central

Spehar, Branka; Wong, Solomon; van de Klundert, Sarah; Lui, Jessie; Clifford, Colin W. G.; Taylor, Richard P.

2015-01-01

For centuries, the essence of aesthetic experience has remained one of the most intriguing mysteries for philosophers, artists, art historians and scientists alike. Recently, views emphasizing the link between aesthetics, perception and brain function have become increasingly prevalent (Ramachandran and Hirstein, 1999; Zeki, 1999; Livingstone, 2002; Ishizu and Zeki, 2013). The link between art and the fractal-like structure of natural images has also been highlighted (Spehar et al., 2003; Graham and Field, 2007; Graham and Redies, 2010). Motivated by these claims and our previous findings that humans display a consistent preference across various images with fractal-like statistics, here we explore the possibility that observers’ preference for visual patterns might be related to their sensitivity for such patterns. We measure sensitivity to simple visual patterns (sine-wave gratings varying in spatial frequency and random textures with varying scaling exponent) and find that they are highly correlated with visual preferences exhibited by the same observers. Although we do not attempt to offer a comprehensive neural model of aesthetic experience, we demonstrate a strong relationship between visual sensitivity and preference for simple visual patterns. Broadly speaking, our results support assertions that there is a close relationship between aesthetic experience and the sensory coding of natural stimuli. PMID:26441611

Hierarchical Encoding of Social Cues in Primate Inferior Temporal Cortex

PubMed Central

Morin, Elyse L.; Hadj-Bouziane, Fadila; Stokes, Mark; Ungerleider, Leslie G.; Bell, Andrew H.

2015-01-01

Faces convey information about identity and emotional state, both of which are important for our social interactions. Models of face processing propose that changeable versus invariant aspects of a face, specifically facial expression/gaze direction versus facial identity, are coded by distinct neural pathways and yet neurophysiological data supporting this separation are incomplete. We recorded activity from neurons along the inferior bank of the superior temporal sulcus (STS), while monkeys viewed images of conspecific faces and non-face control stimuli. Eight monkey identities were used, each presented with 3 different facial expressions (neutral, fear grin, and threat). All facial expressions were displayed with both a direct and averted gaze. In the posterior STS, we found that about one-quarter of face-responsive neurons are sensitive to social cues, the majority of which being sensitive to only one of these cues. In contrast, in anterior STS, not only did the proportion of neurons sensitive to social cues increase, but so too did the proportion of neurons sensitive to conjunctions of identity with either gaze direction or expression. These data support a convergence of signals related to faces as one moves anteriorly along the inferior bank of the STS, which forms a fundamental part of the face-processing network. PMID:24836688

Sensitivity to nitrate and nitrite in pond-breeding amphibians from the Pacific Northwest, USA

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

Marco, A.; Quilchano, C.; Blaustein, A.R.

1999-12-01

In static experiments, the authors studied the effects of nitrate and nitrate solutions on newly hatched larvae of five species of amphibians, namely Rana pretiosa, Rana aurora, Bufo boreas, Hyla regilla, and Ambystoma gracile. When nitrate or nitrite ions were added to the water, some larvae of some species reduced feeding activity, swam less vigorously, showed disequilibrium and paralysis, suffered abnormalities and edemas, and eventually died. The observed effects increased with both concentration and time, and there were significant differences in sensitivity among species. Ambrystoma gracile displayed the highest acute effect in water with nitrate and nitrite. The three ranidmore » species had acute effects in water with nitrite. In chronic exposures, R. pretiosa was the most sensitive species to nitrates and nitrites. All species showed 15-d LC50s lower than 2 mg N-NO{sub 2{sup {minus}}}/L. For both N ions, B. boreas was the least sensitive amphibian. All species showed a high morality at the US Environmental Protection Agency-recommended limits of nitrite for warm-water fishes and a significant larval mortality at the recommended limits of nitrite concentration for drinking water. The recommended levels of nitrate for warm-water fishes were highly toxic for R. pretiosa and A. gracile larvae.« less

A Photostable Silicon Rhodamine Platform for Optical Voltage Sensing

PubMed Central

Huang, Yi-Lin; Walker, Alison S.; Miller, Evan W.

2015-01-01

This paper describes the design and synthesis of a photostable, far-red to near-infrared (NIR) platform for optical voltage sensing. We developed a new, sulfonated silicon rhodamine fluorophore and integrated it with a phenylenevinylene molecular wire to create a Berkeley Red Sensor of Transmembrane potential, or BeRST 1 (“burst”). BeRST 1 is the first member of a class of farred to NIR voltage sensitive dyes that make use of a photoinduced electron transfer (PeT) trigger for optical interrogation of membrane voltage. We show that BeRST 1 displays bright, membrane-localized fluorescence in living cells, high photostability, and excellent voltage sensitivity in neurons. Depolarization of the plasma membrane results in rapid fluorescence increases (24% ΔF/F per 100 mV). BeRST 1 can be used in conjunction with fluorescent stains for organelles, Ca2+ indicators, and voltage-sensitive fluorescent proteins. In addition, the red-shifted spectral profile of BeRST 1, relative to commonly employed optogenetic actuators like ChannelRhodopsin2 (ChR2), which require blue light, enables optical electrophysiology in neurons. The high speed, sensitivity, photostability and long-wavelength fluorescence profiles of BeRST 1 make it a useful platform for the non-invasive, optical dissection of neuronal activity. PMID:26237573

An ultra-sensitive Au nanoparticles functionalized DNA biosensor for electrochemical sensing of mercury ions.

PubMed

Zhang, Yanyan; Zhang, Cong; Ma, Rui; Du, Xin; Dong, Wenhao; Chen, Yuan; Chen, Qiang

2017-06-01

The present work describes an effective strategy to fabricate a highly sensitive and selective DNA-biosensor for the determination of mercury ions (Hg 2+ ). The DNA 1 was modified onto the surface of Au electrode by the interaction between sulfydryl group and Au electrode. DNA probe is complementary with DNA 1. In the presence of Hg 2+ , the electrochemical signal increases owing to that Hg 2+ -mediated thymine bases induce the conformation of DNA probe to change from line to hairpin and less DNA probes adsorb into DNA 1. Taking advantage of its reduction property, methylene blue is considered as the signal indicating molecule. For improving the sensitivity of the biosensor, Au nanoparticles (Au NPs) modified reporter DNA 3 is used to adsorb DNA 1. Electrochemical behaviors of the biosensor were evaluated by electrochemical impedance spectroscopy and cyclic voltammetry. Several important parameters which could affect the property of the biosensor were studied and optimized. Under the optimal conditions, the biosensor exhibits wide linear range, high sensitivity and low detection limit. Besides, it displays superior selectivity and excellent stability. The biosensor was also applied for water sample detection with satisfactory result. The novel strategy of fabricating biosensor provides a potential platform for fabricating a variety of metal ions biosensors. Copyright © 2017 Elsevier B.V. All rights reserved.

Melanocortin-1 receptor gene variants affect pain and µ-opioid analgesia in mice and humans

PubMed Central

Mogil, J; Ritchie, J; Smith, S; Strasburg, K; Kaplan, L; Wallace, M; Romberg, R; Bijl, H; Sarton, E; Fillingim, R; Dahan, A

2005-01-01

Background: A recent genetic study in mice and humans revealed the modulatory effect of MC1R (melanocortin-1 receptor) gene variants on κ-opioid receptor mediated analgesia. It is unclear whether this gene affects basal pain sensitivity or the efficacy of analgesics acting at the more clinically relevant µ-opioid receptor. Objective: To characterise sensitivity to pain and µ-opioid analgesia in mice and humans with non-functional melanocortin-1 receptors. Methods: Comparisons of spontaneous mutant C57BL/6-Mc1re/e mice to C57BL/6 wildtype mice, followed by a gene dosage study of pain and morphine-6-glucuronide (M6G) analgesia in humans with MC1R variants. Results: C57BL/6-Mc1re/e mutant mice and human redheads—both with non-functional MC1Rs—display reduced sensitivity to noxious stimuli and increased analgesic responsiveness to the µ-opioid selective morphine metabolite, M6G. In both species the differential analgesia is likely due to pharmacodynamic factors, as plasma levels of M6G are similar across genotype. Conclusions: Genotype at MC1R similarly affects pain sensitivity and M6G analgesia in mice and humans. These findings confirm the utility of cross species translational strategies in pharmacogenetics. PMID:15994880

Sensitive vs. tolerant Nitzschia palea (Kützing) W. Smith strains to atrazine: a biochemical perspective.

PubMed

Esteves, S M; Almeida, S F P; Gonçalves, S; Rimet, F; Bouchez, A; Figueira, E

2018-06-16

Organic contaminants, and herbicides in particular, represent a risk for aquatic ecosystems. The primary target of herbicides are producers, the base of food webs, but frequently they end up far from the application point affecting non-target species. Its presence can work as sub-lethal stimulus, which sort the genetic and phenotypic differences within a species. Intraspecific variation allows adaptation to changes in the environment but also to new niches due to variations in species' sensitivity and biochemical response to a certain chemical. A better understanding of these variations can lead to the development of improved strategies for ecosystem protection. This research aimed to compare a sensitive and a tolerant strain of the freshwater diatom Nitzschia palea to atrazine. Strains were exposed to three concentrations within their tolerance range, during 96 h. The activity of the antioxidant enzymes superoxide dismutase, catalase, glutathione-S-transferases and glutathione peroxidases was determined. In addition, chlorophylls a and c, carotenoids, reduced glutathione, proteins and lipid peroxidation were quantified. Both strains displayed different strategies to deal with atrazine toxicity: while the sensitive strain decreased the oxidative stress, increasing the activity of antioxidant enzymes such as superoxide dismutase, the tolerant strain invested in conjugation pathways and carotenoids' maintenance.

Non-invasive toluene sensor for early diagnosis of lung cancer

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

Saxena, Rahul; Srivastava, Sudha, E-mail: sudha.srivastava@jiit.ac.in

Here we present, quantification of volatile organic compounds in human breath for early detection of lung cancer to increase survival probability. Graphene oxide nanosheets synthesized by modified Hummer’s method were employed as a sensing element to detect the presence of toluene in the sample. Optical and morphological characterization of synthesized nanomaterial was performed by UV-Visible spectroscopy and scanning electron microscopy (SEM) respectively. Spectroscopic assay shows a linearly decreasing intensity of GO absorption peak with increasing toluene concentration with a linear range from 0-200 pM. While impedimetric sensor developed on a graphene oxide nanosheetsmodified screen printed electrodes displayed a decreasing electronmore » transfer resistance increasing toluene with much larger linear range of 0-1000 pM. Reported techniques are advantageous as these are simple, sensitive and cost effective, which can easily be extended for primary screening of other VOCs.« less

A practical toxicity bioassay for vicine and convicine levels in faba bean (Vicia faba).

PubMed

Getachew, Fitsum; Vandenberg, Albert; Smits, Judit

2018-04-02

Faba bean (Vicia faba) vicine and convicine (V-C) aglycones (divicine and isouramil respectively) provoke an acute hemolytic anemia called favism in individuals with a glucose-6-phosphate dehydrogenase (G6PD) enzyme defect in their red blood cells. Geneticists/plant breeders are working with faba bean to decrease V-C levels to improve public acceptance of this high-protein pulse crop. Here, we present a fast and simple ex vivo in vitro bioassay for V-C toxicity testing of faba bean or faba bean food products. We have shown that 1,3-bis (2-chloroethyl)-1-nitrosourea (BCNU)-treated (i.e., sensitized) normal red blood cells, like G6PD-defective blood, displayed (i) continuous glutathione (GSH) depletion with no regeneration as incubation time and the dose of aglycones increased, (ii) progressive accumulation of denatured hemoglobin products into high molecular weight (HMW) proteins with increased aglycone dose, (iii) both band 3 membrane proteins and hemichromes, in HMW protein aggregates. We have also demonstrated that sensitized red blood cells can effectively differentiate various levels of toxicity among faba bean varieties through the two hemolysis biomarkers: GSH depletion and HMW clumping. BCNU-sensitized red blood cells provide an ideal model for favism blood, to assess and compare the toxicity of faba bean varieties and their food products. © 2018 Society of Chemical Industry. © 2018 Society of Chemical Industry.

Gender-based effects on methylprednisolone pharmacokinetics and pharmacodynamics

PubMed Central

Lew, Kim H.; Ludwig, Elizabeth A.; Milad, Mark A.; Donovan, Kathleen; Middleton, Elliott; Ferry, James J.; Jusko, William J.

2014-01-01

The pharmacokinetics and selected pharmacodynamic responses to methylprednisolone were investigated in six men and six premenopausal women after a dose of 0.6 mg/kg ideal body weight. Women (luteal phase) exhibited a greater methylprednisolone clearance (0.45 versus 0.29 L/hr/kg) and shorter elimination half-life (1.7 versus 2.6 hours) than men. The volume of distribution of methylprednisolone was similar when normalized for ideal body weight. Pharmacodynamic models were used to examine the methylprednisolone suppressive effects on cortisol secretion and basophil and helper T lymphocyte trafficking. A significantly smaller 50% inhibitory concentration (IC50) value (0.1 versus 1.7 ng/ml) was seen in the women for suppression of cortisol secretion, indicating increased sensitivity. However, the area under the concentration-time curve of effect was similar for both groups. The IC50 values for effects of methylprednisolone on basophil trafficking related to estradiol concentrations in a log-linear fashion in women, with increased sensitivity found at higher estradiol concentrations. Men displayed a greater 24-hour net suppression in blood basophil numbers, but no difference was observed in net cortisol and helper T lymphocyte suppression between the sexes. These findings suggest that methylprednisolone dosages should be based on ideal body weight. Although women are more sensitive to methylprednisolone as measured by cortisol suppression, they eliminate the drug more quickly, generally producing a similar net response. PMID:8222483

Sensitivity Differences in Fish Offer Near-Infrared Vision as an Adaptable Evolutionary Trait

PubMed Central

Shcherbakov, Denis; Knörzer, Alexandra; Espenhahn, Svenja; Hilbig, Reinhard; Haas, Ulrich; Blum, Martin

2013-01-01

Near-infrared (NIR) light constitutes an integrated part of solar radiation. The principal ability to sense NIR under laboratory conditions has previously been demonstrated in fish. The availability of NIR in aquatic habitats, and thus its potential use as a cue for distinct behaviors such as orientation and detection of prey, however, depends on physical and environmental parameters. In clear water, blue and green light represents the dominating part of the illumination. In turbid waters, in contrast, the relative content of red and NIR radiation is enhanced, due to increased scattering and absorption of short and middle range wavelengths by suspended particles and dissolved colored materials. We have studied NIR detection thresholds using a phototactic swimming assay in five fish species, which are exposed to different NIR conditions in their natural habitats. Nile and Mozambique tilapia, which inhabit waters with increased turbidity, displayed the highest spectral sensitivity, with thresholds at wavelengths above 930 nm. Zebrafish, guppy and green swordtail, which prefer clearer waters, revealed significantly lower thresholds of spectral sensitivity with 825–845 nm for green swordtail and 845–910 nm for zebrafish and guppy. The present study revealed a clear correlation between NIR sensation thresholds and availability of NIR in the natural habitats, suggesting that NIR vision, as an integral part of the whole spectrum of visual abilities, can serve as an evolutionarily adaptable trait in fish. PMID:23691215

Enhancement of vision by monocular deprivation in adult mice.

PubMed

Prusky, Glen T; Alam, Nazia M; Douglas, Robert M

2006-11-08

Plasticity of vision mediated through binocular interactions has been reported in mammals only during a "critical" period in juvenile life, wherein monocular deprivation (MD) causes an enduring loss of visual acuity (amblyopia) selectively through the deprived eye. Here, we report a different form of interocular plasticity of vision in adult mice in which MD leads to an enhancement of the optokinetic response (OKR) selectively through the nondeprived eye. Over 5 d of MD, the spatial frequency sensitivity of the OKR increased gradually, reaching a plateau of approximately 36% above pre-deprivation baseline. Eye opening initiated a gradual decline, but sensitivity was maintained above pre-deprivation baseline for 5-6 d. Enhanced function was restricted to the monocular visual field, notwithstanding the dependence of the plasticity on binocular interactions. Activity in visual cortex ipsilateral to the deprived eye was necessary for the characteristic induction of the enhancement, and activity in visual cortex contralateral to the deprived eye was necessary for its maintenance after MD. The plasticity also displayed distinct learning-like properties: Active testing experience was required to attain maximal enhancement and for enhancement to persist after MD, and the duration of enhanced sensitivity after MD was extended by increasing the length of MD, and by repeating MD. These data show that the adult mouse visual system maintains a form of experience-dependent plasticity in which the visual cortex can modulate the normal function of subcortical visual pathways.

c-Abl kinase inhibitors overcome CD40-mediated drug resistance in CLL: implications for therapeutic targeting of chemoresistant niches.

PubMed

Hallaert, Delfine Y H; Jaspers, Annelieke; van Noesel, Carel J; van Oers, Marinus H J; Kater, Arnon P; Eldering, Eric

2008-12-15

In lymph node (LN) proliferation centers in chronic lymphocytic leukemia (CLL), the environment protects from apoptotic and cytotoxic triggers. Here, we aimed to define the molecular basis for the increased drug resistance and searched for novel strategies to circumvent it. The situation in CLL LN could be mimicked by prolonged in vitro CD40 stimulation, which resulted in up-regulation of antiapoptotic Bcl-xL, A1/Bfl-1, and Mcl-1 proteins, and afforded resistance to various classes of drugs (fludarabine, bortezomib, roscovitine). CD40 stimulation also caused ERK-dependent reduction of Bim-EL protein, but ERK inhibition did not prevent drug resistance. Drugs combined with sublethal doses of the BH3-mimetic ABT-737 displayed partial and variable effects per individual CD40-stimulated CLL. The antiapoptotic profile of CD40-triggered CLL resembled BCR-Abl-dependent changes seen in chronic myeloid leukemia (CML), which prompted application of c-Abl inhibitors imatinib or dasatinib. Both compounds, but especially dasatinib, prevented the entire antiapoptotic CD40 program in CLL cells, and restored drug sensitivity. These effects also occurred in CLL samples with dysfunctional p53. Importantly, ex vivo CLL LN samples also displayed strong ERK activation together with high Bcl-xL and Mcl-1 but low Bim levels. These data indicate that CLL cells in chemoresistant niches may be sensitive to therapeutic strategies that include c-Abl inhibitors.

Voltammetric determination of attomolar levels of a sequence derived from the genom of hepatitis B virus by using molecular beacon mediated circular strand displacement and rolling circle amplification.

PubMed

Huang, Shan; Feng, Mengmeng; Li, Jiawen; Liu, Yi; Xiao, Qi

2018-03-03

The authors describe an electrochemical method for the determination of the single-stranded DNA (ssDNA) oligonucleotide with a sequence derived from the genom of hepatitis B virus (HBV). It is making use of circular strand displacement (CSD) and rolling circle amplification (RCA) strategies mediated by a molecular beacon (MB). This ssDNA hybridizes with the loop portion of the MB immobilized on the surface of a gold electrode, while primer DNA also hybridizes with the rest of partial DNA sequences of MB. This triggers the MB-mediated CSD. The RCA is then initiated to produce a long DNA strand with multiple tandem-repeat sequences, and this results in a significant increase of the differential pulse voltammetric response of the electrochemical probe Methylene Blue at a rather low working potential of -0.24 V (vs. Ag/AgCl). Under optimal experimental conditions, the assay displays an ultrahigh sensitivity (with a 2.6 aM detection limit) and excellent selectivity. Response is linear in the 10 to 700 aM DNA concentration range. Graphical abstract Schematic of a voltammetric method for the determination of attomolar levels of target DNA. It is based on molecular beacon mediated circular strand displacement and rolling circle amplification strategies. Under optimal experimental conditions, the assay displays an ultrahigh sensitivity with a 2.6 aM detection limit and excellent selectivity.

Abnormalities in brain structure and behavior in GSK-3alpha mutant mice

PubMed Central

2009-01-01

Background Glycogen synthase kinase-3 (GSK-3) is a widely expressed and highly conserved serine/threonine protein kinase encoded by two genes that generate two related proteins: GSK-3α and GSK-3β. Mice lacking a functional GSK-3α gene were engineered in our laboratory; they are viable and display insulin sensitivity. In this study, we have characterized brain functions of GSK-3α KO mice by using a well-established battery of behavioral tests together with neurochemical and neuroanatomical analysis. Results Similar to the previously described behaviours of GSK-3β+/-mice, GSK-3α mutants display decreased exploratory activity, decreased immobility time and reduced aggressive behavior. However, genetic inactivation of the GSK-3α gene was associated with: decreased locomotion and impaired motor coordination, increased grooming activity, loss of social motivation and novelty; enhanced sensorimotor gating and impaired associated memory and coordination. GSK-3α KO mice exhibited a deficit in fear conditioning, however memory formation as assessed by a passive avoidance test was normal, suggesting that the animals are sensitized for active avoidance of a highly aversive stimulus in the fear-conditioning paradigm. Changes in cerebellar structure and function were observed in mutant mice along with a significant decrease of the number and size of Purkinje cells. Conclusion Taken together, these data support a role for the GSK-3α gene in CNS functioning and possible involvement in the development of psychiatric disorders. PMID:19925672

Ultrahigh sensitivity endoscopic camera using a new CMOS image sensor: providing with clear images under low illumination in addition to fluorescent images.

PubMed

Aoki, Hisae; Yamashita, Hiromasa; Mori, Toshiyuki; Fukuyo, Tsuneo; Chiba, Toshio

2014-11-01

We developed a new ultrahigh-sensitive CMOS camera using a specific sensor that has a wide range of spectral sensitivity characteristics. The objective of this study is to present our updated endoscopic technology that has successfully integrated two innovative functions; ultrasensitive imaging as well as advanced fluorescent viewing. Two different experiments were conducted. One was carried out to evaluate the function of the ultrahigh-sensitive camera. The other was to test the availability of the newly developed sensor and its performance as a fluorescence endoscope. In both studies, the distance from the endoscopic tip to the target was varied and those endoscopic images in each setting were taken for further comparison. In the first experiment, the 3-CCD camera failed to display the clear images under low illumination, and the target was hardly seen. In contrast, the CMOS camera was able to display the targets regardless of the camera-target distance under low illumination. Under high illumination, imaging quality given by both cameras was quite alike. In the second experiment as a fluorescence endoscope, the CMOS camera was capable of clearly showing the fluorescent-activated organs. The ultrahigh sensitivity CMOS HD endoscopic camera is expected to provide us with clear images under low illumination in addition to the fluorescent images under high illumination in the field of laparoscopic surgery.

A new firefly luciferase with bimodal spectrum: identification of structural determinants of spectral pH-sensitivity in firefly luciferases.

PubMed

Viviani, Vadim R; Oehlmeyer, T L; Arnoldi, F G C; Brochetto-Braga, M R

2005-01-01

Fireflies emit flashes in the green-yellow region of the spectrum for the purpose of sexual attraction. The bioluminescence color is determined by the luciferases. It is well known that the in vitro bioluminescence color of firefly luciferases can be shifted toward the red by lower pH and higher temperature; for this reason they are classified as pH-sensitive luciferases. However, the mechanism and structural origin of pH sensitivity in fireflies remains unknown. Here we report the cloning of a new luciferase from the Brazilian twilight active firefly Macrolampis sp2, which displays an unusual bimodal spectrum. The recombinant luciferase displays a sensitive spectrum with the peak at 569 nm and a shoulder in the red region. Comparison of the bioluminescence spectra of Macrolampis, Photinus and Cratomorphus firefly luciferases shows that the distinct colors are determined by the ratio between green and red emitters under luciferase influence. Comparison of Macrolampis luciferase with the highly similar North American Photinus pyralis luciferase (91%) showed few substitutions potentially involved with the higher spectral sensitivity in Macrolampis luciferase. Site-directed mutagenesis showed that the natural substitution E354N determines the appearance of the shoulder in the red region of Macrolampis luciferase bioluminescence spectrum, helping to identify important interactions and residues involved in the pH-sensing mechanism in firefly luciferases.

Fungal Allergy: Pattern of sensitization over the past 11 years.

PubMed

Fernández-Soto, R; Navarrete-Rodríguez, E M; Del-Rio-Navarro, B E; Sienra-Monge, J J Luis; Meneses-Sánchez, N A; Saucedo-Ramírez, O J

2018-05-05

Although the prevalence of sensitization to fungi is not precisely known, it can reach 50% in inner cities and has been identified as a risk factor in the development of asthma. Whereas the prevalence of allergic diseases is increasing, it is unclear whether the same occurs with sensitization to fungi. A retrospective study was performed at the "Hospital Infantil de México Federico Gómez". From skin tests taken between 2004 and 2015, information was gathered about Alternaria alternata, Aspergillus fumigatus, Candida albicans, Cladosporium herbarum, Mucor mucedo and Penicillium notatum. The participating patients were 2-18 years old, presented some type of allergic condition, and underwent immediate hypersensitivity tests to the fungi herein examined. Descriptive analysis and chi-squared distribution were used. Of the 8794 patients included in the study, 14% showed a negative result to the entire panel of environmental allergens. The remaining 7565 individuals displayed sensitization to at least one fungus, which most frequently was Aspergillus, with a rate of 16.8%. When the patients were divided into age groups, the same trend was observed. The highest percentage of sensitization (58%) toward at least one type of fungus was found in 2014, and the lowest percentage (49.8%) in 2008. The rate of sensitization to at least one type of fungus was presently over 50%, higher than that detected in other medical centers in Mexico. This rate was constant over the 11-year study, and Aspergillus exhibited the greatest frequency of sensitization among the patients. Copyright © 2018 SEICAP. Published by Elsevier España, S.L.U. All rights reserved.

ROS-mediated decline in maximum Ca2+-activated force in rat skeletal muscle fibers following in vitro and in vivo stimulation.

