Logging utilization in Oregon and Washington, 2011–2015

Treesearch

Eric A. Simmons; Todd A. Morgan; Erik C. Berg; Steven W. Hayes; Glenn A. Christensen

2016-01-01

A study of commercial timber harvesting activities in Oregon and Washington was conducted from 2011 through 2015 to characterize current tree utilization, logging operations, and assist with estimating the amount of woody biomass left onsite after harvesting. Sample logging sites were selected within major geographic regions proportional to regional 5-year timber...

Applications of Remote Sensing to Emergency Management.

DTIC Science & Technology

1980-02-15

Contents: Foundations of Remote Sensing : Data Acquisition and Interpretation; Availability of Remote Sensing Technology for Disaster Response...Imaging Systems, Current and Near Future Satellite and Aircraft Remote Sensing Systems; Utilization of Remote Sensing in Disaster Response: Categories of...Disasters, Phases of Monitoring Activities; Recommendations for Utilization of Remote Sensing Technology in Disaster Response; Selected Reading List.

Processing and fractional utilization of lignocellulosic substrates by "pure" and "natural and defined mixed" culture C.TM1, C.SA IV and rumen mixed culture consortia CD.

PubMed

Sankar, M; Chandra, T S

2003-01-01

A detailed analysis was made of chemical fractions of common agro-residues before and after pretreatment (alkali and hydrogen peroxide), and the selective utilization of components such as WSS, EBS, TSS, lignin, cellulose and hemicellulose by pure and mixed cultures of cellulolytic and xylanolytic Clostridia was monitored and correlated with the organisms' enzyme activity. For all cultures pretreatment gave higher utilization of hemicellulose and cellulose fractions; hydrogen peroxide pretreatment was more effective than NaOH treatment. Lignin utilization was not very significant even on pretreatment. C.TM1 and C.SA IV utilized hemicellulose and cellulose better than mixed cultures in selected substrates. These results help to determine the substrate composition, pretreatment conditions and enzyme system of the organism needed when designing an inoculum for agricultural waste treatment processes such as composting or biogas generation.

Selection of yeast Saccharomyces cerevisiae promoters available for xylose cultivation and fermentation.

PubMed

Nambu-Nishida, Yumiko; Sakihama, Yuri; Ishii, Jun; Hasunuma, Tomohisa; Kondo, Akihiko

2018-01-01

To efficiently utilize xylose, a major sugar component of hemicelluloses, in Saccharomyces cerevisiae requires the proper expression of varied exogenous and endogenous genes. To expand the repertoire of promoters in engineered xylose-utilizing yeast strains, we selected promoters in S. cerevisiae during cultivation and fermentation using xylose as a carbon source. To select candidate promoters that function in the presence of xylose, we performed comprehensive gene expression analyses using xylose-utilizing yeast strains both during xylose and glucose fermentation. Based on microarray data, we chose 29 genes that showed strong, moderate, and weak expression in xylose rather than glucose fermentation. The activities of these promoters in a xylose-utilizing yeast strain were measured by lacZ reporter gene assays over time during aerobic cultivation and microaerobic fermentation, both in xylose and glucose media. In xylose media, P TDH3 , P FBA1 , and P TDH1 were favorable for high expression, and P SED1 , P HXT7 , P PDC1 , P TEF1 , P TPI1 , and P PGK1 were acceptable for medium-high expression in aerobic cultivation, and moderate expression in microaerobic fermentation. P TEF2 allowed moderate expression in aerobic culture and weak expression in microaerobic fermentation, although it showed medium-high expression in glucose media. P ZWF1 and P SOL4 allowed moderate expression in aerobic cultivation, while showing weak but clear expression in microaerobic fermentation. P ALD3 and P TKL2 showed moderate promoter activity in aerobic cultivation, but showed almost no activity in microaerobic fermentation. The knowledge of promoter activities in xylose cultivation obtained in this study will permit the control of gene expression in engineered xylose-utilizing yeast strains that are used for hemicellulose fermentation. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Analysis of ecologically relevant pharmaceuticals in wastewater and surface water using selective solid phase extraction and UPLC/MS/MS

EPA Science Inventory

A rapid and sensitive method has been developed for the analysis of 48 human prescription active pharmaceutical ingredients (APIs) and 6 metabolites of interest, utilizing selective solid-phase extraction (SPE) and ultra performance liquid chromatography in combination with tripl...

Toward seamless wearable sensing: Automatic on-body sensor localization for physical activity monitoring.

PubMed

Saeedi, Ramyar; Purath, Janet; Venkatasubramanian, Krishna; Ghasemzadeh, Hassan

2014-01-01

Mobile wearable sensors have demonstrated great potential in a broad range of applications in healthcare and wellness. These technologies are known for their potential to revolutionize the way next generation medical services are supplied and consumed by providing more effective interventions, improving health outcomes, and substantially reducing healthcare costs. Despite these potentials, utilization of these sensor devices is currently limited to lab settings and in highly controlled clinical trials. A major obstacle in widespread utilization of these systems is that the sensors need to be used in predefined locations on the body in order to provide accurate outcomes such as type of physical activity performed by the user. This has reduced users' willingness to utilize such technologies. In this paper, we propose a novel signal processing approach that leverages feature selection algorithms for accurate and automatic localization of wearable sensors. Our results based on real data collected using wearable motion sensors demonstrate that the proposed approach can perform sensor localization with 98.4% accuracy which is 30.7% more accurate than an approach without a feature selection mechanism. Furthermore, utilizing our node localization algorithm aids the activity recognition algorithm to achieve 98.8% accuracy (an increase from 33.6% for the system without node localization).

In vitro fermentation of prebiotics by Lactobacillus plantarum CFR 2194: selectivity, viability and effect of metabolites on β-glucuronidase activity.

PubMed

Arenahalli Ningegowda, Madhu; Siddalingaiya Gurudutt, Prapulla

2012-03-01

Prebiotic Fructooligosaccharides (FOS) escape metabolism in upper GI tract undergo microbial metabolism in colon and thereby influence the nature, type and number of intestinal microbiota to improve host's health. The present study focuses on the ability of Lactobacillus plantarum CFR 2194 to utilize FOS as a selective carbon and energy source. The effect of fermentative metabolites of L. plantarum on the β-glucuronidase was also investigated. A total of 16 strains of lactobacilli were assessed for their ability to ferment oligosaccharides. L. plantarum CFR 2194, an isolate from kanjika was found to utilize FOS effectively. Lactic acid was the main metabolic end product, followed by acetic acid, butyric acid, formic acid and ethanol. The inhibitory effects of these metabolites have been confirmed through the reduction of β-glucuronidase activity. L. plantarum when co-cultured with β-glucuronidase producing E. coli, in a basal media containing FOS as an energy source, could inhibit the growth of the pathogen during the course of fermentation. The results showed that L. plantarum CFR 2194 has the ability to utilize the prebiotic FOS as a selective carbon and energy source. The organism could inhibit the growth of the pathogen which produces β-glucuronidase and lowered its activity by the metabolites of FOS which indicates the probable use of L. plantarum through dietary intervention in combating colon carcinogenesis.

Active heat exchange system development for latent heat thermal energy storage

NASA Technical Reports Server (NTRS)

Lefrois, R. T.; Mathur, A. K.

1980-01-01

Five tasks to select, design, fabricate, test and evaluate candidate active heat exchanger modules for future applications to solar and conventional utility power plants were discussed. Alternative mechanizations of active heat exchange concepts were analyzed for use with heat of fusion phase change materials (PCMs) in the temperature range of 250 to 350 C. Twenty-six heat exchange concepts were reviewed, and eight were selected for detailed assessment. Two candidates were selected for small-scale experimentation: a coated tube and shell heat exchanger and a direct contact reflux boiler. A dilute eutectic mixture of sodium nitrate and sodium hydroxide was selected as the PCM from over 50 candidate inorganic salt mixtures. Based on a salt screening process, eight major component salts were selected initially for further evaluation. The most attractive major components in the temperature range of 250 to 350 C appeared to be NaNO3, NaNO2, and NaOH. Sketches of the two active heat exchange concepts selected for test are given.

Active heat exchange system development for latent heat thermal energy storage

NASA Astrophysics Data System (ADS)

Lefrois, R. T.; Mathur, A. K.

1980-04-01

Five tasks to select, design, fabricate, test and evaluate candidate active heat exchanger modules for future applications to solar and conventional utility power plants were discussed. Alternative mechanizations of active heat exchange concepts were analyzed for use with heat of fusion phase change materials (PCMs) in the temperature range of 250 to 350 C. Twenty-six heat exchange concepts were reviewed, and eight were selected for detailed assessment. Two candidates were selected for small-scale experimentation: a coated tube and shell heat exchanger and a direct contact reflux boiler. A dilute eutectic mixture of sodium nitrate and sodium hydroxide was selected as the PCM from over 50 candidate inorganic salt mixtures. Based on a salt screening process, eight major component salts were selected initially for further evaluation. The most attractive major components in the temperature range of 250 to 350 C appeared to be NaNO3, NaNO2, and NaOH. Sketches of the two active heat exchange concepts selected for test are given.

Effective, Facile, and Selective Hydrolysis of the Chemical Warfare Agent VX Using Zr6-Based Metal-Organic Frameworks.

PubMed

Moon, Su-Young; Wagner, George W; Mondloch, Joseph E; Peterson, Gregory W; DeCoste, Jared B; Hupp, Joseph T; Farha, Omar K

2015-11-16

The nerve agent VX is among the most toxic chemicals known to mankind, and robust solutions are needed to rapidly and selectively deactivate it. Herein, we demonstrate that three Zr6-based metal-organic frameworks (MOFs), namely, UiO-67, UiO-67-NH2, and UiO-67-N(Me)2, are selective and highly active catalysts for the hydrolysis of VX. Utilizing UiO-67, UiO-67-NH2, and UiO-67-N(Me)2 in a pH 10 buffered solution of N-ethylmorpholine, selective hydrolysis of the P-S bond in VX was observed. In addition, UiO-67-N(Me)2 was found to catalyze VX hydrolysis with an initial half-life of 1.8 min. This half-life is nearly 3 orders of magnitude shorter than that of the only other MOF tested to date for hydrolysis of VX and rivals the activity of the best nonenzymatic materials. Hydrolysis utilizing Zr-based MOFs is also selective and facile in the absence of pH 10 buffer (just water) and for the destruction of the toxic byproduct EA-2192.

Construction of an alkaline phosphatase-specific two-photon probe and its imaging application in living cells and tissues.

PubMed

Zhang, Huatang; Xiao, Peng; Wong, Yin Ting; Shen, Wei; Chhabra, Mohit; Peltier, Raoul; Jiang, Yin; He, Yonghe; He, Jun; Tan, Yi; Xie, Yusheng; Ho, Derek; Lam, Yun-Wah; Sun, Jinpeng; Sun, Hongyan

2017-09-01

Alkaline phosphatase (ALP) is a family of enzymes involved in the regulation of important biological processes such as cell differentiation and bone mineralization. Monitoring the activity of ALP in serum can help diagnose a variety of diseases including bone and liver diseases. There has been growing interest in developing new chemical tools for monitoring ALP activity in living systems. Such tools will help further delineate the roles of ALP in biological and pathological processes. Previously reported fluorescent probes has a number of disadvantages that limit their application, such as poor selectivity and short-wavelength excitation. In this work, we report a new two-photon fluorescent probe (TP-Phos) to selectively detect ALP activity. The probe is composed of a two-photon fluorophore, a phosphate recognition moiety, and a self-cleavable adaptor. It offers a number of advantages over previously reported probes, such as fast reaction kinetics, high sensitivity and low cytotoxicity. Experimental results also showed that TP-Phos displayed improved selectivity over DIFMUP, a commonly utilized ALP probe. The selectivity is attributed to the utilization of an ortho-functionalised phenyl phosphate group, which increases the steric hindrance of the probe and the active site of phosphatases. Moreover, the two-photon nature of the probe confers enhanced imaging properties such as increased penetration depth and lower tissue autofluorescence. TP-Phos was successfully used to image the endogenous ALP activity of hippocampus, kidney and liver tissues from rat. Copyright © 2017 Elsevier Ltd. All rights reserved.

New Wind in Old Sails: Novel Applications of Triphos-based Transition Metal Complexes as Homogeneous Catalysts for Small Molecules and Renewables Activation.

PubMed

Mellone, Irene; Bertini, Federica; Gonsalvi, Luca; Guerriero, Antonella; Peruzzini, Maurizio

2015-01-01

Recent developments in the coordination chemistry and applications of Ru-triphos [triphos = 1,1,1-tris-(diphenylphosphinomethyl)ethane] systems are reviewed, highlighting their role as active and selective homogenous catalysts for small molecule activation, biomass conversions and in carbon dioxide utilization-related processes.

Isolation, Separation, and Preconcentration of Biologically Active Compounds from Plant Matrices by Extraction Techniques.

PubMed

Raks, Victoria; Al-Suod, Hossam; Buszewski, Bogusław

2018-01-01

Development of efficient methods for isolation and separation of biologically active compounds remains an important challenge for researchers. Designing systems such as organomineral composite materials that allow extraction of a wide range of biologically active compounds, acting as broad-utility solid-phase extraction agents, remains an important and necessary task. Selective sorbents can be easily used for highly selective and reliable extraction of specific components present in complex matrices. Herein, state-of-the-art approaches for selective isolation, preconcentration, and separation of biologically active compounds from a range of matrices are discussed. Primary focus is given to novel extraction methods for some biologically active compounds including cyclic polyols, flavonoids, and oligosaccharides from plants. In addition, application of silica-, carbon-, and polymer-based solid-phase extraction adsorbents and membrane extraction for selective separation of these compounds is discussed. Potential separation process interactions are recommended; their understanding is of utmost importance for the creation of optimal conditions to extract biologically active compounds including those with estrogenic properties.

Design of Highly Selective Platinum Nanoparticle Catalysts for the Aerobic Oxidation of KA-Oil using Continuous-Flow Chemistry.

PubMed

Gill, Arran M; Hinde, Christopher S; Leary, Rowan K; Potter, Matthew E; Jouve, Andrea; Wells, Peter P; Midgley, Paul A; Thomas, John M; Raja, Robert

2016-03-08

Highly active and selective aerobic oxidation of KA-oil to cyclohexanone (precursor for adipic acid and ɛ-caprolactam) has been achieved in high yields using continuous-flow chemistry by utilizing uncapped noble-metal (Au, Pt & Pd) nanoparticle catalysts. These are prepared using a one-step in situ methodology, within three-dimensional porous molecular architectures, to afford robust heterogeneous catalysts. Detailed spectroscopic characterization of the nature of the active sites at the molecular level, coupled with aberration-corrected scanning transmission electron microscopy, reveals that the synthetic methodology and associated activation procedures play a vital role in regulating the morphology, shape and size of the metal nanoparticles. These active centers have a profound influence on the activation of molecular oxygen for selective catalytic oxidations. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Biscatecholate-Monohydroxamate Mixed Ligand Siderophore-Carbacephalosporin Conjugates are Selective Sideromycin Antibiotics that Target Acinetobacter baumannii

PubMed Central

Wencewicz, Timothy A.; Miller, Marvin J.

