Display analysis with the optimal control model of the human operator. [pilot-vehicle display interface and information processing

NASA Technical Reports Server (NTRS)

Baron, S.; Levison, W. H.

1977-01-01

Application of the optimal control model of the human operator to problems in display analysis is discussed. Those aspects of the model pertaining to the operator-display interface and to operator information processing are reviewed and discussed. The techniques are then applied to the analysis of advanced display/control systems for a Terminal Configured Vehicle. Model results are compared with those obtained in a large, fixed-base simulation.

Probing Tumor Microenvironment With In Vivo Phage Display

DTIC Science & Technology

2014-10-01

C). (C) Dot plots showing mCherry expression on the X axis and fibroblast activation protein ( FAP ) or rabbit isotype control staining in the Y...by flow cytometry-based cell sorting using an antibody against fibroblast activation protein ( FAP ). During the optimization steps, flow cytometry...expression of αvβ3 and αvβ5 integrins, neuropilin-1 (NRP-1), and fibroblast activation protein ( FAP ) in hb6011 CAFs was analyzed by flow cytometry

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

PubMed

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

2011-06-01

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

The hubris hypothesis: The downside of comparative optimism displays.

PubMed

Hoorens, Vera; Van Damme, Carolien; Helweg-Larsen, Marie; Sedikides, Constantine

2017-04-01

According to the hubris hypothesis, observers respond more unfavorably to individuals who express their positive self-views comparatively than to those who express their positive self-views non-comparatively, because observers infer that the former hold a more disparaging view of others and particularly of observers. Two experiments extended the hubris hypothesis in the domain of optimism. Observers attributed less warmth (but not less competence) to, and showed less interest in affiliating with, an individual displaying comparative optimism (the belief that one's future will be better than others' future) than with an individual displaying absolute optimism (the belief that one's future will be good). Observers responded differently to individuals displaying comparative versus absolute optimism, because they inferred that the former held a gloomier view of the observers' future. Consistent with previous research, observers still attributed more positive traits to a comparative or absolute optimist than to a comparative or absolute pessimist. Copyright © 2016. Published by Elsevier Inc.

A novel lentiviral scFv display library for rapid optimization and selection of high affinity antibodies.

PubMed

Qudsia, Sehar; Merugu, Siva B; Mangukiya, Hitesh B; Hema, Negi; Wu, Zhenghua; Li, Dawei

2018-04-30

Antibody display libraries have become a popular technique to screen monoclonal antibodies for therapeutic purposes. An important aspect of display technology is to generate an optimization library by changing antibody affinity to antigen through mutagenesis and screening the high affinity antibody. In this study, we report a novel lentivirus display based optimization library antibody in which Agtuzumab scFv is displayed on cell membrane of HEK-293T cells. To generate an optimization library, hotspot mutagenesis was performed to achieve diverse antibody library. Based on sequence analysis of randomly selected clones, library size was estimated approximately to be 1.6 × 10 6 . Lentivirus display vector was used to display scFv antibody on cell surface and flow cytometery was performed to check the antibody affinity to antigen. Membrane bound scFv antibodies were then converted to secreted antibody through cre/loxP recombination. One of the mutant clones, M8 showed higher affinity to antigen in flow cytometery analysis. Further characterization of cellular and secreted scFv through western blot showed that antibody affinity was increased by three fold after mutagenesis. This study shows successful construction of a novel antibody library and suggests that hotspot mutagenesis could prove a useful and rapid optimization tool to generate similar libraries with various degree of antigen affinity. Copyright © 2018 Elsevier Inc. All rights reserved.

Information Presentation

NASA Technical Reports Server (NTRS)

Holden, Kritina; Sandor, A.; Thompson, S. G.; McCann, R. S.; Kaiser, M. K.; Begault, D. R.; Adelstein, B. D.; Beutter, B. R.; Stone, L. S.

2008-01-01

The goal of the Information Presentation Directed Research Project (DRP) is to address design questions related to the presentation of information to the crew on flight vehicles, surface landers and habitats, and during extra-vehicular activities (EVA). Designers of displays and controls for exploration missions must be prepared to select the text formats, label styles, alarms, electronic procedure designs, and cursor control devices that provide for optimal crew performance on exploration tasks. The major areas of work, or subtasks, within the Information Presentation DRP are: 1) Controls, 2) Displays, 3) Procedures, and 4) EVA Operations.

Noise tolerant illumination optimization applied to display devices

NASA Astrophysics Data System (ADS)

Cassarly, William J.; Irving, Bruce

2005-02-01

Display devices have historically been designed through an iterative process using numerous hardware prototypes. This process is effective but the number of iterations is limited by the time and cost to make the prototypes. In recent years, virtual prototyping using illumination software modeling tools has replaced many of the hardware prototypes. Typically, the designer specifies the design parameters, builds the software model, predicts the performance using a Monte Carlo simulation, and uses the performance results to repeat this process until an acceptable design is obtained. What is highly desired, and now possible, is to use illumination optimization to automate the design process. Illumination optimization provides the ability to explore a wider range of design options while also providing improved performance. Since Monte Carlo simulations are often used to calculate the system performance but those predictions have statistical uncertainty, the use of noise tolerant optimization algorithms is important. The use of noise tolerant illumination optimization is demonstrated by considering display device designs that extract light using 2D paint patterns as well as 3D textured surfaces. A hybrid optimization approach that combines a mesh feedback optimization with a classical optimizer is demonstrated. Displays with LED sources and cold cathode fluorescent lamps are considered.

Cationic Biomimetic Particles of Polystyrene/Cationic Bilayer/Gramicidin for Optimal Bactericidal Activity.

PubMed

Xavier, Gabriel R S; Carmona-Ribeiro, Ana M

2017-12-02

Nanostructured particles of polystyrene sulfate (PSS) covered by a cationic lipid bilayer of dioctadecyldimethylammonium bromide (DODAB) incorporated gramicidin D (Gr) yielding optimal and broadened bactericidal activity against both Escherichia coli and Staphylococcus aureus . The adsorption of DODAB/Gr bilayer onto PSS nanoparticles (NPs) increased the zeta-average diameter by 8-10 nm, changed the zeta-potential of the NPs from negative to positive, and yielded a narrow size distributions for the PSS/DODAB/Gr NPs, which displayed broad and maximal microbicidal activity at very small concentrations of the antimicrobials, namely, 0.057 and 0.0057 mM DODAB and Gr, respectively. The results emphasized the advantages of highly-organized, nanostructured, and cationic particles to achieve hybrid combinations of antimicrobials with broad spectrum activity at considerably reduced DODAB and Gr concentrations.

Isolation and characterization of two serine proteases from metagenomic libraries of the Gobi and Death Valley deserts.

PubMed

Neveu, Julie; Regeard, Christophe; DuBow, Michael S

2011-08-01

The screening of environmental DNA metagenome libraries for functional activities can provide an important source of new molecules and enzymes. In this study, we identified 17 potential protease-producing clones from two metagenomic libraries derived from samples of surface sand from the Gobi and Death Valley deserts. Two of the proteases, DV1 and M30, were purified and biochemically examined. These two proteases displayed a molecular mass of 41.5 kDa and 45.7 kDa, respectively, on SDS polyacrylamide gels. Alignments with known protease sequences showed less than 55% amino acid sequence identity. These two serine proteases appear to belong to the subtilisin (S8A) family and displayed several unique biochemical properties. Protease DV1 had an optimum pH of 8 and an optimal activity at 55°C, while protease M30 had an optimum pH >11 and optimal activity at 40°C. The properties of these enzymes make them potentially useful for biotechnological applications and again demonstrate that metagenomic approaches can be useful, especially when coupled with the study of novel environments such as deserts.

Image quality affected by diffraction of aperture structure arrangement in transparent active-matrix organic light-emitting diode displays.

PubMed

Tsai, Yu-Hsiang; Huang, Mao-Hsiu; Jeng, Wei-de; Huang, Ting-Wei; Lo, Kuo-Lung; Ou-Yang, Mang

2015-10-01

Transparent display is one of the main technologies in next-generation displays, especially for augmented reality applications. An aperture structure is attached on each display pixel to partition them into transparent and black regions. However, diffraction blurs caused by the aperture structure typically degrade the transparent image when the light from a background object passes through finite aperture window. In this paper, the diffraction effect of an active-matrix organic light-emitting diode display (AMOLED) is studied. Several aperture structures have been proposed and implemented. Based on theoretical analysis and simulation, the appropriate aperture structure will effectively reduce the blur. The analysis data are also consistent with the experimental results. Compared with the various transparent aperture structure on AMOLED, diffraction width (zero energy position of diffraction pattern) of the optimize aperture structure can be reduced 63% and 31% in the x and y directions in CASE 3. Associated with a lenticular lens on the aperture structure, the improvement could reach to 77% and 54% of diffraction width in the x and y directions. Modulation transfer function and practical images are provided to evaluate the improvement of image blurs.

Neural Mechanisms Underlying Visual Short-Term Memory Gain for Temporally Distinct Objects.

PubMed

Ihssen, Niklas; Linden, David E J; Miller, Claire E; Shapiro, Kimron L

2015-08-01

Recent research has shown that visual short-term memory (VSTM) can substantially be improved when the to-be-remembered objects are split in 2 half-arrays (i.e., sequenced) or the entire array is shown twice (i.e., repeated), rather than presented simultaneously. Here we investigate the hypothesis that sequencing and repeating displays overcomes attentional "bottlenecks" during simultaneous encoding. Using functional magnetic resonance imaging, we show that sequencing and repeating displays increased brain activation in extrastriate and primary visual areas, relative to simultaneous displays (Study 1). Passively viewing identical stimuli did not increase visual activation (Study 2), ruling out a physical confound. Importantly, areas of the frontoparietal attention network showed increased activation in repetition but not in sequential trials. This dissociation suggests that repeating a display increases attentional control by allowing attention to be reallocated in a second encoding episode. In contrast, sequencing the array poses fewer demands on control, with competition from nonattended objects being reduced by the half-arrays. This idea was corroborated by a third study in which we found optimal VSTM for sequential displays minimizing attentional demands. Importantly these results provide support within the same experimental paradigm for the role of stimulus-driven and top-down attentional control aspects of biased competition theory in setting constraints on VSTM. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Structural Optimizations of Thieno[3,2-b]pyrrole Derivatives for the Development of Metabolically Stable Inhibitors of Chikungunya Virus.

PubMed

Ching, Kuan-Chieh; Tran, Thi Ngoc Quy; Amrun, Siti Naqiah; Kam, Yiu-Wing; Ng, Lisa F P; Chai, Christina L L

2017-04-13

Chikungunya virus (CHIKV) is a re-emerging vector-borne alphavirus, and there is no approved effective antiviral treatment currently available for CHIKV. We previously reported the discovery of thieno[3,2-b]pyrrole 1b that displayed good antiviral activity against CHIKV infection in vitro. However, it has a short half-life in the presence of human liver microsomes (HLMs) (T 1/2 = 2.91 min). Herein, we report further optimization studies in which potential metabolically labile sites on compound 1b were removed or modified, resulting in the identification of thieno[3,2-b]pyrrole 20 and pyrrolo[2,3-d]thiazole 23c possessing up to 17-fold increase in metabolic half-lives in HLMs and good in vivo pharmacokinetic properties. Compound 20 not only attenuated viral RNA production and displayed broad-spectrum antiviral activity against other alphaviruses and CHIKV isolates but also exhibited limited cytotoxic liability (CC 50 > 100 μM). These studies have identified two compounds that have the potential for further development as antiviral drugs against CHIKV infection.

Using Optimization to Improve Test Planning

DTIC Science & Technology

2017-09-01

friendly and to display the output differently, the test and evaluation test schedule optimization model would be a good tool for the test and... evaluation schedulers. 14. SUBJECT TERMS schedule optimization, test planning 15. NUMBER OF PAGES 223 16. PRICE CODE 17. SECURITY CLASSIFICATION OF...make the input more user-friendly and to display the output differently, the test and evaluation test schedule optimization model would be a good tool

Optimal front light design for reflective displays under different ambient illumination

NASA Astrophysics Data System (ADS)

Wang, Sheng-Po; Chang, Ting-Ting; Li, Chien-Ju; Bai, Yi-Ho; Hu, Kuo-Jui

2011-01-01

The goal of this study is to find out the optimal luminance and color temperature of front light for reflective displays in different ambient illumination by conducting series of psychophysical experiments. A color and brightness tunable front light device with ten LED units was built and been calibrated to present 256 luminance levels and 13 different color temperature at fixed luminance of 200 cd/m2. The experiment results revealed the best luminance and color temperature settings for human observers under different ambient illuminant, which could also assist the e-paper manufacturers to design front light device, and present the best image quality on reflective displays. Furthermore, a similar experiment procedure was conducted by utilizing new flexible e-signage display developed by ITRI and an optimal front light device for the new display panel has been designed and utilized.

Characterization of lignocellulolytic activities from fungi isolated from the deep-sea sponge Stelletta normani.

PubMed

Batista-García, Ramón Alberto; Sutton, Thomas; Jackson, Stephen A; Tovar-Herrera, Omar Eduardo; Balcázar-López, Edgar; Sánchez-Carbente, María Del Rayo; Sánchez-Reyes, Ayixon; Dobson, Alan D W; Folch-Mallol, Jorge Luis

2017-01-01

Extreme habitats have usually been regarded as a source of microorganisms that possess robust proteins that help enable them to survive in such harsh conditions. The deep sea can be considered an extreme habitat due to low temperatures (<5°C) and high pressure, however marine sponges survive in these habitats. While bacteria derived from deep-sea marine sponges have been studied, much less information is available on fungal biodiversity associated with these sponges. Following screening of fourteen fungi isolated from the deep-sea sponge Stelletta normani sampled at a depth of 751 metres, three halotolerant strains (TS2, TS11 and TS12) were identified which displayed high CMCase and xylanase activities. Molecular based taxonomic approaches identified these strains as Cadophora sp. TS2, Emericellopsis sp. TS11 and Pseudogymnoascus sp. TS 12. These three fungi displayed psychrotolerance and halotolerant growth on CMC and xylan as sole carbon sources, with optimal growth rates at 20°C. They produced CMCase and xylanase activities, which displayed optimal temperature and pH values of between 50-70°C and pH 5-8 respectively, together with good thermostability and halotolerance. In solid-state fermentations TS2, TS11 and TS12 produced CMCases, xylanases and peroxidase/phenol oxidases when grown on corn stover and wheat straw. This is the first time that CMCase, xylanase and peroxidase/phenol oxidase activities have been reported in these three fungal genera isolated from a marine sponge. Given the biochemical characteristics of these ligninolytic enzymes it is likely that they may prove useful in future biomass conversion strategies involving lignocellulosic materials.

Characterization of lignocellulolytic activities from fungi isolated from the deep-sea sponge Stelletta normani

PubMed Central

Batista-García, Ramón Alberto; Sutton, Thomas; Jackson, Stephen A.; Tovar-Herrera, Omar Eduardo; Balcázar-López, Edgar; Sánchez-Carbente, María del Rayo; Sánchez-Reyes, Ayixon; Dobson, Alan D. W.

2017-01-01

Extreme habitats have usually been regarded as a source of microorganisms that possess robust proteins that help enable them to survive in such harsh conditions. The deep sea can be considered an extreme habitat due to low temperatures (<5°C) and high pressure, however marine sponges survive in these habitats. While bacteria derived from deep-sea marine sponges have been studied, much less information is available on fungal biodiversity associated with these sponges. Following screening of fourteen fungi isolated from the deep-sea sponge Stelletta normani sampled at a depth of 751 metres, three halotolerant strains (TS2, TS11 and TS12) were identified which displayed high CMCase and xylanase activities. Molecular based taxonomic approaches identified these strains as Cadophora sp. TS2, Emericellopsis sp. TS11 and Pseudogymnoascus sp. TS 12. These three fungi displayed psychrotolerance and halotolerant growth on CMC and xylan as sole carbon sources, with optimal growth rates at 20°C. They produced CMCase and xylanase activities, which displayed optimal temperature and pH values of between 50–70°C and pH 5–8 respectively, together with good thermostability and halotolerance. In solid-state fermentations TS2, TS11 and TS12 produced CMCases, xylanases and peroxidase/phenol oxidases when grown on corn stover and wheat straw. This is the first time that CMCase, xylanase and peroxidase/phenol oxidase activities have been reported in these three fungal genera isolated from a marine sponge. Given the biochemical characteristics of these ligninolytic enzymes it is likely that they may prove useful in future biomass conversion strategies involving lignocellulosic materials. PMID:28339473

Improving the intrinsic electrocatalytic hydrogen evolution activity of few-layer NiPS3 by cobalt doping.

PubMed

Li, Kai; Rakov, Dmitrii; Zhang, Wei; Xu, Ping

2017-07-18

Here we demonstrate the improvement of the intrinsic electrocatalytic hydrogen evolution activity of NiPS 3 by proper cobalt doping. The optimized Ni 0.95 Co 0.05 PS 3 nanosheets display a geometric catalytic current density of -10 mA cm -2 at an overpotential of 71 mV vs. RHE and a Tafel slope of 77 mV dec -1 in 1.0 M KOH.

Discovery and Optimization of Allosteric Inhibitors of Mutant Isocitrate Dehydrogenase 1 (R132H IDH1) Displaying Activity in Human Acute Myeloid Leukemia Cells.

PubMed

Jones, Stuart; Ahmet, Jonathan; Ayton, Kelly; Ball, Matthew; Cockerill, Mark; Fairweather, Emma; Hamilton, Nicola; Harper, Paul; Hitchin, James; Jordan, Allan; Levy, Colin; Lopez, Ruth; McKenzie, Eddie; Packer, Martin; Plant, Darren; Simpson, Iain; Simpson, Peter; Sinclair, Ian; Somervaille, Tim C P; Small, Helen; Spencer, Gary J; Thomson, Graeme; Tonge, Michael; Waddell, Ian; Walsh, Jarrod; Waszkowycz, Bohdan; Wigglesworth, Mark; Wiseman, Daniel H; Ogilvie, Donald

2016-12-22

A collaborative high throughput screen of 1.35 million compounds against mutant (R132H) isocitrate dehydrogenase IDH1 led to the identification of a novel series of inhibitors. Elucidation of the bound ligand crystal structure showed that the inhibitors exhibited a novel binding mode in a previously identified allosteric site of IDH1 (R132H). This information guided the optimization of the series yielding submicromolar enzyme inhibitors with promising cellular activity. Encouragingly, one compound from this series was found to induce myeloid differentiation in primary human IDH1 R132H AML cells in vitro.

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

PubMed

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

2009-03-25

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

Lead Optimization Studies of Cinnamic Amide EP2 Antagonists

PubMed Central

2015-01-01

Prostanoid receptor EP2 can play a proinflammatory role, exacerbating disease pathology in a variety of central nervous system and peripheral diseases. A highly selective EP2 antagonist could be useful as a drug to mitigate the inflammatory consequences of EP2 activation. We recently identified a cinnamic amide class of EP2 antagonists. The lead compound in this class (5d) displays anti-inflammatory and neuroprotective actions. However, this compound exhibited moderate selectivity to EP2 over the DP1 prostanoid receptor (∼10-fold) and low aqueous solubility. We now report compounds that display up to 180-fold selectivity against DP1 and up to 9-fold higher aqueous solubility than our previous lead. The newly developed compounds also display higher selectivity against EP4 and IP receptors and a comparable plasma pharmacokinetics. Thus, these compounds are useful for proof of concept studies in a variety of models where EP2 activation is playing a deleterious role. PMID:24773616

Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques.

PubMed

Borggren, Marie; Vinner, Lasse; Andresen, Betina Skovgaard; Grevstad, Berit; Repits, Johanna; Melchers, Mark; Elvang, Tara Laura; Sanders, Rogier W; Martinon, Frédéric; Dereuddre-Bosquet, Nathalie; Bowles, Emma Joanne; Stewart-Jones, Guillaume; Biswas, Priscilla; Scarlatti, Gabriella; Jansson, Marianne; Heyndrickx, Leo; Grand, Roger Le; Fomsgaard, Anders

2013-07-19

HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb). We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques.

Optimization of HIV-1 Envelope DNA Vaccine Candidates within Three Different Animal Models, Guinea Pigs, Rabbits and Cynomolgus Macaques

PubMed Central

Borggren, Marie; Vinner, Lasse; Andresen, Betina Skovgaard; Grevstad, Berit; Repits, Johanna; Melchers, Mark; Elvang, Tara Laura; Sanders, Rogier W; Martinon, Frédéric; Dereuddre-Bosquet, Nathalie; Bowles, Emma Joanne; Stewart-Jones, Guillaume; Biswas, Priscilla; Scarlatti, Gabriella; Jansson, Marianne; Heyndrickx, Leo; Le Grand, Roger; Fomsgaard, Anders

2013-01-01

HIV-1 DNA vaccines have many advantageous features. Evaluation of HIV-1 vaccine candidates often starts in small animal models before macaque and human trials. Here, we selected and optimized DNA vaccine candidates through systematic testing in rabbits for the induction of broadly neutralizing antibodies (bNAb). We compared three different animal models: guinea pigs, rabbits and cynomolgus macaques. Envelope genes from the prototype isolate HIV-1 Bx08 and two elite neutralizers were included. Codon-optimized genes, encoded secreted gp140 or membrane bound gp150, were modified for expression of stabilized soluble trimer gene products, and delivered individually or mixed. Specific IgG after repeated i.d. inoculations with electroporation confirmed in vivo expression and immunogenicity. Evaluations of rabbits and guinea pigs displayed similar results. The superior DNA construct in rabbits was a trivalent mix of non-modified codon-optimized gp140 envelope genes. Despite NAb responses with some potency and breadth in guinea pigs and rabbits, the DNA vaccinated macaques displayed less bNAb activity. It was concluded that a trivalent mix of non-modified gp140 genes from rationally selected clinical isolates was, in this study, the best option to induce high and broad NAb in the rabbit model, but this optimization does not directly translate into similar responses in cynomolgus macaques. PMID:26344115

Optimizing density patterns to achieve desired light extraction for displays

NASA Astrophysics Data System (ADS)

Davenport, T. L. R.; Cassarly, W. J.

2007-01-01

In displays such as backlights and signage, it is often desirable to produce a particular spatial luminance distribution of light. This work demonstrates an iterative optimization technique for determining the density of light extractors required to produce desired luminance distributions.

Alteration of white-rot basidiomycetes cellulase and xylanase activities in the submerged co-cultivation and optimization of enzyme production by Irpex lacteus and Schizophyllum commune.

PubMed

Metreveli, Eka; Kachlishvili, Eva; Singer, Steven W; Elisashvili, Vladimir

2017-10-01

Mono and dual cultures of four white-rot basidiomycete species were evaluated for cellulase and xylanase activity under submerged fermentation conditions. Co-cultivation of Pycnoporus coccineus or Trametes hirsuta with Schizophyllum commune displayed antagonistic interactions resulting in the decrease of endoglucanase and total cellulase activities. In contrast, increases in cellulase and xylanase activity were revealed through the compatible interactions of Irpex lacteus with S. commune. Co-cultivation conditions were optimized for maximum enzyme production by I. lacteus and S. commune, the best producers of cellulase/xylanase and β-glucosidase, respectively. An optimized medium for the target enzyme production by the mixed culture was established in a laboratory fermenter yielding 7U/mL total cellulase, 142U/mL endoglucanase, 104U/mL xylanase, and 5.2U/mL β-glucosidase. The dual culture approach resulted in an enzymatic mixture with 11% improved lignocellulose saccharification potential compared to enzymes from a monoculture of I. lacteus. Copyright © 2017 Elsevier Ltd. All rights reserved.

A dual host vector for Fab phage display and expression of native IgG in mammalian cells.

PubMed

Tesar, Devin; Hötzel, Isidro

2013-10-01

A significant bottleneck in antibody discovery by phage display is the transfer of immunoglobulin variable regions from phage clones to vectors that express immunoglobulin G (IgG) in mammalian cells for screening. Here, we describe a novel phagemid vector for Fab phage display that allows expression of native IgG in mammalian cells without sub-cloning. The vector uses an optimized mammalian signal sequence that drives robust expression of Fab fragments fused to an M13 phage coat protein in Escherichia coli and IgG expression in mammalian cells. To allow the expression of Fab fragments fused to a phage coat protein in E.coli and full-length IgG in mammalian cells from the same vector without sub-cloning, the sequence encoding the phage coat protein was embedded in an optimized synthetic intron within the immunoglobulin heavy chain gene. This intron is removed from transcripts in mammalian cells by RNA splicing. Using this vector, we constructed a synthetic Fab phage display library with diversity in the heavy chain only and selected for clones binding different antigens. Co-transfection of mammalian cells with DNA from individual phage clones and a plasmid expressing the invariant light chain resulted in the expression of native IgG that was used to assay affinity, ligand blocking activity and specificity.

Proposed evaluation framework for assessing operator performance with multisensor displays

NASA Technical Reports Server (NTRS)

Foyle, David C.

1992-01-01

Despite aggressive work on the development of sensor fusion algorithms and techniques, no formal evaluation procedures have been proposed. Based on existing integration models in the literature, an evaluation framework is developed to assess an operator's ability to use multisensor, or sensor fusion, displays. The proposed evaluation framework for evaluating the operator's ability to use such systems is a normative approach: The operator's performance with the sensor fusion display can be compared to the models' predictions based on the operator's performance when viewing the original sensor displays prior to fusion. This allows for the determination as to when a sensor fusion system leads to: 1) poorer performance than one of the original sensor displays (clearly an undesirable system in which the fused sensor system causes some distortion or interference); 2) better performance than with either single sensor system alone, but at a sub-optimal (compared to the model predictions) level; 3) optimal performance (compared to model predictions); or, 4) super-optimal performance, which may occur if the operator were able to use some highly diagnostic 'emergent features' in the sensor fusion display, which were unavailable in the original sensor displays. An experiment demonstrating the usefulness of the proposed evaluation framework is discussed.

Optimization of reading conditions for flat panel displays.

PubMed

Thomas, J A; Chakrabarti, K; Kaczmarek, R V; Maslennikov, A; Mitchell, C A; Romanyukha, A

2006-06-01

Task Group 18 (TG 18) of the American Association of Physicists in Medicine has developed guidelines for Assessment of Display Performance for Medical Imaging Systems. In this document, a method for determination of the maximum room lighting for displays is suggested. It is based on luminance measurements of a black target displayed on each display device at different room illuminance levels. Linear extrapolation of the above luminance measurements vs. room illuminance allows one to determine diffuse and specular reflection coefficients. TG 18 guidelines have established recommended maximum room lighting. It is based on the characterization of the display by its minimum and maximum luminance and the description of room by diffuse and specular coefficients. We carried out these luminance measurements for three selected displays to determine their optimum viewing conditions: one cathode ray tube and two flat panels. We found some problems with the application of the TG 18 guidelines to optimize viewing conditions for IBM T221 flat panels. Introduction of the requirement for minimum room illuminance allows a more accurate determination of the optimal viewing conditions (maximum and minimum room illuminance) for IBM flat panels. It also addresses the possible loss of contrast in medical images on flat panel displays because of the effect of nonlinearity in the dependence of luminance on room illuminance at low room lighting.

Highly Constrained Bicyclic Scaffolds for the Discovery of Protease-Stable Peptides via mRNA Display.

PubMed

Hacker, David E; Hoinka, Jan; Iqbal, Emil S; Przytycka, Teresa M; Hartman, Matthew C T

2017-03-17

Highly constrained peptides such as the knotted peptide natural products are promising medicinal agents because of their impressive biostability and potent activity. Yet, libraries of highly constrained peptides are challenging to prepare. Here, we present a method which utilizes two robust, orthogonal chemical steps to create highly constrained bicyclic peptide libraries. This technology was optimized to be compatible with in vitro selections by mRNA display. We performed side-by-side monocyclic and bicyclic selections against a model protein (streptavidin). Both selections resulted in peptides with mid-nanomolar affinity, and the bicyclic selection yielded a peptide with remarkable protease resistance.

Sensor fusion display evaluation using information integration models in enhanced/synthetic vision applications

NASA Technical Reports Server (NTRS)

Foyle, David C.

1993-01-01

Based on existing integration models in the psychological literature, an evaluation framework is developed to assess sensor fusion displays as might be implemented in an enhanced/synthetic vision system. The proposed evaluation framework for evaluating the operator's ability to use such systems is a normative approach: The pilot's performance with the sensor fusion image is compared to models' predictions based on the pilot's performance when viewing the original component sensor images prior to fusion. This allows for the determination as to when a sensor fusion system leads to: poorer performance than one of the original sensor displays, clearly an undesirable system in which the fused sensor system causes some distortion or interference; better performance than with either single sensor system alone, but at a sub-optimal level compared to model predictions; optimal performance compared to model predictions; or, super-optimal performance, which may occur if the operator were able to use some highly diagnostic 'emergent features' in the sensor fusion display, which were unavailable in the original sensor displays.

Control strategies for planetary rover motion and manipulator control

NASA Technical Reports Server (NTRS)

Trautwein, W.

1973-01-01

An unusual insect-like vehicle designed for planetary surface exploration is made the occasion for a discussion of control concepts in path selection, hazard detection, obstacle negotiation, and soil sampling. A control scheme which actively articulates the pitching motion between a single-loop front module and a dual loop rear module leads to near optimal behavior in soft soil; at the same time the vehicle's front module acts as a reliable tactile forward probe with a detection range much longer than the stopping distance. Some optimal control strategies are discussed, and the photos of a working scale model are displayed.

Optimization of electro-optical parameters of LCD for advertising systems

NASA Astrophysics Data System (ADS)

Olifierczuk, Marek; Zielinski, Jerzy; Klosowicz, Stanislaw J.

1998-02-01

The analysis of the optimization of negative image twisted nematic LCD is presented. Theoretical considerations are confirmed by experimental results. The effect of material parameters and technology on the contrast ratio and display dynamics is given. The effect in TN display with black dye is presented.

Selection of full-length IgGs by tandem display on filamentous phage particles and Escherichia coli fluorescence-activated cell sorting screening.

PubMed

Mazor, Yariv; Van Blarcom, Thomas; Carroll, Sean; Georgiou, George

2010-05-01

Phage display of antibody libraries is a powerful tool for antibody discovery and evolution. Recombinant antibodies have been displayed on phage particles as scFvs or Fabs, and more recently as bivalent F(ab')(2). We recently developed a technology (E-clonal) for screening of combinatorial IgG libraries using bacterial periplasmic display and selection by fluorescence-activated cell sorting (FACS) [Mazor Y et al. (2007) Nat Biotechnol 25, 563-565]. Although, as a single-cell analysis technique, FACS is very powerful, especially for the isolation of high-affinity binders, even with state of the art instrumentation the screening of libraries with diversity > 10(8) is technically challenging. We report here a system that takes advantage of display of full-length IgGs on filamentous phage particles as a prescreening step to reduce library size and enable subsequent rounds of FACS screening in Escherichia coli. For the establishment of an IgG phage display system, we utilized phagemid-encoded IgG with the fUSE5-ZZ phage as a helper phage. These phage particles display the Fc-binding ZZ protein on all copies of the phage p3 coat protein, and are exploited as both helper phages and anchoring surfaces for the soluble IgG. We demonstrate that tandem phage selection followed by FACS allows the selection of a highly diversified profile of binders from antibody libraries without undersampling, and at the same time capitalizes on the advantages of FACS for real-time monitoring and optimization of the screening process.

Recent progress in low-voltage cathodoluminescent materials: synthesis, improvement and emission properties.

PubMed

Li, Guogang; Lin, Jun

2014-01-01

Nowadays there are several technologies used for flat panel displays (FPDs) and the development of FPDs with enhanced energy efficiency and improved display quality is strongly required. Field emission displays (FEDs) have been considered as one of the most promising next generation flat panel display technologies due to their excellent display performance and low energy consumption. For the development of FEDs, phosphors are irreplaceable components. In the past decade, the study of highly efficient low-voltage cathodoluminescent materials, namely FED phosphors, has become the focus of enhancing energy efficiency and realizing high-quality displays. This review summaries the recent progress in the chemical synthesis and improvement of novel, rare-earth and transition metal ions activated inorganic cathodoluminescent materials in powder and thin film forms. The discussion is focused on the modification of morphology, size, surface, composition and conductivity of phosphors and the corresponding effects on their cathodoluminescent properties. Special emphases are given to the selection of host and luminescent centers, the adjustment of emission colors through doping concentration optimization, energy transfer and mono- or co-doping activator ions, the improvement of chromaticity, color stability and color gamut as well as the saturation behavior and the degradation behavior of phosphors under the excitation of a low-voltage electron beam. Finally, the research prospects and future directions of FED phosphors are discussed with recommendations to facilitate the further study of new and highly efficient low-voltage cathodoluminescent materials.

Analysis of the viewing zone of the Cambridge autostereoscopic display.

PubMed

Dodgson, N A

1996-04-01

The Cambridge autostereoscopic three-dimensional display is a time-multiplexed device that gives both stereo and movement parallax to the viewer without the need for any special glasses. This analysis derives the size and position of the fully illuminated, and hence useful, viewing zone for a Cambridge display. The viewing zone of such a display is shown to be completely determined by four parameters: the width of the screen, the optimal distance of the viewer from the screen, the width over which an image can be seen across the whole screen at this optimal distance, and the number of views. A display's viewing zone can thus be completely described without reference to the internal implementation of the device. An equation that describes what the eye sees from any position in front of the display is derived. The equations derived can be used in both the analysis and design of this type of time-multiplexed autostereoscopic display.

Synthesis of chiral chloroquine and its analogues as antimalarial agents.

PubMed

Sinha, Manish; Dola, Vasanth R; Soni, Awakash; Agarwal, Pooja; Srivastava, Kumkum; Haq, Wahajul; Puri, Sunil K; Katti, Seturam B

2014-11-01

In this investigation, we describe a new approach to chiral synthesis of chloroquine and its analogues. All tested compounds displayed potent activity against chloroquine sensitive as well as chloroquine resistant strains of Plasmodium falciparum in vitro and Plasmodium yoelii in vivo. Compounds S-13 b, S-13c, S-13 d and S-13 i displayed excellent in vitro antimalarial activity with an IC50 value of 56.82, 60.41, 21.82 and 7.94 nM, respectively, in the case of resistant strain. Furthermore, compounds S-13a, S-13c and S-13 d showed in vivo suppression of 100% parasitaemia on day 4 in the mouse model against Plasmodium yoelii when administered orally. These results underscore the application of synthetic methodology and need for further lead optimization. Copyright © 2014 Elsevier Ltd. All rights reserved.

Novel inhibitors of HIV discovered among existing classes of pharmaceutical compounds indicated for unrelated clinical indications.

PubMed

Kucherov, I I; Rytik, P G; Podol'skaya, I A; Mistryukova, L O; Korjev, M O

2009-01-01

In vitro screening of 307 drugs with various clinical indications (cardiotropic, neurotropic, antibacterial, etc.) has revealed 6 compounds which displayed remarkable antiretroviral activity. Three of these drugs had a tendency to have undesirable side effects and were thus excluded from further consideration. Remaining three, i.e., Xantinol Nicotinate, Tardiferon, and Trental may become valid candidates for inclusion into antiviral regimens such as HAART. In vitro tests have shown that xantinol and trental display synergistic effect with azidothymidine, inhibit the replication AZT-resistant strains of HIV, and have no competing undesirable activities. These compounds should be evaluated in safety studies to determine optimal doses for patients with HIV. If these studies confirm in vitro results these compounds may become valid candidates as safe and affordable means to be added into the arsenal of antiretroviral drugs.

Dyes for displays

NASA Astrophysics Data System (ADS)

Claussen, U.

1984-01-01

The improvement of contrast and visibility of LCD by two different means was undertaken. The two methods are: (1) development of fluorescent dyes to increase the visibility of fluorescent activated displays (FLAD); and (2) development of dichroic dyes to increase the contrast of displays. This work was done in close cooperation with the electronic industry, where the newly synthesized dyes were tested. The targets for the chemical synthesis were selected with the help of computer model calculations. A marketable range of dyes was developed. Since the interest of the electronic industries concerning FLAD was low, the investigations were stopped. Dichroic dyes, especially black mixtures with good light fastness, order parameter, and solubility in nematic phases were developed. The application of these dyes is restricted to indoor use because of an increase of viscosity below -10 C. Applications on a technical scale, e.g., for the automotive industry, will be possible if the displays work at temperatures down to -40 C. This problem requires a complex optimization of the dye/nematic phase system.

Assessing the consequences of unrealistic optimism: Challenges and recommendations.

PubMed

Shepperd, James A; Pogge, Gabrielle; Howell, Jennifer L

2017-04-01

Of the hundreds of studies published on unrealistic optimism (i.e., expecting a better personal future than is reasonably likely), most have focused on demonstrating the phenomenon, examining boundary conditions, or documenting causes. Few studies have examined the consequences of unrealistic optimism. In this article, we provide an overview of the measurement of unrealistic optimism, review possible consequences, and identify numerous challenges confronting investigators attempting to understand the consequences. Assessing the consequences of unrealistic optimism is tricky, and ultimately probably impossible when researchers assess unrealistic optimism at the group level (which reveals if a group of people is displaying unrealistic optimism on average) rather than the individual level (which reveals whether a specific individual displays unrealistic optimism). We offer recommendations to researchers who wish to examine the consequences of unrealistic optimism. Copyright © 2016 Elsevier Inc. All rights reserved.

Design of activated serine-containing catalytic triads with atomic level accuracy

PubMed Central

Rajagopalan, Sridharan; Wang, Chu; Yu, Kai; Kuzin, Alexandre P.; Richter, Florian; Lew, Scott; Miklos, Aleksandr E.; Matthews, Megan L.; Seetharaman, Jayaraman; Su, Min; Hunt, John. F.; Cravatt, Benjamin F.; Baker, David

2014-01-01

A challenge in the computational design of enzymes is that multiple properties must be simultaneously optimized -- substrate-binding, transition state stabilization, and product release -- and this has limited the absolute activity of successful designs. Here, we focus on a single critical property of many enzymes: the nucleophilicity of an active site residue that initiates catalysis. We design proteins with idealized serine-containing catalytic triads, and assess their nucleophilicity directly in native biological systems using activity-based organophosphate probes. Crystal structures of the most successful designs show unprecedented agreement with computational models, including extensive hydrogen bonding networks between the catalytic triad (or quartet) residues, and mutagenesis experiments demonstrate that these networks are critical for serine activation and organophosphate-reactivity. Following optimization by yeast-display, the designs react with organophosphate probes at rates comparable to natural serine hydrolases. Co-crystal structures with diisopropyl fluorophosphate bound to the serine nucleophile suggest the designs could provide the basis for a new class of organophosphate captures agents. PMID:24705591

Cell Surface Expression of Bacterial Esterase A by Saccharomyces cerevisiae and Its Enhancement by Constitutive Activation of the Cellular Unfolded Protein Response▿ †

PubMed Central

Breinig, Frank; Diehl, Björn; Rau, Sabrina; Zimmer, Christian; Schwab, Helmut; Schmitt, Manfred J.

2006-01-01

Yeast cell surface display is a powerful tool for expression and immobilization of biocatalytically active proteins on a unicellular eukaryote. Here bacterial carboxylesterase EstA from Burkholderia gladioli was covalently anchored into the cell wall of Saccharomyces cerevisiae by in-frame fusion to the endogenous yeast proteins Kre1p, Cwp2p, and Flo1p. When p-nitrophenyl acetate was used as a substrate, the esterase specific activities of yeast expressing the protein fusions were 103 mU mg−1 protein for Kre1/EstA/Cwp2p and 72 mU mg−1 protein for Kre1/EstA/Flo1p. In vivo cell wall targeting was confirmed by esterase solubilization after laminarinase treatment and immunofluorescence microscopy. EstA expression resulted in cell wall-associated esterase activities of 2.72 U mg−1 protein for Kre1/EstA/Cwp2p and 1.27 U mg−1 protein for Kre1/EstA/Flo1p. Furthermore, esterase display on the yeast cell surface enabled the cells to effectively grow on the esterase-dependent carbon source glycerol triacetate (Triacetin). In the case of Kre1/EstA/Flo1p, in vivo maturation within the yeast secretory pathway and final incorporation into the wall were further enhanced when there was constitutive activation of the unfolded protein response pathway. Our results demonstrate that esterase cell surface display in yeast, which, as shown here, is remarkably more effective than EstA surface display in Escherichia coli, can be further optimized by activating the protein folding machinery in the eukaryotic secretion pathway. PMID:16980424

Cell surface expression of bacterial esterase A by Saccharomyces cerevisiae and its enhancement by constitutive activation of the cellular unfolded protein response.

PubMed

Breinig, Frank; Diehl, Björn; Rau, Sabrina; Zimmer, Christian; Schwab, Helmut; Schmitt, Manfred J

2006-11-01

Yeast cell surface display is a powerful tool for expression and immobilization of biocatalytically active proteins on a unicellular eukaryote. Here bacterial carboxylesterase EstA from Burkholderia gladioli was covalently anchored into the cell wall of Saccharomyces cerevisiae by in-frame fusion to the endogenous yeast proteins Kre1p, Cwp2p, and Flo1p. When p-nitrophenyl acetate was used as a substrate, the esterase specific activities of yeast expressing the protein fusions were 103 mU mg(-1) protein for Kre1/EstA/Cwp2p and 72 mU mg(-1) protein for Kre1/EstA/Flo1p. In vivo cell wall targeting was confirmed by esterase solubilization after laminarinase treatment and immunofluorescence microscopy. EstA expression resulted in cell wall-associated esterase activities of 2.72 U mg(-1) protein for Kre1/EstA/Cwp2p and 1.27 U mg(-1) protein for Kre1/EstA/Flo1p. Furthermore, esterase display on the yeast cell surface enabled the cells to effectively grow on the esterase-dependent carbon source glycerol triacetate (Triacetin). In the case of Kre1/EstA/Flo1p, in vivo maturation within the yeast secretory pathway and final incorporation into the wall were further enhanced when there was constitutive activation of the unfolded protein response pathway. Our results demonstrate that esterase cell surface display in yeast, which, as shown here, is remarkably more effective than EstA surface display in Escherichia coli, can be further optimized by activating the protein folding machinery in the eukaryotic secretion pathway.

Display/control requirements for automated VTOL aircraft

NASA Technical Reports Server (NTRS)

Hoffman, W. C.; Kleinman, D. L.; Young, L. R.

1976-01-01

A systematic design methodology for pilot displays in advanced commercial VTOL aircraft was developed and refined. The analyst is provided with a step-by-step procedure for conducting conceptual display/control configurations evaluations for simultaneous monitoring and control pilot tasks. The approach consists of three phases: formulation of information requirements, configuration evaluation, and system selection. Both the monitoring and control performance models are based upon the optimal control model of the human operator. Extensions to the conventional optimal control model required in the display design methodology include explicit optimization of control/monitoring attention; simultaneous monitoring and control performance predictions; and indifference threshold effects. The methodology was applied to NASA's experimental CH-47 helicopter in support of the VALT program. The CH-47 application examined the system performance of six flight conditions. Four candidate configurations are suggested for evaluation in pilot-in-the-loop simulations and eventual flight tests.

Optimizing visual comfort for stereoscopic 3D display based on color-plus-depth signals.

PubMed

Shao, Feng; Jiang, Qiuping; Fu, Randi; Yu, Mei; Jiang, Gangyi

2016-05-30

Visual comfort is a long-facing problem in stereoscopic 3D (S3D) display. In this paper, targeting to produce S3D content based on color-plus-depth signals, a general framework for depth mapping to optimize visual comfort for S3D display is proposed. The main motivation of this work is to remap the depth range of color-plus-depth signals to a new depth range that is suitable to comfortable S3D display. Towards this end, we first remap the depth range globally based on the adjusted zero disparity plane, and then present a two-stage global and local depth optimization solution to solve the visual comfort problem. The remapped depth map is used to generate the S3D output. We demonstrate the power of our approach on perceptually uncomfortable and comfortable stereoscopic images.

Optimizing Cognitive Load for Learning from Computer-Based Science Simulations

ERIC Educational Resources Information Center

Lee, Hyunjeong; Plass, Jan L.; Homer, Bruce D.

2006-01-01

How can cognitive load in visual displays of computer simulations be optimized? Middle-school chemistry students (N = 257) learned with a simulation of the ideal gas law. Visual complexity was manipulated by separating the display of the simulations in two screens (low complexity) or presenting all information on one screen (high complexity). The…

The thermophilic biomass-degrading fungus Thielavia terrestris Co3Bag1 produces a hyperthermophilic and thermostable β-1,4-xylanase with exo- and endo-activity.

PubMed

García-Huante, Yolanda; Cayetano-Cruz, Maribel; Santiago-Hernández, Alejandro; Cano-Ramírez, Claudia; Marsch-Moreno, Rodolfo; Campos, Jorge E; Aguilar-Osorio, Guillermo; Benitez-Cardoza, Claudia G; Trejo-Estrada, Sergio; Hidalgo-Lara, María Eugenia

2017-01-01

A hyperthermophilic and thermostable xylanase of 82 kDa (TtXynA) was purified from the culture supernatant of T. terrestris Co3Bag1, grown on carboxymethyl cellulose (CMC), and characterized biochemically. TtXynA showed optimal xylanolytic activity at pH 5.5 and at 85 °C, and retained more than 90% of its activity at a broad pH range (4.5-10). The enzyme is highly thermostable with a half-life of 23.1 days at 65 °C, and active in the presence of several metal ions. Circular dichroism spectra strongly suggest the enzyme gains secondary structures when temperature increases. TtXynA displayed higher substrate affinity and higher catalytic efficiency towards beechwood xylan than towards birchwood xylan, oat-spelt xylan, and CMC. According to its final hydrolysis products, TtXynA displays endo-/exo-activity, yielded xylobiose, an unknown oligosaccharide containing about five residues of xylose and a small amount of xylose on beechwood xylan. Finally, this report represents the description of the first fungal hyperthermophilic xylanase which is produced by T. terrestris Co3Bag1. Since TtXynA displays relevant biochemical properties, it may be a suitable candidate for biotechnological applications carried out at high temperatures, like the enzymatic pretreatment of plant biomass for the production of bioethanol.

Systemic study of solvent-assisted active loading of gambogic acid into liposomes and its formulation optimization for improved delivery.

PubMed

Tang, Wei-Lun; Tang, Wei-Hsin; Szeitz, Andras; Kulkarni, Jayesh; Cullis, Pieter; Li, Shyh-Dar

2018-06-01

The solvent-assisted active loading technology (SALT) was developed for encapsulating a water insoluble weak base into the liposomal core in the presence of 5% DMSO. In this study, we further examined the effect of various water miscible solvents in promoting active loading of other types of drugs into liposomes. To achieve complete drug loading, the amount of solvent required must result in complete drug solubilization and membrane permeability enhancement, but must be below the threshold that induces liposomal aggregation or causes bilayer disruption. We then used the SALT to load gambogic acid (GA, an insoluble model drug that shows promising anticancer effect) into liposomes, and optimized the loading gradient and lipid composition to prepare a stable formulation (Lipo-GA) that displayed >95% drug retention after incubation with serum for 3 days. Lipo-GA contained a high drug-to-lipid ratio of 1/5 (w/w) with a mean particle size of ∼75 nm. It also displayed a prolonged circulation half-life (1.5 h vs. 18.6 h) and enhanced antitumor activity in two syngeneic mice models compared to free GA. Particularly, complete tumor regression was observed in the EMT6 tumor model for 14 d with significant inhibition of multiple oncogenes including HIF-1α, VEGF-A, STAT3, BCL-2, and NF-κB. Copyright © 2018 Elsevier Ltd. All rights reserved.

Biotechnology and genetic engineering in the new drug development. Part III. Biocatalysis, metabolic engineering and molecular modelling.

PubMed

Stryjewska, Agnieszka; Kiepura, Katarzyna; Librowski, Tadeusz; Lochyński, Stanisław

2013-01-01

Industrial biotechnology has been defined as the use and application of biotechnology for the sustainable processing and production of chemicals, materials and fuels. It makes use of biocatalysts such as microbial communities, whole-cell microorganisms or purified enzymes. In the review these processes are described. Drug design is an iterative process which begins when a chemist identifies a compound that displays an interesting biological profile and ends when both the activity profile and the chemical synthesis of the new chemical entity are optimized. Traditional approaches to drug discovery rely on a stepwise synthesis and screening program for large numbers of compounds to optimize activity profiles. Over the past ten to twenty years, scientists have used computer models of new chemical entities to help define activity profiles, geometries and relativities. This article introduces inter alia the concepts of molecular modelling and contains references for further reading.

Optimization of culture conditions and medium composition for the production of micrococcin GO5 by Micrococcus sp. GO5.

PubMed

Kim, Mi-Hee; Kong, Yoon-Jung; Baek, Hong; Hyun, Hyung-Hwan

2006-01-02

To enhance the production of micrococcin GO5, a bacteriocin produced by Micrococcus sp. GO5, cultivation conditions and medium composition were optimized. The optimal initial pH and temperature for bacteriocin production were 7.0-9.0 and 37 degrees C, respectively. Micrococcus sp. GO5 displayed the highest micrococcin GO5 activity when grown in modified MRS medium that contained lactose or sucrose, rather than glucose, as a carbon source. The maximum bacteriocin activity was obtained in modified MRS medium containing 0.5% tryptone and 1.0% yeast extract as nitrogen sources instead of the other nitrogen sources present in MRS medium. Bacteriocin production was greatly affected by the concentration of K(2)HPO(4); strain GO5 produced eight-fold more bacteriocin in medium containing 2.0-2.5% K(2)HPO(4) than in medium containing 0.2% K(2)HPO(4). The optimal concentration of MgSO(4).7H(2)O for bacteriocin production was 0.5%. The production of micrococcin GO5 was increased 32-fold in shake flask culture and 16-fold in a bioreactor using the optimized medium (TY medium), compared with culturing in MRS medium.

Techniques for optimizing human-machine information transfer related to real-time interactive display systems

NASA Technical Reports Server (NTRS)

Granaas, Michael M.; Rhea, Donald C.

1989-01-01

The requirements for the development of real-time displays are reviewed. Of particular interest are the psychological aspects of design such as the layout, color selection, real-time response rate, and the interactivity of displays. Some existing Western Aeronautical Test Range displays are analyzed.

Differential Gene Expression of Longan Under Simulated Acid Rain Stress.

PubMed

Zheng, Shan; Pan, Tengfei; Ma, Cuilan; Qiu, Dongliang

2017-05-01

Differential gene expression profile was studied in Dimocarpus longan Lour. in response to treatments of simulated acid rain with pH 2.5, 3.5, and a control (pH 5.6) using differential display reverse transcription polymerase chain reaction (DDRT-PCR). Results showed that mRNA differential display conditions were optimized to find an expressed sequence tag (EST) related with acid rain stress. The potential encoding products had 80% similarity with a transcription initiation factor IIF of Gossypium raimondii and 81% similarity with a protein product of Theobroma cacao. This fragment is the transcription factor activated by second messenger substances in longan leaves after signal perception of acid rain.

Interactive Display of Surfaces Using Subdivision Surfaces and Wavelets

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

Duchaineau, M A; Bertram, M; Porumbescu, S

2001-10-03

Complex surfaces and solids are produced by large-scale modeling and simulation activities in a variety of disciplines. Productive interaction with these simulations requires that these surfaces or solids be viewable at interactive rates--yet many of these surfaced solids can contain hundreds of millions of polygondpolyhedra. Interactive display of these objects requires compression techniques to minimize storage, and fast view-dependent triangulation techniques to drive the graphics hardware. In this paper, we review recent advances in subdivision-surface wavelet compression and optimization that can be used to provide a framework for both compression and triangulation. These techniques can be used to produce suitablemore » approximations of complex surfaces of arbitrary topology, and can be used to determine suitable triangulations for display. The techniques can be used in a variety of applications in computer graphics, computer animation and visualization.« less

Peripheral androgen receptors sustain the acrobatics and fine motor skill of elaborate male courtship.

PubMed

Fuxjager, Matthew J; Longpre, Kristy M; Chew, Jennifer G; Fusani, Leonida; Schlinger, Barney A

2013-09-01

Androgenic hormones regulate many aspects of animal social behavior, including the elaborate display routines on which many species rely for advertisement and competition. One way that this might occur is through peripheral effects of androgens, particularly on skeletal muscles that control complex movements and postures of the body and its limbs. However, the specific contribution of peripheral androgen-muscle interactions to the performance of elaborate behavioral displays in the natural world has never been examined. We study this issue in one of the only natural physiological models of animal acrobatics: the golden-collared manakin (Manacus vitellinus). In this tropical bird, males compete with each other and court females by producing firecracker-like wing- snaps and by rapidly dancing among saplings over the forest floor. To test how activation of peripheral androgen receptors (AR) influences this display, we treat reproductively active adult male birds with the peripherally selective antiandrogen bicalutamide (BICAL) and observe the effects of this manipulation on male display performance. We not only validate the peripheral specificity of BICAL in this species, but we also show that BICAL treatment reduces the frequency with which adult male birds perform their acrobatic display maneuvers and disrupts the overall structure and fine-scale patterning of these birds' main complex wing-snap sonation. In addition, this manipulation has no effect on the behavioral metrics associated with male motivation to display. Together, our findings help differentiate the various effects of peripheral and central AR on the performance of a complex sociosexual behavioral phenotype by indicating that peripheral AR can optimize the motor skills necessary for the production of an elaborate animal display.

User-preferred color temperature adjustment for smartphone display under varying illuminants

NASA Astrophysics Data System (ADS)

Choi, Kyungah; Suk, Hyeon-Jeong

2014-06-01

The study aims to investigate the user-preferred color temperature adjustment for smartphone displays by observing the effect of the illuminant's chromaticity and intensity on the optimal white points preferred by users. For visual examination, subjects evaluated 14 display stimuli presented on the Samsung Galaxy S3 under 19 ambient illuminants. The display stimuli were composed of 14 nuanced whites varying in color temperature from 2900 to 18,900 K. The illuminant conditions varied with combinations of color temperature (2600 to 20,100 K) and illuminance level (30 to 3100 lx) that simulated daily lighting experiences. The subjects were asked to assess the optimal level of the display color temperatures based on their mental representation of the ideal white point. The study observed a positive correlation between the illuminant color temperatures and the optimal display color temperatures (r=0.89, p<0.05). However, the range of the color temperature of the smartphone display was much narrower than that of the illuminants. Based on the assessments by 100 subjects, a regression formula was derived to predict the adjustment of user-preferred color temperature under changing illuminant chromaticity. The formula is as follows: [Display Tcp=6534.75 log (Illuminant Tcp)-16304.68 (R=0.87, p<0.05)]. Moreover, supporting previous studies on color reproduction, the effect of illuminant chromaticity was relatively weaker under lower illuminance. The results of this experiment could be used as a theoretical basis for designers and manufacturers to adjust user-preferred color temperature for smartphone displays under various illuminant conditions.

Rational design of Bacillus stearothermophilus US100 L-arabinose isomerase: potential applications for D-tagatose production.

PubMed

Rhimi, Moez; Aghajari, Nushin; Juy, Michel; Chouayekh, Hichem; Maguin, Emmanuelle; Haser, Richard; Bejar, Samir

2009-05-01

L-arabinose isomerases catalyze the bioconversion of D-galactose into D-tagatose. With the aim of producing an enzyme optimized for D-tagatose production, three Bacillus stearothermophilus US100 L-arabinose isomerase mutants were constructed, purified and characterized. Our results indicate that mutant Q268K was significantly more acidotolerant and more stable at acidic pH than the wild-type enzyme. The N175H mutant has a broad optimal temperature range from 50 to 65 degrees C. With the aim of constructing an acidotolerant mutant working at relatively low temperatures we generated the Q268K/N175H construct. This double mutant displays an optimal pH in the range 6.0-7.0 and an optimal activity around 50-65 degrees C, temperatures at which the enzyme was stable without addition of metal ions.

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.

Optimal color temperature adjustment for mobile devices under varying illuminants

NASA Astrophysics Data System (ADS)

Choi, Kyungah; Suk, Hyeon-Jeong

2014-01-01

With the wide use of mobile devices, display color reproduction has become extremely important. The purpose of this study is to investigate the optimal color temperature for mobile displays under varying illuminants. The effect of the color temperature and the illuminance of ambient lighting on user preferences were observed. For a visual examination, a total of 19 nuanced whites were examined under 20 illuminants. A total of 19 display stimuli with different color temperatures (2,500 K ~ 19,600 K) were presented on an iPad3 (New iPad). The ambient illuminants ranged in color temperature from 2,500 K to 19,800 K and from 0 lx to 3,000 lx in illuminance. Supporting previous studies of color reproduction, there was found to be a positive correlation between the color temperature of illuminants and that of optimal whites. However, the relationship was not linear. Based on assessments by 56 subjects, a regression equation was derived to predict the optimal color temperature adjustment under varying illuminants, as follows: [Display Tcp = 5138.93 log(Illuminant Tcp) - 11956.59, p<.001, R2=0.94]. Moreover, the influence of an illuminant was positively correlated with the illuminance level, confirming the findings of previous studies. It is expected that the findings of this study can be used as the theoretical basis when designing a color strategy for mobile display devices.

An integrated vector system for cellular studies of phage display-derived peptides.

PubMed

Voss, Stephan D; DeGrand, Alec M; Romeo, Giulio R; Cantley, Lewis C; Frangioni, John V

2002-09-15

Peptide phage display is a method by which large numbers of diverse peptides can be screened for binding to a target of interest. Even when successful, the rate-limiting step is usually validation of peptide bioactivity using living cells. In this paper, we describe an integrated system of vectors that expedites both the screening and the characterization processes. Library construction and screening is performed using an optimized type 3 phage display vector, mJ(1), which is shown to accept peptide libraries of at least 23 amino acids in length. Peptide coding sequences are shuttled from mJ(1) into one of three families of mammalian expression vectors for cell physiological studies. The vector pAL(1) expresses phage display-derived peptides as Gal4 DNA binding domain fusion proteins for transcriptional activation studies. The vectors pG(1), pG(1)N, and pG(1)C express phage display-derived peptides as green fluorescent protein fusions targeted to the entire cell, nucleus, or cytoplasm, respectively. The vector pAP(1) expresses phage display-derived peptides as fusions to secreted placental alkaline phosphatase. Such enzyme fusions can be used as highly sensitive affinity reagents for high-throughput assays and for cloning of peptide-binding cell surface receptors. Taken together, this system of vectors should facilitate the development of phage display-derived peptides into useful biomolecules.

An Inventory Model for Special Display Goods with Seasonal Demand

NASA Astrophysics Data System (ADS)

Kawakatsu, Hidefumi

2010-10-01

The present study discusses the retailer's optimal replenishment policy for seasonal products. The demand rate of seasonal merchandise such as clothes, sporting goods, children's toys and electrical home appearances tends to decrease with time after reaching its maximum value. In this study, we focus on "Special Display Goods", which are heaped up in end displays or special areas at retail stores. They are sold at a fast velocity when their quantity displayed is large, but are sold at a low velocity if the quantity becomes small. We develop the model with a finite time horizon (selling period) to determine the optimal replenishment policy, which maximizes the retailer's total profit. Numerical examples are presented to illustrate the theoretical underpinnings of the proposed model.

Optimization of Delayed Tolerance Induction in Swine: A Clinically-Relevant Protocol for Immunosuppression-Free Vascularized Composite Allotransplantation

DTIC Science & Technology

2017-10-01

information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE October...been achieved in nonhuman primates (NHPs) using a the delayed period protocol, i.e combination of post- transplant non -myeloablative conditioning and...seminars, study groups , and individual study. Include participation in conferences, workshops, and seminars not listed under major activities

Virtual Acoustics, Aeronautics and Communications

NASA Technical Reports Server (NTRS)

Begault, Durand R.; Null, Cynthia H. (Technical Monitor)

1996-01-01

An optimal approach to auditory display design for commercial aircraft would utilize both spatialized ("3-D") audio techniques and active noise cancellation for safer operations. Results from several aircraft simulator studies conducted at NASA Ames Research Center are reviewed, including Traffic alert and Collision Avoidance System (TCAS) warnings, spoken orientation "beacons" for gate identification and collision avoidance on the ground, and hardware for improved speech intelligibility. The implications of hearing loss amongst pilots is also considered.

Virtual acoustics, aeronautics, and communications

NASA Technical Reports Server (NTRS)

Begault, D. R.; Wenzel, E. M. (Principal Investigator)

1998-01-01

An optimal approach to auditory display design for commercial aircraft would utilize both spatialized (3-D) audio techniques and active noise cancellation for safer operations. Results from several aircraft simulator studies conducted at NASA Ames Research Center are reviewed, including Traffic alert and Collision Avoidance System (TCAS) warnings, spoken orientation "beacons" for gate identification and collision avoidance on the ground, and hardware for improved speech intelligibility. The implications of hearing loss among pilots is also considered.

Algicidal activity of an actinomycete strain, Streptomyces rameus, against Microcystis aeruginosa.

PubMed

Phankhajon, Kanchariya; Somdee, Anchana; Somdee, Theerasak

2016-09-01

An actinomycete strain (KKU-A3) with algicidal activity against Microcystis aeruginosa was isolated from soil in Khon Kaen Province, Thailand. Based on its phenotypic characteristics and 16S rDNA sequence, strain KKU-A3 was identified as Streptomyces rameus. Strain KKU-A3 also exhibited algicidal activity against the cyanobacteria Synechococcus elongatus, Cylindrospermum sp. and Oscillatoria sp. A mathematical and statistical technique was used to optimize the culture conditions and maximize its anti-Microcystis activity. The single factor experiments indicated that glucose and casein were the most effective carbon and nitrogen sources, respectively, and produced the highest anti-Microcystis activity. Response surface methodology indicated that the optimum culture conditions were 19.81 g/L glucose and 2.0 g/L casein at an initial pH of 7.8 and an incubation temperature of 30 °C. The anti-Microcystis activity increased from 82% to 95% under optimum conditions. In an internal airlift loop bioreactor, the removal of M. aeruginosa KKU-13 by the bacterium was investigated in batch and continuous flow experiments. In the batch experiment, KKU-A3 displayed maximum anti-Microcystis activity of 95% at day 7, whereas in the continuous flow experiment, KKU-A3 displayed maximum anti-Microcystis activity of 95% at day 10.

Multi-oxide active layer deposition using Applied Materials Pivot array coater for high-mobility metal oxide TFT

NASA Astrophysics Data System (ADS)

Park, Hyun Chan; Scheer, Evelyn; Witting, Karin; Hanika, Markus; Bender, Marcus; Hsu, Hao Chien; Yim, Dong Kil

2015-11-01

By controlling a thin indium tin oxide (ITO), indium zinc oxide interface layer between gate insulator and indium gallium zinc oxide (IGZO), the thin-film transistor (TFT) performance can reach higher mobility as conventional IGZO as well as superior stability. For large-area display application, Applied Materials static PVD array coater (Applied Materials GmbH & Co. KG, Alzenau, Germany) using rotary targets has been developed to enable uniform thin layer deposition in display industry. Unique magnet motion parameter optimization in Pivot sputtering coater is shown to provide very uniform thin ITO layer to reach TFT performance with high mobility, not only on small scale, but also on Gen8.5 (2500 × 2200 mm glass size) production system.

Antimicrobial and antioxidant activities of Cichorium intybus root extract using orthogonal matrix design.

PubMed

Liu, Haitao; Wang, Quanzhen; Liu, Yuyan; Chen, Guo; Cui, Jian

2013-02-01

Solvent, impregnation time, sonication repetitions, and ultrasonic power were important factors in the process of ultrasound-assisted extraction from chicory (Cichorium intybus) root, while there were no studies about optimizing these 4 factors for extract yield, total phenolic content (TPC), antioxidant, antibacterial, and antifungal activity of the extracts using orthogonal matrix design. The present research demonstrated that the solvent composition played a significant role in the improving extract yield, TPC, antioxidant, and antibacterial activities. The other 3 factors had inequable effect on different purposes, ultrasonic power could improve TPC and antioxidant activity, but long time of extraction lowered antioxidant activity. The TPC increased from 22.34 to 27.87 mg GAE (gallic acid equivalents)/100 g (dry extracts) with increasing solvent polarity. The half inhibition concentration (IC(50,) μg/mL) of the radical scavenging activity of the chicory extracts ranged from 281.00 to 983.33 μg/mL. The content of caffeoylquinic acids of root extract, which was extracted by the optimal combination was 0.104%. Several extracts displayed antibacterial activities against Escherichia coli, Staphylococcus aureus, Bacillus thuringiensis, Bacillus subtilis, and Salmonella typhi, while Penicillium sp. and Aspergillus sp. resisted against all the extracts. Combination of 70% ethanol v/v, 24-h impregnation time, 3 sonication rounds, and 300-W ultrasonic input power was found to be the optimal combination for the chicory extract yield, TPC, antioxidant activity, and antibacterial activity. © 2012 Institute of Food Technologists®

An optimization study of PtSn/C catalysts applied to direct ethanol fuel cell: Effect of the preparation method on the electrocatalytic activity of the catalysts

NASA Astrophysics Data System (ADS)

Almeida, T. S.; Palma, L. M.; Leonello, P. H.; Morais, C.; Kokoh, K. B.; De Andrade, A. R.

2012-10-01

The aim of this work was to perform a systematic study of the parameters that can influence the composition, morphology, and catalytic activity of PtSn/C nanoparticles and compare two different methods of nanocatalyst preparation, namely microwave-assisted heating (MW) and thermal decomposition of polymeric precursors (DPP). An investigation of the effects of the reducing and stabilizing agents on the catalytic activity and morphology of Pt75Sn25/C catalysts prepared by microwave-assisted heating was undertaken for optimization purposes. The effect of short-chain alcohols such as ethanol, ethylene glycol, and propylene glycol as reducing agents was evaluated, and the use of sodium acetate and citric acid as stabilizing agents for the MW procedure was examined. Catalysts obtained from propylene glycol displayed higher catalytic activity compared with catalysts prepared in ethylene glycol. Introduction of sodium acetate enhanced the catalytic activity, but this beneficial effect was observed until a critical acetate concentration was reached. Optimization of the MW synthesis allowed for the preparation of highly dispersed catalysts with average sizes lying between 2.0 and 5.0 nm. Comparison of the best catalyst prepared by MW with a catalyst of similar composition prepared by the polymeric precursors method showed that the catalytic activity of the material can be improved when a proper condition for catalyst preparation is achieved.

Microscopy illumination engineering using a low-cost liquid crystal display.

PubMed

Guo, Kaikai; Bian, Zichao; Dong, Siyuan; Nanda, Pariksheet; Wang, Ying Min; Zheng, Guoan

2015-02-01

Illumination engineering is critical for obtaining high-resolution, high-quality images in microscope settings. In a typical microscope, the condenser lens provides sample illumination that is uniform and free from glare. The associated condenser diaphragm can be manually adjusted to obtain the optimal illumination numerical aperture. In this paper, we report a programmable condenser lens for active illumination control. In our prototype setup, we used a $15 liquid crystal display as a transparent spatial light modulator and placed it at the back focal plane of the condenser lens. By setting different binary patterns on the display, we can actively control the illumination and the spatial coherence of the microscope platform. We demonstrated the use of such a simple scheme for multimodal imaging, including bright-field microscopy, darkfield microscopy, phase-contrast microscopy, polarization microscopy, 3D tomographic imaging, and super-resolution Fourier ptychographic imaging. The reported illumination engineering scheme is cost-effective and compatible with most existing platforms. It enables a turnkey solution with high flexibility for researchers in various communities. From the engineering point-of-view, the reported illumination scheme may also provide new insights for the development of multimodal microscopy and Fourier ptychographic imaging.

Phosphoglycerate Kinases Are Co-Regulated to Adjust Metabolism and to Optimize Growth.

PubMed

Rosa-Téllez, Sara; Anoman, Armand Djoro; Flores-Tornero, María; Toujani, Walid; Alseek, Saleh; Fernie, Alisdair R; Nebauer, Sergio G; Muñoz-Bertomeu, Jesús; Segura, Juan; Ros, Roc

2018-02-01

In plants, phosphoglycerate kinase (PGK) converts 1,3-bisphosphoglycerate into 3-phosphoglycerate in glycolysis but also participates in the reverse reaction in gluconeogenesis and the Calvin-Benson cycle. In the databases, we found three genes that encode putative PGKs. Arabidopsis ( Arabidopsis thaliana ) PGK1 was localized exclusively in the chloroplasts of photosynthetic tissues, while PGK2 was expressed in the chloroplast/plastid of photosynthetic and nonphotosynthetic cells. PGK3 was expressed ubiquitously in the cytosol of all studied cell types. Measurements of carbohydrate content and photosynthetic activities in PGK mutants and silenced lines corroborated that PGK1 was the photosynthetic isoform, while PGK2 and PGK3 were the plastidial and cytosolic glycolytic isoforms, respectively. The pgk1.1 knockdown mutant displayed reduced growth, lower photosynthetic capacity, and starch content. The pgk3.2 knockout mutant was characterized by reduced growth but higher starch levels than the wild type. The pgk1.1 pgk3.2 double mutant was bigger than pgk3.2 and displayed an intermediate phenotype between the two single mutants in all measured biochemical and physiological parameters. Expression studies in PGK mutants showed that PGK1 and PGK3 were down-regulated in pgk3.2 and pgk1.1 , respectively. These results indicate that the down-regulation of photosynthetic activity could be a plant strategy when glycolysis is impaired to achieve metabolic adjustment and optimize growth. The double mutants of PGK3 and the triose-phosphate transporter ( pgk3.2 tpt3) displayed a drastic growth phenotype, but they were viable. This implies that other enzymes or nonspecific chloroplast transporters could provide 3-phosphoglycerate to the cytosol. Our results highlight both the complexity and the plasticity of the plant primary metabolic network. © 2018 American Society of Plant Biologists. All Rights Reserved.