PubMed

Dutka, Travis L; Verburg, Esther; Larkins, Noni; Hortemo, Kristin H; Lunde, Per K; Sejersted, Ole M; Lamb, Graham D

2012-01-01

We hypothesised that normal skeletal muscle stimulated intensely either in vitro or in situ would exhibit reactive oxygen species (ROS)-mediated contractile apparatus changes common to many pathophysiological conditions. Isolated soleus (SOL) and extensor digitorum longus (EDL) muscles of the rat were bubbled with 95% O(2) and stimulated in vitro at 31°C to give isometric tetani (50 Hz for 0.5 s every 2 s) until maximum force declined to ≤30%. Skinned superficial slow-twitch fibers from the SOL muscles displayed a large reduction (∼41%) in maximum Ca(2+)-activated specific force (F(max)), with Ca(2+)-sensitivity unchanged. Fibers from EDL muscles were less affected. The decrease in F(max) in SOL fibers was evidently due to oxidation effects on cysteine residues because it was reversed if the reducing agent DTT was applied prior to activating the fiber. The GSH:GSSG ratio was ∼3-fold lower in the cytoplasm of superficial fibers from stimulated muscle compared to control, confirming increased oxidant levels. The presence of Tempol and L-NAME during in vitro stimulation prevented reduction in F(max). Skinned fibers from SOL muscles stimulated in vivo at 37°C with intact blood supply also displayed reduction in F(max), though to a much smaller extent (∼12%). Thus, fibers from muscles stimulated even with putatively adequate O(2) supply display a reversible oxidation-induced decrease in F(max) without change in Ca(2+)-sensitivity, consistent with action of peroxynitrite (or possibly superoxide) on cysteine residues of the contractile apparatus. Significantly, the changes closely resemble the contractile deficits observed in a range of pathophysiological conditions. These findings highlight how readily muscle experiences ROS-related deficits, and also point to potential difficulties when defining muscle performance and fatigue.

ROS-Mediated Decline in Maximum Ca2+-Activated Force in Rat Skeletal Muscle Fibers following In Vitro and In Vivo Stimulation

PubMed Central

Dutka, Travis L.; Verburg, Esther; Larkins, Noni; Hortemo, Kristin H.; Lunde, Per K.; Sejersted, Ole M.; Lamb, Graham D.

2012-01-01

We hypothesised that normal skeletal muscle stimulated intensely either in vitro or in situ would exhibit reactive oxygen species (ROS)-mediated contractile apparatus changes common to many pathophysiological conditions. Isolated soleus (SOL) and extensor digitorum longus (EDL) muscles of the rat were bubbled with 95% O2 and stimulated in vitro at 31°C to give isometric tetani (50 Hz for 0.5 s every 2 s) until maximum force declined to ≤30%. Skinned superficial slow-twitch fibers from the SOL muscles displayed a large reduction (∼41%) in maximum Ca2+-activated specific force (Fmax), with Ca2+-sensitivity unchanged. Fibers from EDL muscles were less affected. The decrease in Fmax in SOL fibers was evidently due to oxidation effects on cysteine residues because it was reversed if the reducing agent DTT was applied prior to activating the fiber. The GSH∶GSSG ratio was ∼3-fold lower in the cytoplasm of superficial fibers from stimulated muscle compared to control, confirming increased oxidant levels. The presence of Tempol and L-NAME during in vitro stimulation prevented reduction in Fmax. Skinned fibers from SOL muscles stimulated in vivo at 37°C with intact blood supply also displayed reduction in Fmax, though to a much smaller extent (∼12%). Thus, fibers from muscles stimulated even with putatively adequate O2 supply display a reversible oxidation-induced decrease in Fmax without change in Ca2+-sensitivity, consistent with action of peroxynitrite (or possibly superoxide) on cysteine residues of the contractile apparatus. Significantly, the changes closely resemble the contractile deficits observed in a range of pathophysiological conditions. These findings highlight how readily muscle experiences ROS-related deficits, and also point to potential difficulties when defining muscle performance and fatigue. PMID:22629297

Fructose, but not glucose, impairs insulin signaling in the three major insulin-sensitive tissues

PubMed Central

Baena, Miguel; Sangüesa, Gemma; Dávalos, Alberto; Latasa, María-Jesús; Sala-Vila, Aleix; Sánchez, Rosa María; Roglans, Núria; Laguna, Juan Carlos; Alegret, Marta

2016-01-01

Human studies support the relationship between high intake of fructose-sweetened beverages and type 2 diabetes, but there is a debate on whether this effect is fructose-specific or it is merely associated to an excessive caloric intake. Here we investigate the effects of 2 months’ supplementation to female rats of equicaloric 10% w/v fructose or glucose solutions on insulin sensitivity in target tissues. Fructose supplementation caused hepatic deposition of triglycerides and changed the fatty acid profile of this fraction, with an increase in monounsaturated and a decrease in polyunsaturated species, but did not cause inflammation and oxidative stress. Fructose but not glucose-supplemented rats displayed an abnormal glucose tolerance test, and did not show increased phosphorylation of V-akt murine thymoma viral oncogene homolog-2 (Akt) in white adipose tissue and liver after insulin administration. In skeletal muscle, phosphorylation of Akt and of Akt substrate of 160 kDA (AS160) was not impaired but the expression of the glucose transporter type 4 (GLUT4) in the plasma membrane was reduced only in fructose-fed rats. In conclusion, fructose but not glucose supplementation causes fatty liver without inflammation and oxidative stress and impairs insulin signaling in the three major insulin-responsive tissues independently from the increase in energy intake. PMID:27194405

Maternal Encouragement to Approach Novelty: A Curvilinear Relation to Change in Anxiety for Inhibited Toddlers.

PubMed

Kiel, Elizabeth J; Premo, Julie E; Buss, Kristin A

2016-04-01

Various parenting behaviors (e.g., protection, intrusiveness, sensitivity) have been shown to impact young children's anxiety development, particularly for temperamentally inhibited children. These behaviors have sometimes predicted both increases and decreases in anxiety in inhibited children, suggesting that linear relations may not adequately model their influence. In the current study, we proposed the dimension of encouragement to approach novelty to characterize parenting behavior ranging from very little encouragement (i.e., protective behavior) to very strong encouragement (i.e., intrusiveness), with gentle encouragement residing in the middle. In a sample of 110 toddlers (48 female, 62 male) and their mothers, the linear and curvilinear effects of this parenting dimension were investigated in relation to change in child separation anxiety and shyness from age 2 to age 3. Inhibited temperament was also investigated as a moderator. Encouragement to approach novelty displayed the hypothesized curvilinear relation to change in separation anxiety, but not shyness, at extreme levels of inhibited temperament. Toddlers increased in separation anxiety when mothers' encouragement resided at either extreme end of the continuum, with lower child anxiety occurring when mothers displayed behavior closer to the middle of the continuum. Implications for the study of parenting outcomes for inhibited toddlers are discussed.

Maternal Encouragement to Approach Novelty: A Curvilinear Relation to Change in Anxiety for Inhibited Toddlers

PubMed Central

Kiel, Elizabeth J.; Premo, Julie E.; Buss, Kristin A.

2015-01-01

Various parenting behaviors (e.g., protection, intrusiveness, sensitivity) have been shown to impact young children’s anxiety development, particularly for temperamentally inhibited children. These behaviors have sometimes predicted both increases and decreases in anxiety in inhibited children, suggesting that linear relations may not adequately model their influence. In the current study, we proposed the dimension of encouragement to approach novelty to characterize parenting behavior ranging from very little encouragement (i.e., protective behavior) to very strong encouragement (i.e., intrusiveness), with gentle encouragement residing in the middle. In a sample of 110 toddlers (48 female, 62 male) and their mothers, the linear and curvilinear effects of this parenting dimension were investigated in relation to change in child separation anxiety and shyness from age 2 to age 3. Inhibited temperament was also investigated as a moderator. Encouragement to approach novelty displayed the hypothesized curvilinear relation to change in separation anxiety, but not shyness, at extreme levels of inhibited temperament. Toddlers increased in separation anxiety when mothers’ encouragement resided at either extreme end of the continuum, with lower child anxiety occurring when mothers displayed behavior closer to the middle of the continuum. Implications for the study of parenting outcomes for inhibited toddlers are discussed. PMID:26050798

Adolescent internalizing symptoms and negative life events: the sensitizing effects of earlier life stress and cortisol.

PubMed

Ruttle, Paula L; Armstrong, Jeffrey M; Klein, Marjorie H; Essex, Marilyn J

2014-11-01

Although adolescence is marked by increased negative life events and internalizing problems, few studies investigate this association as an ongoing longitudinal process. Moreover, while there are considerable individual differences in the degree to which these phenomena are linked, little is known about the origins of these differences. The present study examines early life stress (ELS) exposure and early-adolescent longitudinal afternoon cortisol level as predictors of the covariation between internalizing symptoms and negative life events across high school. ELS was assessed by maternal report during infancy, and the measure of cortisol was derived from assessments at ages 11, 13, and 15 years. Life events and internalizing symptoms were assessed at ages 15, 17, and 18 years. A two-level hierarchical linear model revealed that ELS and cortisol were independent predictors of the covariation of internalizing symptoms and negative life events. Compared to those with lower levels of ELS, ELS-exposed adolescents displayed tighter covariation between internalizing symptoms and negative life events. Adolescents with lower longitudinal afternoon cortisol displayed tighter covariation between negative life events and internalizing symptoms, while those with higher cortisol demonstrated weaker covariation, partially due to increased levels of internalizing symptoms when faced with fewer negative life events.

Operating room managerial decision-making on the day of surgery with and without computer recommendations and status displays.

PubMed

Dexter, Franklin; Willemsen-Dunlap, Ann; Lee, John D

2007-08-01

There are three basic types of decision aids to facilitate operating room (OR) management decision-making on the day of surgery. Decision makers can rely on passive status displays (e.g., big screens or whiteboards), active status displays (e.g., text pager notification), and/or command displays (e.g., text recommendations about what to do). Anesthesiologists, OR nurses, and housekeepers were given nine simulated scenarios (vignettes) involving multiple ORs to study their decision-making. Participants were randomized to one of four groups, all with an updated paper OR schedule: with/without command display and with/without passive status display. Participants making decisions without command displays performed no better than random chance in terms of increasing the predictability of work hours, reducing over-utilized OR time, and increasing OR efficiency. Status displays had no effect on these end-points, whereas command displays improved the quality of decisions. In the scenarios for which the command displays provided recommendations that adversely affected safety, participants appropriately ignored advice. Anesthesia providers and nursing staff made decisions that increased clinical work per unit time in each OR, even when doing so resulted in an increase in over-utilized OR time, higher staffing costs, unpredictable work hours, and/or mandatory overtime. Organizational culture and socialization during clinical training may be a cause. Command displays showed promise in mitigating this tendency. Additional investigations are in our companion paper.

Sensitivity to Spatiotemporal Percepts Predicts the Perception of Emotion

PubMed Central

Castro, Vanessa L.; Boone, R. Thomas

2015-01-01

The present studies examined how sensitivity to spatiotemporal percepts such as rhythm, angularity, configuration, and force predicts accuracy in perceiving emotion. In Study 1, participants (N = 99) completed a nonverbal test battery consisting of three nonverbal emotion perception tests and two perceptual sensitivity tasks assessing rhythm sensitivity and angularity sensitivity. Study 2 (N = 101) extended the findings of Study 1 with the addition of a fourth nonverbal test, a third configural sensitivity task, and a fourth force sensitivity task. Regression analyses across both studies revealed partial support for the association between perceptual sensitivity to spatiotemporal percepts and greater emotion perception accuracy. Results indicate that accuracy in perceiving emotions may be predicted by sensitivity to specific percepts embedded within channel- and emotion-specific displays. The significance of such research lies in the understanding of how individuals acquire emotion perception skill and the processes by which distinct features of percepts are related to the perception of emotion. PMID:26339111

Partner-Drug Resistance and Population Substructuring of Artemisinin-Resistant Plasmodium falciparum in Cambodia

PubMed Central

Parobek, Christian M.; Parr, Jonathan B.; Brazeau, Nicholas F.; Lon, Chanthap; Chaorattanakawee, Suwanna; Gosi, Panita; Barnett, Eric J.; Norris, Lauren D.; Meshnick, Steven R.; Spring, Michele D.; Lanteri, Charlotte A.; Bailey, Jeffrey A.; Saunders, David L.; Lin, Jessica T.

2017-01-01

Abstract Plasmodium falciparum in western Cambodia has developed resistance to artemisinin and its partner drugs, causing frequent treatment failure. Understanding this evolution can inform the deployment of new therapies. We investigated the genetic architecture of 78 falciparum isolates using whole-genome sequencing, correlating results to in vivo and ex vivo drug resistance and exploring the relationship between population structure, demographic history, and partner drug resistance. Principle component analysis, network analysis and demographic inference identified a diverse central population with three clusters of clonally expanding parasite populations, each associated with specific K13 artemisinin resistance alleles and partner drug resistance profiles which were consistent with the sequential deployment of artemisinin combination therapies in the region. One cluster displayed ex vivo piperaquine resistance and mefloquine sensitivity with a high rate of in vivo failure of dihydroartemisinin-piperaquine. Another cluster displayed ex vivo mefloquine resistance and piperaquine sensitivity with high in vivo efficacy of dihydroartemisinin-piperaquine. The final cluster was clonal and displayed intermediate sensitivity to both drugs. Variations in recently described piperaquine resistance markers did not explain the difference in mean IC90 or clinical failures between the high and intermediate piperaquine resistance groups, suggesting additional loci may be involved in resistance. The results highlight an important role for partner drug resistance in shaping the P. falciparum genetic landscape in Southeast Asia and suggest that further work is needed to evaluate for other mutations that drive piperaquine resistance. PMID:28854635

Multifocal electroretinographical changes in monkeys with experimental ocular hypertension: a longitudinal study.

PubMed

Kremers, Jan; Doelemeyer, Arno; Polska, Elzbieta A; Moret, Fabrice; Lambert, Christian; Lambrou, George N

2008-07-01

To study the time course of changes in the multifocal electroretinograms (mfERG) in monkeys with experimental ocular hypertension (OHT). The mfERGs were recorded in 12 eyes out of 6 monkeys. Two baseline measurements were used to quantify the reproducibility, the inter-ocular and the inter-individual variability of the ERG signals. Thereafter, the trabeculum of one eye of each animal was laser-coagulated in one to three sessions to induce OHT. ERG measurements were repeated regularly in a period of 18 months and the changes in ERG waveforms were quantified. All animals displayed OHT (between 20 and 50 mmHg) in the laser-coagulated eyes. An ERG change was defined as the sum of differences during the first 90 ms between the laser-coagulated eye and the same eye before laser coagulation and between the laser-coagulated eye and the non-treated fellow eye. Three animals displayed significant changes for nearly all retinal areas and all stimulus conditions. The three remaining animals displayed significant changes only in one comparison, indicating very mild changes. The data indicate that a high stimulus contrast is more sensitive to detect changes, probably because of a better signal-to-noise ratio. Moreover, the comparisons with the fellow eye are more sensitive to detect changes than comparisons with the measurements before laser-coagulation. OHT does not always lead to ERG changes. Comparisons with fellow eyes using high contrast stimuli are more sensitive to detect changes related to OHT.

Right-Wing Politicians Prefer the Emotional Left

PubMed Central

Thomas, Nicole A.; Loetscher, Tobias; Clode, Danielle; Nicholls, Michael E. R.

2012-01-01

Physiological research suggests that social attitudes, such as political beliefs, may be partly hard-wired in the brain. Conservatives have heightened sensitivity for detecting emotional faces and use emotion more effectively when campaigning. As the left face displays emotion more prominently, we examined 1538 official photographs of conservative and liberal politicians from Australia, Canada, the United Kingdom and the United States for an asymmetry in posing. Across nations, conservatives were more likely than liberals to display the left cheek. In contrast, liberals were more likely to face forward than were conservatives. Emotion is important in political campaigning and as portraits influence voting decisions, conservative politicians may intuitively display the left face to convey emotion to voters. PMID:22567166

Highly compressible fluorescent particles for pressure sensing in liquids

NASA Astrophysics Data System (ADS)

Cellini, F.; Peterson, S. D.; Porfiri, M.

2017-05-01

Pressure sensing in liquids is important for engineering applications ranging from industrial processing to naval architecture. Here, we propose a pressure sensor based on highly compressible polydimethylsiloxane foam particles embedding fluorescent Nile Red molecules. The particles display pressure sensitivities as low as 0.0018 kPa-1, which are on the same order of magnitude of sensitivities reported in commercial pressure-sensitive paints for air flows. We envision the application of the proposed sensor in particle image velocimetry toward an improved understanding of flow kinetics in liquids.

Development of loop-mediated isothermal amplification with Plasmodium falciparum unique genes for molecular diagnosis of human malaria.

PubMed

Zhang, Yijing; Yao, Yi; Du, Weixing; Wu, Kai; Xu, Wenyue; Lin, Min; Tan, Huabing; Li, Jian

2017-07-01

In order to achieve better outcomes for treatment and in the prophylaxis of malaria, it is imperative to develop a sensitive, specific, and accurate assay for early diagnosis of Plasmodium falciparum infection, which is the major cause of malaria. In this study, we aimed to develop a loop-mediated isothermal amplification (LAMP) assay with P. falciparum unique genes for sensitive, specific, and accurate detection of P. falciparum infection. The unique genes of P. falciparum were randomly selected from PlasmoDB. The LAMP primers of the unique genes were designed using PrimerExplorer V4. LAMP assays with primers from unique genes of P. falciparum and conserved 18S rRNA gene were developed and their sensitivity was assessed. The specificity of the most sensitive LAMP assay was further examined using genomic DNA from Plasmodium vivax, Plasmodium yoelii and Toxoplasma gondii. Finally, the unique gene-based LAMP assay was validated using clinical samples of P. falciparum infection cases. A total of 31 sets of top-scored LAMP primers from nine unique genes were selected from the pools of designed primers. The LAMP assay with PF3D7_1253300-5 was the most sensitive with the detection limit 5 parasites/μl, and it displayed negative LAMP assay with the genomic DNA samples of P. vivax, P. yoelii, and T. gondii. The LAMP assay with PF3D7_0112300 (18S rRNA) was less sensitive with the detection limit 50 parasites/μl, and it displayed negative LAMP assay with the genomic DNA samples of P. yoelii and T. gondii, but displayed positive LAMP detection with P. vivax. The positive detection rate of the LAMP assay with PF3D7_1253300-5 was 90% (27/30), higher than that (80%, 24/30) of the positive rate of PF3D7_0112300 (18S rRNA) in examining clinical samples of P. falciparum infection cases. The LAMP assay with the primer set PF3D7_1253300-5 was more sensitive, specific, and accurate than those with PF3D7_0112300 (18S rRNA) in examining P. falciparum infection, and therefore it is a promising tool for diagnosis of P. falciparum infection.

Humidity-enhanced sub-ppm sensitivity to ammonia of covalently functionalized single-wall carbon nanotube bundle layers

NASA Astrophysics Data System (ADS)

Rigoni, F.; Freddi, S.; Pagliara, S.; Drera, G.; Sangaletti, L.; Suisse, J.-M.; Bouvet, M.; Malovichko, A. M.; Emelianov, A. V.; Bobrinetskiy, I. I.

2017-06-01

A low-cost method for carbon nanotubes (CNTs) network production from solutions on flexible polyethylene naphthalate substrates has been adopted to prepare high quality and well characterized SWCNT bundle layers to be used as the active layer in chemiresistor gas sensors. Two types of SWCNTs have been tested: pristine SWCNTs, deposited from a surfactant solution, and covalently functionalized SWCNTs, deposited from a dimethyl-acetamide solution. The humidity effects on the sensitivity of the SWCNTs network to NH3 have been investigated. The results show that relative humidity favors the response to NH3, confirming recent theoretical predictions. The COOH-functionalized sample displays the largest response owing to both its hydrophilic nature, favoring the interaction with H2O molecules, and its largest surface area. Compared to data available in the literature, the present sensors display a remarkable sensitivity well below the ppm range, which makes them quite promising for environmental and medical applications, where NH3 concentrations (mostly of the order of tens of ppb) have to be detected.

The directional response of chemotactic cells depends on a balance between cytoskeletal architecture and the external gradient.

PubMed

Wang, Ming-Jie; Artemenko, Yulia; Cai, Wen-Jie; Iglesias, Pablo A; Devreotes, Peter N

2014-11-06

Polarized migrating cells display signal transduction events, such as activation of phosphatidylinositol 3-kinase (PI3K) and Scar/Wave, and respond more readily to chemotactic stimuli at the leading edge. We sought to determine the basis of this polarized sensitivity. Inhibiting actin polymerization leads to uniform sensitivity. However, when human neutrophils were "stalled" by simultaneously blocking actin and myosin dynamics, they maintained the gradient of responsiveness to chemoattractant and also displayed noise-driven PIP3 flashes on the basal membrane, localized toward the front. Thus, polarized sensitivity does not require migration or cytoskeletal dynamics. The threshold for response is correlated with the static F-actin distribution, but not cell shape or volume changes, membrane fluidity, or the preexisting distribution of PI3K. The kinetics of responses to temporal and spatial stimuli were consistent with the local excitation global inhibition model, but the overall direction of the response was biased by the internal axis of polarity. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Fluorescence-guided tumor visualization using a custom designed NIR attachment to a surgical microscope for high sensitivity imaging (Conference Presentation)

NASA Astrophysics Data System (ADS)

Kittle, David S.; Patil, Chirag G.; Mamelak, Adam; Hansen, Stacey; Perry, Jeff; Ishak, Laura; Black, Keith L.; Butte, Pramod V.

2016-03-01

Current surgical microscopes are limited in sensitivity for NIR fluorescence. Recent developments in tumor markers attached with NIR dyes require newer, more sensitive imaging systems with high resolution to guide surgical resection. We report on a small, single camera solution enabling advanced image processing opportunities previously unavailable for ultra-high sensitivity imaging of these agents. The system captures both visible reflectance and NIR fluorescence at 300 fps while displaying full HD resolution video at 60 fps. The camera head has been designed to easily mount onto the Zeiss Pentero microscope head for seamless integration into surgical procedures.

Advanced Aircrew Display Symposium (3rd), 19-20 May.

DTIC Science & Technology

1976-01-01

piozea. This was in 1968. ’hS ese3e -2 -12 CE LS 1s desijn a si’mc;,41ed coiimator (movic diamond . fixed line) ot zo jza cy, .mhch v.as mounted on a...typical of electromechanical sights. The tracer sight displays electronic bullets with stadiametric range marks and a diamond at target range when...hackles on the necks of some engineers and pilots, we have become sensitive to the super-engineer/ super- pilot syndrome . It is very desirable to

Polyphosphate Affects on Breast Cancer Cell Survival

DTIC Science & Technology

2007-04-01

not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE (DD-MM-YYYY) 01-04-2007 2...and verify the strains that were developed. Strains without UvrA are extremely sensitive to UV light so the screen easily displays the strains with...2007) W81XWH-04-1-0379 P.I. Christine Haakenson pPPK 6609 bp Selectable Marker Promoter BAD prom MCS M13 intergenic region pBR322 ORI rrnB araC

The use of the phasor display in studying ionospheric radio echoes

NASA Astrophysics Data System (ADS)

From, W. R.; Whitehead, J. D.

1981-12-01

The phase and amplitude of a radio pulse reflected from the ionosphere usually vary during the pulse. It is convenient to observe these variations using the X-Y mode of an oscilloscope to display the phasor of the echo. The variations are then seen as an oval or spiral shape traced out by the end point of the phasor. These shapes provide a sensitive method of detecting the presence of more than one echo, and are useful as a measure of dispersion.

Computer-aided testing of pilot response to critical in-flight events

NASA Technical Reports Server (NTRS)

Giffin, W. C.; Rockwell, T. H.

1984-01-01

This research on pilot response to critical in-flight events employs a unique methodology including an interactive computer-aided scenario-testing system. Navigation displays, instrument-panel displays, and assorted textual material are presented on a touch-sensitive CRT screen. Problem diagnosis scenarios, destination-diversion scenarios and combined destination/diagnostic tests are available. A complete time history of all data inquiries and responses is maintained. Sample results of diagnosis scenarios obtained from testing 38 licensed pilots are presented and discussed.

Cocaine sensitization increases subthreshold activity in dopamine neurons from the ventral tegmental area.

PubMed

Arencibia-Albite, Francisco; Vázquez-Torres, Rafael; Jiménez-Rivera, Carlos A

2017-02-01

The progressive escalation of psychomotor responses that results from repeated cocaine administration is termed sensitization. This phenomenon alters the intrinsic properties of dopamine (DA) neurons from the ventral tegmental area (VTA), leading to enhanced dopaminergic transmission in the mesocorticolimbic network. The mechanisms underlying this augmented excitation are nonetheless poorly understood. DA neurons display the hyperpolarization-activated, nonselective cation current, dubbed I h We recently demonstrated that I h and membrane capacitance are substantially reduced in VTA DA cells from cocaine-sensitized rats. The present study shows that 7 days of cocaine withdrawal did not normalize I h and capacitance. In cells from cocaine-sensitized animals, the amplitude of excitatory synaptic potentials, at -70 mV, was ∼39% larger in contrast to controls. Raise and decay phases of the synaptic signal were faster under cocaine, a result associated with a reduced membrane time constant. Synaptic summation was paradoxically elevated by cocaine exposure, as it consisted of a significantly reduced summation indexed but a considerably increased depolarization. These effects are at least a consequence of the reduced capacitance. I h attenuation is unlikely to explain such observations, since at -70 mV, no statistical differences exist in I h or input resistance. The neuronal shrinkage associated with a diminished capacitance may help to understand two fundamental elements of drug addiction: incentive sensitization and negative emotional states. A reduced cell size may lead to substantial enhancement of cue-triggered bursting, which underlies drug craving and reward anticipation, whereas it could also result in DA depletion, as smaller neurons might express low levels of tyrosine hydroxylase. This work uses a new approach that directly extracts important biophysical parameters from alpha function-evoked synaptic potentials. Two of these parameters are the cell membrane capacitance (C m ) and rate at any time point of the synaptic waveform. The use of such methodology shows that cocaine sensitization reduces C m and increases the speed of synaptic signaling. Paradoxically, although synaptic potentials show a faster decay under cocaine their temporal summation is substantially elevated. Copyright © 2017 the American Physiological Society.

Medical color displays and their calibration

NASA Astrophysics Data System (ADS)

Fan, Jiahua; Roehrig, Hans; Dallas, W.; Krupinski, Elizabeth

2009-08-01

Color displays are increasingly used for medical imaging, replacing the traditional monochrome displays in radiology for multi-modality applications, 3D representation applications, etc. Color displays are also used increasingly because of wide spread application of Tele-Medicine, Tele-Dermatology and Digital Pathology. At this time, there is no concerted effort for calibration procedures for this diverse range of color displays in Telemedicine and in other areas of the medical field. Using a colorimeter to measure the display luminance and chrominance properties as well as some processing software we developed a first attempt to a color calibration protocol for the medical imaging field.