2013-01-01

Chemical syntheses and biological evaluation of biscatecholate-monohydroxamate mixed ligand sideromycins utilizing the carbacephalosporin β-lactam antibiotic loracarbef and the fluo-roquinolone antibiotic ciprofloxacin are described. The mixed ligand β-lactam sideromycin (1b) had remarkably selective and extremely potent antibacterial activity against the Gram negative pathogen Acinetobacter baumannii ATCC 17961 (MIC = 0.0078 μM). The antibacterial activity of the β-lactam sideromycin was inversely related to the iron(III) concentration in the testing media and was antagonized by the presence of the competing parent siderophore. These data suggested that active transport of the mixed ligand β-lactam sideromycin across the outer cell membrane of A. baumannii via siderophore uptake pathways was responsible for the selective and potent antibacterial activity. PMID:23614627

Use of in vivo Expression Technology for the Identification of Putative Host Adaptation Factors of the Lyme Disease Spirochete.

PubMed

Casselli, Timothy; Bankhead, Troy

2015-01-01

The causative agent of Lyme disease, Borrelia burgdorferi, is an obligate parasite that requires either a tick vector or a mammalian host for survival. Identification of the bacterial genes that are specifically expressed during infection of the mammalian host could provide targets for novel therapeutics and vaccines. In vivo expression technology (IVET) is a reporter-based promoter trap system that utilizes selectable markers to identify promoters of bacterial host-specific genes. Using previously characterized genes for in vivo and in vitro selection, this study utilized an IVET system that allows for selection of B. burgdorferi sequences that act as active promoters only during murine infection. This promoter trap system was able to successfully distinguish active promoter sequences both in vivo and in vitro from control sequences and a library of cloned B. burgdorferi genomic fragments. However, a bottleneck effect during the experimental mouse infection limited the utility for genome-wide promoter screening. Overall, IVET was demonstrated as a tool for the identification of in vivo-induced promoter elements of B. burgdorferi, and the observed infection bottleneck apparent using a polyclonal infection pool provides insight into the dynamics of experimental infection with B. burgdorferi. © 2015 S. Karger AG, Basel.

Near-infrared light controlled photocatalytic activity of carbon quantum dots for highly selective oxidation reaction

NASA Astrophysics Data System (ADS)

Li, Haitao; Liu, Ruihua; Lian, Suoyuan; Liu, Yang; Huang, Hui; Kang, Zhenhui

2013-03-01

Selective oxidation of alcohols is a fundamental and significant transformation for the large-scale production of fine chemicals, UV and visible light driven photocatalytic systems for alcohol oxidation have been developed, however, the long wavelength near infrared (NIR) and infrared (IR) light have not yet fully utilized by the present photocatalytic systems. Herein, we reported carbon quantum dots (CQDs) can function as an effective near infrared (NIR) light driven photocatalyst for the selective oxidation of benzyl alcohol to benzaldehyde. Based on the NIR light driven photo-induced electron transfer property and its photocatalytic activity for H2O2 decomposition, this metal-free catalyst could realize the transformation from benzyl alcohol to benzaldehyde with high selectivity (100%) and conversion (92%) under NIR light irradiation. HO&z.rad; is the main active oxygen specie in benzyl alcohol selective oxidative reaction confirmed by terephthalic acid photoluminescence probing assay (TA-PL), selecting toluene as the substrate. Such metal-free photocatalytic system also selectively converts other alcohol substrates to their corresponding aldehydes with high conversion, demonstrating a potential application of accessing traditional alcohol oxidation chemistry.Selective oxidation of alcohols is a fundamental and significant transformation for the large-scale production of fine chemicals, UV and visible light driven photocatalytic systems for alcohol oxidation have been developed, however, the long wavelength near infrared (NIR) and infrared (IR) light have not yet fully utilized by the present photocatalytic systems. Herein, we reported carbon quantum dots (CQDs) can function as an effective near infrared (NIR) light driven photocatalyst for the selective oxidation of benzyl alcohol to benzaldehyde. Based on the NIR light driven photo-induced electron transfer property and its photocatalytic activity for H2O2 decomposition, this metal-free catalyst could realize the transformation from benzyl alcohol to benzaldehyde with high selectivity (100%) and conversion (92%) under NIR light irradiation. HO&z.rad; is the main active oxygen specie in benzyl alcohol selective oxidative reaction confirmed by terephthalic acid photoluminescence probing assay (TA-PL), selecting toluene as the substrate. Such metal-free photocatalytic system also selectively converts other alcohol substrates to their corresponding aldehydes with high conversion, demonstrating a potential application of accessing traditional alcohol oxidation chemistry. Electronic supplementary information (ESI) available. See DOI: 10.1039/c3nr00092c

[The introduction of generic pharmaceutical products into Galicia].

PubMed

Verdejo González, A; López-Lázaro, L; Rodríguez Moreno, C; Piñeiro Lago, B; Pereira Martínez, M L

1999-11-30

To know the evolution of the introduction of generic drugs (GDs) in Galicia. Secondarily, to evaluate its potential impact on pharmaceutical expenditure. Descriptive study of GDs utilization. Cost-minimization analysis. Galician autonomous region, year 1998. Using data from the prescription billing registry of Social Security we have selected the active ingredients corresponding to GDs with prescriptions in Galicia in 1997. We have analyzed the data for their oral single substance preparations by quarters. Consumption in DHDs of allopurinol, atenolol, captopril, naproxen and ranitidine remained stable during 1998. The market share for their GDs in quantitative terms relative to both total consumption of the active ingredients and to their pharmaceutical equivalents, showed an overall growing trend. The maximum observed value was seen for ranitidine at last quarter. Total expenditure (in final customer prices) during 1998 on the selected active substances was higher than 1864 million pesetas. Potential savings afforded by substitution for the lowest price GD prescribed in Galicia would reach 427 million pesetas. GDs market penetration in Galicia during 1998 was limited but increasing. Its utilization may afford estimated savings of 21-28% of the cost for the selected drugs. However, the expenditure on the above drugs was just 2.7% of total pharmaceutical expenditure.

Design, synthesis and inhibitory activities of 8-(substituted styrol-formamido)phenyl-xanthine derivatives on monoamine oxidase B.

PubMed

Hu, Suwen; Nian, Siyun; Qin, Kuiyou; Xiao, Tong; Li, Lingna; Qi, Xiaolu; Ye, Faqing; Liang, Guang; Hu, Guoxin; He, Jincai; Yu, Yinfei; Song, Bo

2012-01-01

The design and synthesis of two series of 8-(substituted styrol-formamido)phenyl-xanthine derivatives are described. Their in vitro monoamine oxidase B (MAO-B) inhibition were tested and the effect of substituents on the N-7, phenyl and the substituted positions are discussed. It was observed that compound 9b displayed significant MAO-B inhibition activity and selectivity, fluorine substitution plays a key role in the selectivity of MAO-B inhibition, and the styrol-formamido group at position-3' may enhance the activity and selectivity of 8-phenyl-xanthine analogues. These results suggest that such compounds may be utilized for the development of new candidate MAO-B inhibitors for treatment of Parkinson's disease.

Selective enrichment of a methanol-utilizing consortium using pulp & paper mill waste streams

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

Gregory R. Mockos; William A. Smith; Frank J. Loge

Efficient utilization of carbon inputs is critical to the economic viability of the current forest products sector. Input carbon losses occur in various locations within a pulp mill, including losses as volatile organics and wastewater . Opportunities exist to capture this carbon in the form of value-added products such as biodegradable polymers. Waste activated sludge from a pulp mill wastewater facility was enriched for 80 days for a methanol-utilizing consortium with the goal of using this consortium to produce biopolymers from methanol-rich pulp mill waste streams. Five enrichment conditions were utilized: three high-methanol streams from the kraft mill foul condensatemore » system, one methanol-amended stream from the mill wastewater plant, and one methanol-only enrichment. Enrichment reactors were operated aerobically in sequencing batch mode at neutral pH and 25°C with a hydraulic residence time and a solids retention time of four days. Non-enriched waste activated sludge did not consume methanol or reduce chemical oxygen demand. With enrichment, however, the chemical oxygen demand reduction over 24 hour feed/decant cycles ranged from 79 to 89 %, and methanol concentrations dropped below method detection limits. Neither the non-enriched waste activated sludge nor any of the enrichment cultures accumulated polyhydroxyalkanoates (PHAs) under conditions of nitrogen sufficiency. Similarly, the non-enriched waste activated sludge did not accumulate PHAs under nitrogen limited conditions. By contrast, enriched cultures accumulated PHAs to nearly 14% on a dry weight basis under nitrogen limited conditions. This indicates that selectively-enriched pulp mill waste activated sludge can serve as an inoculum for PHA production from methanol-rich pulp mill effluents.« less

Therapeutic utility and medicinal chemistry of cathepsin C inhibitors.

PubMed

Guay, Daniel; Beaulieu, Christian; Percival, M David

2010-01-01

The lysosomal cysteine protease cathepsin C (Cat C), also known as dipeptidyl peptidase I, activates a number of granule-associated serine proteases with pro-inflammatory and immune functions by removal of their inhibitory N-terminal dipeptides. Thus, Cat C is a therapeutic target for the treatment of a number of inflammatory and autoimmune diseases. Cathepsin C null mice and humans with Cat C loss of function mutations (Papillon-Lefèvre syndrome) show deficiencies in disease-relevant proteases including neutrophil elastase, cathepsin G, chymases and granzymes and the Cat C mice are protected in a number of disease models. Several methodologies have been recently reported for assessing the effects of Cat C inhibitors on serine protease activities in cellular assays and prolonged treatment of rats with a reversible, selective Cat C inhibitor reduced the activity of three leukocyte serine proteases. Nearly all potent and selective Cat C inhibitors described are based on the preferred dipeptide substrates bearing either irreversible (e.g. diazomethylketone, acyloxymethyl ketone, o-acyl hydroxamic acid and vinyl sulfone) or reversible (e.g. semicarbazide, nitrile and cyanamide) electrophilic warheads. While potent and highly selective, the best inhibitors described to date still have poor stability and/or rodent pharmacokinetics, likely resulting from their peptidic nature. The lack of selective compounds with appropriate rodent pharmacokinetic properties has hampered the assessment of the effects of Cat C inhibitors on the activation of disease-relevant proteases in vivo and the full evaluation of the therapeutic utility of Cat C inhibitors.

Considering the Role and Nature of the Scientist: The Case of Darwin and Evolution

ERIC Educational Resources Information Center

Aydin, Serap Öz

2015-01-01

For many students, preconceived notions about Darwin are among the most significant obstacles in learning about the theory of evolution by natural selection. I present an activity designed to eliminate this obstacle and encourage empathizing with Darwin, utilizing the history-of-science approach. Through the activity, students' negative thoughts…

A Selected Bibliography of Readings in Management Theory and Practice. Exchange Bibliography No. 637.

ERIC Educational Resources Information Center

Pressley, Milton M., Ed.

Given that management can be defined as the activity that allocates and utilizes resources to achieve group or organizational goals, anyone who is in a position to assign and use a group's or organization's human or nonhuman resuources may benefit by making use of selected readings from this bibliography. The editor has divided the bibliography…

Molding the business end of neurotoxins by diversifying evolution.

PubMed

Kozminsky-Atias, Adi; Zilberberg, Noam

2012-02-01

A diverse range of organisms utilize neurotoxins that target specific ion channels and modulate their activity. Typically, toxins are clustered into several multigene families, providing an organism with the upper hand in the never-ending predator-prey arms race. Several gene families, including those encoding certain neurotoxins, have been subject to diversifying selection forces, resulting in rapid gene evolution. Here we sought a spatial pattern in the distribution of both diversifying and purifying selection forces common to neurotoxin gene families. Utilizing the mechanistic empirical combination model, we analyzed various toxin families from different phyla affecting various receptors and relying on diverse modes of action. Through this approach, we were able to detect clear correlations between the pharmacological surface of a toxin and rapidly evolving domains, rich in positively selected residues. On the other hand, patches of negatively selected residues were restricted to the nontoxic face of the molecule and most likely help in stabilizing the tertiary structure of the toxin. We thus propose a mutual evolutionary strategy of venomous animals in which adaptive molecular evolution is directed toward the toxin active surface. Furthermore, we propose that the binding domains of unstudied toxins could be readily predicted using evolutionary considerations.

Characterization of active paper packaging incorporated with ginger pulp oleoresin

NASA Astrophysics Data System (ADS)

Wiastuti, T.; Khasanah, L. U.; Atmaka Kawiji, W.; Manuhara, G. J.; Utami, R.

2016-02-01

Utilization of ginger pulp waste from herbal medicine and instant drinks industry in Indonesia currently used for fertilizer and fuel, whereas the ginger pulp still contains high oleoresin. Active paper packaging were developed incorporated with ginger pulp oleoresin (0%, 2%, 4%, and 6% w/w). Physical (thickness, tensile strength, and folding endurance, moisture content), sensory characteristics and antimicrobial activity of the active paper were evaluated. Selected active paper then were chemically characterized (functional groups). The additional of ginger pulp oleoresin levels are reduced tensile strength, folding endurance and sensory characteristic (color, texture and overall) and increased antimicrobial activity. Due to physical, sensory characteristic and antimicrobial activity, active paper with 2% ginger pulp oleoresin incorporation was selected. Characteristics of selected paper were 9.93% of water content; 0.81 mm of thickness; 0.54 N / mm of tensile strength; 0.30 of folding endurance; 8.43 mm inhibits the growth of Pseudomonas fluorescence and 27.86 mm inhibits the growth of Aspergillus niger (antimicrobial activity) and neutral preference response for sensory properties. For chemical characteristic, selected paper had OH functional group of ginger in 3422.83 cm-1 of wave number and indicated contain red ginger active compounds.

Dearomative dihydroxylation with arenophiles

NASA Astrophysics Data System (ADS)

Southgate, Emma H.; Pospech, Jola; Fu, Junkai; Holycross, Daniel R.; Sarlah, David

2016-10-01

Aromatic hydrocarbons are some of the most elementary feedstock chemicals, produced annually on a million metric ton scale, and are used in the production of polymers, paints, agrochemicals and pharmaceuticals. Dearomatization reactions convert simple, readily available arenes into more complex molecules with broader potential utility, however, despite substantial progress and achievements in this field, there are relatively few methods for the dearomatization of simple arenes that also selectively introduce functionality. Here we describe a new dearomatization process that involves visible-light activation of small heteroatom-containing organic molecules—arenophiles—that results in their para-cycloaddition with a variety of aromatic compounds. The approach uses N-N-arenophiles to enable dearomative dihydroxylation and diaminodihydroxylation of simple arenes. This strategy provides direct and selective access to highly functionalized cyclohexenes and cyclohexadienes and is orthogonal to existing chemical and biological dearomatization processes. Finally, we demonstrate the synthetic utility of this strategy with the concise synthesis of several biologically active compounds and natural products.

Active colloids as mobile microelectrodes for unified label-free selective cargo transport.