Optimization of Supercritical Fluid Extraction of Total Alkaloids, Peimisine, Peimine and Peiminine from the Bulb of Fritillaria thunbergii Miq, and Evaluation of Antioxidant Activities of the Extracts

PubMed Central

Ruan, Xiao; Yang, Li; Cui, Wen-Xia; Zhang, Men-Xing; Li, Zhao-Hui; Liu, Ben; Wang, Qiang

2016-01-01

Supercritical fluid extraction (SFE) was used to extract total alkaloids, peimisine, peimine and peiminine from the bulb of Fritillaria thunbergii Miq. The antioxidant capacity of the extracts was evaluated by DPPH radical scavenging activity (DPPH-RSA), ABTS radical scavenging activity (ABTS-RSA) and ferric reducing capacity (FRAP) assay. A central composite design (CCD) with four variables and five levels was employed for optimization of process parameters, and response surface plots were constructed in accordance with a second order polynomial model. Under optimal conditions of 3.0 h, 60.4 °C, 26.5 MPa and 89.3% ethanol, the highest yields were predicted to be 3.8 mg/g for total alkaloids, 0.5 mg/g for peimisine, 1.3 mg/g for peimine and 1.3 mg/g for peiminine, and the antioxidant capacity of extracts displayed EC50, DPPH value of 5.5 mg/mL, EC50, ABTS value of 0.3 mg/mL and FRAP value of 118.2 mg ascorbic acid equivalent (AAE)/100 g. PMID:28773648

Scalable large format 3D displays

NASA Astrophysics Data System (ADS)

Chang, Nelson L.; Damera-Venkata, Niranjan

2010-02-01

We present a general framework for the modeling and optimization of scalable large format 3-D displays using multiple projectors. Based on this framework, we derive algorithms that can robustly optimize the visual quality of an arbitrary combination of projectors (e.g. tiled, superimposed, combinations of the two) without manual adjustment. The framework creates for the first time a new unified paradigm that is agnostic to a particular configuration of projectors yet robustly optimizes for the brightness, contrast, and resolution of that configuration. In addition, we demonstrate that our algorithms support high resolution stereoscopic video at real-time interactive frame rates achieved on commodity graphics hardware. Through complementary polarization, the framework creates high quality multi-projector 3-D displays at low hardware and operational cost for a variety of applications including digital cinema, visualization, and command-and-control walls.

Optimization of the primary recovery of human interferon alpha2b from Escherichia coli inclusion bodies.

PubMed

Valente, C A; Monteiro, G A; Cabral, J M S; Fevereiro, M; Prazeres, D M F

2006-01-01

The human interferon alpha2b (hu-IFNalpha2b) gene was cloned in Escherichia coli JM109(DE3) and the recombinant protein was expressed as cytoplasmic inclusion bodies (IB). The present work discusses the recovery of hu-IFNalpha2b IB from the E. coli cells. An optimized protocol is proposed based on the sequential evaluation of recovery steps and parameters: (i) cell disruption, (ii) IB recovery and separation from cell debris, (iii) IB washing, and (iv) IB solubilization. Parameters such as hu-IFNalpha2b purity and recovery yield were measured after each step. The optimized recovery protocol yielded 60% of hu-IFNalpha2b with a purity of up to 80%. The protein was renatured at high concentration after recovery and it was found to display biological activity.

A comparative study of psychophysical judgment of color reproductions on mobile displays between Europeans and Asians

NASA Astrophysics Data System (ADS)

Choi, Kyungah; Suk, Hyeon-Jeong

2015-01-01

The purpose of this study is to investigate the differences in the psychophysical judgment of mobile display color appearances between Europeans and Asians. A total of 50 participants, comprising 20 Europeans (9 French, 6 Swedish, 3 Norwegians, and 2 Germans) and 30 Asians (30 Koreans) participated in this experiment. A total of 18 display stimuli with different correlated color temperatures were presented, varying from 2,470 to 18,330 K. Each stimulus was viewed under 11 illuminants ranging from 2,530 to 19,760 K, while their illuminance was consistent around 500 lux. The subjects were asked to assess the optimal level of the display stimuli under different illuminants. In general, confirming the previous studies on color reproduction, we found a positive correlation in the correlated color temperatures between the illuminants and optimal displays. However, Europeans preferred a lower color temperature compared to Asians along the entire range of the illuminants. Two regression equations were derived to predict the optimal display color temperature (y) under varying illuminants (x) as follows: y = α + β*log(x), where α = -8770.37 and β = 4279.29 for European (R2 = 0.95, p < .05), and α = -16076.35 and β = 6388.41 for Asian (R2 = 0.85, p < .05). The findings provide the theoretical basis from which manufacturers can take a cultural-sensitive approach to enhancing their products' appeal in the global markets.

Visual characteristics of LED display pushbuttons for avionic applications

NASA Astrophysics Data System (ADS)

Vanni, Paolo; Isoldi, Felice

1991-08-01

Programmable LED matrix display push buttons may greatly increase the performances of the computer-based avionic systems. The number of switches in a control panel can be reduced by a factor of 10 or more. This leads to a reduction in weight and size of the control instrumentations and in shorter response time of pilots. This work deals with the study and the optimization of visual performances of these displays in a configuration requiring a low- power consumption and Night Vision Goggles (NVG) compatibility. In considering displays for avionic applications, it is important to take into account sunlight readability. Visibility problems may arise in high ambient illumination. Up to now the only contributions usually considered for reduction of visibility are the diffused and specular reflected luminances that predominate with the sun behind the pilot. But there is another critical condition--the sun in front of the pilot. In this case the equivalent veiling glare predominates. Display performances and contrast enhancement filter characteristics must be optimized to find a compromise between these two extreme ambient conditions. Considering a keyboard with 10 push buttons, with two lines of four characters each and a power consumption less than 14 W with 40 of LEDs on, the authors have obtained good sunlight readability, choosing an optimized combination of NVG and contrast enhancement filter and LED matrix display.

On The Influence Of Vector Design On Antibody Phage Display

PubMed Central

Soltes, Glenn; Hust, Michael; Ng, Kitty K.Y.; Bansal, Aasthaa; Field, Johnathan; Stewart, Donald I.H.; Dübel, Stefan; Cha, Sanghoon; Wiersma, Erik J

2007-01-01

Phage display technology is an established technology particularly useful for the generation of monoclonal antibodies (mAbs). The isolation of phagemid-encoded mAb fragments depends on several features of a phage preparation. The aims of this study were to optimize phage display vectors, and to ascertain if different virion features can be optimized independently of each other. Comparisons were made between phagemid virions assembled by g3p-deficient helper phage, Hyperphage, Ex-phage or Phaberge, or corresponding g3p-sufficient helper phage, M13K07. All g3p-deficient helper phage provided a similar level of antibody display, significantly higher than that of M13K07. Hyperphage packaged virions at least 100-fold more efficiently than did Ex-phage or Phaberge. Phaberge's packaging efficiency improved by using a SupE strain. Different phagemids were also compared. Removal of a 56 base pair fragment from the promoter region resulted in increased display level and increased virion production. This critical fragment encodes a lacZ'-like peptide and is also present in other commonly used phagemids. Increasing display level did not show statistical correlation with phage production, phage infectivity or bacterial growth rate. However, phage production was positively correlated to phage infectivity. In summary, this study demonstrates simultaneously optimization of multiple and independent features of importance for phage selection. PMID:16996161

On the influence of vector design on antibody phage display.

PubMed

Soltes, Glenn; Hust, Michael; Ng, Kitty K Y; Bansal, Aasthaa; Field, Johnathan; Stewart, Donald I H; Dübel, Stefan; Cha, Sanghoon; Wiersma, Erik J

2007-01-20

Phage display technology is an established technology particularly useful for the generation of monoclonal antibodies (mAbs). The isolation of phagemid-encoded mAb fragments depends on several features of a phage preparation. The aims of this study were to optimize phage display vectors, and to ascertain if different virion features can be optimized independently of each other. Comparisons were made between phagemid virions assembled by g3p-deficient helper phage, Hyperphage, Ex-phage or Phaberge, or corresponding g3p-sufficient helper phage, M13K07. All g3p-deficient helper phage provided a similar level of antibody display, significantly higher than that of M13K07. Hyperphage packaged virions at least 100-fold more efficiently than did Ex-phage or Phaberge. Phaberge's packaging efficiency improved by using a SupE strain. Different phagemids were also compared. Removal of a 56 base pair fragment from the promoter region resulted in increased display level and increased virion production. This critical fragment encodes a lacZ'-like peptide and is also present in other commonly used phagemids. Increasing display level did not show statistical correlation with phage production, phage infectivity or bacterial growth rate. However, phage production was positively correlated to phage infectivity. In summary, this study demonstrates simultaneously optimization of multiple and independent features of importance for phage selection.

An experimental and theoretical study of new phosphors for full color field emission displays

NASA Astrophysics Data System (ADS)

Zhang, Fu-Li

An in depth study is reported of the cathodoluminescent (CL) properties of three new highly efficiency blue phosphors for field emission display (FED) applications doped with fast activators. The superior performance of a new Eu-doped green SrGa2S4 will also be reported. This work addresses four main topics: (1) a detailed study of the dependence of the luminescent intensity on activator concentration, as a function of electron beam voltage and current density; (2) the optical properties of thew phosphors and the development of a CL efficiency characterization technique using a critical screen weight method, which can obtain maximum light output and improve measurement accuracy; (3) understanding the low voltage CL mechanism associated with nanocrystal size by developing a thin film and disk model based on transportation theory and experimental results; (4) Development of a comprehensive evaluation method of red, green, and blue (RGB) phosphors for full color displays by calculation of luminance ratios, required luminance, and measurements of spectra, efficiency and saturation behavior. For FEDs which combine the best properties of CRT and flat panel displays, the development of efficient phosphors at low voltages and high current densities is shown to be critical to meet the luminance and power requirement demands for portable displays. Of particular importance is the need for a good blue phosphor, and to understand the dependence of the CL efficiency on nanocrystal size, penetration depth, diffusion length and surface recombination rate. This has been obtained from the thin film and disk models and fits to experiment. Comparisons between full color phosphor sets show that the performance of a display can vary by over a factor of three depending on the choice of the RGB set. Other factors that are important for optimizing the performance of FED phosphors are reviewed.

Virus like particles as a platform for cancer vaccine development.

PubMed

Ong, Hui Kian; Tan, Wen Siang; Ho, Kok Lian

2017-01-01

Cancers have killed millions of people in human history and are still posing a serious health problem worldwide. Therefore, there is an urgent need for developing preventive and therapeutic cancer vaccines. Among various cancer vaccine development platforms, virus-like particles (VLPs) offer several advantages. VLPs are multimeric nanostructures with morphology resembling that of native viruses and are mainly composed of surface structural proteins of viruses but are devoid of viral genetic materials rendering them neither infective nor replicative. In addition, they can be engineered to display multiple, highly ordered heterologous epitopes or peptides in order to optimize the antigenicity and immunogenicity of the displayed entities. Like native viruses, specific epitopes displayed on VLPs can be taken up, processed, and presented by antigen-presenting cells to elicit potent specific humoral and cell-mediated immune responses. Several studies also indicated that VLPs could overcome the immunosuppressive state of the tumor microenvironment and break self-tolerance to elicit strong cytotoxic lymphocyte activity, which is crucial for both virus clearance and destruction of cancerous cells. Collectively, these unique characteristics of VLPs make them optimal cancer vaccine candidates. This review discusses current progress in the development of VLP-based cancer vaccines and some potential drawbacks of VLPs in cancer vaccine development. Extracellular vesicles with close resembling to viral particles are also discussed and compared with VLPs as a platform in cancer vaccine developments.

Structure-Activity Relationships of Nitro-Substituted Aroylhydrazone Iron Chelators with Antioxidant and Antiproliferative Activities.

PubMed

Hrušková, Kateřina; Potůčková, Eliška; Opálka, Lukáš; Hergeselová, Tereza; Hašková, Pavlína; Kovaříková, Petra; Šimůnek, Tomáš; Vávrová, Kateřina

2018-05-23

Aroylhydrazone iron chelators such as salicylaldehyde isonicotinoyl hydrazone (SIH) protect various cells against oxidative injury and display antineoplastic activities. Previous studies have shown that a nitro-substituted hydrazone, namely, NHAPI, displayed markedly improved plasma stability, selective antitumor activity, and moderate antioxidant properties. In this study, we prepared four series of novel NHAPI derivatives and explored their iron chelation activities, anti- or pro-oxidant effects, protection against model oxidative injury in the H9c2 cell line derived from rat embryonic cardiac myoblasts, cytotoxicities to the corresponding noncancerous H9c2 cells, and antiproliferative activities against the MCF-7 human breast adenocarcinoma and HL-60 human promyelocytic leukemia cell lines. Nitro substitution had both negative and positive effects on the examined properties, and we identified new structure-activity relationships. Naphthyl and biphenyl derivatives showed selective antiproliferative action, particularly in the breast adenocarcinoma MCF-7 cell line, where they exceeded the selectivity of the parent compound NHAPI. Of particular interest is a compound prepared from 2-hydroxy-5-methyl-3-nitroacetophenone and biphenyl-4-carbohydrazide, which protected cardiomyoblasts against oxidative injury at 1.8 ± 1.2 μM with 24-fold higher selectivity than SIH. These compounds will serve as leads for further structural optimization and mechanistic studies.

Unsupported Pt-Ni Aerogels with Enhanced High Current Performance and Durability in Fuel Cell Cathodes.

PubMed

Henning, Sebastian; Ishikawa, Hiroshi; Kühn, Laura; Herranz, Juan; Müller, Elisabeth; Eychmüller, Alexander; Schmidt, Thomas J

2017-08-28

Highly active and durable oxygen reduction catalysts are needed to reduce the costs and enhance the service life of polymer electrolyte fuel cells (PEFCs). This can be accomplished by alloying Pt with a transition metal (for example Ni) and by eliminating the corrodible, carbon-based catalyst support. However, materials combining both approaches have seldom been implemented in PEFC cathodes. In this work, an unsupported Pt-Ni alloy nanochain ensemble (aerogel) demonstrates high current PEFC performance commensurate with that of a carbon-supported benchmark (Pt/C) following optimization of the aerogel's catalyst layer (CL) structure. The latter is accomplished using a soluble filler to shift the CL's pore size distribution towards larger pores which improves reactant and product transport. Chiefly, the optimized PEFC aerogel cathodes display a circa 2.5-fold larger surface-specific ORR activity than Pt/C and maintain 90 % of the initial activity after an accelerated stress test (vs. 40 % for Pt/C). © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Optimization of polysaccharides extraction from watermelon rinds: Structure, functional and biological activities.

PubMed

Romdhane, Molka Ben; Haddar, Anissa; Ghazala, Imen; Jeddou, Khawla Ben; Helbert, Claire Boisset; Ellouz-Chaabouni, Semia

2017-02-01

In the present work, optimization of hot water extraction, structural characteristics, functional properties, and biological activities of polysaccharides extracted from watermelon rinds (WMRP) were investigated. The physicochemical characteristics and the monosaccharide composition of these polysaccharides were then determined using chemical composition analysis, Fourier transform infrared (FT-IR) spectroscopy, scanning electron microscopy (SEM) and gas chromatography-flame ionization detection (GC-FID). SEM images showed that extracted polysaccharides had a rough surface with many cavities. GC-FID results proved that galactose was the dominant sugar in the extracted polysaccharides, followed by arabinose, glucose, galacturonic acid, rhamnose, mannose, xylose and traces of glucuronic acid. The findings revealed that WMRP displayed excellent antihypertensive and antioxidant activities. Those polysaccharides had also a protection effect against hydroxyl radical-induced DNA damage. Functional properties of extracted polysaccharides were also evaluated. WMRP showed good interfacial dose-dependent proprieties. Overall, the results suggested that WMRP presents a promising natural source of antioxidants and antihypertensive agents. Copyright © 2016 Elsevier Ltd. All rights reserved.

Pyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H)-dione derivatives as novel small molecule chaperone amplifiers.

PubMed

Zhou, Yuefen; Wei, Linyi; Brady, Thomas P; Murali Mohan Redddy, P S; Nguyen, Tram; Chen, Jinhua; Au, Qingyan; Yoon, Il Sang; Yip, Gary; Zhang, Bin; Barber, Jack R; Ng, Shi Chung

2009-08-01

Pyrimido[5,4-e][1,2,4]triazine-5,7(1H,6H)-dione derivatives were investigated as novel small molecule amplifiers of heat shock factor 1 transcriptional activity. Lead optimization led to the discovery of compound 4A-13, which displayed potent HSF1 activity under mild heat stress (EC(50)=2.5microM) and significant cytoprotection in both rotenone (EC(50)=0.23microM) and oxygen-glucose deprivation cell toxicity models (80% protection at 2.5microM).

Discovery of novel hydroxamates as highly potent tumor necrosis factor-[alpha] converting enzyme inhibitors. Part II: Optimization of the S3′ pocket

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

Mazzola Jr., Robert D.; Zhu, Zhaoning; Sinning, Lisa

2010-10-01

A series of cyclopropyl hydroxamic acids were prepared. Many of the compounds displayed picomolar affinity for the TACE enzyme while maintaining good to excellent selectivity profiles versus MMP-1, -2, -3, -7, -14, and ADAM-10. X-ray analysis of an inhibitor in the TACE active site indicated that the molecules bound to the enzyme in the S1{prime}-S3{prime} pocket.

Purification and characterization of cathepsin L in arrowtooth flounder (Atheresthes stomias) muscle.

PubMed

Visessanguan, Wonnop; Benjakul, Soottawat; An, Haejung

2003-03-01

A predominant, heat-activated proteinase in muscle extract of arrowtooth flounder (Atheresthes stomias) was purified to 55-fold by heat treatment, followed by a series of chromatographic separations. The apparent molecular mass of the purified enzyme was 27 kDa by size exclusion chromatography and sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The proteinase had high affinity and activity toward Z-Phe-Arg-NMec with K(m) and k(cat) values of 8.2 microM and 12.2/s, respectively. Activity was inhibited by sulfhydryl reagents and activated by reducing agents. The purified proteinase displayed optimal activity at pH 5.0-5.5 and 60 degrees C, respectively. Consistent with the properties of proteases from other species, the heat-activated proteinase in arrowtooth flounder can be identified as cathepsin L.

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

PubMed

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

2003-10-25

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

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

PubMed

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

2014-07-16

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

Phage display of an intracellular carboxylesterase of Bacillus subtilis: comparison of Sec and Tat pathway export capabilities.

PubMed

Dröge, Melloney J; Boersma, Ykelien L; Braun, Peter G; Buining, Robbert Jan; Julsing, Mattijs K; Selles, Karin G A; van Dijl, Jan Maarten; Quax, Wim J

2006-07-01

Using the phage display technology, a protein can be displayed at the surface of bacteriophages as a fusion to one of the phage coat proteins. Here we describe development of this method for fusion of an intracellular carboxylesterase of Bacillus subtilis to the phage minor coat protein g3p. The carboxylesterase gene was cloned in the g3p-based phagemid pCANTAB 5E upstream of the sequence encoding phage g3p and downstream of a signal peptide-encoding sequence. The phage-bound carboxylesterase was correctly folded and fully enzymatically active, as determined from hydrolysis of the naproxen methyl ester with Km values of 0.15 mM and 0.22 mM for the soluble and phage-displayed carboxylesterases, respectively. The signal peptide directs the encoded fusion protein to the cell membrane of Escherichia coli, where phage particles are assembled. In this study, we assessed the effects of several signal peptides, both Sec dependent and Tat dependent, on the translocation of the carboxylesterase in order to optimize the phage display of this enzyme normally restricted to the cytoplasm. Functional display of Bacillus carboxylesterase NA could be achieved when Sec-dependent signal peptides were used. Although a Tat-dependent signal peptide could direct carboxylesterase translocation across the inner membrane of E. coli, proper assembly into phage particles did not seem to occur.

Platinum–nickel nanowire catalysts with composition-tunable alloying and faceting for the oxygen reduction reaction

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

Chang, Fangfang; Yu, Gang; Shan, Shiyao

2017-01-01

The ability to tune the alloying properties and faceting characteristics of bimetallic nanocatalysts is essential for designing catalysts with enhanced activity and stability through optimizing strain and ligand effects, which is an important frontier for designing advanced materials as catalysts for fuel cell applications. This report describes composition-controlled alloying and faceting of platinum–nickel nanowires (PtNi NWs) for the electrocatalytic oxygen reduction reaction. The PtNi NWs are synthesized by a surfactant-free method and are shown to display bundled morphologies of nano-tetrahedra or nanowires, featuring an ultrathin and irregular helix morphology with composition-tunable facets. Using high-energy synchrotron X-ray diffraction coupled with atomicmore » pair distribution function analysis, lattice expansion and shrinking are revealed, with the Pt : Ni ratio of ~3 : 2 exhibiting a clear expansion, which coincides with the maximum electrocatalytic activity for the ORR. In comparison with PtNi nanoparticles (NPs), the PtNi NWs display remarkably higher electrocatalytic activity and stability as a result of the composition dependent atomic-scale alloying and faceting, demonstrating a new pathway to the design of alloy nanocatalysts with enhanced activity and durability for fuel cells.« less

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

PubMed

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

2017-01-27

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

Antibody production using a ciliate generates unusual antibody glycoforms displaying enhanced cell-killing activity

PubMed Central

Calow, Jenny; Bockau, Ulrike; Struwe, Weston B.; Nowaczyk, Marc M.; Loser, Karin; Crispin, Max

2016-01-01

ABSTRACT Antibody glycosylation is a key parameter in the optimization of antibody therapeutics. Here, we describe the production of the anti-cancer monoclonal antibody rituximab in the unicellular ciliate, Tetrahymena thermophila. The resulting antibody demonstrated enhanced antibody-dependent cell-mediated cytotoxicity, which we attribute to unusual N-linked glycosylation. Detailed chromatographic and mass spectrometric analysis revealed afucosylated, oligomannose-type glycans, which, as a whole, displayed isomeric structures that deviate from the typical human counterparts, but whose branches were equivalent to fragments of metabolic intermediates observed in human glycoproteins. From the analysis of deposited crystal structures, we predict that the ciliate glycans adopt protein-carbohydrate interactions with the Fc domain that closely mimic those of native complex-type glycans. In addition, terminal glucose structures were identified that match biosynthetic precursors of human glycosylation. Our results suggest that ciliate-based expression systems offer a route to large-scale production of monoclonal antibodies exhibiting glycosylation that imparts enhanced cell killing activity. PMID:27594301

Modular protein expression by RNA trans-splicing enables flexible expression of antibody formats in mammalian cells from a dual-host phage display vector.

PubMed

Shang, Yonglei; Tesar, Devin; Hötzel, Isidro

2015-10-01

A recently described dual-host phage display vector that allows expression of immunoglobulin G (IgG) in mammalian cells bypasses the need for subcloning of phage display clone inserts to mammalian vectors for IgG expression in large antibody discovery and optimization campaigns. However, antibody discovery and optimization campaigns usually need different antibody formats for screening, requiring reformatting of the clones in the dual-host phage display vector to an alternative vector. We developed a modular protein expression system mediated by RNA trans-splicing to enable the expression of different antibody formats from the same phage display vector. The heavy-chain region encoded by the phage display vector is directly and precisely fused to different downstream heavy-chain sequences encoded by complementing plasmids simply by joining exons in different pre-mRNAs by trans-splicing. The modular expression system can be used to efficiently express structurally correct IgG and Fab fragments or other antibody formats from the same phage display clone in mammalian cells without clone reformatting. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

New Materials and Device Designs for Organic Light-Emitting Diodes

NASA Astrophysics Data System (ADS)

O'Brien, Barry Patrick

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

Digi Island: A Serious Game for Teaching and Learning Digital Circuit Optimization

NASA Technical Reports Server (NTRS)

Harper, Michael; Miller, Joseph; Shen, Yuzhong

2011-01-01

Karnaugh maps, also known as K-maps, are a tool used to optimize or simplify digital logic circuits. A K-map is a graphical display of a logic circuit. K-map optimization is essentially the process of finding a minimum number of maximal aggregations of K-map cells. with values of 1 according to a set of rules. The Digi Island is a serious game designed for aiding students to learn K-map optimization. The game takes place on an exotic island (called Digi Island) in the Pacific Ocean . The player is an adventurer to the Digi Island and will transform it into a tourist attraction by developing real estates, such as amusement parks.and hotels. The Digi Island game elegantly converts boring 1s and Os in digital circuits into usable and unusable spaces on a beautiful island and transforms K-map optimization into real estate development, an activity with which many students are familiar and also interested in. This paper discusses the design, development, and some preliminary results of the Digi Island game.

On the dependence of information display quality requirements upon human characteristics and pilot/automatics relations

NASA Technical Reports Server (NTRS)

Wilckens, V.

1972-01-01

Present information display concepts for pilot landing guidance are outlined considering manual control as well as substitution of man by fully competent automatics. Display improvements are achieved by compressing the distributed indicators into an accumulative display and thus reducing information scanning. Complete integration of quantitative indications, outer loop information, and real world display in a pictorial information channel geometry constitutes an interface with human ability to differentiate and integrate for optimal manual control of the aircraft.

Modular Construction of Large Non-Immune Human Antibody Phage-Display Libraries from Variable Heavy and Light Chain Gene Cassettes.

PubMed

Lee, Nam-Kyung; Bidlingmaier, Scott; Su, Yang; Liu, Bin

2018-01-01

Monoclonal antibodies and antibody-derived therapeutics have emerged as a rapidly growing class of biological drugs for the treatment of cancer, autoimmunity, infection, and neurological diseases. To support the development of human antibodies, various display techniques based on antibody gene repertoires have been constructed over the last two decades. In particular, scFv-antibody phage display has been extensively utilized to select lead antibodies against a variety of target antigens. To construct a scFv phage display that enables efficient antibody discovery, and optimization, it is desirable to develop a system that allows modular assembly of highly diverse variable heavy chain and light chain (Vκ and Vλ) repertoires. Here, we describe modular construction of large non-immune human antibody phage-display libraries built on variable gene cassettes from heavy chain and light chain repertoires (Vκ- and Vλ-light can be made into independent cassettes). We describe utility of such libraries in antibody discovery and optimization through chain shuffling.

Polymers containing nickel(II) complexes of Goedken's macrocycle: optimized synthesis and electrochemical characterization.

PubMed

Paquette, Joseph A; Sauvé, Ethan R; Gilroy, Joe B

2015-04-01

The synthesis and characterization of a new class of nickel-containing polymers is described. The optimized copolymerization of alkyne-bearing nickel(II) complexes of Goedken's macrocycle (4,11-dihydro-5,7,12,14-tetramethyldibenzo[b,i][1,4,8,11]tetraazacyclotetradecine) and brominated 9,9-dihexylfluorene produced polymers with potential application as functional redox-active materials. The title polymers exhibit electrochemically reversible, ligand-centered oxidation events at 0.24 and 0.73 V versus the ferrocene/ferrocenium redox couple. They also display exceptional thermal stability and interesting absorption properties due to the presence of the macrocyclic nickel(II) complexes and π-conjugated units incorporated in their backbones. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Ventrolateral prefrontal cortex and the effects of task demand context on facial affect appraisal in schizophrenia.

PubMed

Leitman, David I; Wolf, Daniel H; Loughead, James; Valdez, Jeffrey N; Kohler, Christian G; Brensinger, Colleen; Elliott, Mark A; Turetsky, Bruce I; Gur, Raquel E; Gur, Ruben C

2011-01-01

Schizophrenia patients display impaired performance and brain activity during facial affect recognition. These impairments may reflect stimulus-driven perceptual decrements and evaluative processing abnormalities. We differentiated these two processes by contrasting responses to identical stimuli presented under different contexts. Seventeen healthy controls and 16 schizophrenia patients performed an fMRI facial affect detection task. Subjects identified an affective target presented amongst foils of differing emotions. We hypothesized that targeting affiliative emotions (happiness, sadness) would create a task demand context distinct from that generated when targeting threat emotions (anger, fear). We compared affiliative foil stimuli within a congruent affiliative context with identical stimuli presented in an incongruent threat context. Threat foils were analysed in the same manner. Controls activated right orbitofrontal cortex (OFC)/ventrolateral prefrontal cortex (VLPFC) more to affiliative foils in threat contexts than to identical stimuli within affiliative contexts. Patients displayed reduced OFC/VLPFC activation to all foils, and no activation modulation by context. This lack of context modulation coincided with a 2-fold decrement in foil detection efficiency. Task demands produce contextual effects during facial affective processing in regions activated during affect evaluation. In schizophrenia, reduced modulation of OFC/VLPFC by context coupled with reduced behavioural efficiency suggests impaired ventral prefrontal control mechanisms that optimize affective appraisal.

Highly Selective Bioconversion of Ginsenoside Rb1 to Compound K by the Mycelium of Cordyceps sinensis under Optimized Conditions.

PubMed

Wang, Wei-Nan; Yan, Bing-Xiong; Xu, Wen-Di; Qiu, Ye; Guo, Yun-Long; Qiu, Zhi-Dong

2015-10-23

Compound K (CK), a highly active and bioavailable derivative obtained from protopanaxadiol ginsenosides, displays a wide variety of pharmacological properties, especially antitumor activity. However, the inadequacy of natural sources limits its application in the pharmaceutical industry. In this study, we firstly discovered that Cordyceps sinensis was a potent biocatalyst for the biotransformation of ginsenoside Rb1 into CK. After a series of investigations on the biotransformation parameters, an optimal composition of the biotransformation culture was found to be lactose, soybean powder and MgSO₄ without controlling the pH. Also, an optimum temperature of 30 °C for the biotransformation process was suggested in a range of 25 °C-50 °C. Then, a biotransformation pathway of Rb1→Rd→F2→CK was established using high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS). Our results demonstrated that the molar bioconversion rate of Rb1 to CK was more than 82% and the purity of CK produced by C. sinensis under the optimized conditions was more than 91%. In conclusion, the combination of C. sinensis and the optimized conditions is applicable for the industrial preparation of CK for medicinal purposes.

Optimization of illumination schemes in a head-mounted display integrated with eye tracking capabilities

NASA Astrophysics Data System (ADS)

Pansing, Craig W.; Hua, Hong; Rolland, Jannick P.

2005-08-01

Head-mounted display (HMD) technologies find a variety of applications in the field of 3D virtual and augmented environments, 3D scientific visualization, as well as wearable displays. While most of the current HMDs use head pose to approximate line of sight, we propose to investigate approaches and designs for integrating eye tracking capability into HMDs from a low-level system design perspective and to explore schemes for optimizing system performance. In this paper, we particularly propose to optimize the illumination scheme, which is a critical component in designing an eye tracking-HMD (ET-HMD) integrated system. An optimal design can improve not only eye tracking accuracy, but also robustness. Using LightTools, we present the simulation of a complete eye illumination and imaging system using an eye model along with multiple near infrared LED (IRLED) illuminators and imaging optics, showing the irradiance variation of the different eye structures. The simulation of dark pupil effects along with multiple 1st-order Purkinje images will be presented. A parametric analysis is performed to investigate the relationships between the IRLED configurations and the irradiance distribution at the eye, and a set of optimal configuration parameters is recommended. The analysis will be further refined by actual eye image acquisition and processing.

Optimal investment for enhancing social concern about biodiversity conservation: a dynamic approach.

PubMed

Lee, Joung Hun; Iwasa, Yoh

2012-11-01

To maintain biodiversity conservation areas, we need to invest in activities, such as monitoring the condition of the ecosystem, preventing illegal exploitation, and removing harmful alien species. These require a constant supply of resources, the level of which is determined by the concern of the society about biodiversity conservation. In this paper, we study the optimal fraction of the resources to invest in activities for enhancing the social concern y(t) by environmental education, museum displays, publications, and media exposure. We search for the strategy that maximizes the time-integral of the quality of the conservation area x(t) with temporal discounting. Analyses based on dynamic programming and Pontryagin's maximum principle show that the optimal control consists of two phases: (1) in the first phase, the social concern level approaches to the final optimal value y(∗), (2) in the second phase, resources are allocated to both activities, and the social concern level is kept constant y(t) = y(∗). If the social concern starts from a low initial level, the optimal path includes a period in which the quality of the conservation area declines temporarily, because all the resources are invested to enhance the social concern. When the support rate increases with the quality of the conservation area itself x(t) as well as with the level of social concern y(t), both variables may increase simultaneously in the second phase. We discuss the implication of the results to good management of biodiversity conservation areas. 2012 Elsevier Inc. All rights reserved

Optimizing real-time Web-based user interfaces for observatories

NASA Astrophysics Data System (ADS)

Gibson, J. Duane; Pickering, Timothy E.; Porter, Dallan; Schaller, Skip

2008-08-01

In using common HTML/Ajax approaches for web-based data presentation and telescope control user interfaces at the MMT Observatory (MMTO), we rapidly were confronted with web browser performance issues. Much of the operational data at the MMTO is highly dynamic and is constantly changing during normal operations. Status of telescope subsystems must be displayed with minimal latency to telescope operators and other users. A major motivation of migrating toward web-based applications at the MMTO is to provide easy access to current and past observatory subsystem data for a wide variety of users on their favorite operating system through a familiar interface, their web browser. Performance issues, especially for user interfaces that control telescope subsystems, led to investigations of more efficient use of HTML/Ajax and web server technologies as well as other web-based technologies, such as Java and Flash/Flex. The results presented here focus on techniques for optimizing HTML/Ajax web applications with near real-time data display. This study indicates that direct modification of the contents or "nodeValue" attribute of text nodes is the most efficient method of updating data values displayed on a web page. Other optimization techniques are discussed for web-based applications that display highly dynamic data.

Autostereoscopic 3D display system with dynamic fusion of the viewing zone under eye tracking: principles, setup, and evaluation [Invited].

PubMed

Yoon, Ki-Hyuk; Kang, Min-Koo; Lee, Hwasun; Kim, Sung-Kyu

2018-01-01

We study optical technologies for viewer-tracked autostereoscopic 3D display (VTA3D), which provides improved 3D image quality and extended viewing range. In particular, we utilize a technique-the so-called dynamic fusion of viewing zone (DFVZ)-for each 3D optical line to realize image quality equivalent to that achievable at optimal viewing distance, even when a viewer is moving in a depth direction. In addition, we examine quantitative properties of viewing zones provided by the VTA3D system that adopted DFVZ, revealing that the optimal viewing zone can be formed at viewer position. Last, we show that the comfort zone is extended due to DFVZ. This is demonstrated by a viewer's subjective evaluation of the 3D display system that employs both multiview autostereoscopic 3D display and DFVZ.

Portable waveguide display system with a large field of view by integrating freeform elements and volume holograms.

PubMed

Han, Jian; Liu, Juan; Yao, Xincheng; Wang, Yongtian

2015-02-09

A compact waveguide display system integrating freeform elements and volume holograms is presented here for the first time. The use of freeform elements can broaden the field of view, which limits the applications of a holographic waveguide. An optimized system can achieve a diagonal field of view of 45° when the thickness of the waveguide planar is 3mm. Freeform-elements in-coupler and the volume holograms out-coupler were designed in detail in our study, and the influence of grating configurations on diffraction efficiency was analyzed thoroughly. The off-axis aberrations were well compensated by the in-coupler and the diffraction efficiency of the optimized waveguide display system could reach 87.57%. With integrated design, stability and reliability of this monochromatic display system were achieved and the alignment of the system was easily controlled by the record of the volume holograms, which makes mass production possible.

Portable waveguide display system with a large field of view by integrating freeform elements and volume holograms

PubMed Central

Han, Jian; Liu, Juan; Yao, Xincheng; Wang, Yongtian

2015-01-01

A compact waveguide display system integrating freeform elements and volume holograms is presented here for the first time. The use of freeform elements can broaden the field of view, which limits the applications of a holographic waveguide. An optimized system can achieve a diagonal field of view of 45° when the thickness of the waveguide planar is 3mm. Freeform-elements in-coupler and the volume holograms out-coupler were designed in detail in our study, and the influence of grating configurations on diffraction efficiency was analyzed thoroughly. The off-axis aberrations were well compensated by the in-coupler and the diffraction efficiency of the optimized waveguide display system could reach 87.57%. With integrated design, stability and reliability of this monochromatic display system were achieved and the alignment of the system was easily controlled by the record of the volume holograms, which makes mass production possible. PMID:25836207

Finding-specific display presets for computed radiography soft-copy reading.

PubMed

Andriole, K P; Gould, R G; Webb, W R

1999-05-01

Much work has been done to optimize the display of cross-sectional modality imaging examinations for soft-copy reading (i.e., window/level tissue presets, and format presentations such as tile and stack modes, four-on-one, nine-on-one, etc). Less attention has been paid to the display of digital forms of the conventional projection x-ray. The purpose of this study is to assess the utility of providing presets for computed radiography (CR) soft-copy display, based not on the window/level settings, but on processing applied to the image optimized for visualization of specific findings, pathologies, etc (i.e., pneumothorax, tumor, tube location). It is felt that digital display of CR images based on finding-specific processing presets has the potential to: speed reading of digital projection x-ray examinations on soft copy; improve diagnostic efficacy; standardize display across examination type, clinical scenario, important key findings, and significant negatives; facilitate image comparison; and improve confidence in and acceptance of soft-copy reading. Clinical chest images are acquired using an Agfa-Gevaert (Mortsel, Belgium) ADC 70 CR scanner and Fuji (Stamford, CT) 9000 and AC2 CR scanners. Those demonstrating pertinent findings are transferred over the clinical picture archiving and communications system (PACS) network to a research image processing station (Agfa PS5000), where the optimal image-processing settings per finding, pathologic category, etc, are developed in conjunction with a thoracic radiologist, by manipulating the multiscale image contrast amplification (Agfa MUSICA) algorithm parameters. Soft-copy display of images processed with finding-specific settings are compared with the standard default image presentation for 50 cases of each category. Comparison is scored using a 5-point scale with the positive scale denoting the standard presentation is preferred over the finding-specific processing, the negative scale denoting the finding-specific processing is preferred over the standard presentation, and zero denoting no difference. Processing settings have been developed for several findings including pneumothorax and lung nodules, and clinical cases are currently being collected in preparation for formal clinical trials. Preliminary results indicate a preference for the optimized-processing presentation of images over the standard default, particularly by inexperienced radiology residents and referring clinicians.

Development of a PC interface board for true color control using an Ar Kr white-light laser

NASA Astrophysics Data System (ADS)

Shin, Yongjin; Park, Sohee; Kim, Youngseop; Lee, Jangwoen

2006-06-01

For the optimal laser display, it is crucial to select and control color signals of proper wavelengths in order to construct a wide range of laser display colors. In traditional laser display schemes, color control has been achieved through the mechanical manipulation of red, green, and blue (RGB) laser beam intensities using color filters. To maximize the effect of a laser display and its color contents, it is desirable to generate laser beams with wide selection of wavelengths. We present an innovative laser display control technique, which generates six channel laser wavelengths from a white-light laser using a RF-controlled polychromatic acousto optical modulator (PCAOM). This technique enables us not only to control the intensity of individual channels, but also to achieve true color signals for the laser beam display including RGB, yellow, cyan, and violet (YCV), and other intermediate colors. For the optimal control of the PCAOM and galvano-mirror, we designed and fabricated a PC interface board. Using this PC control, we separated the white-light from an Ar-Kr mixed gas laser into various wavelengths and reconstructed them into different color schemes. Also we demonstrated the effective control and simultaneous display of reconstructed true color laser beams on a flat screen.

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.

State-of-the-Art Diagnosis and Treatment of Melanoma: Optimal Multidetector Computed Tomographic Practice to Identify Metastatic Disease and Review of Innovative Therapeutic Agents.

PubMed

Jones, Blake C; Lipson, Evan J; Childers, Brandon; Fishman, Elliot K; Johnson, Pamela T

The incidence of melanoma has risen dramatically over the past several decades. Oncologists rely on the ability of radiologists to identify subtle radiographic changes representing metastatic and recurrent melanoma in uncommon locations on multidetector computed tomography (MDCT) as the front-line imaging surveillance tool. To accomplish this goal, MDCT acquisition and display must be optimized and radiologist interpretation and search patterns must be tailored to identify the unique and often subtle metastatic lesions of melanoma. This article describes MDCT acquisition and display techniques that optimize the visibility of melanoma lesions, such as high-contrast display windows and multiplanar reconstructions. In addition, innovative therapies for melanoma, such as immunotherapy and small-molecule therapy, have altered clinical management and outcomes and have also changed the spectrum of therapeutic complications that can be detected on MDCT. Recent advances in melanoma therapy and potential complications that the radiologist can identify on MDCT are reviewed.

Formulation of electroclinic, ferroelectric and antiferroelectric liquid crystal mixtures suitable for display devices

NASA Astrophysics Data System (ADS)

Debnath, Asim; Goswami, Debarghya; Mandal, Pradip Kumar

2018-04-01

Most of the liquid crystal display (LCD) devices starting from simplest wrist watches or calculators to complex laptops or flat TV sets are based on nematics. Although a tremendous improvement in the quality of display as well as reduction of manufacturing cost has taken place over the years, there are many issues which the LC industry is trying hard to address. Ferroelectric liquid crystals (FLC) are of current interest in the LCD industry since among various other advantages FLC based displays have micro-second order switching compared to milli-second order switching in nematic based displays. To meet the market demand much effort has been made to optimize the physical parameters of FLCs, such as temperature range, spontaneous polarization (PS), helical pitch (p), switching time (τ), tilt angle (θ) and rotational viscosity (γ). Multicomponent mixtures are, therefore, formulated to optimize all the required properties for practical applications since no single FLC compound can satisfy the above requirements. To the best of our knowledge electroclinic, ferroelectric and antiferroelectric liquid crystal mixtures have been formulated first time by any Indian group which have properties suitable for FLC based display devices and at par with mixtures used in the industry.

Isolation of high-affinity, neutralizing anti-idiotype antibodies by phage and ribosome display for application in immunogenicity and pharmacokinetic analyses.

PubMed

Chin, Stacey E; Ferraro, Franco; Groves, Maria; Liang, Meina; Vaughan, Tristan J; Dobson, Claire L

2015-01-01

Anti-idiotype antibodies against a therapeutic antibody are key reagents for the development of immunogenicity and pharmacokinetic (PK) assays during pre-clinical and clinical development. Here we have used a combination of phage and ribosome display to isolate a panel of monoclonal anti-idiotype antibodies with sub-nanomolar affinity and high specificity to a human anti-IgE monoclonal antibody. Anti-idiotype antibodies were enriched from scFv libraries using phage display, and a biochemical epitope competition assay was used to identify anti-idiotypes which neutralized IgE binding, which was essential for the intended use of the anti-idiotypes as positive controls in neutralizing anti-drug antibody (Nab) assays. The phage display-derived anti-idiotype antibodies were rapidly affinity-matured using a random point mutagenesis approach in ribosome display. Ten anti-idiotype antibodies with improved neutralizing activity relative to the parent antibodies displayed sub-nanomolar affinity for the anti-IgE antibody, representing up to 20-fold improvements in affinity from just two rounds of affinity-based selection. The optimized anti-idiotype antibodies retained the specificity of the parent antibodies, and importantly, were fit for purpose for use in PK and anti-drug antibody (ADA) assays. The approach we describe here for generation of anti-idiotype antibodies to an anti-IgE antibody is generically applicable for the rapid isolation and affinity maturation of anti-idiotype antibodies to any antibody-based drug candidate. Copyright © 2014 Elsevier B.V. All rights reserved.

Phage display of engineered binding proteins.

PubMed

Levisson, Mark; Spruijt, Ruud B; Winkel, Ingrid Nolla; Kengen, Servé W M; van der Oost, John

2014-01-01

In current purification processes optimization of the capture step generally has a large impact on cost reduction. At present, valuable biomolecules are often produced in relatively low concentrations and, consequently, the eventual selective separation from complex mixtures can be rather inefficient. A separation technology based on a very selective high-affinity binding may overcome these problems. Proteins in their natural environment manifest functionality by interacting specifically and often with relatively high affinity with other molecules, such as substrates, inhibitors, activators, or other proteins. At present, antibodies are the most commonly used binding proteins in numerous applications. However, antibodies do have limitations, such as high production costs, low stability, and a complex patent landscape. A novel approach is therefore to use non-immunoglobulin engineered binding proteins in affinity purification. In order to obtain engineered binders with a desired specificity, a large mutant library of the new to-be-developed binding protein has to be created and screened for potential binders. A powerful technique to screen and select for proteins with desired properties from a large pool of variants is phage display. Here, we indicate several criteria for potential binding protein scaffolds and explain the principle of M13 phage display. In addition, we describe experimental protocols for the initial steps in setting up a M13 phage display system based on the pComb3X vector, including construction of the phagemid vector, production of phages displaying the protein of interest, and confirmation of display on the M13 phage.

Decoding emotional valence from electroencephalographic rhythmic activity.

PubMed

Celikkanat, Hande; Moriya, Hiroki; Ogawa, Takeshi; Kauppi, Jukka-Pekka; Kawanabe, Motoaki; Hyvarinen, Aapo

2017-07-01

We attempt to decode emotional valence from electroencephalographic rhythmic activity in a naturalistic setting. We employ a data-driven method developed in a previous study, Spectral Linear Discriminant Analysis, to discover the relationships between the classification task and independent neuronal sources, optimally utilizing multiple frequency bands. A detailed investigation of the classifier provides insight into the neuronal sources related with emotional valence, and the individual differences of the subjects in processing emotions. Our findings show: (1) sources whose locations are similar across subjects are consistently involved in emotional responses, with the involvement of parietal sources being especially significant, and (2) even though the locations of the involved neuronal sources are consistent, subjects can display highly varying degrees of valence-related EEG activity in the sources.

Adventures in Modern Time Series Analysis: From the Sun to the Crab Nebula and Beyond

NASA Technical Reports Server (NTRS)

Scargle, Jeffrey

2014-01-01

With the generation of long, precise, and finely sampled time series the Age of Digital Astronomy is uncovering and elucidating energetic dynamical processes throughout the Universe. Fulfilling these opportunities requires data effective analysis techniques rapidly and automatically implementing advanced concepts. The Time Series Explorer, under development in collaboration with Tom Loredo, provides tools ranging from simple but optimal histograms to time and frequency domain analysis for arbitrary data modes with any time sampling. Much of this development owes its existence to Joe Bredekamp and the encouragement he provided over several decades. Sample results for solar chromospheric activity, gamma-ray activity in the Crab Nebula, active galactic nuclei and gamma-ray bursts will be displayed.

Cellulase-assisted extraction and antibacterial activity of polysaccharides from the dandelion Taraxacum officinale.

PubMed

Wang, Hong-Bin

2014-03-15

In the present study, we investigated the cellulase-assisted extraction and antibacterial activity of water-soluble polysaccharides from the dandelion Taraxacum officinale. The extraction conditions, optimized for improving yield, were as follows: time, 46.11 min; temperature, 54.87 °C; pH, 4.51 and cellulase enzyme, 4000 U/g. Under these conditions, the yield of polysaccharides from dandelion (PD) reached 20.67% (w/w). The sugar content of PD was 95.6% (w/w), and it displayed high antibacterial activity at a concentration of 100mg/mL against Escherichia coli, Bacillus subtilis and Staphylococcus aureus. These results indicate that PD may be a viable option for use as a food preservative. Copyright © 2013 Elsevier Ltd. All rights reserved.

Decolorization of textile dye RB19 using volcanic rock matrix immobilized Bacillus thuringiensis cells with surface displayed laccase.

PubMed

Wan, Juan; Sun, Xiaowen; Liu, Cheng; Tang, Mengjun; Li, Lin; Ni, Hong

2017-06-01

A triplicate volcanic rock matrix-Bacillus thuringiensis-laccase WlacD (VRMs-Bt-WlacD) dye decolorization system was developed. WlacD was displayed on the B. thuringiensis MB174 cell surface to prepare a whole-cell laccase biocatalyst by using two repeat N-terminal domains of autolysin Mbg (Mbgn) 2 as the anchoring motif. Immunofluorescence microscopic assays confirmed that the fusion protein (Mbgn) 2 -WlacD was anchored on the surface of the recombinant B. thuringiensis MB174. After optimization by a single factor test, L 9 (3 4 )-orthogonal test, Plackett-Burman test, steepest ascent method, and Box-Behnken response surface methodology, the whole-cell specific laccase activity of B. thuringiensis MB174 was improved to 555.2 U L -1 , which was 2.25 times than that of the primary culture condition. Optimized B. thuringiensis MB174 cells were further adsorbed by VRMs to prepare VRMs-Bt-WlacD, an immobilized whole-cell laccase biocatalyst. Decolorization capacity of as-prepared VRMs-Bt-WlacD toward an initial concentration of 500 mg L -1 of an textile dye reactive blue 19 (RB19) aqueous solution reached 72.36% at a solid-to-liquid ratio of 10 g-100 mL. Repeated decolorization-activation operations showed the high decolorization capacity of VRMs-Bt-WlacD and have the potential for large-scale or continuous operations.

Optimized S-Trityl-l-cysteine-Based Inhibitors of Kinesin Spindle Protein with Potent in Vivo Antitumor Activity in Lung Cancer Xenograft Models

PubMed Central

2013-01-01

The mitotic kinesin Eg5 is critical for the assembly of the mitotic spindle and is a promising chemotherapy target. Previously, we identified S-trityl-l-cysteine as a selective inhibitor of Eg5 and developed triphenylbutanamine analogues with improved potency, favorable drug-like properties, but moderate in vivo activity. We report here their further optimization to produce extremely potent inhibitors of Eg5 (Kiapp < 10 nM) with broad-spectrum activity against cancer cell lines comparable to the Phase II drug candidates ispinesib and SB-743921. They have good oral bioavailability and pharmacokinetics and induced complete tumor regression in nude mice explanted with lung cancer patient xenografts. Furthermore, they display fewer liabilities with CYP-metabolizing enzymes and hERG compared with ispinesib and SB-743921, which is important given the likely application of Eg5 inhibitors in combination therapies. We present the case for this preclinical series to be investigated in single and combination chemotherapies, especially targeting hematological malignancies. PMID:23394180

Synthesis and biological evaluation of arctigenin ester and ether derivatives as activators of AMPK.

PubMed

Shen, Sida; Zhuang, Jingjing; Chen, Yijia; Lei, Min; Chen, Jing; Shen, Xu; Hu, Lihong

2013-07-01

A series of new arctigenin and 9-deoxy-arctigenin derivatives bearing different ester and ether side chains at the phenolic hydroxyl positions are designed, synthesized, and evaluated for activating AMPK potency in L6 myoblasts. Initial biological evaluation indicates that some alkyl ester and phenethyl ether arctigenin derivatives display potential activities in AMPK phosphorylation improvement. Further structure-activity relationship analysis shows that arctigenin ester derivatives 3a, 3h and 9-deoxy-arctigenin phenethyl ether derivatives 6a, 6c, 6d activate AMPK more potently than arctigenin. Moreover, the 2-(3,4-dimethoxyphenyl)ethyl ether moiety of 6c has been demonstrated as a potential functional group to improve the effect of AMPK phosphorylation. The structural optimization of arctigenin leads to the identification of 6c as a promising lead compound that exhibits excellent activity in AMPK activation. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

Discovery of 2-(3,5-difluoro-4-methylsulfonaminophenyl)propanamides as potent TRPV1 antagonists.

PubMed

Kim, Changhoon; Ann, Jihyae; Lee, Sunho; Sun, Wei; Blumberg, Peter M; Frank-Foltyn, Robert; Bahrenberg, Gregor; Stockhausen, Hannelore; Christoph, Thomas; Lee, Jeewoo

2018-05-23

A series of A-region analogues of 2-(3-fluoro-4-methylsufonamidophenyl) propanamide 1 were investigated as TRPV1 antagonists. The analysis of structure-activity relationship indicated that a fluoro group at the 3- (or/and) 5-position and a methylsulfonamido group at the 4-position were optimal for antagonism of TRPV1 activation by capsaicin. The most potent antagonist 6 not only exhibited potent antagonism of activation of hTRPV1 by capsaicin, low pH and elevated temperature but also displayed highly potent antagonism of activation of rTRPV1 by capsaicin. Further studies demonstrated that antagonist 6 blocked the hypothermic effect of capsaicin in vivo, consistent with its in vitro mechanism, and it showed promising analgesic activity in the formalin animal model. Copyright © 2018 Elsevier Ltd. All rights reserved.

Production of itaconic acid in Escherichia coli expressing recombinant α-amylase using starch as substrate.

PubMed

Okamoto, Shusuke; Chin, Taejun; Nagata, Keisuke; Takahashi, Tetsuya; Ohara, Hitomi; Aso, Yuji

2015-05-01

Several studies on fermentative production of a vinyl monomer itaconic acid from hydrolyzed starch using Aspergillus terreus have been reported. Herein, we report itaconic acid production by Escherichia coli expressing recombinant α-amylase, using soluble starch as its sole carbon source. To express α-amylase in E. coli, we first constructed recombinant plasmids expressing α-amylases by using cell surface display technology derived from two amylolytic bacteria, Bacillus amyloliquefaciens NBRC 15535(T) and Streptococcus bovis NRIC 1535. The recombinant α-amylase from S. bovis (SBA) showed activity at 28°C, which is the optimal temperature for production of itaconic acid, while α-amylase from B. amyloliquefaciens displayed no noticeable activity. E. coli cells expressing SBA produced 0.15 g/L itaconic acid after 69 h cultivation under pH-stat conditions, using 1% starch as the sole carbon source. In fact, E. coli cells expressing SBA had similar growth rates when grown in the presence of 1% glucose or starch, thereby highlighting the expression of an active α-amylase that enabled utilization of starch to produce itaconic acid in E. coli. Copyright © 2014 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Electrical latency predicts the optimal left ventricular endocardial pacing site: results from a multicentre international registry.

PubMed

Sieniewicz, Benjamin J; Behar, Jonathan M; Sohal, Manav; Gould, Justin; Claridge, Simon; Porter, Bradley; Niederer, Steve; Gamble, James H P; Betts, Tim R; Jais, Pierre; Derval, Nicolas; Spragg, David D; Steendijk, Paul; van Gelder, Berry M; Bracke, Frank A; Rinaldi, Christopher A

2018-04-23

The optimal site for biventricular endocardial (BIVENDO) pacing remains undefined. Acute haemodynamic response (AHR) is reproducible marker of left ventricular (LV) contractility, best expressed as the change in the maximum rate of LV pressure (LV-dp/dtmax), from a baseline state. We examined the relationship between factors known to impact LV contractility, whilst delivering BIVENDO pacing at a variety of LV endocardial (LVENDO) locations. We compiled a registry of acute LVENDO pacing studies from five international centres: Johns Hopkins-USA, Bordeaux-France, Eindhoven-The Netherlands, Oxford-United Kingdom, and Guys and St Thomas' NHS Foundation Trust, London-UK. In all, 104 patients incorporating 687 endocardial and 93 epicardial pacing locations were studied. Mean age was 66 ± 11 years, mean left ventricular ejection fraction 24.6 ± 7.7% and mean QRS duration of 163 ± 30 ms. In all, 50% were ischaemic [ischaemic cardiomyopathy (ICM)]. Scarred segments were associated with worse haemodynamics (dp/dtmax; 890 mmHg/s vs. 982 mmHg/s, P < 0.01). Delivering BiVENDO pacing in areas of electrical latency was associated with greater improvements in AHR (P < 0.01). Stimulating late activating tissue (LVLED >50%) achieved greater increases in AHR than non-late activating tissue (LVLED < 50%) (8.6 ± 9.6% vs. 16.1 ± 16.2%, P = 0.002). However, the LVENDO pacing location with the latest Q-LV, was associated with the optimal AHR in just 62% of cases. Identifying viable LVENDO tissue which displays late electrical activation is crucial to identifying the optimal BiVENDO pacing site. Stimulating late activating tissue (LVLED >50%) yields greater improvements in AHR however, the optimal location is frequently not the site of latest activation.

An organic white light-emitting dye: very small molecular architecture displays panchromatic emission.

PubMed

Nandhikonda, Premchendar; Heagy, Michael D

2010-11-14

The synthesis and photophysical characterization of a new white-light fluorophore is described. The optimization of excitation wavelengths allows the naphthalimide (NI) dyes to display blue, green or white light emission depending on the excitation wavelength.

The role of size of input box, location of input box, input method and display size in Chinese handwriting performance and preference on mobile devices.

PubMed

Chen, Zhe; Rau, Pei-Luen Patrick

2017-03-01

This study presented two experiments on Chinese handwriting performance (time, accuracy, the number of protruding strokes and number of rewritings) and subjective ratings (mental workload, satisfaction, and preference) on mobile devices. Experiment 1 evaluated the effects of size of the input box, input method and display size on Chinese handwriting performance and preference. It was indicated that the optimal input sizes were 30.8 × 30.8 mm, 46.6 × 46.6 mm, 58.9 × 58.9 mm and 84.6 × 84.6 mm for devices with 3.5-inch, 5.5-inch, 7.0-inch and 9.7-inch display sizes, respectively. Experiment 2 proved the significant effects of location of the input box, input method and display size on Chinese handwriting performance and subjective ratings. It was suggested that the optimal location was central regardless of display size and input method. Copyright © 2016 Elsevier Ltd. All rights reserved.

Ly49H signaling through DAP10 is essential for optimal natural killer cell responses to mouse cytomegalovirus infection

PubMed Central

Orr, Mark T.; Sun, Joseph C.; Hesslein, David G.T.; Arase, Hisashi; Phillips, Joseph H.; Takai, Toshiyuki

2009-01-01

The activating natural killer (NK) cell receptor Ly49H recognizes the mouse cytomegalovirus (MCMV) m157 glycoprotein expressed on the surface of infected cells and is required for protection against MCMV. Although Ly49H has previously been shown to signal via DAP12, we now show that Ly49H must also associate with and signal via DAP10 for optimal function. In the absence of DAP12, DAP10 enables Ly49H-mediated killing of m157-bearing target cells, proliferation in response to MCMV infection, and partial protection against MCMV. DAP10-deficient Ly49H+ NK cells, expressing only Ly49H–DAP12 receptor complexes, are partially impaired in their ability to proliferate during MCMV infection, display diminished ERK1/2 activation, produce less IFN-γ upon Ly49H engagement, and demonstrate reduced control of MCMV infection. Deletion of both DAP10 and DAP12 completely abrogates Ly49H surface expression and control of MCMV infection. Thus, optimal NK cell–mediated immunity to MCMV depends on Ly49H signaling through both DAP10 and DAP12. PMID:19332875

Organic antireflective coatings for 193-nm lithography

NASA Astrophysics Data System (ADS)

Trefonas, Peter, III; Blacksmith, Robert F.; Szmanda, Charles R.; Kavanagh, Robert J.; Adams, Timothy G.; Taylor, Gary N.; Coley, Suzanne; Pohlers, Gerd

1999-06-01

Organic anti-reflective coatings (ARCs) continue to play an important role in semiconductor manufacturing. These materials provide a convenient means of greatly reducing the resist photospeed swing and reflective notching. In this paper, we describe a novel class of ARC materials optimized for lithographic applications using 193 nm exposure tools. These ARCs are based upon polymers containing hydroxyl-alkyl methacrylate monomers for crosslinkable sites, styrene for a chromophore at 193 nm, and additional alkyl-methacrylate monomers as property modifiers. A glycouril crosslinker and a thermally-activated acidic catalyst provide a route to forming an impervious crosslinked film activate data high bake temperatures. ARC compositions can be adjusted to optimize the film's real and imaginary refractive indices. Selection of optimal target indices for 193 nm lithographic processing through simulations is described. Potential chromophores for 193 nm were explored using ZNDO modeling. We show how these theoretical studies were combined with material selection criteria to yield a versatile organic anti-reflectant film, Shipley 193 G0 ARC. Lithographic process data indicates the materials is capable of supporting high resolution patterning, with the line features displaying a sharp resist/ARC interface with low line edge roughness. The resist Eo swing is successfully reduced from 43 percent to 6 percent.

Low-temperature-active and salt-tolerant β-mannanase from a newly isolated Enterobacter sp. strain N18.

PubMed

You, Jia; Liu, Jin-Feng; Yang, Shi-Zhong; Mu, Bo-Zhong

2016-02-01

A low-temperature-active and salt-tolerant β-mannanase produced by a novel mannanase-producer, Enterobacter sp. strain N18, was isolated, purified and then evaluated for its potential application as a gel-breaker in relation to viscosity reduction of guar-based hydraulic fracturing fluids used in oil field. The enzyme could lower the viscosity of guar gum solution by more than 95% within 10 min. The purified β-mannanase with molecular mass of 90 kDa displayed high activity in a broad range of pH and temperature: more than 70% of activity was retained in the pH range of 3.0-8.0 with the optimal pH 7.5, about 50% activity at 20°C with the optimal temperature 50°C. Furthermore, the enzyme retained >70% activity in the presence of 0.5-4.0 M NaCl. These properties implied that the enzyme from strain N18 had potential for serving as a gel-breaker for low temperature oil wells and other industrial fields, where chemical gel breakers were inactive due to low temperature. Copyright © 2015 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Analytic Energy Gradients for Variational Two-Electron Reduced-Density-Matrix-Driven Complete Active Space Self-Consistent Field Theory.

PubMed

Maradzike, Elvis; Gidofalvi, Gergely; Turney, Justin M; Schaefer, Henry F; DePrince, A Eugene

2017-09-12

Analytic energy gradients are presented for a variational two-electron reduced-density-matrix (2-RDM)-driven complete active space self-consistent field (CASSCF) method. The active-space 2-RDM is determined using a semidefinite programing (SDP) algorithm built upon an augmented Lagrangian formalism. Expressions for analytic gradients are simplified by the fact that the Lagrangian is stationary with respect to variations in both the primal and the dual solutions to the SDP problem. Orbital response contributions to the gradient are identical to those that arise in conventional CASSCF methods in which the electronic structure of the active space is described by a full configuration interaction (CI) wave function. We explore the relative performance of variational 2-RDM (v2RDM)- and CI-driven CASSCF for the equilibrium geometries of 20 small molecules. When enforcing two-particle N-representability conditions, full-valence v2RDM-CASSCF-optimized bond lengths display a mean unsigned error of 0.0060 Å and a maximum unsigned error of 0.0265 Å, relative to those obtained from full-valence CI-CASSCF. When enforcing partial three-particle N-representability conditions, the mean and maximum unsigned errors are reduced to only 0.0006 and 0.0054 Å, respectively. For these same molecules, full-valence v2RDM-CASSCF bond lengths computed in the cc-pVQZ basis set deviate from experimentally determined ones on average by 0.017 and 0.011 Å when enforcing two- and three-particle conditions, respectively, whereas CI-CASSCF displays an average deviation of 0.010 Å. The v2RDM-CASSCF approach with two-particle conditions is also applied to the equilibrium geometry of pentacene; optimized bond lengths deviate from those derived from experiment, on average, by 0.015 Å when using a cc-pVDZ basis set and a (22e,22o) active space.

Micromirror-based real image laser automotive head-up display

NASA Astrophysics Data System (ADS)

Fan, Chao; He, Siyuan

2017-01-01

This paper reports a micromirror-based real image laser automotive head-up display (HUD), which overcomes the limitations of the previous designs by: (1) implementing an advanced display approach which is able to display sharp corners while the previous designs can only display curved lines such as to improve the display fidelity and (2) Optimizing the optical configuration to significantly reduce the HUD module size. The optical design in the HUD is simulated to choose the off-the-shelf concave lens. The vibration test is conducted to verify that the micromirror can survive 5 g. The prototype of the HUD system is fabricated and tested.

Light budget and optimization strategies for display applications of dichroic nematic droplet/polymer films

NASA Astrophysics Data System (ADS)

Drzaic, Paul S.

1991-06-01

A detailed light budget is performed on reflective displays made from nematic droplet/polymer (NCAP) films incorporating dichroic dyes. It is shown that the radiance of these displays can be modeled using a simple scheme involving the convolution of the transmission spectra of the various components of the display. Comparisons are made between the relative importance of these optical elements in the display. It is shown that first-surface reflection (glare) is an important factor in reducing the optical performance of these displays, but that the effect of glare can be minimized through the proper choice of dye concentration.

High hydrostatic pressure affects antigenic pool in tumor cells: Implication for dendritic cell-based cancer immunotherapy.

PubMed

Urbanova, Linda; Hradilova, Nada; Moserova, Irena; Vosahlikova, Sarka; Sadilkova, Lenka; Hensler, Michal; Spisek, Radek; Adkins, Irena

2017-07-01

High hydrostatic pressure (HHP) can be used to generate dendritic cell (DC)-based active immunotherapy for prostate, lung and ovarian cancer. We showed here that HHP treatment of selected human cancer cell lines leads to a degradation of tumor antigens which depends on the magnitude of HHP applied and on the cancer cell line origin. Whereas prostate or ovarian cell lines displayed little protein antigen degradation with HHP treatment up to 300MPa after 2h, tumor antigens are hardly detected in lung cancer cell line after treatment with HHP 250MPa at the same time. On the other hand, quick reduction of tumor antigen-coding mRNA was observed at HHP 200MPa immediately after treatment in all cell lines tested. To optimize the DC-based active cellular therapy protocol for HHP-sensitive cell lines the immunogenicity of HHP-treated lung cancer cells at 150, 200 and 250MPa was compared. Lung cancer cells treated with HHP 150MPa display characteristics of immunogenic cell death, however cells are not efficiently phagocytosed by DC. Despite induction of the highest number of antigen-specific CD8 + T cells, 150 MPa-treated lung cancer cells survive in high numbers. This excludes their use in DC vaccine manufacturing. HHP of 200MPa treatment of lung cancer cells ensures the optimal ratio of efficient immunogenic killing and delivery of protein antigens in DC. These results represent an important pre-clinical data for generation of immunogenic killed lung cancer cells in ongoing NSCLC Phase I/II clinical trial using DC-based active cellular immunotherapy (DCVAC/LuCa). Copyright © 2017 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

Up-conversion in rare-earth doped micro-particles applied to new emissive two-dimensional displays

NASA Astrophysics Data System (ADS)

Milliez, Anne Janet

Up-conversion (UC) in rare-earth co-doped fluorides to convert diode laser light in the near infrared to red, green and blue visible light is applied to make possible high performance emissive displays. The infrared-to-visible UC in the materials we study is a sequential form of non-linear two photon absorption in which a strong absorbing constituent absorbs two low energy photons and transfers this energy to another constituent which emits visible light. Some of the UC emitters' most appealing characteristics for displays are: a wide color gamut with very saturated colors, very high brightness operation without damage to the emitters, long lifetimes and efficiencies comparable to those of existing technologies. Other advantages include simplicity of fabrication, versatility of operating modes, and the potential for greatly reduced display weight and depth. Thanks to recent advances in material science and diode laser technology at the excitation wavelength, UC selected materials can be very efficient visible emitters. However, optimal UC efficiencies strongly depend on chosing proper operating conditions. In this thesis, we studied the conditions required for optimization. We demonstrated that high efficiency UC depends on high pump irradiance, low temperature and low scattering. With this understanding we can predict how to optimally use UC emitters in a wide range of applications. In particular, we showed how our very efficient UC emitters can be applied to make full color displays and very efficient white light sources.

Development and Optimization of a Fluorescent Differential Display PCR System for Analyzing the Stress Response in Lactobacillus sakei Strains

PubMed Central

Bonomo, Maria Grazia; Sico, Maria Anna; Grieco, Simona; Salzano, Giovanni

2009-01-01

Lactobacillus sakei is widely used as starter in the production process of Italian fermented sausages and its growth and survival are affected by various factors. We studied the differential expression of genome in response to different stresses by the fluorescent differential display (FDD) technique. This study resulted in the development and optimization of an innovative technique, with a high level of reproducibility and quality, which allows the identification of gene expression changes associated with different microbial behaviours under different growth conditions. PMID:22253979

Part-Task Simulation of Synthetic and Enhanced Vision Concepts for Lunar Landing

NASA Technical Reports Server (NTRS)

Arthur, Jarvis J., III; Bailey, Randall E.; Jackson, E. Bruce; Williams, Steven P.; Kramer, Lynda J.; Barnes, James R.