Cytochrome P4502E1 primes macrophages to increase TNF-alpha production in response to lipopolysaccharide.

PubMed

Cao, Qi; Mak, Ki M; Lieber, Charles S

2005-07-01

Kupffer cells become activated in response to elevated levels of LPS during ethanol feeding, but the role of ethanol in the molecular processes of activation remains unclear. Because cytochrome P4502E1 (CYP2E1) is upregulated in Kupffer cells after ethanol, we hypothesized that this effect primes Kupffer cells, sensitizing them to increase TNF-alpha production in response to LPS. However, cultured Kupffer cells rapidly lose their CYP2E1. This difficulty was overcome by transfecting CYP2E1 to RAW 264.7 macrophages. Macrophages with stable increased CYP2E1 expression (E2) displayed increased levels of CD14/Toll-like receptor 4, NADPH oxidase and H2O2, accompanied by activation of ERK1/2, p38, and NF-kappaB. These increases primed E2 cells, sensitizing them to LPS stimuli, with amplification of LPS signaling, resulting in increased TNF-alpha production. Diphenyleneiodonium, a NADPH oxidase inhibitor, and diallyl sulfide, a CYP2E1 inhibitor, decreased approximately equally H2O2 levels in E2 cells, suggesting that NADPH oxidase and CYP2E1 contribute equally to H2O2 generation. Because CYP2E1 expression also enhanced the levels of the membrane localized NADPH oxidase subunits p47phox and p67phox, thereby contributing to the oxidase activation, it may augment H2O2 generation via this mechanism. H2O2, derived in part from NADPH and CYP2E1, activated ERK1/2 and p38. ERK1/2 stimulated TNF-alpha production via activation of NF-kappaB, whereas p38 promoted TNF-alpha production by stabilizing TNF-alpha mRNA. Oxidant generation after CYP2E1 overexpression appears to be central to macrophage priming and their sensitization to LPS. Accordingly, CYP2E1 priming could explain the sensitization of Kupffer cells to LPS activation by ethanol, a critical early step in alcoholic liver disease.

Brain dynamics of visual attention during anticipation and encoding of threat- and safe-cues in spider-phobic individuals

PubMed Central

Pané-Farré, Christiane A.; Löw, Andreas; Hamm, Alfons O.

2015-01-01

This study systematically investigated the sensitivity of the phobic attention system by measuring event-related potentials (ERPs) in spider-phobic and non-phobic volunteers in a context where spider and neutral pictures were presented (phobic threat condition) and in contexts where no phobic but unpleasant and neutral or only neutral pictures were displayed (phobia-irrelevant conditions). In a between-group study, participants were assigned to phobia-irrelevant conditions either before or after the exposure to spider pictures (pre-exposure vs post-exposure participants). Additionally, each picture was preceded by a fixation cross presented in one of three different colors that were informative about the category of an upcoming picture. In the phobic threat condition, spider-phobic participants showed a larger P1 than controls for all pictures and signal cues. Moreover, individuals with spider phobia who were sensitized by the exposure to phobic stimuli (i.e. post-exposure participants) responded with an increased P1 also in phobia-irrelevant conditions. In contrast, no group differences between spider-phobic and non-phobic individuals were observed in the P1-amplitudes during viewing of phobia-irrelevant stimuli in the pre-exposure group. In addition, cues signaling neutral pictures elicited decreased stimulus-preceding negativity (SPN) compared with cues signaling emotional pictures. Moreover, emotional pictures and cues signaling emotional pictures evoked larger early posterior negativity (EPN) and late positive potential (LPP) than neutral stimuli. Spider phobics showed greater selective attention effects than controls for phobia-relevant pictures (increased EPN and LPP) and cues (increased LPP and SPN). Increased sensitization of the attention system observed in spider-phobic individuals might facilitate fear conditioning and promote generalization of fear playing an important role in the maintenance of anxiety disorders. PMID:25608985

Monosodium iodoacetate-induced joint pain is associated with increased phosphorylation of mitogen activated protein kinases in the rat spinal cord.

PubMed

Lee, Younglim; Pai, Madhavi; Brederson, Jill-Desiree; Wilcox, Denise; Hsieh, Gin; Jarvis, Michael F; Bitner, Robert S

2011-05-20

Intra-articular injection of monosodium iodoacetate (MIA) in the knee joint of rats disrupts chondrocyte metabolism resulting in cartilage degeneration and subsequent nociceptive behavior that has been described as a model of osteoarthritis (OA) pain. Central sensitization through activation of mitogen activated protein kinases (MAPKs) is recognized as a pathogenic mechanism in chronic pain. In the present studies, induction of central sensitization as indicated by spinal dorsal horn MAPK activation, specifically ERK and p38 phosphorylation, was assessed in the MIA-OA model. Behaviorally, MIA-injected rats displayed reduced hind limb grip force 1, 2, and 3 weeks post-MIA treatment. In the same animals, activation of phospho ERK1/2 was gradually increased, reaching a significant level at post injection week 3. Conversely, phosphorylation of p38 MAPK was enhanced maximally at post injection week 1 and decreased, but remained elevated, thereafter. Double labeling from 3-wk MIA rats demonstrated spinal pERK1/2 expression in neurons, but not glia. In contrast, p-p38 was expressed by microglia and a subpopulation of neurons, but not astrocytes. Additionally, there was increased ipsilateral expression of microglia, but not astrocytes, in 3-wk MIA-OA rats. Consistent with increased MAPK immunoreactivity in the contralateral dorsal horn, mechanical allodynia to the contralateral hind-limb was observed 3-wk following MIA. Finally, intrathecal injection of the MEK1 inhibitor PD98059 blocked both reduced hind-limb grip force and pERK1/2 induction in MIA-OA rats. Results of these studies support the role of MAPK activation in the progression and maintenance of central sensitization in the MIA-OA experimental pain model.

Colorimetry for CRT displays.

PubMed

Golz, Jürgen; MacLeod, Donald I A

2003-05-01

We analyze the sources of error in specifying color in CRT displays. These include errors inherent in the use of the color matching functions of the CIE 1931 standard observer when only colorimetric, not radiometric, calibrations are available. We provide transformation coefficients that prove to correct the deficiencies of this observer very well. We consider four different candidate sets of cone sensitivities. Some of these differ substantially; variation among candidate cone sensitivities exceeds the variation among phosphors. Finally, the effects of the recognized forms of observer variation on the visual responses (cone excitations or cone contrasts) generated by CRT stimuli are investigated and quantitatively specified. Cone pigment polymorphism gives rise to variation of a few per cent in relative excitation by the different phosphors--a variation larger than the errors ensuing from the adoption of the CIE standard observer, though smaller than the differences between some candidate cone sensitivities. Macular pigmentation has a larger influence, affecting mainly responses to the blue phosphor. The estimated combined effect of all sources of observer variation is comparable in magnitude with the largest differences between competing cone sensitivity estimates but is not enough to disrupt very seriously the relation between the L and M cone weights and the isoluminance settings of individual observers. It is also comparable with typical instrumental colorimetric errors, but we discuss these only briefly.

Cell adhesion and guidance by micropost-array chemical sensors

NASA Astrophysics Data System (ADS)

Pantano, Paul; Quah, Soo-Kim; Danowski, Kristine L.

2002-06-01

An array of ~50,000 individual polymeric micropost sensors was patterned across a glass coverslip by a photoimprint lithographic technique. Individual micropost sensors were ~3-micrometers tall and ~8-micrometers wide. The O2-sensitive micropost array sensors (MPASs) comprised a ruthenium complex encapsulated in a gas permeable photopolymerizable siloxane. The pH-sensitive MPASs comprised a fluorescein conjugate encapsulated in a photocrosslinkable poly(vinyl alcohol)-based polymer. PO2 and pH were quantitated by acquiring MPAS luminescence images with an epifluorescence microscope/charge coupled device imaging system. O2-sensitive MPASs displayed linear Stern-Volmer quenching behavior with a maximum Io/I of ~8.6. pH-sensitive MPASs displayed sigmoidal calibration curves with a pKa of ~5.8. The adhesion of undifferentiated rat pheochromocytoma (PC12) cells across these two polymeric surface types was investigated. The greatest PC12 cell proliferation and adhesion occurred across the poly(vinyl alcohol)-based micropost arrays relative to planar poly(vinyl alcohol)-based surfaces and both patterned and planar siloxane surfaces. An additional advantage of the patterned MPAS layers relative to planar sensing layers was the ability to direct the growth of biological cells. Preliminary data is presented whereby nerve growth factor-differentiated PC12 cells grew neurite-like processes that extended along paths defined by the micropost architecture.

The precategorical nature of visual short-term memory.

PubMed

Quinlan, Philip T; Cohen, Dale J

2016-11-01

We conducted a series of recognition experiments that assessed whether visual short-term memory (VSTM) is sensitive to shared category membership of to-be-remembered (tbr) images of common objects. In Experiment 1 some of the tbr items shared the same basic level category (e.g., hand axe): Such items were no better retained than others. In the remaining experiments, displays contained different images of items from the same higher-level category (e.g., food: a bagel, a sandwich, a pizza). Evidence from the later experiments did suggest that participants were sensitive to the categorical relations present in the displays. However, when separate measures of sensitivity and bias were computed, the data revealed no effects on sensitivity, but a greater tendency to respond positively to noncategory items relative to items from the depicted category. Across all experiments, there was no evidence that items from a common category were better remembered than unique items. Previous work has shown that principles of perceptual organization do affect the storage and maintenance of tbr items. The present work shows that there are no corresponding conceptual principles of organization in VSTM. It is concluded that the sort of VSTM tapped by single probe recognition methods is precategorical in nature. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

A gaze-contingent display to study contrast sensitivity under natural viewing conditions

NASA Astrophysics Data System (ADS)

Dorr, Michael; Bex, Peter J.

2011-03-01

Contrast sensitivity has been extensively studied over the last decades and there are well-established models of early vision that were derived by presenting the visual system with synthetic stimuli such as sine-wave gratings near threshold contrasts. Natural scenes, however, contain a much wider distribution of orientations, spatial frequencies, and both luminance and contrast values. Furthermore, humans typically move their eyes two to three times per second under natural viewing conditions, but most laboratory experiments require subjects to maintain central fixation. We here describe a gaze-contingent display capable of performing real-time contrast modulations of video in retinal coordinates, thus allowing us to study contrast sensitivity when dynamically viewing dynamic scenes. Our system is based on a Laplacian pyramid for each frame that efficiently represents individual frequency bands. Each output pixel is then computed as a locally weighted sum of pyramid levels to introduce local contrast changes as a function of gaze. Our GPU implementation achieves real-time performance with more than 100 fps on high-resolution video (1920 by 1080 pixels) and a synthesis latency of only 1.5ms. Psychophysical data show that contrast sensitivity is greatly decreased in natural videos and under dynamic viewing conditions. Synthetic stimuli therefore only poorly characterize natural vision.

Broadband Ce(III)-Sensitized Quantum Cutting in Core-Shell Nanoparticles: Mechanistic Investigation and Photovoltaic Application.

PubMed

Sun, Tianying; Chen, Xian; Jin, Limin; Li, Ho-Wa; Chen, Bing; Fan, Bo; Moine, Bernard; Qiao, Xvsheng; Fan, Xianping; Tsang, Sai-Wing; Yu, Siu Fung; Wang, Feng

2017-10-19

Quantum cutting in lanthanide-doped luminescent materials is promising for applications such as solar cells, mercury-free lamps, and plasma panel displays because of the ability to emit multiple photons for each absorbed higher-energy photon. Herein, a broadband Ce 3+ -sensitized quantum cutting process in Nd 3+ ions is reported though gadolinium sublattice-mediated energy migration in a NaGdF 4 :Ce@NaGdF 4 :Nd@NaYF 4 nanostructure. The Nd 3+ ions show downconversion of one ultraviolet photon through two successive energy transitions, resulting in one visible photon and one near-infrared (NIR) photon. A class of NaGdF 4 :Ce@NaGdF 4 :Nd/Yb@NaYF 4 nanoparticles is further developed to expand the spectrum of quantum cutting in the NIR. When the quantum cutting nanoparticles are incorporated into a hybrid crystalline silicon (c-Si) solar cell, a 1.2-fold increase in short-circuit current and a 1.4-fold increase in power conversion efficiency is demonstrated under short-wavelength ultraviolet irradiation. These insights should enhance our ability to control and utilize spectral downconversion with lanthanide ions.

The dissociation of subjective measures of mental workload and performance

NASA Technical Reports Server (NTRS)

Yeh, Y. H.; Wickens, C. D.

1984-01-01

Dissociation between performance and subjective workload measures was investigated in the theoretical framework of the multiple resources model. Subjective measures do not preserve the vector characteristics in the multidimensional space described by the model. A theory of dissociation was proposed to locate the sources that may produce dissociation between the two workload measures. According to the theory, performance is affected by every aspect of processing whereas subjective workload is sensitive to the amount of aggregate resource investment and is dominated by the demands on the perceptual/central resources. The proposed theory was tested in three experiments. Results showed that performance improved but subjective workload was elevated with an increasing amount of resource investment. Furthermore, subjective workload was not as sensitive as was performance to differences in the amount of resource competition between two tasks. The demand on perceptual/central resources was found to be the most salient component of subjective workload. Dissociation occurred when the demand on this component was increased by the number of concurrent tasks or by the number of display elements. However, demands on response resources were weighted in subjective introspection as much as demands on perceptual/central resources. The implications of these results for workload practitioners are described.

Evidence and arguments on tobacco retail displays: marketing an addictive drug to children?

PubMed

Thomson, George; Hoek, Janet; Edwards, Richard; Gifford, Heather

2008-06-20

To investigate arguments for and against a ban on tobacco displays in New Zealand shops. Analysis of evidence from international experience and research studies, for the arguments used to oppose and support display bans; and 27 qualitative interviews with New Zealand ex-smokers, smokers, and retailers. The main arguments used to oppose display bans identified were: (1) Fears of financial losses for retailers, particularly for small stores; (2) Claims that tobacco is a 'normal' product; (3) 'Lack of evidence' about effectiveness of display bans; and (4) Fears of increased theft and risks to staff. The counter-arguments include: (1) The lack of evidence of significant short term adverse economic effects on retailers (including small stores) where display bans have been implemented; (2) Tobacco is a highly abnormal and hazardous retail product; (3) Evidence that tobacco displays influence initiation of smoking among children, increase impulse purchases, and are crucial to tobacco companies' marketing strategies; (4) Lack of evidence that display bans increase thefts and risks to staff. The qualitative interviews supported the counter arguments. Smokers and ex-smokers interviewed indicated that tobacco displays tempt smokers trying to quit. There was widespread support for a display ban among interviewees (including some retailers) mainly because it might reduce smoking uptake among children. Arguments for tobacco displays are contradictory, flawed, and unsupported by local and international research evidence, and by the overseas experience of tobacco-free display policies.

Proteomic analysis reveals contrasting stress response to uranium in two nitrogen-fixing Anabaena strains, differentially tolerant to uranium.

PubMed

Panda, Bandita; Basu, Bhakti; Acharya, Celin; Rajaram, Hema; Apte, Shree Kumar

2017-01-01

Two strains of the nitrogen-fixing cyanobacterium Anabaena, native to Indian paddy fields, displayed differential sensitivity to exposure to uranyl carbonate at neutral pH. Anabaena sp. strain PCC 7120 and Anabaena sp. strain L-31 displayed 50% reduction in survival (LD 50 dose), following 3h exposure to 75μM and 200μM uranyl carbonate, respectively. Uranium responsive proteome alterations were visualized by 2D gel electrophoresis, followed by protein identification by MALDI-ToF mass spectrometry. The two strains displayed significant differences in levels of proteins associated with photosynthesis, carbon metabolism, and oxidative stress alleviation, commensurate with their uranium tolerance. Higher uranium tolerance of Anabaena sp. strain L-31 could be attributed to sustained photosynthesis and carbon metabolism and superior oxidative stress defense, as compared to the uranium sensitive Anabaena sp. strain PCC 7120. Uranium responsive proteome modulations in two nitrogen-fixing strains of Anabaena, native to Indian paddy fields, revealed that rapid adaptation to better oxidative stress management, and maintenance of metabolic and energy homeostasis underlies superior uranium tolerance of Anabaena sp. strain L-31 compared to Anabaena sp. strain PCC 7120. Copyright © 2016 Elsevier B.V. All rights reserved.

Automation of fluorescent differential display with digital readout.

PubMed

Meade, Jonathan D; Cho, Yong-Jig; Fisher, Jeffrey S; Walden, Jamie C; Guo, Zhen; Liang, Peng

2006-01-01

Since its invention in 1992, differential display (DD) has become the most commonly used technique for identifying differentially expressed genes because of its many advantages over competing technologies such as DNA microarray, serial analysis of gene expression (SAGE), and subtractive hybridization. Despite the great impact of the method on biomedical research, there has been a lack of automation of DD technology to increase its throughput and accuracy for systematic gene expression analysis. Most of previous DD work has taken a "shot-gun" approach of identifying one gene at a time, with a limited number of polymerase chain reaction (PCR) reactions set up manually, giving DD a low-tech and low-throughput image. We have optimized the DD process with a new platform that incorporates fluorescent digital readout, automated liquid handling, and large-format gels capable of running entire 96-well plates. The resulting streamlined fluorescent DD (FDD) technology offers an unprecedented accuracy, sensitivity, and throughput in comprehensive and quantitative analysis of gene expression. These major improvements will allow researchers to find differentially expressed genes of interest, both known and novel, quickly and easily.

Urothelial Tight Junction Barrier Dysfunction Sensitizes Bladder Afferents

PubMed Central

Rued, Anna C.; Taiclet, Stefanie N.; Birder, Lori A.; Kullmann, F. Aura

2017-01-01

Abstract Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic voiding disorder that presents with pain in the urinary bladder and surrounding pelvic region. A growing body of evidence suggests that an increase in the permeability of the urothelium, the epithelial barrier that lines the interior of the bladder, contributes to the symptoms of IC/BPS. To examine the consequence of increased urothelial permeability on pelvic pain and afferent excitability, we overexpressed in the urothelium claudin 2 (Cldn2), a tight junction (TJ)-associated protein whose message is significantly upregulated in biopsies of IC/BPS patients. Consistent with the presence of bladder-derived pain, rats overexpressing Cldn2 showed hypersensitivity to von Frey filaments applied to the pelvic region. Overexpression of Cldn2 increased the expression of c-Fos and promoted the activation of ERK1/2 in spinal cord segments receiving bladder input, which we conceive is the result of noxious stimulation of afferent pathways. To determine whether the mechanical allodynia observed in rats with reduced urothelial barrier function results from altered afferent activity, we examined the firing of acutely isolated bladder sensory neurons. In patch-clamp recordings, about 30% of the bladder sensory neurons from rats transduced with Cldn2, but not controls transduced with GFP, displayed spontaneous activity. Furthermore, bladder sensory neurons with tetrodotoxin-sensitive (TTX-S) action potentials from rats transduced with Cldn2 showed hyperexcitability in response to suprathreshold electrical stimulation. These findings suggest that as a result of a leaky urothelium, the diffusion of urinary solutes through the urothelial barrier sensitizes bladders afferents, promoting voiding at low filling volumes and pain. PMID:28560313

DNA-dependent protein kinase (DNA-PK)-deficient human glioblastoma cells are preferentially sensitized by Zebularine

PubMed Central

Meador, Jarah A.; Su, Yanrong; Ravanat, Jean-Luc; Balajee, Adayabalam S.

2010-01-01

Brain tumor cells respond poorly to radiotherapy and chemotherapy due to inherently efficient anti-apoptotic and DNA repair mechanisms. This necessitates the development of new strategies for brain cancer therapy. Here, we report that the DNA-demethylating agent Zebularine preferentially sensitizes the killing of human glioblastomas deficient in DNA-dependent protein kinase (DNA-PK). In contrast to DNA-PK-proficient human glioblastoma cells (MO59K), cytotoxicity assay with increasing Zebularine concentrations up to 300 μM resulted in a specific elevation of cell killing in DNA-PK-deficient MO59J cells. Further, an elevated frequency of polyploid cells observed in MO59J cells after Zebularine treatment pointed out a deficiency in mitotic checkpoint control. Existence of mitotic checkpoint deficiency in MO59J cells was confirmed by the abnormal centrosome number observed in Zebularine-treated MO59J cells. Although depletion of DNA methyltransferase 1 by Zebularine occurred at similar levels in both cell lines, MO59J cells displayed increased extent of DNA demethylation detected both at the gene promoter-specific level and at the genome overall level. Consistent with increased sensitivity, deoxy-Zebularine adduct level in the genomic DNA was 3- to 6-fold higher in MO59J than in MO59K cells. Elevated micronuclei frequency observed after Zebularine treatment in MO59J cells indicates the impairment of DNA repair response in MO59J cells. Collectively, our study suggests that DNA-PK is the major determining factor for cellular response to Zebularine. PMID:19933707

Noradrenergic modulation of risk/reward decision making.

PubMed

Montes, David R; Stopper, Colin M; Floresco, Stan B

2015-08-01

Catecholamine transmission modulates numerous cognitive and reward-related processes that can subserve more complex functions such as cost/benefit decision making. Dopamine has been shown to play an integral role in decisions involving reward uncertainty, yet there is a paucity of research investigating the contributions of noradrenaline (NA) transmission to these functions. The present study was designed to elucidate the contribution of NA to risk/reward decision making in rats, assessed with a probabilistic discounting task. We examined the effects of reducing noradrenergic transmission with the α2 agonist clonidine (10-100 μg/kg), and increasing activity at α2A receptor sites with the agonist guanfacine (0.1-1 mg/kg), the α2 antagonist yohimbine (1-3 mg/kg), and the noradrenaline transporter (NET) inhibitor atomoxetine (0.3-3 mg/kg) on probabilistic discounting. Rats chose between a small/certain reward and a larger/risky reward, wherein the probability of obtaining the larger reward either decreased (100-12.5 %) or increased (12.5-100 %) over a session. In well-trained rats, clonidine reduced risky choice by decreasing reward sensitivity, whereas guanfacine did not affect choice behavior. Yohimbine impaired adjustments in decision biases as reward probability changed within a session by altering negative feedback sensitivity. In a subset of rats that displayed prominent discounting of probabilistic rewards, the lowest dose of atomoxetine increased preference for the large/risky reward when this option had greater long-term utility. These data highlight an important and previously uncharacterized role for noradrenergic transmission in mediating different aspects of risk/reward decision making and mediating reward and negative feedback sensitivity.

Wafer-level vacuum packaged resonant micro-scanning mirrors for compact laser projection displays

NASA Astrophysics Data System (ADS)

Hofmann, Ulrich; Oldsen, Marten; Quenzer, Hans-Joachim; Janes, Joachim; Heller, Martin; Weiss, Manfred; Fakas, Georgios; Ratzmann, Lars; Marchetti, Eleonora; D'Ascoli, Francesco; Melani, Massimiliano; Bacciarelli, Luca; Volpi, Emilio; Battini, Francesco; Mostardini, Luca; Sechi, Francesco; De Marinis, Marco; Wagner, Bernd

2008-02-01

Scanning laser projection using resonant actuated MEMS scanning mirrors is expected to overcome the current limitation of small display size of mobile devices like cell phones, digital cameras and PDAs. Recent progress in the development of compact modulated RGB laser sources enables to set up very small laser projection systems that become attractive not only for consumer products but also for automotive applications like head-up and dash-board displays. Within the last years continuous progress was made in increasing MEMS scanner performance. However, only little is reported on how mass-produceability of these devices and stable functionality even under harsh environmental conditions can be guaranteed. Automotive application requires stable MEMS scanner operation over a wide temperature range from -40° to +85°Celsius. Therefore, hermetic packaging of electrostatically actuated MEMS scanning mirrors becomes essential to protect the sensitive device against particle contamination and condensing moisture. This paper reports on design, fabrication and test of a resonant actuated two-dimensional micro scanning mirror that is hermetically sealed on wafer level. With resonant frequencies of 30kHz and 1kHz, an achievable Theta-D-product of 13mm.deg and low dynamic deformation <20nm RMS it targets Lissajous projection with SVGA-resolution. Inevitable reflexes at the vacuum package surface can be seperated from the projection field by permanent inclination of the micromirror.

A Virtual Joy-Stick Study of Emotional Responses and Social Motivation in Children with Autism Spectrum Disorder

PubMed Central

Kim, Kwanguk; Rosenthal, M. Zachary; Gwaltney, Mary; Jarrold, William; Hatt, Naomi; McIntyre, Nancy; Swain, Lindsay; Solomon, Marjorie

2017-01-01

A new virtual reality task was employed which uses preference for interpersonal distance to social stimuli to examine social motivation and emotion perception in children with Autism Spectrum Disorders. Nineteen high function children with higher functioning Autism Spectrum Disorder (HFASD) and 23 age, gender, and IQ matched children with typical development (TD) used a joy stick to position themselves closer or further from virtual avatars while attempting to identify six emotions expressed by the avatars, happiness, fear, anger, disgust, sadness, and surprise that were expressed at different levels of intensity. The results indicated that children with HFASD displayed significantly less approach behavior to the positive happy expression than did children with TD, who displayed increases in approach behavior to higher intensities of happy expressions. Alternatively, all groups tended to withdraw from negative emotions to the same extent and there were no diagnostic group differences in accuracy of recognition of any of the six emotions. This pattern of results is consistent with theory that suggests that some children with HFASD display atypical social-approach motivation, or sensitivity to the positive reward value of positive social–emotional events. Conversely, there was little evidence that a tendency to withdraw from social–emotional stimuli, or a failure to process social emotional stimuli, was a component of social behavior task performance in this sample of children with HFASD. PMID:24435405

A Virtual Joy-Stick Study of Emotional Responses and Social Motivation in Children with Autism Spectrum Disorder.