PubMed

Boymelgreen, Alicia M; Balli, Tov; Miloh, Touvia; Yossifon, Gilad

2018-02-22

Utilization of active colloids to transport both biological and inorganic cargo has been widely examined in the context of applications ranging from targeted drug delivery to sample analysis. In general, carriers are customized to load one specific target via a mechanism distinct from that driving the transport. Here we unify these tasks and extend loading capabilities to include on-demand selection of multiple nano/micro-sized targets without the need for pre-labelling or surface functionalization. An externally applied electric field is singularly used to drive the active cargo carrier and transform it into a mobile floating electrode that can attract (trap) or repel specific targets from its surface by dielectrophoresis, enabling dynamic control of target selection, loading and rate of transport via the electric field parameters. In the future, dynamic selectivity could be combined with directed motion to develop building blocks for bottom-up fabrication in applications such as additive manufacturing and soft robotics.

Athletes’ Selected Micro-Activities on Turf Fields: Utilizing Extant Videography for Quantification of Events During Soccer, American Football, and Field Hockey Play

EPA Science Inventory

Concerns have been recently raised about the potential exposures of athletes to chemicals when playing on synthetic turf fields. Previous research has shown that micro-activities (i.e., hand-to mouth and skin-to-surface contacts) are important factors in people’s exposures to che...

Proven in vitro evolution of protease cathepsin E-inhibitors and -activators at pH 4.5 using a paired peptide method.

PubMed

Kitamura, Koichiro; Komatsu, Masayuki; Biyani, Madhu; Futakami, Masae; Kawakubo, Tomoyo; Yamamoto, Kenji; Nishigaki, Koichi

2012-12-01

Improving a particular function of molecules is often more difficult than identifying such molecules ab initio. Here, a method to acquire higher affinity and/or more functional peptides was developed as a progressive library selection method. The primary library selection products were utilized to build a secondary library composed of blocks of 4 amino acids, of which selection led to peptides with increased activity. These peptides were further converted to randomly generate paired peptides. Cathepsin E-inhibitors thus obtained exhibited the highest activities and affinities (pM order). This was also the case with cathepsin E-activating peptides, proving the methodological effectiveness. The primary, secondary, and tertiary library selections can be regarded as module-finding, module-shuffling, and module-pairing, respectively, which resembles the progression of the natural evolution of proteins. The mode of peptide binding to their target proteins is discussed in analogy to antibodies and epitopes of an antigen. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.

Selective Enrichment of a Methanol-Utilizing Consortium Using Pulp and Paper Mill Waste Streams

NASA Astrophysics Data System (ADS)

Mockos, Gregory R.; Smith, William A.; Loge, Frank J.; Thompson, David N.

Efficient utilization of carbon inputs is critical to the economic viability of the current forest products sector. Input carbon losses occur in various locations within a pulp mill, including losses as volatile organics and wastewater. Opportunities exist to capture this carbon in the form of value-added products such as biodegradable polymers. Wasteactivated sludge from a pulp mill wastewater facility was enriched for 80 days for a methanol-utilizing consortium with the goal of using this consortium to produce biopolymers from methanol-rich pulp mill waste streams. Five enrichment conditions were utilized: three high-methanol streams from the kraft mill foul condensate system, one methanol-amended stream from the mill wastewater plant, and one methanol-only enrichment. Enrichment reactors were operated aerobically in sequencing batch mode at neutral pH and 25°C with a hydraulic residence time and a solids retention time of 4 days. Non-enriched waste activated sludge did not consume methanol or reduce chemical oxygen demand. With enrichment, however, the chemical oxygen demand reduction over 24-h feed/ decant cycles ranged from 79 to 89%, and methanol concentrations dropped below method detection limits. Neither the non-enriched waste-activated sludge nor any of the enrichment cultures accumulated polyhydroxyalkanoates (PHAs) under conditions of nitrogen sufficiency. Similarly, the non-enriched waste activated sludge did not accumulate PHAs under nitrogen-limited conditions. By contrast, enriched cultures accumulated PHAs to nearly 14% on a dry weight basis under nitrogen-limited conditions. This indicates that selectively enriched pulp mill waste activated sludge can serve as an inoculum for PHA production from methanol-rich pulp mill effluents.

Active Response Gravity Offload and Method

NASA Technical Reports Server (NTRS)

Dungan, Larry K. (Inventor); Lieberman, Asher P. (Inventor); Shy, Cecil (Inventor); Bankieris, Derek R. (Inventor); Valle, Paul S. (Inventor); Redden, Lee (Inventor)

2015-01-01

A variable gravity field simulator can be utilized to provide three dimensional simulations for simulated gravity fields selectively ranging from Moon, Mars, and micro-gravity environments and/or other selectable gravity fields. The gravity field simulator utilizes a horizontally moveable carriage with a cable extending from a hoist. The cable can be attached to a load which experiences the effects of the simulated gravity environment. The load can be a human being or robot that makes movements that induce swinging of the cable whereby a horizontal control system reduces swinging energy. A vertical control system uses a non-linear feedback filter to remove noise from a load sensor that is in the same frequency range as signals from the load sensor.

High-throughput selection for cellulase catalysts using chemical complementation.

PubMed

Peralta-Yahya, Pamela; Carter, Brian T; Lin, Hening; Tao, Haiyan; Cornish, Virginia W

2008-12-24

Efficient enzymatic hydrolysis of lignocellulosic material remains one of the major bottlenecks to cost-effective conversion of biomass to ethanol. Improvement of glycosylhydrolases, however, is limited by existing medium-throughput screening technologies. Here, we report the first high-throughput selection for cellulase catalysts. This selection was developed by adapting chemical complementation to provide a growth assay for bond cleavage reactions. First, a URA3 counter selection was adapted to link chemical dimerizer activated gene transcription to cell death. Next, the URA3 counter selection was shown to detect cellulase activity based on cleavage of a tetrasaccharide chemical dimerizer substrate and decrease in expression of the toxic URA3 reporter. Finally, the utility of the cellulase selection was assessed by isolating cellulases with improved activity from a cellulase library created by family DNA shuffling. This application provides further evidence that chemical complementation can be readily adapted to detect different enzymatic activities for important chemical transformations for which no natural selection exists. Because of the large number of enzyme variants that selections can now test as compared to existing medium-throughput screens for cellulases, this assay has the potential to impact the discovery of improved cellulases and other glycosylhydrolases for biomass conversion from libraries of cellulases created by mutagenesis or obtained from natural biodiversity.

A High-throughput Selection for Cellulase Catalysts Using Chemical Complementation

PubMed Central

Peralta-Yahya, Pamela; Carter, Brian T.; Lin, Hening; Tao, Haiyan; Cornish, Virginia W.

2010-01-01

Efficient enzymatic hydrolysis of lignocellulosic material remains one of the major bottlenecks to cost-effective conversion of biomass to ethanol. Improvement of glycosylhydrolases however is limited by existing medium-throughput screening technologies. Here, we report the first high-throughput selection for cellulase catalysts. This selection was developed by adapting chemical complementation to provide a growth assay for bond cleavage reactions. First, a URA3 counter selection was adapted to link chemical dimerizer activated gene transcription to cell death. Next, the URA3 counter selection was shown to detect cellulase activity based on cleavage of a tetrasaccharide chemical dimerizer substrate and decrease in expression of the toxic URA3 reporter. Finally, the utility of the cellulase selection was assessed by isolating cellulases with improved activity from a cellulase library created by family DNA shuffling. This application provides further evidence that chemical complementation can be readily adapted to detect different enzymatic activities for important chemical transformations for which no natural selection exists. Due to the large number of enzyme variants selections can test compared to existing medium-throughput screens for cellulases, this assay has the potential to impact the discovery of improved cellulases and other glycosylhydrolases for biomass conversion from libraries of cellulases created by mutagenesis or obtained from natural biodiversity. PMID:19053460

Study on the application of KOH to produce activated carbon to realize the utilization of distiller’s grains

NASA Astrophysics Data System (ADS)

Yang, H. M.; Zhang, D. H.; Chen, Y.; Ran, M. J.; Gu, J. C.

2017-06-01

The distiller’s grains in a liquor factory are selected as the main material to study the preparation of activated carbon with KOH activation. The solid-to-liquid ratio A, KOH concentration B, activation temperature C, activation time D are regarded as variables to produce single factor experiment. The results show that the best preparation conditions of various factors are: 50% KOH concentration, solid-liquid ratio of 1:4, activation temperature of 750°, activation time of 2.0h. The L9 (34) orthogonal experiment is carried out by selecting three levels from each single factor, showing that the importance order of the factors is: B > A > C > D. In addition, when KOH solution concentration is 60%, the solid-liquid ratio is 1:5, activation temperature is 700°, and activation time is 2.0h, the performance of the preparation of activated carbon is the best.

Preparing for Computer Use. Revised.

ERIC Educational Resources Information Center

South Carolina State Dept. of Education, Columbia.

Intended to assist school districts in designing high school credit courses, preparing staff development activities related to computer utilization, and selecting and evaluating instructional software, this document offers outlines for the following student courses: (1) Introduction to Computers, a computer literacy course covering computer…

Encouragement of Enzyme Reaction Utilizing Heat Generation from Ferromagnetic Particles Subjected to an AC Magnetic Field.

PubMed

Suzuki, Masashi; Aki, Atsushi; Mizuki, Toru; Maekawa, Toru; Usami, Ron; Morimoto, Hisao

2015-01-01

We propose a method of activating an enzyme utilizing heat generation from ferromagnetic particles under an ac magnetic field. We immobilize α-amylase on the surface of ferromagnetic particles and analyze its activity. We find that when α-amylase/ferromagnetic particle hybrids, that is, ferromagnetic particles, on which α-amylase molecules are immobilized, are subjected to an ac magnetic field, the particles generate heat and as a result, α-amylase on the particles is heated up and activated. We next prepare a solution, in which α-amylase/ferromagnetic particle hybrids and free, nonimmobilized chitinase are dispersed, and analyze their activities. We find that when the solution is subjected to an ac magnetic field, the activity of α-amylase immobilized on the particles increases, whereas that of free chitinase hardly changes; in other words, only α-amylase immobilized on the particles is selectively activated due to heat generation from the particles.

[Determination of the effectiveness of certain physical conditioning apparatuses for development of muscle quality].

PubMed

Lagassé, P; Godin, G; Brunelle, J; Brunelle, J P

1982-03-01

This study attempted to compare on twenty male subjects the intensity of muscular activity during selected exercises executed with and without physical fitness gadgets. Each subject executed two exercises with or without the Total Body Shaper, three exercises with or without the Power X and one exercise with or without the Prone Cycle. The electrical activity of four muscles was studied for each exercise; theoretical data and the publicity of the manufactures were utilized to select the muscles. The statistical analysis showed that exercises executed with the Total Body Shaper are generally less solicitating than similar exercises executed without the gadget, that the Power X has evident advantages for the muscle groups that it activates but that its manufacturers tend to generalize its effects to muscle groups that it does not solicitate and, finally, that the Prone Cycle is the least valuable of the gadgets tested. The results enlighten the need for consumer protection agencies to look more carefully at the publicity utilized to promote the benefits of physical fitness gadgets.

Microgap flat panel display

DOEpatents

Wuest, C.R.

1998-12-08

A microgap flat panel display is disclosed which includes a thin gas-filled display tube that utilizes switched X-Y ``pixel`` strips to trigger electron avalanches and activate a phosphor at a given location on a display screen. The panel utilizes the principal of electron multiplication in a gas subjected to a high electric field to provide sufficient electron current to activate standard luminescent phosphors located on an anode. The X-Y conductive strips of a few micron widths may for example, be deposited on opposite sides of a thin insulating substrate, or on one side of the adjacent substrates and function as a cathode. The X-Y strips are separated from the anode by a gap filled with a suitable gas. Electrical bias is selectively switched onto X and Y strips to activate a ``pixel`` in the region where these strips overlap. A small amount of a long-lived radioisotope is used to initiate an electron avalanche in the overlap region when bias is applied. The avalanche travels through the gas filled gap and activates a luminescent phosphor of a selected color. The bias is adjusted to give a proportional electron multiplication to control brightness for given pixel. 6 figs.

Hybrid active vibration control of rotorbearing systems using piezoelectric actuators

NASA Technical Reports Server (NTRS)

Palazzolo, A. B.; Jagannathan, S.; Kascak, A. F.; Montague, G. T.; Kiraly, L. J.

1993-01-01

The vibrations of a flexible rotor are controlled using piezoelectric actuators. The controller includes active analog components and a hybrid interface with a digital computer. The computer utilizes a grid search algorithm to select feedback gains that minimize a vibration norm at a specific operating speed. These gains are then downloaded as active stillnesses and dampings with a linear fit throughout the operating speed range to obtain a very effective vibration control.

7 CFR 4284.639 - Grant selection criteria.

Code of Federal Regulations, 2010 CFR

2010-01-01

... RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE GRANTS Rural Business Opportunity Grants § 4284.639... assessment of the extent to which economic development resulting from the proposed project will be... economic activity within the community, such as higher wages, improved benefits, greater career potential...

IMAGING ASSESSMENT OF G-PROTEIN-COUPLED ESTROGEN RECEPTOR ACTIVATION

EPA Science Inventory

We expect to provide a targeted imaging assay that links chemical mechanism of toxicity to target organ effects and heart physiology within individual 96-hpf zebrafish. Importantly, with the utilization of selective, non-toxic agonists or antagonists for additional xenobiot...

RECRUITMENT AND RETENTION ACTIVITIES UTILIZED DURING THE FIRST TWO SEASONS OF THE DEARS

EPA Science Inventory

Identification, recruitment, enrollment, and retention of participants in the Detroit Exposure and Aerosol Research Study (DEARS) presented many challenges. A population-based cohort was chosen to reduce participant selection bias. Contact information for nearly everyone who live...

Current Management Strategy for Active Surveillance in Prostate Cancer.

PubMed

Syed, Jamil S; Javier-Desloges, Juan; Tatzel, Stephanie; Bhagat, Ansh; Nguyen, Kevin A; Hwang, Kevin; Kim, Sarah; Sprenkle, Preston C

2017-02-01

Active surveillance has been increasingly utilized as a strategy for the management of favorable-risk, localized prostate cancer. In this review, we describe contemporary management strategies of active surveillance, with a focus on traditional stratification schemes, new prognostic tools, and patient outcomes. Patient selection, follow-up strategy, and indication for delayed intervention for active surveillance remain centered around PSA, digital rectal exam, and biopsy findings. Novel tools which include imaging, biomarkers, and genetic assays have been investigated as potential prognostic adjuncts; however, their role in active surveillance remains institutionally dependent. Although 30-50% of patients on active surveillance ultimately undergo delayed treatment, the vast majority will remain free of metastasis with a low risk of dying from prostate cancer. The optimal method for patient selection into active surveillance is unknown; however, cancer-specific mortality rates remain excellent. New prognostication tools are promising, and long-term prospective, randomized data regarding their use in active surveillance will be beneficial.

Selective C(sp3)−H Aerobic Oxidation Enabled by Decatungstate Photocatalysis in Flow

PubMed Central

Laudadio, Gabriele; Govaerts, Sebastian; Wang, Ying; Ravelli, Davide; Koolman, Hannes F.; Fagnoni, Maurizio; Djuric, Stevan W.