2010-01-01

During Apollo, the constraints placed by the design of the Lunar Module (LM) window for crew visibility and landing trajectory were a major problem. Lunar landing trajectories were tailored to provide crew visibility using nearly 70 degrees look-down angle from the canted LM windows. Apollo landings were scheduled only at specific times and locations to provide optimal sunlight on the landing site. The complications of trajectory design and crew visibility are still a problem today. Practical vehicle designs for lunar lander missions using optimal or near-optimal fuel trajectories render the natural vision of the crew from windows inadequate for the approach and landing task. Further, the sun angles for the desirable landing areas in the lunar polar regions create visually powerful, season-long shadow effects. Fortunately, Synthetic and Enhanced Vision (S/EV) technologies, conceived and developed in the aviation domain, may provide solutions to this visibility problem and enable additional benefits for safer, more efficient lunar operations. Piloted simulation evaluations have been conducted to assess the handling qualities of the various lunar landing concepts, including the influence of cockpit displays and the informational data and formats. Evaluation pilots flew various landing scenarios with S/EV displays. For some of the evaluation trials, an eye glasses-mounted, monochrome monocular display, coupled with head tracking, was worn. The head-worn display scene consisted of S/EV fusion concepts. The results of this experiment showed that a head-worn system did not increase the pilot s workload when compared to using just the head-down displays. As expected, the head-worn system did not provide an increase in performance measures. Some pilots commented that the head-worn system provided greater situational awareness compared to just head-down displays.

Part-task simulation of synthetic and enhanced vision concepts for lunar landing

NASA Astrophysics Data System (ADS)

Arthur, Jarvis J., III; Bailey, Randall E.; Jackson, E. Bruce; Barnes, James R.; Williams, Steven P.; Kramer, Lynda J.

2010-04-01

During Apollo, the constraints placed by the design of the Lunar Module (LM) window for crew visibility and landing trajectory were "a major problem." Lunar landing trajectories were tailored to provide crew visibility using nearly 70 degrees look-down angle from the canted LM windows. Apollo landings were scheduled only at specific times and locations to provide optimal sunlight on the landing site. The complications of trajectory design and crew visibility are still a problem today. Practical vehicle designs for lunar lander missions using optimal or near-optimal fuel trajectories render the natural vision of the crew from windows inadequate for the approach and landing task. Further, the sun angles for the desirable landing areas in the lunar polar regions create visually powerful, season-long shadow effects. Fortunately, Synthetic and Enhanced Vision (S/EV) technologies, conceived and developed in the aviation domain, may provide solutions to this visibility problem and enable additional benefits for safer, more efficient lunar operations. Piloted simulation evaluations have been conducted to assess the handling qualities of the various lunar landing concepts, including the influence of cockpit displays and the informational data and formats. Evaluation pilots flew various landing scenarios with S/EV displays. For some of the evaluation trials, an eye glasses-mounted, monochrome monocular display, coupled with head tracking, was worn. The head-worn display scene consisted of S/EV fusion concepts. The results of this experiment showed that a head-worn system did not increase the pilot's workload when compared to using just the head-down displays. As expected, the head-worn system did not provide an increase in performance measures. Some pilots commented that the head-worn system provided greater situational awareness compared to just head-down displays.

Development and application of computer assisted optimal method for treatment of femoral neck fracture.

PubMed

Wang, Monan; Zhang, Kai; Yang, Ning

2018-04-09

To help doctors decide their treatment from the aspect of mechanical analysis, the work built a computer assisted optimal system for treatment of femoral neck fracture oriented to clinical application. The whole system encompassed the following three parts: Preprocessing module, finite element mechanical analysis module, post processing module. Preprocessing module included parametric modeling of bone, parametric modeling of fracture face, parametric modeling of fixed screw and fixed position and input and transmission of model parameters. Finite element mechanical analysis module included grid division, element type setting, material property setting, contact setting, constraint and load setting, analysis method setting and batch processing operation. Post processing module included extraction and display of batch processing operation results, image generation of batch processing operation, optimal program operation and optimal result display. The system implemented the whole operations from input of fracture parameters to output of the optimal fixed plan according to specific patient real fracture parameter and optimal rules, which demonstrated the effectiveness of the system. Meanwhile, the system had a friendly interface, simple operation and could improve the system function quickly through modifying single module.

Development and Application of a Virtual Screening Protocol for the Identification of Multitarget Fragments.

PubMed

Bottegoni, Giovanni; Veronesi, Marina; Bisignano, Paola; Kacker, Puneet; Favia, Angelo D; Cavalli, Andrea

2016-06-20

In this study, we report on a virtual ligand screening protocol optimized to identify fragments endowed with activity at multiple targets. Thanks to this protocol, we were able to identify a fragment that displays activity in the low-micromolar range at both β-secretase 1 (BACE-1) and glycogen synthase kinase 3β (GSK-3β). These two structurally and physiologically unrelated enzymes likely contribute, through different pathways, to the onset of Alzheimer's disease (AD). Therefore, their simultaneous inhibition holds great potential in exerting a profound effect on AD. In perspective, the strategy outlined herein can be adapted to other target combinations. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

JTEC panel on display technologies in Japan

NASA Technical Reports Server (NTRS)

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

1992-01-01

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

Contrast Transmission In Medical Image Display

NASA Astrophysics Data System (ADS)

Pizer, Stephen M.; Zimmerman, John B.; Johnston, R. Eugene

1982-11-01

The display of medical images involves transforming recorded intensities such at CT numbers into perceivable intensities such as combinations of color and luminance. For the viewer to extract the most information about patterns of decreasing and increasing recorded intensity, the display designer must pay attention to three issues: 1) choice of display scale, including its discretization; 2) correction for variations in contrast sensitivity across the display scale due to the observer and the display device (producing an honest display); and 3) contrast enhancement based on the information in the recorded image and its importance, determined by viewing objectives. This paper will present concepts and approaches in all three of these areas. In choosing display scales three properties are important: sensitivity, associability, and naturalness of order. The unit of just noticeable difference (jnd) will be carefully defined. An observer experiment to measure the jnd values across a display scale will be specified. The overall sensitivity provided by a scale as measured in jnd's gives a measure of sensitivity called the perceived dynamic range (PDR). Methods for determining the PDR fran the aforementioned PDR values, and PDR's for various grey and pseudocolor scales will be presented. Methods of achieving sensitivity while retaining associability and naturalness of order with pseudocolor scales will be suggested. For any display device and scale it is useful to compensate for the device and observer by preceding the device with an intensity mapping (lookup table) chosen so that perceived intensity is linear with display-driving intensity. This mapping can be determined from the aforementioned jnd values. With a linearized display it is possible to standardize display devices so that the same image displayed on different devices or scales (e.g. video and hard copy) will be in sane sense perceptually equivalent. Furthermore, with a linearized display, it is possible to design contrast enhancement mappings that optimize the transmission of information from the recorded image to the display-driving signal with the assurance that this information will not then be lost by a -further nonlinear relation between display-driving and perceived intensity. It is suggested that optimal contrast enhancement mappings are adaptive to the local distribution of recorded intensities.

A manual control theory analysis of vertical situation displays for STOL aircraft

NASA Technical Reports Server (NTRS)

Baron, S.; Levison, W. H.

1973-01-01

Pilot-vehicle-display systems theory is applied to the analysis of proposed vertical situation displays for manual control in approach-to-landing of a STOL aircraft. The effects of display variables on pilot workload and on total closed-loop system performance was calculated using an optimal-control model for the human operator. The steep approach of an augmentor wing jet STOL aircraft was analyzed. Both random turbulence and mean-wind shears were considered. Linearized perturbation equations were used to describe longitudinal and lateral dynamics of the aircraft. The basic display configuration was one that abstracted the essential status information (including glide-slope and localizer errors) of an EADI display. Proposed flight director displays for both longitudinal and lateral control were also investigated.

Design and Solution-Phase Synthesis of Membrane-Targeting Lipopeptides with Selective Antibacterial Activity.

PubMed

Konai, Mohini M; Adhikary, Utsarga; Haldar, Jayanta

2017-09-18

Designing selective antibacterial molecules remains an unmet goal in the field of membrane-targeting agents. Herein, we report the rational design and synthesis of a new class of lipopeptides, which possess highly selective bacterial killing over mammalian cells. The selective interaction with bacterial over mammalian membranes was established through various spectroscopic, as well as microscopic experiments, including biophysical studies with the model membranes. A detailed antibacterial structure-activity relationship was delineated after preparing a series of molecules consisting of the peptide moieties with varied sequence of amino acids, such as d-phenylalanine, d-leucine, and d-lysine. Antibacterial activity was found to vary with the nature and positioning of hydrophobicity in the molecules, as well as number of positive charges. Optimized lipopeptide 9 did not show any hemolytic activity even at 1000 μg mL -1 and displayed >200-fold and >100-fold selectivity towards S. aureus and E. coli, respectively. More importantly, compound 9 was found to display good antibacterial activity (MIC 6.3-12.5 μg mL -1 ) against the five top most critical bacteria according to World Health Organization (WHO) priority pathogens list. Therefore, the results suggested that this new class of lipopeptides bear real promises for the development as future antibacterial agents. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Identification and statistical optimization of fermentation conditions for a newly isolated extracellular cholesterol oxidase-producing Streptomyces cavourensis strain NEAE-42.

PubMed

El-Naggar, Noura El-Ahmady; El-Shweihy, Nancy M; El-Ewasy, Sara M

2016-09-20

Due to broad range of clinical and industrial applications of cholesterol oxidase, isolation and screening of bacterial strains producing extracellular form of cholesterol oxidase is of great importance. One hundred and thirty actinomycete isolates were screened for their cholesterol oxidase activity. Among them, a potential culture, strain NEAE-42 is displayed the highest extracellular cholesterol oxidase activity. It was selected and identified as Streptomyces cavourensis strain NEAE-42. The optimization of different process parameters for cholesterol oxidase production by Streptomyces cavourensis strain NEAE-42 using Plackett-Burman experimental design and response surface methodology was carried out. Fifteen variables were screened using Plackett-Burman experimental design. Cholesterol, initial pH and (NH4)2SO4 were the most significant positive independent variables affecting cholesterol oxidase production. Central composite design was chosen to elucidate the optimal concentrations of the selected process variables on cholesterol oxidase production. It was found that, cholesterol oxidase production by Streptomyces cavourensis strain NEAE-42 after optimization process was 20.521U/mL which is higher than result obtained from the basal medium before screening process using Plackett-Burman (3.31 U/mL) with a fold of increase 6.19. The cholesterol oxidase level production obtained in this study (20.521U/mL) by the statistical method is higher than many of the reported values.

Discovery of potent 1H-imidazo[4,5-b]pyridine-based c-Met kinase inhibitors via mechanism-directed structural optimization.

PubMed

An, Xiao-De; Liu, Hongyan; Xu, Zhong-Liang; Jin, Yi; Peng, Xia; Yao, Ying-Ming; Geng, Meiyu; Long, Ya-Qiu

2015-02-01

Starting from our previously identified novel c-Met kinase inhibitors bearing 1H-imidazo[4,5-h][1,6]naphthyridin-2(3H)-one scaffold, a global structural exploration was conducted to furnish an optimal binding motif for further development, directed by the enzyme inhibitory mechanism. First round SAR study picked two imidazonaphthyridinone frameworks with 1,8- and 3,5-disubstitution pattern as class I and class II c-Met kinase inhibitors, respectively. Further structural optimization on type II inhibitors by truncation of the imidazonaphthyridinone core and incorporation of an N-phenyl cyclopropane-1,1-dicarboxamide pharmacophore led to the discovery of novel imidazopyridine-based c-Met kinase inhibitors, displaying nanomolar enzyme inhibitory activity and improved Met kinase selectivity. More significantly, the new chemotype c-Met kinase inhibitors effectively inhibited Met phosphorylation and its downstream signaling as well as the proliferation of Met-dependent EBC-1 human lung cancer cells at submicromolar concentrations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Green synthesis of silver nanoparticles using Mentha pulegium and investigation of their antibacterial, antifungal and anticancer activity.

PubMed

Kelkawi, Ali Hamad Abd; Abbasi Kajani, Abolghasem; Bordbar, Abdol-Khalegh

2017-06-01

A simple and eco-friendly method for efficient synthesis of stable colloidal silver nanoparticles (AgNPs) using Mentha pulegium extracts is described. A series of reactions was conducted using different types and concentrations of plant extract as well as metal ions to optimize the reaction conditions. AgNPs were characterized by using UV-vis spectroscopy, transmission electron microscopy, atomic force microscopy, dynamic light scattering, zetasizer, energy-dispersive X-ray spectroscopy (EDAX) and Fourier transform infrared spectroscopy (FTIR). At the optimized conditions, plate shaped AgNPs with zeta potential value of -15.7 and plasmon absorption maximum at 450 nm were obtained using high concentration of aqueous extract. Efficient adsorption of organic compounds on the nanoparticles was confirmed by FTIR and EDAX. The biogenic AgNPs displayed promising antibacterial activity on Escherichia coli , Staphylococcus aureus , and Streptococcus pyogenes . The highest antibacterial activity of 25 µg mL-1 was obtained for all the strains using aqueous extract synthesized AgNPs. The aqueous extract synthesised AgNPs also showed considerable antifungal activity against fluconazole resistant Candida albicans . The cytotoxicity assay revealed considerable anticancer activity of AgNPs on HeLa and MCF-7 cancer cells. Overall results indicated high potential of M. pulegium extract to synthesis high quality AgNPs for biomedical applications.

Electro-Optical Characterization of Bistable Smectic A Liquid Crystal Displays

NASA Astrophysics Data System (ADS)

Buyuktanir, Ebru Aylin

My dissertation focuses the characterization and optimization of the electro-optical properties of smectic A (SmA) based liquid crystal (LC) displays. I present the development of robust and flexible bistable SmA LC displays utilizing polymer dispersed liquid crystal (PDLC) technology. The SmA PDLC displays produced on plastic substrates present electrically reversible memory, high contrast ratio, paper-like sunlight readability, and wide viewing angle characteristics. In order to optimize the SmA PDLC display, I investigated polymerization conditions, such as polymer concentration effect, polymerization temperature, and UV-light intensity variations. I characterized the electro-optical responses-such as static-response, time-response, threshold characteristics, and contrast ratio values' of the optimized SmA PDLC display and compared them to those of the pure SmA LC. The best electro-optical performance of SmA PDLC formulation was obtained using the combination of low mW/cm 2 and high mW/cm2 UV-light curing intensity. The contrast ratio of the optimum SmA PDLC at a 5o collection angle was 83% of that of the pure SmA material on plastic substrates. I fabricated 2.5 x 2.5 in., 4 x 4 in., and 6 x 6 in. sized monochrome flexible SmA PDLC displays, as well as red, yellow, and fluorescent dyes colored SmA PDLC displays on plastic substrates. The electro-optic performance of the bistable SmA LC display consisting of a patterned field-induced polymer wall infrastructure was also studied and compared to those of pure SmA material. I found that the contrast ratio of the SmA LC encapsulated between polymer walls was much greater than that of the SmA PDLC system, approaching the contrast ratio value of the pure SmA material. I also improved the electro-optical characteristics of bistable SmA LC displays by adding ferroparticles into the system. Finally, I illustrated the unique capabilities of polarized confocal Raman microscopy (CRM) to resolve the orientational order of SmA LCs in three-dimension by investigating the characteristic vibrational bands of LC molecules. CRM provides a precise characterization of the molecular order at different depths of the LC films. I examined the director patterns of focal conic defects of smectic A LC, colloidal smectic A LC systems, and the field-oriented nematic LC in the horizontal and vertical planes.

Visual display aid for orbital maneuvering - Design considerations

NASA Technical Reports Server (NTRS)

Grunwald, Arthur J.; Ellis, Stephen R.

1993-01-01

This paper describes the development of an interactive proximity operations planning system that allows on-site planning of fuel-efficient multiburn maneuvers in a potential multispacecraft environment. Although this display system most directly assists planning by providing visual feedback to aid visualization of the trajectories and constraints, its most significant features include: (1) the use of an 'inverse dynamics' algorithm that removes control nonlinearities facing the operator, and (2) a trajectory planning technique that separates, through a 'geometric spreadsheet', the normally coupled complex problems of planning orbital maneuvers and allows solution by an iterative sequence of simple independent actions. The visual feedback of trajectory shapes and operational constraints, provided by user-transparent and continuously active background computations, allows the operator to make fast, iterative design changes that rapidly converge to fuel-efficient solutions. The planning tool provides an example of operator-assisted optimization of nonlinear cost functions.

Archaeal Inorganic Pyrophosphatase Displays Robust Activity under High-Salt Conditions and in Organic Solvents.

PubMed

McMillan, Lana J; Hepowit, Nathaniel L; Maupin-Furlow, Julie A

2016-01-15

Soluble inorganic pyrophosphatases (PPAs) that hydrolyze inorganic pyrophosphate (PPi) to orthophosphate (Pi) are commonly used to accelerate and detect biosynthetic reactions that generate PPi as a by-product. Current PPAs are inactivated by high salt concentrations and organic solvents, which limits the extent of their use. Here we report a class A type PPA of the haloarchaeon Haloferax volcanii (HvPPA) that is thermostable and displays robust PPi-hydrolyzing activity under conditions of 25% (vol/vol) organic solvent and salt concentrations from 25 mM to 3 M. HvPPA was purified to homogeneity as a homohexamer by a rapid two-step method and was found to display non-Michaelis-Menten kinetics with a Vmax of 465 U · mg(-1) for PPi hydrolysis (optimal at 42°C and pH 8.5) and Hill coefficients that indicated cooperative binding to PPi and Mg(2+). Similarly to other class A type PPAs, HvPPA was inhibited by sodium fluoride; however, hierarchical clustering and three-dimensional (3D) homology modeling revealed HvPPA to be distinct in structure from characterized PPAs. In particular, HvPPA was highly negative in surface charge, which explained its extreme resistance to organic solvents. To demonstrate that HvPPA could drive thermodynamically unfavorable reactions to completion under conditions of reduced water activity, a novel coupled assay was developed; HvPPA hydrolyzed the PPi by-product generated in 2 M NaCl by UbaA (a "salt-loving" noncanonical E1 enzyme that adenylates ubiquitin-like proteins in the presence of ATP). Overall, we demonstrate HvPPA to be useful for hydrolyzing PPi under conditions of reduced water activity that are a hurdle to current PPA-based technologies. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

Archaeal Inorganic Pyrophosphatase Displays Robust Activity under High-Salt Conditions and in Organic Solvents

PubMed Central

McMillan, Lana J.; Hepowit, Nathaniel L.

2015-01-01

Soluble inorganic pyrophosphatases (PPAs) that hydrolyze inorganic pyrophosphate (PPi) to orthophosphate (Pi) are commonly used to accelerate and detect biosynthetic reactions that generate PPi as a by-product. Current PPAs are inactivated by high salt concentrations and organic solvents, which limits the extent of their use. Here we report a class A type PPA of the haloarchaeon Haloferax volcanii (HvPPA) that is thermostable and displays robust PPi-hydrolyzing activity under conditions of 25% (vol/vol) organic solvent and salt concentrations from 25 mM to 3 M. HvPPA was purified to homogeneity as a homohexamer by a rapid two-step method and was found to display non-Michaelis-Menten kinetics with a Vmax of 465 U · mg−1 for PPi hydrolysis (optimal at 42°C and pH 8.5) and Hill coefficients that indicated cooperative binding to PPi and Mg2+. Similarly to other class A type PPAs, HvPPA was inhibited by sodium fluoride; however, hierarchical clustering and three-dimensional (3D) homology modeling revealed HvPPA to be distinct in structure from characterized PPAs. In particular, HvPPA was highly negative in surface charge, which explained its extreme resistance to organic solvents. To demonstrate that HvPPA could drive thermodynamically unfavorable reactions to completion under conditions of reduced water activity, a novel coupled assay was developed; HvPPA hydrolyzed the PPi by-product generated in 2 M NaCl by UbaA (a “salt-loving” noncanonical E1 enzyme that adenylates ubiquitin-like proteins in the presence of ATP). Overall, we demonstrate HvPPA to be useful for hydrolyzing PPi under conditions of reduced water activity that are a hurdle to current PPA-based technologies. PMID:26546423

In vitro activity of minimised hammerhead ribozymes.

PubMed Central

Hendry, P; McCall, M J; Santiago, F S; Jennings, P A

1995-01-01

A number of minimised hammerhead ribozymes (minizymes) which lack stem II have been kinetically characterised. These minizymes display optimal cleavage activity at temperatures around 37 degrees C. The cleavage reactions of the minizymes are first order in hydroxide ion concentration up to around pH 9.3 above which the cleavage rate constants decline rapidly. The reactions show a biphasic dependence on magnesium-ion concentration; one of the interactions has an apparent dissociation constant of around 20 mM while the other appears to be very weak, showing no sign of saturation at 200 mM MgCl2. The minizymes are significantly less active than comparable, full-size ribozymes when cleaving short substrates. However, at a particular site in a transcribed TAT gene from HIV-1, minizymes are more effective than ribozymes. PMID:7479037

Sitting in the Pilot's Seat; Optimizing Human-Systems Interfaces for Unmanned Aerial Vehicles

NASA Technical Reports Server (NTRS)

Queen, Steven M.; Sanner, Kurt Gregory

2011-01-01

One of the pilot-machine interfaces (the forward viewing camera display) for an Unmanned Aerial Vehicle called the DROID (Dryden Remotely Operated Integrated Drone) will be analyzed for optimization. The goal is to create a visual display for the pilot that as closely resembles an out-the-window view as possible. There are currently no standard guidelines for designing pilot-machine interfaces for UAVs. Typically, UAV camera views have a narrow field, which limits the situational awareness (SA) of the pilot. Also, at this time, pilot-UAV interfaces often use displays that have a diagonal length of around 20". Using a small display may result in a distorted and disproportional view for UAV pilots. Making use of a larger display and a camera lens with a wider field of view may minimize the occurrences of pilot error associated with the inability to see "out the window" as in a manned airplane. It is predicted that the pilot will have a less distorted view of the DROID s surroundings, quicker response times and more stable vehicle control. If the experimental results validate this concept, other UAV pilot-machine interfaces will be improved with this design methodology.

Reflective and transflective liquid crystal displays

NASA Astrophysics Data System (ADS)

Zhou, Fushan

Recently transflective liquid crystal displays (LCD) received a lot of attention. A transflective display has a transmissive mode and a reflective mode. It combines the high contrast, high brightness of the transmissive mode with energy-saving of reflective mode and has good performance in various illumination conditions. However, state-of-the-art transflective displays have problems such as different electro-optical properties, difficulty in compatibility and optimization of both modes, low efficiency of light utilization, and complexity in structure. This dissertation focuses on finding new designs of transflective displays that address those problems. One way to do this is to study film compensation of LCD. We first studied film compensation of bistable twisted nematic (BTN) LCD. Starting form the reduced (3x3) Mueller matrices, we derived and simplified the conditions that film compensated BTN can be optimized. Based on these relations, electro-optical properties of some particular configurations, and designs of transflective BTN with high brightness and contrast were given. To confirm and get a better understanding of the results, we use the Poincare sphere to analyze film compensated BTN. The key to this approach is the existence of "fixed points". Compared with the matrix approach, this approach is more simple, elegant, and efficient. We then generalized the Poincare sphere approach to a universal approach of LCD. We applied the universal approach to film compensation of ECB and IPS, and the design of achromatic birefringent filters. We also give two more new designs of transflective displays. In the first design, a dichroic mirror is used to split the visible spectrum into two parts used in transmissive and reflective modes, respectively. Both modes can be optimized. It has a simple structure and good light utilization. A design for a full-color transflective display with good performance is also given. In the second design, each pixel is divided into two sub-pixels, a transmissive one and a reflective one. By using polymer stabilization, the birefringence of the transmissive sub-pixels is twice that of the reflective ones. The display has single cell gap, low driving voltage, fast response, high contrast and brightness, and the transmissive and reflective modes are synchronized.

Generation of quinolone antimalarials targeting the Plasmodium falciparum mitochondrial respiratory chain for the treatment and prophylaxis of malaria

PubMed Central

Biagini, Giancarlo A.; Fisher, Nicholas; Shone, Alison E.; Mubaraki, Murad A.; Srivastava, Abhishek; Hill, Alisdair; Antoine, Thomas; Warman, Ashley J.; Davies, Jill; Pidathala, Chandrakala; Amewu, Richard K.; Leung, Suet C.; Sharma, Raman; Gibbons, Peter; Hong, David W.; Pacorel, Bénédicte; Lawrenson, Alexandre S.; Charoensutthivarakul, Sitthivut; Taylor, Lee; Berger, Olivier; Mbekeani, Alison; Stocks, Paul A.; Nixon, Gemma L.; Chadwick, James; Hemingway, Janet; Delves, Michael J.; Sinden, Robert E.; Zeeman, Anne-Marie; Kocken, Clemens H. M.; Berry, Neil G.; O’Neill, Paul M.; Ward, Stephen A.

2012-01-01

There is an urgent need for new antimalarial drugs with novel mechanisms of action to deliver effective control and eradication programs. Parasite resistance to all existing antimalarial classes, including the artemisinins, has been reported during their clinical use. A failure to generate new antimalarials with novel mechanisms of action that circumvent the current resistance challenges will contribute to a resurgence in the disease which would represent a global health emergency. Here we present a unique generation of quinolone lead antimalarials with a dual mechanism of action against two respiratory enzymes, NADH:ubiquinone oxidoreductase (Plasmodium falciparum NDH2) and cytochrome bc1. Inhibitor specificity for the two enzymes can be controlled subtly by manipulation of the privileged quinolone core at the 2 or 3 position. Inhibitors display potent (nanomolar) activity against both parasite enzymes and against multidrug-resistant P. falciparum parasites as evidenced by rapid and selective depolarization of the parasite mitochondrial membrane potential, leading to a disruption of pyrimidine metabolism and parasite death. Several analogs also display activity against liver-stage parasites (Plasmodium cynomolgi) as well as transmission-blocking properties. Lead optimized molecules also display potent oral antimalarial activity in the Plasmodium berghei mouse malaria model associated with favorable pharmacokinetic features that are aligned with a single-dose treatment. The ease and low cost of synthesis of these inhibitors fulfill the target product profile for the generation of a potent, safe, and inexpensive drug with the potential for eventual clinical deployment in the control and eradication of falciparum malaria. PMID:22566611

Crystal Structure of the New Investigational Drug Candidate VT-1598 in Complex with Aspergillus fumigatus Sterol 14α-Demethylase Provides Insights into Its Broad-Spectrum Antifungal Activity

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

Hargrove, Tatiana Y.; Garvey, Edward P.; Hoekstra, William J.

ABSTRACT Within the past few decades, the incidence and complexity of human fungal infections have increased, and therefore, the need for safer and more efficient, broad-spectrum antifungal agents is high. In the study described here, we characterized the new tetrazole-based drug candidate VT-1598 as an inhibitor of sterol 14α-demethylase (CYP51B) from the filamentous fungusAspergillus fumigatus. VT-1598 displayed a high affinity of binding to the enzyme in solution (dissociation constant, 13 ± 1 nM) and in the reconstituted enzymatic reaction was revealed to have an inhibitory potency stronger than the potencies of all other simultaneously tested antifungal drugs, including fluconazole, voriconazole,more » ketoconazole, and posaconazole. The X-ray structure of the VT-1598/A. fumigatusCYP51 complex was determined and depicts the distinctive binding mode of the inhibitor in the enzyme active site, suggesting the molecular basis of the improved drug potency and broad-spectrum antifungal activity. These data show the formation of an optimized hydrogen bond between the phenoxymethyl oxygen of VT-1598 and the imidazole ring nitrogen of His374, the CYP51 residue that is highly conserved across fungal pathogens and fungus specific. Comparative structural analysis ofA. fumigatusCYP51/voriconazole andCandida albicansCYP51/VT-1161 complexes supports the role of H bonding in fungal CYP51/inhibitor complexes and emphasizes the importance of an optimal distance between this interaction and the inhibitor-heme iron interaction. Cellular experiments using twoA. fumigatusstrains (strains 32820 and 1022) displayed a direct correlation between the effects of the drugs on CYP51B activity and fungal growth inhibition, indicating the noteworthy anti-A. fumigatuspotency of VT-1598 and confirming its promise as a broad-spectrum antifungal agent.« less

Development of a glucose oxidase-based biocatalyst adopting both physical entrapment and crosslinking, and its use in biofuel cells

NASA Astrophysics Data System (ADS)

Chung, Yongjin; Ahn, Yeonjoo; Christwardana, Marcelinus; Kim, Hansung; Kwon, Yongchai

2016-04-01

New enzymatic catalysts prepared using physical entrapment and chemical bonding were used as anodic catalysts to enhance the performance of enzymatic biofuel cells (EBCs). For estimating the physical entrapment effect, the best glucose oxidase (GOx) concentration immobilized on polyethyleneimine (PEI) and carbon nanotube (CNT) (GOx/PEI/CNT) was determined, while for inspecting the chemical bonding effect, terephthalaldehyde (TPA) and glutaraldehyde (GA) crosslinkers were employed. According to the enzyme activity and XPS measurements, when the GOx concentration is 4 mg mL-1, they are most effectively immobilized (via the physical entrapment effect) and TPA-crosslinked GOx/PEI/CNT(TPA/[GOx/PEI/CNT]) forms π conjugated bonds via chemical bonding, inducing the promotion of electron transfer by delocalization of electrons. Due to the optimized GOx concentration and π conjugated bonds, TPA/[GOx/PEI/CNT], including 4 mg mL-1 GOx displays a high electron transfer rate, followed by excellent catalytic activity and EBC performance.New enzymatic catalysts prepared using physical entrapment and chemical bonding were used as anodic catalysts to enhance the performance of enzymatic biofuel cells (EBCs). For estimating the physical entrapment effect, the best glucose oxidase (GOx) concentration immobilized on polyethyleneimine (PEI) and carbon nanotube (CNT) (GOx/PEI/CNT) was determined, while for inspecting the chemical bonding effect, terephthalaldehyde (TPA) and glutaraldehyde (GA) crosslinkers were employed. According to the enzyme activity and XPS measurements, when the GOx concentration is 4 mg mL-1, they are most effectively immobilized (via the physical entrapment effect) and TPA-crosslinked GOx/PEI/CNT(TPA/[GOx/PEI/CNT]) forms π conjugated bonds via chemical bonding, inducing the promotion of electron transfer by delocalization of electrons. Due to the optimized GOx concentration and π conjugated bonds, TPA/[GOx/PEI/CNT], including 4 mg mL-1 GOx displays a high electron transfer rate, followed by excellent catalytic activity and EBC performance. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr00902f

Crystal Structure of the New Investigational Drug Candidate VT-1598 in Complex with Aspergillus fumigatus Sterol 14α-Demethylase Provides Insights into Its Broad-Spectrum Antifungal Activity

PubMed Central

Hargrove, Tatiana Y.; Garvey, Edward P.; Hoekstra, William J.; Yates, Christopher M.; Wawrzak, Zdzislaw; Rachakonda, Girish; Villalta, Fernando

2017-01-01

ABSTRACT Within the past few decades, the incidence and complexity of human fungal infections have increased, and therefore, the need for safer and more efficient, broad-spectrum antifungal agents is high. In the study described here, we characterized the new tetrazole-based drug candidate VT-1598 as an inhibitor of sterol 14α-demethylase (CYP51B) from the filamentous fungus Aspergillus fumigatus. VT-1598 displayed a high affinity of binding to the enzyme in solution (dissociation constant, 13 ± 1 nM) and in the reconstituted enzymatic reaction was revealed to have an inhibitory potency stronger than the potencies of all other simultaneously tested antifungal drugs, including fluconazole, voriconazole, ketoconazole, and posaconazole. The X-ray structure of the VT-1598/A. fumigatus CYP51 complex was determined and depicts the distinctive binding mode of the inhibitor in the enzyme active site, suggesting the molecular basis of the improved drug potency and broad-spectrum antifungal activity. These data show the formation of an optimized hydrogen bond between the phenoxymethyl oxygen of VT-1598 and the imidazole ring nitrogen of His374, the CYP51 residue that is highly conserved across fungal pathogens and fungus specific. Comparative structural analysis of A. fumigatus CYP51/voriconazole and Candida albicans CYP51/VT-1161 complexes supports the role of H bonding in fungal CYP51/inhibitor complexes and emphasizes the importance of an optimal distance between this interaction and the inhibitor-heme iron interaction. Cellular experiments using two A. fumigatus strains (strains 32820 and 1022) displayed a direct correlation between the effects of the drugs on CYP51B activity and fungal growth inhibition, indicating the noteworthy anti-A. fumigatus potency of VT-1598 and confirming its promise as a broad-spectrum antifungal agent. PMID:28461309

Display/control requirements for VTOL aircraft

NASA Technical Reports Server (NTRS)

Hoffman, W. C.; Curry, R. E.; Kleinman, D. L.; Hollister, W. M.; Young, L. R.

1975-01-01

Quantative metrics were determined for system control performance, workload for control, monitoring performance, and workload for monitoring. Pilot tasks were allocated for navigation and guidance of automated commercial V/STOL aircraft in all weather conditions using an optimal control model of the human operator to determine display elements and design.

Monitoring and decision making by people in man machine systems

NASA Technical Reports Server (NTRS)

Johannsen, G.

1979-01-01

The analysis of human monitoring and decision making behavior as well as its modeling are described. Classic and optimal control theoretical, monitoring models are surveyed. The relationship between attention allocation and eye movements is discussed. As an example of applications, the evaluation of predictor displays by means of the optimal control model is explained. Fault detection involving continuous signals and decision making behavior of a human operator engaged in fault diagnosis during different operation and maintenance situations are illustrated. Computer aided decision making is considered as a queueing problem. It is shown to what extent computer aids can be based on the state of human activity as measured by psychophysiological quantities. Finally, management information systems for different application areas are mentioned. The possibilities of mathematical modeling of human behavior in complex man machine systems are also critically assessed.

Bacteriocins from Lactobacillus plantarum – production, genetic organization and mode of action

PubMed Central

Todorov, Svetoslav D.

2009-01-01

Bacteriocins are biologically active proteins or protein complexes that display a bactericidal mode of action towards usually closely related species. Numerous strains of bacteriocin producing Lactobacillus plantarum have been isolated in the last two decades from different ecological niches including meat, fish, fruits, vegetables, and milk and cereal products. Several of these plantaricins have been characterized and the aminoacid sequence determined. Different aspects of the mode of action, fermentation optimization and genetic organization of the bacteriocin operon have been studied. However, numerous of bacteriocins produced by different Lactobacillus plantarum strains have not been fully characterized. In this article, a brief overview of the classification, genetics, characterization, including mode of action and production optimization for bacteriocins from Lactic Acid Bacteria in general, and where appropriate, with focus on bacteriocins produced by Lactobacillus plantarum, is presented. PMID:24031346

Discovery of Clinical Candidate 1-{[(2 S ,3 S ,4 S )-3-Ethyl-4-fluoro-5-oxopyrrolidin-2-yl]methoxy}-7-methoxyisoquinoline-6-carboxamide (PF-06650833), a Potent, Selective Inhibitor of Interleukin-1 Receptor Associated Kinase 4 (IRAK4), by Fragment-Based Drug Design

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

Lee, Katherine L.; Ambler, Catherine M.; Anderson, David R.

Through fragment-based drug design focused on engaging the active site of IRAK4 and leveraging three-dimensional topology in a ligand-efficient manner, a micromolar hit identified from a screen of a Pfizer fragment library was optimized to afford IRAK4 inhibitors with nanomolar potency in cellular assays. The medicinal chemistry effort featured the judicious placement of lipophilicity, informed by co-crystal structures with IRAK4 and optimization of ADME properties to deliver clinical candidate PF-06650833 (compound 40). This compound displays a 5-unit increase in lipophilic efficiency from the fragment hit, excellent kinase selectivity, and pharmacokinetic properties suitable for oral administration.

A minimal peptide scaffold for beta-turn display: optimizing a strand position in disulfide-cyclized beta-hairpins.

PubMed

Cochran, A G; Tong, R T; Starovasnik, M A; Park, E J; McDowell, R S; Theaker, J E; Skelton, N J

2001-01-31

Phage display of peptide libraries has become a powerful tool for the evolution of novel ligands that bind virtually any protein target. However, the rules governing conformational preferences in natural peptides are poorly understood, and consequently, structure-activity relationships in these molecules can be difficult to define. In an effort to simplify this process, we have investigated the structural stability of 10-residue, disulfide-constrained beta-hairpins and assessed their suitability as scaffolds for beta-turn display. Using disulfide formation as a probe, relative free energies of folding were measured for 19 peptides that differ at a one strand position. A tryptophan substitution promotes folding to a remarkable degree. NMR analysis confirms that the measured energies correlate well with the degree of beta-hairpin structure in the disulfide-cyclized peptides. Reexamination of a subset of the strand substitutions in peptides with different turn sequences reveals linear free energy relationships, indicating that turns and strand-strand interactions make independent, additive contributions to hairpin stability. Significantly, the tryptophan strand substitution is highly stabilizing with all turns tested, and peptides that display model turns or the less stable C'-C' ' turn of CD4 on this tryptophan "stem" are highly structured beta-hairpins in water. Thus, we have developed a small, structured beta-turn scaffold, containing only natural L-amino acids, that may be used to display peptide libraries of limited conformational diversity on phage.

Revisiting the debate on the relationship between display rules and performance: considering the explicitness of display rules.

PubMed

Christoforou, Paraskevi S; Ashforth, Blake E

2015-01-01

We argue that the strength with which the organization communicates expectations regarding the appropriate emotional expression toward customers (i.e., explicitness of display rules) has an inverted U-shaped relationship with service delivery behaviors, customer satisfaction, and sales performance. Further, we argue that service organizations need a particular blend of explicitness of display rules and role discretion for the purpose of optimizing sales performance. As hypothesized, findings from 2 samples of salespeople suggest that either high or low explicitness of display rules impedes service delivery behaviors and sales performance, which peaks at moderate explicitness of display rules and high role discretion. The findings also suggest that the explicitness of display rules has a positive relationship with customer satisfaction. (c) 2015 APA, all rights reserved.

Attention and amygdala activity: an fMRI study with spider pictures in spider phobia.

PubMed

Alpers, Georg W; Gerdes, Antje B M; Lagarie, Bernadette; Tabbert, Katharina; Vaitl, Dieter; Stark, Rudolf

2009-06-01

Facilitated detection of threatening visual cues is thought to be adaptive. In theory, detection of threat cues should activate the amygdala independently from allocation of attention. However, previous studies using emotional facial expressions as well as phobic cues yielded contradictory results. We used fMRI to examine whether the allocation of attention to components of superimposed spider and bird displays modulates amygdala activation. Nineteen spider-phobic women were instructed to identify either a moving or a stationary animal in briefly presented double-exposure displays. Amygdala activation followed a dose-response relationship: Compared to congruent neutral displays (two birds), amygdala activation was most pronounced in response to congruent phobic displays (two spiders) and less but still significant in response to mixed displays (spider and bird) when attention was focused on the phobic component. When attention was focused on the neutral component, mixed displays did not result in significant amygdala activation. This was confirmed in a significant parametric graduation of the amygdala activation in the order of congruent phobic displays, mixed displays with attention focus on the spider, mixed displays with focus on the bird and congruent neutral displays. These results challenge the notion that amygdala activation in response to briefly presented phobic cues is independent from attention.

Improvement of LysM-Mediated Surface Display of Designed Ankyrin Repeat Proteins (DARPins) in Recombinant and Nonrecombinant Strains of Lactococcus lactis and Lactobacillus Species

PubMed Central

Zadravec, Petra; Štrukelj, Borut

2015-01-01

Safety and probiotic properties make lactic acid bacteria (LAB) attractive hosts for surface display of heterologous proteins. Protein display on nonrecombinant microorganisms is preferred for therapeutic and food applications due to regulatory requirements. We displayed two designed ankyrin repeat proteins (DARPins), each possessing affinity for the Fc region of human IgG, on the surface of Lactococcus lactis by fusing them to the Usp45 secretion signal and to the peptidoglycan-binding C terminus of AcmA, containing lysine motif (LysM) repeats. Growth medium containing a secreted fusion protein was used to test its heterologous binding to 10 strains of species of the genus Lactobacillus, using flow cytometry, whole-cell enzyme-linked immunosorbent assay (ELISA), and fluorescence microscopy. The fusion proteins bound to the surfaces of all lactobacilli; however, binding to the majority of bacteria was only 2- to 5-fold stronger than that of the control. Lactobacillus salivarius ATCC 11741 demonstrated exceptionally strong binding (32- to 55-fold higher than that of the control) and may therefore be an attractive host for nonrecombinant surface display. Genomic comparison of the species indicated the exopolysaccharides of Lb. salivarius as a possible reason for the difference. Additionally, a 15-fold concentration-dependent increase in nonrecombinant surface display on L. lactis was demonstrated by growing bacteria with sublethal concentrations of the antibiotics chloramphenicol and erythromycin. Nonrecombinant surface display on LAB, based on LysM repeats, was optimized by selecting Lactobacillus salivarius ATCC 11741 as the optimal host and by introducing antibiotics as additives for increasing surface display on L. lactis. Additionally, effective display of DARPins on the surfaces of nonrecombinant LAB has opened up several new therapeutic possibilities. PMID:25576617

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 Laccase with Antiproliferative and HIV-I Reverse Transcriptase Inhibitory Activities from the Mycorrhizal Fungus Agaricus placomyces

PubMed Central

Sun, Jian; Chen, Qing-Jun; Cao, Qing-Qin; Wu, Ying-Ying; Xu, Li-Jing; Zhu, Meng-Juan; Ng, Tzi-Bun; Wang, He-Xiang; Zhang, Guo-Qing

2012-01-01

A novel 68 kDa laccase was purified from the mycorrhizal fungus Agaricus placomyces by utilizing a procedure that comprised three successive steps of ion exchange chromatography and gel filtration as the final step. The monomeric enzyme exhibited the N-terminal amino acid sequence of DVIGPQAQVTLANQD, which showed only a low extent of homology to sequences of other fungal laccases. The optimal temperature for A. placomyces laccase was 30°C, and optimal pH values for laccase activity towards the substrates 2,7′-azinobis[3-ethylbenzothiazolone-6-sulfonic acid] diammonium salt (ABTS) and hydroquinone were 5.2 and 6.8, respectively. The laccase displayed, at 30°C and pH 5.2, Km values of 0.392 mM towards hydroquinone and 0.775 mM towards ABTS. It potently suppressed proliferation of MCF 7 human breast cancer cells and Hep G2 hepatoma cells and inhibited human immunodeficiency virus type 1 (HIV-1) reverse transcriptase (RT) activity with an IC50 of 1.8 μM, 1.7 μM, and 1.25 μM, respectively, signifying that it is an antipathogenic protein. PMID:23093860

Spatial Attention Enhances Perceptual Processing of Single-Element Displays

NASA Technical Reports Server (NTRS)

Bacon, William; Johnston, James C.; Remington, Roger W.; Null, Cynthia H. (Technical Monitor)

1994-01-01

Shiu and Pashler (1993) reported that precueing masked, single-element displays had negligible effects on identification accuracy. They argued that spatial attention does not actually enhance stimulus perceptibility, but only reduces decision noise. Alternatively, such negative results may arise if cues are sub-optimal, or if masks place an insufficient premium on timely deployment of attention. We report results showing that valid cueing enhances processing of even single-element displays. Spatial attention does indeed enhance perceptual processes.

Role of messenger RNA-ribosome complex in complementary DNA display.

PubMed

Naimuddin, Mohammed; Ohtsuka, Isao; Kitamura, Koichiro; Kudou, Motonori; Kimura, Shinnosuke

2013-07-15

In vitro display technologies such as ribosome display and messenger RNA (mRNA)/complementary DNA (cDNA) display are powerful methods that can generate library diversities on the order of 10(10-14). However, in mRNA and cDNA display methods, the end use diversity is two orders of magnitude lower than initial diversity and is dependent on the downstream processes that act as limiting factors. We found that in our previous cDNA display protocol, the purification of protein fusions by the use of streptavidin matrices from cell-free translation mixtures had poor efficiency (∼10-15%) that seriously affected the diversity of the purified library. Here, we have investigated and optimized the protocols that provided remarkable purification efficiencies. The stalled ribosome in the mRNA-ribosome complex was found to impede this purification efficiency. Among the various conditions tested, destabilization of ribosomes by appropriate concentration of metal chelating agents in combination with an optimal temperature of 30°C were found to be crucial and effective for nearly complete isolation of protein fusions from the cell-free translation system. Thus, this protocol provided 8- to 10-fold increased efficiency of purification over the previous method and results in retaining the diversity of the library by approximately an order of magnitude-important for directed evolution. We also discuss the possible effects in the fabrication of protein chips. Copyright © 2013 Elsevier Inc. All rights reserved.

Computer-assisted navigation in orthopedic surgery.

PubMed

Mavrogenis, Andreas F; Savvidou, Olga D; Mimidis, George; Papanastasiou, John; Koulalis, Dimitrios; Demertzis, Nikolaos; Papagelopoulos, Panayiotis J

2013-08-01

Computer-assisted navigation has a role in some orthopedic procedures. It allows the surgeons to obtain real-time feedback and offers the potential to decrease intra-operative errors and optimize the surgical result. Computer-assisted navigation systems can be active or passive. Active navigation systems can either perform surgical tasks or prohibit the surgeon from moving past a predefined zone. Passive navigation systems provide intraoperative information, which is displayed on a monitor, but the surgeon is free to make any decisions he or she deems necessary. This article reviews the available types of computer-assisted navigation, summarizes the clinical applications and reviews the results of related series using navigation, and informs surgeons of the disadvantages and pitfalls of computer-assisted navigation in orthopedic surgery. Copyright 2013, SLACK Incorporated.

Discovery of new antimalarial chemotypes through chemical methodology and library development.

PubMed

Brown, Lauren E; Chih-Chien Cheng, Ken; Wei, Wan-Guo; Yuan, Pingwei; Dai, Peng; Trilles, Richard; Ni, Feng; Yuan, Jing; MacArthur, Ryan; Guha, Rajarshi; Johnson, Ronald L; Su, Xin-zhuan; Dominguez, Melissa M; Snyder, John K; Beeler, Aaron B; Schaus, Scott E; Inglese, James; Porco, John A

2011-04-26

In an effort to expand the stereochemical and structural complexity of chemical libraries used in drug discovery, the Center for Chemical Methodology and Library Development at Boston University has established an infrastructure to translate methodologies accessing diverse chemotypes into arrayed libraries for biological evaluation. In a collaborative effort, the NIH Chemical Genomics Center determined IC(50)'s for Plasmodium falciparum viability for each of 2,070 members of the CMLD-BU compound collection using quantitative high-throughput screening across five parasite lines of distinct geographic origin. Three compound classes displaying either differential or comprehensive antimalarial activity across the lines were identified, and the nascent structure activity relationships (SAR) from this experiment used to initiate optimization of these chemotypes for further development.

Display characterization by eye: contrast ratio and discrimination throughout the grayscale

NASA Astrophysics Data System (ADS)

Gille, Jennifer; Arend, Larry; Larimer, James O.

2004-06-01

We have measured the ability of observers to estimate the contrast ratio (maximum white luminance / minimum black or gray) of various displays and to assess luminous discrimination over the tonescale of the display. This was done using only the computer itself and easily-distributed devices such as neutral density filters. The ultimate goal of this work is to see how much of the characterization of a display can be performed by the ordinary user in situ, in a manner that takes advantage of the unique abilities of the human visual system and measures visually important aspects of the display. We discuss the relationship among contrast ratio, tone scale, display transfer function and room lighting. These results may contribute to the development of applications that allow optimization of displays for the situated viewer / display system without instrumentation and without indirect inferences from laboratory to workplace.

Arylazolyl(azinyl)thioacetanilides. Part 16: Structure-based bioisosterism design, synthesis and biological evaluation of novel pyrimidinylthioacetanilides as potent HIV-1 inhibitors.

PubMed

Li, Xiao; Lu, Xueyi; Chen, Wenmin; Liu, Huiqing; Zhan, Peng; Pannecouque, Christophe; Balzarini, Jan; De Clercq, Erik; Liu, Xinyong

2014-10-01

A series of novel pyrimidinylthioacetanilides were designed, synthesized, and evaluated for their biological activity as potent HIV-1 non-nucleoside reverse transcriptase inhibitors (NNRTIs). Most of the tested compounds were proved to be effective in inhibiting HIV-1 (IIIB) replication with EC50 ranging from 0.15 μM to 24.2 μM, thereinto compound 15 was the most active lead with favorable inhibitory activity against HIV-1 (IIIB) (EC50=0.15 μM, SI=684). Besides, compound 6 displayed moderate inhibition against the double-mutated HIV-1 strain (K103N/Y181C) (EC50=3.9 μM). Preliminary structure-activity relationships (SARs), structure-cytotoxicity relationships (SCRs) data, and molecular modeling studies were discussed as well, which may provide valuable insights for further optimizations. Copyright © 2014 Elsevier Ltd. All rights reserved.

Optimal balance of the striatal medium spiny neuron network.

PubMed

Ponzi, Adam; Wickens, Jeffery R

2013-04-01

Slowly varying activity in the striatum, the main Basal Ganglia input structure, is important for the learning and execution of movement sequences. Striatal medium spiny neurons (MSNs) form cell assemblies whose population firing rates vary coherently on slow behaviourally relevant timescales. It has been shown that such activity emerges in a model of a local MSN network but only at realistic connectivities of 10 ~ 20% and only when MSN generated inhibitory post-synaptic potentials (IPSPs) are realistically sized. Here we suggest a reason for this. We investigate how MSN network generated population activity interacts with temporally varying cortical driving activity, as would occur in a behavioural task. We find that at unrealistically high connectivity a stable winners-take-all type regime is found where network activity separates into fixed stimulus dependent regularly firing and quiescent components. In this regime only a small number of population firing rate components interact with cortical stimulus variations. Around 15% connectivity a transition to a more dynamically active regime occurs where all cells constantly switch between activity and quiescence. In this low connectivity regime, MSN population components wander randomly and here too are independent of variations in cortical driving. Only in the transition regime do weak changes in cortical driving interact with many population components so that sequential cell assemblies are reproducibly activated for many hundreds of milliseconds after stimulus onset and peri-stimulus time histograms display strong stimulus and temporal specificity. We show that, remarkably, this activity is maximized at striatally realistic connectivities and IPSP sizes. Thus, we suggest the local MSN network has optimal characteristics - it is neither too stable to respond in a dynamically complex temporally extended way to cortical variations, nor is it too unstable to respond in a consistent repeatable way. Rather, it is optimized to generate stimulus dependent activity patterns for long periods after variations in cortical excitation.

Optimal Balance of the Striatal Medium Spiny Neuron Network

PubMed Central

Ponzi, Adam; Wickens, Jeffery R.

2013-01-01

Slowly varying activity in the striatum, the main Basal Ganglia input structure, is important for the learning and execution of movement sequences. Striatal medium spiny neurons (MSNs) form cell assemblies whose population firing rates vary coherently on slow behaviourally relevant timescales. It has been shown that such activity emerges in a model of a local MSN network but only at realistic connectivities of and only when MSN generated inhibitory post-synaptic potentials (IPSPs) are realistically sized. Here we suggest a reason for this. We investigate how MSN network generated population activity interacts with temporally varying cortical driving activity, as would occur in a behavioural task. We find that at unrealistically high connectivity a stable winners-take-all type regime is found where network activity separates into fixed stimulus dependent regularly firing and quiescent components. In this regime only a small number of population firing rate components interact with cortical stimulus variations. Around connectivity a transition to a more dynamically active regime occurs where all cells constantly switch between activity and quiescence. In this low connectivity regime, MSN population components wander randomly and here too are independent of variations in cortical driving. Only in the transition regime do weak changes in cortical driving interact with many population components so that sequential cell assemblies are reproducibly activated for many hundreds of milliseconds after stimulus onset and peri-stimulus time histograms display strong stimulus and temporal specificity. We show that, remarkably, this activity is maximized at striatally realistic connectivities and IPSP sizes. Thus, we suggest the local MSN network has optimal characteristics – it is neither too stable to respond in a dynamically complex temporally extended way to cortical variations, nor is it too unstable to respond in a consistent repeatable way. Rather, it is optimized to generate stimulus dependent activity patterns for long periods after variations in cortical excitation. PMID:23592954

2D/3D Synthetic Vision Navigation Display

NASA Technical Reports Server (NTRS)

Prinzel, Lawrence J., III; Kramer, Lynda J.; Arthur, J. J., III; Bailey, Randall E.; Sweeters, jason L.

2008-01-01

Flight-deck display software was designed and developed at NASA Langley Research Center to provide two-dimensional (2D) and three-dimensional (3D) terrain, obstacle, and flight-path perspectives on a single navigation display. The objective was to optimize the presentation of synthetic vision (SV) system technology that permits pilots to view multiple perspectives of flight-deck display symbology and 3D terrain information. Research was conducted to evaluate the efficacy of the concept. The concept has numerous unique implementation features that would permit enhanced operational concepts and efficiencies in both current and future aircraft.

Using the Multi-Display Teaching System to Lower Cognitive Load

ERIC Educational Resources Information Center

Cheng, Tsung-Sheng; Lu, Yu-Chun; Yang, Chu-Sing

2015-01-01

Multimedia plays a vital role in both learning systems and the actual education process. However, currently used presentation software is often not optimized and generates a great deal of clutter on the screen. Furthermore, there is often insufficient space on a single display, leading to the division of content. These limitations generally…

Modified atmosphere packaging for fresh-cut ‘Kent’ mango under common retail display conditions

USDA-ARS?s Scientific Manuscript database

A modified atmosphere package (MAP) was designed to optimize the quality and shelf-life of fresh-cut ‘Kent’ mango during exposure to common retail display conditions. The synergism between the MAP system and an antioxidant treatment (calcium ascorbate and citric acid) was also investigated. Mango sl...

Choosing colors for map display icons using models of visual search.

PubMed

Shive, Joshua; Francis, Gregory

2013-04-01

We show how to choose colors for icons on maps to minimize search time using predictions of a model of visual search. The model analyzes digital images of a search target (an icon on a map) and a search display (the map containing the icon) and predicts search time as a function of target-distractor color distinctiveness and target eccentricity. We parameterized the model using data from a visual search task and performed a series of optimization tasks to test the model's ability to choose colors for icons to minimize search time across icons. Map display designs made by this procedure were tested experimentally. In a follow-up experiment, we examined the model's flexibility to assign colors in novel search situations. The model fits human performance, performs well on the optimization tasks, and can choose colors for icons on maps with novel stimuli to minimize search time without requiring additional model parameter fitting. Models of visual search can suggest color choices that produce search time reductions for display icons. Designers should consider constructing visual search models as a low-cost method of evaluating color assignments.

Optimization of a human IgG B-cell ELISpot assay for the analysis of vaccine-induced B-cell responses.

PubMed

Jahnmatz, Maja; Kesa, Gun; Netterlid, Eva; Buisman, Anne-Marie; Thorstensson, Rigmor; Ahlborg, Niklas

2013-05-31

B-cell responses after infection or vaccination are often measured as serum titers of antigen-specific antibodies. Since this does not address the aspect of memory B-cell activity, it may not give a complete picture of the B-cell response. Analysis of memory B cells by ELISpot is therefore an important complement to conventional serology. B-cell ELISpot was developed more than 25 years ago and many assay protocols/reagents would benefit from optimization. We therefore aimed at developing an optimized B-cell ELISpot for the analysis of vaccine-induced human IgG-secreting memory B cells. A protocol was developed based on new monoclonal antibodies to human IgG and biotin-avidin amplification to increase the sensitivity. After comparison of various compounds commonly used to in vitro-activate memory B cells for ELISpot analysis, the TLR agonist R848 plus interleukin (IL)-2 was selected as the most efficient activator combination. The new protocol was subsequently compared to an established protocol, previously used in vaccine studies, based on polyclonal antibodies without biotin avidin amplification and activation of memory B-cells using a mix of antigen, CpG, IL-2 and IL-10. The new protocol displayed significantly better detection sensitivity, shortened the incubation time needed for the activation of memory B cells and reduced the amount of antigen required for the assay. The functionality of the new protocol was confirmed by analyzing specific memory B cells to five different antigens, induced in a limited number of subjects vaccinated against tetanus, diphtheria and pertussis. The limited number of subjects did not allow for a direct comparison with other vaccine studies. Optimization of the B-cell ELISpot will facilitate an improved analysis of IgG-secreting B cells in vaccine studies. Copyright © 2013 Elsevier B.V. All rights reserved.

Optimal control model predictions of system performance and attention allocation and their experimental validation in a display design study

NASA Technical Reports Server (NTRS)

Johannsen, G.; Govindaraj, T.

1980-01-01

The influence of different types of predictor displays in a longitudinal vertical takeoff and landing (VTOL) hover task is analyzed in a theoretical study. Several cases with differing amounts of predictive and rate information are compared. The optimal control model of the human operator is used to estimate human and system performance in terms of root-mean-square (rms) values and to compute optimized attention allocation. The only part of the model which is varied to predict these data is the observation matrix. Typical cases are selected for a subsequent experimental validation. The rms values as well as eye-movement data are recorded. The results agree favorably with those of the theoretical study in terms of relative differences. Better matching is achieved by revised model input data.

Integrated Application of Active Controls (IAAC) technology to an advanced subsonic transport project: Current and advanced act control system definition study, volume 1

NASA Technical Reports Server (NTRS)

Hanks, G. W.; Shomber, H. A.; Dethman, H. A.; Gratzer, L. B.; Maeshiro, A.; Gangsaas, D.; Blight, J. D.; Buchan, S. M.; Crumb, C. B.; Dorwart, R. J.

1981-01-01

An active controls technology (ACT) system architecture was selected based on current technology system elements and optimal control theory was evaluated for use in analyzing and synthesizing ACT multiple control laws. The system selected employs three redundant computers to implement all of the ACT functions, four redundant smaller computers to implement the crucial pitch-augmented stability function, and a separate maintenance and display computer. The reliability objective of probability of crucial function failure of less than 1 x 10 to the -9th power per flight of 1 hr can be met with current technology system components, if the software is assumed fault free and coverage approaching 1.0 can be provided. The optimal control theory approach to ACT control law synthesis yielded comparable control law performance much more systematically and directly than the classical s-domain approach. The ACT control law performance, although somewhat degraded by the inclusion of representative nonlinearities, remained quite effective. Certain high-frequency gust-load alleviation functions may require increased surface rate capability.

Gly184 of the Escherichia coli cAMP receptor protein provides optimal context for both DNA binding and RNA polymerase interaction.

PubMed

Hicks, Matt N; Gunasekara, Sanjiva; Serate, Jose; Park, Jin; Mosharaf, Pegah; Zhou, Yue; Lee, Jin-Won; Youn, Hwan

2017-10-01

The Escherichia coli cAMP receptor protein (CRP) utilizes the helix-turn-helix motif for DNA binding. The CRP's recognition helix, termed F-helix, includes a stretch of six amino acids (Arg180, Glu181, Thr182, Val183, Gly184, and Arg185) for direct DNA contacts. Arg180, Glu181 and Arg185 are known as important residues for DNA binding and specificity, but little has been studied for the other residues. Here we show that Gly184 is another F-helix residue critical for the transcriptional activation function of CRP. First, glycine was repeatedly selected at CRP position 184 for its unique ability to provide wild type-level transcriptional activation activity. To dissect the glycine requirement, wild type CRP and mutants G184A, G184F, G184S, and G184Y were purified and their in vitro DNA-binding activity was measured. G184A and G184F displayed reduced DNA binding, which may explain their low transcriptional activation activity. However, G184S and G184Y displayed apparently normal DNA affinity. Therefore, an additional factor is needed to account for the diminished transcriptional activation function in G184S and G184Y, and the best explanation is perturbations in their interaction with RNA polymerase. The fact that glycine is the smallest amino acid could not fully warrant its suitability, as shown in this study. We hypothesize that Gly184 fulfills the dual functions of DNA binding and RNA polymerase interaction by conferring conformational flexibility to the F-helix.

Fast repurposing of high-resolution stereo video content for mobile use

NASA Astrophysics Data System (ADS)

Karaoglu, Ali; Lee, Bong Ho; Boev, Atanas; Cheong, Won-Sik; Gotchev, Atanas

2012-06-01

3D video content is captured and created mainly in high resolution targeting big cinema or home TV screens. For 3D mobile devices, equipped with small-size auto-stereoscopic displays, such content has to be properly repurposed, preferably in real-time. The repurposing requires not only spatial resizing but also properly maintaining the output stereo disparity, as it should deliver realistic, pleasant and harmless 3D perception. In this paper, we propose an approach to adapt the disparity range of the source video to the comfort disparity zone of the target display. To achieve this, we adapt the scale and the aspect ratio of the source video. We aim at maximizing the disparity range of the retargeted content within the comfort zone, and minimizing the letterboxing of the cropped content. The proposed algorithm consists of five stages. First, we analyse the display profile, which characterises what 3D content can be comfortably observed in the target display. Then, we perform fast disparity analysis of the input stereoscopic content. Instead of returning the dense disparity map, it returns an estimate of the disparity statistics (min, max, meanand variance) per frame. Additionally, we detect scene cuts, where sharp transitions in disparities occur. Based on the estimated input, and desired output disparity ranges, we derive the optimal cropping parameters and scale of the cropping window, which would yield the targeted disparity range and minimize the area of cropped and letterboxed content. Once the rescaling and cropping parameters are known, we perform resampling procedure using spline-based and perceptually optimized resampling (anti-aliasing) kernels, which have also a very efficient computational structure. Perceptual optimization is achieved through adjusting the cut-off frequency of the anti-aliasing filter with the throughput of the target display.

Realizing Rec. 2020 color gamut with quantum dot displays.

PubMed

Zhu, Ruidong; Luo, Zhenyue; Chen, Haiwei; Dong, Yajie; Wu, Shin-Tson

2015-09-07

We analyze how to realize Rec. 2020 wide color gamut with quantum dots. For photoluminescence, our simulation indicates that we are able to achieve over 97% of the Rec. 2020 standard with quantum dots by optimizing the emission spectra and redesigning the color filters. For electroluminescence, by optimizing the emission spectra of quantum dots is adequate to render over 97% of the Rec. 2020 standard. We also analyze the efficiency and angular performance of these devices, and then compare results with LCDs using green and red phosphors-based LED backlight. Our results indicate that quantum dot display is an outstanding candidate for achieving wide color gamut and high optical efficiency.

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

NASA Astrophysics Data System (ADS)

Nichols, Jonathan A.

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

Drivers of Daily Routines in an Ectothermic Marine Predator: Hunt Warm, Rest Warmer?

PubMed Central

Papastamatiou, Yannis P.; Watanabe, Yuuki Y.; Bradley, Darcy; Dee, Laura E.; Weng, Kevin; Lowe, Christopher G.; Caselle, Jennifer E.

2015-01-01

Animal daily routines represent a compromise between maximizing foraging success and optimizing physiological performance, while minimizing the risk of predation. For ectothermic predators, ambient temperature may also influence daily routines through its effects on physiological performance. Temperatures can fluctuate significantly over the diel cycle and ectotherms may synchronize behaviour to match thermal regimes in order to optimize fitness. We used bio-logging to quantify activity and body temperature of blacktip reef sharks (Carcharhinus melanopterus) at a tropical atoll. Behavioural observations were used to concurrently measure bite rates in herbivorous reef fishes, as an index of activity for potential diurnal prey. Sharks showed early evening peaks in activity, particularly during ebbing high tides, while body temperatures peaked several hours prior to the period of maximal activity. Herbivores also displayed peaks in activity several hours earlier than the peaks in shark activity. Sharks appeared to be least active while their body temperatures were highest and most active while temperatures were cooling, although we hypothesize that due to thermal inertia they were still warmer than their smaller prey during this period. Sharks may be most active during early evening periods as they have a sensory advantage under low light conditions and/or a thermal advantage over cooler prey. Sharks swam into shallow water during daytime low tide periods potentially to warm up and increase rates of digestion before the nocturnal activity period, which may be a strategy to maximize ingestion rates. “Hunt warm, rest warmer” may help explain the early evening activity seen in other ectothermic predators. PMID:26061229

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

Dholabhai, Pratik P., E-mail: pratik.dholabhai@asu.ed; Anwar, Shahriar, E-mail: anwar@asu.ed; Adams, James B., E-mail: jim.adams@asu.ed

Kinetic lattice Monte Carlo (KLMC) model is developed for investigating oxygen vacancy diffusion in praseodymium-doped ceria. The current approach uses a database of activation energies for oxygen vacancy migration, calculated using first-principles, for various migration pathways in praseodymium-doped ceria. Since the first-principles calculations revealed significant vacancy-vacancy repulsion, we investigate the importance of that effect by conducting simulations with and without a repulsive interaction. Initially, as dopant concentrations increase, vacancy concentration and thus conductivity increases. However, at higher concentrations, vacancies interfere and repel one another, and dopants trap vacancies, creating a 'traffic jam' that decreases conductivity, which is consistent with themore » experimental findings. The modeled effective activation energy for vacancy migration slightly increased with increasing dopant concentration in qualitative agreement with the experiment. The current methodology comprising a blend of first-principle calculations and KLMC model provides a very powerful fundamental tool for predicting the optimal dopant concentration in ceria related materials. -- graphical abstract: Ionic conductivity in praseodymium doped ceria as a function of dopant concentration calculated using the kinetic lattice Monte Carlo vacancy-repelling model, which predicts the optimal composition for achieving maximum conductivity. Display Omitted Research highlights: {yields} KLMC method calculates the accurate time-dependent diffusion of oxygen vacancies. {yields} KLMC-VR model predicts a dopant concentration of {approx}15-20% to be optimal in PDC. {yields} At higher dopant concentration, vacancies interfere and repel one another, and dopants trap vacancies. {yields} Activation energy for vacancy migration increases as a function of dopant content« less

Microbial diversity in ikaite tufa columns: an alkaline, cold ecological niche in Greenland.

PubMed

Stougaard, Peter; Jørgensen, Flemming; Johnsen, Mads G; Hansen, Ole C

2002-08-01

Ikaite tufa columns from the Ikka Fjord in south-western Greenland constitute a natural, stable environment at low temperature and with a pH ranging from neutral at the exterior to very alkaline (pH 10.4) at the interior of the column. Phylogenetic analysis of culturable organisms revealed ten different isolates representing three of the major bacterial divisions. Nine of the isolates showed 94-99% similarity to known sequences, whereas one isolate displayed a low degree of similarity (less than 90%) to a Cyclobacterium species. Seven of the isolates were shown to be cold active alkaliphiles, whereas three isolates showed optimal growth at neutral pH. Phylogenetic analysis of DNA isolated directly from the ikaite material demonstrated the presence of a microbial flora more diverse than the culturable isolates. Whereas approximately half of the phylotypes showed 90-99% similarity to known meso- or thermophilic alkaliphiles, the rest of the sequences displayed less than 90% similarity when compared to known 16S rRNA gene sequences in databases. Thus, in the present paper, we demonstrate that ikaite columns that host a specialized macroscopic flora and fauna also contain a unique, cold active, alkaliphilic microflora.

The Density Code for the Development of a Vaccine?

PubMed Central

Cheng, Wei

2016-01-01

The development of prophylactic vaccines remains largely empirical in nature and rarely have general rules been applied in the strategic decision and the formulation of a viral vaccine. Currently there are a total of 15 virus agents from 12 unique virus families with vaccines licensed by the US Food and Drug Administration. Extensive structural information on these viral particles and potential mechanisms of protection are available for the majority of these virus pathogens and their respective vaccines. Here I review the quantitative features of these viral surface antigens in relation to the molecular mechanisms of B cell activation, and point out a potential correlation between the density of immunogenic proteins displayed on the surface of the vaccine antigen carrier and the success of a vaccine. These features help us understand the humoral immunity induced by viral vaccines on a quantitative ground and re-emphasize the importance of antigen density on the activation of the immune system. Although the detailed mechanisms behind this phenomenon remain to be explored, it implies that both the size of antigen carriers and the density of immunogenic proteins displayed on these carriers are important parameters that may need to be optimized for the formulation of a vaccine. PMID:27649885

ICI 56,780 Optimization: Structure-Activity Relationship Studies of 7-(2-Phenoxyethoxy)-4(1H)-quinolones with Antimalarial Activity.

PubMed

Maignan, Jordany R; Lichorowic, Cynthia L; Giarrusso, James; Blake, Lynn D; Casandra, Debora; Mutka, Tina S; LaCrue, Alexis N; Burrows, Jeremy N; Willis, Paul A; Kyle, Dennis E; Manetsch, Roman

2016-07-28

Though malaria mortality rates are down 48% globally since 2000, reported occurrences of resistance against current therapeutics threaten to reverse that progress. Recently, antimalarials that were once considered unsuitable therapeutic agents have been revisited to improve physicochemical properties and efficacy required for selection as a drug candidate. One such compound is 4(1H)-quinolone ICI 56,780, which is known to be a causal prophylactic that also displays blood schizonticidal activity against P. berghei. Rapid induction of parasite resistance, however, stalled its further development. We have completed a full structure-activity relationship study on 4(1H)-quinolones, focusing on the reduction of cross-resistance with atovaquone for activity against the clinical isolates W2 and TM90-C2B, as well as the improvement of microsomal stability. These studies revealed several frontrunner compounds with superb in vivo antimalarial activity. The best compounds were found to be curative with all mice surviving a Plasmodium berghei infection after 30 days.