PubMed

Kim, Kwanguk; Rosenthal, M Zachary; Gwaltney, Mary; Jarrold, William; Hatt, Naomi; McIntyre, Nancy; Swain, Lindsay; Solomon, Marjorie; Mundy, Peter

2015-12-01

A new virtual reality task was employed which uses preference for interpersonal distance to social stimuli to examine social motivation and emotion perception in children with Autism Spectrum Disorders. Nineteen high function children with higher functioning Autism Spectrum Disorder (HFASD) and 23 age, gender, and IQ matched children with typical development (TD) used a joy stick to position themselves closer or further from virtual avatars while attempting to identify six emotions expressed by the avatars, happiness, fear, anger, disgust, sadness, and surprise that were expressed at different levels of intensity. The results indicated that children with HFASD displayed significantly less approach behavior to the positive happy expression than did children with TD, who displayed increases in approach behavior to higher intensities of happy expressions. Alternatively, all groups tended to withdraw from negative emotions to the same extent and there were no diagnostic group differences in accuracy of recognition of any of the six emotions. This pattern of results is consistent with theory that suggests that some children with HFASD display atypical social-approach motivation, or sensitivity to the positive reward value of positive social-emotional events. Conversely, there was little evidence that a tendency to withdraw from social-emotional stimuli, or a failure to process social emotional stimuli, was a component of social behavior task performance in this sample of children with HFASD.

Diagnosis of Normal and Abnormal Color Vision with Cone-Specific VEPs.

PubMed

Rabin, Jeff C; Kryder, Andrew C; Lam, Dan

2016-05-01

Normal color vision depends on normal long wavelength (L), middle wavelength (M), and short wavelength sensitive (S) cones. Hereditary "red-green" color vision deficiency (CVD) is due to a shift in peak sensitivity or lack of L or M cones. Hereditary S cone CVD is rare but can be acquired as an early sign of disease. Current tests detect CVD but few diagnose type or severity, critical for linking performance to real-world demands. The anomaloscope and newer subjective tests quantify CVD but are not applicable to infants or cognitively impaired patients. Our purpose was to develop an objective test of CVD with sensitivity and specificity comparable to current tests. A calibrated visual-evoked potential (VEP) display and Food and Drug Administration-approved system was used to record L, M, and S cone-specific pattern-onset VEPs from 18 color vision normals (CVNs) and 13 hereditary CVDs. VEP amplitudes and latencies were compared between groups to establish VEP sensitivity and specificity. Cone VEPs show 100% sensitivity for diagnosis of CVD and 94% specificity for confirming CVN. L cone (protan) CVDs showed a significant increase in L cone latency (53.1 msec, P < 0.003) and decreased amplitude (10.8 uV, P < 0.0000005) but normal M and S cone VEPs ( P > 0.31). M cone (deutan) CVDs showed a significant increase in M cone latency (31.0 msec, P < 0.000004) and decreased amplitude (8.4 uV, P < 0.006) but normal L and S cone VEPs ( P > 0.29). Cone-specific VEPs offer a rapid, objective test to diagnose hereditary CVD and show potential for detecting acquired CVD in various diseases. This paper describes the efficacy of cone-specific color VEPs for quantification of normal and abnormal color vision. The rapid, objective nature of this approach makes it suitable for detecting color sensitivity loss in infants and the cognitively impaired.

MicroRNA-9 enhances sensitivity to cetuximab in epithelial phenotype hepatocellular carcinoma cells through regulation of the eukaryotic translation initiation factor 5A-2.

PubMed

Xue, Fei; Liang, Yuntian; Li, Zhenrong; Liu, Yanhui; Zhang, Hongwei; Wen, Yu; Yan, Lei; Tang, Qiang; Xiao, Erhui; Zhang, Dongyi

2018-01-01

Hepatocellular carcinoma (HCC) is one of the most widespread malignant human tumors worldwide. Treatment options include radiotherapy, surgical intervention and chemotherapy; however, drug resistance is an ongoing treatment concern. In the present study, the effects of a microRNA (miR/miRNA), miR-9, on the sensitivity of HCC cell lines to the epidermal growth factor receptor inhibitor, cetuximab, were examined. miR-9 has been proposed to serve a role in tumorigenesis and tumor progression. In the present study, bioinformatics analyses identified the eukaryotic translation initiation factor 5A2 (eIF-5A-2) as a target of miR-9. The expression levels of miR-9 and eIF-5A-2 were examined by reverse transcription-quantitative polymerase chain reaction and HCC cell lines were transfected with miR-9 mimics and inhibitors to determine the effects of the miRNA on cell proliferation and viability. The miR-9 mimic was revealed to significantly increase the sensitivity of epithelial phenotype HCC cells (Hep3B and Huh7) to cetuximab, while the miR-9 inhibitor triggered the opposite effect. There were no significant differences in sensitivity to cetuximab observed in mesenchymal phenotype HCC cells (SNU387 and SNU449). Cells lines displaying high expression levels of eIF-5A-2 were more resistant to cetuximab. Transfection of cells with a miR-9 mimic resulted in downregulation of the expression of eIF-5A-2 mRNA, while an miR-9 inhibitor increased expression. When expression of eIF-5A-2 was knocked down with siRNA, the effects of miR-9 on cetuximab sensitivity were no longer observed. Taken together, these data support a role for miR-9 in enhancing the sensitivity of epithelial phenotype HCC cells to cetuximab through regulation of eIF-5A-2.

Does Contralateral Delay Activity Reflect Working Memory Storage or the Current Focus of Spatial Attention within Visual Working Memory?

PubMed

Berggren, Nick; Eimer, Martin

2016-12-01

During the retention of visual information in working memory, event-related brain potentials show a sustained negativity over posterior visual regions contralateral to the side where memorized stimuli were presented. This contralateral delay activity (CDA) is generally believed to be a neural marker of working memory storage. In two experiments, we contrasted this storage account of the CDA with the alternative hypothesis that the CDA reflects the current focus of spatial attention on a subset of memorized items set up during the most recent encoding episode. We employed a sequential loading procedure where participants memorized four task-relevant items that were presented in two successive memory displays (M1 and M2). In both experiments, CDA components were initially elicited contralateral to task-relevant items in M1. Critically, the CDA switched polarity when M2 displays appeared on the opposite side. In line with the attentional activation account, these reversed CDA components exclusively reflected the number of items that were encoded from M2 displays, irrespective of how many M1 items were already held in working memory. On trials where M1 and M2 displays were presented on the same side and on trials where M2 displays appeared nonlaterally, CDA components elicited in the interval after M2 remained sensitive to a residual trace of M1 items, indicating that some activation of previously stored items was maintained across encoding episodes. These results challenge the hypothesis that CDA amplitudes directly reflect the total number of stored objects and suggest that the CDA is primarily sensitive to the activation of a subset of working memory representations within the current focus of spatial attention.

Projection-type see-through holographic three-dimensional display

NASA Astrophysics Data System (ADS)

Wakunami, Koki; Hsieh, Po-Yuan; Oi, Ryutaro; Senoh, Takanori; Sasaki, Hisayuki; Ichihashi, Yasuyuki; Okui, Makoto; Huang, Yi-Pai; Yamamoto, Kenji

2016-10-01

Owing to the limited spatio-temporal resolution of display devices, dynamic holographic three-dimensional displays suffer from a critical trade-off between the display size and the visual angle. Here we show a projection-type holographic three-dimensional display, in which a digitally designed holographic optical element and a digital holographic projection technique are combined to increase both factors at the same time. In the experiment, the enlarged holographic image, which is twice as large as the original display device, projected on the screen of the digitally designed holographic optical element was concentrated at the target observation area so as to increase the visual angle, which is six times as large as that for a general holographic display. Because the display size and the visual angle can be designed independently, the proposed system will accelerate the adoption of holographic three-dimensional displays in industrial applications, such as digital signage, in-car head-up displays, smart-glasses and head-mounted displays.

Development of an extended-range fiber optic pH sensor using evanescent wave absorption of sol-gel-entrapped pH indicators

NASA Astrophysics Data System (ADS)

Butler, Thomas M.; MacCraith, Brian D.; McDonagh, Colette M.

1995-09-01

The sol-gel process has been used to entrap pH indicators in porous glass coatings for sensor applications. This sensor is based on evanescent wave absorption using an unclad optical fiber dipcoated with the pH sensitive coating. The entrapped pH indicators show a broadening of the pH range with respect to the behavior in solution giving accurate measurement over three pH units when one indicator is used (bromophenol blue) and over six pH units (pH 3-9) when two indicators are used (bromophenol blue and bromocresol purple). The response of the pH sensor was monitored by measuring absorption at 590 nm referenced against a nonabsorbing region of the spectrum. This enabled the use of LED sources together with low cost photodiodes. The sensor displayed short response time and good repeatability. The thickness and stability of the pH sensitive coatings can be influenced by modifying the composition of the starting sol mixture. The evanescent absorption, and hence the sensitivity of the sensor, can be increased by selectively launching higher order modes in the fiber. These issues together with a full sensor characterization will be reported.

Fluorescence detection of trace TNT by novel cross-linking electropolymerized films both in vapor and aqueous medium.

PubMed

Nie, Heran; Lv, Ying; Yao, Liang; Pan, Yuyu; Zhao, Yang; Li, Peng; Sun, Guannan; Ma, Yuguang; Zhang, Ming

2014-01-15

Electropolymerized (EP) films with high fluorescent efficiency are introduced to the detection of trace 2,4,6-trinitrotoluene (TNT). Three electroactive materials TCPC, OCPC and OCz have been synthesized and their EP films have been demonstrated to be sensitive to TNT. Among them, the TCPC EP films have displayed the highest sensitivity to TNT in both vapor and aqueous medium, even in the natural water. It is proposed that the good performances would be caused by the following two factors: first, the cross-linking network of EP films can generate the cavities which benefit the TNT penetration, and remarkably increase the contact area between the EP films and TNT; second, the frontier orbits distribution leads the fast photo-induced electron transfer (PET) from the TCPC EP films to TNT. Our results prove that these EP films are promising TNT sensing candidates and provide a new method to prepare fluorescent porous films. Copyright © 2013 Elsevier B.V. All rights reserved.

Extreme sensitivity to ultraviolet light in the fungal pathogen causing white-nose syndrome of bats.

PubMed

Palmer, Jonathan M; Drees, Kevin P; Foster, Jeffrey T; Lindner, Daniel L

2018-01-02

Bat white-nose syndrome (WNS), caused by the fungal pathogen Pseudogymnoascus destructans, has decimated North American hibernating bats since its emergence in 2006. Here, we utilize comparative genomics to examine the evolutionary history of this pathogen in comparison to six closely related nonpathogenic species. P. destructans displays a large reduction in carbohydrate-utilizing enzymes (CAZymes) and in the predicted secretome (~50%), and an increase in lineage-specific genes. The pathogen has lost a key enzyme, UVE1, in the alternate excision repair (AER) pathway, which is known to contribute to repair of DNA lesions induced by ultraviolet (UV) light. Consistent with a nonfunctional AER pathway, P. destructans is extremely sensitive to UV light, as well as the DNA alkylating agent methyl methanesulfonate (MMS). The differential susceptibility of P. destructans to UV light in comparison to other hibernacula-inhabiting fungi represents a potential "Achilles' heel" of P. destructans that might be exploited for treatment of bats with WNS.

Characterization of in vitro phenotypes of Burkholderia pseudomallei and Burkholderia mallei strains potentially associated with persistent infection in mice.

PubMed

Bernhards, R C; Cote, C K; Amemiya, K; Waag, D M; Klimko, C P; Worsham, P L; Welkos, S L

2017-03-01

Burkholderia pseudomallei (Bp) and Burkholderia mallei (Bm), the agents of melioidosis and glanders, respectively, are Tier 1 biothreats. They infect humans and animals, causing disease ranging from acute and fatal to protracted and chronic. Chronic infections are especially challenging to treat, and the identification of in vitro phenotypic markers which signal progression from acute to persistent infection would be extremely valuable. First, a phenotyping strategy was developed employing colony morphotyping, chemical sensitivity testing, macrophage infection, and lipopolysaccharide fingerprint analyses to distinguish Burkholderia strains. Then mouse spleen isolates collected 3-180 days after infection were characterized phenotypically. Isolates from long-term infections often exhibited increased colony morphology differences and altered patterns of antimicrobial sensitivity and macrophage infection. Some of the Bp and Bm persistent infection isolates clearly displayed enhanced virulence in mice. Future studies will evaluate the potential role and significance of these phenotypic markers in signaling the establishment of a chronic infection.

In Vivo Regulation of NGF-Mediated Functions by Nedd4-2 Ubiquitination of TrkA

PubMed Central

Yu, Tao; Calvo, Laura; Anta, Begoña; López-Benito, Saray; López-Bellido, Roger; Vicente-García, Cristina; Tessarollo, Lino; Rodriguez, Raquel E.

2014-01-01

Trk neurotrophin receptor ubiquitination in response to ligand activation regulates signaling, trafficking, and degradation of the receptors. However, the in vivo consequences of Trk ubiquitination remain to be addressed. We have developed a mouse model with a mutation in the TrkA neurotrophin receptor (P782S) that results in reduced ubiquitination due to a lack of binding to the E3 ubiquitin ligase, Nedd4-2. In vivo analyses of TrkAP782S indicate that defective ubiquitination of the TrkA mutant results in an altered trafficking and degradation of the receptor that affects the survival of sensory neurons. The dorsal root ganglia from the TrkAP782S knock-in mice display an increased number of neurons expressing CGRP and substance P. Moreover, the mutant mice show enhanced sensitivity to thermal and inflammatory pain. Our results indicate that the ubiquitination of the TrkA neurotrophin receptor plays a critical role in NGF-mediated functions, such as neuronal survival and sensitivity to pain. PMID:24760869

Overexpression of ShCYP51B and ShatrD in Sclerotinia homoeocarpa Isolates Exhibiting Practical Field Resistance to a Demethylation Inhibitor Fungicide

PubMed Central

Hulvey, Jon; Popko, James T.; Sang, Hyunkyu; Berg, Andrew

2012-01-01

We investigated genetic factors that govern the reduced propiconazole sensitivity of Sclerotinia homoeocarpa field isolates collected during a 2-year field efficacy study on dollar spot disease of turf in five New England sites. These isolates displayed a >50-fold range of in vitro sensitivity to a sterol demethylation inhibitor (DMI) fungicide, propiconazole, making them ideal for investigations of genetic mechanisms of reduced DMI sensitivity. The CYP51 gene homolog in S. homoeocarpa (ShCYP51B), encoding the enzyme target of DMIs, is likely a minor genetic factor for reduced propiconazole sensitivity, since there were no differences in constitutive relative expression (RE) values and only 2-fold-higher induced RE values for insensitive than for sensitive isolate groups. Next, we mined RNA-Seq transcriptome data for additional genetic factors and found evidence for the overexpression of a homolog of Botrytis cinerea atrD (BcatrD), ShatrD, a known efflux transporter of DMI fungicides. The ShatrD gene showed much higher constitutive and induced RE values for insensitive isolates. Several polymorphisms were found upstream of ShatrD but were not definitively linked to overexpression. The screening of constitutive RE values of ShCYP51B and ShatrD in isolates from two golf courses that exhibited practical field resistance to propiconazole uncovered evidence for significant population-specific overexpression of both genes. However, linear regression demonstrated that the RE of ShatrD displays a more significant relationship with propiconazole sensitivity than that of ShCYP51B. In summary, our results suggest that efflux is a major determinant of the reduced DMI sensitivity of S. homoeocarpa genotypes in New England, which may have implications for the emergence of practical field resistance in this important turfgrass pathogen. PMID:22798361

Promotion of Cancer Stem-Like Cell Properties in Hepatitis C Virus-Infected Hepatocytes

PubMed Central

Kwon, Young-Chan; Bose, Sandip K.; Steele, Robert; Meyer, Keith; Di Bisceglie, Adrian M.; Ray, Ratna B.

2015-01-01

ABSTRACT We have previously reported that hepatitis C virus (HCV) infection of primary human hepatocytes (PHH) induces the epithelial mesenchymal transition (EMT) state and extends hepatocyte life span (S. K. Bose, K. Meyer, A. M. Di Bisceglie, R. B. Ray, and R. Ray, J Virol 86:13621–13628, 2012, http://dx.doi.org/10.1128/JVI.02016-12). These hepatocytes displayed sphere formation on ultralow binding plates and survived for more than 12 weeks. The sphere-forming hepatocytes expressed a number of cancer stem-like cell (CSC) markers, including high levels of the stem cell factor receptor c-Kit. The c-Kit receptor is regarded as one of the CSC markers in hepatocellular carcinoma (HCC). Analysis of c-Kit mRNA displayed a significant increase in the liver biopsy specimens of chronically HCV-infected patients. We also found c-Kit is highly expressed in transformed human hepatocytes (THH) infected in vitro with cell culture-grown HCV genotype 2a. Further studies suggested that HCV core protein significantly upregulates c-Kit expression at the transcriptional level. HCV infection of THH led to a significant increase in the number of spheres displayed on ultralow binding plates and in enhanced EMT and CSC markers and tumor growth in immunodeficient mice. The use of imatinib or dasatinib as a c-Kit inhibitor reduced the level of sphere-forming cells in culture. The sphere-forming cells were sensitive to treatment with sorafenib, a multikinase inhibitor, that is used for HCC treatment. Further, stattic, an inhibitor of the Stat3 molecule, induced sphere-forming cell death. A combination of sorafenib and stattic had a significantly stronger effect, leading to cell death. These results suggested that HCV infection potentiates CSC generation, and selected drugs can be targeted to efficiently inhibit cell growth. IMPORTANCE HCV infection may develop into HCC as an end-stage liver disease. We focused on understanding the mechanism for the risk of HCC from chronic HCV infection and identified targets for treatment. HCV-infected primary and transformed human hepatocytes (PHH or THH) generated CSC. HCV-induced spheres were highly sensitive to cell death from sorafenib and stattic treatment. Thus, our study is highly significant for HCV-associated HCC, with the potential for developing a target-specific strategy for improved therapies. PMID:26355082

A new helper phage for improved monovalent display of Fab molecules.

PubMed

Beaber, John W; Tam, Eric M; Lao, Llewelyn S; Rondon, Isaac J

2012-02-28

Phage display technology is a powerful tool for the identification of novel antibodies for drug discovery. Phage display libraries have been constructed with massive diversity, but their use may be hindered by limited antibody display levels when rescued with the M13KO7 helper phage. Variants of M13KO7 have been constructed previously that increase the levels of display of rescued phage, but all produce phage that display multiple copies of the antibody fragment on their surface and have reduced titer and infectivity. In this study, we describe a new helper phage, XP5, which increased the display level of Fab molecules more than two-fold compared to phage rescued with M13KO7. XP5 uses a combination of ribosome binding site spacing alterations and rare codon clusters to reduce the expression of pIII from the helper phage. This reduction in pIII expression leads to an increase in the incorporation of pIII-Fab fusions during phage rescue. The rescued phage displayed a single copy of the Fab molecule, preventing any avidity effects during the selection process. This also suggests that the percentage of the population of phage displaying a Fab molecule is increased when rescued with XP5. Additionally, the phage titers and infectivity are comparable to libraries rescued with M13KO7. After two rounds of panning we observed a nearly 5-fold increase in the number of antigen binding Fab molecules compared to panning conducted with the same library rescued with M13KO7. The nature of the mutations in XP5 makes it a universal substitute for M13KO7 in pIII-based phage display, compatible with most phagemids and bacterial strains. Copyright © 2011 Elsevier B.V. All rights reserved.

Repeated Ferret Odor Exposure Induces Different Temporal Patterns of Same-Stressor Habituation and Novel-Stressor Sensitization in Both Hypothalamic-Pituitary-Adrenal Axis Activity and Forebrain c-fos Expression in the Rat

PubMed Central

Weinberg, Marc S.; Bhatt, Aadra P.; Girotti, Milena; Masini, Cher V.; Day, Heidi E. W.; Campeau, Serge; Spencer, Robert L.

2009-01-01

Repeated exposure to a moderately intense stressor typically produces attenuation of the hypothalamic-pituitary-adrenal (HPA) axis response (habituation) on re-presentation of the same stressor; however, if a novel stressor is presented to the same animals, the HPA axis response may be augmented (sensitization). The extent to which this adaptation is also evident within neural activity patterns is unknown. This study tested whether repeated ferret odor (FO) exposure, a moderately intense psychological stressor for rats, leads to both same-stressor habituation and novel-stressor sensitization of the HPA axis response and neuronal activity as determined by immediate early gene induction (c-fos mRNA). Rats were presented with FO in their home cages for 30 min a day for up to 2 wk and subsequently challenged with FO or restraint. Rats displayed HPA axis activity habituation and widespread habituation of c-fos mRNA expression (in situ hybridization) throughout the brain in as few as three repeated presentations of FO. However, repeated FO exposure led to a more gradual development of sensitized HPA-axis and c-fos mRNA responses to restraint that were not fully evident until after 14 d of prior FO exposure. The sensitized response was evident in many of the same brain regions that displayed habituation, including primary sensory cortices and the prefrontal cortex. The shared spatial expression but distinct temporal development of habituation and sensitization neural response patterns suggests two independent processes with opposing influences across overlapping brain systems. PMID:18845631

Designing a system for patients controlling providers' access to their electronic health records: organizational and technical challenges.

PubMed

Leventhal, Jeremy C; Cummins, Jonathan A; Schwartz, Peter H; Martin, Douglas K; Tierney, William M

2015-01-01

Electronic health records (EHRs) are proliferating, and financial incentives encourage their use. Applying Fair Information Practice principles to EHRs necessitates balancing patients' rights to control their personal information with providers' data needs to deliver safe, high-quality care. We describe the technical and organizational challenges faced in capturing patients' preferences for patient-controlled EHR access and applying those preferences to an existing EHR. We established an online system for capturing patients' preferences for who could view their EHRs (listing all participating clinic providers individually and categorically-physicians, nurses, other staff) and what data to redact (none, all, or by specific categories of sensitive data or patient age). We then modified existing data-viewing software serving a state-wide health information exchange and a large urban health system and its primary care clinics to allow patients' preferences to guide data displays to providers. Patients could allow or restrict data displays to all clinicians and staff in a demonstration primary care clinic, categories of providers (physicians, nurses, others), or individual providers. They could also restrict access to all EHR data or any or all of five categories of sensitive data (mental and reproductive health, sexually transmitted diseases, HIV/AIDS, and substance abuse) and for specific patient ages. The EHR viewer displayed data via reports, data flowsheets, and coded and free text data displayed by Google-like searches. Unless patients recorded restrictions, by default all requested data were displayed to all providers. Data patients wanted restricted were not displayed, with no indication they were redacted. Technical barriers prevented redacting restricted information in free textnotes. The program allowed providers to hit a "Break the Glass" button to override patients' restrictions, recording the date, time, and next screen viewed. Establishing patient-control over EHR data displays was complex and required ethical, clinical, database, and programming expertise and difficult choices to overcome technical and health system constraints. Assessing patients' preferences for access to their EHRs and applying them in clinical practice requires wide-ranging technical, clinical, and bioethical expertise, to make tough choices to overcome significant technical and organization challenges.

“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.

S36. DIFFERENTIAL ENCODING OF SENSITIZATION AND CROSS SENSITIZATION TO PSYCHOSTIMULANTS AND ANTIPSYCHOTICS IN NUCLEUS ACCUMBENS D1- AND D2- RECEPTOR EXPRESSING MEDIUM SPINY NEURONS

PubMed Central

Amato, Davide; Heinsbroek, Jasper; Kalivas, Peter W

2018-01-01

Abstract Background Nearly half of all individuals diagnosed with schizophrenia abuse addictive substances such as cocaine. Currently, the neurobiological mechanisms in patients with schizophrenia that lead to cocaine abuse are unknown. A possible explanation for the co-morbidity between schizophrenia and addiction is that the rewarding properties of cocaine reverse the diminished motivational drive caused by chronic antipsychotic regimen. Moreover, chronic antipsychotic treatment can sensitize and amplify cocaine rewarding effects and exacerbate psychoses. Methods The rewarding properties of cocaine are attributed to the differential effects of dopamine on D1 and D2 receptor-expressing medium spiny neurons (MSNs) in the nucleus accumbens (NAc). Using in vivo Ca2+ miniature microscopic imaging, we characterize the role of D1 and D2 MSN in mono- and a cross- sensitization paradigms. D1- and D2-Cre mice were injected with a Cre dependent calcium indicator (gCaMP6f) and implanted with a gradient index (GRIN) lens above the nucleus accumbens and calcium activity was recorded using a head mounted miniature microscope. Cocaine sensitization was measured after a classic repeated cocaine regiment and antipsychotic and psychostimulant cross-sensitization was measured by a single cocaine injection after chronic pre-treatment with haloperidol. Results We found that both D1-MSN and D2-MSN populations are modulated by initial cocaine experience and further modulated during the expression of cocaine sensitization. A subpopulation of D1-MSN displayed initial activation, but reduced activity during the expression of sensitization. By contrast, the majority of D2-MSNs were suppressed by initial cocaine experience, but became active during the expression of sensitization. Furthermore, activity of D1- and D2-MSNs bidirectionally related with the observed behavioral responses to cocaine. Cross-sensitization following haloperidol treatment led to increased behavioral responses to psychostimulants. Current experiments are set out to investigate the neuronal responses of D1 and D2-MSN during cross sensitization between haloperidol and cocaine. Discussion Cocaine sensitization leads to differential neuronal responses in D1- and D2-MSN and these responses are differentially correlated with the magnitude of the sensitized behavioral response. These results reveal important new insights in the neurobiological processes in the nucleus accumbens that underlie psychostimulant sensitization and provide an important new model for studying the pharmacology of antipsychotic effects on striatal function and its potential role in increasing the susceptibility of schizophrenic patients to developing drug addiction.

The sigma-2 receptor as a therapeutic target for drug delivery in triple negative breast cancer

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

Makvandi, Mehran; Tilahun, Estifanos D.; Lieberman, Brian P.

Background: Triple-negative breast cancer (TNBC) is associated with high relapse rates and increased mortality when compared with other breast cancer subtypes. In contrast to receptor positive breast cancers, there are no approved targeted therapies for TNBC. Identifying biomarkers for TNBC is of high importance for the advancement of patient care. The sigma-2 receptor has been shown to be overexpressed in triple negative breast cancer in vivo and has been characterized as a marker of proliferation. The aim of the present study was to define the sigma-2 receptor as a target for therapeutic drug delivery and biomarker in TNBC. Methods: Three TNBCmore » cell lines were evaluated: MDA-MB-231, HCC1937 and HCC1806. Sigma-2 compounds were tested for pharmacological properties specific to the sigma-2 receptor through competitive inhibition assays. Sigma-2 receptor expression was measured through radioligand receptor saturation studies. Drug sensitivity for taxol was compared to a sigma-2 targeting compound conjugated to a cytotoxic payload, SW IV-134. Cell viability was assessed after treatments for 2 or 48 h. Sigma-2 blockade was assessed to define sigma-2 mediated cytotoxicity of SW IV-134. Caspase 3/7 activation induced by SW IV-134 was measured at corresponding treatment time points. Results: SW IV-134 was the most potent compound tested in two of the three cell lines and was similarly effective in all three. MDA-MB-231 displayed a statistically significant higher sigma-2 receptor expression and also was the most sensitive cell line evaluated to SW IV-134. Conclusion: Targeting the sigma-2 receptor with a cytotoxic payload was effective in all the three cell lines evaluated and provides the proof of concept for future development of a therapeutic platform for the treatment of TNBC. - Highlights: • TNBC cells are sensitive to sigma-2 receptor targeted drug conjugate SW IV-134. • MDA-MB-231 displayed the highest amount of sigma-2 receptors and corresponded well with sensitivity. • The sigma-2 receptor is a potential biomarker in TNBC for prognosis and therapy.« less

Introduction: Reengaging with instruments.