2018-01-01

Abstract A mild and selective C(sp3)−H aerobic oxidation enabled by decatungstate photocatalysis has been developed. The reaction can be significantly improved in a microflow reactor enabling the safe use of oxygen and enhanced irradiation of the reaction mixture. Our method allows for the oxidation of both activated and unactivated C−H bonds (30 examples). The ability to selectively oxidize natural scaffolds, such as (−)‐ambroxide, pregnenolone acetate, (+)‐sclareolide, and artemisinin, exemplifies the utility of this new method. PMID:29451725

Variation in teenage mothers' experiences of child care and other components of welfare reform: selection processes and developmental consequences.

PubMed

Yoshikawa, H; Rosman, E A; Hsueh, J

2001-01-01

Developmental evaluations of the current wave of welfare reform programs present challenges with regard to (1) assessing child outcomes; (2) accounting for heterogeneity among low-income families in both baseline characteristics and involvement in self-sufficiency activities and supports, and (3) development of alternatives to experimental approaches to causal inference. This study (N = 1,079) addresses these challenges by examining effects on 4- to 6-year-old children of different patterns of child care, self-sufficiency activities, and other service utilization indicators among experimental-group mothers in a 16-site welfare reform program. Outcomes in areas of cognitive ability and behavior problems were investigated. The study identified seven subgroups of participants engaging in different patterns of service utilization and activity involvement. A two-stage simultaneous equation methodology was used to account for selection, and effects on child cognitive ability of participation in specific patterns of services and activities were found. For example, children of mothers characterized by high levels of involvement in center-based child care, education, and job training showed higher levels of cognitive ability than children of mothers in groups characterized by high involvement in center-based care and education, or center-based care and job training. In addition, children of mothers in groups with high levels of involvement in any of these activities showed higher levels of cognitive ability than those with low levels of involvement. The bulk of selection effects occurred through site-level differences, rather than family-level socio-economic status or maternal depression indicators. Implications for welfare reform program and policy concerns are discussed.

Trends in active pharmaceutical ingredient salt selection based on analysis of the Orange Book database.

PubMed

Paulekuhn, G Steffen; Dressman, Jennifer B; Saal, Christoph

2007-12-27

The Orange Book database published by the U.S. Drug and Food Administration (FDA) was analyzed for the frequency of occurrence of different counterions used for the formation of pharmaceutical salts. The data obtained from the present analysis of the Orange Book are compared to reviews of the Cambridge Structural Database (CSD) and of the Martindale "The Extra Pharmacopoeia". As well as showing overall distributions of counterion usage, results are broken down into 5-year increments to identify trends in counterion selection. Chloride ions continue to be the most frequently utilized anionic counterions for the formation of salts as active pharmaceutical ingredients (APIs), while sodium ions are most widely utilized for the formation of salts starting from acidic molecules. A strong trend toward a wider variety of counterions over the past decade is observed. This trend can be explained by a stronger need to improve physical chemical properties of research and development compounds.

Aerobic and Electrochemical Oxidations with N-Oxyl Reagents

NASA Astrophysics Data System (ADS)

Miles, Kelsey C.

Selective oxidation of organic compounds represents a significant challenge for chemical transformations. Oxidation methods that utilize nitroxyl catalysts have become increasingly attractive and include Cu/nitroxyl and nitroxyl/NO x co-catalyst systems. Electrochemical activation of nitroxyls is also well known and offers an appealing alternative to the use of chemical co-oxidants. However, academic and industrial organic synthetic communities have not widely adopted electrochemical methods. Nitroxyl catalysts facilitate effective and selective oxidation of alcohols and aldehydes to ketones and carboxylic acids. Selective benzylic, allylic, and alpha-heteroatom C-H abstraction can also be achieved with nitroxyls and provides access to oxygenated products when used in combination with molecular oxygen as a radical trap. This thesis reports various chemical and electrochemical oxidation methods that were developed using nitroxyl mediators. Chapter 1 provides a short review on practical aerobic alcohol oxidation with Cu/nitroxyl and nitroxyl/NO x systems and emphasizes the utility of bicyclic nitroxyls as co-catalysts. In Chapter 2, the combination of these bicyclic nitroxyls with NOx is explored for development of a mild oxidation of alpha-chiral aryl aldehydes and showcases a sequential asymmetric hydroformylation/oxidation method. Chapter 3 reports the synthesis and characterization of two novel Cu/bicyclic nitroxyl complexes and the electronic structure analysis of these complexes. Chapter 4 highlights the electrochemical activation of various nitroxyls and reports an in-depth study on electrochemical alcohol oxidation and compares the reactivity of nitroxyls under electrochemical or chemical activation. N-oxyls can also participate in selective C-H abstraction, and Chapter 5 reports the chemical and electrochemical activation of N-oxyls for radical-mediated C-H oxygenation of (hetero)arylmethanes. For these electrochemical transformations, the development of user-friendly methods and analysis techniques is emphasized.

Vulnerable transportation and utility assets near actively migrating streams in Indiana

USGS Publications Warehouse

Sperl, Benjamin J.

2017-11-02

An investigation was completed by the U.S. Geological Survey in cooperation with the Indiana Office of Community and Rural Affairs that found 1,132 transportation and utility assets in Indiana are vulnerable to fluvial erosion hazards due to close proximity to actively migrating streams. Locations of transportation assets (bridges, roadways, and railroad lines) and selected utility assets (high-capacity overhead power-transmission lines, underground pipelines, water treatment facilities, and in-channel dams) were determined using aerial imagery hosted by the Google Earth platform. Identified assets were aggregated by stream reach, county, and class. Accompanying the report is a polyline shapefile of the stream reaches documented by Robinson. The shapefile, derived from line work in the National Hydrography Dataset and attributed with channel migration rates, is released with complete Federal Geographic Data Committee metadata. The data presented in this report are intended to help stakeholders and others identify high-risk areas where transportation and utility assets may be threatened by fluvial erosion hazards thus warranting consideration for mitigation strategies.

Deployment Area Selection and Land Withdrawal/Acquisition. M-X/MPS (M-X/Multiple Protective Shelter) Environmental Technical Report. Native Americans Nevada/Utah.

DTIC Science & Technology

1981-10-02

Northern Paiute, Shoshone, Ute, and Southern Paiute peoples developed solutions to natural limitations based upon botanical and zoological expertise and...Land Management and the Forest Service. Other Land-based Activities (3.1.5.2.2) The tribe intends to build a hydroponic greenhouse which will utilize the...other development goals--notably the development of a hydroponic greenhouse utilizing flow from natural wdrm springs on the reservation, and development

Utilization of organs from donors after circulatory death for vascularized pancreas and islet of Langerhans transplantation: recommendations from an expert group.

PubMed

Berney, Thierry; Boffa, Catherine; Augustine, Titus; Badet, Lionel; de Koning, Eelco; Pratschke, Johann; Socci, Carlo; Friend, Peter

2016-07-01

Donation after circulatory death (DCD) donors are increasingly being used as a source of pancreas allografts for vascularized organ and islet transplantation. We provide practice guidelines aiming to increase DCD pancreas utilization. We review risk assessment and donor selection criteria. We report suggested factors in donor and recipient clinical management and provide an overview of the activities and outcomes of vascularized pancreas and islet transplantation. © 2015 Steunstichting ESOT.

Continuous directed evolution of aminoacyl-tRNA synthetases

PubMed Central

Bryson, David I.; Fan, Chenguang; Guo, Li-Tao; Miller, Corwin; Söll, Dieter; Liu, David R.

2017-01-01

Directed evolution of orthogonal aminoacyl-tRNA synthetases (AARSs) enables site-specific installation of non-canonical amino acids (ncAAs) into proteins. Traditional evolution techniques typically produce AARSs with greatly reduced activity and selectivity compared to their wild-type counterparts. We designed phage-assisted continuous evolution (PACE) selections to rapidly produce highly active and selective orthogonal AARSs through hundreds of generations of evolution. PACE of a chimeric Methanosarcina spp. pyrrolysyl-tRNA synthetase (PylRS) improved its enzymatic efficiency (kcat/KMtRNA) 45-fold compared to the parent enzyme. Transplantation of the evolved mutations into other PylRS-derived synthetases improved yields of proteins containing non-canonical residues up to 9.7-fold. Simultaneous positive and negative selection PACE over 48 h greatly improved the selectivity of a promiscuous Methanocaldococcus jannaschii tyrosyl-tRNA synthetase variant for site-specific incorporation of p-iodo-L-phenylalanine. These findings offer new AARSs that increase the utility of orthogonal translation systems and establish the capability of PACE to efficiently evolve orthogonal AARSs with high activity and amino acid specificity. PMID:29035361

Purification and properties of a novel ferricyanide-linked xanthine dehydrogenase from Pseudomonas putida 40.

PubMed Central

Woolfolk, C A

1985-01-01

The isolation of a xanthine dehydrogenase from Pseudomonas putida 40 which utilizes ferricyanide as an electron acceptor at high efficiency is presented. The new activity is separate from the NAD+ and oxygen-utilizing activities of the same organism but displays a broad pattern for reducing substrates typical of those of previously studied xanthine-oxidizing enzymes. Unlike the previously studied enzymes, the new enzyme appears to lack flavin but possess heme and is resistant to cyanide treatment. However, sensitivity of the purified enzyme to methanol and the selective elimination of the activity when tungstate is added to certain growth media suggest a role for molybdenum. The enzyme is subject to a selective proteolytic action during processing which is not accompanied by denaturation or loss of activity and which is minimized by the continuous exposure of the activity to EDTA and phenylmethylsulfonyl fluoride. Electrophoresis of the denatured enzyme in the presence of sodium dodecyl sulfate suggests that the enzyme is constructed of subunits with a molecular weight of approximately 72,000. Electrophoresis under native conditions of a purified enzyme previously exposed to magnesium ion reveals a series of major and minor activity bands which display some selectivity toward both electron donors and acceptors. An analysis of the effect of gel concentration on this pattern suggests that the enzyme forms a series of charge and size isomers with a pair of trimeric forms predominating. Comparison of the rate of sedimentation of the enzyme in sucrose gradients with its elution profile from standardized Sepharose 6B columns suggests a molecular weight of 255,000 for the major form of the native enzyme. Images PMID:3860496

Brain activity during divided and selective attention to auditory and visual sentence comprehension tasks

PubMed Central

Moisala, Mona; Salmela, Viljami; Salo, Emma; Carlson, Synnöve; Vuontela, Virve; Salonen, Oili; Alho, Kimmo

2015-01-01

Using functional magnetic resonance imaging (fMRI), we measured brain activity of human participants while they performed a sentence congruence judgment task in either the visual or auditory modality separately, or in both modalities simultaneously. Significant performance decrements were observed when attention was divided between the two modalities compared with when one modality was selectively attended. Compared with selective attention (i.e., single tasking), divided attention (i.e., dual-tasking) did not recruit additional cortical regions, but resulted in increased activity in medial and lateral frontal regions which were also activated by the component tasks when performed separately. Areas involved in semantic language processing were revealed predominantly in the left lateral prefrontal cortex by contrasting incongruent with congruent sentences. These areas also showed significant activity increases during divided attention in relation to selective attention. In the sensory cortices, no crossmodal inhibition was observed during divided attention when compared with selective attention to one modality. Our results suggest that the observed performance decrements during dual-tasking are due to interference of the two tasks because they utilize the same part of the cortex. Moreover, semantic dual-tasking did not appear to recruit additional brain areas in comparison with single tasking, and no crossmodal inhibition was observed during intermodal divided attention. PMID:25745395

Brain activity during divided and selective attention to auditory and visual sentence comprehension tasks.

PubMed

Moisala, Mona; Salmela, Viljami; Salo, Emma; Carlson, Synnöve; Vuontela, Virve; Salonen, Oili; Alho, Kimmo

2015-01-01

Using functional magnetic resonance imaging (fMRI), we measured brain activity of human participants while they performed a sentence congruence judgment task in either the visual or auditory modality separately, or in both modalities simultaneously. Significant performance decrements were observed when attention was divided between the two modalities compared with when one modality was selectively attended. Compared with selective attention (i.e., single tasking), divided attention (i.e., dual-tasking) did not recruit additional cortical regions, but resulted in increased activity in medial and lateral frontal regions which were also activated by the component tasks when performed separately. Areas involved in semantic language processing were revealed predominantly in the left lateral prefrontal cortex by contrasting incongruent with congruent sentences. These areas also showed significant activity increases during divided attention in relation to selective attention. In the sensory cortices, no crossmodal inhibition was observed during divided attention when compared with selective attention to one modality. Our results suggest that the observed performance decrements during dual-tasking are due to interference of the two tasks because they utilize the same part of the cortex. Moreover, semantic dual-tasking did not appear to recruit additional brain areas in comparison with single tasking, and no crossmodal inhibition was observed during intermodal divided attention.

Ranking the selectivity of PubChem screening hits by activity-based protein profiling: MMP13 as a case study.

PubMed

Nakai, Ryuichiro; Salisbury, Cleo M; Rosen, Hugh; Cravatt, Benjamin F

2009-02-01

High-throughput screening (HTS) has become an integral part of academic and industrial efforts aimed at developing new chemical probes and drugs. These screens typically generate several 'hits', or lead active compounds, that must be prioritized for follow-up medicinal chemistry studies. Among primary considerations for ranking lead compounds is selectivity for the intended target, especially among mechanistically related proteins. Here, we show how the chemical proteomic technology activity-based protein profiling (ABPP) can serve as a universal assay to rank HTS hits based on their selectivity across many members of an enzyme superfamily. As a case study, four metalloproteinase-13 (MMP13) inhibitors of similar potency originating from a publically supported HTS and reported in PubChem were tested by ABPP for selectivity against a panel of 27 diverse metalloproteases. The inhibitors could be readily separated into two groups: (1) those that were active against several metalloproteases and (2) those that showed high selectivity for MMP13. The latter set of inhibitors was thereby designated as more suitable for future medicinal chemistry optimization. We anticipate that ABPP will find general utility as a platform to rank the selectivity of lead compounds emerging from HTS assays for a wide variety of enzymes.

Utilization of the NASA Robonaut as a Surgical Avatar in Telemedicine

NASA Technical Reports Server (NTRS)

Dean, Marc; Diftler, Myron

2015-01-01

The concept of teleoperated robotic surgery is not new; however, most of the work to date has utilized specialized robots designed for specific set of surgeries. This activity explores the use of a humanoid robot to perform surgical procedures using the same hand held instruments that a human surgeon employs. For this effort, the tele-operated Robonaut (R2) was selected due to its dexterity, its ability to perform a wide range of tasks, and its adaptability to changing environments. To evaluate this concept, a series of challenges was designed with the goal of assessing the feasibility of utilizing Robonaut as a telemedicine based surgical avatar.

Molecular docking, synthesis and biological screening of mefenamic acid derivatives as anti-inflammatory agents.