Bacteriocins from Lactobacillus plantarum - production, genetic organization and mode of action: produção, organização genética e modo de ação.

PubMed

Todorov, Svetoslav D

2009-04-01

Bacteriocins are biologically active proteins or protein complexes that display a bactericidal mode of action towards usually closely related species. Numerous strains of bacteriocin producing Lactobacillus plantarum have been isolated in the last two decades from different ecological niches including meat, fish, fruits, vegetables, and milk and cereal products. Several of these plantaricins have been characterized and the aminoacid sequence determined. Different aspects of the mode of action, fermentation optimization and genetic organization of the bacteriocin operon have been studied. However, numerous of bacteriocins produced by different Lactobacillus plantarum strains have not been fully characterized. In this article, a brief overview of the classification, genetics, characterization, including mode of action and production optimization for bacteriocins from Lactic Acid Bacteria in general, and where appropriate, with focus on bacteriocins produced by Lactobacillus plantarum, is presented.

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

PubMed

Asgher, Muhammad; Noreen, Sadia; Bilal, Muhammad

2017-02-01

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

Discovery of Novel Hepatitis C Virus NS5B Polymerase Inhibitors by Combining Random Forest, Multiple e-Pharmacophore Modeling and Docking

PubMed Central

Wei, Yu; Li, Jinlong; Qing, Jie; Huang, Mingjie; Wu, Ming; Gao, Fenghua; Li, Dongmei; Hong, Zhangyong; Kong, Lingbao; Huang, Weiqiang; Lin, Jianping

2016-01-01

The NS5B polymerase is one of the most attractive targets for developing new drugs to block Hepatitis C virus (HCV) infection. We describe the discovery of novel potent HCV NS5B polymerase inhibitors by employing a virtual screening (VS) approach, which is based on random forest (RB-VS), e-pharmacophore (PB-VS), and docking (DB-VS) methods. In the RB-VS stage, after feature selection, a model with 16 descriptors was used. In the PB-VS stage, six energy-based pharmacophore (e-pharmacophore) models from different crystal structures of the NS5B polymerase with ligands binding at the palm I, thumb I and thumb II regions were used. In the DB-VS stage, the Glide SP and XP docking protocols with default parameters were employed. In the virtual screening approach, the RB-VS, PB-VS and DB-VS methods were applied in increasing order of complexity to screen the InterBioScreen database. From the final hits, we selected 5 compounds for further anti-HCV activity and cellular cytotoxicity assay. All 5 compounds were found to inhibit NS5B polymerase with IC50 values of 2.01–23.84 μM and displayed anti-HCV activities with EC50 values ranging from 1.61 to 21.88 μM, and all compounds displayed no cellular cytotoxicity (CC50 > 100 μM) except compound N2, which displayed weak cytotoxicity with a CC50 value of 51.3 μM. The hit compound N2 had the best antiviral activity against HCV, with a selective index of 32.1. The 5 hit compounds with new scaffolds could potentially serve as NS5B polymerase inhibitors through further optimization and development. PMID:26845440

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

PubMed

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

2010-09-01

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

Perceptual Optimization of DCT Color Quantization Matrices

NASA Technical Reports Server (NTRS)

Watson, Andrew B.; Statler, Irving C. (Technical Monitor)

1994-01-01

Many image compression schemes employ a block Discrete Cosine Transform (DCT) and uniform quantization. Acceptable rate/distortion performance depends upon proper design of the quantization matrix. In previous work, we showed how to use a model of the visibility of DCT basis functions to design quantization matrices for arbitrary display resolutions and color spaces. Subsequently, we showed how to optimize greyscale quantization matrices for individual images, for optimal rate/perceptual distortion performance. Here we describe extensions of this optimization algorithm to color images.

Discovery of SMP-304, a novel benzylpiperidine derivative with serotonin transporter inhibitory activity and 5-HT1A weak partial agonistic activity showing the antidepressant-like effect.

PubMed

Yoshinaga, Hidefumi; Masumoto, Shuji; Koyama, Koji; Kinomura, Naoya; Matsumoto, Yuji; Kato, Taro; Baba, Satoko; Matsumoto, Kenji; Horisawa, Tomoko; Oki, Hitomi; Yabuuchi, Kazuki; Kodo, Toru

2017-01-01

We report the discovery of a novel benzylpiperidine derivative with serotonin transporter (SERT) inhibitory activity and 5-HT 1A receptor weak partial agonistic activity showing the antidepressant-like effect. The 3-methoxyphenyl group and the phenethyl group of compound 1, which has weak SERT binding activity, but potent 5-HT 1A binding activity, were optimized, leading to compound 35 with potent and balanced dual SERT and 5-HT 1A binding activity, but also potent CYP2D6 inhibitory activity. Replacement of the methoxy group in the left part of compound 35 with a larger alkoxy group, such as ethoxy, isopropoxy or methoxy-ethoxy group ameliorated CYP2D6 inhibition, giving SMP-304 as a candidate. SMP-304 with serotonin uptake inhibitory activity and 5-HT 1A weak partial agonistic activity, which could work as a 5-HT 1A antagonist, displayed faster onset of antidepressant-like effect than a representative SSRI paroxetine in an animal model. Copyright © 2016 Elsevier Ltd. All rights reserved.

Large Area Microencapsulated Reflective Guest-Host Liquid Crystal Displays and Their Applications

NASA Astrophysics Data System (ADS)

Nakai, Yutaka; Tanaka, Masao; Enomoto, Shintaro; Iwanaga, Hiroki; Hotta, Aira; Kobayashi, Hitoshi; Oka, Toshiyuki; Kizaki, Yukio; Kidzu, Yuko; Naito, Katsuyuki

2002-07-01

We have developed reflective liquid crystal displays using microencapsulated guest-host liquid crystals, whose size was sufficiently large for viewing documents. A high-brightness image can be realized because there is no need for polarizers. Easy fabrication processes, consisting of screen-printing of microencapsulated liquid crystal and film adhesion, have enabled the realization of thinner and lighter cell structures. It has been confirmed that the display is tolerant of the pressures to which it would be subject in actual use. The optimization of fabrication processes has enabled the realization of reflectance uniformity in the display area and reduction of the driving voltage. Our developed display is suitable for portable information systems, such as electronic book applications.

Antibody VH and VL recombination using phage and ribosome display technologies reveals distinct structural routes to affinity improvements with VH-VL interface residues providing important structural diversity

PubMed Central

Groves, Maria AT; Amanuel, Lily; Campbell, Jamie I; Rees, D Gareth; Sridharan, Sudharsan; Finch, Donna K; Lowe, David C; Vaughan, Tristan J

2014-01-01

In vitro selection technologies are an important means of affinity maturing antibodies to generate the optimal therapeutic profile for a particular disease target. Here, we describe the isolation of a parent antibody, KENB061 using phage display and solution phase selections with soluble biotinylated human IL-1R1. KENB061 was affinity matured using phage display and targeted mutagenesis of VH and VL CDR3 using NNS randomization. Affinity matured VHCDR3 and VLCDR3 library blocks were recombined and selected using phage and ribosome display protocol. A direct comparison of the phage and ribosome display antibodies generated was made to determine their functional characteristics. PMID:24256948

Numerical investigation on the viewing angle of a lenticular three-dimensional display with a triplet lens array.

PubMed

Kim, Hwi; Hahn, Joonku; Choi, Hee-Jin

2011-04-10

We investigate the viewing angle enhancement of a lenticular three-dimensional (3D) display with a triplet lens array. The theoretical limitations of the viewing angle and view number of the lenticular 3D display with the triplet lens array are analyzed numerically. For this, the genetic-algorithm-based design method of the triplet lens is developed. We show that a lenticular 3D display with viewing angle of 120° and 144 views without interview cross talk can be realized with the use of an optimally designed triplet lens array. © 2011 Optical Society of America

Review of fluorescence guided surgery visualization and overlay techniques

PubMed Central

Elliott, Jonathan T.; Dsouza, Alisha V.; Davis, Scott C.; Olson, Jonathan D.; Paulsen, Keith D.; Roberts, David W.; Pogue, Brian W.

2015-01-01

In fluorescence guided surgery, data visualization represents a critical step between signal capture and display needed for clinical decisions informed by that signal. The diversity of methods for displaying surgical images are reviewed, and a particular focus is placed on electronically detected and visualized signals, as required for near-infrared or low concentration tracers. Factors driving the choices such as human perception, the need for rapid decision making in a surgical environment, and biases induced by display choices are outlined. Five practical suggestions are outlined for optimal display orientation, color map, transparency/alpha function, dynamic range compression, and color perception check. PMID:26504628

Meeting the challenges of developing LED-based projection displays

NASA Astrophysics Data System (ADS)

Geißler, Enrico

2006-04-01

The main challenge in developing a LED-based projection system is to meet the brightness requirements of the market. Therefore a balanced combination of optical, electrical and thermal parameters must be reached to achieve these performance and cost targets. This paper describes the system design methodology for a digital micromirror display (DMD) based optical engine using LEDs as the light source, starting at the basic physical and geometrical parameters of the DMD and other optical elements through characterization of the LEDs to optimizing the system performance by determining optimal driving conditions. LEDs have a luminous flux density which is just at the threshold of acceptance in projection systems and thus only a fully optimized optical system with a matched set of LEDs can be used. This work resulted in two projection engines, one for a compact pocket projector and the other for a rear projection television, both of which are currently in commercialization.

Evaluation of in vitro antidiabetic and antioxidant characterizations of Elettaria cardamomum (L.) Maton (Zingiberaceae), Piper cubeba L. f. (Piperaceae), and Plumeria rubra L. (Apocynaceae).

PubMed

Ahmed, Afnan Sh; Ahmed, Qamaruddin; Saxena, Anil Kumar; Jamal, Parveen

2017-01-01

Inhibition of intestinal α-amylase and α-glucosidase is an important strategy to regulate diabetes mellitus (DM). Antioxidants from plants are widely regarded in the prevention of diabetes. Fruits of Elettaria cardamomum (L.) Maton (Zingiberaceae) and Piper cubeba L. f. (Piperaceae) and flowers of Plumeria rubra L. (Apocynaceae) are traditionally used to cure DM in different countries. However, the role of these plants has been grossly under reported and is yet to receive proper scientific evaluation with respect to understand their traditional role in the management of diabetes especially as digestive enzymes inhibitors. Hence, methanol and aqueous extracts of the aforementioned plants were evaluated for their in vitro α-glucosidase and α-amylase inhibition at 1 mg/mL and quantification of their antioxidant properties (DPPH, FRAP tests, total phenolic and total flavonoids contents). In vitro optimization studies for the extracts were also performed to enhance in vitro biological activities. The % inhibition of α-glucosidase by the aqueous extracts of the fruits of E. cardamomum, P. cubeba and flowers of P. rubra were 10.41 (0.03), 95.19 (0.01), and -2.92 (0.03), while the methanol extracts exhibited % inhibition 13.73 (0.02), 92.77 (0.01), and -0.98 (0.01), respectively. The % inhibition of α-amylase by the aqueous extracts were 82.99 (0.01), 64.35 (0.01), and 20.28 (0.02), while the methanol extracts displayed % inhibition 39.93 (0.01), 31.06 (0.02), and 39.40 (0.01), respectively. Aqueous extracts displayed good in vitro antidiabetic and antioxidant activities. Moreover, in vitro optimization experiments helped to increase the α-glucosidase inhibitory activity of E. cardamomum. Our findings further justify the traditional claims of these plants as folk medicines to manage diabetes, however, through digestive enzymes inhibition effect.

A kinesthetic-tactual display concept for helicopter-pilot workload reduction

NASA Technical Reports Server (NTRS)

Gilson, R. D.; Dunn, R. S.; Sun, P.

1977-01-01

A kinesthetic-tactual (K-T) display concept is now under research and development (R & D) at the Ohio State University. It appears to offer considerable promise for useful application in helicopters by conveying control information via the sense of touch. This is a review of the overall R & D program including the original K-T display design, initial studies in automobile and fixed-wing vehicles, and feasibility experiments in a helicopter simulator. In addition to investigations of control and potential workload reduction, present efforts are directed toward establishing optimal design requirements for K-T helicopter displays. Potential applications, modes of usage, and the kinds of information that may be displayed in helicopter applications are discussed along with a brief forecast of future R & D. A brief description of the latest multi-axis laboratory prototype K-T display is also provided.

Effect of display size on utilization of traffic situation display for self-spacing task. [transport aircraft

NASA Technical Reports Server (NTRS)

Abbott, T. S.; Moen, G. C.

1981-01-01

The weather radar cathode ray tube (CRT) is the prime candidate for presenting cockpit display of traffic information (CDTI) in current, conventionally equipped transport aircraft. Problems may result from this, since the CRT size is not optimized for CDTI applications and the CRT is not in the pilot's primary visual scan area. The impact of display size on the ability of pilots to utilize the traffic information to maintain a specified spacing interval behind a lead aircraft during an approach task was studied. The five display sizes considered are representative of the display hardware configurations of airborne weather radar systems. From a pilot's subjective workload viewpoint, even the smallest display size was usable for performing the self spacing task. From a performane viewpoint, the mean spacing values, which are indicative of how well the pilots were able to perform the task, exhibit the same trends, irrespective of display size; however, the standard deviation of the spacing intervals decreased (performance improves) as the display size increased. Display size, therefore, does have a significant effect on pilot performance.

Evaluation of potential for reuse of industrial wastewater using metal-immobilized catalysts and reverse osmosis.

PubMed

Choi, Jeongyun; Chung, Jinwook

2015-04-01

This report describes a novel technology of reusing the wastewater discharged from the display manufacturing industry through an advanced oxidation process (AOP) with a metal-immobilized catalyst and reverse osmosis (RO) in the pilot scale. The reclaimed water generated from the etching and cleaning processes in display manufacturing facilities was low-strength organic wastewater and was required to be recycled to secure a water source. For the reuse of reclaimed water to ultrapure water (UPW), a combination of solid-phase AOP and RO was implemented. The removal efficiency of TOC by solid-phase AOP and RO was 92%. Specifically, the optimal acid, pH, and H2O2 concentrations in the solid-phase AOP were determined. With regard to water quality and operating costs, the combination of solid-phase AOP and RO was superior to activated carbon/RO and ultraviolet AOP/anion polisher/coal carbon. Copyright © 2014 Elsevier Ltd. All rights reserved.

Quantitative analysis reveals how EGFR activation and downregulation are coupled in normal but not in cancer cells

PubMed Central

Capuani, Fabrizio; Conte, Alexia; Argenzio, Elisabetta; Marchetti, Luca; Priami, Corrado; Polo, Simona; Di Fiore, Pier Paolo; Sigismund, Sara; Ciliberto, Andrea

2015-01-01

Ubiquitination of the epidermal growth factor receptor (EGFR) that occurs when Cbl and Grb2 bind to three phosphotyrosine residues (pY1045, pY1068 and pY1086) on the receptor displays a sharp threshold effect as a function of EGF concentration. Here we use a simple modelling approach together with experiments to show that the establishment of the threshold requires both the multiplicity of binding sites and cooperative binding of Cbl and Grb2 to the EGFR. While the threshold is remarkably robust, a more sophisticated model predicted that it could be modulated as a function of EGFR levels on the cell surface. We confirmed experimentally that the system has evolved to perform optimally at physiological levels of EGFR. As a consequence, this system displays an intrinsic weakness that causes—at the supraphysiological levels of receptor and/or ligand associated with cancer—uncoupling of the mechanisms leading to signalling through phosphorylation and attenuation through ubiquitination. PMID:26264748

N-terminal acylation of somatostatin analog with long chain fatty acids enhances its stability and anti-proliferative activity in human breast adenocarcinoma cells.

PubMed

Dasgupta, Piyali; Singh, Anu; Mukherjee, Rama

2002-01-01

The anti-proliferative activity of the somatostatin analog RC-160 is limited by its short serum half life. To circumvent this limitation, fatty acids of chain lengths ranging from 4 to 18 were individually conjugated to the N-terminal residue of RC-160. The lipophilized derivatives of RC-160 were synthesized, purified and characterized. The anti-proliferative activity of lipophilized-RC-160 on the human breast carcinoma cell line MCF-7, was evaluated in vitro. The long chain lipopeptides like pamitoyl-RC-160 exhibited significantly higher anti-proliferative activity on MCF-7 cells (p<0.001), relative to RC-160. The affinity of RC-160 towards somatostatin receptors remained unaltered by pamitoylation. However, the observed increase in bioactivity was manifested within an optimum range of chain length of the lipoppetide. Increasing the peptide hydrophobicity beyond this range reduced the bioactivity of lipophilized-RC-160. Accordingly, stearoyl-RC-160, manifested lower anti-neoplastic activity and receptor affinity relative to pamitoyl-RC-160 and RC-160 itself. The signaling pathways underlying the antineoplastic activity of these lipopeptides were found to be similar to RC-160. Pamitoyl-RC-160 displayed enhanced inhibition of protein tyrosine kinase activity and intracellular cAMP levels in MCF-7 cells, relative to butanoyl-RC-160 or RC-160 itself. Pamitoyl-RC-160 also displayed greater resistance towards trypsin and serum degradation than RC-160. Lipophilization of RC-160 with long chain fatty acids like pamitic acid improves its stability and anti-proliferative activity, thereby improving the scope of enhancing its therapeutic index. However, the optimization of peptide hydrophobicity seems to be a crucial factor governing the efficacy of bioactive lipopeptides.

Structural and biological evaluation of a novel series of benzimidazole inhibitors of Francisella tularensis enoyl-ACP reductase (FabI)

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

Mehboob, Shahila; Song, Jinhua; Hevener, Kirk E.

Francisella tularensis, the causative agent of tularemia, presents a significant biological threat and is a Category A priority pathogen due to its potential for weaponization. In the bacterial FASII pathway we found it a viable target for the development of novel antibacterial agents treating Gram-negative infections. Here, we report the advancement of a promising series of benzimidazole FabI (enoyl-ACP reductase) inhibitors to a second-generation using a systematic, structure-guided lead optimization strategy, and the determination of several co-crystal structures that confirm the binding mode of designed inhibitors. Furthermore, these compounds display an improved low nanomolar enzymatic activity as well as promisingmore » low microgram/mL antibacterial activity against both F. tularensis and Staphylococcus aureus and its methicillin-resistant strain (MRSA). Finally, the improvements in activity accompanying structural modifications lead to a better understanding of the relationship between the chemical structure and biological activity that encompasses both enzymatic and whole-cell activity.« less

Structural and biological evaluation of a novel series of benzimidazole inhibitors of Francisella tularensis enoyl-ACP reductase (FabI)

DOE PAGES

Mehboob, Shahila; Song, Jinhua; Hevener, Kirk E.; ...

2015-01-29

Francisella tularensis, the causative agent of tularemia, presents a significant biological threat and is a Category A priority pathogen due to its potential for weaponization. In the bacterial FASII pathway we found it a viable target for the development of novel antibacterial agents treating Gram-negative infections. Here, we report the advancement of a promising series of benzimidazole FabI (enoyl-ACP reductase) inhibitors to a second-generation using a systematic, structure-guided lead optimization strategy, and the determination of several co-crystal structures that confirm the binding mode of designed inhibitors. Furthermore, these compounds display an improved low nanomolar enzymatic activity as well as promisingmore » low microgram/mL antibacterial activity against both F. tularensis and Staphylococcus aureus and its methicillin-resistant strain (MRSA). Finally, the improvements in activity accompanying structural modifications lead to a better understanding of the relationship between the chemical structure and biological activity that encompasses both enzymatic and whole-cell activity.« less

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

PubMed

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

2008-08-01

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

Stimulation seeking and hyperactivity in children with ADHD. Attention Deficit Hyperactivity Disorder.

PubMed

Antrop, I; Roeyers, H; Van Oost, P; Buysse, A

2000-02-01

Thirty hyperactive and 30 non-hyperactive children were confronted with a delay, consisting of a waiting situation of 15 minutes, either with or without extra stimulation provided by the presentation of a videotape. The behaviour of the child during the waiting period was videotaped and later coded by two naive observers. In line with theories that emphasise the stimulation-seeking function of hyperactive behaviours, such as the optimal stimulation account and the delay aversion theory, a group by stimulation effect was hypothesised. For two categories of activity this was found, with ADHD children displaying more activity than non-ADHD children in the no-stimulation but not in the stimulation condition. These data provide support for the stimulation-seeking function of certain features of ADHD hyperactivity.

Design and implementation of organic LED-based displays for signage application

NASA Astrophysics Data System (ADS)

Sharma, Pratibha; Kwok, Harry

2006-06-01

Organic light-emitting diodes (OLEDs) have been utilized successfully for various applications such as microdisplays in cell-phones and digital cameras. However, the application of OLEDs for large area signage displays has not yet been established. This paper presents novel design techniques for implementing OLEDs as light sources for signage application. The designs are examined on the basis of signage uniformity, cost and manufacturing complexity. Advantages and limitations of each design are described. It is determined that a trade-off is required to choose a design for implementation. After evaluation and comparison of the designs, the most optimal design is chosen and implemented. Measurement results with the optimal design are described.

Convergent evolution of vascular optimization in kelp (Laminariales).

PubMed

Drobnitch, Sarah Tepler; Jensen, Kaare H; Prentice, Paige; Pittermann, Jarmila

2015-10-07

Terrestrial plants and mammals, although separated by a great evolutionary distance, have each arrived at a highly conserved body plan in which universal allometric scaling relationships govern the anatomy of vascular networks and key functional metabolic traits. The universality of allometric scaling suggests that these phyla have each evolved an 'optimal' transport strategy that has been overwhelmingly adopted by extant species. To truly evaluate the dominance and universality of vascular optimization, however, it is critical to examine other, lesser-known, vascularized phyla. The brown algae (Phaeophyceae) are one such group--as distantly related to plants as mammals, they have convergently evolved a plant-like body plan and a specialized phloem-like transport network. To evaluate possible scaling and optimization in the kelp vascular system, we developed a model of optimized transport anatomy and tested it with measurements of the giant kelp, Macrocystis pyrifera, which is among the largest and most successful of macroalgae. We also evaluated three classical allometric relationships pertaining to plant vascular tissues with a diverse sampling of kelp species. Macrocystis pyrifera displays strong scaling relationships between all tested vascular parameters and agrees with our model; other species within the Laminariales display weak or inconsistent vascular allometries. The lack of universal scaling in the kelps and the presence of optimized transport anatomy in M. pyrifera raises important questions about the evolution of optimization and the possible competitive advantage conferred by optimized vascular systems to multicellular phyla. © 2015 The Author(s).

Searching for Signs, Symbols, and Icons: Effects of Time of Day, Visual Complexity, and Grouping

ERIC Educational Resources Information Center

McDougall, Sine; Tyrer, Victoria; Folkard, Simon

2006-01-01

Searching for icons, symbols, or signs is an integral part of tasks involving computer or radar displays, head-up displays in aircraft, or attending to road traffic signs. Icons therefore need to be designed to optimize search times, taking into account the factors likely to slow down visual search. Three factors likely to adversely affect visual…

Neurosteroid-like Inhibitors of N-Methyl-d-aspartate Receptor: Substituted 2-Sulfates and 2-Hemisuccinates of Perhydrophenanthrene.

PubMed

Slavikova, Barbora; Chodounska, Hana; Nekardova, Michaela; Vyklicky, Vojtech; Ladislav, Marek; Hubalkova, Pavla; Krausova, Barbora; Vyklicky, Ladislav; Kudova, Eva

2016-05-26

N-Methyl-d-aspartate receptors (NMDARs) display a critical role in various diseases of the central nervous system. The activity of NMDARs can be modulated by neurosteroids. Herein, we report a structure-activity relationship study for perhydrophenanthrene analogues possessing a framework that mimics the steroidal ring system. This study comprises the design, synthesis, and assessment of the biological activity of a library of perhydrophenanthrene 2-sulfates and 2-hemisuccinates (1-10). Their ability to modulate NMDAR-induced currents was tested on recombinant GluN1/GluN2B receptors. Our results demonstrate that such structural optimization leads to compounds that are inhibitors of NMDARs. Notably, compound 9 (IC50 = 15.6 μM) was assessed as a more potent inhibitor of NMDAR-induced currents than the known endogenous neurosteroid, pregnanolone sulfate (IC50 = 24.6 μM).

Production of Delta(1)-tetrahydrocannabinolic acid by the biosynthetic enzyme secreted from transgenic Pichia pastoris.

PubMed

Taura, Futoshi; Dono, Emi; Sirikantaramas, Supaart; Yoshimura, Kohji; Shoyama, Yukihiro; Morimoto, Satoshi

2007-09-28

Delta(1)-Tetrahydrocannabinolic acid (THCA) synthase is the enzyme that catalyzes the oxidative cyclization of cannabigerolic acid into THCA, the acidic precursor of Delta(1)-tetrahydrocannabinol. We developed a novel expression system for THCA synthase using a methylotrophic yeast Pichia pastoris as a host. Under optimized conditions, the transgenic P. pastoris secreted approximately 1.32nkat/l of THCA synthase activity, and the culture medium, from which the cells were removed, effectively synthesized THCA from cannabigerolic acid with a approximately 98% conversion rate. The secreted THCA synthase was readily purified to homogeneity. Interestingly, endoglycosidase treatment afforded a deglycosylated THCA synthase with more catalytic activity than that of the glycosylated form. The non-glycosylated THCA synthase should be suitable for structure-function studies because it displayed much more activity than the previously reported native enzyme from Cannabis sativa as well as the recombinant enzyme from insect cell cultures.

Cationic lipids: molecular structure/ transfection activity relationships and interactions with biomembranes.

PubMed

Koynova, Rumiana; Tenchov, Boris

2010-01-01

Abstract Synthetic cationic lipids, which form complexes (lipoplexes) with polyanionic DNA, are presently the most widely used constituents of nonviral gene carriers. A large number of cationic amphiphiles have been synthesized and tested in transfection studies. However, due to the complexity of the transfection pathway, no general schemes have emerged for correlating the cationic lipid chemistry with their transfection efficacy and the approaches for optimizing their molecular structures are still largely empirical. Here we summarize data on the relationships between transfection activity and cationic lipid molecular structure and demonstrate that the transfection activity depends in a systematic way on the lipid hydrocarbon chain structure. A number of examples, including a large series of cationic phosphatidylcholine derivatives, show that optimum transfection is displayed by lipids with chain length of approximately 14 carbon atoms and that the transfection efficiency strongly increases with increase of chain unsaturation, specifically upon replacement of saturated with monounsaturated chains.

Algorithms for bilevel optimization

NASA Technical Reports Server (NTRS)

Alexandrov, Natalia; Dennis, J. E., Jr.

1994-01-01

General multilevel nonlinear optimization problems arise in design of complex systems and can be used as a means of regularization for multi-criteria optimization problems. Here, for clarity in displaying our ideas, we restrict ourselves to general bi-level optimization problems, and we present two solution approaches. Both approaches use a trust-region globalization strategy, and they can be easily extended to handle the general multilevel problem. We make no convexity assumptions, but we do assume that the problem has a nondegenerate feasible set. We consider necessary optimality conditions for the bi-level problem formulations and discuss results that can be extended to obtain multilevel optimization formulations with constraints at each level.

Establishing Dual Electrogenerated Chemiluminescence and Multi-Color Electrochromism in Functional Ionic Transition Metal Complexes

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

Puodziukynaite, Egle; Oberst, Justin L.; Dyer, Aubrey L.

A combination of electrochromism and electroluminescence in functional materials could lead to single-layer dual electrochromic/electroluminescent (EC/EL) display devices, capable of simultaneous operation in emissive and reflective modes. Whereas such next generation displays could provide optimal visibility in any ambient lighting situation, materials available that exhibit such characteristics in the active layer are limited due to the required intrinsic multifunctionality (i.e., redox activity, electroluminescence, electrochromism, and ion conductivity) and to date can only be achieved via the rational design of ionic transition-metal complexes. Reported herein is the synthesis and characterization of a new family of acrylate-containing ruthenium (tris)bipyridine-based coordination complexes withmore » multifunctional characteristics. Potential use of the presented compounds in EC/EL devices is established, as they are applied as cross-linked electrochromic films and electrochemiluminescent layers in light-emitting electrochemical cell devices. Electrochromic switching of the polymeric networks between yellow, orange, green, brown and transmissive states is demonstrated, and electrochemiluminescent devices based on the complexes synthesized show red-orange to deep red emission with λ{sub max} ranging from 680 to 722 nm and luminance up to 135 cd/m{sup 2}. Additionally, a dual EC/EL device prototype is presented where light emission and multicolor electrochromism occur from the same pixel comprised of a single active layer, demonstrating a true combination of these properties in ionic transition-metal complexes.« less

Establishing Dual Electrogenerated Chemiluminescence and Multicolor Electrochromism in Functional Ionic Transition-Metal Complexes

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

Puodziukynaite, Egle; Oberst, Justin L.; Dyer, Aubrey L.

A combination of electrochromism and electroluminescence in functional materials could lead to single-layer dual electrochromic/electroluminescent (EC/EL) display devices, capable of simultaneous operation in emissive and reflective modes. Whereas such next generation displays could provide optimal visibility in any ambient lighting situation, materials available that exhibit such characteristics in the active layer are limited due to the required intrinsic multifunctionality (i.e., redox activity, electroluminescence, electrochromism, and ion conductivity) and to date can only be achieved via the rational design of ionic transition-metal complexes. Reported herein is the synthesis and characterization of a new family of acrylate-containing ruthenium (tris)bipyridine-based coordination complexes withmore » multifunctional characteristics. Potential use of the presented compounds in EC/EL devices is established, as they are applied as cross-linked electrochromic films and electrochemiluminescent layers in light-emitting electrochemical cell devices. Electrochromic switching of the polymeric networks between yellow, orange, green, brown and transmissive states is demonstrated, and electrochemiluminescent devices based on the complexes synthesized show red-orange to deep red emission with λmax ranging from 680 to 722 nm and luminance up to 135 cd/m². Additionally, a dual EC/EL device prototype is presented where light emission and multicolor electrochromism occur from the same pixel comprised of a single active layer, demonstrating a true combination of these properties in ionic transition-metal complexes.« less

Evaluation of antimicrobial properties of cork.

PubMed

Gonçalves, Filipa; Correia, Patrícia; Silva, Susana P; Almeida-Aguiar, Cristina

2016-02-01

Cork presents a range of diverse and versatile properties making this material suitable for several and extremely diverse industrial applications. Despite the wide uses of cork, its antimicrobial properties and potential applications have deserved little attention from industry and the scientific community. Thus, the main purpose of this work was the evaluation of the antibacterial properties of cork, by comparison with commercially available antimicrobial materials (Ethylene-Vinyl Acetate copolymer and a currently used antimicrobial commercial additive (ACA)), following the previous development and optimization of a method for such antimicrobial assay. The AATCC 100-2004 standard method, a quantitative procedure developed for the assessment of antimicrobial properties in textile materials, was used as reference and optimized to assess cork antibacterial activity. Cork displayed high antibacterial activity against Staphylococcus aureus, with a bacterial reduction of almost 100% (96.93%) after 90 minutes of incubation, similar to the one obtained with ACA. A more reduced but time-constant antibacterial action was observed against Escherichia coli (36% reduction of the initial number of bacterial colonies). To complement this study, antibacterial activity was further evaluated for a water extract of cork and an MIC of 6 mg mL(-1) was obtained against the reference strain S. aureus. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Repressive LTR Nucleosome Positioning by the BAF Complex Is Required for HIV Latency

PubMed Central

Hakre, Shweta; Moshkin, Yuri; Verdin, Eric; Mahmoudi, Tokameh

2011-01-01

Persistence of a reservoir of latently infected memory T cells provides a barrier to HIV eradication in treated patients. Several reports have implicated the involvement of SWI/SNF chromatin remodeling complexes in restricting early steps in HIV infection, in coupling the processes of integration and remodeling, and in promoter/LTR transcription activation and repression. However, the mechanism behind the seemingly contradictory involvement of SWI/SNF in the HIV life cycle remains unclear. Here we addressed the role of SWI/SNF in regulation of the latent HIV LTR before and after transcriptional activation. We determined the predicted nucleosome affinity of the LTR sequence and found a striking reverse correlation when compared to the strictly positioned in vivo LTR nucleosomal structure; sequences encompassing the DNase hypersensitive regions displayed the highest nucleosome affinity, while the strictly positioned nucleosomes displayed lower affinity for nucleosome formation. To examine the mechanism behind this reverse correlation, we used a combinatorial approach to determine DNA accessibility, histone occupancy, and the unique recruitment and requirement of BAF and PBAF, two functionally distinct subclasses of SWI/SNF at the LTR of HIV-infected cells before and after activation. We find that establishment and maintenance of HIV latency requires BAF, which removes a preferred nucleosome from DHS1 to position the repressive nucleosome-1 over energetically sub-optimal sequences. Depletion of BAF resulted in de-repression of HIV latency concomitant with a dramatic alteration in the LTR nucleosome profile as determined by high resolution MNase nucleosomal mapping. Upon activation, BAF was lost from the HIV promoter, while PBAF was selectively recruited by acetylated Tat to facilitate LTR transcription. Thus BAF and PBAF, recruited during different stages of the HIV life cycle, display opposing function on the HIV promoter. Our data point to the ATP-dependent BRG1 component of BAF as a putative therapeutic target to deplete the latent reservoir in patients. PMID:22140357

Repressive LTR nucleosome positioning by the BAF complex is required for HIV latency.

PubMed

Rafati, Haleh; Parra, Maribel; Hakre, Shweta; Moshkin, Yuri; Verdin, Eric; Mahmoudi, Tokameh

2011-11-01

Persistence of a reservoir of latently infected memory T cells provides a barrier to HIV eradication in treated patients. Several reports have implicated the involvement of SWI/SNF chromatin remodeling complexes in restricting early steps in HIV infection, in coupling the processes of integration and remodeling, and in promoter/LTR transcription activation and repression. However, the mechanism behind the seemingly contradictory involvement of SWI/SNF in the HIV life cycle remains unclear. Here we addressed the role of SWI/SNF in regulation of the latent HIV LTR before and after transcriptional activation. We determined the predicted nucleosome affinity of the LTR sequence and found a striking reverse correlation when compared to the strictly positioned in vivo LTR nucleosomal structure; sequences encompassing the DNase hypersensitive regions displayed the highest nucleosome affinity, while the strictly positioned nucleosomes displayed lower affinity for nucleosome formation. To examine the mechanism behind this reverse correlation, we used a combinatorial approach to determine DNA accessibility, histone occupancy, and the unique recruitment and requirement of BAF and PBAF, two functionally distinct subclasses of SWI/SNF at the LTR of HIV-infected cells before and after activation. We find that establishment and maintenance of HIV latency requires BAF, which removes a preferred nucleosome from DHS1 to position the repressive nucleosome-1 over energetically sub-optimal sequences. Depletion of BAF resulted in de-repression of HIV latency concomitant with a dramatic alteration in the LTR nucleosome profile as determined by high resolution MNase nucleosomal mapping. Upon activation, BAF was lost from the HIV promoter, while PBAF was selectively recruited by acetylated Tat to facilitate LTR transcription. Thus BAF and PBAF, recruited during different stages of the HIV life cycle, display opposing function on the HIV promoter. Our data point to the ATP-dependent BRG1 component of BAF as a putative therapeutic target to deplete the latent reservoir in patients.

CR softcopy display presets based on optimum visualization of specific findings

NASA Astrophysics Data System (ADS)

Andriole, Katherine P.; Gould, Robert G.; Webb, W. R.

1999-07-01

The purpose of this research is to assess the utility of providing presets for computed radiography (CR) softcopy display, based not on the window/level settings, but on image processing applied to the image based on optimization for visualization of specific findings, pathologies, etc. Clinical chest images are acquired using an Agfa ADC 70 CR scanner, and transferred over the PACS network to an image processing station which has the capability to perform multiscale contrast equalization. The optimal image processing settings per finding are developed in conjunction with a thoracic radiologist by manipulating the multiscale image contrast amplification algorithm parameters. Softcopy display of images processed with finding-specific settings are compared with the standard default image presentation for fifty cases of each category. Comparison is scored using a five point scale with positive one and two denoting the standard presentation is preferred over the finding-specific presets, negative one and two denoting the finding-specific preset is preferred over the standard presentation, and zero denoting no difference. Presets have been developed for pneumothorax and clinical cases are currently being collected in preparation for formal clinical trials. Subjective assessments indicate a preference for the optimized-preset presentation of images over the standard default, particularly by inexperienced radiology residents and referring clinicians.

Discovery of orally efficacious RORγt inverse agonists, part 1: Identification of novel phenylglycinamides as lead scaffolds.

PubMed

Shirai, Junya; Tomata, Yoshihide; Kono, Mitsunori; Ochida, Atsuko; Fukase, Yoshiyuki; Sato, Ayumu; Masada, Shinichi; Kawamoto, Tetsuji; Yonemori, Kazuko; Koyama, Ryoukichi; Nakagawa, Hideyuki; Nakayama, Masaharu; Uga, Keiko; Shibata, Akira; Koga, Keiko; Okui, Toshitake; Shirasaki, Mikio; Skene, Robert; Sang, BiChing; Hoffman, Isaac; Lane, Wes; Fujitani, Yasushi; Yamasaki, Masashi; Yamamoto, Satoshi

2018-01-15

A series of novel phenylglycinamides as retinoic acid receptor-related orphan receptor-gamma t (RORγt) inverse agonists were discovered through optimization of a high-throughput screen hit 1. (R)-N-(2-((3,5-Difluoro-4-(trimethylsilyl)phenyl) amino)-1-(4-methoxyphenyl)-2-oxoethyl)-3-hydroxy-N-methylisoxazole-5-carboxamide (22) was identified as one of the best of these compounds. It displayed higher subtype selectivity and specificity over other nuclear receptors and demonstrated in vivo potency to suppress the transcriptional activity of RORγt in a mouse PD (pharmacodynamic) model upon oral administration. Copyright © 2017 Elsevier Ltd. All rights reserved.

Identification of a Potential Antimalarial Drug Candidate from a Series of 2-Aminopyrazines by Optimization of Aqueous Solubility and Potency across the Parasite Life Cycle.

PubMed

Le Manach, Claire; Nchinda, Aloysius T; Paquet, Tanya; Gonzàlez Cabrera, Diego; Younis, Yassir; Han, Ze; Bashyam, Sridevi; Zabiulla, Mohammed; Taylor, Dale; Lawrence, Nina; White, Karen L; Charman, Susan A; Waterson, David; Witty, Michael J; Wittlin, Sergio; Botha, Mariëtte E; Nondaba, Sindisiswe H; Reader, Janette; Birkholtz, Lyn-Marie; Jiménez-Díaz, María Belén; Martínez, María Santos; Ferrer, Santiago; Angulo-Barturen, Iñigo; Meister, Stephan; Antonova-Koch, Yevgeniya; Winzeler, Elizabeth A; Street, Leslie J; Chibale, Kelly

2016-11-10

Introduction of water-solubilizing groups on the 5-phenyl ring of a 2-aminopyrazine series led to the identification of highly potent compounds against the blood life-cycle stage of the human malaria parasite Plasmodium falciparum. Several compounds displayed high in vivo efficacy in two different mouse models for malaria, P. berghei-infected mice and P. falciparum-infected NOD-scid IL-2Rγ null mice. One of the frontrunners, compound 3, was identified to also have good pharmacokinetics and additionally very potent activity against the liver and gametocyte parasite life-cycle stages.

Discovery of 3-morpholino-imidazole[1,5- a ]pyrazine BTK inhibitors for rheumatoid arthritis

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

Boga, Sobhana Babu; Alhassan, Abdul-Basit; Liu, Jian

8-Amino-imidazo[1,5-a]pyrazine-based Bruton’s tyrosine kinase (BTK) inhibitors, such as 6, exhibited potent inhibition of BTK but required improvements in both kinase and hERG selectivity (Liu et al., 2016; Gao et al., 2017). In an effort to maintain the inhibitory activity of these analogs and improve their selectivity profiles, we carried out SAR exploration of groups at the 3-position of pyrazine compound 6. This effort led to the discovery of the morpholine group as an optimized pharmacophore. Compounds 13, 23 and 38 displayed excellent BTK potencies, kinase and hERG selectivities, and pharmacokinetic profiles.

Visual display angles of conventional and a remotely piloted aircraft.

PubMed

Kamine, Tovy Haber; Bendrick, Gregg A

2009-04-01

Instrument display separation and proximity are important human factor elements used in the design and grouping of aircraft instrument displays. To assess display proximity in practical operations, the viewing visual angles of various displays in several conventional aircraft and in a remotely piloted vehicle were assessed. The horizontal and vertical instrument display visual angles from the pilot's eye position were measured in 12 different types of conventional aircraft, and in the ground control station (GCS) of a remotely piloted aircraft (RPA). A total of 18 categories of instrument display were measured and compared. In conventional aircraft almost all of the vertical and horizontal visual display angles lay within a "cone of easy eye movement" (CEEM). Mission-critical instruments particular to specific aircraft types sometimes displaced less important instruments outside the CEEM. For the RPA, all horizontal visual angles lay within the CEEM, but most vertical visual angles lay outside this cone. Most instrument displays in conventional aircraft were consistent with display proximity principles, but several RPA displays lay outside the CEEM in the vertical plane. Awareness of this fact by RPA operators may be helpful in minimizing information access cost, and in optimizing RPA operations.

Interest of cyclodextrins in spray-dried microparticles formulation for sustained pulmonary delivery of budesonide.

PubMed

Dufour, Gilles; Bigazzi, William; Wong, Nelson; Boschini, Frederic; de Tullio, Pascal; Piel, Geraldine; Cataldo, Didier; Evrard, Brigitte

2015-11-30

To achieve an efficient lung delivery and efficacy, both active ingredient aerosolisation properties and permeability through the lung need to be optimized. To overcome these challenges, the present studies aim to develop cyclodextrin-based spray-dried microparticles containing a therapeutic corticosteroid (budesonide) that could be used to control airway inflammation associated with asthma. The complexation between budesonide and hydroxypropyl-β-cyclodextrin (HPBCD) has been investigated. Production of inhalation powders was carried out using a bi-fluid nozzle spray dryer and was optimized based on a design of experiments. Spray-dried microparticles display a specific "deflated-ball like shape" associated with an appropriate size for inhalation. Aerodynamic assessment show that the fine particle fraction was increased compared to a classical lactose-based budesonide formulation (44.05 vs 26.24%). Moreover, the budesonide permeability out of the lung was shown to be reduced in the presence of cyclodextrin complexes. The interest of this sustained budesonide release was evaluated in a mouse model of asthma. The anti-inflammatory effect was compared to a non-complexed budesonide formulation at the same concentration and attests the higher anti-inflammatory activity reach with the cyclodextrin-based formulation. This strategy could therefore be of particular interest for improving lung targeting while decreasing systemic side effects associated with high doses of corticosteroids. In conclusion, this works reports that cyclodextrins could be used in powder for inhalation, both for their abilities to improve active ingredient aerosolisation properties and further to their dissolution in lung fluid, to decrease permeability out of the lungs leading to an optimized activity profile. Copyright © 2015 Elsevier B.V. All rights reserved.

Gene cloning and enzymatic characterization of an alkali-tolerant endo-1,4-β-mannanase from Rhizomucor miehei.

PubMed

Katrolia, Priti; Yan, Qiaojuan; Zhang, Pan; Zhou, Peng; Yang, Shaoqing; Jiang, Zhengqiang

2013-01-16

An endo-1,4-β-mannanase gene (RmMan5A) was cloned from the thermophilic fungus Rhizomucor miehei for the first time and expressed in Escherichia coli . The gene had an open reading frame of 1330 bp encoding 378 amino acids and contained four introns. It displayed the highest amino acid sequence identity (42%) with the endo-1,4-β-mannanases from glycoside hydrolase family 5. The purified enzyme was a monomer of 43 kDa. RmMan5A displayed maximum activity at 55 °C and an optimal pH of 7.0. It was thermostable up to 55 °C and alkali-tolerant, displaying excellent stability over a broad pH range of 4.0-10.0, when incubated for 30 min without substrate. The enzyme displayed the highest specificity for locust bean gum (K(m) = 3.78 mg mL⁻¹), followed by guar gum (K(m) = 7.75 mg mL⁻¹) and konjac powder (K(m) = 22.7 mg mL⁻¹). RmMan5A hydrolyzed locust bean gum and konjac powder yielding mannobiose, mannotriose, and a mixture of various mannose-linked oligosaccharides. It was confirmed to be a true endo-acting β-1,4-mannanase, which showed requirement of four mannose residues for hydrolysis, and was also capable of catalyzing transglycosylation reactions. These properties make RmMan5A highly useful in the food/feed, paper and pulp, and detergent industries.

Optimal inductive and cultural conditions of Polygonum multiflorum transgenic hairy roots mediated with Agrobacterium rhizogenes R1601 and an analysis of their anthraquinone constituents.

PubMed

Huang, Bing; Lin, Huanjie; Yan, Chuanyan; Qiu, Hongyan; Qiu, Lipeng; Yu, Rongmin

2014-01-01

Polygonum multiflorum is an important medicinal plant. Hairy roots systems obtained by transforming plant tissues with the natural genetic engineer Agrobacterium rhizogenes can produce valuable biological active substances, which have immense potential in the pharmaceutical industry. To optimize the inductive and cultural conditions of P. multiflorum hairy roots and to identify the major active secondary metabolites in hairy roots. P. multiflorum hairy root were mediated with A. rhizogenes R1601 to induce hairy roots. Four combinations, including Murashige-Skoog (MS), 1/2 MS, B5, and White, were investigated to optimize the culture medium. MS medium was selected for the growth measurement. The qualitative and quantitative determinations of free anthraquinone in hairy roots were compared with the calli and aseptic plantlets using high-performance liquid chromatography. The inductive rates of hairy roots by leaves were higher than for any other explants. The presence of agropine in the P. multiflorum hairy roots confirmed that they were indeed transgenic. MS medium was the most suitable of the four media for hairy root growth. Meanwhile, the growth kinetics and nutrient consumption results showed that the hairy roots displayed a sigmoidal growth curve and that their optimal inoculation time was 18-21 days. The determination of the anthraquinone constituents indicated that the rhein content of the hairy roots reached 2.495 μg g(-1) and was 2.55-fold higher than that of natural plants. Transgenic hairy roots of P. multiflorum could be one of the most potent materials for industrial-scale production of bioactive anthraquinone constituents.

(1S,2E,4S,7E,11E)-2,7,11-Cembratriene-4,6-diol semisynthetic analogs as novel c-Met inhibitors for the control of c-Met-dependent breast malignancies.

PubMed

Ebrahim, Hassan Y; Mohyeldin, Mohamed M; Hailat, Mohammad M; El Sayed, Khalid A

2016-11-15

(1S,2E,4S,6R,7E,11E)-2,7,11-Cembratriene-4,6-diol (1) and its 4-epi-analog (2) are the cembranoid precursors to several key flavor ingredients in most Nicotiana (tobacco) species. Nearly 40-60% of 1 and 2 are purposely degraded during the commercial tobacco fermentation. However, 1 and 2 display promising bioactivities, including anticancer. Breast cancer is the most diagnosed cancer in women and ranked second female disease killer. The receptor tyrosine kinase c-Met correlates with aggressiveness of certain breast cancer phenotypes and thus considered a valid therapeutic target. This study reports the discovery and optimization of the tobacco-based cembranoid 1 as a novel c-Met inhibitory scaffold using combined structure- and ligand-based approaches. 1 displayed antiproliferative, anti-migratory and anti-invasive effects against the c-Met overexpressing MDA-MB-231 breast cancer cells at moderate μM concentrations. The Z'-LYTE kinase platform and Western blot analysis identified c-Met as a potential macromolecular target. Rationally designed carbamate analogs were proposed to probe additional targeted c-Met interactions and improve the cellular potency. The 6-phenyl carbamate 3 showed enhanced c-Met inhibitory activity. Structure-activity relationships of different substituents on the 3's phenyl moiety were studied. The most active analog 20 showed potent in vitro anticancer activity against the MDA-MB-231 breast cancer cells at low μM concentrations, with minimal toxicity on the non-tumorigenic MCF-10A mammary epithelial cells. Cembranoid 20 potently inhibited the c-Met catalytic activity in Z'-LYTE kinase assay and various cellular c-Met-driven signaling pathways. Furthermore, 20 displayed a robust antitumor activity in a breast cancer xenograft athymic mouse model and thus promoted to the lead rank. Cembranoids are novel c-Met inhibitors appropriate for future use to control c-Met dependent malignancies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Optimization and in Vivo Validation of Peptide Vectors Targeting the LDL Receptor.

PubMed

Jacquot, Guillaume; Lécorché, Pascaline; Malcor, Jean-Daniel; Laurencin, Mathieu; Smirnova, Maria; Varini, Karine; Malicet, Cédric; Gassiot, Fanny; Abouzid, Karima; Faucon, Aude; David, Marion; Gaudin, Nicolas; Masse, Maxime; Ferracci, Géraldine; Dive, Vincent; Cisternino, Salvatore; Khrestchatisky, Michel

2016-12-05

Active targeting and delivery to pathophysiological organs of interest is of paramount importance to increase specific accumulation of therapeutic drugs or imaging agents while avoiding systemic side effects. We recently developed a family of new peptide ligands of the human and rodent LDL receptor (LDLR), an attractive cell-surface receptor with high uptake activity and local enrichment in several normal or pathological tissues (Malcor et al., J. Med. Chem. 2012, 55 (5), 2227). Initial chemical optimization of the 15-mer, all natural amino acid compound 1/VH411 (DSGL[CMPRLRGC] c DPR) and structure-activity relationship (SAR) investigation led to the cyclic 8 amino acid analogue compound 22/VH445 ([cMPRLRGC] c ) which specifically binds hLDLR with a K D of 76 nM and has an in vitro blood half-life of ∼3 h. Further introduction of non-natural amino acids led to the identification of compound 60/VH4106 ([(d)-"Pen"M"Thz"RLRGC] c ), which showed the highest K D value of 9 nM. However, this latter analogue displayed the lowest in vitro blood half-life (∼1.9 h). In the present study, we designed a new set of peptide analogues, namely, VH4127 to VH4131, with further improved biological properties. Detailed analysis of the hLDLR-binding kinetics of previous and new analogues showed that the latter all displayed very high on-rates, in the 10 6 s -1. M -1 range, and off-rates varying from the low 10 -2 s -1 to the 10 -1 s -1 range. Furthermore, all these new analogues showed increased blood half-lives in vitro, reaching ∼7 and 10 h for VH4129 and VH4131, respectively. Interestingly, we demonstrate in cell-based assays using both VH445 and the most balanced optimized analogue VH4127 ([cM"Thz"RLRG"Pen"] c ), showing a K D of 18 nM and a blood half-life of ∼4.3 h, that its higher on-rate correlated with a significant increase in both the extent of cell-surface binding to hLDLR and the endocytosis potential. Finally, intravenous injection of tritium-radiolabeled 3 H-VH4127 in wild-type or ldlr -/- mice confirmed their active LDLR targeting in vivo. Overall, this study extends our previous work toward a diversified portfolio of LDLR-targeted peptide vectors with validated LDLR-targeting potential in vivo.

Extremely Vivid, Highly Transparent, and Ultrathin Quantum Dot Light-Emitting Diodes.

PubMed

Choi, Moon Kee; Yang, Jiwoong; Kim, Dong Chan; Dai, Zhaohe; Kim, Junhee; Seung, Hyojin; Kale, Vinayak S; Sung, Sae Jin; Park, Chong Rae; Lu, Nanshu; Hyeon, Taeghwan; Kim, Dae-Hyeong

2018-01-01

Displaying information on transparent screens offers new opportunities in next-generation electronics, such as augmented reality devices, smart surgical glasses, and smart windows. Outstanding luminance and transparency are essential for such "see-through" displays to show vivid images over clear background view. Here transparent quantum dot light-emitting diodes (Tr-QLEDs) are reported with high brightness (bottom: ≈43 000 cd m -2 , top: ≈30 000 cd m -2 , total: ≈73 000 cd m -2 at 9 V), excellent transmittance (90% at 550 nm, 84% over visible range), and an ultrathin form factor (≈2.7 µm thickness). These superb characteristics are accomplished by novel electron transport layers (ETLs) and engineered quantum dots (QDs). The ETLs, ZnO nanoparticle assemblies with ultrathin alumina overlayers, dramatically enhance durability of active layers, and balance electron/hole injection into QDs, which prevents nonradiative recombination processes. In addition, the QD structure is further optimized to fully exploit the device architecture. The ultrathin nature of Tr-QLEDs allows their conformal integration on various shaped objects. Finally, the high resolution patterning of red, green, and blue Tr-QLEDs (513 pixels in. -1 ) shows the potential of the full-color transparent display. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Life test results of OLED-XL long-life devices for use in active matrix organic light emitting diode (AMOLED) displays for head mounted applications

NASA Astrophysics Data System (ADS)

Fellowes, David A.; Wood, Michael V.; Hastings, Arthur R., Jr.; Ghosh, Amalkumar P.; Prache, Olivier

2007-04-01

eMagin Corporation has recently developed long-life OLED-XL devices for use in their AMOLED microdisplays for head-worn applications. AMOLED displays have been known to exhibit high levels of performance with regards to contrast, response time, uniformity, and viewing angle, but a lifetime improvement has been perceived to be essential for broadening the applications of OLED's in the military and in the commercial market. The new OLED-XL devices gave the promise of improvements in usable lifetime over 6X what the standard full color, white, and green devices could provide. The US Army's RDECOM CERDEC NVESD performed life tests on several standard and OLED-XL panels from eMagin under a Cooperative Research and Development Agreement (CRADA). Displays were tested at room temperature, utilizing eMagin's Design Reference Kit driver, allowing computer controlled optimization, brightness adjustment, and manual temperature compensation. The OLED Usable Lifetime Model, developed under a previous NVESD/eMagin SPIE paper presented at DSS 2005, has been adjusted based on the findings of these tests. The result is a better understanding of the applicability of AMOLEDs in military and commercial head mounted systems: where good fits are made, and where further development might be needed.

Quantitative Damage Detection and Sparse Sensor Array Optimization of Carbon Fiber Reinforced Resin Composite Laminates for Wind Turbine Blade Structural Health Monitoring

PubMed Central

Li, Xiang; Yang, Zhibo; Chen, Xuefeng

2014-01-01

The active structural health monitoring (SHM) approach for the complex composite laminate structures of wind turbine blades (WTBs), addresses the important and complicated problem of signal noise. After illustrating the wind energy industry's development perspectives and its crucial requirement for SHM, an improved redundant second generation wavelet transform (IRSGWT) pre-processing algorithm based on neighboring coefficients is introduced for feeble signal denoising. The method can avoid the drawbacks of conventional wavelet methods that lose information in transforms and the shortcomings of redundant second generation wavelet (RSGWT) denoising that can lead to error propagation. For large scale WTB composites, how to minimize the number of sensors while ensuring accuracy is also a key issue. A sparse sensor array optimization of composites for WTB applications is proposed that can reduce the number of transducers that must be used. Compared to a full sixteen transducer array, the optimized eight transducer configuration displays better accuracy in identifying the correct position of simulated damage (mass of load) on composite laminates with anisotropic characteristics than a non-optimized array. It can help to guarantee more flexible and qualified monitoring of the areas that more frequently suffer damage. The proposed methods are verified experimentally on specimens of carbon fiber reinforced resin composite laminates. PMID:24763210

Extracellular Matrix-Mediated Maturation of Human Pluripotent Stem Cell-Derived Cardiac Monolayer Structure and Electrophysiological Function.

PubMed

Herron, Todd J; Rocha, Andre Monteiro Da; Campbell, Katherine F; Ponce-Balbuena, Daniela; Willis, B Cicero; Guerrero-Serna, Guadalupe; Liu, Qinghua; Klos, Matt; Musa, Hassan; Zarzoso, Manuel; Bizy, Alexandra; Furness, Jamie; Anumonwo, Justus; Mironov, Sergey; Jalife, José

2016-04-01

Human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) monolayers generated to date display an immature embryonic-like functional and structural phenotype that limits their utility for research and cardiac regeneration. In particular, the electrophysiological function of hPSC-CM monolayers and bioengineered constructs used to date are characterized by slow electric impulse propagation velocity and immature action potential profiles. Here, we have identified an optimal extracellular matrix for significant electrophysiological and structural maturation of hPSC-CM monolayers. hPSC-CM plated in the optimal extracellular matrix combination have impulse propagation velocities ≈2× faster than previously reported (43.6±7.0 cm/s; n=9) and have mature cardiomyocyte action potential profiles, including hyperpolarized diastolic potential and rapid action potential upstroke velocity (146.5±17.7 V/s; n=5 monolayers). In addition, the optimal extracellular matrix promoted hypertrophic growth of cardiomyocytes and the expression of key mature sarcolemmal (SCN5A, Kir2.1, and connexin43) and myofilament markers (cardiac troponin I). The maturation process reported here relies on activation of integrin signaling pathways: neutralization of β1 integrin receptors via blocking antibodies and pharmacological blockade of focal adhesion kinase activation prevented structural maturation. Maturation of human stem cell-derived cardiomyocyte monolayers is achieved in a 1-week period by plating cardiomyocytes on PDMS (polydimethylsiloxane) coverslips rather than on conventional 2-dimensional cell culture formats, such as glass coverslips or plastic dishes. Activation of integrin signaling and focal adhesion kinase is essential for significant maturation of human cardiac monolayers. © 2016 American Heart Association, Inc.

Application of DuPont photopolymer films to automotive holographic display

NASA Astrophysics Data System (ADS)

Nakazawa, Norihito; Ono, Motoshi; Takeuchi, Shoichi; Sakurai, Hiromi; Hirano, Masahiro

1998-03-01

Automotive holographic head-up display (HUD) systems employing DuPont holographic photopolymer films are presented. Holographic materials for automotive application are exposed to severe environmental conditions and are required high performance. This paper describes the improvement of DuPont photopolymer films for the automotive use, critical technical issues such as optical design, external color and stray light. The holographic HUD combiner embedded in a windshield of an automobile has peculiar problems called external color. Diffraction light from holographic combiner makes its external color tone stimulative. We have introduced RGB three color recording and color simulation in order to improve the external color. A moderate external color tone was realized by the optimization in terms of wavelengths and diffraction efficiencies of the combiner hologram. The stray light called flare arises from a reflection by glass surface of windshield. We have developed two techniques to avoid the flare. First is a diffuser type trap beam guard hologram which reduces the intensity of the flare. Second is the optimization of the design of hologram so that the incident direction of flare is lower than the horizon line. As an example of automotive display a stand-alone type holographic HUD system attached on the dashboard of an automobile is demonstrated, which provides useful driving information such as route guidance. The display has a very simple optical system that consists of only a holographic combiner and a vacuum fluorescent display. Its thin body is only 35 mm high and does not obstruct driver's view. The display gives high contrast and wide image.

European display scene

NASA Astrophysics Data System (ADS)

Bartlett, Christopher T.

2000-08-01

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

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.

Rapid discovery of peptide capture candidates with demonstrated specificity for structurally similar toxins

NASA Astrophysics Data System (ADS)

Sarkes, Deborah A.; Hurley, Margaret M.; Coppock, Matthew B.; Farrell, Mikella E.; Pellegrino, Paul M.; Stratis-Cullum, Dimitra N.

2016-05-01

Peptides have emerged as viable alternatives to antibodies for molecular-based sensing due to their similarity in recognition ability despite their relative structural simplicity. Various methods for peptide capture reagent discovery exist, including phage display, yeast display, and bacterial display. One of the primary advantages of peptide discovery by bacterial display technology is the speed to candidate peptide capture agent, due to both rapid growth of bacteria and direct utilization of the sorted cells displaying each individual peptide for the subsequent round of biopanning. We have previously isolated peptide affinity reagents towards protective antigen of Bacillus anthracis using a commercially available automated magnetic sorting platform with improved enrichment as compared to manual magnetic sorting. In this work, we focus on adapting our automated biopanning method to a more challenging sort, to demonstrate the specificity possible with peptide capture agents. This was achieved using non-toxic, recombinant variants of ricin and abrin, RiVax and abrax, respectively, which are structurally similar Type II ribosomal inactivating proteins with significant sequence homology. After only two rounds of biopanning, enrichment of peptide capture candidates binding abrax but not RiVax was achieved as demonstrated by Fluorescence Activated Cell Sorting (FACS) studies. Further sorting optimization included negative sorting against RiVax, proper selection of autoMACS programs for specific sorting rounds, and using freshly made buffer and freshly thawed protein target for each round of biopanning for continued enrichment over all four rounds. Most of the resulting candidates from biopanning for abrax binding peptides were able to bind abrax but not RiVax, demonstrating that short peptide sequences can be highly specific even at this early discovery stage.

Optimization and antioxidant activity of polysaccharides from Plantago depressa.

PubMed

Han, Na; Wang, Lin; Song, Zehai; Lin, Junyu; Ye, Chun; Liu, Zhihui; Yin, Jun

2016-12-01

Polysaccharide from the herb of Plantago depressa (PDP) was obtained through ethanol precipitation preceded by a water extraction step. The optimum extraction yield of 5.68±0.46% was obtained with the treatment of raw material in water (w/v, 1:25.34) at 80.44°C during 1.97h, 3.28 times. Under these conditions, obtained yield value was in total agreement with value predicted by the model executed by Box-Behnken design (BBD). Following analysis by IR, HPLC-UV, MS and 1 H NMR, the composition of PDP was found to be l-rhamnose, galactose, arabinose, glucose and d-galacturonic acid. The maximum tolerated dose of PDP was 10g/kg. The antioxidant activity of PDP was investigated using five tests and it was found that PDP was able to scavenge hydroxyl, DPPH and ABTS radicals, besides their β-carotene bleaching inhibitory activity. In particular, in the test of β-carotene bleaching inhibition, PDP displayed higher activity than Vitamin C. Copyright © 2016 Elsevier B.V. All rights reserved.

Stepwise Adaptations to Low Temperature as Revealed by Multiple Mutants of Psychrophilic α-Amylase from Antarctic Bacterium*

PubMed Central

Cipolla, Alexandre; D'Amico, Salvino; Barumandzadeh, Roya; Matagne, André; Feller, Georges

2011-01-01

The mutants Mut5 and Mut5CC from a psychrophilic α-amylase bear representative stabilizing interactions found in the heat-stable porcine pancreatic α-amylase but lacking in the cold-active enzyme from an Antarctic bacterium. From an evolutionary perspective, these mutants can be regarded as structural intermediates between the psychrophilic and the mesophilic enzymes. We found that these engineered interactions improve all the investigated parameters related to protein stability as follows: compactness; kinetically driven stability; thermodynamic stability; resistance toward chemical denaturation, and the kinetics of unfolding/refolding. Concomitantly to this improved stability, both mutants have lost the kinetic optimization to low temperature activity displayed by the parent psychrophilic enzyme. These results provide strong experimental support to the hypothesis assuming that the disappearance of stabilizing interactions in psychrophilic enzymes increases the amplitude of concerted motions required by catalysis and the dynamics of active site residues at low temperature, leading to a higher activity. PMID:21900238

Conformationally restricted C-terminal peptides of substance P. Synthesis, mass spectral analysis and pharmacological properties.

PubMed

Theodoropoulos, D; Poulos, C; Gatos, D; Cordopatis, P; Escher, E; Mizrahi, J; Regoli, D; Dalietos, D; Furst, A; Lee, T D

1985-10-01

Four cyclic analogues of the C-terminal hepta- or hexapeptide of substance P were prepared by the solution method. The cyclizations were obtained by substituting with cysteine the residues normally present in positions 5 or 6 or 11 of substance P and by subsequent disulfide bond formation. The final products were identified by ordinary analytical procedures and advanced mass spectroscopy. The biological activities were determined on three bioassays: the guinea pig ileum, the guinea pig trachea and the rabbit mesenteric vein. Results obtained with these assays indicate that all peptides with a disulfide bridgehead in position 11 are inactive and that a cycle between positions 5 and 6 already strongly reduces the biological activity. The acyclic precursors containing thiol protection groups display weak biological activities. These results further underline the importance of the side chain in position 11 of substance P and suggest that optimal biological activities may require a linear peptide sequence.

Hydrolysis of lignocellulosic feedstock by novel cellulases originating from Pseudomonas sp. CL3 for fermentative hydrogen production.

PubMed

Cheng, Chieh-Lun; Chang, Jo-Shu

2011-09-01

A newly isolated indigenous bacterium Pseudomonas sp. CL3 was able to produce novel cellulases consisting of endo-β-1,4-d-glucanase (80 and 100 kDa), exo-β-1,4-d-glucanase (55 kDa) and β-1,4-d-glucosidase (65 kDa) characterized by enzyme assay and zymography analysis. In addition, the CL3 strain also produced xylanase with a molecular weight of 20 kDa. The optimal temperature for enzyme activity was 50, 45, 45 and 55 °C for endo-β-1,4-d-glucanase, exo-β-1,4-d-glucanase, β-1,4-d-glucosidase and xylanase, respectively. All the enzymes displayed optimal activity at pH 6.0. The cellulases/xylanase could hydrolyze cellulosic materials very effectively and were thus used to hydrolyze natural agricultural waste (i.e., bagasse) for clean energy (H2) production by Clostridium pasteurianum CH4 using separate hydrolysis and fermentation process. The maximum hydrogen production rate and cumulative hydrogen production were 35 ml/L/h and 1420 ml/L, respectively, with a hydrogen yield of around 0.96 mol H2/mol glucose. Copyright © 2011 Elsevier Ltd. All rights reserved.

Polyplex-mediated inhibition of chemokine receptor CXCR4 and chromatin-remodeling enzyme NCOA3 impedes pancreatic cancer progression and metastasis.

PubMed

Wang, Yan; Kumar, Sushil; Rachagani, Satyanarayana; Sajja, Balasrinivasa R; Xie, Ying; Hang, Yu; Jain, Maneesh; Li, Jing; Boska, Michael D; Batra, Surinder K; Oupický, David

2016-09-01

Pancreatic cancer (PC) is one of the most aggressive malignancies due to intense desmoplasia, extreme hypoxia and inherent chemoresistance. Studies have implicated the expression of chemokine receptor CXCR4 and nuclear receptor co-activator-3 (NCOA3) in the development of desmoplasia and metastatic spread of PC. Using a series of polymeric CXCR4 antagonists (PCX), we optimized formulation of PCX/siNCOA3 polyplexes to simultaneously target CXCR4 and NCOA3 in PC. Cholesterol-modified PCX showed maximum CXCR4 antagonism, NCOA3 silencing and inhibition of PC cell migration in vitro. The optimized PCX/siNCOA3 polyplexes were used in evaluating antitumor and antimetastatic activity in orthotopic mouse model of metastatic PC. The polyplexes displayed significant inhibition of primary tumor growth, which was accompanied by a decrease in tumor necrosis and increased tumor perfusion. The polyplexes also showed significant antimetastatic effect and effective suppression of metastasis to distant organs. Overall, dual-function PCX/siNCOA3 polyplexes can effectively regulate tumor microenvironment to decrease progression and dissemination of PC. Copyright © 2016 Elsevier Ltd. All rights reserved.

Multifunctional microcontrollable interface module

NASA Astrophysics Data System (ADS)

Spitzer, Mark B.; Zavracky, Paul M.; Rensing, Noa M.; Crawford, J.; Hockman, Angela H.; Aquilino, P. D.; Girolamo, Henry J.

2001-08-01

This paper reports the development of a complete eyeglass- mounted computer interface system including display, camera and audio subsystems. The display system provides an SVGA image with a 20 degree horizontal field of view. The camera system has been optimized for face recognition and provides a 19 degree horizontal field of view. A microphone and built-in pre-amp optimized for voice recognition and a speaker on an articulated arm are included for audio. An important feature of the system is a high degree of adjustability and reconfigurability. The system has been developed for testing by the Military Police, in a complete system comprising the eyeglass-mounted interface, a wearable computer, and an RF link. Details of the design, construction, and performance of the eyeglass-based system are discussed.

Quality metrics for sensor images

NASA Technical Reports Server (NTRS)

Ahumada, AL

1993-01-01

Methods are needed for evaluating the quality of augmented visual displays (AVID). Computational quality metrics will help summarize, interpolate, and extrapolate the results of human performance tests with displays. The FLM Vision group at NASA Ames has been developing computational models of visual processing and using them to develop computational metrics for similar problems. For example, display modeling systems use metrics for comparing proposed displays, halftoning optimizing methods use metrics to evaluate the difference between the halftone and the original, and image compression methods minimize the predicted visibility of compression artifacts. The visual discrimination models take as input two arbitrary images A and B and compute an estimate of the probability that a human observer will report that A is different from B. If A is an image that one desires to display and B is the actual displayed image, such an estimate can be regarded as an image quality metric reflecting how well B approximates A. There are additional complexities associated with the problem of evaluating the quality of radar and IR enhanced displays for AVID tasks. One important problem is the question of whether intruding obstacles are detectable in such displays. Although the discrimination model can handle detection situations by making B the original image A plus the intrusion, this detection model makes the inappropriate assumption that the observer knows where the intrusion will be. Effects of signal uncertainty need to be added to our models. A pilot needs to make decisions rapidly. The models need to predict not just the probability of a correct decision, but the probability of a correct decision by the time the decision needs to be made. That is, the models need to predict latency as well as accuracy. Luce and Green have generated models for auditory detection latencies. Similar models are needed for visual detection. Most image quality models are designed for static imagery. Watson has been developing a general spatial-temporal vision model to optimize video compression techniques. These models need to be adapted and calibrated for AVID applications.