PubMed

Taub, Liba

2011-12-01

Over the past twenty years or so, historians of science have become increasingly sensitized to issues involved in studying and interpreting scientific and medical instruments. The contributors to this Focus section are historians of science who have worked closely with museum objects and collections, specifically instruments used in scientific and medical contexts. Such close engagement by historians of science is somewhat rare, provoking distinctive questions as to how we define and understand instruments, opening up issues regarding the value of broken or incomplete objects, and raising concerns about which scientific and medical artifacts are displayed and interpreted in museums and in what manner. It is hoped that these essays point historians of science in new directions for reengaging with scientific objects and collections.

Achieving consistent color and grayscale presentation on medial color displays

NASA Astrophysics Data System (ADS)

Fan, Jiahua; Roehrig, Hans; Dallas, William; Krupinski, Elizabeth A.

2008-03-01

Color displays are increasingly used for medical imaging, replacing the traditional monochrome displays in radiology for multi-modality applications, 3D representation applications, etc. Color displays are also used increasingly because of wide spread application of Tele-Medicine, Tele-Dermatology and Digital Pathology. At this time, there is no concerted effort for calibration procedures for this diverse range of color displays in Telemedicine and in other areas of the medical field. Using a colorimeter to measure the display luminance and chrominance properties as well as some processing software we developed a first attempt to a color calibration protocol for the medical imaging field.

Conducting glasses recovered from thin film transistor liquid crystal display wastes for dye-sensitized solar cell cathodes.

PubMed

Chen, C-C; Chang, F-C; Peng, C Y; Wang, H Paul

2015-01-01

Transparent conductive glasses such as thin film transistor (TFT) array and colour filter glasses were recovered from the TFT-liquid crystal display panel wastes by dismantling and sonic cleaning. Noble metals (i.e. platinum (Pt)) and indium tin oxide (ITO) are generally used in the cathode of a dye-sensitized solar cell (DSSC). To reduce the DSSC cost, Pt was replaced with nano nickel-encapsulated carbon-shell (Ni@C) nanoparticles, which were prepared by carbonization of Ni²⁺-β-cyclodextrin at 673 K for 2 h. The recovered conductive glasses were used in the DSSC electrodes in the substitution of relatively expensive ITO. Interestingly, the efficiency of the DSSC having the Ni@C-coated cathode is as high as 2.54%. Moreover, the cost of the DSSC using the recovered materials can be reduced by at least 24%.

Photokinesis and Djopsin gene expression analysis during the regeneration of planarian eyes.

PubMed

Dong, Zimei; Yuwen, Yanqing; Sima, Yingxu; Dong, Yanping; Zhan, Huina; Chen, Guangwen; Liu, Dezeng

2017-03-01

Planarians provide the ideal model for studying eye development, with their simple eye structure and exceptionally rapid regeneration. Here, we observed the eye morphogenesis, photophobic behavior, spectral sensitivity and expression pattern of Djopsin in the freshwater planarian Dugesia japonica. The results showed that: (i) Djopsin encoding the putative protein belonged to the rhabdomeric opsins group and displayed high conservation during animal evolution; (ii) planarians displayed diverse photophobic response to different visible wavelengths and were more sensitive to light blue (495 nm) and yellow (635 nm); (iii) the morphogenesis and functional recovery of eyes were related to the expression pattern of Djopsin during head regeneration; and (iv) Djopsin gene plays a major role in functional recovery during eye regeneration and visual system maintenance in adult planarians. © 2016 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

Grasp posture alters visual processing biases near the hands

PubMed Central

Thomas, Laura E.

2015-01-01

Observers experience biases in visual processing for objects within easy reach of their hands that may assist them in evaluating items that are candidates for action. I investigated the hypothesis that hand postures affording different types of actions differentially bias vision. Across three experiments, participants performed global motion detection and global form perception tasks while their hands were positioned a) near the display in a posture affording a power grasp, b) near the display in a posture affording a precision grasp, or c) in their laps. Although the power grasp posture facilitated performance on the motion task, the precision grasp posture instead facilitated performance on the form task. These results suggest that the visual system weights processing based on an observer’s current affordances for specific actions: fast and forceful power grasps enhance temporal sensitivity, while detail-oriented precision grasps enhance spatial sensitivity. PMID:25862545

Holographic diffuser by use of a silver halide sensitized gelatin process

NASA Astrophysics Data System (ADS)

Kim, Sun Il; Choi, Yoon Sun; Ham, Yong Nam; Park, Chong Yun; Kim, Jong Man

2003-05-01

Diffusers play an important role in liquid-crystal display (LCD) application as a beam-shaping device, a brightness homogenizer, a light-scattering device, and an imaging screen. The transmittance and diffusing angle of the diffusers are the critical aspects for the applications to the LCD. The holographic diffusers by use of various processing methods have been investigated. The diffusing characteristics of different diffusing materials and processing methods have been evaluated and compared. The micro-structures of holographic diffusers have been investigated by use of using scanning electron microscopy. The holographic diffusers by use of the silver halide sensitized gelatin (SHSG) method have the structural merits for the improvement of the quality of diffusers. The features of holographic diffuser were exceptional in terms of transmittance and diffusing angle. The replication method by use of the SHSG process can be directly used for the manufacturing of diffusers for the display application.

Anticipatory sensitization to repeated stressors: the role of initial cortisol reactivity and meditation/emotion skills training.

PubMed

Turan, Bulent; Foltz, Carol; Cavanagh, James F; Wallace, B Alan; Cullen, Margaret; Rosenberg, Erika L; Jennings, Patricia A; Ekman, Paul; Kemeny, Margaret E

2015-02-01

Anticipation may play a role in shaping biological reactions to repeated stressors-a common feature of modern life. We aimed to demonstrate that: (a) individuals who display a larger cortisol response to an initial stressor exhibit progressive anticipatory sensitization, showing progressively higher cortisol levels before subsequent exposures, and (b) attention/emotional skills training can reduce the magnitude of this effect on progressive anticipatory sensitization. Female school teachers (N=76) were randomly assigned to attention/emotion skills and meditation training or to a control group. Participants completed 3 separate Trier Social Stress Tests (TSST): at baseline (Session 1), post-training (Session 2), and five months post (Session 3). Each TSST session included preparing and delivering a speech and performing an arithmetic task in front of critical evaluators. In each session participants' salivary cortisol levels were determined before and after the stressor. Control participants with larger cortisol reactivity to the first stressor showed increasing anticipatory (pre-stressor) cortisol levels with each successive stressor exposure (TSST session)-suggesting progressive anticipatory sensitization. Yet this association was absent in the training group. Supplementary analyses indicated that these findings occurred in the absence of group differences in cortisol reactivity. Findings suggest that the stress response can undergo progressive anticipatory sensitization, which may be modulated by attention/emotion-related processes. An important implication of the construct of progressive anticipatory sensitization is a possible self-perpetuating effect of stress reactions, providing a candidate mechanism for the translation of short-to-long-term stress reactions. Copyright © 2014 Elsevier Ltd. All rights reserved.

Novel Connections Between DNA Replication, Telomere Homeostasis, and the DNA Damage Response Revealed by a Genome-Wide Screen for TEL1/ATM Interactions in Saccharomyces cerevisiae

PubMed Central

Piening, Brian D.; Huang, Dongqing; Paulovich, Amanda G.

2013-01-01

Tel1 is the budding yeast ortholog of the mammalian tumor suppressor and DNA damage response (DDR) kinase ATM. However, tel1-Δ cells, unlike ATM-deficient cells, do not exhibit sensitivity to DNA-damaging agents, but do display shortened (but stably maintained) telomere lengths. Neither the extent to which Tel1p functions in the DDR nor the mechanism by which Tel1 contributes to telomere metabolism is well understood. To address the first question, we present the results from a comprehensive genome-wide screen for genetic interactions with tel1-Δ that cause sensitivity to methyl methanesulfonate (MMS) and/or ionizing radiation, along with follow-up characterizations of the 13 interactions yielded by this screen. Surprisingly, many of the tel1-Δ interactions that confer DNA damage sensitivity also exacerbate the short telomere phenotype, suggesting a connection between these two phenomena. Restoration of normal telomere length in the tel1-Δ xxx-Δ mutants results in only minor suppression of the DNA damage sensitivity, demonstrating that the sensitivity of these mutants must also involve mechanisms independent of telomere length. In support of a model for increased replication stress in the tel1-Δ xxx-Δ mutants, we show that depletion of dNTP pools through pretreatment with hydroxyurea renders tel1-Δ cells (but not wild type) MMS-sensitive, demonstrating that, under certain conditions, Tel1p does indeed play a critical role in the DDR. PMID:23378069

A green-color portable waveguide eyewear display system

NASA Astrophysics Data System (ADS)

Xia, Lingbo; Xu, Ke; Wu, Zhengming; Hu, Yingtian; Li, Zhenzhen; Wang, Yongtian; Liu, Juan

2013-08-01

Waveguide display systems are widely used in various display fields, especially in head mounted display. Comparing with the traditional head mounted display system, this device dramatically reduce the size and mass. However, there are still several fatal problems such as high scatting, the cumbersome design and chromatic aberration that should be solved. We designed and fabricated a monochromatic portable eyewear display system consist of a comfortable eyewear device and waveguide system with two holographic gratings located on the substrate symmetrically. We record the gratings on the photopolymer medium with high efficiency and wavelength sensitivity. The light emitting from the micro-display is diffracted by the grating and trapped in the glass substrate by total internal reflection. The relationship between the diffraction efficiency and exposure value is studied and analyzed, and we fabricated the gratings with appropriate diffraction efficiency in a optimization condition. To avoid the disturbance of the stray light, we optimize the waveguide system numerically and perform the optical experiments. With this system, people can both see through the waveguide to obtain the information outside and catch the information from the micro display. After considering the human body engineering and industrial production, we design the structure in a compact and portable way. It has the advantage of small-type configuration and economic acceptable. It is believe that this kind of planar waveguide system is a potentially replaceable choice for the portable devices in future mobile communications.

[Odor sensing system and olfactory display].

PubMed

Nakamoto, Takamichi

2014-01-01

In this review, an odor sensing system and an olfactory display are introduced into people in pharmacy. An odor sensing system consists of an array of sensors with partially overlapping specificities and pattern recognition technique. One of examples of odor sensing systems is a halitosis sensor which quantifies the mixture composition of three volatile sulfide compounds. A halitosis sensor was realized using a preconcentrator to raise sensitivity and an electrochemical sensor array to suppress the influence of humidity. Partial least squares (PLS) method was used to quantify the mixture composition. The experiment reveals that the sufficient accuracy was obtained. Moreover, the olfactory display, which present scents to human noses, is explained. A multi-component olfactory display enables the presentation of a variety of smells. The two types of multi-component olfactory display are described. The first one uses many solenoid valves with high speed switching. The valve ON frequency determines the concentration of the corresponding odor component. The latter one consists of miniaturized liquid pumps and a surface acoustic wave (SAW) atomizer. It enables the wearable olfactory display without smell persistence. Finally, the application of the olfactory display is demonstrated. Virtual ice cream shop with scents was made as a content of interactive art. People can enjoy harmony among vision, audition and olfaction. In conclusion, both odor sensing system and olfactory display can contribute to the field of human health care.

A review of the thermal sensitivity of the mechanics of vertebrate skeletal muscle.

PubMed

James, Rob S

2013-08-01

Environmental temperature varies spatially and temporally, affecting many aspects of an organism's biology. In ectotherms, variation in environmental temperature can cause parallel changes in skeletal muscle temperature, potentially leading to significant alterations in muscle performance. Endotherms can also undergo meaningful changes in skeletal muscle temperature that can affect muscle performance. Alterations in skeletal muscle temperature can affect contractile performance in both endotherms and ectotherms, changing the rates of force generation and relaxation, shortening velocity, and consequently mechanical power. Such alterations in the mechanical performance of skeletal muscle can in turn affect locomotory performance and behaviour. For instance, as temperature increases, a consequent improvement in limb muscle performance causes some lizard species to be more likely to flee from a potential predator. However, at lower temperatures, they are much more likely to stand their ground, show threatening displays and even bite. There is no consistent pattern in reported effects of temperature on skeletal muscle fatigue resistance. This review focuses on the effects of temperature variation on skeletal muscle performance in vertebrates, and investigates the thermal sensitivity of different mechanical measures of skeletal muscle performance. The plasticity of thermal sensitivity in skeletal muscle performance has been reviewed to investigate the extent to which individuals can acclimate to chronic changes in their thermal environment. The effects of thermal sensitivity of muscle performance are placed in a wider context by relating thermal sensitivity of skeletal muscle performance to aspects of vertebrate species distribution.

The highly sensitive brain: an fMRI study of sensory processing sensitivity and response to others' emotions.

PubMed

Acevedo, Bianca P; Aron, Elaine N; Aron, Arthur; Sangster, Matthew-Donald; Collins, Nancy; Brown, Lucy L

2014-07-01

Theory and research suggest that sensory processing sensitivity (SPS), found in roughly 20% of humans and over 100 other species, is a trait associated with greater sensitivity and responsiveness to the environment and to social stimuli. Self-report studies have shown that high-SPS individuals are strongly affected by others' moods, but no previous study has examined neural systems engaged in response to others' emotions. This study examined the neural correlates of SPS (measured by the standard short-form Highly Sensitive Person [HSP] scale) among 18 participants (10 females) while viewing photos of their romantic partners and of strangers displaying positive, negative, or neutral facial expressions. One year apart, 13 of the 18 participants were scanned twice. Across all conditions, HSP scores were associated with increased brain activation of regions involved in attention and action planning (in the cingulate and premotor area [PMA]). For happy and sad photo conditions, SPS was associated with activation of brain regions involved in awareness, integration of sensory information, empathy, and action planning (e.g., cingulate, insula, inferior frontal gyrus [IFG], middle temporal gyrus [MTG], and PMA). As predicted, for partner images and for happy facial photos, HSP scores were associated with stronger activation of brain regions involved in awareness, empathy, and self-other processing. These results provide evidence that awareness and responsiveness are fundamental features of SPS, and show how the brain may mediate these traits.

Chronic Opioid Therapy and Central Sensitization in Sickle Cell Disease

PubMed Central

Carroll, C. Patrick; Lanzkron, Sophie; Haywood, Carlton; Kiley, Kasey; Pejsa, Megan; Moscou-Jackson, Gyasi; Haythornthwaite, Jennifer A.; Campbell, Claudia M.

2016-01-01

Chronic opioid therapy (COT) for chronic non-cancer pain is frequently debated, and its effectiveness is unproven in sickle cell disease (SCD). The authors conducted a descriptive study among 83 adult SCD patients and compared severity of disease and pain symptoms among those who were prescribed COT (n=29) with those who were not using COT. All patients completed baseline laboratory pain assessment and questionnaires between January 2010 and June 2014. Thereafter, participants recorded daily pain, crises, function, and healthcare utilization for 90 days using electronic diaries. Analyses were conducted shortly after the final diary data collection period. Patients on COT did not differ on age, sex, or measures of disease severity. However, patients on COT exhibited greater levels of clinical pain (particularly non-crisis), central sensitization, depression, and increased diary measures of pain severity, function, and healthcare utilization on crisis and non-crisis diary days, as well as a greater proportion of days in crisis. Including depressive symptoms in multivariate models did not change the associations between COT and pain, interference, central sensitization, or utilization. Additionally, participants not on COT displayed the expected positive relationship between central sensitization and clinical pain, whereas those on COT demonstrated no such relationship, despite having both higher central sensitization and higher clinical pain. Overall, the results point out a high symptom burden in SCD patients on COT, including those on high-dose COT, and suggest that nociceptive processing in SCD patients on COT differs from those who are not. PMID:27320469

Hunted Woolly Monkeys (Lagothrix poeppigii) Show Threat-Sensitive Responses to Human Presence

PubMed Central

Papworth, Sarah; Milner-Gulland, E. J.; Slocombe, Katie

2013-01-01

Responding only to individuals of a predator species which display threatening behaviour allows prey species to minimise energy expenditure and other costs of predator avoidance, such as disruption of feeding. The threat sensitivity hypothesis predicts such behaviour in prey species. If hunted animals are unable to distinguish dangerous humans from non-dangerous humans, human hunting is likely to have a greater effect on prey populations as all human encounters should lead to predator avoidance, increasing stress and creating opportunity costs for exploited populations. We test the threat sensitivity hypothesis in wild Poeppigi's woolly monkeys (Lagothrix poeppigii) in Yasuní National Park, Ecuador, by presenting human models engaging in one of three behaviours “hunting”, “gathering” or “researching”. These experiments were conducted at two sites with differing hunting pressures. Visibility, movement and vocalisations were recorded and results from two sites showed that groups changed their behaviours after being exposed to humans, and did so in different ways depending on the behaviour of the human model. Results at the site with higher hunting pressure were consistent with predictions based on the threat sensitivity hypothesis. Although results at the site with lower hunting pressure were not consistent with the results at the site with higher hunting pressure, groups at this site also showed differential responses to different human behaviours. These results provide evidence of threat-sensitive predator avoidance in hunted primates, which may allow them to conserve both time and energy when encountering humans which pose no threat. PMID:23614003

The highly sensitive brain: an fMRI study of sensory processing sensitivity and response to others' emotions

PubMed Central

Acevedo, Bianca P; Aron, Elaine N; Aron, Arthur; Sangster, Matthew-Donald; Collins, Nancy; Brown, Lucy L

2014-01-01

Background Theory and research suggest that sensory processing sensitivity (SPS), found in roughly 20% of humans and over 100 other species, is a trait associated with greater sensitivity and responsiveness to the environment and to social stimuli. Self-report studies have shown that high-SPS individuals are strongly affected by others' moods, but no previous study has examined neural systems engaged in response to others' emotions. Methods This study examined the neural correlates of SPS (measured by the standard short-form Highly Sensitive Person [HSP] scale) among 18 participants (10 females) while viewing photos of their romantic partners and of strangers displaying positive, negative, or neutral facial expressions. One year apart, 13 of the 18 participants were scanned twice. Results Across all conditions, HSP scores were associated with increased brain activation of regions involved in attention and action planning (in the cingulate and premotor area [PMA]). For happy and sad photo conditions, SPS was associated with activation of brain regions involved in awareness, integration of sensory information, empathy, and action planning (e.g., cingulate, insula, inferior frontal gyrus [IFG], middle temporal gyrus [MTG], and PMA). Conclusions As predicted, for partner images and for happy facial photos, HSP scores were associated with stronger activation of brain regions involved in awareness, empathy, and self-other processing. These results provide evidence that awareness and responsiveness are fundamental features of SPS, and show how the brain may mediate these traits. PMID:25161824

Computer-animated stimuli to measure motion sensitivity: constraints on signal design in the Jacky dragon.

PubMed

Woo, Kevin L; Rieucau, Guillaume; Burke, Darren

2017-02-01

Identifying perceptual thresholds is critical for understanding the mechanisms that underlie signal evolution. Using computer-animated stimuli, we examined visual speed sensitivity in the Jacky dragon Amphibolurus muricatus , a species that makes extensive use of rapid motor patterns in social communication. First, focal lizards were tested in discrimination trials using random-dot kinematograms displaying combinations of speed, coherence, and direction. Second, we measured subject lizards' ability to predict the appearance of a secondary reinforcer (1 of 3 different computer-generated animations of invertebrates: cricket, spider, and mite) based on the direction of movement of a field of drifting dots by following a set of behavioural responses (e.g., orienting response, latency to respond) to our virtual stimuli. We found an effect of both speed and coherence, as well as an interaction between these 2 factors on the perception of moving stimuli. Overall, our results showed that Jacky dragons have acute sensitivity to high speeds. We then employed an optic flow analysis to match the performance to ecologically relevant motion. Our results suggest that the Jacky dragon visual system may have been shaped to detect fast motion. This pre-existing sensitivity may have constrained the evolution of conspecific displays. In contrast, Jacky dragons may have difficulty in detecting the movement of ambush predators, such as snakes and of some invertebrate prey. Our study also demonstrates the potential of the computer-animated stimuli technique for conducting nonintrusive tests to explore motion range and sensitivity in a visually mediated species.

Efficacy of ventilator waveform observation for detection of patient-ventilator asynchrony during NIV: a multicentre study.

PubMed

Longhini, Federico; Colombo, Davide; Pisani, Lara; Idone, Francesco; Chun, Pan; Doorduin, Jonne; Ling, Liu; Alemani, Moreno; Bruni, Andrea; Zhaochen, Jin; Tao, Yu; Lu, Weihua; Garofalo, Eugenio; Carenzo, Luca; Maggiore, Salvatore Maurizio; Qiu, Haibo; Heunks, Leo; Antonelli, Massimo; Nava, Stefano; Navalesi, Paolo

2017-10-01

The objective of this study was to assess ability to identify asynchronies during noninvasive ventilation (NIV) through ventilator waveforms according to experience and interface, and to ascertain the influence of breathing pattern and respiratory drive on sensitivity and prevalence of asynchronies. 35 expert and 35 nonexpert physicians evaluated 40 5-min NIV reports displaying flow-time and airway pressure-time tracings; identified asynchronies were compared with those ascertained by three examiners who evaluated the same reports displaying, additionally, tracings of diaphragm electrical activity. We determined: 1) sensitivity, specificity, and positive and negative predictive values; 2) the correlation between the double true index (DTI) of each report ( i.e., the ratio between the sum of true positives and true negatives, and the overall breath count) and the corresponding asynchrony index (AI); and 3) the influence of breathing pattern and respiratory drive on both AI and sensitivity. Sensitivities to detect asynchronies were low either according to experience (0.20 (95% CI 0.14-0.29) for expert versus 0.21 (95% CI 0.12-0.30) for nonexpert, p=0.837) or interface (0.28 (95% CI 0.17-0.37) for mask versus 0.10 (95% CI 0.05-0.16) for helmet, p<0.0001). DTI inversely correlated with the AI (r 2 =0.67, p<0.0001). Breathing pattern and respiratory drive did not affect prevalence of asynchronies and sensitivity. Patient-ventilator asynchrony during NIV is difficult to recognise solely by visual inspection of ventilator waveforms.

Vagal Flexibility: A Physiological Predictor of Social Sensitivity

PubMed Central

Muhtadie, Luma; Akinola, Modupe; Koslov, Katrina; Mendes, Wendy Berry

2015-01-01

This research explores vagal flexibility— dynamic modulation of cardiac vagal control—as an individual-level physiological index of social sensitivity. In 4 studies, we test the hypothesis that individuals with greater cardiac vagal flexibility, operationalized as higher cardiac vagal tone at rest and greater cardiac vagal withdrawal (indexed by a decrease in respiratory sinus arrhythmia) during cognitive or attentional demand, perceive social-emotional information more accurately and show greater sensitivity to their social context. Study 1 sets the foundation for this investigation by establishing that vagal flexibility can be elicited consistently in the laboratory and reliably over time. Study 2 demonstrates that vagal flexibility has different associations with psychological characteristics than does vagal tone, and that these characteristics are primarily social in nature. Study 3 links individual differences in vagal flexibility with accurate detection of social and emotional cues depicted in still facial images. Study 4 demonstrates that individuals with greater vagal flexibility respond to dynamic social feedback in a more context-sensitive manner than do individuals with less vagal flexibility. Specifically, compared with their less flexible counterparts, individuals with greater vagal flexibility, when assigned to receive negative social feedback, report more shame, show more pronounced blood pressure responses, and display less sociable behavior, but when receiving positive social feedback display more sociable behavior. Taken together, these findings suggest that vagal flexibility is a useful individual difference physiological predictor of social sensitivity, which may have implications for clinical, developmental, and health psychologists. PMID:25545841

The impact of numeracy on reactions to different graphic risk presentation formats: An experimental analogue study.

PubMed

Wright, Alison J; Whitwell, Sophia C L; Takeichi, Chika; Hankins, Matthew; Marteau, Theresa M

2009-02-01

Numeracy, the ability to process basic mathematical concepts, may affect responses to graphical displays of health risk information. Displays of probabilistic risk information using grouped dots are easier to understand than displays using dispersed dots. However, dispersed dots may better convey the randomness with which health threats occur, so increasing perceived susceptibility. We hypothesized that low numeracy participants would better understand risks presented using grouped dot displays, while high numeracy participants would have good understanding, regardless of display type. Moreover, we predicted that dispersed dot displays, in contrast to grouped dot displays, would increase risk perceptions and worry only for highly numerate individuals. One hundred and forty smokers read vignettes asking them to imagine being at risk of Crohn's disease, in a 2(display type: dispersed/grouped dots) x 3(risk magnitude: 3%/6%/50%) x 2(numeracy: high/low) design. They completed measures of risk comprehension, perceived susceptibility and worry. More numerate participants had better objective risk comprehension, but this effect was not moderated by display type. There was marginally significant support for the predicted numeracy x display type interaction for worry about Crohn's disease, but not for perceived susceptibility to the condition. Dispersed dot displays somewhat increase worry in highly numerate individuals, but only numeracy influenced objective risk comprehension. The most effective display type for communicating risk information will depend on the numeracy of the population and the goal(s) of the communication.

A novel approach to assess the spontaneous gastrointestinal bleeding risk of antithrombotic agents using Apc(min/+) mice.