PubMed

Savjani, Jignasa K; Mulamkattil, Suja; Variya, Bhavesh; Patel, Snehal

2017-04-15

Drug induced gastrointestinal ulceration, renal side effects and hepatotoxicity are the main causes of numerous Non-Steroidal Anti-inflammatory Drugs (NSAIDs). Cyclooxygenase-2 (COX-2) inhibitors discovered to decrease the gastrointestinal issues, but unfortunately, most of them are associated with major cardiovascular adverse effects. Along these lines, various new strategies and frameworks were developed wherein basic alterations of the present medications were accounted for. The aim of the study was to prepare derivatives of mefenamic acid to evaluate anti-inflammatory activity with fewer adverse reactions. In this study, molecular docking investigations of outlined derivatives were done utilizing Protein Data Bank (PDB ID-4PH9). Synthesis of heterocyclic compounds was carried out utilizing Dicyclohexylcarbodiimide/4-Dimethylaminopyridine (DCC/DMAP) coupling. Acute toxicity prediction was performed using free online GUSAR (General Unrestricted Structure-Activity Relationships) software. The study indicated most of the compounds under safe category. In-vitro pharmacological assessment of heterocyclic compounds was done for COX-1 and COX-2 enzymes for the determination of selectivity. In vivo pharmacological screening for anti-inflammatory activity and ED 50 value were determined utilizing carrageenan induced rat paw edema. Gastro intestinal safety study was carried out on selected compounds and found to be devoid of any gastric ulcer toxicity. Most of the compounds indicated high scores as compared to standard during molecular modelling, analysis and displayed interactions with active amino acids of a COX-2 enzyme. The pharmacological screening uncovered that compound substituted with p-bromophenyl indicated maximum potency. Copyright © 2017 Elsevier B.V. All rights reserved.

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.

Application of activity-based protein profiling to study enzyme function in adipocytes.

PubMed

Galmozzi, Andrea; Dominguez, Eduardo; Cravatt, Benjamin F; Saez, Enrique

2014-01-01

Activity-based protein profiling (ABPP) is a chemical proteomics approach that utilizes small-molecule probes to determine the functional state of enzymes directly in native systems. ABPP probes selectively label active enzymes, but not their inactive forms, facilitating the characterization of changes in enzyme activity that occur without alterations in protein levels. ABPP can be a tool superior to conventional gene expression and proteomic profiling methods to discover new enzymes active in adipocytes and to detect differences in the activity of characterized enzymes that may be associated with disorders of adipose tissue function. ABPP probes have been developed that react selectively with most members of specific enzyme classes. Here, using as an example the serine hydrolase family that includes many enzymes with critical roles in adipocyte physiology, we describe methods to apply ABPP analysis to the study of adipocyte enzymatic pathways. © 2014 Elsevier Inc. All rights reserved.

Towards mild metal-catalyzed C-H bond activation.

PubMed

Wencel-Delord, Joanna; Dröge, Thomas; Liu, Fan; Glorius, Frank

2011-09-01

Functionalizing traditionally inert carbon-hydrogen bonds represents a powerful transformation in organic synthesis, providing new entries to valuable structural motifs and improving the overall synthetic efficiency. C-H bond activation, however, often necessitates harsh reaction conditions that result in functional group incompatibilities and limited substrate scope. An understanding of the reaction mechanism and rational design of experimental conditions have led to significant improvement in both selectivity and applicability. This critical review summarizes and discusses endeavours towards the development of mild C-H activation methods and wishes to trigger more research towards this goal. In addition, we examine select examples in complex natural product synthesis to demonstrate the synthetic utility of mild C-H functionalization (84 references). This journal is © The Royal Society of Chemistry 2011

A four-dimensional virtual hand brain-machine interface using active dimension selection.

PubMed

Rouse, Adam G

2016-06-01

Brain-machine interfaces (BMI) traditionally rely on a fixed, linear transformation from neural signals to an output state-space. In this study, the assumption that a BMI must control a fixed, orthogonal basis set was challenged and a novel active dimension selection (ADS) decoder was explored. ADS utilizes a two stage decoder by using neural signals to both (i) select an active dimension being controlled and (ii) control the velocity along the selected dimension. ADS decoding was tested in a monkey using 16 single units from premotor and primary motor cortex to successfully control a virtual hand avatar to move to eight different postures. Following training with the ADS decoder to control 2, 3, and then 4 dimensions, each emulating a grasp shape of the hand, performance reached 93% correct with a bit rate of 2.4 bits s(-1) for eight targets. Selection of eight targets using ADS control was more efficient, as measured by bit rate, than either full four-dimensional control or computer assisted one-dimensional control. ADS decoding allows a user to quickly and efficiently select different hand postures. This novel decoding scheme represents a potential method to reduce the complexity of high-dimension BMI control of the hand.

Discovery of Dinaciclib (SCH 727965): A Potent and Selective Inhibitor of Cyclin-Dependent Kinases

PubMed Central

2010-01-01

Inhibition of cyclin-dependent kinases (CDKs) has emerged as an attractive strategy for the development of novel oncology therapeutics. Herein is described the utilization of an in vivo screening approach with integrated efficacy and tolerability parameters to identify candidate CDK inhibitors with a suitable balance of activity and tolerability. This approach has resulted in the identification of SCH 727965, a potent and selective CDK inhibitor that is currently undergoing clinical evaluation. PMID:24900195

Discovery of Dinaciclib (SCH 727965): A Potent and Selective Inhibitor of Cyclin-Dependent Kinases.

PubMed

Paruch, Kamil; Dwyer, Michael P; Alvarez, Carmen; Brown, Courtney; Chan, Tin-Yau; Doll, Ronald J; Keertikar, Kerry; Knutson, Chad; McKittrick, Brian; Rivera, Jocelyn; Rossman, Randall; Tucker, Greg; Fischmann, Thierry; Hruza, Alan; Madison, Vincent; Nomeir, Amin A; Wang, Yaolin; Kirschmeier, Paul; Lees, Emma; Parry, David; Sgambellone, Nicole; Seghezzi, Wolfgang; Schultz, Lesley; Shanahan, Frances; Wiswell, Derek; Xu, Xiaoying; Zhou, Quiao; James, Ray A; Paradkar, Vidyadhar M; Park, Haengsoon; Rokosz, Laura R; Stauffer, Tara M; Guzi, Timothy J

2010-08-12

Inhibition of cyclin-dependent kinases (CDKs) has emerged as an attractive strategy for the development of novel oncology therapeutics. Herein is described the utilization of an in vivo screening approach with integrated efficacy and tolerability parameters to identify candidate CDK inhibitors with a suitable balance of activity and tolerability. This approach has resulted in the identification of SCH 727965, a potent and selective CDK inhibitor that is currently undergoing clinical evaluation.

Reading the Tea Leaves: How Utilities in the West Are Managing Carbon Regulatory Risk in their Resource Plans

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

Barbose, Galen; Wiser, Ryan; Phadke, Amol

2008-02-01

The long economic lifetime and development lead-time of many electric infrastructure investments requires that utility resource planning consider potential costs and risks over a lengthy time horizon. One long-term -- and potentially far-reaching -- risk currently facing the electricity industry is the uncertain cost of future carbon dioxide (CO2) regulations. Recognizing the importance of this issue, many utilities (sometimes spurred by state regulatory requirements) are beginning to actively assess carbon regulatory risk within their resource planning processes, and to evaluate options for mitigating that risk. However, given the relatively recent emergence of this issue and the rapidly changing political landscape,more » methods and assumptions used to analyze carbon regulatory risk, and the impact of this analysis on the selection of a preferred resource portfolio, vary considerably across utilities. In this study, we examine the treatment of carbon regulatory risk in utility resource planning, through a comparison of the most-recent resource plans filed by fifteen investor-owned and publicly-owned utilities in the Western U.S. Together, these utilities account for approximately 60percent of retail electricity sales in the West, and cover nine of eleven Western states. This report has two related elements. First, we compare and assess utilities' approaches to addressing key analytical issues that arise when considering the risk of future carbon regulations. Second, we summarize the composition and carbon intensity of the preferred resource portfolios selected by these fifteen utilities and compare them to potential CO2 emission benchmark levels.« less

Active/Passive Control of Sound Radiation from Panels using Constrained Layer Damping

NASA Technical Reports Server (NTRS)

Gibbs, Gary P.; Cabell, Randolph H.

2003-01-01

A hybrid passive/active noise control system utilizing constrained layer damping and model predictive feedback control is presented. This system is used to control the sound radiation of panels due to broadband disturbances. To facilitate the hybrid system design, a methodology for placement of constrained layer damping which targets selected modes based on their relative radiated sound power is developed. The placement methodology is utilized to determine two constrained layer damping configurations for experimental evaluation of a hybrid system. The first configuration targets the (4,1) panel mode which is not controllable by the piezoelectric control actuator, and the (2,3) and (5,2) panel modes. The second configuration targets the (1,1) and (3,1) modes. The experimental results demonstrate the improved reduction of radiated sound power using the hybrid passive/active control system as compared to the active control system alone.

Carboxylesterase inhibitors

PubMed Central

Hatfield, M. Jason; Potter, Philip M.

2011-01-01

Introduction Carboxylesterases play major roles in the hydrolysis of numerous therapeutically active compounds. This is, in part, due to the prevalence of the ester moiety in these small molecules. However, the impact these enzymes may play on drug stability and pharmacokinetics is rarely considered prior to molecule development. Therefore, the application of selective inhibitors of this class of proteins may have utility in modulating the metabolism, distribution and toxicity of agents that are subjected to enzyme hydrolysis. Areas covered This review details the development of all such compounds dating back to 1986, but principally focuses on the very recent identification of selective human carboxylesterases inhibitors. Expert opinion The implementation of carboxylesterase inhibitors may significantly revolutionize drug discovery. Such molecules may allow for improved efficacy of compounds inactivated by this class of enzymes and/or reduce the toxicity of agents that are activated by these proteins. Furthermore, since lack of carboxylesterase activity appears to have no obvious biological consequence, these compounds could be applied in combination with virtually any esterified drug. Therefore, inhibitors of these proteins may have utility in altering drug hydrolysis and distribution in vivo. The characteristics, chemical and biological properties, and potential uses of such agents, are discussed here. PMID:21609191

A Case Study of Leadership Pedagogy in an Organizational Behavior Class

ERIC Educational Resources Information Center

Ingerson, Kati; Bruce, Jackie

2015-01-01

The purpose of this study was to understand if selected leadership pedagogy (hands on activities) utilized in an organizational behavior classroom contributed to the development of workplace readiness skills. Since successful organizational behavior classes and hands on learning can lead to successful graduates, the importance of leadership…

Encouragement of Enzyme Reaction Utilizing Heat Generation from Ferromagnetic Particles Subjected to an AC Magnetic Field

PubMed Central

Suzuki, Masashi; Aki, Atsushi; Mizuki, Toru; Maekawa, Toru; Usami, Ron; Morimoto, Hisao

2015-01-01

We propose a method of activating an enzyme utilizing heat generation from ferromagnetic particles under an ac magnetic field. We immobilize α-amylase on the surface of ferromagnetic particles and analyze its activity. We find that when α-amylase/ferromagnetic particle hybrids, that is, ferromagnetic particles, on which α-amylase molecules are immobilized, are subjected to an ac magnetic field, the particles generate heat and as a result, α-amylase on the particles is heated up and activated. We next prepare a solution, in which α-amylase/ferromagnetic particle hybrids and free, nonimmobilized chitinase are dispersed, and analyze their activities. We find that when the solution is subjected to an ac magnetic field, the activity of α-amylase immobilized on the particles increases, whereas that of free chitinase hardly changes; in other words, only α-amylase immobilized on the particles is selectively activated due to heat generation from the particles. PMID:25993268

Knowledge representation of motor activity of patients with Parkinson's disease.

PubMed

Kostek, Bożena; Kupryjanow, Adam; Czyżewski, Andrzej

An approach to the knowledge representation extraction from biomedical signals analysis concerning motor activity of Parkinson disease patients is proposed in this paper. This is done utilizing accelerometers attached to their body as well as exploiting video image of their hand movements. Experiments are carried out employing artificial neural networks and support vector machine to the recognition of characteristic motor activity disorders in patients. Obtained results indicate that it is possible to interpret some selected patient's body movements with a sufficiently high effectiveness.

Systems-level computational modeling demonstrates fuel selection switching in high capacity running and low capacity running rats

PubMed Central

Qi, Nathan R.

2018-01-01

High capacity and low capacity running rats, HCR and LCR respectively, have been bred to represent two extremes of running endurance and have recently demonstrated disparities in fuel usage during transient aerobic exercise. HCR rats can maintain fatty acid (FA) utilization throughout the course of transient aerobic exercise whereas LCR rats rely predominantly on glucose utilization. We hypothesized that the difference between HCR and LCR fuel utilization could be explained by a difference in mitochondrial density. To test this hypothesis and to investigate mechanisms of fuel selection, we used a constraint-based kinetic analysis of whole-body metabolism to analyze transient exercise data from these rats. Our model analysis used a thermodynamically constrained kinetic framework that accounts for glycolysis, the TCA cycle, and mitochondrial FA transport and oxidation. The model can effectively match the observed relative rates of oxidation of glucose versus FA, as a function of ATP demand. In searching for the minimal differences required to explain metabolic function in HCR versus LCR rats, it was determined that the whole-body metabolic phenotype of LCR, compared to the HCR, could be explained by a ~50% reduction in total mitochondrial activity with an additional 5-fold reduction in mitochondrial FA transport activity. Finally, we postulate that over sustained periods of exercise that LCR can partly overcome the initial deficit in FA catabolic activity by upregulating FA transport and/or oxidation processes. PMID:29474500

Technology transfer to a developing nation, Korea

NASA Technical Reports Server (NTRS)

Stone, C. A.; Uccetta, S. J.

1973-01-01

An experimental project is reported which was undertaken. to determine if selected types of technology developed for the aerospace program during the past decade are relevant to specific industrial problems of a developing nation and to test whether a structured program could facilitate the transfer of relevant technologies. The Korea Institute of Science and Technology and the IIT Research Institute were selected as the active transfer agents to participate in the program. The pilot project was based upon the approach to the transfer of domestic technology developed by the NASA Technology Utilization Division and utilized the extensive data and technical resources available through the Space Agency and its contractors. This pilot project has helped to clarify some aspects of the international technology transfer process and to upgrade Korean technological capabilities.

Selective C(sp3 )-H Aerobic Oxidation Enabled by Decatungstate Photocatalysis in Flow.