Operator Influence of Unexploded Ordnance Sensor Technologies

DTIC Science & Technology

2007-03-01

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

Hubble Legacy Archive And The Public

NASA Astrophysics Data System (ADS)

Harris, Jessica; Whitmore, B.; Eisenhamer, B.; Bishop, M.; Knisely, L.

2012-01-01

The Hubble Legacy Archive (HLA) at the Space Telescope Science Institute (STScI) hosts the Image of the Month (IOTM) Series. The HLA is a joint project of STScI, the Space Telescope European Coordinating Facility (ST-ECF), and the Canadian Astronomy Data Centre (CADC). The HLA is designed optimize science from the Hubble Space Telescope by providing online enhanced Hubble products and advanced browsing capabilities. The IOTM's are created for astronomers and the public to highlight various features within HLA, such as the "Interactive Display", "Footprint” and "Inventory” features to name a few. We have been working with the Office of Public Outreach (OPO) to create a standards based educational module for middle school to high school students of the IOTM: Rings and the Moons of Uranus. The set of Uranus activities are highlighted by a movie that displays the orbit of five of Uranus’ largest satellites. We made the movie based on eight visits of Uranus from 2000-06-16 to 2000-06-18, using the PC chip on the Wide Field Planetary Camera 2 (WFPC2) and filter F850LP (proposal ID: 8680). Students will be engaged in activities that will allow them to "discover” the rings and satellites around Uranus, calculate the orbit of the satellites, and introduces students to analyze real data from Hubble.

Design and verification of a hybrid nonlinear MRE vibration absorber for controllable broadband performance

NASA Astrophysics Data System (ADS)

Sun, S. S.; Yildirim, T.; Wu, Jichu; Yang, J.; Du, H.; Zhang, S. W.; Li, W. H.

2017-09-01

In this work, a hybrid nonlinear magnetorheological elastomer (MRE) vibration absorber has been designed, theoretically investigated and experimentally verified. The proposed nonlinear MRE absorber has the dual advantages of a nonlinear force-displacement relationship and variable stiffness technology; the purpose for coupling these two technologies is to achieve a large broadband vibration absorber with controllable capability. To achieve a nonlinear stiffness in the device, two pairs of magnets move at a rotary angle against each other, and the theoretical nonlinear force-displacement relationship has been theoretically calculated. For the experimental investigation, the effects of base excitation, variable currents applied to the device (i.e. variable stiffness of the MRE) and semi-active control have been conducted to determine the enhanced broadband performance of the designed device. It was observed the device was able to change resonance frequency with the applied current; moreover, the hybrid nonlinear MRE absorber displayed a softening-type nonlinear response with clear discontinuous bifurcations observed. Furthermore, the performance of the device under a semi-active control algorithm displayed the optimal performance in attenuating the vibration from a primary system to the absorber over a large frequency bandwidth from 4 to 12 Hz. By coupling nonlinear stiffness attributes with variable stiffness MRE technology, the performance of a vibration absorber is substantially improved.

Effects of surface displayed targeting ligand GE11 on liposome distribution and extravasation in tumor.

PubMed

Tang, Hailing; Chen, Xiaojing; Rui, Mengjie; Sun, Wenqiang; Chen, Jian; Peng, Jinliang; Xu, Yuhong

2014-10-06

Targeting ligands displayed on liposome surface had been used to mediate specific interactions and drug delivery to target cells. However, they also affect liposome distribution in vivo, as well as the tissue extravasation processes after IV injection. In this study, we incorporated an EGFR targeting peptide GE11 on liposome surfaces in addition to PEG at different densities and evaluated their targeting properties and antitumor effects. We found that the densities of surface ligand and PEG were critical to target cell binding in vitro as well as pharmacokinetic profiles in vivo. The inclusion of GE11-PEG-DSPE and PEG-DSPE at 2% and 4% mol ratios in the liposome formulation mediated a rapid accumulation of liposomes within 1 h after IV injection in the tumor tissues surrounding neovascular structures. This is in addition to the EPR effect that was most prominently described for surface PEG modified liposomes. Therefore, despite the fact that the distribution of liposomes into interior tumor tissues was still limited by diffusion, GE11 targeted doxorubicin loaded liposomes showed significantly better antitumor activity in tumor bearing mice as a result of the fast active-targeting efficiency. We anticipate these understandings can benefit further optimization of targeted drug delivery systems for improving efficacy in vivo.

Flexible active-matrix displays and shift registers based on solution-processed organic transistors.

PubMed

Gelinck, Gerwin H; Huitema, H Edzer A; van Veenendaal, Erik; Cantatore, Eugenio; Schrijnemakers, Laurens; van der Putten, Jan B P H; Geuns, Tom C T; Beenhakkers, Monique; Giesbers, Jacobus B; Huisman, Bart-Hendrik; Meijer, Eduard J; Benito, Estrella Mena; Touwslager, Fred J; Marsman, Albert W; van Rens, Bas J E; de Leeuw, Dago M

2004-02-01

At present, flexible displays are an important focus of research. Further development of large, flexible displays requires a cost-effective manufacturing process for the active-matrix backplane, which contains one transistor per pixel. One way to further reduce costs is to integrate (part of) the display drive circuitry, such as row shift registers, directly on the display substrate. Here, we demonstrate flexible active-matrix monochrome electrophoretic displays based on solution-processed organic transistors on 25-microm-thick polyimide substrates. The displays can be bent to a radius of 1 cm without significant loss in performance. Using the same process flow we prepared row shift registers. With 1,888 transistors, these are the largest organic integrated circuits reported to date. More importantly, the operating frequency of 5 kHz is sufficiently high to allow integration with the display operating at video speed. This work therefore represents a major step towards 'system-on-plastic'.

Predictive display design for the vehicles with time delay in dynamic response

NASA Astrophysics Data System (ADS)

Efremov, A. V.; Tiaglik, M. S.; Irgaleev, I. H.; Efremov, E. V.

2018-02-01

The two ways for the improvement of flying qualities are considered: the predictive display (PD) and the predictive display integrated with the flight control system (FCS). The both ways allow to transforming the controlled element dynamics in the crossover frequency range, to improve the accuracy of tracking and to suppress the effect of time delay in the vehicle response too. The technique for optimization of the predictive law is applied to the landing task. The results of the mathematical modeling and experimental investigations carried out for this task are considered in the paper.

Optimization of Cat's Whiskers Tea (Orthosiphon stamineus) Using Supercritical Carbon Dioxide and Selective Chemotherapeutic Potential against Prostate Cancer Cells

PubMed Central

Al-Suede, Fouad Saleih R.; Khadeer Ahamed, Mohamed B.; Abdul Majid, Aman S.; Baharetha, Hussin M.; Hassan, Loiy E. A.; Kadir, Mohd Omar A.; Nassar, Zeyad D.; Abdul Majid, Amin M. S.

2014-01-01

Cat's whiskers (Orthosiphon stamineus) leaves extracts were prepared using supercritical CO2 (SC-CO2) with full factorial design to determine the optimum extraction parameters. Nine extracts were obtained by varying pressure, temperature, and time. The extracts were analysed using FTIR, UV-Vis, and GC-MS. Cytotoxicity of the extracts was evaluated on human (colorectal, breast, and prostate) cancer and normal fibroblast cells. Moderate pressure (31.1 MPa) and temperature (60°C) were recorded as optimum extraction conditions with high yield (1.74%) of the extract (B2) at 60 min extraction time. The optimized extract (B2) displayed selective cytotoxicity against prostate cancer (PC3) cells (IC50 28 µg/mL) and significant antioxidant activity (IC50 42.8 µg/mL). Elevated levels of caspases 3/7 and 9 in B2-treated PC3 cells suggest the induction of apoptosis through nuclear and mitochondrial pathways. Hoechst and rhodamine assays confirmed the nuclear condensation and disruption of mitochondrial membrane potential in the cells. B2 also demonstrated inhibitory effects on motility and colonies of PC3 cells at its subcytotoxic concentrations. It is noteworthy that B2 displayed negligible toxicity against the normal cells. Chemometric analysis revealed high content of essential oils, hydrocarbon, fatty acids, esters, and aromatic sesquiterpenes in B2. This study highlights the therapeutic potentials of SC-CO2 extract of cat's whiskers in targeting prostate carcinoma. PMID:25276215

Operating Room of the Future: Advanced Technologies in Safe and Efficient Operating Rooms

DTIC Science & Technology

2008-10-01

fit” or compatibility with different tasks. Ideally, the optimal match between tasks and well-designed display alternatives will be self -apparent...hierarchical display environment. The FARO robot arm is used as an accurate and reliable tracker to control a virtual camera. The virtual camera pose is...in learning outcomes due to self -feedback, improvements in learning outcomes due to instructor feedback and synchronous versus asynchronous

Application of holographic elements in displays and planar illuminators

NASA Astrophysics Data System (ADS)

Putilin, Andrew; Gustomiasov, Igor

2007-05-01

Holographic Optical Elements (HOE's) on planar waveguides can be used to design the planar optics for backlit units, color selectors or filters, lenses for virtual reality displays. The several schemes for HOE recording are proposed to obtain planar stereo backlit unit and private eye displays light source. It is shown in the paper that the specific light transformation grating permits to construct efficient backlit units for display holograms and LCD. Several schemes of reflection/transmission backlit units and scattering films based on holographic optical elements are also proposed. The performance of the waveguide HOE can be optimized using the parameters of recording scheme and etching parameters. The schemes of HOE application are discussed and some experimental results are shown.

Assessment of pilot workload with the introduction of an airborne threat-alert system

NASA Technical Reports Server (NTRS)

Battiste, Vernol; Bortolussi, Michael R.

1989-01-01

Simulated line operations were used to assess the value of the TCAS on the pilot's ability to avoid a collision and to determine the effects of various display configurations and information contents on the flight-crew performance and workload. The crew flew a Phase II Link/Boeing 727 simulator in a simulated ATC environment. Four levels of collision avoidance information were evaluated using the following TCAS display formats: no TCAS information, TCAS information with no traffic display information, TCAS information with threat-activated traffic display information, and TCAS information with a full-time traffic display of threat information. It was found that the use of a threat-activated TCAS display significantly reduced the first officers' workload was significantly reduced by the threat-activated TCAS display, as were the workloads of the captain and the second officer.

Proceedings of the Symposium on the Interface of Computer Science and Statistics (17th) Held in Lexington, Kentucky on 17-19 March 1985.

DTIC Science & Technology

1986-03-04

satisfied, but the availability of the machinery will entice developments to appear over the next few years. TABULATION AND DISPLAY To gain access to...independent, identicallyof the optimal predictor and the mean square distributed random variables with mean 0 and difference between the optimal forecast... optimal forecast (the conditional mean of YT+, given qute approximation to a2 1 j For the% Yl ~ ~ ~ ~ ~ ~ ~ . ... ,FT) thehtm-[ ]# rn-1 Y1...;,YT) and

Solving the optimal attention allocation problem in manual control

NASA Technical Reports Server (NTRS)

Kleinman, D. L.

1976-01-01

Within the context of the optimal control model of human response, analytic expressions for the gradients of closed-loop performance metrics with respect to human operator attention allocation are derived. These derivatives serve as the basis for a gradient algorithm that determines the optimal attention that a human should allocate among several display indicators in a steady-state manual control task. Application of the human modeling techniques are made to study the hover control task for a CH-46 VTOL flight tested by NASA.

A cost–benefit analysis of acclimation to low irradiance in tropical rainforest tree seedlings: leaf life span and payback time for leaf deployment

PubMed Central

Coste, Sabrina; Roggy, Jean-Christophe; Schimann, Heidy; Epron, Daniel; Dreyer, Erwin

2011-01-01

The maintenance in the long run of a positive carbon balance under very low irradiance is a prerequisite for survival of tree seedlings below the canopy or in small gaps in a tropical rainforest. To provide a quantitative basis for this assumption, experiments were carried out to determine whether construction cost (CC) and payback time for leaves and support structures, as well as leaf life span (i) differ among species and (ii) display an irradiance-elicited plasticity. Experiments were also conducted to determine whether leaf life span correlates to CC and payback time and is close to the optimal longevity derived from an optimization model. Saplings from 13 tropical tree species were grown under three levels of irradiance. Specific-CC was computed, as well as CC scaled to leaf area at the metamer level. Photosynthesis was recorded over the leaf life span. Payback time was derived from CC and a simple photosynthesis model. Specific-CC displayed only little interspecific variability and irradiance-elicited plasticity, in contrast to CC scaled to leaf area. Leaf life span ranged from 4 months to >26 months among species, and was longest in seedlings grown under lowest irradiance. It was always much longer than payback time, even under the lowest irradiance. Leaves were shed when their photosynthesis had reached very low values, in contrast to what was predicted by an optimality model. The species ranking for the different traits was stable across irradiance treatments. The two pioneer species always displayed the smallest CC, leaf life span, and payback time. All species displayed a similar large irradiance-elicited plasticity. PMID:21511904

Optimal bone strength and mineralization requires the type 2 iodothyronine deiodinase in osteoblasts

PubMed Central

Bassett, J. H. Duncan; Boyde, Alan; Howell, Peter G. T.; Bassett, Richard H.; Galliford, Thomas M.; Archanco, Marta; Evans, Holly; Lawson, Michelle A.; Croucher, Peter; St. Germain, Donald L.; Galton, Valerie Anne; Williams, Graham R.

2010-01-01

Hypothyroidism and thyrotoxicosis are each associated with an increased risk of fracture. Although thyroxine (T4) is the predominant circulating thyroid hormone, target cell responses are determined by local intracellular availability of the active hormone 3,5,3′-L-triiodothyronine (T3), which is generated from T4 by the type 2 deiodinase enzyme (D2). To investigate the role of locally produced T3 in bone, we characterized mice deficient in D2 (D2KO) in which the serum T3 level is normal. Bones from adult D2KO mice have reduced toughness and are brittle, displaying an increased susceptibility to fracture. This phenotype is characterized by a 50% reduction in bone formation and a generalized increase in skeletal mineralization resulting from a local deficiency of T3 in osteoblasts. These data reveal an essential role for D2 in osteoblasts in the optimization of bone strength and mineralization. PMID:20368437

Molecular beam epitaxy growth of high electron mobility InAs/AlSb deep quantum well structure

NASA Astrophysics Data System (ADS)

Wang, Juan; Wang, Guo-Wei; Xu, Ying-Qiang; Xing, Jun-Liang; Xiang, Wei; Tang, Bao; Zhu, Yan; Ren, Zheng-Wei; He, Zhen-Hong; Niu, Zhi-Chuan

2013-07-01

InAs/AlSb deep quantum well (QW) structures with high electron mobility were grown by molecular beam epitaxy (MBE) on semi-insulating GaAs substrates. AlSb and Al0.75Ga0.25Sb buffer layers were grown to accommodate the lattice mismatch (7%) between the InAs/AlSb QW active region and GaAs substrate. Transmission electron microscopy shows abrupt interface and atomic force microscopy measurements display smooth surface morphology. Growth conditions of AlSb and Al0.75Ga0.25Sb buffer were optimized. Al0.75Ga0.25Sb is better than AlSb as a buffer layer as indicated. The sample with optimal Al0.75Ga0.25Sb buffer layer shows a smooth surface morphology with root-mean-square roughness of 6.67 Å. The electron mobility has reached as high as 27 000 cm2/Vs with a sheet density of 4.54 × 1011/cm2 at room temperature.

Recent Progress on Flexible and Wearable Supercapacitors.

PubMed

Xue, Qi; Sun, Jinfeng; Huang, Yan; Zhu, Minshen; Pei, Zengxia; Li, Hongfei; Wang, Yukun; Li, Na; Zhang, Haiyan; Zhi, Chunyi

2017-12-01

Recently, wearable electronic devices including electrical sensors, flexible displays, and health monitors have received considerable attention and experienced rapid progress. Wearable supercapacitors attract tremendous attention mainly due to their high stability, low cost, fast charging/discharging, and high efficiency; properties that render them value for developing fully flexible devices. In this Concept, the recent achievements and advances made in flexible and wearable supercapacitors are presented, especially highlighting the promising performances of yarn/fiber-shaped and planar supercapacitors. On the basis of their working mechanism, electrode materials including carbon-based materials, metal oxide-based materials, and conductive polymers with an emphasis on the performance-optimization method are introduced. The latest representative techniques and active materials of recently developed supercapacitors with superior performance are summarized. Furthermore, the designs of 1D and 2D electrodes are discussed according to their electrically conductive supporting materials. Finally, conclusions, challenges, and perspective in optimizing and developing the electrochemical performance and function of wearable supercapacitors for their practical utility are addressed. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The relation of blood pressure and carotid intima-media thickness with the glutathione cycle in a young bi-ethnic population: the African-PREDICT study.

PubMed

Myburgh, Caitlynd; Huisman, Hugo W; Mels, Catharina M C

2018-04-01

Oxidative stress has been implicated in the development of hypertension, arterial stiffness and atherosclerosis. Optimal functioning of the enzymatic antioxidant system is central to prevent increased oxidative stress and its consequences. We aimed to investigate the relationships of ambulatory blood pressure and carotid intima-media thickness with enzyme activities of the glutathione cycle in 396 young, black and white South Africans of the African-PREDICT study. Ambulatory blood pressure and carotid intima-media thickness were measured and glutathione peroxidase and glutathione reductase activities were analyzed. Black participants had higher reactive oxygen species (men: p = 0.019; women: borderline p = 0.064) and total glutathione (both p < 0.001), but lower glutathione peroxidase activity and total antioxidant status (all p < 0.001). In black men, ambulatory pulse pressure was negatively associated with glutathione peroxidase activity (R 2  = 0.19; β = -0.25; p = 0.06). Black and white women displayed positive associations of ambulatory systolic blood pressure (black: R 2  = 0.25; β = 0.21; p = 0.048; white: R 2  = 0.44; β = 0.18; p = 0.016) with glutathione reductase activity, whereas white men displayed a positive association of ambulatory pulse pressure with glutathione reductase activity (R 2  = 0.25; β = 0.29; p = 0.01). The lower glutathione peroxidase activity and total antioxidant status, the higher reactive oxygen species, as well as the negative association between ambulatory pulse pressure and glutathione peroxidase activity in the black men suggest that oxidative stress may be associated with early vascular changes in this group. In the other three groups, the positive associations of blood pressure with glutathione reductase activity suggest a possible role for adequate glutathione reductase activity in preventing or delaying the development of hypertension.

Decision Aids for Naval Air ASW

DTIC Science & Technology

1980-03-15

Algorithm for Zone Optimization Investigation) NADC Developing Sonobuoy Pattern for Air ASW Search DAISY (Decision Aiding Information System) Wharton...sion making behavior. 0 Artificial intelligence sequential pattern recognition algorithm for reconstructing the decision maker’s utility functions. 0...display presenting the uncertainty area of the target. 3.1.5 Algorithm for Zone Optimization Investigation (AZOI) -- Naval Air Development Center 0 A

Optimized universal color palette design for error diffusion

NASA Astrophysics Data System (ADS)

Kolpatzik, Bernd W.; Bouman, Charles A.

1995-04-01

Currently, many low-cost computers can only simultaneously display a palette of 256 color. However, this palette is usually selectable from a very large gamut of available colors. For many applications, this limited palette size imposes a significant constraint on the achievable image quality. We propose a method for designing an optimized universal color palette for use with halftoning methods such as error diffusion. The advantage of a universal color palette is that it is fixed and therefore allows multiple images to be displayed simultaneously. To design the palette, we employ a new vector quantization method known as sequential scalar quantization (SSQ) to allocate the colors in a visually uniform color space. The SSQ method achieves near-optimal allocation, but may be efficiently implemented using a series of lookup tables. When used with error diffusion, SSQ adds little computational overhead and may be used to minimize the visual error in an opponent color coordinate system. We compare the performance of the optimized algorithm to standard error diffusion by evaluating a visually weighted mean-squared-error measure. Our metric is based on the color difference in CIE L*AL*B*, but also accounts for the lowpass characteristic of human contrast sensitivity.

Weather Avoidance Using Route Optimization as a Decision Aid: An AWIN Topical Study. Phase 1

NASA Technical Reports Server (NTRS)

1998-01-01

The aviation community is faced with reducing the fatal aircraft accident rate by 80 percent within 10 years. This must be achieved even with ever increasing, traffic and a changing National Airspace System. This is not just an altruistic goal, but a real necessity, if our growing level of commerce is to continue. Honeywell Technology Center's topical study, "Weather Avoidance Using Route Optimization as a Decision Aid", addresses these pressing needs. The goal of this program is to use route optimization and user interface technologies to develop a prototype decision aid for dispatchers and pilots. This decision aid will suggest possible diversions through single or multiple weather hazards and present weather information with a human-centered design. At the conclusion of the program, we will have a laptop prototype decision aid that will be used to demonstrate concepts to industry for integration into commercialized products for dispatchers and/or pilots. With weather a factor in 30% of aircraft accidents, our program will prevent accidents by strategically avoiding weather hazards in flight. By supplying more relevant weather information in a human-centered format along with the tools to generate flight plans around weather, aircraft exposure to weather hazards can be reduced. Our program directly addresses the NASA's five year investment areas of Strategic Weather Information and Weather Operations (simulation/hazard characterization and crew/dispatch/ATChazard monitoring, display, and decision support) (NASA Aeronautics Safety Investment Strategy: Weather Investment Recommendations, April 15, 1997). This program is comprised of two phases, Phase I concluded December 31, 1998. This first phase defined weather data requirements, lateral routing algorithms, an conceptual displays for a user-centered design. Phase II runs from January 1999 through September 1999. The second phase integrates vertical routing into the lateral optimizer and combines the user interface into a prototype software testbed. Phase II concludes with a dispatcher and pilot evaluation of the route optimizer decision aid. This document describes work completed in Phase I in contract with NASA Langley August 1998 - December 1998. This report includes: (1) Discuss how weather hazards were identified in partnership with experts, and how weather hazards were prioritized; (2) Static representations of display layouts for integrated planning function (3) Cost function for the 2D route optimizer; (4) Discussion of the method for obtaining, access to raw data of, and the results of the flight deck user information requirements definition; (5) Itemized display format requirements identified for representing weather hazards in a route planning aid.

Color standardization and optimization in whole slide imaging.

PubMed

Yagi, Yukako

2011-03-30

Standardization and validation of the color displayed by digital slides is an important aspect of digital pathology implementation. While the most common reason for color variation is the variance in the protocols and practices in the histology lab, the color displayed can also be affected by variation in capture parameters (for example, illumination and filters), image processing and display factors in the digital systems themselves. We have been developing techniques for color validation and optimization along two paths. The first was based on two standard slides that are scanned and displayed by the imaging system in question. In this approach, one slide is embedded with nine filters with colors selected especially for H&E stained slides (looking like tiny Macbeth color chart); the specific color of the nine filters were determined in our previous study and modified for whole slide imaging (WSI). The other slide is an H&E stained mouse embryo. Both of these slides were scanned and the displayed images were compared to a standard. The second approach was based on our previous multispectral imaging research. As a first step, the two slide method (above) was used to identify inaccurate display of color and its cause, and to understand the importance of accurate color in digital pathology. We have also improved the multispectral-based algorithm for more consistent results in stain standardization. In near future, the results of the two slide and multispectral techniques can be combined and will be widely available. We have been conducting a series of researches and developing projects to improve image quality to establish Image Quality Standardization. This paper discusses one of most important aspects of image quality - color.

Long-term information and distributed neural activation are relevant for the "internal features advantage" in face processing: electrophysiological and source reconstruction evidence.

PubMed

Olivares, Ela I; Saavedra, Cristina; Trujillo-Barreto, Nelson J; Iglesias, Jaime

2013-01-01

In face processing tasks, prior presentation of internal facial features, when compared with external ones, facilitates the recognition of subsequently displayed familiar faces. In a previous ERP study (Olivares & Iglesias, 2010) we found a visibly larger N400-like effect when identity mismatch familiar faces were preceded by internal features, as compared to prior presentation of external ones. In the present study we contrasted the processing of familiar and unfamiliar faces in the face-feature matching task to assess whether the so-called "internal features advantage" relies mainly on the use of stored face-identity-related information or if it might operate independently from stimulus familiarity. Our participants (N = 24) achieved better performance with internal features as primes and, significantly, with familiar faces. Importantly, ERPs elicited by identity mismatch complete faces displayed a negativity around 300-600 msec which was clearly enhanced for familiar faces primed by internal features when compared with the other experimental conditions. Source reconstruction showed incremented activity elicited by familiar stimuli in both posterior (ventral occipitotemporal) and more anterior (parahippocampal (ParaHIP) and orbitofrontal) brain regions. The activity elicited by unfamiliar stimuli was, in general, located in more posterior regions. Our findings suggest that the activation of multiple neural codes is required for optimal individuation in face-feature matching and that a cortical network related to long-term information for face-identity processing seems to support the internal feature effect. Copyright © 2013 Elsevier Ltd. All rights reserved.

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

NASA Astrophysics Data System (ADS)

Chen, Shu-Hsia; Wu, Shin-Tson

1992-10-01

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

Injectable Chitosan/β-Glycerophosphate System for Sustained Release: Gelation Study, Structural Investigation, and Erosion Tests.

PubMed

Dalmoro, Annalisa; Abrami, Michela; Galzerano, Barbara; Bochicchio, Sabrina; Barba, Anna Angela; Grassi, Mario; Larobina, Domenico

2017-01-01

Hydrogels can constitute reliable delivery systems of drugs, including those based on nucleic acids (NABDs) such as small interfering ribonucleic acid (siRNA). Their nature, structure, and response to physiological or external stimuli strongly influence the delivery mechanisms of entrapped active molecules, and, in turn, their possible uses in pharmacological and biomedical applications. In this study, a thermo-gelling chitosan/β-glycero-phosphate system has been optimized in order to assess its use as injectable system able to: i) gelling at physiological pH and temperature, and ii) modulate the release of included active ingredients. To this aim, we first analyzed the effect of acetic acid concentration on the gelation temperature. We then found the "optimized composition", namely, the one in which the Tgel is equal to the physiological temperature. The resulting gel was tested, by low field nuclear magnetic resonance (LF-NMR), to evaluate its average mesh-size, which can affect release kinetics of loaded drug. Finally, films of gelled chitosan, loaded with a model drug, have been tested in vitro to monitor their characteristic times, i.e. diffusion and erosion time, when they are exposed to a medium mimicking a physiological environment (buffer solution at pH 7.4). Results display that the optimized system is deemed to be an ideal candidate as injectable gelling material for a sustained release. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Discovery of 3-morpholino-imidazole[1,5-a]pyrazine BTK inhibitors for rheumatoid arthritis.

PubMed

Boga, Sobhana Babu; Alhassan, Abdul-Basit; Liu, Jian; Guiadeen, Deodial; Krikorian, Arto; Gao, Xiaolei; Wang, James; Yu, Younong; Anand, Rajan; Liu, Shilan; Yang, Chundao; Wu, Hao; Cai, Jiaqiang; Zhu, Hugh; Desai, Jagdish; Maloney, Kevin; Gao, Ying-Duo; Fischmann, Thierry O; Presland, Jeremy; Mansueto, My; Xu, Zangwei; Leccese, Erica; Knemeyer, Ian; Garlisi, Charles G; Bays, Nathan; Stivers, Peter; Brandish, Philip E; Hicks, Alexandra; Cooper, Alan; Kim, Ronald M; Kozlowski, Joseph A

2017-08-15

8-Amino-imidazo[1,5-a]pyrazine-based Bruton's tyrosine kinase (BTK) inhibitors, such as 6, exhibited potent inhibition of BTK but required improvements in both kinase and hERG selectivity (Liu et al., 2016; Gao et al., 2017). In an effort to maintain the inhibitory activity of these analogs and improve their selectivity profiles, we carried out SAR exploration of groups at the 3-position of pyrazine compound 6. This effort led to the discovery of the morpholine group as an optimized pharmacophore. Compounds 13, 23 and 38 displayed excellent BTK potencies, kinase and hERG selectivities, and pharmacokinetic profiles. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

PubMed

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

2014-02-01

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

Evaluation of a computer-generated perspective tunnel display for flight path following

NASA Technical Reports Server (NTRS)

Grunwald, A. J.; Robertson, J. B.; Hatfield, J. J.

1980-01-01

The display was evaluated by monitoring pilot performance in a fixed base simulator with the vehicle dynamics of a CH-47 tandem rotor helicopter. Superposition of the predicted future vehicle position on the tunnel image was also investigated to determine whether, and to what extent, it contributes to better system performance (the best predicted future vehicle position was sought). Three types of simulator experiments were conducted: following a desired trajectory in the presence of disturbances; entering the trajectory from a random position, outside the trajectory; detecting and correcting failures in automatic flight. The tunnel display with superimposed predictor/director symbols was shown to be a very successful combination, which outperformed the other two displays in all three experiments. A prediction time of 4 to 7 sec. was found to optimize trajectory tracking for the given vehicle dynamics and flight condition. Pilot acceptance of the tunnel plus predictor/director display was found to be favorable and the time the pilot needed for familiarization with the display was found to be relatively short.

New Evidence for Strategic Differences between Static and Dynamic Search Tasks: An Individual Observer Analysis of Eye Movements

PubMed Central

Dickinson, Christopher A.; Zelinsky, Gregory J.

2013-01-01

Two experiments are reported that further explore the processes underlying dynamic search. In Experiment 1, observers’ oculomotor behavior was monitored while they searched for a randomly oriented T among oriented L distractors under static and dynamic viewing conditions. Despite similar search slopes, eye movements were less frequent and more spatially constrained under dynamic viewing relative to static, with misses also increasing more with target eccentricity in the dynamic condition. These patterns suggest that dynamic search involves a form of sit-and-wait strategy in which search is restricted to a small group of items surrounding fixation. To evaluate this interpretation, we developed a computational model of a sit-and-wait process hypothesized to underlie dynamic search. In Experiment 2 we tested this model by varying fixation position in the display and found that display positions optimized for a sit-and-wait strategy resulted in higher d′ values relative to a less optimal location. We conclude that different strategies, and therefore underlying processes, are used to search static and dynamic displays. PMID:23372555

A phage display vector optimized for the generation of human antibody combinatorial libraries and the molecular cloning of monoclonal antibody fragments.

PubMed

Solforosi, Laura; Mancini, Nicasio; Canducci, Filippo; Clementi, Nicola; Sautto, Giuseppe Andrea; Diotti, Roberta Antonia; Clementi, Massimo; Burioni, Roberto

2012-07-01

A novel phagemid vector, named pCM, was optimized for the cloning and display of antibody fragment (Fab) libraries on the surface of filamentous phage. This vector contains two long DNA "stuffer" fragments for easier differentiation of the correctly cut forms of the vector. Moreover, in pCM the fragment at the heavy-chain cloning site contains an acid phosphatase-encoding gene allowing an easy distinction of the Escherichia coli cells containing the unmodified form of the phagemid versus the heavy-chain fragment coding cDNA. In pCM transcription of heavy-chain Fd/gene III and light chain is driven by a single lacZ promoter. The light chain is directed to the periplasm by the ompA signal peptide, whereas the heavy-chain Fd/coat protein III is trafficked by the pelB signal peptide. The phagemid pCM was used to generate a human combinatorial phage display antibody library that allowed the selection of a monoclonal Fab fragment antibody directed against the nucleoprotein (NP) of Influenza A virus.

Medicinal chemistry optimization of antiplasmodial imidazopyridazine hits from high throughput screening of a SoftFocus kinase library: part 1.

PubMed

Le Manach, Claire; Gonzàlez Cabrera, Diego; Douelle, Frederic; Nchinda, Aloysius T; Younis, Yassir; Taylor, Dale; Wiesner, Lubbe; White, Karen L; Ryan, Eileen; March, Corinne; Duffy, Sandra; Avery, Vicky M; Waterson, David; Witty, Michael J; Wittlin, Sergio; Charman, Susan A; Street, Leslie J; Chibale, Kelly

2014-03-27

A novel class of imidazopyridazines identified from whole cell screening of a SoftFocus kinase library was synthesized and evaluated for antiplasmodial activity against K1 (multidrug resistant strain) and NF54 (sensitive strain). Structure-activity relationship studies led to the identification of highly potent compounds against both strains. Compound 35 was highly active (IC50: K1 = 6.3 nM, NF54 = 7.3 nM) and comparable in potency to artesunate, and 35 exhibited 98% activity in the in vivo P. berghei mouse model (4-day test by Peters) at 4 × 50 mg/kg po. Compound 35 was also assessed against P. falciparum in the in vivo SCID mouse model where the efficacy was found to be more consistent with the in vitro activity. Furthermore, 35 displayed high (78%) rat oral bioavailability with good oral exposure and plasma half-life. Mice exposure at the same dose was 10-fold lower than in rat, suggesting lower oral absorption and/or higher metabolic clearance in mice.

Polysaccharides from bamboo shoots processing by-products: New insight into extraction and characterization.

PubMed

Chen, Guangjing; Chen, Kewei; Zhang, Renfeng; Chen, Xiaolong; Hu, Peng; Kan, Jianquan

2018-04-15

In this study, an efficient accelerated solvent extraction (ASE) technology was applied for rapid extraction of polysaccharides from the processing by-products of Chimonobambusa quadrangularis (CPS). The extraction yields, physicochemical characterization, and antioxidant activities of CPS obtained by ASE and hot water extraction (HWE) were further compared. A maximal ASE-CPS yield was obtained by optimized extraction conditions (temperature 126 °C, 2 cycles, and 22 min) using response surface methodology. The yield of polysaccharides from ASE (9.96% ± 0.39%) was significantly higher than that from HWE (7.16% ± 0.32%). Differences were found between ASE and HWE with the chemical composition, molecular weight distribution, rheological property, and antioxidant activities of the obtained polysaccharides, while the primary structure remained the same. ASE-CPS exhibited better chemical antioxidant activities in oxygen radical absorbance capacity (ORAC), reducing power, and DPPH and hydroxyl radical scavenging ability, whereas HWE-CPS displayed higher activity in metal chelating activity assay. Copyright © 2017 Elsevier Ltd. All rights reserved.

An efficient ribitol-specific dehydrogenase from Enterobacter aerogenes.

PubMed

Singh, Ranjitha; Singh, Raushan; Kim, In-Won; Sigdel, Sujan; Kalia, Vipin C; Kang, Yun Chan; Lee, Jung-Kul

2015-05-01

An NAD(+)-dependent ribitol dehydrogenase from Enterobacter aerogenes KCTC 2190 (EaRDH) was cloned and successfully expressed in Escherichia coli. The complete 729-bp gene was amplified, cloned, expressed, and subsequently purified in an active soluble form using nickel affinity chromatography. The enzyme had an optimal pH and temperature of 11.0 and 45°C, respectively. Among various polyols, EaRDH exhibited activity only toward ribitol, with Km, Vmax, and kcat/Km values of 10.3mM, 185Umg(-1), and 30.9s(-1)mM(-1), respectively. The enzyme showed strong preference for NAD(+) and displayed no detectable activity with NADP(+). Homology modeling and sequence analysis of EaRDH, along with its biochemical properties, confirmed that EaRDH belongs to the family of NAD(+)-dependent ribitol dehydrogenases, a member of short-chain dehydrogenase/reductase (SCOR) family. EaRDH showed the highest activity and unique substrate specificity among all known RDHs. Homology modeling and docking analysis shed light on the molecular basis of its unusually high activity and substrate specificity. Copyright © 2015 Elsevier Inc. All rights reserved.

L1C signal design options

USGS Publications Warehouse

Betz, J.W.; Cahn, C.R.; Dafesh, P.A.; Hegarty, C.J.; Hudnut, K.W.; Jones, A.J.; Keegan, R.; Kovach, K.; Lenahan, L.S.; Ma, H.H.; Rushanan, J.J.; Stansell, T.A.; Wang, C.C.; Yi, S.K.

2006-01-01

Design activities for a new civil signal centered at 1575.42 MHz, called L1C, began in 2003, and the Phase 1 effort was completed in 2004. The L1C signal design has evolved and matured during a Phase 2 design activity that began in 2005. Phase 2 has built on the initial design activity, guided by responses to international user surveys conducted during Phase 1. A common core of signal characteristics has been developed to provide advances in robustness and performance. The Phase 2 activity produced five design options, all drawing upon the core signal characteristics, while representing different blends of characteristics and capabilities. A second round of international user surveys was completed to solicit advice concerning these design options. This paper provides an update of the L1C design process, and describes the current L1C design options. Initial performance estimates are presented for each design option, displaying trades between signal tracking robustness, the speed and robustness of clock and ephemeris data, and the rate and robustness of other data message contents. Planned remaining activities are summarized, leading to optimization of the L1C design.

A Dereplication and Bioguided Discovery Approach to Reveal New Compounds from a Marine-Derived Fungus Stilbella fimetaria

PubMed Central

Kildgaard, Sara; Subko, Karolina; Phillips, Emma; Goidts, Violaine; de la Cruz, Mercedes; Díaz, Caridad; Gotfredsen, Charlotte H.; Frisvad, Jens C.; Nielsen, Kristian F.; Larsen, Thomas O.

2017-01-01

A marine-derived Stilbella fimetaria fungal strain was screened for new bioactive compounds based on two different approaches: (i) bio-guided approach using cytotoxicity and antimicrobial bioassays; and (ii) dereplication based approach using liquid chromatography with both diode array detection and high resolution mass spectrometry. This led to the discovery of several bioactive compound families with different biosynthetic origins, including pimarane-type diterpenoids and hybrid polyketide-non ribosomal peptide derived compounds. Prefractionation before bioassay screening proved to be a great aid in the dereplication process, since separate fractions displaying different bioactivities allowed a quick tentative identification of known antimicrobial compounds and of potential new analogues. A new pimarane-type diterpene, myrocin F, was discovered in trace amounts and displayed cytotoxicity towards various cancer cell lines. Further media optimization led to increased production followed by the purification and bioactivity screening of several new and known pimarane-type diterpenoids. A known broad-spectrum antifungal compound, ilicicolin H, was purified along with two new analogues, hydroxyl-ilicicolin H and ilicicolin I, and their antifungal activity was evaluated. PMID:28805711

Synthesis and biological evaluation of 5-(fluoro-substituted-6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)imidazoles as inhibitors of transforming growth factor-β type I receptor kinase.

PubMed

Krishnaiah, Maddeboina; Jin, Cheng Hua; Sheen, Yhun Yhong; Kim, Dae-Kee

2015-11-15

To further optimize a clinical candidate 5 (EW-7197), a series of 5-(3-, 4-, or 5-fluoro-substituted-6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)imidazoles 19a-l have been synthesized and evaluated for their TGF-β type I receptor kinase (ALK5) and p38α MAP kinase inhibitory activity in an enzyme assay. The 5-(5-fluoro-substituted-6-methylpyridin-2-yl)-4-([1,2,4]triazolo[1,5-a]pyridin-6-yl)imidazoles 19h-l displayed the similar level of potency to that of 5 against both ALK5 (IC50=7.68-13.70 nM) and p38α MAP kinase (IC50=1240-3370 nM). Among them, 19j inhibited ALK5 with IC50 value of 7.68 nM in a kinase assay and displayed 82% inhibition at 100 nM in a luciferase reporter assay. Copyright © 2015 Elsevier Ltd. All rights reserved.

Characterization of a thermostable glycoside hydrolase (CMbg0408) from the hyperthermophilic archaeon Caldivirga maquilingensis IC-167.

PubMed

Letsididi, Rebaone; Hassanin, Hinawi Am; Koko, Marwa Yf; Ndayishimiye, Jean B; Zhang, Tao; Jiang, Bo; Stressler, Timo; Fischer, Lutz; Mu, Wanmeng

2017-05-01

Hyperthermophilic archaea capable of functioning optimally at very high temperatures are a good source of unique and industrially important thermostable enzymes. A glycoside hydrolase family 1 β-galactosidase gene (BglB) from a hyperthermophilic archaeon Caldivirga maquilingensis IC-167 was cloned and expressed in Escherichia coli. The recombinant enzyme (CMbg0408) displayed optimum activity at 110 °C and pH 5.0. It also retained 92% and 70% of its maximal activity at 115 and 120 °C, respectively. The enzyme was completely thermostable and active after 120 min of incubation at 80 and 90 °C. It also showed broad substrate specificity with activities of 8876 ± 185 U mg -1 for p-nitrophenyl-β-d-galactopyranoside, 4464 ± 172 U mg -1 for p-nitrophenyl-β-d-glucopyranoside, 1486 ± 68 U mg -1 for o-nitrophenyl-β-d-galactopyranoside, 2250 ± 86 U mg -1 for o-nitrophenyl-β-d-xylopyranoside and 175 ± 4 U mg -1 for lactose. A catalytic efficiency (k cat /K m ) of 3059 ± 122 mmol L -1  s -1 and K m value of 8.1 ± 0.08 mmol L -1 were displayed towards p-nitrophenyl-β-d-galactopyranoside. As a result of its remarkable thermostability and high activity at high temperatures, this novel β-galactosidase may be useful for food and pharmaceutical applications. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Performance considerations for high-definition head-mounted displays

NASA Technical Reports Server (NTRS)

Edwards, Oliver J.; Larimer, James; Gille, Jennifer

1992-01-01

Design image-optimization for helmet-mounted displays (HMDs) for military systems is presently discussed within the framework of a systems-engineering approach that encompasses (1) a description of natural targets in the field; (2) the characteristics of human visual perception; and (3) device specifications that directly relate to these ecological and human-factors parameters. Attention is given to target size and contrast and the relationship of the modulation transfer function to image resolution.

Genomic Approaches for Detection and Treatment of Breast Cancer

DTIC Science & Technology

2009-07-01

phage display, the oligos were cloned into the T7Select (Novagen) system, allowing for low copy number display fused to the T7 coat protein, 10B. The...immunoprecipitating antibody-bound phage . To this end, we have optimized the conditions for enrichment since our last report. By diluting a FLAG-tagged T7 ...assay) by systematically varying the following parameters: T7 phage concentration, antibody concentration, time of immunoprecipitation, and number of

Simulating multiprimary LCDs on standard tri-stimulus LC displays

NASA Astrophysics Data System (ADS)

Lebowsky, Fritz; Vonneilich, Katrin; Bonse, Thomas

2008-01-01

Large-scale, direct view TV screens, in particular those based on liquid crystal technology, are beginning to use subpixel structures with more than three subpixels to implement a multi-primary display with up to six primaries. Since their input color space is likely to remain tri-stimulus RGB we first focus on some fundamental constraints. Among them, we elaborate simplified gamut mapping architectures as well as color filter geometry, transparency, and chromaticity coordinates in color space. Based on a 'display centric' RGB color space tetrahedrization combined with linear interpolation we describe a simulation framework which enables optimization for up to 7 primaries. We evaluated the performance through mapping the multi-primary design back onto a RGB LC display gamut without building a prototype multi-primary display. As long as we kept the RGB equivalent output signal within the display gamut we could analyze all desirable multi-primary configurations with regard to colorimetric variance and visually perceived quality. Not only does our simulation tool enable us to verify a novel concept it also demonstrates how carefully one needs to design a multiprimary display for LCD TV applications.

Human platelet lysate is a successful alternative serum supplement for propagation of monocyte-derived dendritic cells.

PubMed

Švajger, Urban

2017-04-01

Clinical protocols for dendritic cell (DC) generation from monocytes require the use of animal serum-free supplements. Serum-free media can also require up to 1% of serum supplementation. In addition, recommendations based on the 3Rs (Refinement, Reduction, Replacement) principle also recommend the use of non-animal sera in in vitro studies. The aim of this study was to explore the potential use of platelet lysate (PL) for generation of optimally differentiated DCs from monocytes. Cells were isolated from buffy coats from healthy volunteers using immunomagnetic selection. DCs were differentiated in RPMI1640 supplemented with either 10% fetal bovine serum (FBS), 10% AB serum or 10% PL with the addition of granulocyte monocyte colony stimulating factor and interleukin-4. Generated DCs were assessed for their morphology, viability, endocytotic capacity, surface phenotype (immature, mature and tolerogenic DCs) and activation of important signaling pathways. DC function was evaluated on the basis of their allostimulatory capacity, cytokine profile and ability to induce different T-helper subsets. DCs generated with PL displayed normal viability, morphology and endocytotic capacity. Their differentiation and maturation phenotype was comparable to FBS-cultured DCs. They showed functional plasticity and up-regulated tolerogenic markers in response to their environment. PL-cultured mature DCs displayed unhindered allostimulatory potential and the capacity to induce Th1 responses. The use of PL allowed for activation of crucial signaling proteins associated with DC differentiation and maturation. This study demonstrates for the first time that human PL represents a successful alternative to FBS in differentiation of DCs from monocytes. DCs display the major phenotypic and functional characteristics compared with existing culture protocols. Copyright © 2017 International Society for Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Fused monochromatic imaging acquired by single source dual energy CT in hepatocellular carcinoma during arterial phase: an initial experience.

PubMed

Gao, Shun-Yu; Zhang, Xiao-Peng; Cui, Yong; Sun, Ying-Shi; Tang, Lei; Li, Xiao-Ting; Zhang, Xiao-Yan; Shan, Jun

2014-08-01

To explore whether single and fused monochromatic images can improve liver tumor detection and delineation by single source dual energy CT (ssDECT) in patients with hepatocellular carcinoma (HCC) during arterial phase. Fifty-seven patients with HCC who underwent ssDECT scanning at Beijing Cancer Hospital were enrolled retrospectively. Twenty-one sets of monochromatic images from 40 to 140 keV were reconstructed at 5 keV intervals in arterial phase. The optimal contrast-noise ratio (CNR) monochromatic images of the liver tumor and the lowest-noise monochromatic images were selected for image fusion. We evaluated the image quality of the optimal-CNR monochromatic images, the lowest-noise monochromatic images and the fused monochromatic images, respectively. The evaluation indicators included the spatial resolution of the anatomical structure, the noise level, the contrast and CNR of the tumor. In arterial phase, the anatomical structure of the liver can be displayed most clearly in the 65-keV monochromatic images, with the lowest image noise. The optimal-CNR monochromatic images of HCC tumor were 50-keV monochromatic images in which the internal structural features of the liver tumors were displayed most clearly and meticulously. For tumor detection, the fused monochromatic images and the 50-keV monochromatic images had similar performances, and were more sensitive than 65-keV monochromatic images. We achieved good arterial phase images by fusing the optimal-CNR monochromatic images of the HCC tumor and the lowest-noise monochromatic images. The fused images displayed liver tumors and anatomical structures more clearly, which is potentially helpful for identifying more and smaller HCC tumors.

Assessment of Antioxidant and Antimicrobial Properties of Lignin from Corn Stover Residue Pretreated with Low-Moisture Anhydrous Ammonia and Enzymatic Hydrolysis Process.

PubMed

Guo, Mingming; Jin, Tony; Nghiem, Nhuan P; Fan, Xuetong; Qi, Phoebe X; Jang, Chan Ho; Shao, Lingxiao; Wu, Changqing

2018-01-01

Lignin accounts for 15-35% of dry biomass materials. Therefore, developing value-added co-products from lignin residues is increasingly important to improve the economic viability of biofuel production from biomass resources. The main objective of this work was to study the lignin extracts from corn stover residue obtained from a new and improved process for bioethanol production. Extraction conditions that favored high lignin yield were optimized, and antioxidant and antimicrobial activities of the resulting lignin were investigated. Potential estrogenic toxicity of lignin extracts was also evaluated. The corn stover was pretreated by low-moisture anhydrous ammonia (LMAA) and then subjected to enzymatic hydrolysis using cellulase and hemicellulase. The residues were then added with sodium hydroxide and extracted for different temperatures and times for enhancing lignin yield and the bioactivities. The optimal extraction conditions using 4% (w/v) sodium hydroxide were determined to be 50 °C, 120 min, and 1:8 (w:v), the ratio between corn stover solids and extracting liquid. Under the optimal condition, 33.92 g of lignin yield per 100 g of corn stover residue was obtained. Furthermore, the extracts produced using these conditions showed the highest antioxidant activity by the hydrophilic oxygen radical absorbance capacity (ORAC) assay. The extracts also displayed significant antimicrobial activities against Listeria innocua. Minimal estrogenic impacts were observed for all lignin extracts when tested using the MCF-7 cell proliferation assay. Thus, the lignin extracts could be used for antioxidant and antimicrobial applications, and improve the value of the co-products from the biomass-based biorefinery.

Research of an optimization design method of integral imaging three-dimensional display system

NASA Astrophysics Data System (ADS)

Gao, Hui; Yan, Zhiqiang; Wen, Jun; Jiang, Guanwu

2016-03-01

The information warfare needs a highly transparent environment of battlefield, it follows that true three-dimensional display technology has obvious advantages than traditional display technology in the current field of military science and technology. It also focuses on the research progress of lens array imaging technology and aims at what restrict the development of integral imaging, main including low spatial resolution, narrow depth range and small viewing angle. This paper summarizes the principle, characteristics and development history of the integral imaging. A variety of methods are compared and analyzed that how to improve the resolution, extend depth of field, increase scope and eliminate the artifact aiming at problems currently. And makes a discussion about the experimental results of the research, comparing the display performance of different methods.

Therapeutic Antibodies by Phage Display.

PubMed

Shim, Hyunbo

2016-01-01

Antibody phage display is a major technological platform for the generation of fully human antibodies for therapeutic purposes. The in vitro binder selection by phage display allows researchers to have more extensive control over binding parameters and facilitates the isolation of clinical candidate antibodies with desired binding and/or functional profiles. Since the invention of antibody phage display in late 1980s, significant technological advancements in the design, construction, and selection of the antibody libraries have been made, and several fully human antibodies generated by phage display are currently approved or in various clinical development stages. In this review, the background and details of antibody phage display technology, and representative antibody libraries with natural or synthetic sequence diversity and different construction strategies are described. The generation, optimization, functional and biophysical properties, and preclinical and clinical developments of some of the phage display-derived therapeutic antibodies approved for use in patients or in late-stage clinical trials are also discussed. With evolving novel disease targets and therapeutic strategies, antibody phage display is expected to continue to play a central role in the development of the next generation of therapeutic antibodies. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Sustained Axenic Metabolic Activity by the Obligate Intracellular Bacterium Coxiella burnetii▿ †

PubMed Central

Omsland, Anders; Cockrell, Diane C.; Fischer, Elizabeth R.; Heinzen, Robert A.

2008-01-01

Growth of Coxiella burnetii, the agent of Q fever, is strictly limited to colonization of a viable eukaryotic host cell. Following infection, the pathogen replicates exclusively in an acidified (pH 4.5 to 5) phagolysosome-like parasitophorous vacuole. Axenic (host cell free) buffers have been described that activate C. burnetii metabolism in vitro, but metabolism is short-lived, with bacterial protein synthesis halting after a few hours. Here, we describe a complex axenic medium that supports sustained (>24 h) C. burnetii metabolic activity. As an initial step in medium development, several biological buffers (pH 4.5) were screened for C. burnetii metabolic permissiveness. Based on [35S]Cys-Met incorporation, C. burnetii displayed optimal metabolic activity in citrate buffer. To compensate for C. burnetii auxotrophies and other potential metabolic deficiencies, we developed a citrate buffer-based medium termed complex Coxiella medium (CCM) that contains a mixture of three complex nutrient sources (neopeptone, fetal bovine serum, and RPMI cell culture medium). Optimal C. burnetii metabolism occurred in CCM with a high chloride concentration (140 mM) while the concentrations of sodium and potassium had little effect on metabolism. CCM supported prolonged de novo protein and ATP synthesis by C. burnetii (>24 h). Moreover, C. burnetii morphological differentiation was induced in CCM as determined by the transition from small-cell variant to large-cell variant. The sustained in vitro metabolic activity of C. burnetii in CCM provides an important tool to investigate the physiology of this organism including developmental transitions and responses to antimicrobial factors associated with the host cell. PMID:18310349

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.

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.

Biochemical characterization of a recombinant plant class III chitinase from the pitcher of the carnivorous plant Nepenthes alata.

PubMed

Ishisaki, Kana; Arai, Sachiko; Hamada, Tatsuro; Honda, Yuji

2012-11-01

A class III chitinase belonging to the GH18 family from Nepenthes alata (NaCHIT3) was expressed in Escherichia coli. The enzyme exhibited hydrolytic activity toward colloidal chitin, ethylene glycol chitin, and (GlcNAc)(n) (n=5 and 6). The enzyme hydrolyzed the fourth glycosidic linkage from the non-reducing end of (GlcNAc)(6). The anomeric form of the products indicated it was a retaining enzyme. The colloidal chitin hydrolytic reaction displayed high activity between pH 3.9 and 6.9, but the pH optimum of the (GlcNAc)(6) hydrolytic reaction was 3.9 at 37 °C. The optimal temperature for activity was 65 °C in 50 mM sodium acetate buffer (pH 3.9). The pH optima of NaCHIT3 and NaCHIT1 might be related to their roles in chitin degradation in the pitcher fluid. Copyright © 2012 Elsevier Ltd. All rights reserved.

A dominant role for the methyl-CpG-binding protein Mbd2 in controlling Th2 induction by dendritic cells.

PubMed

Cook, Peter C; Owen, Heather; Deaton, Aimée M; Borger, Jessica G; Brown, Sheila L; Clouaire, Thomas; Jones, Gareth-Rhys; Jones, Lucy H; Lundie, Rachel J; Marley, Angela K; Morrison, Vicky L; Phythian-Adams, Alexander T; Wachter, Elisabeth; Webb, Lauren M; Sutherland, Tara E; Thomas, Graham D; Grainger, John R; Selfridge, Jim; McKenzie, Andrew N J; Allen, Judith E; Fagerholm, Susanna C; Maizels, Rick M; Ivens, Alasdair C; Bird, Adrian; MacDonald, Andrew S

2015-04-24

Dendritic cells (DCs) direct CD4(+) T-cell differentiation into diverse helper (Th) subsets that are required for protection against varied infections. However, the mechanisms used by DCs to promote Th2 responses, which are important both for immunity to helminth infection and in allergic disease, are currently poorly understood. We demonstrate a key role for the protein methyl-CpG-binding domain-2 (Mbd2), which links DNA methylation to repressive chromatin structure, in regulating expression of a range of genes that are associated with optimal DC activation and function. In the absence of Mbd2, DCs display reduced phenotypic activation and a markedly impaired capacity to initiate Th2 immunity against helminths or allergens. These data identify an epigenetic mechanism that is central to the activation of CD4(+) T-cell responses by DCs, particularly in Th2 settings, and reveal methyl-CpG-binding proteins and the genes under their control as possible therapeutic targets for type-2 inflammation.

High Performance Reduction of H2O2 with an Electron Transport Decaheme Cytochrome on a Porous ITO Electrode

PubMed Central

2017-01-01

The decaheme cytochrome MtrC from Shewanella oneidensis MR-1 immobilized on an ITO electrode displays unprecedented H2O2 reduction activity. Although MtrC showed lower peroxidase activity in solution compared to horseradish peroxidase, the ten heme cofactors enable excellent electronic communication and a superior activity on the electrode surface. A hierarchical ITO electrode enabled optimal immobilization of MtrC and a high current density of 1 mA cm–2 at 0.4 V vs SHE could be obtained at pH 6.5 (Eonset = 0.72 V). UV–visible and Resonance Raman spectroelectrochemical studies suggest the formation of a high valent iron-oxo species as the catalytic intermediate. Our findings demonstrate the potential of multiheme cytochromes to catalyze technologically relevant reactions and establish MtrC as a new benchmark in biotechnological H2O2 reduction with scope for applications in fuel cells and biosensors. PMID:28221032

The discovery and preclinical evaluation of BMS-707035, a potent HIV-1 integrase strand transfer inhibitor.

PubMed

Naidu, B Narasimhulu; Walker, Michael A; Sorenson, Margaret E; Ueda, Yasutsugu; Matiskella, John D; Connolly, Timothy P; Dicker, Ira B; Lin, Zeyu; Bollini, Sagarika; Terry, Brian J; Higley, Helen; Zheng, Ming; Parker, Dawn D; Wu, Dedong; Adams, Stephen; Krystal, Mark R; Meanwell, Nicholas A

2018-07-01

BMS-707035 is an HIV-1 integrase strand transfer inhibitor (INSTI) discovered by systematic optimization of N-methylpyrimidinone carboxamides guided by structure-activity relationships (SARs) and the single crystal X-ray structure of compound 10. It was rationalized that the unexpectedly advantageous profiles of N-methylpyrimidinone carboxamides with a saturated C2-substitutent may be due, in part, to the geometric relationship between the C2-substituent and the pyrimidinone core. The single crystal X-ray structure of 10 provided support for this reasoning and guided the design of a spirocyclic series 12 which led to discovery of the morpholino-fused pyrimidinone series 13. Several carboxamides derived from this bicyclic scaffold displayed improved antiviral activity and pharmacokinetic profiles when compared with corresponding spirocyclic analogs. Based on the excellent antiviral activity, preclinical profiles and acceptable in vitro and in vivo toxicity profiles, 13a (BMS-707035) was selected for advancement into phase I clinical trials. Copyright © 2018 Elsevier Ltd. All rights reserved.

Synthesis and biological evaluation of aryl-oxadiazoles as inhibitors of Mycobacterium tuberculosis.

PubMed

Martinez-Grau, Maria Angeles; Valcarcel, Isabel C Gonzalez; Early, Julie V; Gessner, Richard Klaus; de Melo, Candice Soares; de la Nava, Eva Maria Martin; Korkegian, Aaron; Ovechkina, Yulia; Flint, Lindsay; Gravelle, Anisa; Cramer, Jeff W; Desai, Prashant V; Street, Leslie J; Odingo, Joshua; Masquelin, Thierry; Chibale, Kelly; Parish, Tanya

2018-06-01

Despite increased research efforts to find new treatments for tuberculosis in recent decades, compounds with novel mechanisms of action are still required. We previously identified a series of novel aryl-oxadiazoles with anti-tubercular activity specific for bacteria using butyrate as a carbon source. We explored the structure activity relationship of this series. Structural modifications were performed in all domains to improve potency and physico-chemical properties. A number of compounds displayed sub-micromolar activity against M. tuberculosis utilizing butyrate, but not glucose as the carbon source. Compounds showed no or low cytotoxicity against eukaryotic cells. Three compounds were profiled in mouse pharmacokinetic studies. Plasma clearance was low to moderate but oral exposure suggested solubility-limited drug absorption in addition to first pass metabolism. The presence of a basic nitrogen in the linker slightly increased solubility, and salt formation optimized aqueous solubility. Our findings suggest that the 1,3,4-oxadiazoles are useful tools and warrant further investigation. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Rationally Designed Hierarchically Structured Tungsten Nitride and Nitrogen-Rich Graphene-Like Carbon Nanocomposite as Efficient Hydrogen Evolution Electrocatalyst.

PubMed

Zhu, Yanping; Chen, Gao; Zhong, Yijun; Zhou, Wei; Shao, Zongping

2018-02-01

Practical application of hydrogen production from water splitting relies strongly on the development of low-cost and high-performance electrocatalysts for hydrogen evolution reaction (HER). The previous researches mainly focused on transition metal nitrides as HER catalysts due to their electrical conductivity and corrosion stability under acidic electrolyte, while tungsten nitrides have reported poorer activity for HER. Here the activity of tungsten nitride is optimized through rational design of a tungsten nitride-carbon composite. More specifically, tungsten nitride (WN x ) coupled with nitrogen-rich porous graphene-like carbon is prepared through a low-cost ion-exchange/molten-salt strategy. Benefiting from the nanostructured WN x , the highly porous structure and rich nitrogen dopant (9.5 at%) of the carbon phase with high percentage of pyridinic-N (54.3%), and more importantly, their synergistic effect, the composite catalyst displays remarkably high catalytic activity while maintaining good stability. This work highlights a powerful way to design more efficient metal-carbon composites catalysts for HER.

Option pricing for stochastic volatility model with infinite activity Lévy jumps

NASA Astrophysics Data System (ADS)

Gong, Xiaoli; Zhuang, Xintian

2016-08-01

The purpose of this paper is to apply the stochastic volatility model driven by infinite activity Lévy processes to option pricing which displays infinite activity jumps behaviors and time varying volatility that is consistent with the phenomenon observed in underlying asset dynamics. We specially pay attention to three typical Lévy processes that replace the compound Poisson jumps in Bates model, aiming to capture the leptokurtic feature in asset returns and volatility clustering effect in returns variance. By utilizing the analytical characteristic function and fast Fourier transform technique, the closed form formula of option pricing can be derived. The intelligent global optimization search algorithm called Differential Evolution is introduced into the above highly dimensional models for parameters calibration so as to improve the calibration quality of fitted option models. Finally, we perform empirical researches using both time series data and options data on financial markets to illustrate the effectiveness and superiority of the proposed method.

Purification, characterization, and biological activities of broccolini lectin.

PubMed

Xu, Pingping; Zhang, Ting; Guo, Xiaolei; Ma, Chungwah; Zhang, Xuewu

2015-01-01

Plant lectins have displayed a variety of biological activities. In this study, for the first time, a 27 kDa arabinose- and mannose-specific lectin from Broccolini (Brassica oleracea Italica × Alboglabra), named as BL (Broccolini lectin), was purified by an activity-driven protocol. Mass spectrometry analysis and database search indicated that no matches with any plant lectin were found, but BL contained some peptide fragments (QQQGQQGQQLQQVISR, QQGQQQGQQGQQLQQVISR and VCNIPQVSVCPF QK). BL exhibited hemagglutinating activity against chicken erythrocytes at 4 µg/mL. BL retained full hemagglutinating activity at pH 7-8 and temperature 30-40°C, and had an optimal activity in Ca(2+) solution. Bioactivity assay revealed that BL exhibited dose-dependent inhibition activity on 5 bacterial species with IC50 values of 143.95-486.33 μg/mL, and on 3 cancer cells with IC50 values of 178.82-350.93 μg/mL. Notably, 5-fold reduction in IC50 values was observed on normal L-O2 vs cancerous HepG-2 cells (924.35 vs. 178.82 μg/mL). This suggests that BL should be promising in food and medicine. © 2015 American Institute of Chemical Engineers.

Partial purification and characterization of a novel histidine decarboxylase from Enterobacter aerogenes DL-1.

PubMed

Zou, Yu; Hu, Wenzhong; Jiang, Aili; Tian, Mixia

2015-08-18

Histidine decarboxylase (HDC) from Enterobacter aerogenes DL-1 was purified in a three-step procedure involving ammonium sulfate precipitation, Sephadex G-100, and DEAE-Sepharose column chromatography. The partially purified enzyme showed a single protein band of 52.4 kD on sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). The optimum pH for HDC activity was 6.5, and the enzyme was stable between pH 4 and 8. Enterobacter aerogenes HDC had optimal activity at 40°C and retained most of its activity between 4 and 50°C. HDC activity was reduced in the presence of numerous tested compounds. Particularly with SDS, it significantly (p < 0.01) inhibited enzyme activity. Conversely, Ca(2+) and Mn(2+) showed prominent activation effects (p < 0.01) with activity increasing to 117.20% and 123.42%, respectively. The Lineweaver-Burk plot showed that K m and V max values of the enzyme for L-histidine were 0.21 mM and 71.39 µmol/min, respectively. In comparison with most HDCs from other microorganisms and animals, HDC from E. aerogenes DL-1 displayed higher affinity and greater reaction velocity toward L-histidine.

Inhibitory effect of liposome-entrapped lemongrass oil on the growth of Listeria monocytogenes in cheese.

PubMed

Cui, H Y; Wu, J; Lin, L

2016-08-01

Listeria monocytogenes infection in dairy products is of mounting public concern. To inhibit bacterial growth, we engineered stimuli-responsive liposomes containing lemongrass oil for this study. The controlled release of liposome-entrapped lemongrass oil is triggered by listerolysin O, secreted by L. monocytogenes. We investigated the antibiotic activities of lemongrass oil liposomes against L. monocytogenes in cheese. We also assessed their possible effects on the quality of the cheese. Liposomes containing lemongrass oil (5.0mg/mL) presented the optimal polydispersity index (0.246), zeta-potential (-58.9mV) and entrapment efficiency (25.7%). The liposomes displayed satisfactory antibiotic activity against L. monocytogenes in cheese over the storage period at 4°C. We observed no effects on the physical and sensory properties of the cheese after the liposome treatment. Copyright © 2016 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

Hidden scaling patterns and universality in written communication

NASA Astrophysics Data System (ADS)

Formentin, M.; Lovison, A.; Maritan, A.; Zanzotto, G.

2014-07-01

The temporal statistics exhibited by written correspondence appear to be media dependent, with features which have so far proven difficult to characterize. We explain the origin of these difficulties by disentangling the role of spontaneous activity from decision-based prioritizing processes in human dynamics, clocking all waiting times through each agent's "proper time" measured by activity. This unveils the same fundamental patterns in written communication across all media (letters, email, sms), with response times displaying truncated power-law behavior and average exponents near -3/2. When standard time is used, the response time probabilities are theoretically predicted to exhibit a bimodal character, which is empirically borne out by our newly collected years-long data on email. These perspectives on the temporal dynamics of human correspondence should aid in the analysis of interaction phenomena in general, including resource management, optimal pricing and routing, information sharing, and emergency handling.

Mechanobiocatalysis: Modulating Enzymatic Activity with Mechanical Force

DTIC Science & Technology

2015-09-28

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

Percolation in insect nest networks: Evidence for optimal wiring

NASA Astrophysics Data System (ADS)

Valverde, Sergi; Corominas-Murtra, Bernat; Perna, Andrea; Kuntz, Pascale; Theraulaz, Guy; Solé, Ricard V.

2009-06-01

Optimization has been shown to be a driving force for the evolution of some biological structures, such as neural maps in the brain or transport networks. Here we show that insect networks also display characteristic traits of optimality. By using a graph representation of the chamber organization of termite nests and a disordered lattice model, it is found that these spatial nests are close to a percolation threshold. This suggests that termites build efficient systems of galleries spanning most of the nest volume at low cost. The evolutionary consequences are outlined.

Integrating Patient-Reported Outcomes into Spine Surgical Care through Visual Dashboards: Lessons Learned from Human-Centered Design.

PubMed

Hartzler, Andrea L; Chaudhuri, Shomir; Fey, Brett C; Flum, David R; Lavallee, Danielle

2015-01-01

The collection of patient-reported outcomes (PROs) draws attention to issues of importance to patients-physical function and quality of life. The integration of PRO data into clinical decisions and discussions with patients requires thoughtful design of user-friendly interfaces that consider user experience and present data in personalized ways to enhance patient care. Whereas most prior work on PROs focuses on capturing data from patients, little research details how to design effective user interfaces that facilitate use of this data in clinical practice. We share lessons learned from engaging health care professionals to inform design of visual dashboards, an emerging type of health information technology (HIT). We employed human-centered design (HCD) methods to create visual displays of PROs to support patient care and quality improvement. HCD aims to optimize the design of interactive systems through iterative input from representative users who are likely to use the system in the future. Through three major steps, we engaged health care professionals in targeted, iterative design activities to inform the development of a PRO Dashboard that visually displays patient-reported pain and disability outcomes following spine surgery. Design activities to engage health care administrators, providers, and staff guided our work from design concept to specifications for dashboard implementation. Stakeholder feedback from these health care professionals shaped user interface design features, including predefined overviews that illustrate at-a-glance trends and quarterly snapshots, granular data filters that enable users to dive into detailed PRO analytics, and user-defined views to share and reuse. Feedback also revealed important considerations for quality indicators and privacy-preserving sharing and use of PROs. Our work illustrates a range of engagement methods guided by human-centered principles and design recommendations for optimizing PRO Dashboards for patient care and quality improvement. Engaging health care professionals as stakeholders is a critical step toward the design of user-friendly HIT that is accepted, usable, and has the potential to enhance quality of care and patient outcomes.

Optimizing virtual reality for all users through gaze-contingent and adaptive focus displays.

PubMed

Padmanaban, Nitish; Konrad, Robert; Stramer, Tal; Cooper, Emily A; Wetzstein, Gordon

2017-02-28

From the desktop to the laptop to the mobile device, personal computing platforms evolve over time. Moving forward, wearable computing is widely expected to be integral to consumer electronics and beyond. The primary interface between a wearable computer and a user is often a near-eye display. However, current generation near-eye displays suffer from multiple limitations: they are unable to provide fully natural visual cues and comfortable viewing experiences for all users. At their core, many of the issues with near-eye displays are caused by limitations in conventional optics. Current displays cannot reproduce the changes in focus that accompany natural vision, and they cannot support users with uncorrected refractive errors. With two prototype near-eye displays, we show how these issues can be overcome using display modes that adapt to the user via computational optics. By using focus-tunable lenses, mechanically actuated displays, and mobile gaze-tracking technology, these displays can be tailored to correct common refractive errors and provide natural focus cues by dynamically updating the system based on where a user looks in a virtual scene. Indeed, the opportunities afforded by recent advances in computational optics open up the possibility of creating a computing platform in which some users may experience better quality vision in the virtual world than in the real one.