PubMed

Wei, Huijun; Shang, Jin; Keohane, CarolAnn; Wang, Min; Li, Qiu; Ni, Weihua; O'Neill, Kim; Chintala, Madhu

2014-06-01

Assessment of the bleeding risk of antithrombotic agents is usually performed in healthy animals with some form of vascular injury to peripheral organs to induce bleeding. However, bleeding observed in patients with currently marketed antithrombotic drugs is typically spontaneous in nature such as intracranial haemorrhage (ICH) and gastrointestinal (GI) bleeding, which happens most frequently on top of preexisting pathologies such as GI ulcerations and polyps. Apc(min/+) mice are reported to develop multiple adenomas through the entire intestinal tract and display progressive anaemia.In this study, we evaluated the potential utility of Apc(min/+) mice as a model for assessing spontaneous GI bleeding with antithrombotic agents. Apc(min/+) mice exhibited progressive blood loss starting at the age of nine weeks. Despite the increase in bleeding, Apc(min/+) mice were in a hypercoagulable state and displayed an age-dependent increase in thrombin generation and circulating fibrinogen as well as a significant decrease in clotting times. We evaluated the effect of warfarin, dabigatran etexilate, apixaban and clopidogrel in this model by administering them in diet or in the drinking water to mice for 1-4 weeks. All of these marketed drugs significantly increased GI bleeding in Apc(min/+) mice, but not in wild-type mice. Although different exposure profiles of these antithrombotic agents make it challenging to compare the bleeding risk of compounds, our results indicate that the Apc(min/+) mouse may be a sensitive preclinical model for assessing the spontaneous GI bleeding risk of novel antithrombotic agents.

The Whitish Inner Mantle of the Giant Clam, Tridacna squamosa, Expresses an Apical Plasma Membrane Ca2+-ATPase (PMCA) Which Displays Light-Dependent Gene and Protein Expressions

PubMed Central

Ip, Yuen K.; Hiong, Kum C.; Goh, Enan J. K.; Boo, Mel V.; Choo, Celine Y. L.; Ching, Biyun; Wong, Wai P.; Chew, Shit F.

2017-01-01

Giant clams live in symbiosis with extracellular zooxanthellae and display high rates of growth and shell formation (calcification) in light. Light-enhanced calcification requires an increase in the supply of Ca2+ to, and simultaneously an augmented removal of H+ from, the extrapallial fluid where shell formation occurs. We have obtained the complete coding cDNA sequence of Plasma Membrane Ca2+-ATPase (PMCA) from the thin and whitish inner mantle, which is in touch with the extrapallial fluid, of the giant clam Tridacna squamosa. The deduced PMCA sequence consisted of an apical targeting element. Immunofluorescence microscopy confirmed that PMCA had an apical localization in the shell-facing epithelium of the inner mantle, whereby it can actively secrete Ca2+ in exchange for H+. More importantly, the apical PMCA-immunofluorescence of the shell-facing epithelium of the inner mantle increased significantly after 12 h of exposure to light. The transcript and protein levels of PMCA/PMCA also increased significantly in the inner mantle after 6 or 12 h of light exposure. These results offer insights into a light-dependable mechanism of shell formation in T. squamosa and a novel explanation of light-enhanced calcification in general. As the inner mantle normally lacks light sensitive pigments, our results support a previous proposition that symbiotic zooxanthellae, particularly those in the colorful and extensible outer mantle, may act as light-sensing elements for the host clam. PMID:29066980

The Whitish Inner Mantle of the Giant Clam, Tridacna squamosa, Expresses an Apical Plasma Membrane Ca2+-ATPase (PMCA) Which Displays Light-Dependent Gene and Protein Expressions.

PubMed

Ip, Yuen K; Hiong, Kum C; Goh, Enan J K; Boo, Mel V; Choo, Celine Y L; Ching, Biyun; Wong, Wai P; Chew, Shit F

2017-01-01

Giant clams live in symbiosis with extracellular zooxanthellae and display high rates of growth and shell formation (calcification) in light. Light-enhanced calcification requires an increase in the supply of Ca 2+ to, and simultaneously an augmented removal of H + from, the extrapallial fluid where shell formation occurs. We have obtained the complete coding cDNA sequence of Plasma Membrane Ca 2+ -ATPase ( PMCA ) from the thin and whitish inner mantle, which is in touch with the extrapallial fluid, of the giant clam Tridacna squamosa . The deduced PMCA sequence consisted of an apical targeting element. Immunofluorescence microscopy confirmed that PMCA had an apical localization in the shell-facing epithelium of the inner mantle, whereby it can actively secrete Ca 2+ in exchange for H + . More importantly, the apical PMCA-immunofluorescence of the shell-facing epithelium of the inner mantle increased significantly after 12 h of exposure to light. The transcript and protein levels of PMCA /PMCA also increased significantly in the inner mantle after 6 or 12 h of light exposure. These results offer insights into a light-dependable mechanism of shell formation in T. squamosa and a novel explanation of light-enhanced calcification in general. As the inner mantle normally lacks light sensitive pigments, our results support a previous proposition that symbiotic zooxanthellae, particularly those in the colorful and extensible outer mantle, may act as light-sensing elements for the host clam.

Kinematic responses to changes in walking orientation and gravitational load in Drosophila melanogaster.

PubMed

Mendes, César S; Rajendren, Soumya V; Bartos, Imre; Márka, Szabolcs; Mann, Richard S

2014-01-01

Walking behavior is context-dependent, resulting from the integration of internal and external influences by specialized motor and pre-motor centers. Neuronal programs must be sufficiently flexible to the locomotive challenges inherent in different environments. Although insect studies have contributed substantially to the identification of the components and rules that determine locomotion, we still lack an understanding of how multi-jointed walking insects respond to changes in walking orientation and direction and strength of the gravitational force. In order to answer these questions we measured with high temporal and spatial resolution the kinematic properties of untethered Drosophila during inverted and vertical walking. In addition, we also examined the kinematic responses to increases in gravitational load. We find that animals are capable of shifting their step, spatial and inter-leg parameters in order to cope with more challenging walking conditions. For example, flies walking in an inverted orientation decreased the duration of their swing phase leading to increased contact with the substrate and, as a result, greater stability. We also find that when flies carry additional weight, thereby increasing their gravitational load, some changes in step parameters vary over time, providing evidence for adaptation. However, above a threshold that is between 1 and 2 times their body weight flies display locomotion parameters that suggest they are no longer capable of walking in a coordinated manner. Finally, we find that functional chordotonal organs are required for flies to cope with additional weight, as animals deficient in these proprioceptors display increased sensitivity to load bearing as well as other locomotive defects.

Behavioural and cognitive abnormalities in an imprinting centre deletion mouse model for Prader-Willi syndrome.

PubMed

Relkovic, Dinko; Doe, Christine M; Humby, Trevor; Johnstone, Karen A; Resnick, James L; Holland, Anthony J; Hagan, Jim J; Wilkinson, Lawrence S; Isles, Anthony R

2010-01-01

The genes in the imprinted cluster on human chromosome 15q11-q13 are known to contribute to psychiatric conditions such as schizophrenia and autism. Major disruptions of this interval leading to a lack of paternal allele expression give rise to Prader-Willi syndrome (PWS), a neurodevelopmental disorder with core symptoms of a failure to thrive in infancy and, on emergence from infancy, learning disabilities and over-eating. Individuals with PWS also display a number of behavioural problems and an increased incidence of neuropsychiatric abnormalities, which recent work indicates involve aspects of frontal dysfunction. To begin to examine the contribution of genes in this interval to relevant psychological and behavioural phenotypes, we exploited the imprinting centre (IC) deletion mouse model for PWS (PWS-IC(+/-)) and the five-choice serial reaction time task (5-CSRTT), which is primarily an assay of visuospatial attention and response control that is highly sensitive to frontal manipulations. Locomotor activity, open-field behaviour and sensorimotor gating were also assessed. PWS-IC(+/-) mice displayed reduced locomotor activity, increased acoustic startle responses and decreased prepulse inhibition of startle responses. In the 5-CSRTT, the PWS-IC(+/-) mice showed deficits in discriminative response accuracy, increased correct reaction times and increased omissions. Task manipulations confirmed that these differences were likely to be due to impaired attention. Our data recapitulate several aspects of the PWS clinical condition, including findings consistent with frontal abnormalities, and may indicate novel contributions of the imprinted genes found in 15q11-q13 to behavioural and cognitive function generally.

Sensitivity of Salivary Glands to Radiation

PubMed Central

Grundmann, O.; Mitchell, G.C.; Limesand, K.H.

2009-01-01

Radiation therapy for head and neck cancer causes significant secondary side-effects in normal salivary glands, resulting in diminished quality of life for these individuals. Salivary glands are exquisitely sensitive to radiation and display acute and chronic responses to radiotherapy. This review will discuss clinical implications of radiosensitivity in normal salivary glands, compare animal models used to investigate radiation-induced salivary gland damage, address therapeutic advances, and project future directions in the field. PMID:19783796

The difference between temperate and tropical saltwater species' acute sensitivity to chemicals is relatively small.

PubMed

Wang, Zhen; Kwok, Kevin W H; Lui, Gilbert C S; Zhou, Guang-Jie; Lee, Jae-Seong; Lam, Michael H W; Leung, Kenneth M Y

2014-06-01

Due to a lack of saltwater toxicity data in tropical regions, toxicity data generated from temperate or cold water species endemic to North America and Europe are often adopted to derive water quality guidelines (WQG) for protecting tropical saltwater species. If chemical toxicity to most saltwater organisms increases with water temperature, the use of temperate species data and associated WQG may result in under-protection to tropical species. Given the differences in species composition and environmental attributes between tropical and temperate saltwater ecosystems, there are conceivable uncertainties in such 'temperate-to-tropic' extrapolations. This study aims to compare temperate and tropical saltwater species' acute sensitivity to 11 chemicals through a comprehensive meta-analysis, by comparing species sensitivity distributions (SSDs) between the two groups. A 10 percentile hazardous concentration (HC10) is derived from each SSD, and then a temperate-to-tropic HC10 ratio is computed for each chemical. Our results demonstrate that temperate and tropical saltwater species display significantly different sensitivity towards all test chemicals except cadmium, although such differences are small with the HC10 ratios ranging from 0.094 (un-ionised ammonia) to 2.190 (pentachlorophenol) only. Temperate species are more sensitive to un-ionised ammonia, chromium, lead, nickel and tributyltin, whereas tropical species are more sensitive to copper, mercury, zinc, phenol and pentachlorophenol. Through comparison of a limited number of taxon-specific SSDs, we observe that there is a general decline in chemical sensitivity from algae to crustaceans, molluscs and then fishes. Following a statistical analysis of the results, we recommend an extrapolation factor of two for deriving tropical WQG from temperate information. Copyright © 2013 Elsevier Ltd. All rights reserved.

Differences in exosome populations in human breast milk in relation to allergic sensitization and lifestyle.

PubMed

Torregrosa Paredes, P; Gutzeit, C; Johansson, S; Admyre, C; Stenius, F; Alm, J; Scheynius, A; Gabrielsson, S

2014-04-01

Breast-feeding has many beneficial effects on the developing immune system of the newborn. Breast milk contains immunoregulatory factors, such as nano-sized vesicles named exosomes. This study aimed at characterizing breast milk exosomes from human early milk and mature milk and to investigate whether allergic sensitization and an anthroposophic lifestyle could influence the exosome profile. Breast milk was collected from 22 mothers at day 3-8 and from 61 mothers at 2 months postpartum, all part of the ALADDIN birth cohort. Isolated exosomes were captured on anti-MHC-class II- or anti-CD63 beads and analyzed by flow cytometry. Exosomal phenotype was related to lifestyle and allergic sensitization of the mothers, and sensitization of the child at 2 years of age. We found a higher content of exosomes in early milk compared with mature milk. Early milk exosomes were enriched in HLA-DR molecules and displayed significantly lower levels of HLA-ABC compared with those in mature milk. Phenotypically different subpopulations of exosomes were found in mature milk. Significantly lower levels of MUC1 were detected on CD63-enriched exosomes from sensitized mothers compared with nonsensitized. Furthermore, women with an anthroposophic lifestyle had significantly lower MUC1 expression on their HLA-DR-enriched milk exosomes and up-regulated levels of CD63 on CD63-enriched exosomes compared with nonanthroposophic mothers. Notably, mothers whose children developed sensitization had an increased amount of HLA-ABC on their milk exosomes enriched for CD63. The phenotype of exosomes in breast milk varies with maternal sensitization and lifestyle, which might influence allergy development in the child. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Perimenstrual-Like Hormonal Regulation of Extrasynaptic δ-Containing GABAA Receptors Mediating Tonic Inhibition and Neurosteroid Sensitivity

PubMed Central

Carver, Chase Matthew; Wu, Xin; Gangisetty, Omkaram

2014-01-01

Neurosteroids are endogenous regulators of neuronal excitability and seizure susceptibility. Neurosteroids, such as allopregnanolone (AP; 3α-hydroxy-5α-pregnan-20-one), exhibit enhanced anticonvulsant activity in perimenstrual catamenial epilepsy, a neuroendocrine condition in which seizures are clustered around the menstrual period associated with neurosteroid withdrawal (NSW). However, the molecular mechanisms underlying such enhanced neurosteroid sensitivity remain unclear. Neurosteroids are allosteric modulators of both synaptic (αβγ2-containing) and extrasynaptic (αβδ-containing) GABAA receptors, but they display greater sensitivity toward δ-subunit receptors in dentate gyrus granule cells (DGGCs). Here we report a novel plasticity of extrasynaptic δ-containing GABAA receptors in the dentate gyrus in a mouse perimenstrual-like model of NSW. In molecular and immunofluorescence studies, a significant increase occurred in δ subunits, but not α1, α2, β2, and γ2 subunits, in the dentate gyrus of NSW mice. Electrophysiological studies confirmed enhanced sensitivity to AP potentiation of GABA-gated currents in DGGCs, but not in CA1 pyramidal cells, in NSW animals. AP produced a greater potentiation of tonic currents in DGGCs of NSW animals, and such enhanced AP sensitivity was not evident in δ-subunit knock-out mice subjected to a similar withdrawal paradigm. In behavioral studies, mice undergoing NSW exhibited enhanced seizure susceptibility to hippocampus kindling. AP has enhanced anticonvulsant effects in fully kindled wild-type mice, but not δ-subunit knock-out mice, undergoing NSW-induced seizures, confirming δ-linked neurosteroid sensitivity. These results indicate that perimenstrual NSW is associated with striking upregulation of extrasynaptic, δ-containing GABAA receptors that mediate tonic inhibition and neurosteroid sensitivity in the dentate gyrus. These findings may represent a molecular rationale for neurosteroid therapy of catamenial epilepsy. PMID:25339733

Regulation of extracellular copper-binding proteins in copper-resistant and copper-sensitive mutants of Vibrio alginolyticus.

PubMed Central

Harwood, V J; Gordon, A S

1994-01-01

Extracellular proteins of wild-type Vibrio alginolyticus were compared with those of copper-resistant and copper-sensitive mutants. One copper-resistant mutant (Cu40B3) constitutively produced an extracellular protein with the same apparent molecular mass (21 kDa) and chromatographic behavior as copper-binding protein (CuBP), a copper-induced supernatant protein which has been implicated in copper detoxification in wild-type V. alginolyticus. Copper-sensitive V. alginolyticus mutants displayed a range of alterations in supernatant protein profiles. CuBP was not detected in supernatants of one copper-sensitive mutant after cultures had been stressed with 50 microM copper. Increased resistance to copper was not induced by preincubation with subinhibitory levels of copper in the wild type or in the copper-resistant mutant Cu40B3. Copper-resistant mutants maintained the ability to grow on copper-amended agar after 10 or more subcultures on nonselective agar, demonstrating the stability of the phenotype. A derivative of Cu40B3 with wild-type sensitivity to copper which no longer constitutively expressed CuBP was isolated. The simultaneous loss of both constitutive CuBP production and copper resistance in Cu40B3 indicates that constitutive CuBP production is necessary for copper resistance in this mutant. These data support the hypothesis that the extracellular, ca. 20-kDa protein(s) of V. alginolyticus is an important factor in survival and growth of the organism at elevated copper concentrations. The range of phenotypes observed in copper-resistant and copper-sensitive V. alginolyticus indicate that altered sensitivity to copper was mediated by a variety of physiological changes. Images PMID:8031076

Impulsivity in spontaneously hypertensive rats: Within-subjects comparison of sensitivity to delay and to amount of reinforcement.

PubMed

Orduña, Vladimir; Mercado, Eduardo

2017-06-15

Previous research has shown that spontaneously hypertensive rats (SHR) display higher levels of impulsive choice behavior, which is accompanied by a higher sensitivity to the delay of reinforcement, and by a normal sensitivity to the amount of reinforcement. Because those results were based on three different samples of subjects, in the present report we evaluated these three processes in the same individuals. SHR and WIS rats were exposed to concurrent-chains schedules in which the terminal links were manipulated to assess impulsivity, sensitivity to delay, and sensitivity to amount. For exploring impulsivity, a terminal link was associated with a small reinforcer (1 pellet) delivered after a short delay (2s) while the other terminal link was associated with a larger reinforcer (4 pellets) delivered after a longer delay (28s). For assessing sensitivity to delay, both alternatives delivered the same amount of reinforcement (1 pellet) and the only difference between them was in the delay before reinforcement delivery (2s vs 28s). For assessing sensitivity to amount, both alternatives were associated with the same delay (15s), but the alternatives differed in the amount of reinforcement (1 vs 4 pellets). In addition to replicating previously observed effects within-subjects, we were interested in analyzing different aspects of the regularity of rats' actions in the choice task. The results confirmed that previous findings were not a consequence of between-group differences: SHR were more impulsive and more sensitive to delay, while their sensitivity to amount was normal. Analyses of response regularity indicated that SHR subjects were more periodic in their responses to levers and in their feeder entries, had a higher number of short-duration bouts of responding, and made a substantially higher number of switches between the alternatives. We discuss the potential implications of these findings for the possible behavioral mechanisms driving the increased sensitivity to delay in SHR. Copyright © 2017 Elsevier B.V. All rights reserved.

Dasatinib is preclinically active against Src-overexpressing human transitional cell carcinoma of the urothelium with activated Src signaling.

PubMed

Levitt, Jonathan M; Yamashita, Hideyuki; Jian, Weiguo; Lerner, Seth P; Sonpavde, Guru

2010-05-01

Dasatinib is an orally administered multitargeted kinase inhibitor that targets Src family tyrosine kinases, Abl, c-Kit, and PDGFR. A preclinical study was conducted to evaluate dasatinib alone or combined with cisplatin for human transitional cell carcinoma (TCC). Expression of Src in a human TCC tissue microarray was evaluated by immunohistochemistry. The activity of dasatinib and/or cisplatin was evaluated in six human TCC cell lines. Western blot was done to assess Src and phosphorylated-Src (p-Src) expression. The activity of dasatinib alone and in combination with cisplatin was determined in murine subcutaneous xenografts. Sixty-two percent to 75% of human TCC expressed Src. Dasatinib displayed significant antiproliferative activity at nanomolar concentrations against two human TCC cell lines (RT4 and Hu456) that exhibited high Src and p-Src expression and were cisplatin-resistant. RT4 cells were the most sensitive and displayed the highest level of Src pathway activation (p-Src/Src ratio). Dasatinib downregulated p-Src in either sensitive or resistant cells. TCC cells that were sensitive to cisplatin (5637 and TCC-SUP) were highly resistant to dasatinib and exhibited low Src expression. Dasatinib showed antitumor activity in RT4 murine xenografts, and the combination of dasatinib and cisplatin was significantly more active than placebo. Combination dasatinib plus cisplatin significantly inhibited proliferation and promoted apoptosis in vivo. In conclusion, dasatinib displayed significant preclinical antitumor activity against Src-overexpressing human TCC with active Src signaling and was highly active in combination with cisplatin in vivo. Further clinical development might be warranted in selected human subjects.

Generation of a Highly Reactive Chicken-Derived Single-Chain Variable Fragment against Fusarium verticillioides by Phage Display

PubMed Central

Hu, Zu-Quan; Liu, Jin-Long; Li, He-Ping; Xing, Shu; Xue, Sheng; Zhang, Jing-Bo; Wang, Jian-Hua; Nölke, Greta; Liao, Yu-Cai

2012-01-01

Fusarium verticillioides is the primary causal agent of Fusarium ear and kernel rot in maize, producing fumonisin mycotoxins that are toxic to humans and domestic animals. Rapid detection and monitoring of fumonisin-producing fungi are pivotally important for the prevention of mycotoxins from entering into food/feed products. Chicken-derived single-chain variable fragments (scFvs) against cell wall-bound proteins from F. verticillioides were isolated from an immunocompetent phage display library. Comparative phage enzyme-linked immunosorbant assays (ELISAs) and sequencing analyses identified four different scFv antibodies with high sensitivity. Soluble antibody ELISAs identified two highly sensitive scFv antibodies, FvCA3 and FvCA4, with the latter being slightly more sensitive. Three-dimensional modeling revealed that the FvCA4 may hold a better overall structure with CDRH3, CDRL1 and CDRL3 centered in the core region of antibody surface compared with that of other scFvs. Immunofluorescence labeling revealed that the binding of FvCA4 antibody was localized to the cell walls of conidiospores and hyphae of F. verticillioides, confirming the specificity of this antibody for a surface target. This scFv antibody was able to detect the fungal mycelium as low as 10−2 μg/mL and contaminating mycelium at a quantity of 10−2 mg/g maize. This is the first report that scFv antibodies derived from phage display have a wide application for rapid and accurate detection and monitoring of fumonisin-producing pathogens in agricultural samples. PMID:22837678

Display dimensionality and conflict geometry effects on maneuver preferences for resolving in-flight conflicts.

PubMed

Thomas, Lisa C; Wickens, Christopher D

2008-08-01

Two experiments explored the effects of display dimensionality, conflict geometry, and time pressure on pilot maneuvering preferences for resolving en route conflicts. With the presence of a cockpit display of traffic information (CDTI) that provides graphical airspace information, pilots can use a variety of conflict resolution maneuvers in response to how they perceive the conflict. Inconsistent preference findings from previous research on conflict resolution using CDTIs may be attributable to inherent ambiguities in 3-D perspective displays and/or a limited range of conflict geometries. Pilots resolved predicted conflicts using CDTIs with three levels of display dimensionality; the first had two 2-D orthogonal views, the second depicted the airspace in two alternating 3-D perspective views, and the third had a pilot-controlled swiveling viewpoint. Pilots demonstrated the same preferences that have been observed in previous research for vertical over lateral maneuvers in low workload and climbs over descents for level-flight conflicts. With increasing workload the two 3-D perspective displays, but not the 2-D displays, resulted in an increased preference for lateral over vertical maneuvers. Increased time pressure resulted in increased vertical maneuvers, an effect again limited to the two 3-D perspective displays. Resolution preferences were more affected by workload and time pressure when the 3-D perspective displays were used, as compared with the 2-D displays, although overall preferences were milder than in previous studies. Investigating maneuver preferences using the strategic flight planning paradigm employed in this study may be the key to better ensure pilot acceptance of computer-generated resolution maneuvers.

The Added Diagnostic Value of 18F-Fluorodihydroxyphenylalanine PET/CT in the Preoperative Work-Up of Small Bowel Neuroendocrine Tumors.

PubMed

Addeo, Pietro; Poncet, Gilles; Goichot, Bernard; Leclerc, Loic; Brigand, Cécile; Mutter, Didier; Romain, Benoit; Namer, Izzie-Jacques; Bachellier, Philippe; Imperiale, Alessio

2018-04-01

The precise localization of the primary tumor and/or the identification of multiple primary tumors improves the preoperative work-up in patients with small bowel (SB) neuroendocrine tumor (NET). The present study assesses the diagnostic value of 18 F-fluorodihydroxyphenylalanine ( 18 F-FDOPA) positron emission tomography/computed tomography (PET/CT) during the preoperative wok-up of SB NETs. Between January 2010 and June 2017, all consecutive patients with SB NETs undergoing preoperative 18 F-FDOPA PET/CT and successive resection were analyzed. Preoperative work-up included computed tomography (CT), somatostatin receptor scintigraphy (SRS), and 18 F-FDOPA PET/CT. Sensitivity and accuracy ratio for primary and multiple tumor detection were compared with data from surgery and pathology. There were 17 consecutive patients with SB NETs undergoing surgery. Nine patients (53%) had multiple tumors, 15 (88%) metastatic lymph nodes, 3 (18%) peritoneal carcinomatosis, and 9 patients (53%) liver metastases. A total of 70 SB NETs were found by pathology. Surgery identified the primary in 17/17 (100%) patients and recognized seven of 9 patients (78%) with multiple synchronous SB. Preoperatively, 18 F-FDOPA PET/CT displayed a statistically significant higher sensitivity for primary tumor localization (100 vs. 23.5 vs. 29.5%) and multiple tumor detection (78 vs. 22 vs. 11%) over SRS and CT. Compared with pathology, 18 F-FDOPA PET/CT displayed the highest accuracy ratio for number of tumor detected over CT and SRS (2.0 ± 2.2 vs. 0.4 ± 0.7 vs. 0.6 ± 1.5, p = 0.0003). 18 F-FDOPA PET/CT significantly increased the sensitivity and accuracy for primary and multiple SB NET identification. 18 F-FDOPA PET/CT should be included systematically in the preoperative work-up of SB NET.

Corticospinal excitability measurements using transcranial magnetic stimulation are valid with intramuscular electromyography.

PubMed

Summers, Rebekah L S; Chen, Mo; Kimberley, Teresa J

2017-01-01

Muscular targets that are deep or inaccessible to surface electromyography (sEMG) require intrinsic recording using fine-wire electromyography (fEMG). It is unknown if fEMG validly record cortically evoked muscle responses compared to sEMG. The purpose of this investigation was to establish the validity and agreement of fEMG compared to sEMG to quantify typical transcranial magnetic stimulation (TMS) measures pre and post repetitive TMS (rTMS). The hypotheses were that fEMG would demonstrate excellent validity and agreement compared with sEMG. In ten healthy volunteers, paired pulse and cortical silent period (CSP) TMS measures were collected before and after 1200 pulses of 1Hz rTMS to the motor cortex. Data were simultaneously recorded with sEMG and fEMG in the first dorsal interosseous. Concurrent validity (r and rho) and agreement (Tukey mean-difference) were calculated. fEMG quantified corticospinal excitability with good to excellent validity compared to sEMG data at both pretest (r = 0.77-0.97) and posttest (r = 0.83-0.92). Pairwise comparisons indicated no difference between sEMG and fEMG for all outcomes; however, Tukey mean-difference plots display increased variance and questionable agreement for paired pulse outcomes. CSP displayed the highest estimates of validity and agreement. Paired pulse MEP responses recorded with fEMG displayed reduced validity, agreement and less sensitivity to changes in MEP amplitude compared to sEMG. Change scores following rTMS were not significantly different between sEMG and fEMG. fEMG electrodes are a valid means to measure CSP and paired pulse MEP responses. CSP displays the highest validity estimates, while caution is warranted when assessing paired pulse responses with fEMG. Corticospinal excitability and neuromodulatory aftereffects from rTMS may be assessed using fEMG.