PubMed

Laudadio, Gabriele; Govaerts, Sebastian; Wang, Ying; Ravelli, Davide; Koolman, Hannes F; Fagnoni, Maurizio; Djuric, Stevan W; Noël, Timothy

2018-04-03

A mild and selective C(sp 3 )-H aerobic oxidation enabled by decatungstate photocatalysis has been developed. The reaction can be significantly improved in a microflow reactor enabling the safe use of oxygen and enhanced irradiation of the reaction mixture. Our method allows for the oxidation of both activated and unactivated C-H bonds (30 examples). The ability to selectively oxidize natural scaffolds, such as (-)-ambroxide, pregnenolone acetate, (+)-sclareolide, and artemisinin, exemplifies the utility of this new method. © 2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Individual and contextual factors influencing dental health care utilization by preschool children: a multilevel analysis

PubMed

Piovesan, Chaiana; Ardenghi, Thiago Machado; Mendes, Fausto Medeiros; Agostini, Bernardo Antonio; Michel-Crosato, Edgard

2017-03-30

The effect of contextual factors on dental care utilization was evaluated after adjustment for individual characteristics of Brazilian preschool children. This cross-sectional study assessed 639 preschool children aged 1 to 5 years from Santa Maria, a town in Rio Grande do Sul State, located in southern Brazil. Participants were randomly selected from children attending the National Children's Vaccination Day and 15 health centers were selected for this research. Visual examinations followed the ICDAS criteria. Parents answered a questionnaire about demographic and socioeconomic characteristics. Contextual influences on children's dental care utilization were obtained from two community-related variables: presence of dentists and presence of workers' associations in the neighborhood. Unadjusted and adjusted multilevel logistic regression models were used to describe the association between outcome and predictor variables. A prevalence of 21.6% was found for regular use of dental services. The unadjusted assessment of the associations of dental health care utilization with individual and contextual factors included children's ages, family income, parents' schooling, mothers' participation in their children's school activities, dental caries, and presence of workers' associations in the neighborhood as the main outcome covariates. Individual variables remained associated with the outcome after adding contextual variables in the model. In conclusion, individual and contextual variables were associated with dental health care utilization by preschool children.

Oral antibodies to human intestinal alkaline phosphatase reduce dietary phytate phosphate bioavailability in the presence of dietary 1α-hydroxycholecalciferol.

PubMed

Bobeck, Elizabeth A; Hellestad, Erica M; Helvig, Christian F; Petkovich, P Martin; Cook, Mark E

2016-03-01

While it is well established that active vitamin D treatment increases dietary phytate phosphate utilization, the mechanism by which intestinal alkaline phosphatase (IAP) participates in phytate phosphate use is less clear. The ability of human IAP (hIAP) oral antibodies to prevent dietary phytate phosphate utilization in the presence of 1α-hydroxycholecalciferol (1α-(OH) D3) in a chick model was investigated. hIAP specific chicken immunoglobulin Y (IgY) antibodies were generated by inoculating laying hens with 17 synthetic peptides derived from the human IAP amino acid sequence and harvesting egg yolk. Western blot analysis showed all antibodies recognized hIAP and 6 of the 8 antibodies selected showed modest inhibition of hIAP activity in vitro (6 to 33% inhibition). In chicks where dietary phosphate was primarily in the form of phytate, 4 selected hIAP antibodies inhibited 1α-(OH) D3-induced increases in blood phosphate, one of which, generated against selected peptide (MFPMGTPD), was as effective as sevelamer hydrochloride in preventing the 1α-(OH) D3-induced increase in blood phosphate, but ineffective in preventing an increase in body weight gain and bone ash induced by 1α-(OH) D3. These studies demonstrated that orally-delivered antibodies to IAP limit dietary phytate-phosphate utilization in chicks treated with 1α-(OH) D3, and implicate IAP as an important host enzyme in increasing phytate phosphate bioavailability in 1α-(OH) D3 fed chicks. © 2015 Poultry Science Association Inc.

Role of vegetation and edaphic factors in controlling diversity and use of different carbon sources in semi-arid ecosystems

NASA Astrophysics Data System (ADS)

Lohse, K. A.; McLain, J. E.; Harman, C. J.; Sivapalan, M.; Troch, P. A.

2010-12-01

Microbially-mediated soil carbon cycling is closely linked to soil moisture and temperature. Climate change is predicted to increase intra-annual precipitation variability (i.e. less frequent yet more intense precipitation events) and alter biogeochemical processes due to shifts in soil moisture dynamics and inputs of carbon. However, the responses of soil biology and chemistry to predicted climate change, and their concomitant feedbacks on ecosystem productivity and biogeochemical processes are poorly understood. We collected soils at three different elevations in the Santa Catalina Mountains, AZ and quantified carbon utilization during pre-monsoon precipitation conditions. Contrasting parent materials (schist and granite) were paired at each elevation. We expected climate to determine the overall activity of soil fungal and bacterial communities and diversity of soil C utilization, and differences in parent material to modify these responses through controls on soil physical properties. We used EcoPlateTM C utilization assays to determine the relative abundance of soil bacterial and fungal populations and rate and diversity of carbon utilization. Additional plates were incubated with inhibitors selective to fungal or bacterial activity to assess relative contribution of these microbial groups to overall C utilization. We analyzed soils for soil organic matter, total C and N, particle size analysis and soil moisture content via both gravimetric and volumetric methods to assess the influences of soil physical and chemical properties on the measured biological responses. Consistent with our expectations, overall microbial activity was highest at the uppermost conifer elevation sites compared to the middle and lower elevation sites. In contrast to our expectations, however, overall activity was lower at the mid elevation oak woodland sites compared to the low elevation desert sites. Also consistent with our expectations was the observation that overall activities were consistently higher in schist parent material compared to granite. Though differences between canopy and intercanopy carbon utilization were subtle, the diversity of carbon utilization differed, suggesting a potential role of root exudates in governing C utilization in these semiarid soils. Findings from this study suggest that soil physical properties due to parent material have primary impacts in constraining microbial growth and carbon utilization under changing climate conditions.

Suzaku  Observations of Heavily Obscured (Compton-thick) Active Galactic Nuclei Selected by the Swift/BAT Hard X-Ray Survey

NASA Astrophysics Data System (ADS)

Tanimoto, Atsushi; Ueda, Yoshihiro; Kawamuro, Taiki; Ricci, Claudio; Awaki, Hisamitsu; Terashima, Yuichi

2018-02-01

We present a uniform broadband X-ray (0.5–100.0 keV) spectral analysis of 12 Swift/Burst Alert Telescope selected Compton-thick ({log}{N}{{H}}/{{cm}}-2≥slant 24) active galactic nuclei (CTAGNs) observed with Suzaku. The Suzaku data of three objects are published here for the first time. We fit the Suzaku and Swift spectra with models utilizing an analytic reflection code and those utilizing the Monte-Carlo-based model from an AGN torus by Ikeda et al. The main results are as follows: (1) The estimated intrinsic luminosity of a CTAGN strongly depends on the model; applying Compton scattering to the transmitted component in an analytic model may largely overestimate the intrinsic luminosity at large column densities. (2) Unabsorbed reflection components are commonly observed, suggesting that the tori are clumpy. (3) Most of CTAGNs show small scattering fractions (<0.5%), implying a buried AGN nature. (4) Comparison with the results obtained for Compton-thin AGNs suggests that the properties of these CTAGNs can be understood as a smooth extension from Compton-thin AGNs with heavier obscuration; we find no evidence that the bulk of the population of hard-X-ray-selected CTAGNs are different from less obscured objects.

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

Stevens, S.E. Jr.; Chung, K.T.

Anaerobic bacteria were isolated from deep subsurface sediment samples taken at study sites in Idaho (INEL) and Washington (HR) by culturing on dilute and concentrated medium. Morphologically distinct colonies were purified, and their responses to 21 selected physiological tests were determined. Although the number of isolates was small (18 INEL, 27 HR) some general patterns could be determined. Most strains could utilize all the carbon sources, however the glycerol and melizitose utilization was positive for 50% or less of the HR isolates. Catalase activity (27.78% at INEL, 74.07% at HR) and tryptophan metabolism (11.12% at INEL, 40.74% at HR) weremore » significantly different between the two study sites. MPN and viable counts indicate that sediments near the water table yield the greatest numbers of anaerobes. Deeper sediments also appear to be more selective with the greatest number of viable counts on low-nutrient mediums. Likewise, only strictly obligate anaerobes were found in the deepest sediment samples. Selective media indicated the presence of methanogens, acetogens, and sulfate reducers at only the HR site.« less

RDF (Refuse Derived Fuel) Utilization in a Navy Stoker Coal-Fired Boiler.

DTIC Science & Technology

1984-10-01

the energy production in any coal-fired boiler conversion consideration. The selection of the actual RDF to be used in a converted boiler should be... industrial boilers by gathering information from the Navy Energy and Environmental Support Activity, engineering field divi- sions, and field...activities. Currently the Navy has 27 industrial size boilers firing coal as a primary fuel and 10 firing coal as a secondary fuel. The four principal factors

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

Evans, V.; Foltz, D.

In 1990, the Clean Air Act was amended amidst a flurry of lobbying. One of the special provisions added was Section 404(d) (see also 40 CFR 72.42) to extend the deadline for compliance under Title IV from 1995 to 1997 for units that committed to install high-efficiency SO{sub 2} scrubbers. Title IV created the Acid Rain Program to reduce emissions of SO{sub 2} and NO{sub x} from electric utility boilers. Section 404(d) was added as a result of the efforts to encourage the continued use of high sulfur coal. Congress allocated 3.5 million allowances for EPA to award under thesemore » provisions. To reduce the uncertainty of being selected to receive extension allowances through EPA`s lottery system, utilities interested in participating in the Program formed the Extension Allowance Pool. The Extension Allowance Pooling Agreement was executed as of March 1992 by 16 utilities. The underlying principle of the Pool is that those utilities whose control units were selected to receive extension allowances would share a portion of those allowances with those Pool participants that were not chosen by EPA. The Pool also provided for the various activities required to implement these arrangements.« less

Anisotropic Covalency Contributions to Superexchange Pathways in Type One Copper Active Sites

PubMed Central

2015-01-01

Type one (T1) Cu sites deliver electrons to catalytic Cu active sites: the mononuclear type two (T2) Cu site in nitrite reductases (NiRs) and the trinuclear Cu cluster in the multicopper oxidases (MCOs). The T1 Cu and the remote catalytic sites are connected via a Cys-His intramolecular electron-transfer (ET) bridge, which contains two potential ET pathways: P1 through the protein backbone and P2 through the H-bond between the Cys and the His. The high covalency of the T1 Cu–S(Cys) bond is shown here to activate the T1 Cu site for hole superexchange via occupied valence orbitals of the bridge. This covalency-activated electronic coupling (HDA) facilitates long-range ET through both pathways. These pathways can be selectively activated depending on the geometric and electronic structure of the T1 Cu site and thus the anisotropic covalency of the T1 Cu–S(Cys) bond. In NiRs, blue (π-type) T1 sites utilize P1 and green (σ-type) T1 sites utilize P2, with P2 being more efficient. Comparing the MCOs to NiRs, the second-sphere environment changes the conformation of the Cys-His pathway, which selectively activates HDA for superexchange by blue π sites for efficient turnover in catalysis. These studies show that a given protein bridge, here Cys-His, provides different superexchange pathways and electronic couplings depending on the anisotropic covalencies of the donor and acceptor metal sites. PMID:25310460

Measurement properties of self-report physical activity assessment tools in stroke: a protocol for a systematic review

PubMed Central

Martins, Júlia Caetano; Aguiar, Larissa Tavares; Nadeau, Sylvie; Scianni, Aline Alvim; Teixeira-Salmela, Luci Fuscaldi; Faria, Christina Danielli Coelho de Morais

2017-01-01

Introduction Self-report physical activity assessment tools are commonly used for the evaluation of physical activity levels in individuals with stroke. A great variety of these tools have been developed and widely used in recent years, which justify the need to examine their measurement properties and clinical utility. Therefore, the main objectives of this systematic review are to examine the measurement properties and clinical utility of self-report measures of physical activity and discuss the strengths and limitations of the identified tools. Methods and analysis A systematic review of studies that investigated the measurement properties and/or clinical utility of self-report physical activity assessment tools in stroke will be conducted. Electronic searches will be performed in five databases: Medical Literature Analysis and Retrieval System Online (MEDLINE) (PubMed), Excerpta Medica Database (EMBASE), Physiotherapy Evidence Database (PEDro), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) and Scientific Electronic Library Online (SciELO), followed by hand searches of the reference lists of the included studies. Two independent reviewers will screen all retrieve titles, abstracts, and full texts, according to the inclusion criteria and will also extract the data. A third reviewer will be referred to solve any disagreement. A descriptive summary of the included studies will contain the design, participants, as well as the characteristics, measurement properties, and clinical utility of the self-report tools. The methodological quality of the studies will be evaluated using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist and the clinical utility of the identified tools will be assessed considering predefined criteria. This systematic review will follow the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement. Discussion This systematic review will provide an extensive review of the measurement properties and clinical utility of self-report physical activity assessment tools used in individuals with stroke, which would benefit clinicians and researchers. Trial registration number PROSPERO CRD42016037146. PMID:28193848

Selection, Inclusion, Evaluation and Defense of Transgender-Inclusive Fiction for Young Adults: A Resource Guide

ERIC Educational Resources Information Center

Rockefeller, Elsworth I.

2009-01-01

An increasingly visible youth transgender population is emerging and the number of transgender-inclusive fiction texts for young adults is growing. Adults serving teens in schools, libraries, and community agencies must begin actively pursuing, utilizing, and incorporating these texts into resource collections. This article provides an overview of…

An evaluation of selected in silico models for the assessment of skin sensitization potential – performance and practical utility considerations (QSAR conference)

EPA Science Inventory

Skin sensitization remains an important endpoint for consumers, manufacturers and regulators. Although the development of alternative approaches to assess skin sensitization potential has been extremely active over many years, the implication of regulations such as REACH and the ...

75 FR 59293 - Agency Information Collection Activities: Reinstatement, With Change, of a Previously Approved...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-27

... selection of judicial officers, the governance of the judicial branch, the funding and budgets of state..., information will be collected on the utilization of information technology systems in state courts. All data... Amount of Time Estimated for an Average Respondent to Respond: The State Court Organization (SCO) data...

75 FR 72840 - Agency Information Collection Activities: Reinstatement, With Change of a Previously Approved...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-11-26

... selection of judicial officers, the governance of the judicial branch, the funding and budgets of state..., information will be collected on the utilization of information technology systems in state courts. All data... Amount of Time Estimated for an Average Respondent to Respond: The State Court Organization (SCO) data...

Comprehensive Technology Utilization Leading to Excellence in Medium Sized Schools.

ERIC Educational Resources Information Center

Diercks, Eileen; And Others

Although limited finances and a student body of 3,200 have made it necessary to be selective in acquiring educational technology, the Plainfield (Illinois) Community Consolidated School District No. 202 has been very active in the regional partnership for excellence. Curricular programs at the Plainfield High School include use of…

Getting the Message Across; Non-Verbal Communication in the Classroom.

ERIC Educational Resources Information Center

Levy, Jack

This handbook presents selected theories, activities, and resources which can be utilized by educators in the area of non-verbal communication. Particular attention is given to the use of non-verbal communication in a cross-cultural context. Categories of non-verbal communication such as proxemics, haptics, kinesics, smiling, sound, clothing, and…

A Study of Planetarium Effectiveness on Student Achievement, Perceptions and Retention.

ERIC Educational Resources Information Center

Ridky, Robert William

Reported is a study to determine the effect of planetarium instruction in terms of immediate attainment, attitude, and retention in the teaching of selected celestial motion and non-celestial motion concepts, when contrasted to or combined with the inquiry activities utilized by the nationally developed science curricula. Observations were made on…

Magnetically-focusing biochip structures for high-speed active biosensing with improved selectivity.