Optimizing virtual reality for all users through gaze-contingent and adaptive focus displays

NASA Astrophysics Data System (ADS)

Padmanaban, Nitish; Konrad, Robert; Stramer, Tal; Cooper, Emily A.; Wetzstein, Gordon

2017-02-01

From the desktop to the laptop to the mobile device, personal computing platforms evolve over time. Moving forward, wearable computing is widely expected to be integral to consumer electronics and beyond. The primary interface between a wearable computer and a user is often a near-eye display. However, current generation near-eye displays suffer from multiple limitations: they are unable to provide fully natural visual cues and comfortable viewing experiences for all users. At their core, many of the issues with near-eye displays are caused by limitations in conventional optics. Current displays cannot reproduce the changes in focus that accompany natural vision, and they cannot support users with uncorrected refractive errors. With two prototype near-eye displays, we show how these issues can be overcome using display modes that adapt to the user via computational optics. By using focus-tunable lenses, mechanically actuated displays, and mobile gaze-tracking technology, these displays can be tailored to correct common refractive errors and provide natural focus cues by dynamically updating the system based on where a user looks in a virtual scene. Indeed, the opportunities afforded by recent advances in computational optics open up the possibility of creating a computing platform in which some users may experience better quality vision in the virtual world than in the real one.

Optimizing electricity consumption: A case of function learning.

PubMed

Guath, Mona; Millroth, Philip; Juslin, Peter; Elwin, Ebba

2015-12-01

A popular way to improve consumers' control over their electricity consumption is by providing outcome feedback on the cost with in-home displays. Research on function learning, however, suggests that outcome feedback may not always be ideal for learning, especially if the feedback signal is noisy. In this study, we relate research on function learning to in-home displays and use a laboratory task simulating a household to investigate the role of outcome feedback and function learning on electricity optimization. Three function training schemes (FTSs) are presented that convey specific properties of the functions that relate the electricity consumption to the utility and cost. In Experiment 1, we compared learning from outcome feedback with 3 FTSs, 1 of which allowed maximization of the utility while keeping the budget, despite no feedback about the total monthly cost. In Experiment 2, we explored the combination of this FTS and outcome feedback. The results suggested that electricity optimization may be facilitated if feedback learning is preceded by a brief period of function training. (c) 2015 APA, all rights reserved).

Controllable Construction of Core-Shell Polymer@Zeolitic Imidazolate Frameworks Fiber Derived Heteroatom-Doped Carbon Nanofiber Network for Efficient Oxygen Electrocatalysis.

PubMed

Zhao, Yingxuan; Lai, Qingxue; Zhu, Junjie; Zhong, Jia; Tang, Zeming; Luo, Yan; Liang, Yanyu

2018-05-01

Designing rational nanostructures of metal-organic frameworks based carbon materials to promote the bifunctional catalytic activity of the oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) is highly desired but still remains a great challenge. Herein, an in situ growth method to achieve 1D structure-controllable zeolitic imidazolate frameworks (ZIFs)/polyacrylonitrile (PAN) core/shell fiber (PAN@ZIFs) is developed. Subsequent pyrolysis of this precursor can obtain a heteroatom-doped carbon nanofiber network as an efficient bifunctional oxygen electrocatalyst. The electrocatalytic performance of derived carbon nanofiber is dominated by the structures of PAN@ZIFs fiber, which is facilely regulated by efficiently controlling the nucleation and growth process of ZIFs on the surface of polymer fiber as well as optimizing the components of ZIFs. Benefiting from the core-shell structures with appropriate dopants and porosity, as-prepared catalysts show brilliant bifunctional ORR/OER catalytic activity and durability. Finally, the rechargeable Zn-air battery assembled from the optimized catalyst (CNF@Zn/CoNC) displays a peak power density of 140.1 mW cm -2 , energy density of 878.9 Wh kg Zn -1 , and excellent cyclic stability over 150 h, giving a promising performance in realistic application. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structure-activity relationship of the ionic cocrystal: 5-amino-2-naphthalene sulfonate·ammonium ions for pharmaceutical applications

NASA Astrophysics Data System (ADS)

Sangeetha, M.; Mathammal, R.

2018-02-01

The ionic cocrystals of 5-amino-2-naphthalene sulfonate · ammonium ions (ANSA-ṡNH4+) were grown under slow evaporation method and examined in detail for pharmaceutical applications. The crystal structure and intermolecular interactions were studied from the single X-ray diffraction analysis and the Hirshfeld surfaces. The 2D fingerprint plots displayed the inter-contacts possible in the ionic crystal. Computational DFT method was established to determine the structural, physical and chemical properties. The molecular geometries obtained from the X-ray studies were compared with the optimized geometrical parameters calculated using DFT/6-31 + G(d,p) method. The band gap energy calculated from the UV-Visible spectral analysis and the HOMO-LUMO energy gap are compared. The theoretical UV-Visible calculations helped in determining the type of electronic transition taking place in the title molecule. The maximum absorption bands and transitions involved in the molecule represented the drug reaction possible. Non-linear optical properties were characterized from SHG efficiency measurements experimentally and the NLO parameters are also calculated from the optimized structure. The reactive sites within the molecule are detailed from the MEP surface maps. The molecular docking studies evident the structure-activity of the ionic cocrystal for anti-cancer drug property.

Inhibitors of human immunodeficiency virus type 1 (HIV-1) attachment. 5. An evolution from indole to azaindoles leading to the discovery of 1-(4-benzoylpiperazin-1-yl)-2-(4,7-dimethoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dione (BMS-488043), a drug candidate that demonstrates antiviral activity in HIV-1-infected subjects.

PubMed

Wang, Tao; Yin, Zhiwei; Zhang, Zhongxing; Bender, John A; Yang, Zhong; Johnson, Graham; Yang, Zheng; Zadjura, Lisa M; D'Arienzo, Celia J; DiGiugno Parker, Dawn; Gesenberg, Christophe; Yamanaka, Gregory A; Gong, Yi-Fei; Ho, Hsu-Tso; Fang, Hua; Zhou, Nannan; McAuliffe, Brian V; Eggers, Betsy J; Fan, Li; Nowicka-Sans, Beata; Dicker, Ira B; Gao, Qi; Colonno, Richard J; Lin, Pin-Fang; Meanwell, Nicholas A; Kadow, John F

2009-12-10

Azaindole derivatives derived from the screening lead 1-(4-benzoylpiperazin-1-yl)-2-(1H-indol-3-yl)ethane-1,2-dione (1) were prepared and characterized to assess their potential as inhibitors of HIV-1 attachment. Systematic replacement of each of the unfused carbon atoms in the phenyl ring of the indole moiety by a nitrogen atom provided four different azaindole derivatives that displayed a clear SAR for antiviral activity and all of which displayed marked improvements in pharmaceutical properties. Optimization of these azaindole leads resulted in the identification of two compounds that were advanced to clinical studies: (R)-1-(4-benzoyl-2-methylpiperazin-1-yl)-2-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)ethane-1,2-dione (BMS-377806, 3) and 1-(4-benzoylpiperazin-1-yl)-2-(4,7-dimethoxy-1H-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dione (BMS-488043, 4). In a preliminary clinical study, 4 administered as monotherapy for 8 days, reduced viremia in HIV-1-infected subjects, providing proof of concept for this mechanistic class.

Epitope Specificity Delimits the Functional Capabilities of Vaccine-Induced CD8 T Cell Populations

PubMed Central

Hill, Brenna J.; Darrah, Patricia A.; Ende, Zachary; Ambrozak, David R.; Quinn, Kylie M.; Darko, Sam; Gostick, Emma; Wooldridge, Linda; van den Berg, Hugo A.; Venturi, Vanessa; Larsen, Martin; Davenport, Miles P.; Seder, Robert A.

2014-01-01

Despite progress toward understanding the correlates of protective T cell immunity in HIV infection, the optimal approach to Ag delivery by vaccination remains uncertain. We characterized two immunodominant CD8 T cell populations generated in response to immunization of BALB/c mice with a replication-deficient adenovirus serotype 5 vector expressing the HIV-derived Gag and Pol proteins at equivalent levels. The Gag-AI9/H-2Kd epitope elicited high-avidity CD8 T cell populations with architecturally diverse clonotypic repertoires that displayed potent lytic activity in vivo. In contrast, the Pol-LI9/H-2Dd epitope elicited motif-constrained CD8 T cell repertoires that displayed lower levels of physical avidity and lytic activity despite equivalent measures of overall clonality. Although low-dose vaccination enhanced the functional profiles of both epitope-specific CD8 T cell populations, greater polyfunctionality was apparent within the Pol-LI9/H-2Dd specificity. Higher proportions of central memory-like cells were present after low-dose vaccination and at later time points. However, there were no noteworthy phenotypic differences between epitope-specific CD8 T cell populations across vaccine doses or time points. Collectively, these data indicate that the functional and phenotypic properties of vaccine-induced CD8 T cell populations are sensitive to dose manipulation, yet constrained by epitope specificity in a clonotype-dependent manner. PMID:25348625

Diel periodicity of pheromone release by females of Planococcus citri and Planococcus ficus and the temporal flight activity of their conspecific males

NASA Astrophysics Data System (ADS)

Levi-Zada, Anat; Fefer, Daniela; David, Maayan; Eliyahu, Miriam; Franco, José Carlos; Protasov, Alex; Dunkelblum, Ezra; Mendel, Zvi

2014-08-01

The diel periodicity of sex pheromone release was monitored in two mealybug species, Planococcus citri and Planococcus ficus (Hemiptera; Pseudococcidae), using sequential SPME/GCMS analysis. A maximal release of 2 ng/h pheromone by 9-12-day-old P. citri females occurred 1-2 h before the beginning of photophase. The highest release of pheromone by P. ficus females was 1-2 ng/2 h of 10-20-day-old females, approximately 2 h after the beginning of photophase. Mating resulted in termination of the pheromone release in both mealybug species. The temporal flight activity of the males was monitored in rearing chambers using pheromone baited delta traps. Males of both P. citri and P. ficus displayed the same flight pattern and began flying at 06:00 hours when the light was turned on, reaching a peak during the first and second hour of the photophase. Our results suggest that other biparental mealybug species display also diel periodicities of maximal pheromone release and response. Direct evaluation of the diel periodicity of the pheromone release by the automatic sequential analysis is convenient and will be very helpful in optimizing the airborne collection and identification of other unknown mealybug pheromones and to study the calling behavior of females. Considering this behavior pattern may help to develop more effective pheromone-based management strategies against mealybugs.

Residues of E. coli topoisomerase I conserved for interaction with a specific cytosine base to facilitate DNA cleavage

PubMed Central

Narula, Gagandeep; Tse-Dinh, Yuk-Ching

2012-01-01

Bacterial and archaeal topoisomerase I display selectivity for a cytosine base 4 nt upstream from the DNA cleavage site. Recently, the solved crystal structure of Escherichia coli topoisomerase I covalently linked to a single-stranded oligonucleotide revealed that R169 and R173 interact with the cytosine base at the −4 position via hydrogen bonds while the phenol ring of Y177 wedges between the bases at the −4 and the −5 position. Substituting R169 to alanine changed the selectivity of the enzyme for the base at the −4 position from a cytosine to an adenine. The R173A mutant displayed similar sequence selectivity as the wild-type enzyme, but weaker cleavage and relaxation activity. Mutation of Y177 to serine or alanine rendered the enzyme inactive. Although mutation of each of these residues led to different outcomes, R169, R173 and Y177 work together to interact with a cytosine base at the −4 position to facilitate DNA cleavage. These strictly conserved residues might act after initial substrate binding as a Molecular Ruler to form a protein–DNA complex with the scissile phosphate positioned at the active site for optimal DNA cleavage by the tyrosine hydroxyl nucleophile to facilitate DNA cleavage in the reaction pathway. PMID:22833607

Meeting the challenges with the Douglas Aircraft Company Aeroelastic Design Optimization Program (ADOP)

NASA Technical Reports Server (NTRS)

Rommel, Bruce A.

1989-01-01

An overview of the Aeroelastic Design Optimization Program (ADOP) at the Douglas Aircraft Company is given. A pilot test program involving the animation of mode shapes with solid rendering as well as wire frame displays, a complete aircraft model of a high-altitude hypersonic aircraft to test ADOP procedures, a flap model, and an aero-mesh modeler for doublet lattice aerodynamics are discussed.

Optimization of knowledge sharing through multi-forum using cloud computing architecture

NASA Astrophysics Data System (ADS)

Madapusi Vasudevan, Sriram; Sankaran, Srivatsan; Muthuswamy, Shanmugasundaram; Ram, N. Sankar

2011-12-01

Knowledge sharing is done through various knowledge sharing forums which requires multiple logins through multiple browser instances. Here a single Multi-Forum knowledge sharing concept is introduced which requires only one login session which makes user to connect multiple forums and display the data in a single browser window. Also few optimization techniques are introduced here to speed up the access time using cloud computing architecture.

Modulation of PPAR-γ by Nutraceutics as Complementary Treatment for Obesity-Related Disorders and Inflammatory Diseases

PubMed Central

Ortuño Sahagún, D.; Márquez-Aguirre, A. L.; Quintero-Fabián, S.; López-Roa, R. I.; Rojas-Mayorquín, A. E.

2012-01-01

A direct correlation between adequate nutrition and health is a universally accepted truth. The Western lifestyle, with a high intake of simple sugars, saturated fat, and physical inactivity, promotes pathologic conditions. The main adverse consequences range from cardiovascular disease, type 2 diabetes, and metabolic syndrome to several cancers. Dietary components influence tissue homeostasis in multiple ways and many different functional foods have been associated with various health benefits when consumed. Natural products are an important and promising source for drug discovery. Many anti-inflammatory natural products activate peroxisome proliferator-activated receptors (PPAR); therefore, compounds that activate or modulate PPAR-gamma (PPAR-γ) may help to fight all of these pathological conditions. Consequently, the discovery and optimization of novel PPAR-γ agonists and modulators that would display reduced side effects is of great interest. In this paper, we present some of the main naturally derived products studied that exert an influence on metabolism through the activation or modulation of PPAR-γ, and we also present PPAR-γ-related diseases that can be complementarily treated with nutraceutics from functional foods. PMID:23251142

Auditory, visual, and bimodal data link displays and how they support pilot performance.

PubMed

Steelman, Kelly S; Talleur, Donald; Carbonari, Ronald; Yamani, Yusuke; Nunes, Ashley; McCarley, Jason S

2013-06-01

The design of data link messaging systems to ensure optimal pilot performance requires empirical guidance. The current study examined the effects of display format (auditory, visual, or bimodal) and visual display position (adjacent to instrument panel or mounted on console) on pilot performance. Subjects performed five 20-min simulated single-pilot flights. During each flight, subjects received messages from a simulated air traffic controller. Messages were delivered visually, auditorily, or bimodally. Subjects were asked to read back each message aloud and then perform the instructed maneuver. Visual and bimodal displays engendered lower subjective workload and better altitude tracking than auditory displays. Readback times were shorter with the two unimodal visual formats than with any of the other three formats. Advantages for the unimodal visual format ranged in size from 2.8 s to 3.8 s relative to the bimodal upper left and auditory formats, respectively. Auditory displays allowed slightly more head-up time (3 to 3.5 seconds per minute) than either visual or bimodal displays. Position of the visual display had only modest effects on any measure. Combined with the results from previous studies by Helleberg and Wickens and Lancaster and Casali the current data favor visual and bimodal displays over auditory displays; unimodal auditory displays were favored by only one measure, head-up time, and only very modestly. Data evinced no statistically significant effects of visual display position on performance, suggesting that, contrary to expectations, the placement of a visual data link display may be of relatively little consequence to performance.

Directional backlight liquid crystal autostereoscopic display: technical challenges, research progress, and prospect (Conference Presentation)

NASA Astrophysics Data System (ADS)

Fan, Hang; Li, Kunyang; Zhou, Yangui; Liang, Haowen; Wang, Jiahui; Zhou, Jianying

2016-09-01

Recent upsurge on virtual and augmented realities (VR and AR) has re-ignited the interest to the immerse display technology. The VR/AR technology based on stereoscopic display is believed in its early stage as glasses-free, or autostereoscopic display, will be ultimately adopted for the viewing convenience, visual comfort and for the multi-viewer purposes. On the other hand, autostereoscopic display has not yet received positive market response for the past years neither with stereoscopic displays using shutter or polarized glasses. We shall present the analysis on the real-world applications, rigid user demand, the drawbacks to the existing barrier- and lenticular lens-based LCD autostereoscopy. We shall emphasize the emerging autostereoscopic display, and notably on directional backlight LCD technology using a hybrid spatial- and temporal-control scenario. We report the numerical simulation of a display system using Monte-Carlo ray-tracing method with the human retina as the real image receiver. The system performance is optimized using newly developed figure of merit for system design. The reduced crosstalk in an autostereoscopic system, the enhanced display quality, including the high resolution received by the retina, the display homogeneity without Moiré- and defect-pattern, will be highlighted. Recent research progress including a novel scheme for diffraction-free backlight illumination, the expanded viewing zone for autostereoscopic display, and the novel Fresnel lens array to achieve a near perfect display in 2D/3D mode will be introduced. The experimental demonstration will be presented to the autostereoscopic display with the highest resolution, low crosstalk, Moiré- and defect- pattern free.

Symbolic enhancement of perspective displays

NASA Technical Reports Server (NTRS)

Ellis, Stephen R.; Hacisalihzade, Selim S.

1990-01-01

Two exocentric azimuth judgment experiments with a perspective display were conducted with 16 subjects. Previous work has shown these judgments to exhibit a bias possibly due to misinterpretation of the viewing parameters used to generate the display. Though geometric compensations may be used to correct for the bias, an alternate technique selected in the following 2 experiments was the introduction of symbolic enhancements in the form of compass roses. It is suggested that a compass rose with 30 deg divisions results in overall optimal azimuth estimation accuracy when accuracy and decision time are both considered. The data also suggest that the added radial lines on the compass roses may interact with normalization processes that influence the judgment errors.

Effet de l'encombrement visuel de l'ecran primaire de vol sur la performance du pilote, la charge de travail et le parcours visuel

NASA Astrophysics Data System (ADS)

Doyon-Poulin, Philippe

Flight deck of 21st century commercial aircrafts does not look like the one the Wright brothers used for their first flight. The rapid growth of civilian aviation resulted in an increase in the number of flight deck instruments and of their complexity, in order to complete a safe and ontime flight. However, presenting an abundance of visual information using visually cluttered flight instruments might reduce the pilot's flight performance. Visual clutter has received an increased interest by the aerospace community to understand the effects of visual density and information overload on pilots' performance. Aerospace regulations demand to minimize visual clutter of flight deck displays. Past studies found a mixed effect of visual clutter of the primary flight display on pilots' technical flight performance. More research is needed to better understand this subject. In this thesis, we did an experimental study in a flight simulator to test the effects of visual clutter of the primary flight display on the pilot's technical flight performance, mental workload and gaze pattern. First, we identified a gap in existing definitions of visual clutter and we proposed a new definition relevant to the aerospace community that takes into account the context of use of the display. Then, we showed that past research on the effects of visual clutter of the primary flight display on pilots' performance did not manipulate the variable of visual clutter in a similar manner. Past research changed visual clutter at the same time than the flight guidance function. Using a different flight guidance function between displays might have masked the effect of visual clutter on pilots' performance. To solve this issue, we proposed three requirements that all tested displays must satisfy to assure that only the variable of visual clutter is changed during study while leaving other variables unaffected. Then, we designed three primary flight displays with a different visual clutter level (low, medium, high) but with the same flight guidance function, by respecting the previous requirements. Twelve pilots, with a mean experience of over 4000 total flight hours, completed an instrument landing in a flight simulator using all three displays for a total of nine repetitions. Our results showed that pilots reported lower workload level and had better lateral precision during the approach using the medium-clutter display compared to the low- and high-clutter displays. Also, pilots reported that the medium-clutter display was the most useful for the flight task compared to the two other displays. Eye tracker results showed that pilots' gaze pattern was less efficient for the high-clutter display compared to the low- and medium-clutter displays. Overall, these new experimental results emphasize the importance of optimizing visual clutter of flight displays as it affects both objective and subjective performance of experienced pilots in their flying task. This thesis ends with practical recommendations to help designers optimize visual clutter of displays used for man-machine interface.

Optimizing height presentation for aircraft cockpit displays

NASA Astrophysics Data System (ADS)

Jordan, Chris S.; Croft, D.; Selcon, Stephen J.; Markin, H.; Jackson, M.

1997-02-01

This paper describes an experiment conducted to investigate the type of display symbology that most effectively conveys height information to users of head-down plan-view radar displays. The experiment also investigated the use of multiple information sources (redundancy) in the design of such displays. Subjects were presented with eight different height display formats. These formats were constructed from a control, and/or one, two, or three sources of redundant information. The three formats were letter coding, analogue scaling, and toggling (spatially switching the position of the height information from above to below the aircraft symbol). Subjects were required to indicate altitude awareness via a four-key, forced-choice keyboard response. Error scores and response times were taken as performance measures. There were three main findings. First, there was a significant performance advantage when the altitude information was presented above and below the symbol to aid the representation of height information. Second, the analogue scale, a line whose length indicated altitude, proved significantly detrimental to performance. Finally, no relationship was found between the number of redundant information sources employed and performance. The implications for future aircraft and displays are discussed in relation to current aircraft tactical displays and in the context of perceptual psychological theory.

Chemical and genetic wrappers for improved phage and RNA display.

PubMed

Lamboy, Jorge A; Tam, Phillip Y; Lee, Lucie S; Jackson, Pilgrim J; Avrantinis, Sara K; Lee, Hye J; Corn, Robert M; Weiss, Gregory A

2008-11-24

An Achilles heel inherent to all molecular display formats, background binding between target and display system introduces false positives into screens and selections. For example, the negatively charged surfaces of phage, mRNA, and ribosome display systems bind with unacceptably high nonspecificity to positively charged target molecules, which represent an estimated 35% of proteins in the human proteome. Here we report the first systematic attempt to understand why a broad class of molecular display selections fail, and then solve the underlying problem for both phage and RNA display. Firstly, a genetic strategy was used to introduce a short, charge-neutralizing peptide into the solvent-exposed, negatively charged phage coat. The modified phage (KO7(+)) reduced or eliminated nonspecific binding to the problematic high-pI proteins. In the second, chemical approach, nonspecific interactions were blocked by oligolysine wrappers in the cases of phage and total RNA. For phage display applications, the peptides Lys(n) (where n=16 to 24) emerged as optimal for wrapping the phage. Lys(8), however, provided effective wrappers for RNA binding in assays against the RNA binding protein HIV-1 Vif. The oligolysine peptides blocked nonspecific binding to allow successful selections, screens, and assays with five previously unworkable protein targets.

Dual redundant display in bubble canopy applications

NASA Astrophysics Data System (ADS)

Mahdi, Ken; Niemczyk, James

2010-04-01

Today's cockpit integrator, whether for state of the art military fast jet, or piston powered general aviation, is striving to utilize all available panel space for AMLCD based displays to enhance situational awareness and increase safety. The benefits of a glass cockpit have been well studied and documented. The technology used to create these glass cockpits, however, is driven by commercial AMLCD demand which far outstrips the combined worldwide avionics requirements. In order to satisfy the wide variety of human factors and environmental requirements, large area displays have been developed to maximize the usable display area while also providing necessary redundancy in case of failure. The AMLCD has been optimized for extremely wide viewing angles driven by the flat panel TV market. In some cockpit applications, wide viewing cones are desired. In bubble canopy cockpits, however, narrow viewing cones are desired to reduce canopy reflections. American Panel Corporation has developed AMLCD displays that maximize viewing area, provide redundancy, while also providing a very narrow viewing cone even though commercial AMLCD technology is employed suitable for high performance AMLCD Displays. This paper investigates both the large area display architecture with several available options to solve redundancy as well as beam steering techniques to also limit canopy reflections.

High-performance 4x4-inch AMLCD for avionic applications

NASA Astrophysics Data System (ADS)

Syroid, Daniel D.; Hansen, Glenn A.; Boling, Ed

1996-05-01

There is a need for high performance flat panel displays to replace and upgrade the electromechanical flight indicators and CRT based displays used in the cockpits of many older aircraft that are in active service today. The need for replacement of these older generation instruments is well known in the industry and was discussed in a previous paper by Duane Grave of Rockwell Collins. Furthermore, because of the limited activity in new aircraft development today, the need to upgrade existing aircraft avionics is accelerating. Many of the electromechanical instruments currently provide flight indications to the pilot and include horizontal situation (HSI) and attitude director indicators (ADI). These instruments are used on both military and commercial aircraft. The indicators are typically housed in a 5ATI case that slides into a 5 inch square opening in the cockpit. Image Quest has developed a 4 by 4 inch active area, flight quality, high resolution, full color, high luminance, wide temperature range display module based on active matrix liquid crystal display (AMLCD) technology that has excellent contrast in full sunlight. The display module is well suited for use in electronic instruments to replace or upgrade the electro-mechanical 5ATI flight indicators. THe AMLCD based display offers greatly improved display format flexibility, operating reliability and display contrast in all ambient lighting conditions as well as significant short and long term cost of ownership advantages.

Validation of a new digital breast tomosynthesis medical display

NASA Astrophysics Data System (ADS)

Marchessoux, Cédric; Vivien, Nicolas; Kumcu, Asli; Kimpe, Tom

2011-03-01

The main objective of this study is to evaluate and validate the new Barco medical display MDMG-5221 which has been optimized for the Digital Breast Tomosynthesis (DBT) imaging modality system, and to prove the benefit of the new DBT display in terms of image quality and clinical performance. The clinical performance is evaluated by the detection of micro-calcifications inserted in reconstructed Digital Breast Tomosynthesis slices. The slices are shown in dynamic cine loops, at two frames rates. The statistical analysis chosen for this study is the Receiver Operating Characteristic Multiple-Reader, Multiple-Case methodology, in order to measure the clinical performance of the two displays. Four experienced radiologists are involved in this study. For this clinical study, 50 normal and 50 abnormal independent datasets were used. The result is that the new display outperforms the mammography display for a signal detection task using real DBT images viewed at 25 and 50 slices per second. In the case of 50 slices per second, the p-value = 0.0664. For a cut-off where alpha=0.05, the conclusion is that the null hypothesis cannot be rejected, however the trend is that the new display performs 6% better than the old display in terms of AUC. At 25 slices per second, the difference between the two displays is very apparent. The new display outperforms the mammography display by 10% in terms of AUC, with a good statistical significance of p=0.0415.

High Frequency Active Auroral Research Program (HAARP) imager. Final report, 29 August 1991-29 August 1993

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

Lance, C.; Eather, R.

1993-09-30

A low-light-level monochromatic imaging system was designed and fabricated which was optimized to detect and record optical emissions associated with high-power rf heating of the ionosphere. The instrument is capable of detecting very low intensities, of the order of 1 Rayleigh, from typical ionospheric atomic and molecular emissions. This is achieved through co-adding of ON images during heater pulses and subtraction of OFF (background) images between pulses. Images can be displayed and analyzed in real time and stored in optical disc for later analysis. Full image processing software is provided which was customized for this application and uses menu ormore » mouse user interaction.« less

Interactive Visualization of Parking Orbits Around the Moon: An X3D Application for a NASA Lunar Mission Study

NASA Technical Reports Server (NTRS)

Murphy, Douglas G.; Qu, Min; Salas, Andrea O.

2006-01-01

The NASA Integrated Modeling and Simulation (IM&S) project aims to develop a collaborative engineering system to include distributed analysis, integrated tools, and web-enabled graphics. Engineers on the IM&S team were tasked with applying IM&S capabilities to an orbital mechanics analysis for a lunar mission study. An interactive lunar globe was created to show 7 landing sites, contour lines depicting the energy required to reach a given site, and the optimal lunar orbit orientation to meet the mission constraints. Activation of the lunar globe rotation shows the change of the angle between the landing site latitude and the orbit plane. A heads-up-display was used to embed straightforward interface elements.

Overview of research in progress at the Center of Excellence

NASA Technical Reports Server (NTRS)

Wandell, Brian A.

1993-01-01

The Center of Excellence (COE) was created nine years ago to facilitate active collaboration between the scientists at Ames Research Center and the Stanford Psychology Department. Significant interchange of ideas and personnel continues between Stanford and participating groups at NASA-Ames; the COE serves its function well. This progress report is organized into sections divided by project. Each section contains a list of investigators, a background statement, progress report, and a proposal for work during the coming year. The projects are: Algorithms for development and calibration of visual systems, Visually optimized image compression, Evaluation of advanced piloting displays, Spectral representations of color, Perception of motion in man and machine, Automation and decision making, and Motion information used for navigation and control.

Application of a Parallelizable Perfusion Bioreactor for Physiologic 3D Cell Culture.

PubMed

Egger, Dominik; Spitz, Sarah; Fischer, Monica; Handschuh, Stephan; Glösmann, Martin; Friemert, Benedikt; Egerbacher, Monika; Kasper, Cornelia

2017-01-01

It is crucial but challenging to keep physiologic conditions during the cultivation of 3D cell scaffold constructs for the optimization of 3D cell culture processes. Therefore, we demonstrate the benefits of a recently developed miniaturized perfusion bioreactor together with a specialized incubator system that allows for the cultivation of multiple samples while screening different conditions. Hence, a decellularized bone matrix was tested towards its suitability for 3D osteogenic differentiation under flow perfusion conditions. Subsequently, physiologic shear stress and hydrostatic pressure (HP) conditions were optimized for osteogenic differentiation of human mesenchymal stem cells (MSCs). X-ray computed microtomography and scanning electron microscopy (SEM) revealed a closed cell layer covering the entire matrix. Osteogenic differentiation assessed by alkaline phosphatase activity and SEM was found to be increased in all dynamic conditions. Furthermore, screening of different fluid shear stress (FSS) conditions revealed 1.5 mL/min (equivalent to ∼10 mPa shear stress) to be optimal. However, no distinct effect of HP compared to flow perfusion without HP on osteogenic differentiation was observed. Notably, throughout all experiments, cells cultivated under FSS or HP conditions displayed increased osteogenic differentiation, which underlines the importance of physiologic conditions. In conclusion, the bioreactor system was used for biomaterial testing and to develop and optimize a 3D cell culture process for the osteogenic differentiation of MSCs. Due to its versatility and higher throughput efficiency, we hypothesize that this bioreactor/incubator system will advance the development and optimization of a variety of 3D cell culture processes. © 2017 S. Karger AG, Basel.

Optimization of caseinate-coated simvastatin-zein nanoparticles: improved bioavailability and modified release characteristics.

PubMed

Ahmed, Osama A A; Hosny, Khaled M; Al-Sawahli, Majid M; Fahmy, Usama A

2015-01-01

The current study focuses on utilization of the natural biocompatible polymer zein to formulate simvastatin (SMV) nanoparticles coated with caseinate, to improve solubility and hence bioavailability, and in addition, to modify SMV-release characteristics. This formulation can be utilized for oral or possible depot parenteral applications. Fifteen formulations were prepared by liquid-liquid phase separation method, according to the Box-Behnken design, to optimize formulation variables. Sodium caseinate was used as an electrosteric stabilizer. The factors studied were: percentage of SMV in the SMV-zein mixture (X1), ethanol concentration (X2), and caseinate concentration (X3). The selected dependent variables were mean particle size (Y1), SMV encapsulation efficiency (Y2), and cumulative percentage of drug permeated after 1 hour (Y3). The diffusion of SMV from the prepared nanoparticles specified by the design was carried out using an automated Franz diffusion cell apparatus. The optimized SMV-zein formula was investigated for in vivo pharmacokinetic parameters compared with an oral SMV suspension. The optimized nanosized SMV-zein formula showed a 131 nm mean particle size and 89% encapsulation efficiency. In vitro permeation studies displayed delayed permeation characteristics, with about 42% and 85% of SMV cumulative amount released after 12 and 48 hours, respectively. Bioavailability estimation in rats revealed an augmentation in SMV bioavailability from the optimized SMV-zein formulation, by fourfold relative to SMV suspension. Formulation of caseinate-coated SMV-zein nanoparticles improves the pharmacokinetic profile and bioavailability of SMV. Accordingly, improved hypolipidemic activities for longer duration could be achieved. In addition, the reduced dosage rate of SMV-zein nanoparticles improves patient tolerability and compliance.

Pollen-tube tip growth requires a balance of lateral propagation and global inhibition of Rho-family GTPase activity

PubMed Central

Hwang, Jae-Ung; Wu, Guang; Yan, An; Lee, Yong-Jik; Grierson, Claire S.; Yang, Zhenbiao

2010-01-01

Rapid tip growth allows for efficient development of highly elongated cells (e.g. neuronal axons, fungal hyphae and pollen tubes) and requires an elaborate spatiotemporal regulation of the growing region. Here, we use the pollen tube as a model to investigate the mechanism regulating the growing region. ROPs (Rho-related GTPases from plants) are essential for pollen tip growth and display oscillatory activity changes in the apical plasma membrane (PM). By manipulating the ROP activity level, we showed that the PM distribution of ROP activity as an apical cap determines the tip growth region and that efficient tip growth requires an optimum level of the apical ROP1 activity. Excessive ROP activation induced the enlargement of the tip growth region, causing growth depolarization and reduced tube elongation. Time-lapse analysis suggests that the apical ROP1 cap is generated by lateral propagation of a localized ROP activity. Subcellular localization and gain- and loss-of-function analyses suggest that RhoGDI- and RhoGAP-mediated global inhibition limits the lateral propagation of apical ROP1 activity. We propose that the balance between the lateral propagation and the global inhibition maintains an optimal apical ROP1 cap and generates the apical ROP1 activity oscillation required for efficient pollen-tube elongation. PMID:20053639

Vibratory tactile display for textures

NASA Technical Reports Server (NTRS)

Ikei, Yasushi; Ikeno, Akihisa; Fukuda, Shuichi

1994-01-01

We have developed a tactile display that produces vibratory stimulus to a fingertip in contact with a vibrating tactor matrix. The display depicts tactile surface textures while the user is exploring a virtual object surface. A piezoelectric actuator drives the individual tactor in accordance with both the finger movement and the surface texture being traced. Spatiotemporal display control schemes were examined for presenting the fundamental surface texture elements. The temporal duration of vibratory stimulus was experimentally optimized to simulate the adaptation process of cutaneous sensation. The selected duration time for presenting a single line edge agreed with the time threshold of tactile sensation. Then spatial stimulus disposition schemes were discussed for representation of other edge shapes. As an alternative means not relying on amplitude control, a method of augmented duration at the edge was investigated. Spatial resolution of the display was measured for the lines presented both in perpendicular and parallel to a finger axis. Discrimination of texture density was also measured on random dot textures.

Structural Characterizations of Glycerol Kinase: Unraveling Phosphorylation-Induced Long-Range Activation

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

Yeh, Joanne I.; Kettering, Regina; Saxl, Ruth

2009-09-11

Glycerol metabolism provides a central link between sugar and fatty acid catabolism. In most bacteria, glycerol kinase plays a crucial role in regulating channel/facilitator-dependent uptake of glycerol into the cell. In the firmicute Enterococcus casseliflavus, this enzyme's activity is enhanced by phosphorylation of the histidine residue (His232) located in its activation loop, approximately 25 A from its catalytic cleft. We reported earlier that some mutations of His232 altered enzyme activities; we present here the crystal structures of these mutant GlpK enzymes. The structure of a mutant enzyme with enhanced enzymatic activity, His232Arg, reveals that residues at the catalytic cleft aremore » more optimally aligned to bind ATP and mediate phosphoryl transfer. Specifically, the position of Arg18 in His232Arg shifts by approximately 1 A when compared to its position in wild-type (WT), His232Ala, and His232Glu enzymes. This new conformation of Arg18 is more optimally positioned at the presumed gamma-phosphate location of ATP, close to the glycerol substrate. In addition to structural changes exhibited at the active site, the conformational stability of the activation loop is decreased, as reflected by an approximately 35% increase in B factors ('thermal factors') in a mutant enzyme displaying diminished activity, His232Glu. Correlating conformational changes to alteration of enzymatic activities in the mutant enzymes identifies distinct localized regions that can have profound effects on intramolecular signal transduction. Alterations in pairwise interactions across the dimer interface can communicate phosphorylation states over 25 A from the activation loop to the catalytic cleft, positioning Arg18 to form favorable interactions at the beta,gamma-bridging position with ATP. This would offset loss of the hydrogen bonds at the gamma-phosphate of ATP during phosphoryl transfer to glycerol, suggesting that appropriate alignment of the second substrate of glycerol kinase, the ATP molecule, may largely determine the rate of glycerol 3-phosphate production.« less

Robust optimization of front members in a full frontal car impact

NASA Astrophysics Data System (ADS)

Aspenberg (né Lönn), David; Jergeus, Johan; Nilsson, Larsgunnar

2013-03-01

In the search for lightweight automobile designs, it is necessary to assure that robust crashworthiness performance is achieved. Structures that are optimized to handle a finite number of load cases may perform poorly when subjected to various dispersions. Thus, uncertainties must be accounted for in the optimization process. This article presents an approach to optimization where all design evaluations include an evaluation of the robustness. Metamodel approximations are applied both to the design space and the robustness evaluations, using artifical neural networks and polynomials, respectively. The features of the robust optimization approach are displayed in an analytical example, and further demonstrated in a large-scale design example of front side members of a car. Different optimization formulations are applied and it is shown that the proposed approach works well. It is also concluded that a robust optimization puts higher demands on the finite element model performance than normally.

Algorithm and Software for Calculating Optimal Regimes of the Process Water Supply System at the Kalininskaya NPP{sup 1}

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

Murav’ev, V. P., E-mail: murval@mail.ru; Kochetkov, A. V.; Glazova, E. G.

An algorithm and software for calculating the optimal operating regimes of the process water supply system at the Kalininskaya NPP are described. The parameters of the optimal regimes are determined for time varying meteorological conditions and condensation loads of the NPP. The optimal flow of the cooling water in the turbines is determined computationally; a regime map with the data on the optimal water consumption distribution between the coolers and displaying the regimes with an admissible heat load on the natural cooling lakes is composed. Optimizing the cooling system for a 4000-MW NPP will make it possible to conserve atmore » least 155,000 MW · h of electricity per year. The procedure developed can be used to optimize the process water supply systems of nuclear and thermal power plants.« less

Translator for Optimizing Fluid-Handling Components

NASA Technical Reports Server (NTRS)

Landon, Mark; Perry, Ernest

2007-01-01

A software interface has been devised to facilitate optimization of the shapes of valves, elbows, fittings, and other components used to handle fluids under extreme conditions. This software interface translates data files generated by PLOT3D (a NASA grid-based plotting-and- data-display program) and by computational fluid dynamics (CFD) software into a format in which the files can be read by Sculptor, which is a shape-deformation- and-optimization program. Sculptor enables the user to interactively, smoothly, and arbitrarily deform the surfaces and volumes in two- and three-dimensional CFD models. Sculptor also includes design-optimization algorithms that can be used in conjunction with the arbitrary-shape-deformation components to perform automatic shape optimization. In the optimization process, the output of the CFD software is used as feedback while the optimizer strives to satisfy design criteria that could include, for example, improved values of pressure loss, velocity, flow quality, mass flow, etc.

Motion Cueing Algorithm Development: Piloted Performance Testing of the Cueing Algorithms

NASA Technical Reports Server (NTRS)

Houck, Jacob A. (Technical Monitor); Telban, Robert J.; Cardullo, Frank M.; Kelly, Lon C.

2005-01-01

The relative effectiveness in simulating aircraft maneuvers with both current and newly developed motion cueing algorithms was assessed with an eleven-subject piloted performance evaluation conducted on the NASA Langley Visual Motion Simulator (VMS). In addition to the current NASA adaptive algorithm, two new cueing algorithms were evaluated: the optimal algorithm and the nonlinear algorithm. The test maneuvers included a straight-in approach with a rotating wind vector, an offset approach with severe turbulence and an on/off lateral gust that occurs as the aircraft approaches the runway threshold, and a takeoff both with and without engine failure after liftoff. The maneuvers were executed with each cueing algorithm with added visual display delay conditions ranging from zero to 200 msec. Two methods, the quasi-objective NASA Task Load Index (TLX), and power spectral density analysis of pilot control, were used to assess pilot workload. Piloted performance parameters for the approach maneuvers, the vertical velocity upon touchdown and the runway touchdown position, were also analyzed but did not show any noticeable difference among the cueing algorithms. TLX analysis reveals, in most cases, less workload and variation among pilots with the nonlinear algorithm. Control input analysis shows pilot-induced oscillations on a straight-in approach were less prevalent compared to the optimal algorithm. The augmented turbulence cues increased workload on an offset approach that the pilots deemed more realistic compared to the NASA adaptive algorithm. The takeoff with engine failure showed the least roll activity for the nonlinear algorithm, with the least rudder pedal activity for the optimal algorithm.

Ultra-High-Throughput Screening of an In Vitro-Synthesized Horseradish Peroxidase Displayed on Microbeads Using Cell Sorter

PubMed Central

Zhu, Bo; Mizoguchi, Takuro; Kojima, Takaaki; Nakano, Hideo

2015-01-01

The C1a isoenzyme of horseradish peroxidase (HRP) is an industrially important heme-containing enzyme that utilizes hydrogen peroxide to oxidize a wide variety of inorganic and organic compounds for practical applications, including synthesis of fine chemicals, medical diagnostics, and bioremediation. To develop a ultra-high-throughput screening system for HRP, we successfully produced active HRP in an Escherichia coli cell-free protein synthesis system, by adding disulfide bond isomerase DsbC and optimizing the concentrations of hemin and calcium ions and the temperature. The biosynthesized HRP was fused with a single-chain Cro (scCro) DNA-binding tag at its N-terminal and C-terminal sites. The addition of the scCro-tag at both ends increased the solubility of the protein. Next, HRP and its fusion proteins were successfully synthesized in a water droplet emulsion by using hexadecane as the oil phase and SunSoft No. 818SK as the surfactant. HRP fusion proteins were displayed on microbeads attached with double-stranded DNA (containing the scCro binding sequence) via scCro-DNA interactions. The activities of the immobilized HRP fusion proteins were detected with a tyramide-based fluorogenic assay using flow cytometry. Moreover, a model microbead library containing wild type hrp (WT) and inactive mutant (MUT) genes was screened using fluorescence-activated cell-sorting, thus efficiently enriching the WT gene from the 1:100 (WT:MUT) library. The technique described here could serve as a novel platform for the ultra-high-throughput discovery of more useful HRP mutants and other heme-containing peroxidases. PMID:25993095

Improving the quality of care of patients with rheumatic disease using patient-centric electronic redesign software.

PubMed

Newman, Eric D; Lerch, Virginia; Billet, Jon; Berger, Andrea; Kirchner, H Lester

2015-04-01

Electronic health records (EHRs) are not optimized for chronic disease management. To improve the quality of care for patients with rheumatic disease, we developed electronic data capture, aggregation, display, and documentation software. The software integrated and reassembled information from the patient (via a touchscreen questionnaire), nurse, physician, and EHR into a series of actionable views. Core functions included trends over time, rheumatology-related demographics, and documentation for patient and provider. Quality measures collected included patient-reported outcomes, disease activity, and function. The software was tested and implemented in 3 rheumatology departments, and integrated into routine care delivery. Post-implementation evaluation measured adoption, efficiency, productivity, and patient perception. Over 2 years, 6,725 patients completed 19,786 touchscreen questionnaires. The software was adopted for use by 86% of patients and rheumatologists. Chart review and documentation time trended downward, and productivity increased by 26%. Patient satisfaction, activation, and adherence remained unchanged, although pre-implementation values were high. A strong correlation was seen between use of the software and disease control (weighted Pearson's correlation coefficient 0.5927, P = 0.0095), and a relative increase in patients with low disease activity of 3% per quarter was noted. We describe innovative software that aggregates, stores, and displays information vital to improving the quality of care for patients with chronic rheumatic disease. The software was well-adopted by patients and providers. Post-implementation, significant improvements in quality of care, efficiency of care, and productivity were demonstrated. Copyright © 2015 by the American College of Rheumatology.

A trimeric structural fusion of an antagonistic tumor necrosis factor-α mutant enhances molecular stability and enables facile modification.

PubMed

Inoue, Masaki; Ando, Daisuke; Kamada, Haruhiko; Taki, Shintaro; Niiyama, Mayumi; Mukai, Yohei; Tadokoro, Takashi; Maenaka, Katsumi; Nakayama, Taisuke; Kado, Yuji; Inoue, Tsuyoshi; Tsutsumi, Yasuo; Tsunoda, Shin-Ichi

2017-04-21

Tumor necrosis factor-α (TNF) exerts its biological effect through two types of receptors, p55 TNF receptor (TNFR1) and p75 TNF receptor (TNFR2). An inflammatory response is known to be induced mainly by TNFR1, whereas an anti-inflammatory reaction is thought to be mediated by TNFR2 in some autoimmune diseases. We have been investigating the use of an antagonistic TNF mutant (TNFR1-selective antagonistic TNF mutant (R1antTNF)) to reveal the pharmacological effect of TNFR1-selective inhibition as a new therapeutic modality. Here, we aimed to further improve and optimize the activity and behavior of this mutant protein both in vitro and in vivo Specifically, we examined a trimeric structural fusion of R1antTNF, formed via the introduction of short peptide linkers, as a strategy to enhance bioactivity and molecular stability. By comparative analysis with R1antTNF, the trimeric fusion, referred to as single-chain R1antTNF (scR1antTNF), was found to retain in vitro molecular properties of receptor selectivity and antagonistic activity but displayed a marked increase in thermal stability. The residence time of scR1antTNF in vivo was also significantly prolonged. Furthermore, molecular modification using polyethylene glycol (PEG) was easily controlled by limiting the number of reactive sites. Taken together, our findings show that scR1antTNF displays enhanced molecular stability while maintaining biological activity compared with R1antTNF. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

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

PubMed

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

2015-12-01

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

A Generalized Orienteering Problem for Optimal Search and Interdiction Planning

DTIC Science & Technology

2013-09-01

NAVAL POSTGRADUATE SCHOOL MONTEREY, CALIFORNIA DISSERTATION A GENERALIZED ORIENTEERING PROBLEM FOR OPTIMAL SEARCH AND INTERDICTION PLANNING by Jesse...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 currently...16. SECURITY CLASSIFICATION OF: a . REPORT b. ABSTRACT c. THIS PAGE 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON 19b

Optimization of the polyplanar optical display electronics for a monochrome B-52 display

NASA Astrophysics Data System (ADS)

DeSanto, Leonard

1998-09-01

The Polyplanar Optical Display (POD) is a unique display screen which can be used with any projection source. The prototype ten-inch display is two inches thick and has a matte black face which allows for high contrast images. The prototype being developed is a form, fit and functional replacement display for the B-52 aircraft which uses a monochrome ten-inch display. In order to achieve a long lifetime, the new display uses a new 200 mW green solid-state laser (10,000 hr. life) at 532 nm as its light source. To produce real-time video, the laser light is being modulated by a Digital Light Processing (DLPTM) chip manufactured by Texas Instruments (TI). In order to use the solid-state laser as the light source and also fit within the constraints of the B-52 display, the Digital Micromirror Device (DMDTM) chip is operated remotely from the Texas Instruments circuit board. In order to achieve increased brightness a monochrome digitizing interface was investigated. The operation of the DMDTM divorced from the light engine and the interfacing of the DMDTM board with the RS-170 video format specific to the B-52 aircraft will be discussed, including the increased brightness of the monochrome digitizing interface. A brief description of the electronics required to drive the new 200 mW laser is also presented.

Optimizing virtual reality for all users through gaze-contingent and adaptive focus displays

PubMed Central

Padmanaban, Nitish; Konrad, Robert; Stramer, Tal; Wetzstein, Gordon

2017-01-01

From the desktop to the laptop to the mobile device, personal computing platforms evolve over time. Moving forward, wearable computing is widely expected to be integral to consumer electronics and beyond. The primary interface between a wearable computer and a user is often a near-eye display. However, current generation near-eye displays suffer from multiple limitations: they are unable to provide fully natural visual cues and comfortable viewing experiences for all users. At their core, many of the issues with near-eye displays are caused by limitations in conventional optics. Current displays cannot reproduce the changes in focus that accompany natural vision, and they cannot support users with uncorrected refractive errors. With two prototype near-eye displays, we show how these issues can be overcome using display modes that adapt to the user via computational optics. By using focus-tunable lenses, mechanically actuated displays, and mobile gaze-tracking technology, these displays can be tailored to correct common refractive errors and provide natural focus cues by dynamically updating the system based on where a user looks in a virtual scene. Indeed, the opportunities afforded by recent advances in computational optics open up the possibility of creating a computing platform in which some users may experience better quality vision in the virtual world than in the real one. PMID:28193871

Nonlinear mechanics of thermoreversibly associating dendrimer glasses

NASA Astrophysics Data System (ADS)

Srikanth, Arvind; Hoy, Robert S.; Rinderspacher, Berend C.; Andzelm, Jan W.

2013-10-01

We model the mechanics of associating trivalent dendrimer network glasses with a focus on their energy dissipation properties. Various combinations of sticky bond (SB) strength and kinetics are employed. The toughness (work to fracture) of these systems displays a surprising deformation-protocol dependence; different association parameters optimize different properties. In particular, “strong, slow” SBs optimize strength, while “weak, fast” SBs optimize ductility via self-healing during deformation. We relate these observations to breaking, reformation, and partner switching of SBs during deformation. These studies point the way to creating associating-polymer network glasses with tailorable mechanical properties.

Spectral synthesis in the ultraviolet. II - Stellar populations and star formation in blue compact galaxies

NASA Technical Reports Server (NTRS)

Fanelli, Michael N.; O'Connell, Robert W.; Thuan, Trinh X.

1988-01-01

An initial attempt to apply optimizing spectral synthesis techniques to the far-UV spectra of blue compact galaxies (BCGs) is presented. The far-UV absorption-line spectra of the galaxies are clearly composite, with the signatures of the main-sequence types between O3 and mid-A. Most of the low-ionization absorption lines have a stellar origin. The Si IV and C IV features in several objects have P Cygni profiles. In Haro I the strength of Si IV indicates a significant blue supergiant population. The metal-poor blue compact dwarf Mrk 209 displays weak absorption lines, evidence that the stellar component has the same low metallicity as observed in the ionized gas. Good fits to the data are obtained the technique of optimizing population synthesis. The solutions yield stellar luminosity functions which display large discontinuities, indicative of discrete star formation episodes or bursts. The amount of UV extinction is low.

Subpixel area-based evaluation for crosstalk suppression in quasi-three-dimensional displays.

PubMed

Zhuang, Zhenfeng; Surman, Phil; Cheng, Qijia; Thibault, Simon; Zheng, Yuanjin; Sun, Xiao Wei

2017-07-01

A subpixel area-based evaluation method for an improved slanted lenticular film that minimizes the crosstalk in a quasi-three-dimensional (Q3D) display is proposed in this paper. To identify an optimal slant angle of the film, a subpixel area-based measurement is derived to evaluate the crosstalk among viewing regions of the intended subpixel and adjacent unintended subpixel by taking the real subpixel shape and black matrix into consideration. The subpixel mapping, which corresponds to the optimal slant angle of the film, can then be determined. Meanwhile, the viewing zone characteristics are analyzed to balance the light intensity in both right and left eye channels. A compact and portable Q3D system has been built and appropriate experiments have been applied. The results indicate that significant improvements in both crosstalk and resolution can be obtained with the proposed technique.

Testing of New Materials and Computer Aided Optimization of Process Parameters and Clamping Device During Predevelopment of Laser Welding Processes

NASA Astrophysics Data System (ADS)

Weidinger, Peter; Günther, Kay; Fitzel, Martin; Logvinov, Ruslan; Ilin, Alexander; Ploshikhin, Vasily; Hugger, Florian; Mann, Vincent; Roth, Stephan; Schmidt, Michael

The necessity for weight reduction in motor vehicles in order to save fuel consumption pushes automotive suppliers to use materials of higher strength. Due to their excellent crash behavior high strength steels are increasingly applied in various structures. In this paper some predevelopment steps for a material change from a micro alloyed to dual phase and complex phase steels of a T-joint assembly are displayed. Initially the general weldability of the materials regarding pore formation, hardening in the heat affected zone and hot cracking susceptibility is discussed. After this basic investigation, the computer aided design optimization of a clamping device is shown, in which influences of the clamping jaw, the welding position and the clamping forces upon weld quality are presented. Finally experimental results of the welding process are displayed, which validate the numerical simulation.

Image management research

NASA Technical Reports Server (NTRS)

Watson, Andrew B.

1988-01-01

Two types of research issues are involved in image management systems with space station applications: image processing research and image perception research. The image processing issues are the traditional ones of digitizing, coding, compressing, storing, analyzing, and displaying, but with a new emphasis on the constraints imposed by the human perceiver. Two image coding algorithms have been developed that may increase the efficiency of image management systems (IMS). Image perception research involves a study of the theoretical and practical aspects of visual perception of electronically displayed images. Issues include how rapidly a user can search through a library of images, how to make this search more efficient, and how to present images in terms of resolution and split screens. Other issues include optimal interface to an IMS and how to code images in a way that is optimal for the human perceiver. A test-bed within which such issues can be addressed has been designed.

Designing Websites for Displaying Large Data Sets and Images on Multiple Platforms

NASA Astrophysics Data System (ADS)

Anderson, A.; Wolf, V. G.; Garron, J.; Kirschner, M.

2012-12-01

The desire to build websites to analyze and display ever increasing amounts of scientific data and images pushes for web site designs which utilize large displays, and to use the display area as efficiently as possible. Yet, scientists and users of their data are increasingly wishing to access these websites in the field and on mobile devices. This results in the need to develop websites that can support a wide range of devices and screen sizes, and to optimally use whatever display area is available. Historically, designers have addressed this issue by building two websites; one for mobile devices, and one for desktop environments, resulting in increased cost, duplicity of work, and longer development times. Recent advancements in web design technology and techniques have evolved which allow for the development of a single website that dynamically adjusts to the type of device being used to browse the website (smartphone, tablet, desktop). In addition they provide the opportunity to truly optimize whatever display area is available. HTML5 and CSS3 give web designers media query statements which allow design style sheets to be aware of the size of the display being used, and to format web content differently based upon the queried response. Web elements can be rendered in a different size, position, or even removed from the display entirely, based upon the size of the display area. Using HTML5/CSS3 media queries in this manner is referred to as "Responsive Web Design" (RWD). RWD in combination with technologies such as LESS and Twitter Bootstrap allow the web designer to build web sites which not only dynamically respond to the browser display size being used, but to do so in very controlled and intelligent ways, ensuring that good layout and graphic design principles are followed while doing so. At the University of Alaska Fairbanks, the Alaska Satellite Facility SAR Data Center (ASF) recently redesigned their popular Vertex application and converted it from a traditional, fixed-layout website into a RWD site built on HTML5, LESS and Twitter Bootstrap. Vertex is a data portal for remotely sensed imagery of the earth, offering Synthetic Aperture Radar (SAR) data products from the global ASF archive. By using Responsive Web Design, ASF is able to provide access to a massive collection of SAR imagery and allow the user to use mobile devices and desktops to maximum advantage. ASF's Vertex web site demonstrates that with increased interface flexibility, scientists, managers and users can increase their personal effectiveness by accessing data portals from their preferred device as their science dictates.

Subtilisin QK-2: secretory expression in Lactococcus lactis and surface display onto gram-positive enhancer matrix (GEM) particles.

PubMed

Mao, Ruifeng; Zhou, Kangping; Han, Zhenwei; Wang, Yefu

2016-05-12

Purified from the supernatant of Bacillus subtilis QK02 culture broth, Subtilisin QK-2 is a type of effective thrombolytic reagent that has great exploitable potential. However, the unbearable flavor that occurs with fermentation and the complicated methods that are required to obtain pure products limit the application of this enzyme. Lactic acid bacteria (LAB)-based delivery vehicles are promising as cheap and safe options for medicinal compounds. The secretory expression and surface display using LAB may popularize Subtilisin QK-2 more easily and conveniently with minimal adverse effects. Subtilisin QK-2 was expressed successfully in two forms using lactic acid bacteria. For the secretory expression in Lactococcus lactis, Subtilisin QK-2 was efficiently secreted into the culture using the promoter P nisA and signal peptide SPUsp. The expression levels were not different in L. lactis NZ9000 and NZ3900 without the effect of different selection markers. However, leaky expression was only detected in L. lactis NZ3900. The biological activity of this secreted Subtilisin QK-2 was enhanced by modulating the pH of medium to slightly alkaline during induction and by codon optimization of either the entire gene sequence (qk') or only the propeptide gene sequence (qkpro'). For surface display onto gram-positive enhancer matrix (GEM) particles, n LysM repeats from the C-terminal region of the major autolysin AcmA of L. lactis were fused to either the C-terminus (n = 1, 3, 5) or the N-terminus (n = 1) of the Subtilisin QK-2. These fusion proteins were secreted into the culture medium, and the QK-3LysM was able to bind to the surface of various LAB GEM particles without a loss of fibrinolytic activity. Furthermore, the binding capacity significantly increased with a higher concentration of QK-3LysM. Compared to the free-form Subtilisin QK-2, the QK-3LysM displayed on the surface of GEM particles was more stable in the simulated gastric juice. Combined with the safety and popularity of LAB, Subtilisin QK-2 may be easily applied worldwide to prevent and control thrombosis diseases.

Isolation and characterization of a cold-active, alkaline, detergent stable α-amylase from a novel bacterium Bacillus subtilis N8.

PubMed

Arabacı, Nihan; Arıkan, Burhan

2018-05-28

A cold-active alkaline amylase producer Bacillus subtilis N8 was isolated from soil samples. Amylase synthesis optimally occurred at 15°C and pH 10.0 on agar plates containing starch. The molecular weight of the enzyme was found to be 205 kDa by performing SDS-PAGE. While the enzyme exhibited the highest activity at 25°C and pH 8.0, it was highly stable in alkaline media (pH 8.0-12.0) and retained 96% of its original activity at low temperatures (10-40°C) for 24 hr. While the amylase activity increased in the presence of β-mercaptoethanol (103%); Ba 2+ , Ca 2+ , Na + , Zn 2+ , Mn 2+ , H 2 O 2 , and Triton X-100 slightly inhibited the activity. The enzyme showed resistance to some denaturants: such as SDS, EDTA, and urea (52, 65, and 42%, respectively). N8 α-amylase displayed the maximum remaining activity of 56% with 3% NaCl. The major final products of starch were glucose, maltose, and maltose-derived oligosaccharides. This novel cold-active α-amylase has the potential to be used in the industries of detergent and food, bioremediation process and production of prebiotics.

Transition metal-modified zinc oxides for UV and visible light photocatalysis.

PubMed

Bloh, J Z; Dillert, R; Bahnemann, D W

2012-11-01

In order to use photocatalysis with solar light, finding more active and especially visible light active photocatalysts is a very important challenge. Also, studies of these photocatalysts should employ a standardized test procedure so that their results can be accurately compared and evaluated with one another. A systematic study of transition metal-modified zinc oxide was conducted to determine whether they are suitable as visible light photocatalysts. The photocatalytic activity of ZnO modified with eight different transition metals (Cu, Co, Fe, Mn, Ni, Ru, Ti, Zr) in three different concentrations (0.01, 0.1, and 1 at.%) was investigated under irradiation with UV as well as with visible light. The employed activity test is the gas-phase degradation of acetaldehyde as described by the ISO standard 22197-2. The results suggest that the UV activity can be improved with almost any modification element and that there exists an optimal modification ratio at about 0.1 at.%. Additionally, Mn- and Ru-modified ZnO display visible light activity. Especially the Ru-modified ZnO is highly active and surpasses the visible light activity of all studied titania standards. These findings suggest that modified zinc oxides may be a viable alternative to titanium dioxide-based catalysts for visible light photocatalysis. Eventually, possible underlying mechanisms are proposed and discussed.

Optimal growth condition of earthworms and their vermicompost features during recycling of five different fresh fruit and vegetable wastes.

PubMed

Huang, Kui; Xia, Hui; Li, Fusheng; Wei, Yongfen; Cui, Guangyu; Fu, Xiaoyong; Chen, Xuemin

2016-07-01

This study aimed to promote vermicomposting performance for recycling fresh fruit and vegetable wastes (FVWs) and to assess microbial population and community of final products. Five fresh FVWs including banana peels, cabbage, lettuce, potato, and watermelon peels were chosen as earthworms' food. The fate test of earthworms showed that 30 g fresh FVWs/day was the optimal loading and the banana peels was harmful for the survival of Eisenia fetida. The followed vermicomposting test revealed lower contents of total carbon and weaker microbial activity in final vermicomposts, relative to those in compared systems without earthworms worked. The leachate from FVWs carried away great amounts of nutrients from reactors. Additionally, different fresh FVWs displayed dissimilar stabilization process. Molecular biological approaches revealed that earthworms could broaden bacterial diversity in their products, with significant greater populations of actinobacteria and ammonia oxidizing bacteria than in control. This study evidences that vermicomposting efficiency differs with the types and loadings of fresh FVWs and vermicomposts are rich in agricultural probiotics.

Inhibition of HIV-1 by a peptide ligand of the genomic RNA packaging signal Psi.

PubMed

Dietz, Julia; Koch, Joachim; Kaur, Ajit; Raja, Chinnappan; Stein, Stefan; Grez, Manuel; Pustowka, Anette; Mensch, Sarah; Ferner, Jan; Möller, Lars; Bannert, Norbert; Tampé, Robert; Divita, Gilles; Mély, Yves; Schwalbe, Harald; Dietrich, Ursula

2008-05-01

The interaction of the nucleocapsid NCp7 of the human immunodeficiency virus type 1 (HIV-1) Gag polyprotein with the RNA packaging signal Psi ensures specific encapsidation of the dimeric full length viral genome into nascent virus particles. Being an essential step in the HIV-1 replication cycle, specific genome encapsidation represents a promising target for therapeutic intervention. We previously selected peptides binding to HIV-1 Psi-RNA or stem loops (SL) thereof by phage display. Herein, we describe synthesis of peptide variants of the consensus HWWPWW motif on membrane supports to optimize Psi-RNA binding. The optimized peptide, psi-pepB, was characterized in detail with respect to its conformation and binding properties for the SL3 of the Psi packaging signal by NMR and tryptophan fluorescence quenching. Functional analysis revealed that psi-pepB caused a strong reduction of virus release by infected cells as monitored by reduced transduction efficiencies, capsid p24 antigen levels, and electron microscopy. Thus, this peptide shows antiviral activity and could serve as a lead compound to develop new drugs targeting HIV-1.

Targeting Prolyl-tRNA Synthetase to Accelerate Drug Discovery against Malaria, Leishmaniasis, Toxoplasmosis, Cryptosporidiosis, and Coccidiosis.

PubMed

Jain, Vitul; Yogavel, Manickam; Kikuchi, Haruhisa; Oshima, Yoshiteru; Hariguchi, Norimitsu; Matsumoto, Makoto; Goel, Preeti; Touquet, Bastien; Jumani, Rajiv S; Tacchini-Cottier, Fabienne; Harlos, Karl; Huston, Christopher D; Hakimi, Mohamed-Ali; Sharma, Amit

2017-10-03

Developing anti-parasitic lead compounds that act on key vulnerabilities are necessary for new anti-infectives. Malaria, leishmaniasis, toxoplasmosis, cryptosporidiosis and coccidiosis together kill >500,000 humans annually. Their causative parasites Plasmodium, Leishmania, Toxoplasma, Cryptosporidium and Eimeria display high conservation in many housekeeping genes, suggesting that these parasites can be attacked by targeting invariant essential proteins. Here, we describe selective and potent inhibition of prolyl-tRNA synthetases (PRSs) from the above parasites using a series of quinazolinone-scaffold compounds. Our PRS-drug co-crystal structures reveal remarkable active site plasticity that accommodates diversely substituted compounds, an enzymatic feature that can be leveraged for refining drug-like properties of quinazolinones on a per parasite basis. A compound we termed In-5 exhibited a unique double conformation, enhanced drug-like properties, and cleared malaria in mice. It thus represents a new lead for optimization. Collectively, our data offer insights into the structure-guided optimization of quinazolinone-based compounds for drug development against multiple human eukaryotic pathogens. Copyright © 2017 Elsevier Ltd. All rights reserved.

Aggregation state and magnetic properties of magnetite nanoparticles controlled by an optimized silica coating

NASA Astrophysics Data System (ADS)

Pérez, Nicolás; Moya, C.; Tartaj, P.; Labarta, A.; Batlle, X.

2017-01-01

The control of magnetic interactions is becoming essential to expand/improve the applicability of magnetic nanoparticles (NPs). Here, we show that an optimized microemulsion method can be used to obtain homogenous silica coatings on even single magnetic nuclei of highly crystalline Fe3-xO4 NPs (7 and 16 nm) derived from a high-temperature method. We show that the thickness of this coating is controlled almost at will allowing much higher average separation among particles as compared to the oleic acid coating present on pristine NPs. Magnetic susceptibility studies show that the thickness of the silica coating allows the control of magnetic interactions. Specifically, as this effect is better displayed for the smallest particles, we show that dipole-dipole interparticle interactions can be tuned progressively for the 7 nm NPs, from almost non-interacting to strongly interacting particles at room temperature. The quantitative analysis of the magnetic properties unambiguously suggests that dipolar interactions significantly broaden the effective distribution of energy barriers by spreading the distribution of activation magnetic volumes.

Design and Synthesis of High Affinity Inhibitors of Plasmodium falciparum and Plasmodium vivax N-Myristoyltransferases Directed by Ligand Efficiency Dependent Lipophilicity (LELP)

PubMed Central

2014-01-01

N-Myristoyltransferase (NMT) is an essential eukaryotic enzyme and an attractive drug target in parasitic infections such as malaria. We have previously reported that 2-(3-(piperidin-4-yloxy)benzo[b]thiophen-2-yl)-5-((1,3,5-trimethyl-1H-pyrazol-4-yl)methyl)-1,3,4-oxadiazole (34c) is a high affinity inhibitor of both Plasmodium falciparum and P. vivax NMT and displays activity in vivo against a rodent malaria model. Here we describe the discovery of 34c through optimization of a previously described series. Development, guided by targeting a ligand efficiency dependent lipophilicity (LELP) score of less than 10, yielded a 100-fold increase in enzyme affinity and a 100-fold drop in lipophilicity with the addition of only two heavy atoms. 34c was found to be equipotent on chloroquine-sensitive and -resistant cell lines and on both blood and liver stage forms of the parasite. These data further validate NMT as an exciting drug target in malaria and support 34c as an attractive tool for further optimization. PMID:24641010

Spore cells from BPA degrading bacteria Bacillus sp. GZB displaying high laccase activity and stability for BPA degradation.

PubMed

Das, Ranjit; Li, Guiying; Mai, Bixian; An, Taicheng

2018-06-04

Laccase has been applied extensively as a biocatalyst to remove different organic pollutants. This study characterized a spore-laccase from the bisphenol A (BPA)-degrading strain Bacillus sp. GZB. The spore-laccase was encoded with 513 amino acids, containing spore coat protein A (CotA). It showed optimal activity at 70 °C and pH = 7.2 in presence of 2, 6-dimethoxyphenol. At 60 °C, optimal activity was also seen at pH = 3.0 and pH = 6.8 with 2, 2'-azino-bis (3-ethylbenzothiazoline-6-sulfonate) and syringaldazine, respectively. The spore-laccase was stable at high temperature, at acidic to alkaline pH values, and in the presence of different organic solvents. Spore-laccase activity was increased by introducing Cu 2+ , Mg 2+ , and Na + , but was strongly inhibited by Fe 2+ , Ag + , l-cysteine, dithiothreitol, and NaN 3 . The cotA gene was cloned and expressed in E. coli BL21 (DE3); the purified protein was estimated as having a molecular weight of ~63 kDa. Different synthetic dyes and BPA were effectively decolorized or degraded both by the spore laccase and recombinant laccase. When BPA oxidation was catalyzed using laccase, there was an initial formation of phenoxy radicals and further oxidation or CC bond cleavage of the radicals produced different organic acids. Detailed reaction pathways were developed based on nine identified intermediates. The acute toxicity decreased gradually during BPA degradation by laccase. This study is the first report about a genus of Bacillus that can produce a highly active and stable laccase to degrade BPA. Copyright © 2018 Elsevier B.V. All rights reserved.

Target identification, lead optimization and antitumor evaluation of some new 1,2,4-triazines as c-Met kinase inhibitors.