Information transmission and detection thresholds in the vestibular nuclei: single neurons vs. population encoding

PubMed Central

Massot, Corentin; Chacron, Maurice J.

2011-01-01

Understanding how sensory neurons transmit information about relevant stimuli remains a major goal in neuroscience. Of particular relevance are the roles of neural variability and spike timing in neural coding. Peripheral vestibular afferents display differential variability that is correlated with the importance of spike timing; regular afferents display little variability and use a timing code to transmit information about sensory input. Irregular afferents, conversely, display greater variability and instead use a rate code. We studied how central neurons within the vestibular nuclei integrate information from both afferent classes by recording from a group of neurons termed vestibular only (VO) that are known to make contributions to vestibulospinal reflexes and project to higher-order centers. We found that, although individual central neurons had sensitivities that were greater than or equal to those of individual afferents, they transmitted less information. In addition, their velocity detection thresholds were significantly greater than those of individual afferents. This is because VO neurons display greater variability, which is detrimental to information transmission and signal detection. Combining activities from multiple VO neurons increased information transmission. However, the information rates were still much lower than those of equivalent afferent populations. Furthermore, combining responses from multiple VO neurons led to lower velocity detection threshold values approaching those measured from behavior (∼2.5 vs. 0.5–1°/s). Our results suggest that the detailed time course of vestibular stimuli encoded by afferents is not transmitted by VO neurons. Instead, they suggest that higher vestibular pathways must integrate information from central vestibular neuron populations to give rise to behaviorally observed detection thresholds. PMID:21307329

ALS3 encodes a phloem-localized ABC transporter-like protein that is required for aluminum tolerance in Arabidopsis.

PubMed

Larsen, Paul B; Geisler, Matt J B; Jones, Carol A; Williams, Kelly M; Cancel, Jesse D

2005-02-01

Aluminum (Al) toxicity in acid soils is a worldwide agricultural problem that severely limits crop productivity through inhibition of root growth. Previously, Arabidopsis mutants with increased Al sensitivity were isolated in order to identify genes important for Al tolerance in plants. One mutant, als3, exhibited extreme root growth inhibition in the presence of Al, suggesting that this mutation negatively impacts a gene required for Al tolerance. Map-based cloning of the als3-1 mutation resulted in the isolation of a novel gene that encodes a previously undescribed ABC transporter-like protein, which is highly homologous to a putative bacterial metal resistance protein, ybbM. Northern analysis for ALS3 expression revealed that it is found in all organs examined, which is consistent with the global nature of Al sensitivity displayed by als3, and that expression increases in roots following Al treatment. Based on GUS fusion and in situ hybridization analyses, ALS3 is primarily expressed in leaf hydathodes and the phloem throughout the plant, along with the root cortex following Al treatment. Immunolocalization indicates that ALS3 predominantly accumulates in the plasma membrane of cells that express ALS3. From our results, it appears that ALS3 encodes an ABC transporter-like protein that is required for Al resistance/tolerance and may function to redistribute accumulated Al away from sensitive tissues in order to protect the growing root from the toxic effects of Al.

Modifying Expression Modes of Human Neurotensin Receptor Type 1 Alters Sensing Capabilities for Agonists in Yeast Signaling Biosensor.

PubMed

Hashi, Hiroki; Nakamura, Yasuyuki; Ishii, Jun; Kondo, Akihiko

2018-04-01

Neurotensin receptor type 1 (NTSR1), a member of the G-protein-coupled receptor (GPCR) family, is naturally activated by binding of a neurotensin peptide, leading to a variety of physiological effects. The budding yeast Saccharomyces cerevisiae is a proven host organism for assaying the agonistic activation of human GPCRs. Previous studies showed that yeast cells can functionally express human NTSR1 receptor, permitting the detection of neurotensin-promoted signaling using a ZsGreen fluorescent reporter gene. However, the fluorescence intensity (sensitivity) of NTSR1-expressing yeast cells is low compared to that of yeast cells expressing other human GPCRs (e.g., human somatostatin receptors). The present study sought to increase the sensitivity of the NTSR1-expressing yeast for use as a fluorescent biosensor, including modification of the expression of human NTSR1 in yeast. Changes in the transcription, translation, and transport of the receptor are attempted by altering the promoter, consensus Kozak-like sequence, and secretion signal sequences of the NTSR1-encoding gene. The resulting yeast cells exhibited increased sensitivity to exogenously added peptide. The cells are further engineered by using cell-surface display technology to ensure that the agonistic peptides are secreted and tethered to the yeast cell wall, yielding cells with enhanced NTSR1 activation. This yeast biosensor holds promise for the identification of agonists to treat NTSR1-related diseases. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Inhibition of the RhoA GTPase Activity Increases Sensitivity of Melanoma Cells to UV Radiation Effects

PubMed Central

Espinha, Gisele; Osaki, Juliana Harumi; Costa, Erico Tosoni; Forti, Fabio Luis

2016-01-01

Ultraviolet radiation is the main cause of DNA damage to melanocytes and development of melanoma, one of the most lethal human cancers, which leads to metastasis due to uncontrolled cell proliferation and migration. These phenotypes are mediated by RhoA, a GTPase overexpressed or overactivated in highly aggressive metastatic tumors that plays regulatory roles in cell cycle progression and cytoskeleton remodeling. This work explores whether the effects of UV on DNA damage, motility, proliferation, and survival of human metastatic melanoma cells are mediated by the RhoA pathway. Mutant cells expressing dominant-negative (MeWo-RhoA-N19) or constitutively active RhoA (MeWo-RhoA-V14) were generated and subjected to UV radiation. A slight reduction in migration and invasion was observed in MeWo and MeWo-RhoA-V14 cells but not in MeWo-RhoA-N19 cells, which presented inefficient motility and invasiveness associated with stress fibers fragmentation. Proliferation and survival of RhoA-deficient cells were drastically reduced by UV compared to cells displaying normal or high RhoA activity, suggesting increased sensitivity to UV. Loss of RhoA activity also caused less efficient DNA repair, with elevated levels of DNA lesions such as strand breaks and cyclobutane pyrimidine dimers (CPDs). Thus, RhoA mediates genomic stability and represents a potential target for sensitizing metastatic tumors to genotoxic agents. PMID:26823948

Highly Sensitive Thin-Film Field-Effect Transistor Sensor for Ammonia with the DPP-Bithiophene Conjugated Polymer Entailing Thermally Cleavable tert-Butoxy Groups in the Side Chains.

PubMed

Yang, Yang; Zhang, Guanxin; Luo, Hewei; Yao, Jingjing; Liu, Zitong; Zhang, Deqing

2016-02-17

The sensing and detection of ammonia have received increasing attention in recent years because of the growing emphasis on environmental and health issues. In this paper, we report a thin-film field-effect transistor (FET)-based sensor for ammonia and other amines with remarkable high sensitivity and satisfactory selectivity by employing the DPP-bithiophene conjugated polymer pDPPBu-BT in which tert-butoxycarboxyl groups are incorporated in the side chains. This polymer thin film shows p-type semiconducting property. On the basis of TGA and FT-IR analysis, tert-butoxycarboxyl groups can be transformed into the -COOH ones by eliminating gaseous isobutylene after thermal annealing of pDPPBu-BT thin film at 240 °C. The FET with the thermally treated thin film of pDPPBu-BT displays remarkably sensitive and selective response toward ammonia and volatile amines. This can be attributed to the fact that the elimination of gaseous isobutylene accompanies the formation of nanopores with the thin film, which will facilitate the diffusion and interaction of ammonia and other amines with the semiconducting layer, leading to high sensitivity and fast response for this FET sensor. This FET sensor can detect ammonia down to 10 ppb and the interferences from other volatile analytes except amines can be negligible.

Hierarchical Encoding of Social Cues in Primate Inferior Temporal Cortex.

PubMed

Morin, Elyse L; Hadj-Bouziane, Fadila; Stokes, Mark; Ungerleider, Leslie G; Bell, Andrew H

2015-09-01

Faces convey information about identity and emotional state, both of which are important for our social interactions. Models of face processing propose that changeable versus invariant aspects of a face, specifically facial expression/gaze direction versus facial identity, are coded by distinct neural pathways and yet neurophysiological data supporting this separation are incomplete. We recorded activity from neurons along the inferior bank of the superior temporal sulcus (STS), while monkeys viewed images of conspecific faces and non-face control stimuli. Eight monkey identities were used, each presented with 3 different facial expressions (neutral, fear grin, and threat). All facial expressions were displayed with both a direct and averted gaze. In the posterior STS, we found that about one-quarter of face-responsive neurons are sensitive to social cues, the majority of which being sensitive to only one of these cues. In contrast, in anterior STS, not only did the proportion of neurons sensitive to social cues increase, but so too did the proportion of neurons sensitive to conjunctions of identity with either gaze direction or expression. These data support a convergence of signals related to faces as one moves anteriorly along the inferior bank of the STS, which forms a fundamental part of the face-processing network. Published by Oxford University Press 2014. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Physical and sporting activities improve vestibular afferent usage and balance in elderly human subjects.

PubMed

Gauchard, G C; Jeandel, C; Perrin, P P

2001-01-01

Ageing is associated with a reduction in balance, in particular through dysfunction of each level of postural control, which results in an increased risk of falling. Conversely, the practice of physical activities has been shown to modulate postural control in elderly people. This study examined the potential positive effects of two types of regular physical and sporting activities on vestibular information and their relation to posture. Gaze and postural stabilisation was evaluated by caloric and rotational vestibular tests on 18 healthy subjects over the age of 60 who regularly practised low-energy or bioenergetic physical activities and on 18 controls of a similar age who only walked on a regular basis. These subjects were also submitted to static and dynamic posturographic tests. The control group displayed less balance control, with a lower vestibular sensitivity and a relatively high dependency on vision compared to the group practising low-energy physical activities, which had better postural control with good vestibular sensitivity and less dependency on vision. The postural control and vestibular sensitivity of subjects practising bioenergetic activities was average, and required higher visual afferent contribution. Low-energy exercises, already shown to have the most positive impact on balance control by relying more on proprioception, also appear to develop or maintain a high level of vestibular sensitivity allowing elderly people practising such exercises to reduce the weight of vision. Copyright 2001 S. Karger AG, Basel

Basics of Antibody Phage Display Technology.

PubMed

Ledsgaard, Line; Kilstrup, Mogens; Karatt-Vellatt, Aneesh; McCafferty, John; Laustsen, Andreas H

2018-06-09

Antibody discovery has become increasingly important in almost all areas of modern medicine. Different antibody discovery approaches exist, but one that has gained increasing interest in the field of toxinology and antivenom research is phage display technology. In this review, the lifecycle of the M13 phage and the basics of phage display technology are presented together with important factors influencing the success rates of phage display experiments. Moreover, the pros and cons of different antigen display methods and the use of naïve versus immunized phage display antibody libraries is discussed, and selected examples from the field of antivenom research are highlighted. This review thus provides in-depth knowledge on the principles and use of phage display technology with a special focus on discovery of antibodies that target animal toxins.

Urine Scent Marking (USM): A Novel Test for Depressive-Like Behavior and a Predictor of Stress Resiliency in Mice

PubMed Central

Lehmann, Michael L.; Geddes, Claire E.; Lee, Jennifer L.; Herkenham, Miles

2013-01-01

Decreased interest in pleasurable stimuli including social withdrawal and reduced libido are some of the key symptomatic criteria for major depression, and thus assays that measure social and sexual behavior in rodents may be highly appropriate for modeling depressive states. Here we present a novel approach for validating rodent models of depression by assessing male urine scent marking (USM) made in consequence to a spot of urine from a proestrous female. USM is an ethologically important form of sexual communication expressed by males to attract females. The expression of this behavior is highly sensitive and adaptive to environmental cues and social status. We hypothesized that male USM behavior offers a naturalistic measure of social motivation that can be used to evaluate hedonic behaviors relevant to the study of mood disorders. We demonstrated that 1) adult male mice displayed a strong preference for marking proestrous female urine with a high degree of specificity, 2) exposure to chronic social defeat profoundly decreased USM whereas exposure to environmental enrichment increased USM, 3) the standard antidepressant fluoxetine reversed declines in USM induced by social defeat, 4) USM behavior closely correlated with other hedonic measures, and 5) USM scores in non-stressed mice predicted behavioral outcomes after defeat exposure such that mice displaying high preference for marking female urine prior to social defeat showed behavioral resiliency after social defeat. The findings indicate that the USM test is a sensitive, validated measure of psychosocial stress effects that has high predictive value for examination of stress resiliency and vulnerability and their neurobiological substrates. PMID:23875001

Highly Sensitive Biosensing with Solid-State Nanopores Displaying Enzymatically Reconfigurable Rectification Properties.

PubMed

Pérez-Mitta, Gonzalo; Peinetti, Ana S; Cortez, M Lorena; Toimil-Molares, María Eugenia; Trautmann, Christina; Azzaroni, Omar

2018-05-09

Molecular design of biosensors based on enzymatic processes taking place in nanofluidic elements is receiving increasing attention by the scientific community. In this work, we describe the construction of novel ultrasensitive enzymatic nanopore biosensors employing "reactive signal amplifiers" as key elements coupled to the transduction mechanism. The proposed framework offers innovative design concepts not only to amplify the detected ionic signal and develop ultrasensitive nanopore-based sensors but also to construct nanofluidic diodes displaying specific chemo-reversible rectification properties. The integrated approach is demonstrated by electrostatically assembling poly(allylamine) on the anionic pore walls followed by the assembly of urease. We show that the cationic weak polyelectrolyte acts as a "reactive signal amplifier" in the presence of local pH changes induced by the enzymatic reaction. These bioinduced variations in proton concentration ultimately alter the protonation degree of the polyamine resulting in amplifiable, controlled, and reproducible changes in the surface charge of the pore walls, and consequently on the generated ionic signals. The "iontronic" response of the as-obtained devices is fully reversible, and nanopores are reused and assayed with different urea concentrations, thus ensuring reliable design. The limit of detection (LOD) was 1 nM. To the best of our knowledge, this value is the lowest LOD reported to date for enzymatic urea detection. In this context, we envision that this approach based on the use of "reactive signal amplifiers" into solid-state nanochannels will provide new alternatives for the molecular design of highly sensitive nanopore biosensors as well as (bio)chemically addressable nanofluidic elements.

New procedures to evaluate visually lossless compression for display systems

NASA Astrophysics Data System (ADS)

Stolitzka, Dale F.; Schelkens, Peter; Bruylants, Tim

2017-09-01

Visually lossless image coding in isochronous display streaming or plesiochronous networks reduces link complexity and power consumption and increases available link bandwidth. A new set of codecs developed within the last four years promise a new level of coding quality, but require new techniques that are sufficiently sensitive to the small artifacts or color variations induced by this new breed of codecs. This paper begins with a summary of the new ISO/IEC 29170-2, a procedure for evaluation of lossless coding and reports the new work by JPEG to extend the procedure in two important ways, for HDR content and for evaluating the differences between still images, panning images and image sequences. ISO/IEC 29170-2 relies on processing test images through a well-defined process chain for subjective, forced-choice psychophysical experiments. The procedure sets an acceptable quality level equal to one just noticeable difference. Traditional image and video coding evaluation techniques, such as, those used for television evaluation have not proven sufficiently sensitive to the small artifacts that may be induced by this breed of codecs. In 2015, JPEG received new requirements to expand evaluation of visually lossless coding for high dynamic range images, slowly moving images, i.e., panning, and image sequences. These requirements are the basis for new amendments of the ISO/IEC 29170-2 procedures described in this paper. These amendments promise to be highly useful for the new content in television and cinema mezzanine networks. The amendments passed the final ballot in April 2017 and are on track to be published in 2018.

In the absence of phosphate shuttling, exercise reveals the in vivo importance of creatine-independent mitochondrial ADP transport.

PubMed

Miotto, Paula M; Holloway, Graham P

2016-09-15

The transport of cytosolic adenosine diphosphate (ADP) into the mitochondria is a major control point in metabolic homeostasis, as ADP concentrations directly affect glycolytic flux and oxidative phosphorylation rates within mitochondria. A large contributor to the efficiency of this process is thought to involve phosphocreatine (PCr)/Creatine (Cr) shuttling through mitochondrial creatine kinase (Mi-CK), whereas the biological importance of alterations in Cr-independent ADP transport during exercise remains unknown. Therefore, we utilized an Mi-CK knockout (KO) model to determine whether in vivo Cr-independent mechanisms are biologically important for sustaining energy homeostasis during exercise. Ablating Mi-CK did not alter exercise tolerance, as the time to volitional fatigue was similar between wild-type (WT) and KO mice at various exercise intensities. In addition, skeletal muscle metabolic profiles after exercise, including glycogen, PCr/Cr ratios, free ADP/adenosine monophosphate (AMP), and lactate, were similar between genotypes. While these data suggest that the absence of PCr/Cr shuttling is not detrimental to maintaining energy homeostasis during exercise, KO mice displayed a dramatic increase in Cr-independent mitochondrial ADP sensitivity after exercise. Specifically, whereas mitochondrial ADP sensitivity decreased with exercise in WT mice, in stark contrast, exercise increased mitochondrial Cr-independent ADP sensitivity in KO mice. As a result, the apparent ADP Km was 50% lower in KO mice after exercise, suggesting that in vivo activation of voltage-dependent anion channel (VDAC)/adenine nucleotide translocase (ANT) can support mitochondrial ADP transport. Altogether, we provide insight that Cr-independent ADP transport mechanisms are biologically important for regulating ADP sensitivity during exercise, while highlighting complex regulation and the plasticity of the VDAC/ANT axis to support adenosine triphosphate demand. © 2016 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

PCB 136 Atropselectively Alters Morphometric and Functional Parameters of Neuronal Connectivity in Cultured Rat Hippocampal Neurons via Ryanodine Receptor-Dependent Mechanisms

PubMed Central

Yang, Dongren; Kania-Korwel, Izabela; Ghogha, Atefeh; Chen, Hao; Stamou, Marianna; Bose, Diptiman D.; Pessah, Isaac N.; Lehmler, Hans-Joachim; Lein, Pamela J.

2014-01-01

We recently demonstrated that polychlorinated biphenyl (PCB) congeners with multiple ortho chlorine substitutions sensitize ryanodine receptors (RyRs), and this activity promotes Ca2+-dependent dendritic growth in cultured neurons. Many ortho-substituted congeners display axial chirality, and we previously reported that the chiral congener PCB 136 (2,2′,3,3′,6,6′-hexachlorobiphenyl) atropselectively sensitizes RyRs. Here, we test the hypothesis that PCB 136 atropisomers differentially alter dendritic growth and other parameters of neuronal connectivity influenced by RyR activity. (−)-PCB 136, which potently sensitizes RyRs, enhances dendritic growth in primary cultures of rat hippocampal neurons, whereas (+)-PCB 136, which lacks RyR activity, has no effect on dendritic growth. The dendrite-promoting activity of (−)-PCB 136 is observed at concentrations ranging from 0.1 to 100nM and is blocked by pharmacologic RyR antagonism. Neither atropisomer alters axonal growth or cell viability. Quantification of PCB 136 atropisomers in hippocampal cultures indicates that atropselective effects on dendritic growth are not due to differential partitioning of atropisomers into cultured cells. Imaging of hippocampal neurons loaded with Ca2+-sensitive dye demonstrates that (−)-PCB 136 but not (+)-PCB 136 increases the frequency of spontaneous Ca2+ oscillations. Similarly, (−)-PCB 136 but not (+)-PCB 136 increases the activity of hippocampal neurons plated on microelectrode arrays. These data support the hypothesis that atropselective effects on RyR activity translate into atropselective effects of PCB 136 atropisomers on neuronal connectivity, and suggest that the variable atropisomeric enrichment of chiral PCBs observed in the human population may be a significant determinant of individual susceptibility for adverse neurodevelopmental outcomes following PCB exposure. PMID:24385416

Knock-in mice harboring a Ca(2+) desensitizing mutation in cardiac troponin C develop early onset dilated cardiomyopathy.

PubMed

McConnell, Bradley K; Singh, Sonal; Fan, Qiying; Hernandez, Adriana; Portillo, Jesus P; Reiser, Peter J; Tikunova, Svetlana B

2015-01-01

The physiological consequences of aberrant Ca(2+) binding and exchange with cardiac myofilaments are not clearly understood. In order to examine the effect of decreasing Ca(2+) sensitivity of cTnC on cardiac function, we generated knock-in mice carrying a D73N mutation (not known to be associated with heart disease in human patients) in cTnC. The D73N mutation was engineered into the regulatory N-domain of cTnC in order to reduce Ca(2+) sensitivity of reconstituted thin filaments by increasing the rate of Ca(2+) dissociation. In addition, the D73N mutation drastically blunted the extent of Ca(2+) desensitization of reconstituted thin filaments induced by cTnI pseudo-phosphorylation. Compared to wild-type mice, heterozygous knock-in mice carrying the D73N mutation exhibited a substantially decreased Ca(2+) sensitivity of force development in skinned ventricular trabeculae. Kaplan-Meier survival analysis revealed that median survival time for knock-in mice was 12 weeks. Echocardiographic analysis revealed that knock-in mice exhibited increased left ventricular dimensions with thinner walls. Echocardiographic analysis also revealed that measures of systolic function, such as ejection fraction (EF) and fractional shortening (FS), were dramatically reduced in knock-in mice. In addition, knock-in mice displayed electrophysiological abnormalities, namely prolonged QRS and QT intervals. Furthermore, ventricular myocytes isolated from knock-in mice did not respond to β-adrenergic stimulation. Thus, knock-in mice developed pathological features similar to those observed in human patients with dilated cardiomyopathy (DCM). In conclusion, our results suggest that decreasing Ca(2+) sensitivity of the regulatory N-domain of cTnC is sufficient to trigger the development of DCM.

Mitochondria Are Critical for BDNF-Mediated Synaptic and Vascular Plasticity of Hippocampus following Repeated Electroconvulsive Seizures.

PubMed

Chen, Fenghua; Ardalan, Maryam; Elfving, Betina; Wegener, Gregers; Madsen, Torsten M; Nyengaard, Jens R

2018-03-01

Electroconvulsive therapy is a fast-acting and efficient treatment of depression used in the clinic. The underlying mechanism of its therapeutic effect is still unclear. However, recovery of synaptic connections and synaptic remodeling is thought to play a critical role for the clinical efficacy obtained from a rapid antidepressant response. Here, we investigated the relationship between synaptic changes and concomitant nonneuronal changes in microvasculature and mitochondria and its relationship to brain-derived neurotrophic factor level changes after repeated electroconvulsive seizures, an animal model of electroconvulsive therapy. Electroconvulsive seizures or sham treatment was given daily for 10 days to rats displaying a genetically driven phenotype modelling clinical depression: the Flinders Sensitive and Resistant Line rats. Stereological principles were employed to quantify numbers of synapses and mitochondria, and the length of microvessels in the hippocampus. The brain-derived neurotrophic factor protein levels were quantified with immunohistochemistry. In untreated controls, a lower number of synapses and mitochondria was accompanied by shorter microvessels of the hippocampus in "depressive" phenotype (Flinders Sensitive Line) compared with the "nondepressed" phenotype (Flinders Resistant Line). Electroconvulsive seizure administration significantly increased the number of synapses and mitochondria, and length of microvessels both in Flinders Sensitive Line-electroconvulsive seizures and Flinders Resistant Line-electroconvulsive seizures rats. In addition, the amount of brain-derived neurotrophic factor protein was significantly increased in Flinders Sensitive Line and Flinders Resistant Line rats after electroconvulsive seizures. Furthermore, there was a significant positive correlation between brain-derived neurotrophic factor level and mitochondria/synapses. Our results indicate that rapid and efficient therapeutic effect of electroconvulsive seizures may be related to synaptic plasticity, accompanied by brain-derived neurotrophic factor protein level elevation and mitochondrial and vascular support. © The Author(s) 2017. Published by Oxford University Press on behalf of CINP.

Race-related differences in left ventricular structural and functional remodeling in response to increased afterload: the Atherosclerosis Risk in Communities Study

PubMed Central

Fernandes-Silva, Miguel M; Shah, Amil M; Hegde, Sheila; Goncalves, Alexandra; Claggett, Brian; Cheng, Susan; Nadruz, Wilson; Kitzman, Dalane W.; Konety, Suma H.; Matsushita, Kunihiro; Mosley, Thomas; Lam, Carolyn S.P.; Borlaug, Barry A.; Solomon, Scott D

2016-01-01

Background Chronic increasing in arterial afterload may be an important trigger for left ventricular (LV) remodeling and dysfunction that lead to heart failure (HF). Racial differences in the predisposition to HF are well described, but the underlying mechanisms remain unclear. Objective We evaluated the racial differences in arterial elastance (Ea), which reflects the arterial afterload faced by the LV, and its associations with cardiac structure and function. We hypothesize that the LV in blacks displays heightened afterload sensitivity as compared to whites. Methods We studied 5727 community-based, elderly Atherosclerosis Risk in Community (ARIC) Study participants (22% black), who underwent echocardiography between 2011 and 2013. Results Blacks were younger (75 ± 5 vs 76 ± 5 years old), more frequently women (66 vs 57%), and had higher prevalence of obesity (46 vs 31%), hypertension (94 vs 80%), and diabetes mellitus (47 vs 34%) than whites. Adjusting for these baseline differences, Ea was higher among blacks (1.96 ± 0.01 vs 1.80 ± 0.01 mmHg/mL). In blacks, Ea was associated with greater LV remodeling (LV mass index, β = 3.21 ± 0.55 g/m2, p<0.001) and higher LV filling pressures (E/e′ ratio, β = 0.42 ± 0.11, p<0.001). These relationships were not observed in whites (LV mass, β = 0.16 ± 0.32 g/m2, p=0.61, p for interaction <0.001; E/e′ratio, β = −0.32 ± 0.06, p<0.001, p for interaction <0.001).. Conclusion These community-based data suggest that black Americans display heightened afterload sensitivity as a stimulus for LV structural and functional remodeling, which may contribute to their greater risk of HF, as compared to white Americans. PMID:28017356

Influence of high ambient illuminance and display luminance on readability and subjective preference

NASA Astrophysics Data System (ADS)

De Moor, Katrien; Andrén, Börje; Guo, Yi; Brunnström, Kjell; Wang, Kun; Drott, Anton; Hermann, David S.