PubMed

Yoo, Haneul; Lee, Dong Jun; Kim, Daesan; Park, Juhun; Chen, Xing; Hong, Seunghun

2018-06-29

We report a magnetically-focusing biochip structure enabling a single layered magnetic trap-and-release cycle for biosensors with an improved detection speed and selectivity. Here, magnetic beads functionalized with specific receptor molecules were utilized to trap target molecules in a solution and transport actively to and away from the sensor surfaces to enhance the detection speed and reduce the non-specific bindings, respectively. Using our method, we demonstrated the high speed detection of IL-13 antigens with the improved detection speed by more than an order of magnitude. Furthermore, the release step in our method was found to reduce the non-specific bindings and improve the selectivity and sensitivity of biosensors. This method is a simple but powerful strategy and should open up various applications such as ultra-fast biosensors for point-of-care services.

Magnetically-focusing biochip structures for high-speed active biosensing with improved selectivity

NASA Astrophysics Data System (ADS)

Yoo, Haneul; Lee, Dong Jun; Kim, Daesan; Park, Juhun; Chen, Xing; Hong, Seunghun

2018-06-01

We report a magnetically-focusing biochip structure enabling a single layered magnetic trap-and-release cycle for biosensors with an improved detection speed and selectivity. Here, magnetic beads functionalized with specific receptor molecules were utilized to trap target molecules in a solution and transport actively to and away from the sensor surfaces to enhance the detection speed and reduce the non-specific bindings, respectively. Using our method, we demonstrated the high speed detection of IL-13 antigens with the improved detection speed by more than an order of magnitude. Furthermore, the release step in our method was found to reduce the non-specific bindings and improve the selectivity and sensitivity of biosensors. This method is a simple but powerful strategy and should open up various applications such as ultra-fast biosensors for point-of-care services.

Leisure riding horses: research topics versus the needs of stakeholders.

PubMed

Janczarek, Iwona; Wilk, Izabela

2017-07-01

Horses intended for leisure riding do not undergo any selection and most often retired sports horses or defective horses are chosen, as a low selling price determines their purchase by a leisure riding center. Unfortunately, horses bought at low prices usually have low utility value, are difficult to handle, require a special or individual approach and do not provide satisfaction in riding. However, neither modern horse breeding nor scientific research address the need to breed horses for leisure activities. There is no clear definition of a model leisure horse and criteria or information for its selection are not readily available in scientific publications. A wide spectrum of research methods may be used to evaluate various performance traits in horses intended for leisure activities. The fact that the population of recreational horses and their riders outnumber sporting horses should attract the special attention of scientific research. Their utility traits need to be determined with modern technology and methods in the same way they are for sporting horses. Such a system of evaluation would be very helpful for riders. © 2017 Japanese Society of Animal Science.

The Effects of Variability and Risk in Selection Utility Analysis: An Empirical Comparison.

ERIC Educational Resources Information Center

Rich, Joseph R.; Boudreau, John W.

1987-01-01

Investigated utility estimate variability for the selection utility of using the Programmer Aptitude Test to select computer programmers. Comparison of Monte Carlo results to other risk assessment approaches (sensitivity analysis, break-even analysis, algebraic derivation of the distribtion) suggests that distribution information provided by Monte…

The First Structure–Activity Relationship Studies for Designer Receptors Exclusively Activated by Designer Drugs

PubMed Central

2016-01-01

Over the past decade, two independent technologies have emerged and been widely adopted by the neuroscience community for remotely controlling neuronal activity: optogenetics which utilize engineered channelrhodopsin and other opsins, and chemogenetics which utilize engineered G protein-coupled receptors (Designer Receptors Exclusively Activated by Designer Drugs (DREADDs)) and other orthologous ligand–receptor pairs. Using directed molecular evolution, two types of DREADDs derived from human muscarinic acetylcholine receptors have been developed: hM3Dq which activates neuronal firing, and hM4Di which inhibits neuronal firing. Importantly, these DREADDs were not activated by the native ligand acetylcholine (ACh), but selectively activated by clozapine N-oxide (CNO), a pharmacologically inert ligand. CNO has been used extensively in rodent models to activate DREADDs, and although CNO is not subject to significant metabolic transformation in mice, a small fraction of CNO is apparently metabolized to clozapine in humans and guinea pigs, lessening the translational potential of DREADDs. To effectively translate the DREADD technology, the next generation of DREADD agonists are needed and a thorough understanding of structure–activity relationships (SARs) of DREADDs is required for developing such ligands. We therefore conducted the first SAR studies of hM3Dq. We explored multiple regions of the scaffold represented by CNO, identified interesting SAR trends, and discovered several compounds that are very potent hM3Dq agonists but do not activate the native human M3 receptor (hM3). We also discovered that the approved drug perlapine is a novel hM3Dq agonist with >10 000-fold selectivity for hM3Dq over hM3. PMID:25587888

A four-dimensional virtual hand brain-machine interface using active dimension selection

NASA Astrophysics Data System (ADS)

Rouse, Adam G.

2016-06-01

Objective. Brain-machine interfaces (BMI) traditionally rely on a fixed, linear transformation from neural signals to an output state-space. In this study, the assumption that a BMI must control a fixed, orthogonal basis set was challenged and a novel active dimension selection (ADS) decoder was explored. Approach. ADS utilizes a two stage decoder by using neural signals to both (i) select an active dimension being controlled and (ii) control the velocity along the selected dimension. ADS decoding was tested in a monkey using 16 single units from premotor and primary motor cortex to successfully control a virtual hand avatar to move to eight different postures. Main results. Following training with the ADS decoder to control 2, 3, and then 4 dimensions, each emulating a grasp shape of the hand, performance reached 93% correct with a bit rate of 2.4 bits s-1 for eight targets. Selection of eight targets using ADS control was more efficient, as measured by bit rate, than either full four-dimensional control or computer assisted one-dimensional control. Significance. ADS decoding allows a user to quickly and efficiently select different hand postures. This novel decoding scheme represents a potential method to reduce the complexity of high-dimension BMI control of the hand.

A four-dimensional virtual hand brain-machine interface using active dimension selection

PubMed Central

Rouse, Adam G.

2018-01-01

Objective Brain-machine interfaces (BMI) traditionally rely on a fixed, linear transformation from neural signals to an output state-space. In this study, the assumption that a BMI must control a fixed, orthogonal basis set was challenged and a novel active dimension selection (ADS) decoder was explored. Approach ADS utilizes a two stage decoder by using neural signals to both i) select an active dimension being controlled and ii) control the velocity along the selected dimension. ADS decoding was tested in a monkey using 16 single units from premotor and primary motor cortex to successfully control a virtual hand avatar to move to eight different postures. Main Results Following training with the ADS decoder to control 2, 3, and then 4 dimensions, each emulating a grasp shape of the hand, performance reached 93% correct with a bit rate of 2.4 bits/s for eight targets. Selection of eight targets using ADS control was more efficient, as measured by bit rate, than either full four-dimensional control or computer assisted one-dimensional control. Significance ADS decoding allows a user to quickly and efficiently select different hand postures. This novel decoding scheme represents a potential method to reduce the complexity of high-dimension BMI control of the hand. PMID:27171896

First-Principles Integrated Adsorption Modeling for Selective Capture of Uranium from Seawater by Polyamidoxime Sorbent Materials

DOE PAGES

Ladshaw, Austin P.; Ivanov, Alexander S.; Das, Sadananda; ...

2018-03-27

Nuclear power is a relatively carbon-free energy source that has the capacity to be utilized today in an effort to stem the tides of global warming. The growing demand for nuclear energy, however, could put significant strain on our uranium ore resources, and the mining activities utilized to extract that ore can leave behind long-term environmental damage. A potential solution to enhance the supply of uranium fuel is to recover uranium from seawater using amidoximated adsorbent fibers. This technology has been studied for decades but is currently plagued by the material’s relatively poor selectivity of uranium over its main competitormore » vanadium. In this work, we investigate the binding schemes between uranium, vanadium, and the amidoxime functional groups on the adsorbent surface. Using quantum chemical methods, binding strengths are approximated for a set of complexation reactions between uranium and vanadium with amidoxime functionalities. Those approximations are then coupled with a comprehensive aqueous adsorption model developed in this work to simulate the adsorption of uranium and vanadium under laboratory conditions. Experimental adsorption studies with uranium and vanadium over a wide pH range are performed, and the data collected are compared against simulation results to validate the model. It was found that coupling ab initio calculations with process level adsorption modeling provides accurate predictions of the adsorption capacity and selectivity of the sorbent materials. Furthermore, this work demonstrates that this multiscale modeling paradigm could be utilized to aid in the selection of superior ligands or ligand compositions for the selective capture of metal ions. Furthermore, this first-principles integrated modeling approach opens the door to the in silico design of next-generation adsorbents with potentially superior efficiency and selectivity for uranium over vanadium in seawater.« less

First-Principles Integrated Adsorption Modeling for Selective Capture of Uranium from Seawater by Polyamidoxime Sorbent Materials

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

Ladshaw, Austin P.; Ivanov, Alexander S.; Das, Sadananda

Nuclear power is a relatively carbon-free energy source that has the capacity to be utilized today in an effort to stem the tides of global warming. The growing demand for nuclear energy, however, could put significant strain on our uranium ore resources, and the mining activities utilized to extract that ore can leave behind long-term environmental damage. A potential solution to enhance the supply of uranium fuel is to recover uranium from seawater using amidoximated adsorbent fibers. This technology has been studied for decades but is currently plagued by the material’s relatively poor selectivity of uranium over its main competitormore » vanadium. In this work, we investigate the binding schemes between uranium, vanadium, and the amidoxime functional groups on the adsorbent surface. Using quantum chemical methods, binding strengths are approximated for a set of complexation reactions between uranium and vanadium with amidoxime functionalities. Those approximations are then coupled with a comprehensive aqueous adsorption model developed in this work to simulate the adsorption of uranium and vanadium under laboratory conditions. Experimental adsorption studies with uranium and vanadium over a wide pH range are performed, and the data collected are compared against simulation results to validate the model. It was found that coupling ab initio calculations with process level adsorption modeling provides accurate predictions of the adsorption capacity and selectivity of the sorbent materials. Furthermore, this work demonstrates that this multiscale modeling paradigm could be utilized to aid in the selection of superior ligands or ligand compositions for the selective capture of metal ions. Furthermore, this first-principles integrated modeling approach opens the door to the in silico design of next-generation adsorbents with potentially superior efficiency and selectivity for uranium over vanadium in seawater.« less

First-Principles Integrated Adsorption Modeling for Selective Capture of Uranium from Seawater by Polyamidoxime Sorbent Materials.

PubMed

Ladshaw, Austin P; Ivanov, Alexander S; Das, Sadananda; Bryantsev, Vyacheslav S; Tsouris, Costas; Yiacoumi, Sotira

2018-04-18

Nuclear power is a relatively carbon-free energy source that has the capacity to be utilized today in an effort to stem the tides of global warming. The growing demand for nuclear energy, however, could put significant strain on our uranium ore resources, and the mining activities utilized to extract that ore can leave behind long-term environmental damage. A potential solution to enhance the supply of uranium fuel is to recover uranium from seawater using amidoximated adsorbent fibers. This technology has been studied for decades but is currently plagued by the material's relatively poor selectivity of uranium over its main competitor vanadium. In this work, we investigate the binding schemes between uranium, vanadium, and the amidoxime functional groups on the adsorbent surface. Using quantum chemical methods, binding strengths are approximated for a set of complexation reactions between uranium and vanadium with amidoxime functionalities. Those approximations are then coupled with a comprehensive aqueous adsorption model developed in this work to simulate the adsorption of uranium and vanadium under laboratory conditions. Experimental adsorption studies with uranium and vanadium over a wide pH range are performed, and the data collected are compared against simulation results to validate the model. It was found that coupling ab initio calculations with process level adsorption modeling provides accurate predictions of the adsorption capacity and selectivity of the sorbent materials. Furthermore, this work demonstrates that this multiscale modeling paradigm could be utilized to aid in the selection of superior ligands or ligand compositions for the selective capture of metal ions. Therefore, this first-principles integrated modeling approach opens the door to the in silico design of next-generation adsorbents with potentially superior efficiency and selectivity for uranium over vanadium in seawater.

Stable and solubilized active Au atom clusters for selective epoxidation of cis-cyclooctene with molecular oxygen

DOE PAGES

Qian, Linping; Wang, Zhen; Beletskiy, Evgeny V.; ...

2017-03-28

Here, the ability of Au catalysts to effect the challenging task of utilizing molecular oxygen for the selective epoxidation of cyclooctene is fascinating. Although supported nanometre-size Au particles are poorly active, here we show that solubilized atomic Au clusters, present in ng ml –1 concentrations and stabilized by ligands derived from the oxidized hydrocarbon products, are active. They can be formed from various Au sources. They generate initiators and propagators to trigger the onset of the auto-oxidation reaction with an apparent turnover frequency of 440 s –1, and continue to generate additional initiators throughout the auto-oxidation cycle without direct participationmore » in the cycle. Spectroscopic characterization suggests that 7–8 atom clusters are effective catalytically. Extension of work based on these understandings leads to the demonstration that these Au clusters are also effective in selective oxidation of cyclohexene, and that solubilized Pt clusters are also capable of generating initiators for cyclooctene epoxidation.« less

Stable and solubilized active Au atom clusters for selective epoxidation of cis-cyclooctene with molecular oxygen

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

Qian, Linping; Wang, Zhen; Beletskiy, Evgeny V.

Here, the ability of Au catalysts to effect the challenging task of utilizing molecular oxygen for the selective epoxidation of cyclooctene is fascinating. Although supported nanometre-size Au particles are poorly active, here we show that solubilized atomic Au clusters, present in ng ml –1 concentrations and stabilized by ligands derived from the oxidized hydrocarbon products, are active. They can be formed from various Au sources. They generate initiators and propagators to trigger the onset of the auto-oxidation reaction with an apparent turnover frequency of 440 s –1, and continue to generate additional initiators throughout the auto-oxidation cycle without direct participationmore » in the cycle. Spectroscopic characterization suggests that 7–8 atom clusters are effective catalytically. Extension of work based on these understandings leads to the demonstration that these Au clusters are also effective in selective oxidation of cyclohexene, and that solubilized Pt clusters are also capable of generating initiators for cyclooctene epoxidation.« less

What's wrong with hazard-ranking systems? An expository note.

PubMed

Cox, Louis Anthony Tony

2009-07-01

Two commonly recommended principles for allocating risk management resources to remediate uncertain hazards are: (1) select a subset to maximize risk-reduction benefits (e.g., maximize the von Neumann-Morgenstern expected utility of the selected risk-reducing activities), and (2) assign priorities to risk-reducing opportunities and then select activities from the top of the priority list down until no more can be afforded. When different activities create uncertain but correlated risk reductions, as is often the case in practice, then these principles are inconsistent: priority scoring and ranking fails to maximize risk-reduction benefits. Real-world risk priority scoring systems used in homeland security and terrorism risk assessment, environmental risk management, information system vulnerability rating, business risk matrices, and many other important applications do not exploit correlations among risk-reducing opportunities or optimally diversify risk-reducing investments. As a result, they generally make suboptimal risk management recommendations. Applying portfolio optimization methods instead of risk prioritization ranking, rating, or scoring methods can achieve greater risk-reduction value for resources spent.