PubMed

El-Wakil, Marwa H; Ashour, Hayam M; Saudi, Manal N; Hassan, Ahmed M; Labouta, Ibrahim M

2017-08-01

In silico target fishing approach using PharmMapper server identified c-Met kinase as the selective target for our previously synthesized compound NCI 748494/1. This approach was validated by in vitro kinase assay which showed that NCI 748494/1 possessed promising inhibitory activity against c-Met kinase (IC 50 =31.70μM). Assessment of ADMET profiling, drug-likeness, drug score as well as docking simulation for the binding pose of that compound in the active site of c-Met kinase domain revealed that NCI 748494/1 could be considered as a promising drug lead. Based on target identification and validation, it was observed that there is structure similarity between NCI 748494/1 and the reported type II c-Met kinase inhibitor BMS-777607. Optimization of our lead NCI 748494/1 furnished newly synthesized 1,2,4-triazine derivatives based on well-established structure-activity relationships, whereas three compounds namely; 4d, 7a and 8c displayed excellent in vitro cytotoxicity against three c-Met addicted cancer cell lines; A549 (lung adenocarcinoma), HT-29 (colon cancer) and MKN-45 (gastric carcinoma); with IC 50 values in the range 0.01-1.86µM. In vitro c-Met kinase assay showed 8c to possess the highest c-Met kinase inhibition profile (IC 50 =4.31µM). Docking of the active compounds in c-Met kinase active site revealed strong binding interactions comparable to the lead NCI 748494/1 and BMS-777607, suggesting that c-Met inhibition is very likely to be the mechanism of the antitumor effect of these derivatives. Copyright © 2017 Elsevier Inc. All rights reserved.

Specific amino acids responsible for the cold adaptedness of Micrococcus antarcticus β-glucosidase BglU.

PubMed

Miao, Li-Li; Fan, Hong-Xia; Qu, Jie; Liu, Ying; Liu, Zhi-Pei

2017-03-01

Psychrophilic enzymes display efficient activity at moderate or low temperatures (4-25 °C) and are therefore of great interest in biotechnological industries. We previously examined the crystal structure of BglU, a psychrophilic β-glucosidase from the bacterium Micrococcus antarcticus, at 2.2 Å resolution. In structural comparison and sequence alignment with mesophilic (BglB) and thermophilic (GlyTn) counterpart enzymes, BglU showed much lower contents of Pro residue and of charged amino acids (particularly positively charged) on the accessible surface area. In the present study, we investigated the roles of specific amino acid residues in the cold adaptedness of BglU. Mutagenesis assays showed that the mutations G261R and Q448P increased optimal temperature (from 25 to 40-45 °C) at the expense of low-temperature activity, but had no notable effects on maximal activity or heat lability. Mutations A368P, T383P, and A389E significantly increased optimal temperature (from 25 to 35-40 °C) and maximal activity (~1.5-fold relative to BglU). Thermostability of A368P and A389E increased slightly at 30 °C. Mutations K163P, N228P, and H301A greatly reduced enzymatic activity-almost completely in the case of H301A. Low contents of Pro, Arg, and Glu are important factors contributing to BglU's psychrophilic properties. Our findings will be useful in structure-based engineering of psychrophilic enzymes and in production of mutants suitable for a variety of industrial processes (e.g., food production, sewage treatment) at cold or moderate temperatures.

Isolation, characterization and heterologous expression of a novel chitosanase from Janthinobacterium sp. strain 4239

PubMed Central

2010-01-01

Background Chitosanases (EC 3.2.1.132) hydrolyze the polysaccharide chitosan, which is composed of partially acetylated β-(1,4)-linked glucosamine residues. In nature, chitosanases are produced by a number of Gram-positive and Gram-negative bacteria, as well as by fungi, probably with the primary role of degrading chitosan from fungal and yeast cell walls for carbon metabolism. Chitosanases may also be utilized in eukaryotic cell manipulation for intracellular delivery of molecules formulated with chitosan as well as for transformation of filamentous fungi by temporal modification of the cell wall structures. However, the chitosanases used so far in transformation and transfection experiments show optimal activity at high temperature, which is incompatible with most transfection and transformation protocols. Thus, there is a need for chitosanases, which display activity at lower temperatures. Results This paper describes the isolation of a chitosanase-producing, cold-active bacterium affiliated to the genus Janthinobacterium. The 876 bp chitosanase gene from the Janthinobacterium strain was isolated and characterized. The chitosanase was related to the Glycosyl Hydrolase family 46 chitosanases with Streptomyces chitosanase as the closest related (64% amino acid sequence identity). The chitosanase was expressed recombinantly as a periplasmic enzyme in Escherichia coli in amounts about 500 fold greater than in the native Janthinobacterium strain. Determination of temperature and pH optimum showed that the native and the recombinant chitosanase have maximal activity at pH 5-7 and at 45°C, but with 30-70% of the maximum activity at 10°C and 30°C, respectively. Conclusions A novel chitosanase enzyme and its corresponding gene was isolated from Janthinobacterium and produced recombinantly in E. coli as a periplasmic enzyme. The Janthinobacterium chitosanase displayed reasonable activity at 10°C to 30°C, temperatures that are preferred in transfection and transformation experiments. PMID:20096097

Detection and display of acoustic window for guiding and training cardiac ultrasound users

NASA Astrophysics Data System (ADS)

Huang, Sheng-Wen; Radulescu, Emil; Wang, Shougang; Thiele, Karl; Prater, David; Maxwell, Douglas; Rafter, Patrick; Dupuy, Clement; Drysdale, Jeremy; Erkamp, Ramon

2014-03-01

Successful ultrasound data collection strongly relies on the skills of the operator. Among different scans, echocardiography is especially challenging as the heart is surrounded by ribs and lung tissue. Less experienced users might acquire compromised images because of suboptimal hand-eye coordination and less awareness of artifacts. Clearly, there is a need for a tool that can guide and train less experienced users to position the probe optimally. We propose to help users with hand-eye coordination by displaying lines overlaid on B-mode images. The lines indicate the edges of blockages (e.g., ribs) and are updated in real time according to movement of the probe relative to the blockages. They provide information about how probe positioning can be improved. To distinguish between blockage and acoustic window, we use coherence, an indicator of channel data similarity after applying focusing delays. Specialized beamforming was developed to estimate coherence. Image processing is applied to coherence maps to detect unblocked beams and the angle of the lines for display. We built a demonstrator based on a Philips iE33 scanner, from which beamsummed RF data and video output are transferred to a workstation for processing. The detected lines are overlaid on B-mode images and fed back to the scanner display to provide users real-time guidance. Using such information in addition to B-mode images, users will be able to quickly find a suitable acoustic window for optimal image quality, and improve their skill.

Platinum and Palladium Overlayers Dramatically Enhance the Activity of Ruthenium Nanotubes for Alkaline Hydrogen Oxidation

DOE PAGES

St. John, Samuel; Atkinson, Robert W.; Unocic, Kinga A.; ...

2015-10-18

Templated vapor synthesis and thermal annealing were used to synthesize unsupported metallic Ru nanotubes with Pt or Pd overlayers. By controlling the elemental composition and thickness of these overlayers, we obtain nanostructures with very high alkaline hydrogen oxidation activity. For nanotubes with a nominal atomic composition of Ru 0.90Pt 0.10 display a surface-specific activity (2.4 mA/cm 2) that is 35 times greater than that of pure Ru nanotubes at a 50 mV overpotential and 2.5 times greater than that of pure Pt nanotubes (0.98 mA/cm 2). The surface-segregated structure also confers dramatically increased Pt utilization efficiency. We find a platinum-mass-specificmore » activity of 1240 A/gPt for the optimized nanotube versus 280 A/gPt for carbon-supported Pt nanoparticles and 109 A/gPt for monometallic Pt nanotubes. Here, we attribute the enhancement of both area- and platinum-mass-specific activity to the atomic-scale homeomorphism of the nanotube form factor with adlayer-modified polycrystals. Subsurface ligand and bifunctional effects previously observed on segregated, adlayer-modified polycrystals are translated to nanoscale catalysts.« less

Lattice Matched Carbide–Phosphide Composites with Superior Electrocatalytic Activity and Stability

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

Regmi, Yagya N.; Roy, Asa; King, Laurie A.

Composites of electrocatalytically active transition-metal compounds present an intriguing opportunity toward enhanced activity and stability. Here, to identify potentially scalable pairs of a catalytically active family of compounds, we demonstrate that phosphides of iron, nickel, and cobalt can be deposited on molybdenum carbide to generate nanocrystalline heterostructures. Composites synthesized via solvothermal decomposition of metal acetylacetonate salts in the presence of highly dispersed carbide nanoparticles show hydrogen evolution activities comparable to those of state-of-the-art non-noble metal catalysts. Investigation of the spent catalyst using high resolution microscopy and elemental analysis reveals that formation of carbide–phosphide composite prevents catalyst dissolution in acid electrolyte.more » Lattice mismatch between the two constituent electrocatalysts can be used to rationally improve electrochemical stability. Among the composites of iron, nickel, and cobalt phosphide, iron phosphide displays the lowest degree of lattice mismatch with molybdenum carbide and shows optimal electrochemical stability. Turnover rates of the composites are higher than that of the carbide substrate and compare favorably to other electrocatalysts based on earth-abundant elements. Lastly, our findings will inspire further investigation into composite nanocrystalline electrocatalysts that use molybdenum carbide as a stable catalyst support.« less

Lattice Matched Carbide–Phosphide Composites with Superior Electrocatalytic Activity and Stability

DOE PAGES

Regmi, Yagya N.; Roy, Asa; King, Laurie A.; ...

2017-10-19

Composites of electrocatalytically active transition-metal compounds present an intriguing opportunity toward enhanced activity and stability. Here, to identify potentially scalable pairs of a catalytically active family of compounds, we demonstrate that phosphides of iron, nickel, and cobalt can be deposited on molybdenum carbide to generate nanocrystalline heterostructures. Composites synthesized via solvothermal decomposition of metal acetylacetonate salts in the presence of highly dispersed carbide nanoparticles show hydrogen evolution activities comparable to those of state-of-the-art non-noble metal catalysts. Investigation of the spent catalyst using high resolution microscopy and elemental analysis reveals that formation of carbide–phosphide composite prevents catalyst dissolution in acid electrolyte.more » Lattice mismatch between the two constituent electrocatalysts can be used to rationally improve electrochemical stability. Among the composites of iron, nickel, and cobalt phosphide, iron phosphide displays the lowest degree of lattice mismatch with molybdenum carbide and shows optimal electrochemical stability. Turnover rates of the composites are higher than that of the carbide substrate and compare favorably to other electrocatalysts based on earth-abundant elements. Lastly, our findings will inspire further investigation into composite nanocrystalline electrocatalysts that use molybdenum carbide as a stable catalyst support.« less

Multivalent display of proteins on viral nanoparticles using molecular recognition and chemical ligation strategies

PubMed Central

Venter, P. Arno; Dirksen, Anouk; Thomas, Diane; Manchester, Marianne; Dawson, Philip E.; Schneemann, Anette

2011-01-01

Multivalent display of heterologous proteins on viral nanoparticles forms a basis for numerous applications in nanotechnology, including vaccine development, targeted therapeutic delivery and tissue-specific bio-imaging. In many instances, precise placement of proteins is required for optimal functioning of the supramolecular assemblies, but orientation- and site-specific coupling of proteins to viral scaffolds remains a significant technical challenge. We have developed two strategies that allow for controlled attachment of a variety of proteins on viral particles using covalent and noncovalent principles. In one strategy, an interaction between domain 4 of anthrax protective antigen and its receptor was used to display multiple copies of a target protein on virus-like particles. In the other, expressed protein ligation and aniline-catalyzed oximation was used to covalently display a model protein. The latter strategy, in particular, yielded nanoparticles that induced potent immune responses to the coupled protein, suggesting potential applications in vaccine development. PMID:21545187

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.

Real-time image reconstruction and display system for MRI using a high-speed personal computer.

PubMed

Haishi, T; Kose, K

1998-09-01

A real-time NMR image reconstruction and display system was developed using a high-speed personal computer and optimized for the 32-bit multitasking Microsoft Windows 95 operating system. The system was operated at various CPU clock frequencies by changing the motherboard clock frequency and the processor/bus frequency ratio. When the Pentium CPU was used at the 200 MHz clock frequency, the reconstruction time for one 128 x 128 pixel image was 48 ms and that for the image display on the enlarged 256 x 256 pixel window was about 8 ms. NMR imaging experiments were performed with three fast imaging sequences (FLASH, multishot EPI, and one-shot EPI) to demonstrate the ability of the real-time system. It was concluded that in most cases, high-speed PC would be the best choice for the image reconstruction and display system for real-time MRI. Copyright 1998 Academic Press.

Compressing Aviation Data in XML Format

NASA Technical Reports Server (NTRS)

Patel, Hemil; Lau, Derek; Kulkarni, Deepak

2003-01-01

Design, operations and maintenance activities in aviation involve analysis of variety of aviation data. This data is typically in disparate formats making it difficult to use with different software packages. Use of a self-describing and extensible standard called XML provides a solution to this interoperability problem. XML provides a standardized language for describing the contents of an information stream, performing the same kind of definitional role for Web content as a database schema performs for relational databases. XML data can be easily customized for display using Extensible Style Sheets (XSL). While self-describing nature of XML makes it easy to reuse, it also increases the size of data significantly. Therefore, transfemng a dataset in XML form can decrease throughput and increase data transfer time significantly. It also increases storage requirements significantly. A natural solution to the problem is to compress the data using suitable algorithm and transfer it in the compressed form. We found that XML-specific compressors such as Xmill and XMLPPM generally outperform traditional compressors. However, optimal use of Xmill requires of discovery of optimal options to use while running Xmill. This, in turn, depends on the nature of data used. Manual disc0ver.y of optimal setting can require an engineer to experiment for weeks. We have devised an XML compression advisory tool that can analyze sample data files and recommend what compression tool would work the best for this data and what are the optimal settings to be used with a XML compression tool.

Demonstration of high current carbon nanotube enabled vertical organic field effect transistors at industrially relevant voltages

NASA Astrophysics Data System (ADS)

McCarthy, Mitchell

The display market is presently dominated by the active matrix liquid crystal display (LCD). However, the active matrix organic light emitting diode (AMOLED) display is argued to become the successor to the LCD, and is already beginning its way into the market, mainly in small size displays. But, for AMOLED technology to become comparable in market share to LCD, larger size displays must become available at a competitive price with their LCD counterparts. A major issue preventing low-cost large AMOLED displays is the thin-film transistor (TFT) technology. Unlike the voltage driven LCD, the OLEDs in the AMOLED display are current driven. Because of this, the mature amorphous silicon TFT backplane technology used in the LCD must be upgraded to a material possessing a higher mobility. Polycrystalline silicon and transparent oxide TFT technologies are being considered to fill this need. But these technologies bring with them significant manufacturing complexity and cost concerns. Carbon nanotube enabled vertical organic field effect transistors (CN-VFETs) offer a unique solution to this problem (now known as the AMOLED backplane problem). The CN-VFET allows the use of organic semiconductors to be used for the semiconductor layer. Organics are known for their low-cost large area processing compatibility. Although the mobility of the best organics is only comparable to that of amorphous silicon, the CN-VFET makes up for this by orienting the channel vertically, as opposed to horizontally (like in conventional TFTs). This allows the CN-VFET to achieve sub-micron channel lengths without expensive high resolution patterning. Additionally, because the CN-VFET can be easily converted into a light emitting transistor (called the carbon nanotube enabled vertical organic light emitting transistor---CN-VOLET) by essentially stacking an OLED on top of the CN-VFET, more potential benefits can be realized. These potential benefits include, increased aperture ratio, increased OLED lifetime and the potential for an all transparent display. And because carbon nanotubes (CNTs) and organics are used, CN-VFET and CN-VOLET devices are compatible with flexible displays. This dissertation describes the first ever demonstration of CN-VFETs and CN-VOLETs and relates their performance to the specific properties of the CNTs and the new device architecture. In the work that followed, the CN-VFET was systematically optimized overcoming the problems revealed in the demonstration devices. The large undesired hysteresis was decreased by 96%, the on/off ratio was improved three orders of magnitude and the operating voltages were reduced to state of the art values. Additionally, the current output per device area of the CN-VFET was demonstrated to be greater than any other low resolution patterned organic transistor by a factor of 3.9. Moreover, it was demonstrated that the CNTs induce a reorientation of the high mobility plane in small molecule organics like pentacene to coincide with the vertical direction, giving additional explanation for the large currents observed in the CN-VFET. The ability to drive high currents and potentially inexpensive fabrication may provide the solution for the AMOLED backplane problem.

Rosetta:MSF: a modular framework for multi-state computational protein design.

PubMed

Löffler, Patrick; Schmitz, Samuel; Hupfeld, Enrico; Sterner, Reinhard; Merkl, Rainer

2017-06-01

Computational protein design (CPD) is a powerful technique to engineer existing proteins or to design novel ones that display desired properties. Rosetta is a software suite including algorithms for computational modeling and analysis of protein structures and offers many elaborate protocols created to solve highly specific tasks of protein engineering. Most of Rosetta's protocols optimize sequences based on a single conformation (i. e. design state). However, challenging CPD objectives like multi-specificity design or the concurrent consideration of positive and negative design goals demand the simultaneous assessment of multiple states. This is why we have developed the multi-state framework MSF that facilitates the implementation of Rosetta's single-state protocols in a multi-state environment and made available two frequently used protocols. Utilizing MSF, we demonstrated for one of these protocols that multi-state design yields a 15% higher performance than single-state design on a ligand-binding benchmark consisting of structural conformations. With this protocol, we designed de novo nine retro-aldolases on a conformational ensemble deduced from a (βα)8-barrel protein. All variants displayed measurable catalytic activity, testifying to a high success rate for this concept of multi-state enzyme design.

Rosetta:MSF: a modular framework for multi-state computational protein design

PubMed Central

Hupfeld, Enrico; Sterner, Reinhard

2017-01-01

Computational protein design (CPD) is a powerful technique to engineer existing proteins or to design novel ones that display desired properties. Rosetta is a software suite including algorithms for computational modeling and analysis of protein structures and offers many elaborate protocols created to solve highly specific tasks of protein engineering. Most of Rosetta’s protocols optimize sequences based on a single conformation (i. e. design state). However, challenging CPD objectives like multi-specificity design or the concurrent consideration of positive and negative design goals demand the simultaneous assessment of multiple states. This is why we have developed the multi-state framework MSF that facilitates the implementation of Rosetta’s single-state protocols in a multi-state environment and made available two frequently used protocols. Utilizing MSF, we demonstrated for one of these protocols that multi-state design yields a 15% higher performance than single-state design on a ligand-binding benchmark consisting of structural conformations. With this protocol, we designed de novo nine retro-aldolases on a conformational ensemble deduced from a (βα)8-barrel protein. All variants displayed measurable catalytic activity, testifying to a high success rate for this concept of multi-state enzyme design. PMID:28604768

Efficient Color-Stable Inverted White Organic Light-Emitting Diodes with Outcoupling-Enhanced ZnO Layer.

PubMed

Zhao, Xin-Dong; Li, Yan-Qing; Xiang, Heng-Yang; Zhang, Yi-Bo; Chen, Jing-De; Xu, Lu-Hai; Tang, Jian-Xin

2017-01-25

Inverted organic light-emitting diode (OLED) has attracted extensive attention due to the demand in active-matrix OLED display panels as its geometry enables the direct connection with n-channel transistor backplane on the substrate. One key challenge of high-performance inverted OLED is an efficient electron-injection layer with superior electrical and optical properties to match the indium tin oxide cathode on substrate. We here propose a synergistic electron-injection architecture using surface modification of ZnO layer to simultaneously promote electron injection into organic emitter and enhance out-coupling of waveguided light. An efficient inverted white OLED is realized by introducing the nanoimprinted aperiodic nanostructure of ZnO for broadband and angle-independent light out-coupling and inserting an n-type doped interlayer for energy level tuning and injection barrier lowering. As a result, the optimized inverted white OLEDs have an external quantum efficiency of 42.4% and a power efficiency of 85.4 lm W 1- , which are accompanied by the superiority of angular color stability over the visible wavelength range. Our results may inspire a promising approach to fabricate high-efficiency inverted OLEDs for large-scale display panels.

Vegetation engineers marsh morphology through multiple competing stable states

NASA Astrophysics Data System (ADS)

Marani, Marco; Da Lio, Cristina; D'Alpaos, Andrea

2013-02-01

Marshes display impressive biogeomorphic features, such as zonation, a mosaic of extensive vegetation patches of rather uniform composition, exhibiting sharp transitions in the presence of extremely small topographic gradients. Although generally associated with the accretion processes necessary for marshes to keep up with relative sea level rise, competing environmental constraints, and ecologic controls, zonation is still poorly understood in terms of the underlying biogeomorphic mechanisms. Here we find, through observations and modeling interpretation, that zonation is the result of coupled geomorphological-biological dynamics and that it stems from the ability of vegetation to actively engineer the landscape by tuning soil elevation within preferential ranges of optimal adaptation. We find multiple peaks in the frequency distribution of observed topographic elevation and identify them as the signature of biologic controls on geomorphodynamics through competing stable states modulated by the interplay of inorganic and organic deposition. Interestingly, the stable biogeomorphic equilibria correspond to suboptimal rates of biomass production, a result coherent with recent observations. The emerging biogeomorphic structures may display varying degrees of robustness to changes in the rate of sea level rise and sediment availability, with implications for the overall resilience of marsh ecosystems to climatic changes.

Vegetation engineers marsh morphology through multiple competing stable states

PubMed Central

Marani, Marco; Da Lio, Cristina; D’Alpaos, Andrea

2013-01-01

Marshes display impressive biogeomorphic features, such as zonation, a mosaic of extensive vegetation patches of rather uniform composition, exhibiting sharp transitions in the presence of extremely small topographic gradients. Although generally associated with the accretion processes necessary for marshes to keep up with relative sea level rise, competing environmental constraints, and ecologic controls, zonation is still poorly understood in terms of the underlying biogeomorphic mechanisms. Here we find, through observations and modeling interpretation, that zonation is the result of coupled geomorphological–biological dynamics and that it stems from the ability of vegetation to actively engineer the landscape by tuning soil elevation within preferential ranges of optimal adaptation. We find multiple peaks in the frequency distribution of observed topographic elevation and identify them as the signature of biologic controls on geomorphodynamics through competing stable states modulated by the interplay of inorganic and organic deposition. Interestingly, the stable biogeomorphic equilibria correspond to suboptimal rates of biomass production, a result coherent with recent observations. The emerging biogeomorphic structures may display varying degrees of robustness to changes in the rate of sea level rise and sediment availability, with implications for the overall resilience of marsh ecosystems to climatic changes. PMID:23401529

Projection type transparent 3D display using active screen

NASA Astrophysics Data System (ADS)

Kamoshita, Hiroki; Yendo, Tomohiro

2015-05-01

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

3-D surface reconstruction of patient specific anatomic data using a pre-specified number of polygons.

PubMed

Aharon, S; Robb, R A

1997-01-01

Virtual reality environments provide highly interactive, natural control of the visualization process, significantly enhancing the scientific value of the data produced by medical imaging systems. Due to the computational and real time display update requirements of virtual reality interfaces, however, the complexity of organ and tissue surfaces which can be displayed is limited. In this paper, we present a new algorithm for the production of a polygonal surface containing a pre-specified number of polygons from patient or subject specific volumetric image data. The advantage of this new algorithm is that it effectively tiles complex structures with a specified number of polygons selected to optimize the trade-off between surface detail and real-time display rates.

Predicting Visual Consciousness Electrophysiologically from Intermittent Binocular Rivalry

PubMed Central

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

2013-01-01

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

Effects of fulvic acid on growth performance and intestinal health of juvenile loach Paramisgurnus dabryanus (Sauvage).

PubMed

Gao, Yang; He, Jie; He, Zhuliu; Li, Zhiwei; Zhao, Bo; Mu, Yi; Lee, Jeong-Yeol; Chu, Zhangjie

2017-03-01

A 60-day feeding trial was conducted to determine the effect of dietary fulvic acid supplements on intestinal digestive activity (enzymatic analysis), antioxidant activity, immune enzyme activity and microflora composition of juvenile loach (initial weight of 6.2 ± 0.1 g) reared in experimental aquaria. Five test diets containing 0, 0.5, 1.0, 1.5, and 2% fulvic acid were randomly assigned to three aquaria, respectively. Elevated growth performance including final weight, weight gain (WG), specific growth rate (SGR) and feed conversion ratio (FCR) was observed in loaches that were fed fulvic acid. Maximal weight gain rates and specific growth rates occurred at the 1.5% additive level. The optimal dietary fulvic requirement for maximal growth of juvenile loach is 16.4 g per kg of the diet based on the quadratic regression analysis of specific growth rate against dietary fulvic acid levels. Furthermore, intestinal protease activity, antioxidant activity, lysozyme activity (LZM), complement 3 (C3) content, immunoglobulin M (IgM) content, acid phosphatase activity (ACP) and alkaline phosphatase activity (AKP) were significantly elevated with concomitant increasing levels of dietary fulvic acid. Following a deep sequencing analysis, a total of 42,058 valid reads and 609 OTUs (operational taxonomic units) obtained from the control group and the group displaying the most optimal growth rate were analyzed. Fulvic acid supplementation resulted in an abundance of Firmicute and Actinobacteria sequences, with a concomitant reduction in the abundance of Proteobacteria. Results indicated that fulvic acid supplementation resulted in a reduction in the relative abundance of Serratia, Acinetobacter, Aeromonas and Edwardsiella, and a relative increase in the abundance of Lactobacillus in the intestine. In conclusion, these results suggest that fulvic acid improves growth performance and intestinal health condition of loach, indicates that fulvic acid could be used as an immunoenhancer in loach culture. Copyright © 2017. Published by Elsevier Ltd.

Age differences in optimism bias are mediated by reliance on intuition and religiosity.

PubMed

Klaczynski, Paul A

2017-11-01

The relationships among age, optimism bias, religiosity, creationist beliefs, and reliance on intuition were examined in a sample of 211 high school students (M age =16.54years). Optimism bias was defined as the difference between predictions for positive and negative live events (e.g., divorce) for the self and age peers. Results indicated that older adolescents displayed less optimism bias, were less religious, believed less in creationism, and relied on intuition less than younger adolescents. Furthermore, the association between age and optimism bias was mediated by religiosity and reliance on intuition but not by creationist beliefs. These findings are considered from a dual-process theoretic perspective that emphasizes age increases in metacognitive abilities and epistemological beliefs and age declines in impulsive judgments. Research directed toward examining alternative explanations of the association among religiosity, age, and optimism bias is recommended. Copyright © 2017 Elsevier Inc. All rights reserved.

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

PubMed

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

2008-04-01

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

Recent patents on electrophoretic displays and materials.

PubMed

Christophersen, Marc; Phlips, Bernard F

2010-11-01

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

Quantitative Analysis of Color Differences within High Contrast, Low Power Reversible Electrophoretic Displays

DOE PAGES

Giera, Brian; Bukosky, Scott; Lee, Elaine; ...

2018-01-23

Here, quantitative color analysis is performed on videos of high contrast, low power reversible electrophoretic deposition (EPD)-based displays operated under different applied voltages. This analysis is coded in an open-source software, relies on a color differentiation metric, ΔE * 00, derived from digital video, and provides an intuitive relationship between the operating conditions of the devices and their performance. Time-dependent ΔE * 00 color analysis reveals color relaxation behavior, recoverability for different voltage sequences, and operating conditions that can lead to optimal performance.

Quantitative Analysis of Color Differences within High Contrast, Low Power Reversible Electrophoretic Displays

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

Giera, Brian; Bukosky, Scott; Lee, Elaine

Here, quantitative color analysis is performed on videos of high contrast, low power reversible electrophoretic deposition (EPD)-based displays operated under different applied voltages. This analysis is coded in an open-source software, relies on a color differentiation metric, ΔE * 00, derived from digital video, and provides an intuitive relationship between the operating conditions of the devices and their performance. Time-dependent ΔE * 00 color analysis reveals color relaxation behavior, recoverability for different voltage sequences, and operating conditions that can lead to optimal performance.

Optical design and testing: introduction.

PubMed

Liang, Chao-Wen; Koshel, John; Sasian, Jose; Breault, Robert; Wang, Yongtian; Fang, Yi Chin

2014-10-10

Optical design and testing has numerous applications in industrial, military, consumer, and medical settings. Assembling a complete imaging or nonimage optical system may require the integration of optics, mechatronics, lighting technology, optimization, ray tracing, aberration analysis, image processing, tolerance compensation, and display rendering. This issue features original research ranging from the optical design of image and nonimage optical stimuli for human perception, optics applications, bio-optics applications, 3D display, solar energy system, opto-mechatronics to novel imaging or nonimage modalities in visible and infrared spectral imaging, modulation transfer function measurement, and innovative interferometry.

Examination of optimal upgrade timing and best value: DoD acquisition of commercial vs. military custom flat panel displays

NASA Astrophysics Data System (ADS)

Lippitz, Michael J.

1999-08-01

This paper proposes a framework for quantitatively balancing the costs, benefits, and risks of alternate upgrade strategies, with Department of Defense (DoD) acquisition of flat panel display as an example. A key issue in DoD Acquisition Reform is the rapid product turnover in commercial markets and the difficulties DoD has traditionally faced in adopting these advances in a timely manner. This paper aims to clarify when commercial technology represents 'best value' to DoD.

The Development and Evaluation of Color Systems for Airborne Applications: Fundamental Visual, Perceptual, and Display Systems Considerations.

DTIC Science & Technology

1986-02-01

Ellipses Derived from Both MacAdam’s Empirically Derived Color Matching Standard Deviation and Stiles’ Line Element Predictions 28 2.1.1.2-9 CIELUV Color...Coordinates 141 2.2.2-3 Derivation of CIE (L*, U*, V*) Coordinates 145 2.2.2-4 Three-Dimensional Representation of CIELUV Colcr Difference Estimates...145 2.2.2-5 Application of CIELUV for Estimating Color Difference on an Electronic Color Display 146 2.2.2-6 Color Performance Envelopes and Optimized

Antibody Fab display and selection through fusion to the pIX coat protein of filamentous phage.

PubMed

Tornetta, Mark; Baker, Scott; Whitaker, Brian; Lu, Jin; Chen, Qiang; Pisors, Eileen; Shi, Lei; Luo, Jinquan; Sweet, Raymond; Tsui, Ping

2010-08-31

Fab antibody display on filamentous phage is widely applied to de novo antibody discovery and engineering. Here we describe a phagemid system for the efficient display and affinity selection of Fabs through linkage to the minor coat protein pIX. Display was successful by fusion of either Fd or Lc through a short linker to the amino terminus of pIX and co-expression of the counter Lc or Fd as a secreted, soluble fragment. Assembly of functional Fab was confirmed by demonstration of antigen-specific binding using antibodies of known specificity. Phage displaying a Fab specific for RSV-F protein with Fd linked to pIX showed efficient, antigen-specific enrichment when mixed with phage displaying a different specificity. The functionality of this system for antibody engineering was evaluated in an optimization study. A RSV-F protein specific antibody with an affinity of about 2nM was randomized at 4 positions in light chain CDR1. Three rounds of selection with decreasing antigen concentration yielded Fabs with an affinity improvement up to 70-fold and showed a general correlation between enrichment frequency and affinity. We conclude that the pIX coat protein complements other display systems in filamentous phage as an efficient vehicle for low copy display and selection of Fab proteins. 2010 Elsevier B.V. All rights reserved.

Diffraction effects incorporated design of a parallax barrier for a high-density multi-view autostereoscopic 3D display.

PubMed

Yoon, Ki-Hyuk; Ju, Heongkyu; Kwon, Hyunkyung; Park, Inkyu; Kim, Sung-Kyu

2016-02-22

We present optical characteristics of view image provided by a high-density multi-view autostereoscopic 3D display (HD-MVA3D) with a parallax barrier (PB). Diffraction effects that become of great importance in such a display system that uses a PB, are considered in an one-dimensional model of the 3D display, in which the numerical simulation of light from display panel pixels through PB slits to viewing zone is performed. The simulation results are then compared to the corresponding experimental measurements with discussion. We demonstrate that, as a main parameter for view image quality evaluation, the Fresnel number can be used to determine the PB slit aperture for the best performance of the display system. It is revealed that a set of the display parameters, which gives the Fresnel number of ∼ 0.7 offers maximized brightness of the view images while that corresponding to the Fresnel number of 0.4 ∼ 0.5 offers minimized image crosstalk. The compromise between the brightness and crosstalk enables optimization of the relative magnitude of the brightness to the crosstalk and lead to the choice of display parameter set for the HD-MVA3D with a PB, which satisfies the condition where the Fresnel number lies between 0.4 and 0.7.

See-through 3D technology for augmented reality

NASA Astrophysics Data System (ADS)

Lee, Byoungho; Lee, Seungjae; Li, Gang; Jang, Changwon; Hong, Jong-Young

2017-06-01

Augmented reality is recently attracting a lot of attention as one of the most spotlighted next-generation technologies. In order to get toward realization of ideal augmented reality, we need to integrate 3D virtual information into real world. This integration should not be noticed by users blurring the boundary between the virtual and real worlds. Thus, ultimate device for augmented reality can reconstruct and superimpose 3D virtual information on the real world so that they are not distinguishable, which is referred to as see-through 3D technology. Here, we introduce our previous researches to combine see-through displays and 3D technologies using emerging optical combiners: holographic optical elements and index matched optical elements. Holographic optical elements are volume gratings that have angular and wavelength selectivity. Index matched optical elements are partially reflective elements using a compensation element for index matching. Using these optical combiners, we could implement see-through 3D displays based on typical methodologies including integral imaging, digital holographic displays, multi-layer displays, and retinal projection. Some of these methods are expected to be optimized and customized for head-mounted or wearable displays. We conclude with demonstration and analysis of fundamental researches for head-mounted see-through 3D displays.

Response Surface Methodology Modelling of an Aqueous Two-Phase System for Purification of Protease from Penicillium candidum (PCA 1/TT031) under Solid State Fermentation and Its Biochemical Characterization.

PubMed

Alhelli, Amaal M; Abdul Manap, Mohd Yazid; Mohammed, Abdulkarim Sabo; Mirhosseini, Hamed; Suliman, Eilaf; Shad, Zahra; Mohammed, Nameer Khairulla; Meor Hussin, Anis Shobirin

2016-11-11

Penicillium candidum (PCA 1/TT031) synthesizes different types of extracellular proteases. The objective of this study is to optimize polyethylene glycol (PEG)/citrate based on an aqueous two-phase system (ATPS) and Response Surface Methodology (RSM) to purify protease from Penicillium candidum (PCA 1/TT031). The effects of different PEG molecular weights (1500-10,000 g/mol), PEG concentration (9%-20%), concentrations of NaCl (0%-10%) and the citrate buffer (8%-16%) on protease were also studied. The best protease purification could be achieved under the conditions of 9.0% ( w / w ) PEG 8000, 5.2% NaCl, and 15.9% sodium citrate concentration, which resulted in a one-sided protease partitioning for the bottom phase with a partition coefficient of 0.2, a 6.8-fold protease purification factor, and a yield of 93%. The response surface models displayed a significant ( p ≤ 0.05) response which was fit for the variables that were studied as well as a high coefficient of determination (R²). Similarly, the predicted and observed values displayed no significant ( p > 0.05) differences. In addition, our enzyme characterization study revealed that Penicillium candidum (PCA 1/TT031) produced a slight neutral protease with a molecular weight between 100 and 140 kDa. The optimal activity of the purified enzyme occurred at a pH of 6.0 and at a temperature of 50 ° C. The stability between different pH and temperature ranges along with the effect of chemical metal ions and inhibitors were also studied. Our results reveal that the purified enzyme could be used in the dairy industry such as in accelerated cheese ripening.

Response Surface Methodology Modelling of an Aqueous Two-Phase System for Purification of Protease from Penicillium candidum (PCA 1/TT031) under Solid State Fermentation and Its Biochemical Characterization

PubMed Central

Alhelli, Amaal M.; Abdul Manap, Mohd Yazid; Mohammed, Abdulkarim Sabo; Mirhosseini, Hamed; Suliman, Eilaf; Shad, Zahra; Mohammed, Nameer Khairulla; Meor Hussin, Anis Shobirin

2016-01-01

Penicillium candidum (PCA 1/TT031) synthesizes different types of extracellular proteases. The objective of this study is to optimize polyethylene glycol (PEG)/citrate based on an aqueous two-phase system (ATPS) and Response Surface Methodology (RSM) to purify protease from Penicillium candidum (PCA 1/TT031). The effects of different PEG molecular weights (1500–10,000 g/mol), PEG concentration (9%–20%), concentrations of NaCl (0%–10%) and the citrate buffer (8%–16%) on protease were also studied. The best protease purification could be achieved under the conditions of 9.0% (w/w) PEG 8000, 5.2% NaCl, and 15.9% sodium citrate concentration, which resulted in a one-sided protease partitioning for the bottom phase with a partition coefficient of 0.2, a 6.8-fold protease purification factor, and a yield of 93%. The response surface models displayed a significant (p ≤ 0.05) response which was fit for the variables that were studied as well as a high coefficient of determination (R2). Similarly, the predicted and observed values displayed no significant (p > 0.05) differences. In addition, our enzyme characterization study revealed that Penicillium candidum (PCA 1/TT031) produced a slight neutral protease with a molecular weight between 100 and 140 kDa. The optimal activity of the purified enzyme occurred at a pH of 6.0 and at a temperature of 50 °C. The stability between different pH and temperature ranges along with the effect of chemical metal ions and inhibitors were also studied. Our results reveal that the purified enzyme could be used in the dairy industry such as in accelerated cheese ripening. PMID:27845736

Bimetallic Platinum-Rhodium Alloy Nanodendrites as Highly Active Electrocatalyst for the Ethanol Oxidation Reaction.

PubMed

Bai, Juan; Xiao, Xue; Xue, Yuan-Yuan; Jiang, Jia-Xing; Zeng, Jing-Hui; Li, Xi-Fei; Chen, Yu

2018-06-13

Rationally designing and manipulating composition and morphology of precious metal-based bimetallic nanostructures can markedly enhance their electrocatalytic performance, including selectivity, activity, and durability. We herein report the synthesis of bimetallic PtRh alloy nanodendrites (ANDs) with tunable composition by a facile complex-reduction synthetic method under hydrothermal conditions. The structural/morphologic features, formation mechanism, and electrocatalytic performance of PtRh ANDs are investigated thoroughly by various physical characterization and electrochemical methods. The preformed Rh crystal nuclei effectively catalyze the reduction of Pt 2+ precursor, resulting in PtRh alloy generation due to the catalytic growth and atoms interdiffusion process. The Pt atoms deposition distinctly interferes in Rh atoms deposition on Rh crystal nuclei, resulting in dendritic morphology of PtRh ANDs. For the ethanol oxidation reaction (EOR), PtRh ANDs display the chemical composition and solution pH co-dependent electrocatalytic activity. Because of the alloy effect and particular morphologic feature, Pt 1 Rh 1 ANDs with optimized composition exhibit better reactivity and stability for the EOR than commercial Pt nanocrystals electrocatalyst.

A Bottom-Up Proteomic Approach to Identify Substrate Specificity of Outer-Membrane Protease OmpT.

PubMed

Wood, Sarah E; Sinsinbar, Gaurav; Gudlur, Sushanth; Nallani, Madhavan; Huang, Che-Fan; Liedberg, Bo; Mrksich, Milan

2017-12-22

Identifying peptide substrates that are efficiently cleaved by proteases gives insights into substrate recognition and specificity, guides development of inhibitors, and improves assay sensitivity. Peptide arrays and SAMDI mass spectrometry were used to identify a tetrapeptide substrate exhibiting high activity for the bacterial outer-membrane protease (OmpT). Analysis of protease activity for the preferred residues at the cleavage site (P1, P1') and nearest-neighbor positions (P2, P2') and their positional interdependence revealed FRRV as the optimal peptide with the highest OmpT activity. Substituting FRRV into a fragment of LL37, a natural substrate of OmpT, led to a greater than 400-fold improvement in OmpT catalytic efficiency, with a k cat /K m value of 6.1×10 6  L mol -1  s -1 . Wild-type and mutant OmpT displayed significant differences in their substrate specificities, demonstrating that even modest mutants may not be suitable substitutes for the native enzyme. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Cloning and expression of the Aspergillus oryzae glucan 1,3-beta-glucosidase A (exgA) in Pichia pastoris.

PubMed

Boonvitthya, Nassapat; Tanapong, Phatrapan; Kanngan, Patcharaporn; Burapatana, Vorakan; Chulalaksananukul, Warawut

2012-10-01

The glucan 1,3-beta-glucosidase A gene (exgA) from Aspergillus oryzae and fused to the Saccharomyces cerevisiae signal peptide (α-factor) was expressed under the control of either a constitutive (GAP) or an inducible (AOX1) promoter in Pichia pastoris. A 1.4-fold higher extracellular enzyme activity (2 U/ml) was obtained using the AOX1 inducible expression system than with the GAP constitutive promoter (1.4 U/ml). The purified recombinant ExgA enzyme, with a yield of 10 mg protein/l culture supernatant, was about 40 kDa by SDS-PAGE analysis with a specific activity of 289 U/mg protein. The enzyme was optimally active at 35 °C and pH 5.0 and displayed a K(M) and V(max) of 0.56 mM and 10,042 μmol/(min mg protein), respectively, with p-nitrophenyl-β-D-glucopyranoside as the substrate. Moreover, it was tolerant to glucose inhibition with a K(i) of 365 mM.

Morphology induced photo-degradation study of low temperature, chemically derived ZnO/SnO{sub 2} heterostructure

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

Pal, Shreyasi, E-mail: Shreyasi.tua@gamil.com; Maiti, Soumen; Chattopadhyay, Kalyan Kumar, E-mail: kalyan-chattopadhyay@yahoo.com

2016-05-06

Rational construction of heterostructure is a key pathway to pursue highly active photocatalysts that also offers prospects to explore the relationship between structural aspect and photocatalytic efficiency. Here, we adopted a two-step wet chemical protocol for decoration of ZnO nanowires with SnO{sub 2} nanoclusters. ZnO nanowires were prepared by one pot ambient conditioned synthesis from commercial zinc powder. In sequence, synthesized ZnO nanowires were engineered with varying quantity SnO{sub 2} nanoclusters via low temperature hydrothermal method. Environmental remediation through catalytic activity of the samples was inspected taking two dyes having different ionic character (Methyl Orange and Rhodamine B) under UVmore » irradiation where the optimized hybrid displayed better performance than mono component oxides. Enhancement in catalytic performance could be enlightened by the heterostructure formation at the ZnO/SnO{sub 2} interface which in turns prolonged photogenerated carrier separation and extend the photo response range. Furthermore, the photocatalysis performance by heterostructure could be recycled for several times without noticeable decrease in their catalytic activity.« less

Characterization of oil-palm trunk residue degradation enzymes derived from the isolated fungus, Penicillium rolfsii c3-2(1) IBRL.

PubMed

Lee, Kok Chang; Arai, Takamitsu; Ibrahim, Darah; Deng, Lan; Murata, Yoshinori; Mori, Yutaka; Kosugi, Akihiko

2016-01-01

This study characterizes crude enzymes derived from Penicillium rolfsii c3-2(1) IBRL, a mesophilic fungus isolated from the local soil of Malaysia. Prior to enzyme activity evaluation, P. rolfsii c3-2(1) IBRL was inoculated into a broth medium containing oil-palm trunk residues for the preparation of crude enzymes. Oil-palm trunk residues were optimally hydrolysed at pH5.0 and 50°C. P. rolfsii c3-2(1) IBRL-derived crude enzymes displayed higher thermal stability compared with the commercial enzymes, Celluclast 1.5 L and Acellerase 1500. Moreover, the hydrolysing activities of the P. rolfsii c3-2(1) IBRL-derived crude enzymes (xylan, arabinan, and laminarin) were superior compared to that of Celluclast 1.5 L and Acellerase 1500, and exhibit 2- to 3-fold and 3- to 4-fold higher oil-palm trunk residues-hydrolysing specific activity, respectively. This higher hydrolysis efficiency may be attributed to the weak 'lignin-binding' ability of the P. rolfsii c3-2(1) IBRL-derived enzymes compared to the commercial enzymes.

Structure-Based Design and Optimization of Multitarget-Directed 2H-Chromen-2-one Derivatives as Potent Inhibitors of Monoamine Oxidase B and Cholinesterases.

PubMed

Farina, Roberta; Pisani, Leonardo; Catto, Marco; Nicolotti, Orazio; Gadaleta, Domenico; Denora, Nunzio; Soto-Otero, Ramon; Mendez-Alvarez, Estefania; Passos, Carolina S; Muncipinto, Giovanni; Altomare, Cosimo D; Nurisso, Alessandra; Carrupt, Pierre-Alain; Carotti, Angelo

2015-07-23

The multifactorial nature of Alzheimer's disease calls for the development of multitarget agents addressing key pathogenic processes. To this end, by following a docking-assisted hybridization strategy, a number of aminocoumarins were designed, prepared, and tested as monoamine oxidases (MAOs) and acetyl- and butyryl-cholinesterase (AChE and BChE) inhibitors. Highly flexible N-benzyl-N-alkyloxy coumarins 2-12 showed good inhibitory activities at MAO-B, AChE, and BChE but low selectivity. More rigid inhibitors, bearing meta- and para-xylyl linkers, displayed good inhibitory activities and high MAO-B selectivity. Compounds 21, 24, 37, and 39, the last two featuring an improved hydrophilic/lipophilic balance, exhibited excellent activity profiles with nanomolar inhibitory potency toward hMAO-B, high hMAO-B over hMAO-A selectivity and submicromolar potency at hAChE. Cell-based assays of BBB permeation, neurotoxicity, and neuroprotection supported the potential of compound 37 as a BBB-permeant neuroprotective agent against H2O2-induced oxidative stress with poor interaction as P-gp substrate and very low cytotoxicity.

Beyond Helper Phage: Using "Helper Cells" to Select Peptide Affinity Ligands.

PubMed

Phipps, M Lisa; Lillo, Antoinetta M; Shou, Yulin; Schmidt, Emily N; Paavola, Chad D; Naranjo, Leslie; Bemdich, Sara; Swanson, Basil I; Bradbury, Andrew R M; Martinez, Jennifer S

2016-01-01

Peptides are important affinity ligands for microscopy, biosensing, and targeted delivery. However, because they can have low affinity for their targets, their selection from large naïve libraries can be challenging. When selecting peptidic ligands from display libraries, it is important to: 1) ensure efficient display; 2) maximize the ability to select high affinity ligands; and 3) minimize the effect of the display context on binding. The "helper cell" packaging system has been described as a tool to produce filamentous phage particles based on phagemid constructs with varying display levels, while remaining free of helper phage contamination. Here we report on the first use of this system for peptide display, including the systematic characterization and optimization of helper cells, their inefficient use in antibody display and their use in creating and selecting from a set of phage display peptide libraries. Our libraries were analyzed with unprecedented precision by standard or deep sequencing, and shown to be superior in quality than commercial gold standards. Using our helper cell libraries, we have obtained ligands recognizing Yersinia pestis surface antigen F1V and L-glutamine-binding periplasmic protein QBP. In the latter case, unlike any of the peptide library selections described so far, we used a combination of phage and yeast display to select intriguing peptide ligands. Based on the success of our selections we believe that peptide libraries obtained with helper cells are not only suitable, but preferable to traditional phage display libraries for selection of peptidic ligands.

Selection and maturation of antibodies by phage display through fusion to pIX.

PubMed

Tornetta, Mark; Reddy, Ramachandra; Wheeler, John C

2012-09-01

Antibody discovery and optimization by M13 phage display have evolved significantly over the past twenty years. Multiple methods of antibody display and selection have been developed - direct display on pIII or indirect display through a Cysteine disulfide linkage or a coiled-coil adapter protein. Here we describe display of Fab libraries on the smaller pIX protein at the opposite end of the virion and its application to discovery of novel antibodies from naive libraries. Antibody selection based on pIX-mediated display produces results comparable to other in vitro methods and uses an efficient direct infection of antigen-bound phages, eliminating any chemical dissociation step(s). Additionally, some evidence suggests that pIX-mediated display can be more efficient than pIII-mediated display in affinity selections. Functional assessment of phage-derived antibodies can be hindered by insufficient affinities or lack of epitopic diversity. Here we describe an approach to managing primary hits from our Fab phage libraries into epitope bins and subsequent high-throughput maturation of clones to isolate epitope- and sequence-diverse panels of high affinity binders. Use of the Octet biosensor was done to examine Fab binding in a facile label-free method and determine epitope competition groups. A receptor extracellular domain and chemokine were subjected to this method of binning and affinity maturation. Parental clones demonstrated improvement in affinity from 1-100nM to 10-500pM. Copyright © 2012 Elsevier Inc. All rights reserved.

Optimization of the polyplanar optical display electronics for a monochrome B-52 display

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

DeSanto, L.

The Polyplanar Optical Display (POD) is a unique display screen which can be used with any projection source. The prototype ten-inch display is two inches thick and has a matte black face which allows for high contrast images. The prototype being developed is a form, fit and functional replacement display for the B-52 aircraft which uses a monochrome ten-inch display. In order to achieve a long lifetime, the new display uses a new 200 mW green solid-state laser (10,000 hr. life) at 532 nm as its light source. To produce real-time video, the laser light is being modulated by amore » Digital Light Processing (DLP{trademark}) chip manufactured by Texas Instruments (TI). In order to use the solid-state laser as the light source and also fit within the constraints of the B-52 display, the Digital Micromirror Device (DMD{trademark}) chip is operated remotely from the Texas Instruments circuit board. In order to achieve increased brightness a monochrome digitizing interface was investigated. The operation of the DMD{trademark} divorced from the light engine and the interfacing of the DMD{trademark} board with the RS-170 video format specific to the B-52 aircraft will be discussed, including the increased brightness of the monochrome digitizing interface. A brief description of the electronics required to drive the new 200 mW laser is also presented.« less

Functional expression, production, and biochemical characterization of a laccase using yeast surface display technology.

PubMed

Bertrand, Brandt; Trejo-Hernández, María R; Morales-Guzmán, Daniel; Caspeta, Luis; Suárez Rodríguez, Ramón; Martínez-Morales, Fernando

2016-12-01

A Trametes versicolor laccase was functionally expressed on the membrane surface of Saccharomyces cerevisiae EBY100. Laccase expression was increased 6.57-fold by medium optimization and surpassed production by the native strain. Maximal laccase and biomass production reached 19 735 ± 1719 Ug -1 and 6.22 ± 0.53 gL -1 respectively, after 2 d of culture. Optimum oxidization of all substrates by laccase was observed at pH 3. Laccase showed high affinity towards substrates used with Km (mM) and Vmax (μmol min -1 ) values of 0.57 ± 0.0047 and 24.55 ± 0.64, 1.52 ± 0.52 and 9.25 ± 1.78, and 2.67 ± 0.12 and 11.26 ± 0.75, were reported for ABTS, 2, 6-DMP and GUA, respectively. EDTA and NaN 3 displayed none competitive inhibition towards laccase activity. The optimum temperature for activity was 50 °C; however, the enzyme was stable over a wide range of temperatures (25-70 °C). The biologically immobilized laccase showed high reusability towards phenolic substrates and low reusability with non-phenolic substrates. High affinity for a diversity phenolic compounds and great ethanol tolerance substantiates this laccase/yeast biocatalyst potential for application in the production of bioethanol. Copyright © 2016 British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Life cycle thinking and assessment tools on environmentally-benign electronics: Convergent optimization of materials use, end-of-life strategy and environmental policies

NASA Astrophysics Data System (ADS)

Zhou, Xiaoying

The purpose of this study is to integrate the quantitative environmental performance assessment tools and the theory of multi-objective optimization within the boundary of electronic product systems to support the selection among design alternatives in terms of environmental impact, technical criteria, and economic feasibility. To meet with the requirements that result from emerging environmental legislation targeting electronics products, the research addresses an important analytical methodological approach to facilitate environmentally conscious design and end-of-life management with a life cycle viewpoint. A synthesis of diverse assessment tools is applied on a set of case studies: lead-free solder materials selection, cellular phone design, and desktop display technology assessment. In the first part of this work, an in-depth industrial survey of the status and concerns of the U.S. electronics industry on the elimination of lead (Pb) in solders is described. The results show that the trade-offs among environmental consequences, technology challenges, business risks, legislative compliance and stakeholders' preferences must be explicitly, simultaneously, and systematically addressed in the decision-making process used to guide multi-faceted planning of environmental solutions. In the second part of this work, the convergent optimization of the technical cycle, economic cycle and environmental cycle is addressed in a coherent and systematic way using the application of environmentally conscious design of cellular phones. The technical understanding of product structure, components analysis, and materials flow facilitates the development of "Design for Disassembly" guidelines. A bottom-up disassembly analysis on a "bill of materials" based structure at a micro-operational level is utilized to select optimal end-of-life strategies on the basis of economic feasibility. A macro-operational level life cycle model is used to investigate the environmental consequences linking environmental impact with the cellular phone production activities focusing on the upstream manufacturing and end-of-life life cycle stages. The last part of this work, the quantitative elicitation of weighting factors facilitates the comparison of trade-offs in the context of a multi-attribute problem. An integrated analytical approach, Integrated Industrial Ecology Function Deployment (I2-EFD), is proposed to assess alternatives at the design phase of a product system and is validated with the assessment of desktop display technologies and lead-free solder alternatives.

Structural Performance’s Optimally Analysing and Implementing Based on ANSYS Technology

NASA Astrophysics Data System (ADS)

Han, Na; Wang, Xuquan; Yue, Haifang; Sun, Jiandong; Wu, Yongchun

2017-06-01

Computer-aided Engineering (CAE) is a hotspot both in academic field and in modern engineering practice. Analysis System(ANSYS) simulation software for its excellent performance become outstanding one in CAE family, it is committed to the innovation of engineering simulation to help users to shorten the design process, improve product innovation and performance. Aimed to explore a structural performance’s optimally analyzing model for engineering enterprises, this paper introduced CAE and its development, analyzed the necessity for structural optimal analysis as well as the framework of structural optimal analysis on ANSYS Technology, used ANSYS to implement a reinforced concrete slab structural performance’s optimal analysis, which was display the chart of displacement vector and the chart of stress intensity. Finally, this paper compared ANSYS software simulation results with the measured results,expounded that ANSYS is indispensable engineering calculation tools.

Content-aware photo collage using circle packing.

PubMed

Yu, Zongqiao; Lu, Lin; Guo, Yanwen; Fan, Rongfei; Liu, Mingming; Wang, Wenping

2014-02-01

In this paper, we present a novel approach for automatically creating the photo collage that assembles the interest regions of a given group of images naturally. Previous methods on photo collage are generally built upon a well-defined optimization framework, which computes all the geometric parameters and layer indices for input photos on the given canvas by optimizing a unified objective function. The complex nonlinear form of optimization function limits their scalability and efficiency. From the geometric point of view, we recast the generation of collage as a region partition problem such that each image is displayed in its corresponding region partitioned from the canvas. The core of this is an efficient power-diagram-based circle packing algorithm that arranges a series of circles assigned to input photos compactly in the given canvas. To favor important photos, the circles are associated with image importances determined by an image ranking process. A heuristic search process is developed to ensure that salient information of each photo is displayed in the polygonal area resulting from circle packing. With our new formulation, each factor influencing the state of a photo is optimized in an independent stage, and computation of the optimal states for neighboring photos are completely decoupled. This improves the scalability of collage results and ensures their diversity. We also devise a saliency-based image fusion scheme to generate seamless compositive collage. Our approach can generate the collages on nonrectangular canvases and supports interactive collage that allows the user to refine collage results according to his/her personal preferences. We conduct extensive experiments and show the superiority of our algorithm by comparing against previous methods.

Antimicrobial and antiprotozoal activities of secondary metabolites from the fungus Eurotium repens

PubMed Central

Gao, Jiangtao; Radwan, Mohamed M.; León, Francisco; Wang, Xiaoning; Jacob, Melissa R.; Tekwani, Babu L.; Khan, Shabana I.; Lupien, Shari; Hill, Robert A.; Dugan, Frank M.; Cutler, Horace G.

2011-01-01

In this study, we examined in vitro antibacterial, antifungal, antimalarial, and antileishmanial activities of secondary metabolites (1–8) isolated from the fungus Eurotium repens. All compounds showed mild to moderate antibacterial or antifungal or both activities except 7. The activity of compound 6 was the best of the group tested. The in vitro antimalarial evaluation of these compounds revealed that compounds 1–3, 5, and 6 showed antimalarial activities against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum with IC50 values in the range of 1.1–3.0 μg/ml without showing any cytotoxicity to the mammalian cells. Compound 5 displayed the highest antimalarial activity. Antileishmanial activity against Leishmania donovani promastigotes was observed for compounds 1–6 with IC50 values ranging from 6.2 to 23 μg/ml. Antileishmanial activity of compounds 5 and 6 (IC50 values of 7.5 and 6.2 μg/ml, respectively) was more potent than 1–4 (IC50 values ranging from 19–23 μg/ml). Compounds 7 and 8 did not show any antiprotozoal effect. Preliminary structure and activity relationship studies indicated that antibacterial, antifungal, antimalarial, and antileishmanial activities associated with phenol derivates (1–6) seem to be dependent on the number of double bonds in the side chain, which would be important for lead optimization in the future. PMID:23024574

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

NASA Astrophysics Data System (ADS)

Choe, Giseok; Nang, Jongho

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

Time is money: Rational life cycle inertia and the delegation of investment management.

PubMed

Kim, Hugh Hoikwang; Maurer, Raimond; Mitchell, Olivia S

2016-08-01

Many households display inertia in investment management over their life cycles. Our calibrated dynamic life cycle portfolio choice model can account for such an apparently 'irrational' outcome, by incorporating the fact that investors must forgo acquiring job-specific skills when they spend time managing their money, and their efficiency in financial decision making varies with age. Resulting inertia patterns mesh well with findings from prior studies and our own empirical results from Panel Study of Income Dynamics (PSID) data. We also analyze how people optimally choose between actively managing their assets versus delegating the task to financial advisors. Delegation proves valuable to both the young and the old. Our calibrated model quantifies welfare gains from including investment time and money costs as well as delegation in a life cycle setting.

Tricyclic [1,2,4]triazine 1,4-dioxides as hypoxia selective cytotoxins.

PubMed

Hay, Michael P; Hicks, Kevin O; Pchalek, Karin; Lee, Ho H; Blaser, Adrian; Pruijn, Frederik B; Anderson, Robert F; Shinde, Sujata S; Wilson, William R; Denny, William A

2008-11-13

A series of novel tricyclic triazine-di- N-oxides (TTOs) related to tirapazamine have been designed and prepared. A wide range of structural arrangements with cycloalkyl, oxygen-, and nitrogen-containing saturated rings fused to the triazine core, coupled with various side chains linked to either hemisphere, resulted in TTO analogues that displayed hypoxia-selective cytotoxicity in vitro. Optimal rates of hypoxic metabolism and tissue diffusion coefficients were achieved with fused cycloalkyl rings in combination with both the 3-aminoalkyl or 3-alkyl substituents linked to weakly basic soluble amines. The selection was further refined using pharmacokinetic/pharmacodynamic model predictions of the in vivo hypoxic potency (AUC req) and selectivity (HCD) with 12 TTO analogues predicted to be active in vivo, subject to the achievement of adequate plasma pharmacokinetics.

Tricyclic [1,2,4]Triazine 1,4-Dioxides As Hypoxia Selective Cytotoxins

PubMed Central

Hay, Michael P.; Hicks, Kevin O.; Pchalek, Karin; Lee, Ho H.; Blaser, Adrian; Pruijn, Frederik B.; Anderson, Robert F.; Shinde, Sujata S.; Wilson, William R.; Denny, William A.

2009-01-01

A series of novel tricyclic triazine-di-N-oxides (TTOs) related to tirapazamine have been designed and prepared. A wide range of structural arrangements with cycloalkyl, oxygen- and nitrogen-containing saturated rings fused to the triazine core, coupled with various side chains linked to either hemisphere, resulted in TTO analogues that displayed hypoxia-selective cytotoxicity in vitro. Optimal rates of hypoxic metabolism and tissue diffusion coefficients were achieved with fused cycloalkyl rings in combination with both the 3-aminoalkyl or 3-alkyl substituents linked to weakly basic soluble amines. The selection was further refined using pharmacokinetic/pharmacodynamic model predictions of the in vivo hypoxic potency (AUCreq) and selectivity (HCD) with 12 TTO analogues predicted to be active in vivo, subject to the achievement of adequate plasma pharmacokinetics. PMID:18847185

The discovery of thienopyridine analogues as potent IkappaB kinase beta inhibitors. Part II.

PubMed

Wu, Jiang-Ping; Fleck, Roman; Brickwood, Janice; Capolino, Alison; Catron, Katrina; Chen, Zhidong; Cywin, Charles; Emeigh, Jonathan; Foerst, Melissa; Ginn, John; Hrapchak, Matt; Hickey, Eugene; Hao, Ming-Hong; Kashem, Mohammed; Li, Jun; Liu, Weimin; Morwick, Tina; Nelson, Richard; Marshall, Daniel; Martin, Leslie; Nemoto, Peter; Potocki, Ian; Liuzzi, Michel; Peet, Gregory W; Scouten, Erika; Stefany, David; Turner, Michael; Weldon, Steve; Zimmitti, Clare; Spero, Denise; Kelly, Terence A

2009-10-01

An SAR study that identified a series of thienopyridine-based potent IkappaB Kinase beta (IKKbeta) inhibitors is described. With focuses on the structural optimization at C4 and C6 of structure 1 (Fig. 1), the study reveals that small alkyl and certain aromatic groups are preferred at C4, whereas polar groups with proper orientation at C6 efficiently enhance compound potency. The most potent analogues inhibit IKKbeta with IC50s as low as 40 nM, suppress LPS-induced TNF-alpha production in vitro and in vivo, display good kinase selectivity profiles, and are active in a HeLa cell NF-kappaB reporter gene assay, demonstrating that they directly interfere with the NF-kappaB signaling pathway.

GTP regeneration influences interactions of microtubules, neurofilaments, and microtubule-associated proteins in vitro.

PubMed

Flynn, G; Purich, D L

1987-11-15

Interactions of microtubules, neurofilaments, and microtubule-associated proteins were investigated by turbidity and falling-ball viscometry measurements. We found evidence of endogenous GTPase activity in neurofilaments and microtubule-associated proteins (MAPs) in preparations that do not include urea or heat treatment, respectively. The absence or presence of either adenyl-5'-yl imidodiphosphonic acid or a GTP-regenerating system markedly influenced observed polymerization and gelation characteristics. Most significantly, the apparent viscosity of neurofilament and microtubule samples did not display a biphasic optimal MAP concentration profile when a GTP-regenerating system was operant. Likewise, GTP regeneration promoted the recovery of gelation following mechanical disruption of neurofilament/MAP/microtubule mixtures. These and other observations require some reassessment of proposed roles for microtubule-associated proteins in modulating neurofilament-microtubule interactions in vitro.

Aspergillus oryzae S2 alpha-amylase production under solid state fermentation: optimization of culture conditions.

PubMed

Sahnoun, Mouna; Kriaa, Mouna; Elgharbi, Fatma; Ayadi, Dorra-Zouari; Bejar, Samir; Kammoun, Radhouane

2015-04-01

Aspergillus oryzae S2 was assayed for alpha-amylase production under solid state fermentation (SSF). In addition to AmyA and AmyB already produced in monitored submerged culture, the strain was noted to produce new AmyB oligomeric forms, in particular a dominant tetrameric form named AmyC. The latter was purified to homogeneity through fractional acetone precipitation and size exclusion chromatography. SDS-PAGE and native PAGE analyses revealed that, purified AmyC was an approximately 172 kDa tetramer of four 42 kDa subunits. AmyC was also noted to display the same NH2-terminal amino acid sequence residues and approximately the same physico-chemical properties of AmyA and AmyB, to exhibit maximum activity at pH 5.6 and 60 °C, and to produce maltose and maltotriose as major starch hydrolysis end-products. Soyabean meal was the best substitute to yeast extract compared to fish powder waste and wheat gluten waste. AmyC production was optimized under SSF using statistical design methodology. Moisture content of 76.25%, C/N substrate ratio of 0.62, and inoculum size of 10(6.87) spores allowed maximum activity of 22118.34 U/g of dried substrate, which was 33 times higher than the one obtained before the application of the central composite design (CCD). Copyright © 2015 Elsevier B.V. All rights reserved.

Ergonomic principles of task alignment, visual display, and direction of execution of laparoscopic bowel suturing.

PubMed

Emam, T A; Hanna, G; Cuschieri, A

2002-02-01

Laparoscopic suturing is technically a demanding skill in laparoscopic surgery. Ergonomic experimental studies provide objective information on the important factors and variables that govern optimal endoscopic suturing. Our objective was to determine the optimum physical alignment, visual display, and direction of intracorporeal laparoscopic bowel suturing using infrared motion analysis and telemetric electromyography (EMG) systems. Ten surgeons participated in the study; each sutured 50-mm porcine small bowel enterotomies toward and away from the surgeon in the vertical and horizontal bowel plane with either isoplanar (image display corresponds with actual lie of the bowel) or nonisoplanar (bowel displayed horizontally but mounted vertically in the trainer and vice versa) display. The end points were the placement error score, execution time, leakage pressure, motion analysis, and telemetric EMG parameters of the surgeon's dominant upper limb. Suturing was demonstrably easier in the vertical than in the horizontal plane, resulting in a better task quality (placement error score, p < 0.0001; leakage pressure, p < 0.005) and shorter execution time (p < 0.05). Nonisoplanar display of the surgical anatomy degrades performance in terms of both task efficiency and task quality. On motion analysis, a wider angle of excursion and lower angular velocity were observed during the vertical suturing with isoplaner display. Compared to horizontal suturing, supination at the wrist was significantly greater during vertical than horizontal suturing (p < 0.05). Within each category (vertical vs horizontal suturing), the direction of suturing (toward/away from the surgeon) did not influence the extent of pronation/ supination at the wrist. In line with the degraded performance, significantly more muscle work was expended during horizontal suturing. This affected the forearm flexors (p < 0.05), arm flexors and extensors (p < 0.005 and p < 0.05, respectively), and deltoid muscles (p < 0.005) and was accompanied by significantly more fatigue in the related muscles. Small bowel enterotomies sutured toward the surgeon in both the vertical and the horizontal planes exhibited less placement error score than when sutured away from the surgeon, with no significant difference in the motion analysis and EMG parameters. Optimal laparoscopic suturing (better task quality and reduced execution time) is achieved with vertical suturing toward the surgeon with isoplanar monitor display of the operative field. The poorer task performance observed during horizontal suturing is accompanied by more muscle work and fatigue, and it is not improved by monitor display of the enterotomy in the vertical plane.

Optimal Product Placement.

PubMed

Hsu, Chia-Ling; Matta, Rafael; Popov, Sergey V; Sogo, Takeharu

2017-01-01

We model a market, such as an online software market, in which an intermediary connects sellers and buyers by displaying sellers' products. With two vertically-differentiated products, an intermediary can place either: (1) one product, not necessarily the better one, on the first page, and the other hidden on the second page; or (2) both products on the first page. We show that it can be optimal for the intermediary to obfuscate a product-possibly the better one-since this weakens price competition and allows the sellers to extract a greater surplus from buyers; however, it is not socially optimal. The choice of which one to obfuscate depends on the distribution of search costs.

The pursuit of optimal distinctiveness and consumer preferences.

PubMed

He, Lingnan; Cong, Feng; Liu, Yanping; Zhou, Xinyue

2010-10-01

This article investigates the effect of optimal distinctiveness on consumer product consumption. The authors argue that consumers acquire and display material possessions to restore their optimal levels of distinctiveness. Results showed that placing consumers in a state of low distinctiveness increased desire to acquire distinctive products, whereas perceptions of high distinctiveness reduced desire to acquire such products. Consumers' desire for distinctiveness-related products held true for various consumer choices, including willingness to pay more for limited-edition products and preference for unpopular gifts. This finding has implications for understanding consumer choice in expressing identity. © 2010 The Authors. Scandinavian Journal of Psychology © 2010 The Scandinavian Psychological Associations.

An optimal control model approach to the design of compensators for simulator delay

NASA Technical Reports Server (NTRS)

Baron, S.; Lancraft, R.; Caglayan, A.

1982-01-01

The effects of display delay on pilot performance and workload and of the design of the filters to ameliorate these effects were investigated. The optimal control model for pilot/vehicle analysis was used both to determine the potential delay effects and to design the compensators. The model was applied to a simple roll tracking task and to a complex hover task. The results confirm that even small delays can degrade performance and impose a workload penalty. A time-domain compensator designed by using the optimal control model directly appears capable of providing extensive compensation for these effects even in multi-input, multi-output problems.

Volumetric depth peeling for medical image display

NASA Astrophysics Data System (ADS)

Borland, David; Clarke, John P.; Fielding, Julia R.; TaylorII, Russell M.