2015-03-01

Many devices, such as tablets, smartphones, notebooks, fixed and portable navigation systems are used on a (nearly) daily basis, both in in- and outdoor environments. It is often argued that contextual factors, such as the ambient illuminance in relation to characteristics of the display (e.g., surface treatment, screen reflectance, display luminance …) may have a strong influence on the use of such devices and corresponding user experiences. However, the current understanding of these influence factors is still rather limited. In this work, we therefore focus in particular on the impact of lighting and display luminance on readability, visual performance, subjective experience and preference. A controlled lab study (N=18) with a within-subjects design was performed to evaluate two car displays (one glossy and one matte display) in conditions that simulate bright outdoor lighting conditions. Four ambient luminance levels and three display luminance settings were combined into 7 experimental conditions. More concretely, we investigated for each display: (1) whether and how readability and visual performance varied with the different combinations of ambient luminance and display luminance and (2) whether and how they influenced the subjective experience (through self-reported valence, annoyance, visual fatigue) and preference. The results indicate a limited, yet negative influence of increased ambient luminance and reduced contrast on visual performance and readability for both displays. Similarly, we found that the self-reported valence decreases and annoyance and visual fatigue increase as the contrast ratio decreases and ambient luminance increases. Overall, the impact is clearer for the matte display than for the glossy display.

The well-coordinated linkage between acidogenicity and aciduricity via insoluble glucans on the surface of Streptococcus mutans

PubMed Central

Guo, Lihong; McLean, Jeffrey S.; Lux, Renate; He, Xuesong; Shi, Wenyuan

2015-01-01

Streptococcus mutans is considered the principal cariogenic bacterium for dental caries. Despite the recognition of their importance for cariogenesis, the possible coordination among S. mutans’ main virulence factors, including glucan production, acidogenicity and aciduricity, has been less well studied. In the present study, using S. mutans strains with surface-displayed pH-sensitive pHluorin, we revealed sucrose availability- and Gtf functionality-dependent proton accumulation on S. mutans surface. Consistent with this, using a pH-sensitive dye, we demonstrated that both in vivo cell-produced and in vitro enzymatically synthesized insoluble glucans displayed proton-concentrating ability. Global transcriptomics revealed proton accumulation triggers the up-regulation of genes encoding functions involved in acid tolerance response in a glucan-dependent manner. Our data suggested that this proton enrichment around S. mutans could pre-condition the bacterium for acid-stress. Consistent with this hypothesis, we found S. mutans strains defective in glucan production were more acid sensitive. Our study revealed for the first time that insoluble glucans is likely an essential factor linking acidogenicity with aciduricity. The coordination of these key virulence factors could provide new insights on how S. mutans may have become a major cariogenic pathogen. PMID:26657939

Spatial noise and threshold contrasts in LCD displays

NASA Astrophysics Data System (ADS)

Roehrig, Hans; Krupinski, Elizabeth A.; Chawla, Amarpreet S.; Fan, Jiahua; Gandhi, Kunal

2003-05-01

This paper presents the results of initial physical and psycho-physical evaluations of the noise of high resolution LCDs. 5 LCDs were involved, having 4 different pixel structures. Spatial as well as temporal noise was physically measured with the aid of a high-performance CCD camera. Human contrast sensitivity in the presence of spatial noise was determined psycho-physically using periodic stimuli (square-wave patterns) as well as aperiodic stimuli (squares). For the measurements of the human contrast sensitivity, all LCDs were calibrated to the DICOM 14 Grayscale Standard Display Function (GSDF). The results demonstrate that spatial noise is the dominant noise in all LCDs, while temporal noise is insignificant and plays only a minor part. The magnitude of spatial noise of LCDs is in the range between that of CRTs with a P104 and that of CRTs with a P45. Of particular importance with respect to LCD noise is the contribution of the pixel structure to the Noise Power Spectrum, which shows up as sharp spikes at spatial frequencies beyond the LCDs" Nyquist frequency. The paper does not offer any clues about the importance of these spikes on the human contrast sensitivity.

Issues in symbol design for electronic displays of navigation information

DOT National Transportation Integrated Search

2004-10-24

An increasing number of electronic displays, ranging from small hand-held displays for general aviation to installed displays for air transport, are showing navigation information, such as symbols representing navigational aids. The wide range of dis...

Mitochondrial-related gene expression changes are sensitive to agonal-pH state: implications for brain disorders

PubMed Central

Vawter, MP; Tomita, H; Meng, F; Bolstad, B; Li, J; Evans, S; Choudary, P; Atz, M; Shao, L; Neal, C; Walsh, DM; Burmeister, M; Speed, T; Myers, R; Jones, EG; Watson, SJ; Akil, H; Bunney, WE

2010-01-01

Mitochondrial defects in gene expression have been implicated in the pathophysiology of bipolar disorder and schizophrenia. We have now contrasted control brains with low pH versus high pH and showed that 28% of genes in mitochondrial-related pathways meet criteria for differential expression. A majority of genes in the mitochondrial, chaperone and proteasome pathways of nuclear DNA-encoded gene expression were decreased with decreased brain pH, whereas a majority of genes in the apoptotic and reactive oxygen stress pathways showed an increased gene expression with a decreased brain pH. There was a significant increase in mitochondrial DNA copy number and mitochondrial DNA gene expression with increased agonal duration. To minimize effects of agonal-pH state on mood disorder comparisons, two classic approaches were used, removing all subjects with low pH and agonal factors from analysis, or grouping low and high pH as a separate variable. Three groups of potential candidate genes emerged that may be mood disorder related: (a) genes that showed no sensitivity to pH but were differentially expressed in bipolar disorder or major depressive disorder; (b) genes that were altered by agonal-pH in one direction but altered in mood disorder in the opposite direction to agonal-pH and (c) genes with agonal-pH sensitivity that displayed the same direction of changes in mood disorder. Genes from these categories such as NR4A1 and HSPA2 were confirmed with Q-PCR. The interpretation of postmortem brain studies involving broad mitochondrial gene expression and related pathway alterations must be monitored against the strong effect of agonal-pH state. Genes with the least sensitivity to agonal-pH could present a starting point for candidate gene search in neuropsychiatric disorders. PMID:16636682

The Impact of Electronic Knowledge-Based Nursing Content and Decision-Support on Nursing-Sensitive Patient Outcomes

DTIC Science & Technology

2016-02-01

other provision of law, no person shall be subject to any penalty for failing to comply with a collection of information if it does not display a ...Based Nursing (KBN) innovation, a customized design featuring actionable EB recommendations embedded into policy and the content and CDS tools in the...will have a positive effect on nursing knowledge, use of evidence-based practices, and the achievement of nurse-sensitive patient outcomes at

Forecast of Remote Underwater Sensing Technology.

DTIC Science & Technology

1980-07-01

hr T. MAGNETICS (2 Replies) Q. What will be sensitivities of fluxgate , proton, optical pump, SQUID (superconducting) magnetometers ? A. Fluxgate 0.1...ft Oujtpuit Analog, digital and B3CD Cost $65.K 227 Manu factu rer EG&G Geometric Unit G-806M System Marine Search Proton Magnetometer Sensitivity...optional) Depth Range 0 to 100 m or 6000 m Precision +0.15% FS Time Constant 60 ms Output Digital display, analog and digital BCD output Cost $13.K 243

The Effects of Exposure Time, Pressure and Cold on Hand Skin Temperature and Manual Performance When Wearing Three-Fingered Neoprene Gloves

DTIC Science & Technology

2008-04-01

summarised below. Grip strength was measured using a hand grip dynamometer. Tactile sensitivity was measured using modified (enlarged) Braille ...characters. Subjects had to sense and identify the Braille characters by touch using a visual display of Braille characters as a reference source... Braille characters were presented on a board in 4 rows, with each row having progressively smaller character size and spacing. Tactile sensitivity score

A new pH-sensitive rectifying potassium channel in mitochondria from the embryonic rat hippocampus.

PubMed

Kajma, Anna; Szewczyk, Adam

2012-10-01

Patch-clamp single-channel studies on mitochondria isolated from embryonic rat hippocampus revealed the presence of two different potassium ion channels: a large-conductance (288±4pS) calcium-activated potassium channel and second potassium channel with outwardly rectifying activity under symmetric conditions (150/150mM KCl). At positive voltages, this channel displayed a conductance of 67.84pS and a strong voltage dependence at holding potentials from -80mV to +80mV. The open probability was higher at positive than at negative voltages. Patch-clamp studies at the mitoplast-attached mode showed that the channel was not sensitive to activators and inhibitors of mitochondrial potassium channels but was regulated by pH. Moreover, we demonstrated that the channel activity was not affected by the application of lidocaine, an inhibitor of two-pore domain potassium channels, or by tertiapin, an inhibitor of inwardly rectifying potassium channels. In summary, based on the single-channel recordings, we characterised for the first time mitochondrial pH-sensitive ion channel that is selective for cations, permeable to potassium ions, displays voltage sensitivity and does not correspond to any previously described potassium ion channels in the inner mitochondrial membrane. This article is part of a Special Issue entitled: 17th European Bioenergetics Conference (EBEC 2012). Copyright © 2012 Elsevier B.V. All rights reserved.

Telomere attrition and genomic instability in xeroderma pigmentosum type-b deficient fibroblasts under oxidative stress

PubMed Central

Ting, Aloysius Poh Leong; Low, Grace Kah Mun; Gopalakrishnan, Kalpana; Hande, M Prakash

2010-01-01

Abstract Xeroderma pigmentosum B (XPB/ERCC3/p89) is an ATP-dependent 3′→5′ directed DNA helicase involved in basal RNA transcription and the nucleotide excision repair (NER) pathway. While the role of NER in alleviating oxidative DNA damage has been acknowledged it remains poorly understood. To study the involvement of XPB in repair of oxidative DNA damage, we utilized primary fibroblasts from a patient suffering from XP with Cockayne syndrome and hydrogen peroxide (H2O2) to induce oxidative stress. Mutant cells retained higher viability and cell cycle dysfunction after H2O2 exposure. Cytokinesis blocked micronucleus assay revealed increased genome instability induced by H2O2. Single cell gel electrophoresis (comet) assay showed that the missense mutation caused a reduced repair capacity for oxidative DNA damage. Mutant fibroblasts also displayed decreased population doubling rate, increased telomere attrition rate and early emergence of senescent characteristics under chronic low dose exposure to H2O2. Fibroblasts from a heterozygous individual displayed intermediate traits in some assays and normal traits in others, indicating possible copy number dependence. The results show that a deficiency in functional XPB paradoxically renders cells more sensitive to the genotoxic effects of oxidative stress while reducing the cytotoxic effects. These findings have implications in the mechanisms of DNA repair, mutagenesis and carcinogenesis and ageing in normal physiological systems. PMID:19840190

Clinicopathologic characteristics of light chain proximal tubulopathy with light chain inclusions involving multiple renal cell types
.

PubMed

Li, Xiaomei; Xu, Feng; Liang, Dandan; Liang, Shaoshan; Zhu, Xiaodong; Zhang, Mingchao; Huang, Xianghua; Liu, Zhihong; Zeng, Caihong

2018-02-01

Light chain proximal tubulopathy (LCPT) associated with plasma cell dyscrasias is a rare abnormality, especially cases involving multiple cell types. The aim of this study is to explore the characteristics and outcomes of these diseases. We comprehensively evaluated the clinical-pathological data, treatment, and outcomes of 6 LCPT patients with involvement of multiple cell types. In 3 cases, we found that the inclusions largely existed in tubular cells, while in 2 cases they coexisted in podocytes and tubular cells, and in 1 case they coexisted in histiocytes and tubular cells. The stain features and appearances of inclusions were specific and varied. Five patients displayed κ-light chains with crystal formation, while 1 patient displayed a λ subtype with increased lysosomes instead of crystals. Six patients presented with proteinuria, 4 with renal insufficiency, and 4 with complete or partial Fanconi syndrome. Our findings indicate that tubular cells are the most common location of cytoplasmic inclusions. Cases with κ-light chain storage are more common than λ, and the formation of crystals may be associated with the subtype of light chains. Immunoelectron microscopy could be used to increase sensitivity for the detection and location of monoclonal light chains. Therefore, these patients have some common clinical features with varied pathologic characteristics and prognoses but the same subtype of light chains.
.

Multiple Genetic Mechanisms Contribute to Visual Sensitivity Variation in the Labridae

PubMed Central

Phillips, Genevieve A.C.; Carleton, Karen L.; Marshall, N. Justin

2016-01-01

Coral reefs are one of the most spectrally diverse environments, both in terms of habitat and animal color. Species identity, sex, and camouflage are drivers of the phenotypic diversity seen in coral reef fishes, but how the phenotypic diversity is reflected in the genotype remains to be answered. The labrids are a large, polyphyletic family of coral reef fishes that display a diverse range of colors, including developmental color morphs and extensive behavioral ecologies. Here, we assess the opsin sequence and expression diversity among labrids from the Great Barrier Reef, Australia. We found that labrids express a diverse palette of visual opsins, with gene duplications in both RH2 and LWS genes. The majority of opsins expressed were within the mid-to-long wavelength sensitive classes (RH2 and LWS). Three of the labrid species expressed SWS1 (ultra-violet sensitive) opsins with the majority expressing the violet-sensitive SWS2B gene and none expressing SWS2A. We used knowledge about spectral tuning sites to calculate approximate spectral sensitivities (λmax) for individual species’ visual pigments, which corresponded well with previously published λmax values for closely related species (SWS1: 356–370 nm; SWS2B: 421–451 nm; RH2B: 452–492 nm; RH2A: 516–528 nm; LWS1: 554–555 nm; LWS2: 561–562 nm). In contrast to the phenotypic diversity displayed via color patterns and feeding ecology, there was little amino acid diversity within the known opsin sequence tuning sites. However, gene duplications and differential expression provide alternative mechanisms for tuning visual pigments, resulting in variable visual sensitivities among labrid species. PMID:26464127

Metabolomics from the Lab to the Field: Lessons Learned Along the Way

EPA Science Inventory

Use of metabolomics in laboratory studies for chemical toxicity evaluation is fast becoming an established technique in environmental science, displaying excellent sensitivity, physiological relevance, and providing valuable information regarding toxic mode(s)-of-action. These qu...

77 FR 37879 - 36(b)(1) Arms Sales Notification

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-25

... provide greater security for its critical oil and natural gas infrastructure, and significant national... survivability equipment, displays, and sensors. The airframe itself does not contain sensitive technology...), Electro-Optic Missile Sensors (EOMSs), and Sequencer and Improved Countermeasures Dispenser (ICMD). The...

Development of Relative Disparity Sensitivity in Human Visual Cortex.

PubMed

Norcia, Anthony M; Gerhard, Holly E; Meredith, Wesley J

2017-06-07

Stereopsis is the primary cue underlying our ability to make fine depth judgments. In adults, depth discriminations are supported largely by relative rather than absolute binocular disparity, and depth is perceived primarily for horizontal rather than vertical disparities. Although human infants begin to exhibit disparity-specific responses between 3 and 5 months of age, it is not known how relative disparity mechanisms develop. Here we show that the specialization for relative disparity is highly immature in 4- to 6-month-old infants but is adult-like in 4- to 7-year-old children. Disparity-tuning functions for horizontal and vertical disparities were measured using the visual evoked potential. Infant relative disparity thresholds, unlike those of adults, were equal for vertical and horizontal disparities. Their horizontal disparity thresholds were a factor of ∼10 higher than adults, but their vertical disparity thresholds differed by a factor of only ∼4. Horizontal relative disparity thresholds for 4- to 7-year-old children were comparable with those of adults at ∼0.5 arcmin. To test whether infant immaturity was due to spatial limitations or insensitivity to interocular correlation, highly suprathreshold horizontal and vertical disparities were presented in alternate regions of the display, and the interocular correlation of the interdigitated regions was varied from 0% to 100%. This manipulation regulated the availability of coarse-scale relative disparity cues. Adult and infant responses both increased with increasing interocular correlation by similar magnitudes, but adult responses increased much more for horizontal disparities, further evidence for qualitatively immature stereopsis based on relative disparity at 4-6 months of age. SIGNIFICANCE STATEMENT Stereopsis, our ability to sense depth from horizontal image disparity, is among the finest spatial discriminations made by the primate visual system. Fine stereoscopic depth discriminations depend critically on comparisons of disparity relationships in the image that are supported by relative disparity cues rather than the estimation of single, absolute disparities. Very young human and macaque infants are sensitive to absolute disparity, but no previous study has specifically studied the development of relative disparity sensitivity, a hallmark feature of adult stereopsis. Here, using high-density EEG recordings, we show that 4- to 6-month-old infants display both quantitative and qualitative response immaturities for relative disparity information. Relative disparity responses are adult-like no later than 4-7 years of age. Copyright © 2017 the authors 0270-6474/17/375608-12$15.00/0.

Display-based communications for advanced transport aircraft

NASA Technical Reports Server (NTRS)

Lee, Alfred T.

1989-01-01

The next generation of civil transport aircraft will depend increasingly upon ground-air-ground and satellite data link for information critical to safe and efficient air transportation. Previous studies which examined the concept of display-based communications in addition to, or in lieu of, conventional voice transmissions are reviewed. A full-mission flight simulation comparing voice and display-based communication modes in an advanced transport aircraft is also described. The results indicate that a display-based mode of information transfer does not result in significantly increased aircrew workload, but does result in substantially increased message acknowledgment times when compared to conventional voice transmissions. User acceptance of the display-based communication system was generally high, replicating the findings of previous studies. However, most pilots tested expressed concern over the potential loss of information available from frequency monitoring which might result from the introduction of discrete address communications. Concern was expressed by some pilots for the reduced time available to search for conflicting traffic when using the communications display system. The implications of the findings for the design of display-based communications are discussed.

Sensitive detection of maltose and glucose based on dual enzyme-displayed bacteria electrochemical biosensor.

PubMed

Liu, Aihua; Lang, Qiaolin; Liang, Bo; Shi, Jianguo

2017-01-15

Glucoamylase-displayed bacteria (GA-bacteria) and glucose dehydrogenase-displayed bacteria (GDH-bacteria) were co-immobilized on multi-walled carbon nanotubes (MWNTs) modified glassy carbon electrode (GCE) to construct GA-bacteria/GDH-bacteria/MWNTs/GCE biosensor. The biosensor was developed by optimizing the loading amount and the ratio of GA-bacteria to GDH-bacteria. The as-prepared biosensor exhibited a wide dynamic range of 0.2-10mM and a low detection limit of 0.1mM maltose (S/N=3). The biosensor also had a linear response to glucose in the range of 0.1-2.0mM and a low detection limit of 0.04mM glucose (S/N=3). Interestingly, at the same concentration, glucose was 3.75-fold sensitive than that of maltose at the proposed biosensor. No interferences were observed for other possible mono- and disaccharides. The biosensor also demonstrated good long-term storage stability and repeatability. Further, using both GDH-bacteria/MWNTs/GCE biosensor and GA-bacteria/GDH-bacteria/MWNTs/GCE biosensor, glucose and maltose in real samples can be detected. Therefore, the proposed biosensor is capable of monitoring the food manufacturing and fermentation process. Copyright © 2016 Elsevier B.V. All rights reserved.

Forward/up directional incompatibilities during cursor placement within graphical user interfaces.

PubMed

Phillips, James G; Triggs, Thomas J; Meehan, James W

2005-05-15

Within graphical user interfaces, an indirect relationship between display and control may lead to directional incompatibilities when a forward mouse movement codes upward cursor motions. However, this should not occur for left/right movements or direct cursor controllers (e.g. touch sensitive screens). In a four-choice reaction time task, 12 participants performed movements from a central start location to a target situated at one of four cardinal points (top, bottom, left, right). A 2 x 2 x 2 design varied directness of controller (moving cursor on computer screen or pen on graphics tablet), compatibility of orientation of cursor controller with screen (horizontal or vertical) and axis of desired cursor motion (left/right or up/down). Incompatibility between orientation of controller and motion of cursor did not affect response latencies, possibly because both forward and upward movements are away from the midline and go up the visual field. However, directional incompatibilities between display and controller led to slower movement with prolonged accelerative phases. Indirect relationships between display and control led to less efficient movements with prolonged decelerative phases and a tendency to undershoot movements along the bottom/top axis. More direct cursor control devices, such as touch sensitive screens, should enhance the efficiency of aspects of cursor trajectories.

Direct expression and validation of phage-selected peptide variants in mammalian cells.

PubMed

Quinlan, Brian D; Gardner, Matthew R; Joshi, Vinita R; Chiang, Jessica J; Farzan, Michael

2013-06-28

Phage display is a key technology for the identification and maturation of high affinity peptides, antibodies, and other proteins. However, limitations of bacterial expression restrict the range and sensitivity of assays that can be used to evaluate phage-selected variants. To address this problem, selected genes are typically transferred to mammalian expression vectors, a major rate-limiting step in the iterative improvement of peptides and proteins. Here we describe a system that combines phage display and efficient mammalian expression in a single vector, pDQ1. This system permits immediate expression of phage-selected genes as IgG1-Fc fusions in mammalian cells, facilitating the rapid, sensitive characterization of a large number of library outputs for their biochemical and functional properties. We demonstrate the utility of this system by improving the ability of a CD4-mimetic peptide to bind the HIV-1 envelope glycoprotein and neutralize HIV-1 entry. We further improved the potency of the resulting peptide, CD4mim6, by limiting its ability to induce the CD4-bound conformation of the envelope glycoprotein. Thus, CD4mim6 and its variants can be used to investigate the properties of the HIV-1 envelope glycoprotein, and pDQ1 can accelerate the discovery of new peptides and proteins through phage display.

2-aminoimidazoles potentiate ß-lactam antimicrobial activity against Mycobacterium tuberculosis by reducing ß-lactamase secretion and increasing cell envelope permeability

PubMed Central

Obregón-Henao, Andrés; Ackart, David F.; Podell, Brendan K.; Belardinelli, Juan M.; Jackson, Mary; Nguyen, Tuan V.; Blackledge, Meghan S.; Melander, Roberta J.; Melander, Christian; Johnson, Benjamin K.; Abramovitch, Robert B.

2017-01-01

There is an urgent need to develop new drug treatment strategies to control the global spread of drug-sensitive and multidrug-resistant Mycobacterium tuberculosis (M. tuberculosis). The ß-lactam class of antibiotics is among the safest and most widely prescribed antibiotics, but they are not effective against M. tuberculosis due to intrinsic resistance. This study shows that 2-aminoimidazole (2-AI)-based small molecules potentiate ß-lactam antibiotics against M. tuberculosis. Active 2-AI compounds significantly reduced the minimal inhibitory and bactericidal concentrations of ß-lactams by increasing M. tuberculosis cell envelope permeability and decreasing protein secretion including ß-lactamase. Metabolic labeling and transcriptional profiling experiments revealed that 2-AI compounds impair mycolic acid biosynthesis, export and linkage to the mycobacterial envelope, counteracting an important defense mechanism reducing permeability to external agents. Additionally, other important constituents of the M. tuberculosis outer membrane including sulfolipid-1 and polyacyltrehalose were also less abundant in 2-AI treated bacilli. As a consequence of 2-AI treatment, M. tuberculosis displayed increased sensitivity to SDS, increased permeability to nucleic acid staining dyes, and rapid binding of cell wall targeting antibiotics. Transcriptional profiling analysis further confirmed that 2-AI induces transcriptional regulators associated with cell envelope stress. 2-AI based small molecules potentiate the antimicrobial activity of ß-lactams by a mechanism that is distinct from specific inhibitors of ß-lactamase activity and therefore may have value as an adjunctive anti-TB treatment. PMID:28749949

Playing a first-person shooter video game induces neuroplastic change.

PubMed

Wu, Sijing; Cheng, Cho Kin; Feng, Jing; D'Angelo, Lisa; Alain, Claude; Spence, Ian

2012-06-01

Playing a first-person shooter (FPS) video game alters the neural processes that support spatial selective attention. Our experiment establishes a causal relationship between playing an FPS game and neuroplastic change. Twenty-five participants completed an attentional visual field task while we measured ERPs before and after playing an FPS video game for a cumulative total of 10 hr. Early visual ERPs sensitive to bottom-up attentional processes were little affected by video game playing for only 10 hr. However, participants who played the FPS video game and also showed the greatest improvement on the attentional visual field task displayed increased amplitudes in the later visual ERPs. These potentials are thought to index top-down enhancement of spatial selective attention via increased inhibition of distractors. Individual variations in learning were observed, and these differences show that not all video game players benefit equally, either behaviorally or in terms of neural change.

Quantum Google in a Complex Network

PubMed Central

Paparo, Giuseppe Davide; Müller, Markus; Comellas, Francesc; Martin-Delgado, Miguel Angel

2013-01-01

We investigate the behaviour of the recently proposed Quantum PageRank algorithm, in large complex networks. We find that the algorithm is able to univocally reveal the underlying topology of the network and to identify and order the most relevant nodes. Furthermore, it is capable to clearly highlight the structure of secondary hubs and to resolve the degeneracy in importance of the low lying part of the list of rankings. The quantum algorithm displays an increased stability with respect to a variation of the damping parameter, present in the Google algorithm, and a more clearly pronounced power-law behaviour in the distribution of importance, as compared to the classical algorithm. We test the performance and confirm the listed features by applying it to real world examples from the WWW. Finally, we raise and partially address whether the increased sensitivity of the quantum algorithm persists under coordinated attacks in scale-free and random networks. PMID:24091980

Practical holography III; Proceedings of the Meeting, Los Angeles, CA, Jan. 17, 18, 1989

NASA Astrophysics Data System (ADS)

Benton, Stephen A.

Various papers on practical holography are presented. Individual topics addressed include: design of large format commercial display holograms, design of a one-step full-color holographic recording system, color reflection holography, full color rainbow hologram using a photoresist plate, secondary effects in processing holograms, archival properties of holograms, survey of properties of volume holographic materials, image stability of DMP-128 holograms, activation monitor for DMP-128, microwave drying effects on dichromated gelatin holograms, sensitization process of dichromated gelatin, holographic optics for vision systems, holographic fingerprint sensor, cross-talk and cross-coupling in multiplexed holographic gratings, compact illuminators for transmission holograms, solar holoconcentrators in dichromated grains, three-dimensional display of scientific data, holographic liquid crystal displays, in situ swelling for hologaphic color control.