2006-01-01

Volumetric depth peeling (VDP) is an extension to volume rendering that enables display of otherwise occluded features in volume data sets. VDP decouples occlusion calculation from the volume rendering transfer function, enabling independent optimization of settings for rendering and occlusion. The algorithm is flexible enough to handle multiple regions occluding the object of interest, as well as object self-occlusion, and requires no pre-segmentation of the data set. VDP was developed as an improvement for virtual arthroscopy for the diagnosis of shoulder-joint trauma, and has been generalized for use in other simple and complex joints, and to enable non-invasive urology studies. In virtual arthroscopy, the surfaces in the joints often occlude each other, allowing limited viewpoints from which to evaluate these surfaces. In urology studies, the physician would like to position the virtual camera outside the kidney collecting system and see inside it. By rendering invisible all voxels between the observer's point of view and objects of interest, VDP enables viewing from unconstrained positions. In essence, VDP can be viewed as a technique for automatically defining an optimal data- and task-dependent clipping surface. Radiologists using VDP display have been able to perform evaluations of pathologies more easily and more rapidly than with clinical arthroscopy, standard volume rendering, or standard MRI/CT slice viewing.

Characterization of shape and deformation of MEMS by quantitative optoelectronic metrology techniques

NASA Astrophysics Data System (ADS)

Furlong, Cosme; Pryputniewicz, Ryszard J.

2002-06-01

Recent technological trends based on miniaturization of mechanical, electro-mechanical, and photonic devices to the microscopic scale, have led to the development of microelectromechanical systems (MEMS). Effective development of MEMS components requires the synergism of advanced design, analysis, and fabrication methodologies, and also of quantitative metrology techniques for characterizing their performance, reliability, and integrity during the electronic packaging cycle. In this paper, we describe opto-electronic techniques for measuring, with sub-micrometer accuracy, shape and changes in states of deformation of MEMS strictures. With the described opto-electronic techniques, it is possible to characterize MEMS components using the display and data modes. In the display mode, interferometric information related to shape and deformation is displayed at video frame rates, providing the capability for adjusting and setting experimental conditions. In the data mode, interferometric information related to shape and deformation is recorded as high-spatial and high-digital resolution images, which are further processed to provide quantitative 3D information. Furthermore, the quantitative 3D data are exported to computer-aided design (CAD) environments and utilized for analysis and optimization of MEMS devices. Capabilities of opto- electronic techniques are illustrated with representative applications demonstrating their applicability to provide indispensable quantitative information for the effective development and optimization of MEMS devices.

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

PubMed

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

2016-11-22

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

Courtship display dynamics, iridescent structural color and nanostructural pattern formation in ocellated pheasants

NASA Astrophysics Data System (ADS)

Kane, Suzanne Amador; Dakin, Roslyn; Fang, Rui; Lu, Yabin

Peacocks court females by tilting a fan-like array of feathers decorated with multicolored eyespots (ocelli). Previous research has shown that half of the variation in peacock mating success can be attributed to eyespot iridescence. Several closely-related pheasant species perform similar, but less complex, courtship displays using ocellated feathers with less complex coloration, patterns and underlying nanostructures. This study explores the relationship between the dynamics of male courtship behavior and optical properties and nanostructure of each species' iridescent feather ornaments. In particular, we examined videos of courting males and of individual feathers to measure how the angles used during displays compared to those corresponding to optimal eyespot reflected intensity and iridescent contrast. Bidirectional reflectance spectroscopy was used to measure how the spectrum of reflected light depends on the characteristic angles used during displays, and hence how displays stimulate the four classes of cones found in the color vision systems of these birds. This work reveals a close correlation between the complexity of the angular dependence of iridescent feather reflectance properties and that of the motions used by males of each species.

Evaluation of Helmet Mounted Display Alerting Symbology

NASA Technical Reports Server (NTRS)

DeMaio, Joe; Rutkowski, Michael (Technical Monitor)

2000-01-01

Proposed helicopter helmet mounted displays will be used to alert the pilot to a variety of conditions, from threats to equipment problems. The present research was performed under the NASA Safe All-weather Flight Operations Research (SAFOR) program supported by a joint Army/NASA research agreement. The purpose of the research was to examine ways to optimize the alerting effectiveness of helmet display symbology. The research used two approaches to increasing the effectiveness of alerts. One was to increase the ability of the alert to attract attention by using the entire display surface. The other was to include information about the required response in the alert itself. The investigation was conducted using the NASA Ames Research Center's six-degree-of-freedom vertical motion simulator (VMS) with a rotorcraft cockpit. Helmet display symbology was based on the AH-64's pilot night vision system (PNVS), cruise mode symbology. A standardized mission was developed, that consisted of 11 legs. The mission included four tasks, which allowed variation in the frequency of alerts. The general trend in the data points to a small benefit from both the full-screen alert and the partial information alert.

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

NASA Astrophysics Data System (ADS)

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

2003-09-01

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

Optimization of caseinate-coated simvastatin-zein nanoparticles: improved bioavailability and modified release characteristics

PubMed Central

Ahmed, Osama AA; Hosny, Khaled M; Al-Sawahli, Majid M; Fahmy, Usama A

2015-01-01

The current study focuses on utilization of the natural biocompatible polymer zein to formulate simvastatin (SMV) nanoparticles coated with caseinate, to improve solubility and hence bioavailability, and in addition, to modify SMV-release characteristics. This formulation can be utilized for oral or possible depot parenteral applications. Fifteen formulations were prepared by liquid–liquid phase separation method, according to the Box–Behnken design, to optimize formulation variables. Sodium caseinate was used as an electrosteric stabilizer. The factors studied were: percentage of SMV in the SMV-zein mixture (X1), ethanol concentration (X2), and caseinate concentration (X3). The selected dependent variables were mean particle size (Y1), SMV encapsulation efficiency (Y2), and cumulative percentage of drug permeated after 1 hour (Y3). The diffusion of SMV from the prepared nanoparticles specified by the design was carried out using an automated Franz diffusion cell apparatus. The optimized SMV-zein formula was investigated for in vivo pharmacokinetic parameters compared with an oral SMV suspension. The optimized nanosized SMV-zein formula showed a 131 nm mean particle size and 89% encapsulation efficiency. In vitro permeation studies displayed delayed permeation characteristics, with about 42% and 85% of SMV cumulative amount released after 12 and 48 hours, respectively. Bioavailability estimation in rats revealed an augmentation in SMV bioavailability from the optimized SMV-zein formulation, by fourfold relative to SMV suspension. Formulation of caseinate-coated SMV-zein nanoparticles improves the pharmacokinetic profile and bioavailability of SMV. Accordingly, improved hypolipidemic activities for longer duration could be achieved. In addition, the reduced dosage rate of SMV-zein nanoparticles improves patient tolerability and compliance. PMID:25670883

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

PubMed Central

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

2017-01-01

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

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

PubMed

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

2017-01-01

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

Synthesis, molecular modeling and biological evaluation of PSB as targeted antibiotics.

PubMed

Cheng, Kui; Zheng, Qing-Zhong; Hou, Jin; Zhou, Yang; Liu, Chang-Hong; Zhao, Jing; Zhu, Hai-Liang

2010-04-01

We described here the design, synthesis, molecular modeling, and biological evaluation of a series of peptide and Schiff bases (PSB) small molecules, inhibitors of Escherichia coli beta-Ketoacyl-acyl carrier protein synthase III (ecKAS III). The initial lead compound was reported by us previously, we continued to carry out structure-activity relationship studies and optimize the lead structure to potent inhibitors in this research. The results demonstrated that both N-(2-(3,5-dichloro-2-hydroxybenzylideneamino)propyl)-2-hydroxybenzamide (1f) and 2-hydroxy-N-(2-(2-hydroxy-5-iodobenzylideneamino)propyl)-4-methylbenzamide (3e) posses good ecKAS III inhibitory activity and well binding affinities by bonding Gly152/Gly209 of ecKAS III and fit into the mouth of the substrate tunnel, and can be as potential antibiotics agent, displaying minimal inhibitory concentration values in the range 0.20-3.13microg/mL and 0.39-3.13microg/mL against various bacteria. Copyright 2010 Elsevier Ltd. All rights reserved.

Low-Cost, Portable, Multi-Wall Virtual Reality

NASA Technical Reports Server (NTRS)

Miller, Samuel A.; Misch, Noah J.; Dalton, Aaron J.

2005-01-01

Virtual reality systems make compelling outreach displays, but some such systems, like the CAVE, have design features that make their use for that purpose inconvenient. In the case of the CAVE, the equipment is difficult to disassemble, transport, and reassemble, and typically CAVEs can only be afforded by large-budget research facilities. We implemented a system like the CAVE that costs less than $30,000, weighs about 500 pounds, and fits into a fifteen-passenger van. A team of six people have unpacked, assembled, and calibrated the system in less than two hours. This cost reduction versus similar virtual-reality systems stems from the unique approach we took to stereoscopic projection. We used an assembly of optical chopper wheels and commodity LCD projectors to create true active stereo at less than a fifth of the cost of comparable active-stereo technologies. The screen and frame design also optimized portability; the frame assembles in minutes with only two fasteners, and both it and the screen pack into small bundles for easy and secure shipment.

New 5-benzylidenethiazolidin-4-one inhibitors of bacterial MurD ligase: design, synthesis, crystal structures, and biological evaluation.

PubMed

Zidar, Nace; Tomašić, Tihomir; Šink, Roman; Kovač, Andreja; Patin, Delphine; Blanot, Didier; Contreras-Martel, Carlos; Dessen, Andréa; Premru, Manica Müller; Zega, Anamarija; Gobec, Stanislav; Mašič, Lucija Peterlin; Kikelj, Danijel

2011-11-01

Mur ligases (MurC-MurF), a group of bacterial enzymes that catalyze four consecutive steps in the formation of cytoplasmic peptidoglycan precursor, are becoming increasingly adopted as targets in antibacterial drug design. Based on the crystal structure of MurD cocrystallized with thiazolidine-2,4-dione inhibitor I, we have designed, synthesized, and evaluated a series of improved glutamic acid containing 5-benzylidenerhodanine and 5-benzylidenethiazolidine-2,4-dione inhibitors of MurD with IC(50) values up to 28 μM. Inhibitor 37, with an IC(50) of 34 μM, displays a weak antibacterial activity against S. aureus ATCC 29213 and E. faecalis ATCC 29212 with minimal inhibitory concentrations of 128 μg/mL. High-resolution crystal structures of MurD in complex with two new inhibitors (compounds 23 and 51) reveal details of their binding modes within the active site and provide valuable information for further structure-based optimization. Copyright © 2011 Elsevier Masson SAS. All rights reserved.

DI: An interactive debugging interpreter for applicative languages

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

Skedzielewski, S.K.; Yates, R.K.; Oldehoeft, R.R.

1987-03-12

The DI interpreter is both a debugger and interpreter of SISLAL programs. Its use as a program interpreter is only a small part of its role; it is designed to be a tool for studying compilation techniques for applicative languages. DI interprets dataflow graphs expressed in the IF1 and IF2 languages, and is heavily instrumented to report the activity of dynamic storage activity, reference counting, copying and updating of structured data values. It also aids the SISAL language evaluation by providing an interim execution vehicle for SISAL programs. DI provides determinate, sequential interpretation of graph nodes for sequential and parallelmore » operations in a canonical order. As a debugging aid, DI allows tracing, breakpointing, and interactive display of program data values. DI handles creation of SISAL and IF1 error values for each data type and propagates them according to a well-defined algebra. We have begun to implement IF1 optimizers and have measured the improvements with DI.« less

Multiple chitinases of an endophytic Serratia proteamaculans 568 generate chitin oligomers.

PubMed

Purushotham, Pallinti; Sarma, P V S R N; Podile, Appa Rao

2012-05-01

Serratia proteamaculans 568 genome revealed the presence of four family 18 chitinases (Sp ChiA, Sp ChiB, Sp ChiC, and Sp ChiD). Heterologous expression and characterization of Sp ChiA, Sp ChiB, and Sp ChiC showed that these enzymes were optimally active at pH 6.0-7.0, and 40°C. The three Sp chitinases displayed highest activity/binding to β-chitin and showed broad range of substrate specificities, and released dimer as major end product from oligomeric and polymeric substrates. Longer incubation was required for hydrolysis of trimer for the three Sp chitinases. The three Sp chitinases released up to tetramers from colloidal chitin substrate. Sp ChiA and Sp ChiB were processive chitinases, while Sp ChiC was a non-processive chitinase. Based on the known structures of ChiA and ChiB from S. marcescens, 3D models of Sp ChiA and Sp ChiB were generated. Copyright © 2012 Elsevier Ltd. All rights reserved.

PCFT/SLC46A1 promoter methylation and restoration of gene expression in human leukemia cells

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

Gonen, Nitzan; Bram, Eran E.; Assaraf, Yehuda G.

2008-11-28

The proton-coupled folate transporter (PCFT/SLC46A1) displays optimal and prominent folate and antifolate transport activity at acidic pH in human carcinoma cells but poor activity in leukemia cells. Consistently herein, human leukemia cell lines expressed poor PCFT transcript levels, whereas various carcinoma cell lines showed substantial PCFT gene expression. We identified a CpG island with high density at nucleotides -200 through +100 and explored its role in PCFT promoter silencing. Leukemia cells with barely detectable PCFT transcripts consistently harbored 85-100% methylation of this CpG island, whereas no methylation was found in carcinoma cells. Treatment with 5-Aza-2'-deoxycytidine which induced demethylation but notmore » with the histone deacetylase inhibitor trichostatin A, restored 50-fold PCFT expression only in leukemia cells. These findings constitute the first demonstration of the dominant epigenetic silencing of the PCFT gene in leukemia cells. The potential translational implications of the restoration of PCFT expression in chemotherapy of leukemia are discussed.« less

Design and Development of Stable, Water-soluble, Human Toll-like Receptor 2-Specific, Monoacyl Lipopeptides as Candidate Vaccine Adjuvants

PubMed Central

Salunke, Deepak B.; Connelly, Seth W.; Shukla, Nikunj M.; Hermanson, Alec R.; Fox, Lauren M.; David, Sunil A.

2013-01-01

Antigens in modern subunit vaccines are largely soluble and poorly immunogenic proteins inducing relatively short-lived immune responses. Appropriate adjuvants initiate early innate immune responses, amplifying subsequent adaptive immune responses. Agonists of TLR2 are devoid of significant pro-inflammatory activity in ex vivo human blood models, and yet potently adjuvantic, suggesting that this chemotype may be a safe and effective adjuvant. Our earlier work on the monoacyl lipopeptide class of TLR2 agonists led to the design of a highly potent lead, but with negligible aqueous solubility, necessitating the reintroduction of aqueous solubility. We explored several strategies of introducing ionizable groups on the lipopeptide, as well as the systematic evaluation of chemically stable bioisosteres of the ester-linked palmitoyl group. These studies have led to a fully optimized, chemically stable, and highly water-soluble, human TLR2-specific agonist, which was found to have an excellent safety profile and displayed prominent adjuvantic activities in rabbit models. PMID:23795818

Graphitic carbon nitride nanosheet electrode-based high-performance ionic actuator

PubMed Central

Wu, Guan; Hu, Ying; Liu, Yang; Zhao, Jingjing; Chen, Xueli; Whoehling, Vincent; Plesse, Cédric; Nguyen, Giao T. M.; Vidal, Frédéric; Chen, Wei

2015-01-01

Ionic actuators have attracted attention due to their remarkably large strain under low-voltage stimulation. Because actuation performance is mainly dominated by the electrochemical and electromechanical processes of the electrode layer, the electrode material and structure are crucial. Here, we report a graphitic carbon nitride nanosheet electrode-based ionic actuator that displays high electrochemical activity and electromechanical conversion abilities, including large specific capacitance (259.4 F g−1) with ionic liquid as the electrolyte, fast actuation response (0.5±0.03% in 300 ms), large electromechanical strain (0.93±0.03%) and high actuation stability (100,000 cycles) under 3 V. The key to the high performance lies in the hierarchical pore structure with dominant size <2 nm, optimal pyridinic nitrogen active sites (6.78%) and effective conductivity (382 S m−1) of the electrode. Our study represents an important step towards artificial muscle technology in which heteroatom modulation in electrodes plays an important role in promoting electrochemical actuation performance. PMID:26028354

Flexible Conductive Composite Integrated with Personal Earphone for Wireless, Real-Time Monitoring of Electrophysiological Signs.

PubMed

Lee, Joong Hoon; Hwang, Ji-Young; Zhu, Jia; Hwang, Ha Ryeon; Lee, Seung Min; Cheng, Huanyu; Lee, Sang-Hoon; Hwang, Suk-Won

2018-06-14

We introduce optimized elastomeric conductive electrodes using a mixture of silver nanowires (AgNWs) with carbon nanotubes/polydimethylsiloxane (CNTs/PDMS), to build a portable earphone type of wearable system that is designed to enable recording electrophysiological activities as well as listening to music at the same time. A custom-built, plastic frame integrated with soft, deformable fabric-based memory foam of earmuffs facilitates essential electronic components, such as conductive elastomers, metal strips, signal transducers and a speaker. Such platform incorporates with accessory cables to attain wireless, real-time monitoring of electrical potentials whose information can be displayed on a cell phone during outdoor activities and music appreciation. Careful evaluations on experimental results reveal that the performance of fabricated dry electrodes are comparable to that of commercial wet electrodes, and position-dependent signal behaviors provide a route toward accomplishing maximized signal quality. This research offers a facile approach for a wearable healthcare monitor via integration of soft electronic constituents with personal belongings.

Novel small molecule inhibitors targeting the "switch region" of bacterial RNAP: structure-based optimization of a virtual screening hit.

PubMed

Sahner, J Henning; Groh, Matthias; Negri, Matthias; Haupenthal, Jörg; Hartmann, Rolf W

2013-07-01

Rising resistance against current antibiotics necessitates the development of antibacterial agents with alternative targets. The "switch region" of RNA polymerase (RNAP), addressed by the myxopyronins, could be such a novel target site. Based on a hit candidate discovered by virtual screening, a small library of 5-phenyl-3-ureidothiophene-2-carboxylic acids was synthesized resulting in compounds with increased RNAP inhibition. Hansch analysis revealed π (lipophilicity constant) and σ (Hammet substituent constant) of the substituents at the 5-phenyl moiety to be crucial for activity. The binding mode was proven by the targeted introduction of a moiety mimicking the enecarbamate side chain of myxopyronin into the hit compound, accompanied by enhanced RNAP inhibitory potency. The new compounds displayed good antibacterial activities against Gram positive bacteria and Gram negative Escherichia coli TolC and a reduced resistance frequency compared to the established antibiotic rifampicin. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Tactile Sensory Supplementation of Gravitational References to Optimize Sensorimotor Recovery

NASA Technical Reports Server (NTRS)

Black, F. O.; Paloski, W. H.; Bloomberg, J. J.; Wood, S. J.

2007-01-01

Integration of multi-sensory inputs to detect tilts relative to gravity is critical for sensorimotor control of upright orientation. Displaying body orientation using electrotactile feedback to the tongue has been developed by Bach-y- Rita and colleagues as a sensory aid to maintain upright stance with impaired vestibular feedback. This investigation has explored the effects of Tongue Elecrotactile Feedback (TEF) for control of posture and movement as a sensorimotor countermeasure, specifically addressing the optimal location of movement sensors.

Biochemical Characterization of An Arginine-Specific Alkaline Trypsin from Bacillus licheniformis.

PubMed

Gong, Jin-Song; Li, Wei; Zhang, Dan-Dan; Xie, Min-Feng; Yang, Biao; Zhang, Rong-Xian; Li, Heng; Lu, Zhen-Ming; Xu, Zheng-Hong; Shi, Jin-Song

2015-12-17

In the present study, we isolated a trypsin-producing strain DMN6 from the leather waste and identified it as Bacillus licheniformis through a two-step screening strategy. The trypsin activity was increased up to 140 from 20 U/mL through culture optimization. The enzyme was purified to electrophoretic homogeneity with a molecular mass of 44 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and the specific activity of purified enzyme is 350 U/mg with Nα-Benzoyl-L-arginine ethylester as the substrate. The optimum temperature and pH for the trypsin are 65 °C and pH 9.0, respectively. Also, the enzyme can be significantly activated by Ba(2+). This enzyme is relatively stable in alkaline environment and displays excellent activity at low temperatures. It could retain over 95% of enzyme activity after 180 min of incubation at 45 °C. The distinguished activity under low temperature and prominent stability enhance its catalytic potential. In the current work, the open reading frame was obtained with a length of 1371 nucleotides that encoded a protein of 456 amino acids. These data would warrant the B. licheniformis trypsin as a promising candidate for catalytic application in collagen preparation and leather bating through further protein engineering.

Molecular properties of steroids involved in their effects on the biophysical state of membranes.

PubMed

Wenz, Jorge J

2015-10-01

The activity of steroids on membranes was studied in relation to their ordering, rigidifying, condensing and/or raft promoting ability. The structures of 82 steroids were modeled by a semi-empirical procedure (AM1) and 245 molecular descriptors were next computed on the optimized energy conformations. Principal component analysis, mean contrasting and logistic regression were used to correlate the molecular properties with 212 cases of documented activities. It was possible to group steroids based on their properties and activities, indicating that steroids having similar molecular properties have similar activities on membranes. Steroids having high values of area, partition coefficient, volume, number of rotatable bonds, molar refractivity, polarizability or mass displayed ordering, rigidifying, condensing and/or raft promoting activity on membranes higher than those steroids having low values in such molecular properties. After a variable selection procedure circumventing correlation problems among descriptors, area and log P were found as the most relevant properties in governing and predicting the activity of steroids on membranes. A logistic regression model as a function of the area and log P of the steroids is proposed, which is able to predict correctly 92.5% of the cases. A rationale of the findings is discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

The microsomal dicarboxylyl-CoA synthetase.

PubMed Central

Vamecq, J; de Hoffmann, E; Van Hoof, F

1985-01-01

Dicarboxylic acids are products of the omega-oxidation of monocarboxylic acids. We demonstrate that in rat liver dicarboxylic acids (C5-C16) can be converted into their CoA esters by a dicarboxylyl-CoA synthetase. During this activation ATP, which cannot be replaced by GTP, is converted into AMP and PPi, both acting as feedback inhibitors of the reaction. Thermolabile at 37 degrees C, and optimally active at pH 6.5, dicarboxylyl-CoA synthetase displays the highest activity on dodecanedioic acid (2 micromol/min per g of liver). Cell-fractionation studies indicate that this enzyme belongs to the hepatic microsomal fraction. Investigations about the fate of dicarboxylyl-CoA esters disclosed the existence of an oxidase, which could be measured by monitoring the production of H2O2. In our assay conditions this H2O2 production is dependent on and closely follows the CoA consumption. It appears that the chain-length specificity of the handling of dicarboxylic acids by this catabolic pathway (activation to acyl-CoA and oxidation with H2O2 production) parallels the pattern of the degradation of exogenous dicarboxylic acids in vivo. PMID:4062873

Fabrication, characterization and bioevaluation of silibinin loaded chitosan nanoparticles.

PubMed

Pooja, Deep; Babu Bikkina, Dileep J; Kulhari, Hitesh; Nikhila, Nalla; Chinde, Srinivas; Raghavendra, Y M; Sreedhar, B; Tiwari, Ashok K

2014-08-01

Silibinin is reported to possess multiple biological activities. However, its hydrophobic nature limits its bioavailability compromising in vivo biological activities. Nanoparticles-based delivery of such molecules has emerged as new technique to resolve these issues. Bio-degradable, compatible and adhesive nature of chitosan has recently attracted its suitability as a carrier for biologically active molecules. This study presents fabrication and characterization of chitosan-tripolyphosphate based encapsulation of silibinin. Various preparations of silibinin encapsulated chitosan-tripolyphosphate nanoparticles were studied for particle size, morphology, zeta-potential, and encapsulation efficiencies. Preparations were also evaluated for cytotoxic activities in vitro. The optimized silibinin loaded chitosan nanoparticles were of 263.7±4.1nm in particle size with zeta potential 37.4±1.57mV. Nanoparticles showed high silibinin encapsulation efficiencies (82.94±1.82%). No chemical interactions between silibinin and chitosan were observed in FTIR analysis. Powder X-ray diffraction analysis revealed transformed physical state of silibinin after encapsulation. Surface morphology and thermal behaviour were determined using TEM and DSC analysis. Encapsulated silibinin displayed increased dissolution and better cytotoxicity against human prostate cancer cells (DU145) than silibinin alone. Copyright © 2014 Elsevier B.V. All rights reserved.

Optimal read/write memory system components

NASA Technical Reports Server (NTRS)

Kozma, A.; Vander Lugt, A.; Klinger, D.

1972-01-01

Two holographic data storage and display systems, voltage gradient ionization system, and linear strain manipulation system are discussed in terms of creating fast, high bit density, storage device. Components described include: novel mounting fixture for photoplastic arrays; corona discharge device; and block data composer.

Structure-function characterization and optimization of a plant-derived antibacterial peptide.

PubMed

Suarez, Mougli; Haenni, Marisa; Canarelli, Stéphane; Fisch, Florian; Chodanowski, Pierre; Servis, Catherine; Michielin, Olivier; Freitag, Ruth; Moreillon, Philippe; Mermod, Nicolas

2005-09-01

Crushed seeds of the Moringa oleifera tree have been used traditionally as natural flocculants to clarify drinking water. We previously showed that one of the seed peptides mediates both the sedimentation of suspended particles such as bacterial cells and a direct bactericidal activity, raising the possibility that the two activities might be related. In this study, the conformational modeling of the peptide was coupled to a functional analysis of synthetic derivatives. This indicated that partly overlapping structural determinants mediate the sedimentation and antibacterial activities. Sedimentation requires a positively charged, glutamine-rich portion of the peptide that aggregates bacterial cells. The bactericidal activity was localized to a sequence prone to form a helix-loop-helix structural motif. Amino acid substitution showed that the bactericidal activity requires hydrophobic proline residues within the protruding loop. Vital dye staining indicated that treatment with peptides containing this motif results in bacterial membrane damage. Assembly of multiple copies of this structural motif into a branched peptide enhanced antibacterial activity, since low concentrations effectively kill bacteria such as Pseudomonas aeruginosa and Streptococcus pyogenes without displaying a toxic effect on human red blood cells. This study thus identifies a synthetic peptide with potent antibacterial activity against specific human pathogens. It also suggests partly distinct molecular mechanisms for each activity. Sedimentation may result from coupled flocculation and coagulation effects, while the bactericidal activity would require bacterial membrane destabilization by a hydrophobic loop.

Structure-Function Characterization and Optimization of a Plant-Derived Antibacterial Peptide

PubMed Central

Suarez, Mougli; Haenni, Marisa; Canarelli, Stéphane; Fisch, Florian; Chodanowski, Pierre; Servis, Catherine; Michielin, Olivier; Freitag, Ruth; Moreillon, Philippe; Mermod, Nicolas

2005-01-01

Crushed seeds of the Moringa oleifera tree have been used traditionally as natural flocculants to clarify drinking water. We previously showed that one of the seed peptides mediates both the sedimentation of suspended particles such as bacterial cells and a direct bactericidal activity, raising the possibility that the two activities might be related. In this study, the conformational modeling of the peptide was coupled to a functional analysis of synthetic derivatives. This indicated that partly overlapping structural determinants mediate the sedimentation and antibacterial activities. Sedimentation requires a positively charged, glutamine-rich portion of the peptide that aggregates bacterial cells. The bactericidal activity was localized to a sequence prone to form a helix-loop-helix structural motif. Amino acid substitution showed that the bactericidal activity requires hydrophobic proline residues within the protruding loop. Vital dye staining indicated that treatment with peptides containing this motif results in bacterial membrane damage. Assembly of multiple copies of this structural motif into a branched peptide enhanced antibacterial activity, since low concentrations effectively kill bacteria such as Pseudomonas aeruginosa and Streptococcus pyogenes without displaying a toxic effect on human red blood cells. This study thus identifies a synthetic peptide with potent antibacterial activity against specific human pathogens. It also suggests partly distinct molecular mechanisms for each activity. Sedimentation may result from coupled flocculation and coagulation effects, while the bactericidal activity would require bacterial membrane destabilization by a hydrophobic loop. PMID:16127062

Developing a Prototype ALHAT Human System Interface for Landing

NASA Technical Reports Server (NTRS)

Hirsh, Robert L.; Chua, Zarrin K.; Heino, Todd A.; Strahan, Al; Major, Laura; Duda, Kevin

2011-01-01

The goal of the Autonomous Landing and Hazard Avoidance Technology (ALHAT) project is to safely execute a precision landing anytime/anywhere on the moon. This means the system must operate in any lighting conditions, operate in the presence of any thruster generated regolith clouds, and operate without the help of redeployed navigational aids or prepared landing site at the landing site. In order to reach this ambitious goal, computer aided technologies such as ALHAT will be needed in order to permit these landings to be done safely. Although there will be advanced autonomous capabilities onboard future landers, humans will still be involved (either onboard as astronauts or remotely from mission control) in any mission to the moon or other planetary body. Because many time critical decisions must be made quickly and effectively during the landing sequence, the Descent and Landing displays need to be designed to be as effective as possible at presenting the pertinent information to the operator, and allow the operators decisions to be implemented as quickly as possible. The ALHAT project has established the Human System Interface (HSI) team to lead in the development of these displays and to study the best way to provide operators enhanced situational awareness during landing activities. These displays are prototypes that were developed based on multiple design and feedback sessions with the astronaut office at NASA/ Johnson Space Center. By working with the astronauts in a series of plan/build/evaluate cycles, the HSI team has obtained astronaut feedback from the very beginning of the design process. In addition to developing prototype displays, the HSI team has also worked to provide realistic lunar terrain (and shading) to simulate a "out the window" view that can be adjusted to various lighting conditions (based on a desired date/time) to allow the same terrain to be viewed under varying lighting terrain. This capability will be critical to determining the effect of terrain/lighting on the human pilot, and how they use windows and displays during landing activities. The Apollo missions were limited to about 28 possible launch days a year due to lighting and orbital constraints. In order to take advantage of more landing opportunities and venture to more challenging landing locations, future landers will need to utilize sensors besides human eyes for scanning the surface. The ALHAT HSI system must effectively convey ALHAT produced information to the operator, so that landings can occur during less "optimal" conditions (lighting, surface terrain, slopes, etc) than was possible during Apollo missions. By proving this capability, ALHAT will simultaneously provide more flexible access to the moon, and greater safety margins for future landers. This paper will specifically focus on the development of prototype displays (the Trajectory Profile Display (TPD), Landing Point Designation (LPD), and Crew Camera View (CCV) ), implementation of realistic planetary terrain, human modeling, and future HSI plans.

Toward the establishment of design guidelines for effective 3D perspective interfaces

NASA Astrophysics Data System (ADS)

Fitzhugh, Elisabeth; Dixon, Sharon; Aleva, Denise; Smith, Eric; Ghrayeb, Joseph; Douglas, Lisa

2009-05-01

The propagation of information operation technologies, with correspondingly vast amounts of complex network information to be conveyed, significantly impacts operator workload. Information management research is rife with efforts to develop schemes to aid operators to identify, review, organize, and retrieve the wealth of available data. Data may take on such distinct forms as intelligence libraries, logistics databases, operational environment models, or network topologies. Increased use of taxonomies and semantic technologies opens opportunities to employ network visualization as a display mechanism for diverse information aggregations. The broad applicability of network visualizations is still being tested, but in current usage, the complexity of densely populated abstract networks suggests the potential utility of 3D. Employment of 2.5D in network visualization, using classic perceptual cues, creates a 3D experience within a 2D medium. It is anticipated that use of 3D perspective (2.5D) will enhance user ability to visually inspect large, complex, multidimensional networks. Current research for 2.5D visualizations demonstrates that display attributes, including color, shape, size, lighting, atmospheric effects, and shadows, significantly impact operator experience. However, guidelines for utilization of attributes in display design are limited. This paper discusses pilot experimentation intended to identify potential problem areas arising from these cues and determine how best to optimize perceptual cue settings. Development of optimized design guidelines will ensure that future experiments, comparing network displays with other visualizations, are not confounded or impeded by suboptimal attribute characterization. Current experimentation is anticipated to support development of cost-effective, visually effective methods to implement 3D in military applications.

Enhanced Images for Checked and Carry-on Baggage and Cargo Screening

NASA Technical Reports Server (NTRS)

Woodell, Glenn; Rahman, Zia-ur; Jobson, Daniel J.; Hines, Glenn

2004-01-01

The current X-ray systems used by airport security personnel for the detection of contraband, and objects such as knives and guns that can impact the security of a flight, have limited effect because of the limited display quality of the X-ray images. Since the displayed images do not possess optimal contrast and sharpness, it is possible for the security personnel to miss potentially hazardous objects. This problem is also common to other disciplines such as medical Xrays, and can be mitigated, to a large extent, by the use of state-of-the-art image processing techniques to enhance the contrast and sharpness of the displayed image. The NASA Langley Research Center's Visual Information Processing Group has developed an image enhancement technology that has direct applications to this problem of inadequate display quality. Airport security X-ray imaging systems would benefit considerably by using this novel technology, making the task of the personnel who have to interpret the X-ray images considerably easier, faster, and more reliable. This improvement would translate into more accurate screening as well as minimizing the screening time delays to airline passengers. This technology, Retinex, has been optimized for consumer applications but has been applied to medical X-rays on a very preliminary basis. The resultant technology could be incorporated into a new breed of commercial x-ray imaging systems which would be transparent to the screener yet allow them to see subtle detail much more easily, reducing the amount of time needed for screening while greatly increasing the effectiveness of contraband detection and thus public safety.

Enhanced Images for Checked and Carry-on Baggage and Cargo Screening

NASA Technical Reports Server (NTRS)

Woodell, Glen; Rahman, Zia-ur; Jobson, Daniel J.; Hines, Glenn

2004-01-01

The current X-ray systems used by airport security personnel for the detection of contraband, and objects such as knives and guns that can impact the security of a flight, have limited effect because of the limited display quality of the X-ray images. Since the displayed images do not possess optimal contrast and sharpness, it is possible for the security personnel to miss potentially hazardous objects. This problem is also common to other disciplines such as medical X-rays, and can be mitigated, to a large extent, by the use of state-of-the-art image processing techniques to enhance the contrast and sharpness of the displayed image. The NASA Langley Research Centers Visual Information Processing Group has developed an image enhancement technology that has direct applications to this problem of inadequate display quality. Airport security X-ray imaging systems would benefit considerably by using this novel technology, making the task of the personnel who have to interpret the X-ray images considerably easier, faster, and more reliable. This improvement would translate into more accurate screening as well as minimizing the screening time delays to airline passengers. This technology, Retinex, has been optimized for consumer applications but has been applied to medical X-rays on a very preliminary basis. The resultant technology could be incorporated into a new breed of commercial x-ray imaging systems which would be transparent to the screener yet allow them to see subtle detail much more easily, reducing the amount of time needed for screening while greatly increasing the effectiveness of contraband detection and thus public safety.

Boosting ORR Catalytic Activity by Integrating Pyridine-N Dopants, a High Degree of Graphitization, and Hierarchical Pores into a MOF-Derived N-Doped Carbon in a Tandem Synthesis.

PubMed

Liu, Dandan; Li, Liangjun; Xu, Huanfei; Dai, Pengcheng; Wang, Ying; Gu, Xin; Yan, Liting; Zhao, Guoming; Zhao, Xuebo

2018-05-18

N-doped carbon materials represent promising metal-free electrocatalysts for the oxygen reduction reaction (ORR), the cathode reaction in fuel cells, metal-air batteries, and so on. A challenge for optimizing the ORR catalytic activities of these electrocatalysts is to tune their local structures and chemical compositions in a rational and controlled way that can achieve the synergistic function of each factor. Herein, we report a tandem synthetic strategy that integrates multiple contributing factors into an N-doped carbon. With an N-containing MOF (ZIF-8) as the precursor, carbonization at higher temperatures leads to a higher degree of graphitization. Subsequent NH 3 etching of this highly graphitic carbon enabled the introduction of a higher content of pyridine-N sites and higher porosity. By optimizing these three factors, the resultant carbon materials displayed ORR activity that was far superior to that of carbon derived from a one-step pyrolysis. The onset potential of 0.955 V versus a reversible hydrogen electrode (RHE) and the half-wave potential of 0.835 V versus RHE are among the top ranks of metal-free ORR catalysts and are comparable to commercial Pt/C (20 wt %) catalysts. Kinetic studies revealed lower H 2 O 2 yields, higher electron-transfer numbers, and lower Tafel slopes for these carbon materials compared with that derived from a one-step carbonization. These findings verify the effectiveness of this tandem synthetic strategy to enhance the ORR activity of N-doped carbon materials. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Human T cells engineered to express a programmed death 1/28 costimulatory retargeting molecule display enhanced antitumor activity.

PubMed

Ankri, Chen; Shamalov, Katerina; Horovitz-Fried, Miryam; Mauer, Shmuel; Cohen, Cyrille J

2013-10-15

Adoptive transfer of T cells genetically modified to express cancer-specific receptors can mediate impressive tumor regression in terminally ill patients. However, T cell function and persistence over time could be hampered by the activation of inhibitory costimulatory pathways, such as programmed death 1 (PD1)/programmed death ligand 1, leading to T cell exhaustion and providing tumor cells with an escape mechanism from immunosurveillance. In addition, the lack of positive costimulation at the tumor site can further dampen T cell response. Thus, as T cell genetic engineering has become clinically relevant, we aimed at enhancing T cell antitumor activity by genetically diverting T cell-negative costimulatory signals into positive ones using chimeric costimulatory retargeting molecules and which are composed of the PD1 extracellular domain fused to the signaling domains of positive costimulatory molecules such as CD28 and 4-1BB. After characterizing the optimal PD1 chimera, we designed and optimized a tripartite retroviral vector that enables the simultaneous expression of this chimeric molecule in conjunction with a cancer-specific TCR. Human T cells, transduced to express a PD1/28 chimeric molecule, exhibited enhanced cytokine secretion and upregulation of activation markers upon coculture with tumor cells. These engineered cells also proliferated better compared with control cells. Finally, we tested the function of these cells in two xenograft models of human melanoma tumors and show that PD1/28-engineered human T cells demonstrated superior antitumor function. Overall, we propose that engineering T cells with a costimulatory retargeting molecule can enhance their function, which bears important implications for the improvement of T cell immunotherapy.

On-Line Safe Flight Envelope Determination for Impaired Aircraft

NASA Technical Reports Server (NTRS)

Lombaerts, Thomas; Schuet, Stefan; Acosta, Diana; Kaneshige, John

2015-01-01

The design and simulation of an on-line algorithm which estimates the safe maneuvering envelope of aircraft is discussed in this paper. The trim envelope is estimated using probabilistic methods and efficient high-fidelity model based computations of attainable equilibrium sets. From this trim envelope, a robust reachability analysis provides the maneuverability limitations of the aircraft through an optimal control formulation. Both envelope limits are presented to the flight crew on the primary flight display. In the results section, scenarios are considered where this adaptive algorithm is capable of computing online changes to the maneuvering envelope due to impairment. Furthermore, corresponding updates to display features on the primary flight display are provided to potentially inform the flight crew of safety critical envelope alterations caused by the impairment.

An Introduction to 3-D Sound

NASA Technical Reports Server (NTRS)

Begault, Durand R.; Null, Cynthia H. (Technical Monitor)

1997-01-01

This talk will overview the basic technologies related to the creation of virtual acoustic images, and the potential of including spatial auditory displays in human-machine interfaces. Research into the perceptual error inherent in both natural and virtual spatial hearing is reviewed, since the formation of improved technologies is tied to psychoacoustic research. This includes a discussion of Head Related Transfer Function (HRTF) measurement techniques (the HRTF provides important perceptual cues within a virtual acoustic display). Many commercial applications of virtual acoustics have so far focused on games and entertainment ; in this review, other types of applications are examined, including aeronautic safety, voice communications, virtual reality, and room acoustic simulation. In particular, the notion that realistic simulation is optimized within a virtual acoustic display when head motion and reverberation cues are included within a perceptual model.

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

NASA Astrophysics Data System (ADS)

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

2002-02-01

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

Advanced and tendencies in the development of display technologies

NASA Astrophysics Data System (ADS)

Kompanets, I. N.

2006-06-01

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

LCTV Holographic Imaging

NASA Technical Reports Server (NTRS)

Knopp, Jerome

1996-01-01

Astronauts are required to interface with complex systems that require sophisticated displays to communicate effectively. Lightweight, head-mounted real-time displays that present holographic images for comfortable viewing may be the ideal solution. We describe an implementation of a liquid crystal television (LCTV) as a spatial light modulator (SLM) for the display of holograms. The implementation required the solution of a complex set of problems. These include field calculations, determination of the LCTV-SLM complex transmittance characteristics and a precise knowledge of the signal mapping between the LCTV and frame grabbing board that controls it. Realizing the hologram is further complicated by the coupling that occurs between the phase and amplitude in the LCTV transmittance. A single drive signal (a gray level signal from a framegrabber) determines both amplitude and phase. Since they are not independently controllable (as is true in the ideal SLM) one must deal with the problem of optimizing (in some sense) the hologram based on this constraint. Solutions for the above problems have been found. An algorithm has been for field calculations that uses an efficient outer product formulation. Juday's MEDOF 7 (Minimum Euclidean Distance Optimal Filter) algorithm used for originally for filter calculations has been successfully adapted to handle metrics appropriate for holography. This has solved the problem of optimizing the hologram to the constraints imposed by coupling. Two laboratory methods have been developed for determining an accurate mapping of framegrabber pixels to LCTV pixels. A friendly software system has been developed that integrates the hologram calculation and realization process using a simple set of instructions. The computer code and all the laboratory measurement techniques determining SLM parameters have been proven with the production of a high quality test image.

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

NASA Astrophysics Data System (ADS)

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

2011-03-01

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

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

PubMed

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

2015-01-01

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

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

PubMed

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

2011-08-01

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

Temporal filtering of reward signals in the dorsal anterior cingulate cortex during a mixed-strategy game

PubMed Central

Seo, Hyojung; Lee, Daeyeol

2008-01-01

The process of decision making in humans and other animals is adaptive and can be tuned through experience so as to optimize the outcomes of their choices in a dynamic environment. Previous studies have demonstrated that the anterior cingulate cortex plays an important role in updating the animal’s behavioral strategies when the action-outcome contingencies change. Moreover, neurons in the anterior cingulate cortex often encode the signals related to expected or actual reward. We investigated whether reward-related activity in the anterior cingulate cortex is affected by the animal’s previous reward history. This was tested in rhesus monkeys trained to make binary choices in a computer-simulated competitive zero-sum game. The animal’s choice behavior was relatively close to the optimal strategy, but also revealed small but systematic biases that are consistent with the use of a reinforcement learning algorithm. In addition, the activity of neurons in the dorsal anterior cingulate cortex that was related to the reward received by the animal in a given trial was often modulated by the rewards in the previous trials. Some of these neurons encoded the rate of rewards in previous trials, whereas others displayed activity modulations more closely related to the reward prediction errors. By contrast, signals related to the animal’s choices were only weakly represented in this cortical area. These results suggest that neurons in the dorsal anterior cingulate cortex might be involved in the subjective evaluation of choice outcomes based on the animal’s reward history. PMID:17670983

Efficient Electron Transfer across a ZnO-MoS2 -Reduced Graphene Oxide Heterojunction for Enhanced Sunlight-Driven Photocatalytic Hydrogen Evolution.

PubMed

Kumar, Suneel; Reddy, Nagappagari Lakshmana; Kushwaha, Himmat Singh; Kumar, Ashish; Shankar, Muthukonda Venkatakrishnan; Bhattacharyya, Kaustava; Halder, Aditi; Krishnan, Venkata

2017-09-22

The development of noble metal-free catalysts for hydrogen evolution is required for energy applications. In this regard, ternary heterojunction nanocomposites consisting of ZnO nanoparticles anchored on MoS 2 -RGO (RGO=reduced graphene oxide) nanosheets as heterogeneous catalysts show highly efficient photocatalytic H 2 evolution. In the photocatalytic process, the catalyst dispersed in an electrolytic solution (S 2- and SO 3 2- ions) exhibits an enhanced rate of H 2 evolution, and optimization experiments reveal that ZnO with 4.0 wt % of MoS 2 -RGO nanosheets gives the highest photocatalytic H 2 production of 28.616 mmol h -1  g cat -1 under sunlight irradiation; approximately 56 times higher than that on bare ZnO and several times higher than those of other ternary photocatalysts. The superior catalytic activity can be attributed to the in situ generation of ZnS, which leads to improved interfacial charge transfer to the MoS 2 cocatalyst and RGO, which has plenty of active sites available for photocatalytic reactions. Recycling experiments also proved the stability of the optimized photocatalyst. In addition, the ternary nanocomposite displayed multifunctional properties for hydrogen evolution activity under electrocatalytic and photoelectrocatalytic conditions owing to the high electrode-electrolyte contact area. Thus, the present work provides very useful insights for the development of inexpensive, multifunctional catalysts without noble metal loading to achieve a high rate of H 2 generation. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

DOEpatents

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

1999-01-05

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

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

DOEpatents

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

1999-01-01

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

A Novel Alkaliphilic Bacillus Esterase Belongs to the 13th Bacterial Lipolytic Enzyme Family

PubMed Central

Rao, Lang; Xue, Yanfen; Zheng, Yingying; Lu, Jian R.; Ma, Yanhe

2013-01-01

Background Microbial derived lipolytic hydrolysts are an important class of biocatalysts because of their huge abundance and ability to display bioactivities under extreme conditions. In spite of recent advances, our understanding of these enzymes remains rudimentary. The aim of our research is to advance our understanding by seeking for more unusual lipid hydrolysts and revealing their molecular structure and bioactivities. Methodology/Principal Findings Bacillus. pseudofirmus OF4 is an extreme alkaliphile with tolerance of pH up to 11. In this work we successfully undertook a heterologous expression of a gene estof4 from the alkaliphilic B. pseudofirmus sp OF4. The recombinant protein called EstOF4 was purified into a homologous product by Ni-NTA affinity and gel filtration. The purified EstOF4 was active as dimer with the molecular weight of 64 KDa. It hydrolyzed a wide range of substrates including p-nitrophenyl esters (C2–C12) and triglycerides (C2–C6). Its optimal performance occurred at pH 8.5 and 50°C towards p-nitrophenyl caproate and triacetin. Sequence alignment revealed that EstOF4 shared 71% identity to esterase Est30 from Geobacillus stearothermophilus with a typical lipase pentapeptide motif G91LS93LG95. A structural model developed from homology modeling revealed that EstOF4 possessed a typical esterase 6α/7β hydrolase fold and a cap domain. Site-directed mutagenesis and inhibition studies confirmed the putative catalytic triad Ser93, Asp190 and His220. Conclusion EstOF4 is a new bacterial esterase with a preference to short chain ester substrates. With a high sequence identity towards esterase Est30 and several others, EstOF4 was classified into the same bacterial lipolytic family, Family XIII. All the members in this family originate from the same bacterial genus, bacillus and display optimal activities from neutral pH to alkaline conditions with short and middle chain length substrates. However, with roughly 70% sequence identity, these enzymes showed hugely different thermal stabilities, indicating their diverse thermal adaptations via just changing a few amino acid residues. PMID:23577139

Integrating Patient-Reported Outcomes into Spine Surgical Care through Visual Dashboards: Lessons Learned from Human-Centered Design

PubMed Central

Hartzler, Andrea L.; Chaudhuri, Shomir; Fey, Brett C.; Flum, David R.; Lavallee, Danielle

2015-01-01

Introduction: The collection of patient-reported outcomes (PROs) draws attention to issues of importance to patients—physical function and quality of life. The integration of PRO data into clinical decisions and discussions with patients requires thoughtful design of user-friendly interfaces that consider user experience and present data in personalized ways to enhance patient care. Whereas most prior work on PROs focuses on capturing data from patients, little research details how to design effective user interfaces that facilitate use of this data in clinical practice. We share lessons learned from engaging health care professionals to inform design of visual dashboards, an emerging type of health information technology (HIT). Methods: We employed human-centered design (HCD) methods to create visual displays of PROs to support patient care and quality improvement. HCD aims to optimize the design of interactive systems through iterative input from representative users who are likely to use the system in the future. Through three major steps, we engaged health care professionals in targeted, iterative design activities to inform the development of a PRO Dashboard that visually displays patient-reported pain and disability outcomes following spine surgery. Findings: Design activities to engage health care administrators, providers, and staff guided our work from design concept to specifications for dashboard implementation. Stakeholder feedback from these health care professionals shaped user interface design features, including predefined overviews that illustrate at-a-glance trends and quarterly snapshots, granular data filters that enable users to dive into detailed PRO analytics, and user-defined views to share and reuse. Feedback also revealed important considerations for quality indicators and privacy-preserving sharing and use of PROs. Conclusion: Our work illustrates a range of engagement methods guided by human-centered principles and design recommendations for optimizing PRO Dashboards for patient care and quality improvement. Engaging health care professionals as stakeholders is a critical step toward the design of user-friendly HIT that is accepted, usable, and has the potential to enhance quality of care and patient outcomes. PMID:25988187

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

NASA Astrophysics Data System (ADS)

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

2016-09-01

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

Expression and Characterization of a Novel Thermo-Alkalistable Lipase from Hyperthermophilic Bacterium Thermotoga maritima.

PubMed

Tian, Rui; Chen, Huayou; Ni, Zhong; Zhang, Qing; Zhang, Zhongge; Zhang, Tianxi; Zhang, Chunxia; Yang, Shengli

2015-07-01

A gene coding for lipase (Tm1350) from the hyperthermophilic bacterium Thermotoga maritima MSB8 was cloned and overexpressed by Escherichia coli. The enzyme can degrade substrates with both short and long acyl chain lengths. The apparent Km and Vmax values for p-nitrophenyl butyrate were 8 mM and 333 U/mg, respectively. The enzyme displayed optimal activity at pH 7.5 and 70 °C, maintained 66 % of the original activity after 8 h of incubation, and its half-lives at pHs 9 and 10 were 8 and 1 h. The activity of Tm1350 was stimulated up to 131 or 151 % of the original activity by incubating with 4 M urea or 20 % (v/v) methanol, and 90.1 or 70.2 % of the activity was maintained after 8 h incubation of the enzyme in 20 or 75 % (v/v) of the methanol, showing potential for biodiesel production. The activity of the enzyme without cysteine residue was stimulated up to 618 and 550 % of the original activity by incubating with dithiothreitol (DTT) and reduced glutathione (GSH) at a concentration of 1 mM. However, the circular dichroism spectra of the enzyme have no obvious change after DTT treatment. It is speculated that DTT interacts with potential residues in some key active sites without influence of structure.

Demonstration of Vibrational Braille Code Display Using Large Displacement Micro-Electro-Mechanical Systems Actuators

NASA Astrophysics Data System (ADS)

Watanabe, Junpei; Ishikawa, Hiroaki; Arouette, Xavier; Matsumoto, Yasuaki; Miki, Norihisa

2012-06-01

In this paper, we present a vibrational Braille code display with large-displacement micro-electro-mechanical systems (MEMS) actuator arrays. Tactile receptors are more sensitive to vibrational stimuli than to static ones. Therefore, when each cell of the Braille code vibrates at optimal frequencies, subjects can recognize the codes more efficiently. We fabricated a vibrational Braille code display that used actuators consisting of piezoelectric actuators and a hydraulic displacement amplification mechanism (HDAM) as cells. The HDAM that encapsulated incompressible liquids in microchambers with two flexible polymer membranes could amplify the displacement of the MEMS actuator. We investigated the voltage required for subjects to recognize Braille codes when each cell, i.e., the large-displacement MEMS actuator, vibrated at various frequencies. Lower voltages were required at vibration frequencies higher than 50 Hz than at vibration frequencies lower than 50 Hz, which verified that the proposed vibrational Braille code display is efficient by successfully exploiting the characteristics of human tactile receptors.

In vitro Fab display: a cell-free system for IgG discovery

PubMed Central

Stafford, Ryan L.; Matsumoto, Marissa L.; Yin, Gang; Cai, Qi; Fung, Juan Jose; Stephenson, Heather; Gill, Avinash; You, Monica; Lin, Shwu-Hwa; Wang, Willie D.; Masikat, Mary Rose; Li, Xiaofan; Penta, Kalyani; Steiner, Alex R.; Baliga, Ramesh; Murray, Christopher J.; Thanos, Christopher D.; Hallam, Trevor J.; Sato, Aaron K.

2014-01-01

Selection technologies such as ribosome display enable the rapid discovery of novel antibody fragments entirely in vitro. It has been assumed that the open nature of the cell-free reactions used in these technologies limits selections to single-chain protein fragments. We present a simple approach for the selection of multi-chain proteins, such as antibody Fab fragments, using ribosome display. Specifically, we show that a two-chain trastuzumab (Herceptin) Fab domain can be displayed in a format which tethers either the heavy or light chain to the ribosome while retaining functional antigen binding. Then, we constructed synthetic Fab HC and LC libraries and performed test selections against carcinoembryonic antigen (CEA) and vascular endothelial growth factor (VEGF). The Fab selection output was reformatted into full-length immunoglobulin Gs (IgGs) and directly expressed at high levels in an optimized cell-free system for immediate screening, purification and characterization. Several novel IgGs were identified using this cell-free platform that bind to purified CEA, CEA positive cells and VEGF. PMID:24586053

Optimization of medical imaging display systems: using the channelized Hotelling observer for detecting lung nodules: experimental study

NASA Astrophysics Data System (ADS)

Platisa, Ljiljana; Vansteenkiste, Ewout; Goossens, Bart; Marchessoux, Cédric; Kimpe, Tom; Philips, Wilfried

2009-02-01

Medical-imaging systems are designed to aid medical specialists in a specific task. Therefore, the physical parameters of a system need to optimize the task performance of a human observer. This requires measurements of human performance in a given task during the system optimization. Typically, psychophysical studies are conducted for this purpose. Numerical observer models have been successfully used to predict human performance in several detection tasks. Especially, the task of signal detection using a channelized Hotelling observer (CHO) in simulated images has been widely explored. However, there are few studies done for clinically acquired images that also contain anatomic noise. In this paper, we investigate the performance of a CHO in the task of detecting lung nodules in real radiographic images of the chest. To evaluate variability introduced by the limited available data, we employ a commonly used study of a multi-reader multi-case (MRMC) scenario. It accounts for both case and reader variability. Finally, we use the "oneshot" methods to estimate the MRMC variance of the area under the ROC curve (AUC). The obtained AUC compares well to those reported for human observer study on a similar data set. Furthermore, the "one-shot" analysis implies a fairly consistent performance of the CHO with the variance of AUC below 0.002. This indicates promising potential for numerical observers in optimization of medical imaging displays and encourages further investigation on the subject.

Understanding the Cognitive and Affective Mechanisms that Underlie Proxy Risk Perceptions among Caregivers of Asthmatic Children.

PubMed

Shepperd, James A; Lipsey, Nikolette P; Pachur, Thorsten; Waters, Erika A

2018-07-01

Medical decisions made on behalf of another person-particularly those made by adult caregivers for their minor children-are often informed by the decision maker's beliefs about the treatment's risks and benefits. However, we know little about the cognitive and affective mechanisms influencing such "proxy" risk perceptions and about how proxy risk perceptions are related to prominent judgment phenomena. Adult caregivers of minor children with asthma ( N = 132) completed an online, cross-sectional survey assessing 1) cognitions and affects that form the basis of the availability, representativeness, and affect heuristics; 2) endorsement of the absent-exempt and the better-than-average effect; and 3) proxy perceived risk and unrealistic comparative optimism of an asthma exacerbation. We used the Pediatric Asthma Control and Communication Instrument (PACCI) to assess asthma severity. Respondents with higher scores on availability, representativeness, and negative affect indicated higher proxy risk perceptions and (for representativeness only) lower unrealistic optimism, irrespective of asthma severity. Conversely, respondents who showed a stronger display of the better-than-average effect indicated lower proxy risk perceptions but did not differ in unrealistic optimism. The absent-exempt effect was unrelated to proxy risk perceptions and unrealistic optimism. Heuristic judgment processes appear to contribute to caregivers' proxy risk perceptions of their child's asthma exacerbation risk. Moreover, the display of other, possibly erroneous, judgment phenomena is associated with lower caregiver risk perceptions. Designing interventions that target these mechanisms may help caregivers work with their children to reduce exacerbation risk.

Self-healing of damage in fibre-reinforced polymer-matrix composites.

PubMed

Hayes, S A; Zhang, W; Branthwaite, M; Jones, F R

2007-04-22

Self-healing resin systems have been discussed for over a decade and four different technologies had been proposed. However, little work on their application as composite matrices has been published although this was one of the stated aims of the earliest work in the field. This paper reports on the optimization of a solid-state self-healing resin system and its subsequent use as a matrix for high volume fraction glass fibre-reinforced composites. The resin system was optimized using Charpy impact testing and repeated healing, while the efficiency of healing in composites was determined by analysing the growth of delaminations following repeated impacts with or without a healing cycle. To act as a reference, a non-healing resin system was subjected to the same treatments and the results are compared with the healable system. The optimized resin system displays a healing efficiency of 65% after the first healing cycle, dropping to 35 and 30% after the second and third healing cycles, respectively. Correction for any healability due to further curing showed that approximately 50% healing efficiency could be achieved with the bisphenol A-based epoxy resin containing 7.5% of polybisphenol-A-co-epichlorohydrin. The composite, on the other hand, displays a healing efficiency of approximately 30%. It is therefore clear that the solid-state self-healing system is capable of healing transverse cracks and delaminations in a composite, but that more work is needed to optimize matrix healing within a composite and to develop a methodology for assessing recovery in performance.

Antimicrobial activity of synthetic cationic peptides and lipopeptides derived from human lactoferricin against Pseudomonas aeruginosa planktonic cultures and biofilms.

PubMed

Sánchez-Gómez, Susana; Ferrer-Espada, Raquel; Stewart, Philip S; Pitts, Betsey; Lohner, Karl; Martínez de Tejada, Guillermo

2015-07-07

Infections by Pseudomonas aeruginosa constitute a serious health threat because this pathogen -particularly when it forms biofilms - can acquire resistance to the majority of conventional antibiotics. This study evaluated the antimicrobial activity of synthetic peptides based on LF11, an 11-mer peptide derived from human lactoferricin against P. aeruginosa planktonic and biofilm-forming cells. We included in this analysis selected N-acylated derivatives of the peptides to analyze the effect of acylation in antimicrobial activity. To assess the efficacy of compounds against planktonic bacteria, microdilution assays to determine the minimal inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time-kill studies were conducted. The anti-biofilm activity of the agents was assessed on biofilms grown under static (on microplates) and dynamic (in a CDC-reactor) flow regimes. The antimicrobial activity of lipopeptides differed from that of non-acylated peptides in their killing mechanisms on planktonic and biofilm-forming cells. Thus, acylation enhanced the bactericidal activity of the parental peptides and resulted in lipopeptides that were uniformly bactericidal at their MIC. In contrast, acylation of the most potent anti-biofilm peptides resulted in compounds with lower anti-biofilm activity. Both peptides and lipopeptides displayed very rapid killing kinetics and all of them required less than 21 min to reduce 1,000 times the viability of planktonic cells when tested at 2 times their MBC. The peptides, LF11-215 (FWRIRIRR) and LF11-227 (FWRRFWRR), displayed the most potent anti-biofilm activity causing a 10,000 fold reduction in cell viability after 1 h of treatment at 10 times their MIC. At that concentration, these two compounds exhibited low citotoxicity on human cells. In addition to its bactericidal activity, LF11-227 removed more that 50 % of the biofilm mass in independent assays. Peptide LF11-215 and two of the shortest and least hydrophobic lipopeptides, DI-MB-LF11-322 (2,2-dimethylbutanoyl-PFWRIRIRR) and DI-MB-LF11-215, penetrated deep into the biofilm structure and homogenously killed biofilm-forming bacteria. We identified peptides derived from human lactoferricin with potent antimicrobial activity against P. aeruginosa growing either in planktonic or in biofilm mode. Although further structure-activity relationship analyses are necessary to optimize the anti-biofilm activity of these compounds, the results indicate that lactoferricin derived peptides are promising anti-biofilm agents.

Generation and analysis of the improved human HAL9/10 antibody phage display libraries.

PubMed

Kügler, Jonas; Wilke, Sonja; Meier, Doris; Tomszak, Florian; Frenzel, André; Schirrmann, Thomas; Dübel, Stefan; Garritsen, Henk; Hock, Björn; Toleikis, Lars; Schütte, Mark; Hust, Michael

2015-02-19

Antibody phage display is a proven key technology that allows the generation of human antibodies for diagnostics and therapy. From naive antibody gene libraries - in theory - antibodies against any target can be selected. Here we describe the design, construction and characterization of an optimized antibody phage display library. The naive antibody gene libraries HAL9 and HAL10, with a combined theoretical diversity of 1.5×10(10) independent clones, were constructed from 98 healthy donors using improved phage display vectors. In detail, most common phagemids employed for antibody phage display are using a combined His/Myc tag for detection and purification. We show that changing the tag order to Myc/His improved the production of soluble antibodies, but did not affect antibody phage display. For several published antibody libraries, the selected number of kappa scFvs were lower compared to lambda scFvs, probably due to a lower kappa scFv or Fab expression rate. Deletion of a phenylalanine at the end of the CL linker sequence in our new phagemid design increased scFv production rate and frequency of selected kappa antibodies significantly. The HAL libraries and 834 antibodies selected against 121 targets were analyzed regarding the used germline V-genes, used V-gene combinations and CDR-H3/-L3 length and composition. The amino acid diversity and distribution in the CDR-H3 of the initial library was retrieved in the CDR-H3 of selected antibodies showing that all CDR-H3 amino acids occurring in the human antibody repertoire can be functionally used and is not biased by E. coli expression or phage selection. Further, the data underline the importance of CDR length variations. The highly diverse universal antibody gene libraries HAL9/10 were constructed using an optimized scFv phagemid vector design. Analysis of selected antibodies revealed that the complete amino acid diversity in the CDR-H3 was also found in selected scFvs showing the functionality of the naive CDR-H3 diversity.

Beyond helper phage: Using "helper cells" to select peptide affinity ligands

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

Phipps, Mary Lisa; Lillo, Antoinetta M.; Shou, Yulin

Peptides are important affinity ligands for microscopy, biosensing, and targeted delivery. However, because they can have low affinity for their targets, their selection from large naïve libraries can be challenging. When selecting peptidic ligands from display libraries, it is important to: 1) ensure efficient display; 2) maximize the ability to select high affinity ligands; and 3) minimize the effect of the display context on binding. The “helper cell” packaging system has been described as a tool to produce filamentous phage particles based on phagemid constructs with varying display levels, while remaining free of helper phage contamination. Here we report onmore » the first use of this system for peptide display, including the systematic characterization and optimization of helper cells, their inefficient use in antibody display and their use in creating and selecting from a set of phage display peptide libraries. Our libraries were analyzed with unprecedented precision by standard or deep sequencing, and shown to be superior in quality than commercial gold standards. Using our helper cell libraries, we have obtained ligands recognizing Yersinia pestis surface antigen F1V and L-glutamine-binding periplasmic protein QBP. In the latter case, unlike any of the peptide library selections described so far, we used a combination of phage and yeast display to select intriguing peptide ligands. Here, based on the success of our selections we believe that peptide libraries obtained with helper cells are not only suitable, but preferable to traditional phage display libraries for selection of peptidic ligands.« less

Beyond helper phage: Using "helper cells" to select peptide affinity ligands

DOE PAGES

Phipps, Mary Lisa; Lillo, Antoinetta M.; Shou, Yulin; ...

2016-09-14

Peptides are important affinity ligands for microscopy, biosensing, and targeted delivery. However, because they can have low affinity for their targets, their selection from large naïve libraries can be challenging. When selecting peptidic ligands from display libraries, it is important to: 1) ensure efficient display; 2) maximize the ability to select high affinity ligands; and 3) minimize the effect of the display context on binding. The “helper cell” packaging system has been described as a tool to produce filamentous phage particles based on phagemid constructs with varying display levels, while remaining free of helper phage contamination. Here we report onmore » the first use of this system for peptide display, including the systematic characterization and optimization of helper cells, their inefficient use in antibody display and their use in creating and selecting from a set of phage display peptide libraries. Our libraries were analyzed with unprecedented precision by standard or deep sequencing, and shown to be superior in quality than commercial gold standards. Using our helper cell libraries, we have obtained ligands recognizing Yersinia pestis surface antigen F1V and L-glutamine-binding periplasmic protein QBP. In the latter case, unlike any of the peptide library selections described so far, we used a combination of phage and yeast display to select intriguing peptide ligands. Here, based on the success of our selections we believe that peptide libraries obtained with helper cells are not only suitable, but preferable to traditional phage display libraries for selection of peptidic ligands.« less

Patterns of sarcomere activation, temperature dependence, and effect of ryanodine in chemically skinned cardiac fibers

PubMed Central

1986-01-01

Functionally skinned and electrochemically shunted myocytes were prepared by perfusing rat hearts with collagenase in order to obtain a technically improved measurement of sarcomere dynamics and to evaluate the role of sarcoplasmic reticulum in situ with respect to contractile activation. In the presence of micromolar calcium, the myocytes exhibited phasic and propagated contraction waves beginning at one end and proceeding along the myocyte. Beating rates, the propagation velocity of the activation wave, and single sarcomere shortening and relaxation velocities were obtained by manual or automated analysis of 16-mm film recorded at 170 frames/s from a camera attached to a microscope that was equipped with a temperature-controlled stage. In parallel experiments, calcium accumulation by the sarcoplasmic reticulum of the myocytes in situ was measured by direct isotopic tracer methods. The frequency (10-38 min-1) of spontaneous contractions, the velocity (1.9-7.4 microns . s-1) of sarcomere shortening, and the velocity (1.7-6.8 microns . s-1) of sarcomere relaxation displayed identical temperature dependences (Q10 = 2.2), which are similar to that of the calcium pump of sarcoplasmic reticulum and are consistent with a rate limit imposed by enzyme-catalyzed mechanisms on all these parameters. On the other hand, the velocity (77- 159 microns . s-1) of sequential sarcomere activation displayed a lower temperature dependence (Q10 = 1.5), which is consistent with a diffusion-limited and self-propagating release of calcium from one sarcomere to the other. The phasic contractile activity of the dissociated myocytes was inhibited by 10(-8)-10(6) M ryanodine (and not by myolemmal calcium blockers) under conditions in which calcium accumulation by sarcoplasmic reticulum in situ was demonstrated to proceed optimally. The effect of ryanodine is attributed to an interaction of this drug with sarcotubular structures, producing inhibition of calcium release from the sarcoplasmic reticulum. The consequent lack of sarcomere activation underlines the role of sarcoplasmic reticulum uptake and release in the phasic contractile activation of the electrochemically shunted myocytes. PMID:3522803

Electroencephalogram (EEG) and Magnetoencephalogram (MEG) as Tools for Evaluation of Cognitive Function

NASA Technical Reports Server (NTRS)

Fender, Derek H.; Hestenes, John D.

1985-01-01

We have developed computerized analysis and display techniques to help identify the origins of visually evoked scalped potentials (VESP). The potentials are recorded simultaneously from many electrodes (usually 40 to 48) spaced over the region of the scalp where appreciable evoked potentials are found in response to particular stimulus. Contour mapping algorithms are then used to display the time behavior of equipotential surfaces on the scalp during the VESP. We then use an optimization technique to select the parameters of arrays of current dipole sources within the model until the model equipotential field distribution closely fits the measured data. Computer graphics are then used to display, as a movie, the actual and model scalp potential fields and the parameters of the dipole generators within the model head during the course of VESP activity. We have devised reaction time tests that involve potentially separable stages of cognitive processing and utilize stimuli that produce measurable cognition-related features in the late component of the evoked potential. We have used these techniques to determine the loci in the brain where known cognition-related features in the evoked potential are generated and we have explored the extent to which each of these features can be related to the reaction time tasks. We have also examined the temporal-spatial aspects of their cerebral involvement. Our current work is planned to characterize the age-related changes in the processes performed by such sources. We also use a neuromagnetometer to measure the evoked magnetic fields in similar circumstances; we will discuss the relative merits of the two methodologies.

Cross-talk reduction by correcting the subpixel position in a multiview autostereoscopic three-dimensional display based on a lenticular sheet.

PubMed

Wang, Qiong-Hua; Li, Xiao-Fang; Zhou, Lei; Wang, Ai-Hong; Li, Da-Hai

2011-03-01

A method is proposed to alleviate the cross talk in multiview autostereoscopic three-dimensional displays based on a lenticular sheet. We analyze the positional relationship between subpixels on the image panel and the lenticular sheet. According to this relationship, optimal synthetic images are synthesized to minimize cross talk by correcting the positions of subpixels on the image panel. Experimental results show that the proposed method significantly reduces the cross talk of view images and improves the quality of stereoscopic images. © 2010 Optical Society of America

A faster technique for rendering meshes in multiple display systems

NASA Astrophysics Data System (ADS)

Hand, Randall E.; Moorhead, Robert J., II

2003-05-01

Level of detail algorithms have widely been implemented in architectural VR walkthroughs and video games, but have not had widespread use in VR terrain visualization systems. This thesis explains a set of optimizations to allow most current level of detail algorithms run in the types of multiple display systems used in VR. It improves both the visual quality of the system through use of graphics hardware acceleration, and improves the framerate and running time through moifications to the computaitons that drive the algorithms. Using ROAM as a testbed, results show improvements between 10% and 100% on varying machines.