Efficiency of "Prescribe Vida Saludable", a health promotion innovation. Pilot phase.

PubMed

Sanz-Guinea, Aitor; Espinosa, Maite; Grandes, Gonzalo; Sáncheza, Álvaro; Martínez, Catalina; Pombo, Haizea; Bully, Paola; Cortada, Josep

"Prescribe Vida Saludable" (PVS) is an organisational innovation designed to optimise the promotion of multiple healthy habits in primary healthcare. It aims to estimate the cost effectiveness and cost-utility of prescribing physical activity in the pilot phase of the PVS programme, compared to the routine clinical practice of promoting physical activity in primary healthcare. An economic evaluation of the quasi-experimental pilot phase of PVS was carried out. In the four control centres, a systematic sample was selected of 194 patients who visited the centre in a single year and who did not comply with physical activity recommendations. In the four intervention centres, 122 patients who received their first physical activity prescription were consecutively enrolled. The costs were evaluated from the perspective of the PVS programme using bottom-up methodology. The effectiveness (proportion of patients who changed their physical activity) as well as the utility were evaluated at baseline and after 3 months. The incremental cost-utility ratio (ICUR) and the incremental cost-effectiveness ratio (ICER) were calculated and a sensitivity analysis was performed with bootstrapping and 1,000 replications. Information was obtained from 35% of control cases and 62% of intervention cases. The ICUR was €1,234.66/Quality Adjusted Life Years (QALY) and the ICER was €4.12. In 98.3% of the simulations, the ICUR was below the €30,000/QALY threshold. The prescription of physical activity was demonstrably within acceptable cost-utility limits in the pilot PVS phase, even from a conservative perspective. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

A Novel Mechanism of Sugar Selection Utilized by a Human X-family DNA Polymerase†

PubMed Central

Brown, Jessica A.; Fiala, Kevin A.; Fowler, Jason D.; Sherrer, Shanen M.; Newmister, Sean A.; Dyum, Wade W.; Suo, Zucai

2009-01-01

During DNA synthesis, most DNA polymerases and reverse transcriptases select against ribonucleotides via a steric clash between the ribose 2′-hydroxyl group and the bulky side chain of an active site residue. Here, we demonstrated that human DNA polymerase λ used a novel sugar selection mechanism to discriminate against ribonucleotides, whereby the ribose 2′-hydroxyl group was excluded mostly by a backbone segment and slightly by the side chain of Y505. Such a steric clash was further demonstrated to be dependent on the size and orientation of the substituent covalently attached at the ribonucleotide C2′ position. PMID:19900463

Chemical tailoring of teicoplanin with site-selective reactions.

PubMed

Pathak, Tejas P; Miller, Scott J

2013-06-05

Semisynthesis of natural product derivatives combines the power of fermentation with orthogonal chemical reactions. Yet, chemical modification of complex structures represents an unmet challenge, as poor selectivity often undermines efficiency. The complex antibiotic teicoplanin eradicates bacterial infections. However, as resistance emerges, the demand for improved analogues grows. We have discovered chemical reactions that achieve site-selective alteration of teicoplanin. Utilizing peptide-based additives that alter reaction selectivities, certain bromo-teicoplanins are accessible. These new compounds are also scaffolds for selective cross-coupling reactions, enabling further molecular diversification. These studies enable two-step access to glycopeptide analogues not available through either biosynthesis or rapid total chemical synthesis alone. The new compounds exhibit a spectrum of activities, revealing that selective chemical alteration of teicoplanin may lead to analogues with attenuated or enhanced antibacterial properties, in particular against vancomycin- and teicoplanin-resistant strains.

Interplay between the spin-selection rule and frontier orbital theory in O2 activation and CO oxidation by single-atom-sized catalysts on TiO2(110).

PubMed

Li, Shunfang; Zhao, Xingju; Shi, Jinlei; Jia, Yu; Guo, Zhengxiao; Cho, Jun-Hyung; Gao, Yanfei; Zhang, Zhenyu

2016-09-28

Exploration of the catalytic activity of low-dimensional transition metal (TM) or noble metal catalysts is a vital subject of modern materials science because of their instrumental role in numerous industrial applications. Recent experimental advances have demonstrated the utilization of single atoms on different substrates as effective catalysts, which exhibit amazing catalytic properties such as more efficient catalytic performance and higher selectivity in chemical reactions as compared to their nanostructured counterparts; however, the underlying microscopic mechanisms operative in these single atom catalysts still remain elusive. Based on first-principles calculations, herein, we present a comparative study of the key kinetic rate processes involved in CO oxidation using a monomer or dimer of two representative TMs (Pd and Ni) on defective TiO2(110) substrates (TMn@TiO2(110), n = 1, 2) to elucidate the underlying mechanism of single-atom catalysis. We reveal that the O2 activation rates of the single atom TM catalysts deposited on TiO2(110) are governed cooperatively by the classic spin-selection rule and the well-known frontier orbital theory (or generalized d-band picture) that emphasizes the energy gap between the frontier orbitals of the TM catalysts and O2 molecule. We further illuminate that the subsequent CO oxidation reactions proceed via the Langmuir-Hinshelwood mechanism with contrasting reaction barriers for the Pd monomer and dimer catalysts. These findings not only provide an explanation for existing observations of distinctly different catalytic activities of Pd@TiO2(110) and Pd2@TiO2(110) [Kaden et al., Science, 2009, 326, 826-829] but also shed new insights into future utilization and optimization of single-atom catalysis.

Z-Selective Catalytic Olefin Cross-Metathesis

PubMed Central

Meek, Simon J.; O’Brien, Robert V.; Llaveria, Josep; Schrock, Richard R.; Hoveyda, Amir H.

2011-01-01

Alkenes are found in a great number of biologically active molecules and are employed in numerous transformations in organic chemistry. Many olefins exist as E or higher energy Z isomers. Catalytic procedures for stereoselective formation of alkenes are therefore valuable; nonetheless, methods for synthesis of 1,2-disubstituted Z olefins are scarce. Here we report catalytic Z-selective cross-metathesis reactions of terminal enol ethers, which have not been reported previously, and allylic amides, employed thus far only in E-selective processes; the corresponding disubstituted alkenes are formed in up to >98% Z selectivity and 97% yield. Transformations, promoted by catalysts that contain the highly abundant and inexpensive molybdenum, are amenable to gram scale operations. Use of reduced pressure is introduced as a simple and effective strategy for achieving high stereoselectivity. Utility is demonstrated by syntheses of anti-oxidant C18 (plasm)-16:0 (PC), found in electrically active tissues and implicated in Alzheimer’s disease, and the potent immunostimulant KRN7000. PMID:21430774

Highly Active and Selective Hydrogenation of CO2 to Ethanol by Ordered Pd-Cu Nanoparticles.

PubMed

Bai, Shuxing; Shao, Qi; Wang, Pengtang; Dai, Qiguang; Wang, Xingyi; Huang, Xiaoqing

2017-05-24

Carbon dioxide (CO 2 ) hydrogenation to ethanol (C 2 H 5 OH) is considered a promising way for CO 2 conversion and utilization, whereas desirable conversion efficiency remains a challenge. Herein, highly active, selective and stable CO 2 hydrogenation to C 2 H 5 OH was enabled by highly ordered Pd-Cu nanoparticles (NPs). By tuning the composition of the Pd-Cu NPs and catalyst supports, the efficiency of CO 2 hydrogenation to C 2 H 5 OH was well optimized with Pd 2 Cu NPs/P25 exhibiting high selectivity to C 2 H 5 OH of up to 92.0% and the highest turnover frequency of 359.0 h -1 . Diffuse reflectance infrared Fourier transform spectroscopy results revealed the high C 2 H 5 OH production and selectivity of Pd 2 Cu NPs/P25 can be ascribed to boosting *CO (adsorption CO) hydrogenation to *HCO, the rate-determining step for the CO 2 hydrogenation to C 2 H 5 OH.

Assessment of active methods for removal of LEO debris

NASA Astrophysics Data System (ADS)

Hakima, Houman; Emami, M. Reza

2018-03-01

This paper investigates the applicability of five active methods for removal of large low Earth orbit debris. The removal methods, namely net, laser, electrodynamic tether, ion beam shepherd, and robotic arm, are selected based on a set of high-level space mission constraints. Mission level criteria are then utilized to assess the performance of each redirection method in light of the results obtained from a Monte Carlo simulation. The simulation provides an insight into the removal time, performance robustness, and propellant mass criteria for the targeted debris range. The remaining attributes are quantified based on the models provided in the literature, which take into account several important parameters pertaining to each removal method. The means of assigning attributes to each assessment criterion is discussed in detail. A systematic comparison is performed using two different assessment schemes: Analytical Hierarchy Process and utility-based approach. A third assessment technique, namely the potential-loss analysis, is utilized to highlight the effect of risks in each removal methods.

Cost Analysis of Selected Patient Categories within a Dermatology Department Using an ABC Approach

PubMed Central

Papadaki, Šárka; Popesko, Boris

2016-01-01

Background: Present trends in hospital management are facilitating the utilization of more accurate costing methods, which potentially results in superior cost-related information and improved managerial decision-making. However, the Activity-Based Costing method (ABC), which was designed for cost allocation purposes in the 1980s, is not widely used by healthcare organizations. This study analyzes costs related to selected categories of patients, those suffering from psoriasis, varicose ulcers, eczema and other conditions, within a dermatology department at a Czech regional hospital. Methods: The study was conducted in a hospital department where both inpatient and outpatient care are offered. Firstly, the diseases treated at the department were identified. Further costs were determined for each activity using ABC. The study utilized data from managerial and financial accounting, as well as data obtained through interviews with departmental staff. Using a defined cost-allocation procedure makes it possible to determine the cost of an individual patient with a given disease more accurately than via traditional costing procedures. Results: The cost analysis focused on the differences between the costs related to individual patients within the selected diagnoses, variations between inpatient and outpatient treatments and the costs of activities performed by the dermatology department. Furthermore, comparing the costs identified through this approach and the revenue stemming from the health insurance system is an option. Conclusions: Activity-Based Costing is more accurate and relevant than the traditional costing method. The outputs of ABC provide an abundance of additional information for managers. The benefits of this research lie in its practically-tested outputs, resulting from calculating the costs of hospitalization, which could prove invaluable to persons involved in hospital management and decision-making. The study also defines the managerial implications of the performed cost analysis for the hospital management. Based on the analysis results, it is possible to standardize activities and performance appraisal (Benchmarking), and provide all necessary information for hospital budgeting practices, especially Activity-Based Budgeting (ABB). PMID:26755477

Cost Analysis of Selected Patient Categories Within A Dermatology Department Using an ABC Approach.

PubMed

Papadaki, Šárka; Popesko, Boris

2015-11-17

Present trends in hospital management are facilitating the utilization of more accurate costing methods, which potentially results in superior cost-related information and improved managerial decision-making. However, the Activity-Based Costing method (ABC), which was designed for cost allocation purposes in the 1980s, is not widely used by healthcare organizations. This study analyzes costs related to selected categories of patients, those suffering from psoriasis, varicose ulcers, eczema and other conditions, within a dermatology department at a Czech regional hospital. The study was conducted in a hospital department where both inpatient and outpatient care are offered. Firstly, the diseases treated at the department were identified. Further costs were determined for each activity using ABC. The study utilized data from managerial and financial accounting, as well as data obtained through interviews with departmental staff. Using a defined cost-allocation procedure makes it possible to determine the cost of an individual patient with a given disease more accurately than via traditional costing procedures. The cost analysis focused on the differences between the costs related to individual patients within the selected diagnoses, variations between inpatient and outpatient treatments and the costs of activities performed by the dermatology department. Furthermore, comparing the costs identified through this approach and the revenue stemming from the health insurance system is an option. Activity-Based Costing is more accurate and relevant than the traditional costing method. The outputs of ABC provide an abundance of additional information for managers. The benefits of this research lie in its practically-tested outputs, resulting from calculating the costs of hospitalization, which could prove invaluable to persons involved in hospital management and decision-making. The study also defines the managerial implications of the performed cost analysis for the hospital management. Based on the analysis results, it is possible to standardize activities and performance appraisal (Benchmarking), and provide all necessary information for hospital budgeting practices, especially Activity-Based Budgeting (ABB).

Response of timber growth and avian communities to quality vegetation management in mid-rotation crp pine plantations

Treesearch

Brandon G. Sladek; Ian A. Munn; L. Wes Burder; Scott D. Roberts

2006-01-01

Provisions of the 2002 Farm Bill gave Conservation Reserve Program (CRP) participants greater flexibility to implement mid-contract management activities that encourage wildlife habitat improvement and timber production. Quality Vegetation Management (QVM) is one such technique that utilizes the selective herbicide Imazapyr and prescribed burning. Timber growth (d.b.h...

Current Trends in Microform Use by Secondary Schools: Four Case Studies.

ERIC Educational Resources Information Center

Lee, Thomas Graham

The case study section of this booklet discusses a number of current microform programs in secondary schools. The remainder of the booklet presents an overview of microform activity, including comments on the history of secondary school microform utilization and an up-to-date listing of microform selection aids. The amount of information available…

Fundamental Skills Needs Assessment Methods

DTIC Science & Technology

1992-05-01

abstract classification procedures are alien. Lima credited formal schooling with fostering the ability to generalize and think ...lessons to improve students ’ abilities to learn and benefit from instruction . Students are guided through lessons selected for them ("Prescriptions...contrasts between in- school and out-of- school learning and thinking activities that raise serious questions about the general utility of schooling

Integration of Nutrient and Activity Analysis Software into a Worksite Weight Management Program.

ERIC Educational Resources Information Center

Dennison, Darwin; And Others

1990-01-01

A weight management program utilized the participant's own data for the participant to (1) understand energy balance; (2) compare his/her diet with U.S. dietary codes; (3) know which food selections were high in calories, fat, and cholesterol, and low in complex carbohydrates and fiber; and (4) understand weight management. (JD)

Green synthesis of Nerium oleander-conjugated gold nanoparticles and study of its in vitro anticancer activity on MCF-7 cell lines and catalytic activity

NASA Astrophysics Data System (ADS)

Barai, Abir Chandan; Paul, Koushik; Dey, Aditi; Manna, Subhankar; Roy, Somenath; Bag, Braja Gopal; Mukhopadhyay, Chiradeep

2018-04-01

The phytochemicals present in the stem bark extract of Nerium oleander (commonly known as Karabi) have been utilized for the green synthesis of stable gold-conjugated nanoparticles at room temperature under very mild conditions. The green synthesized gold-conjugated nanoparticles were characterized by surface plasmon resonance spectroscopy, High resolution transmission electron microscopy, X-ray diffraction studies and dynamic light scattering. A mechanism for the synthesis and stabilization of gold-conjugated nanoparticles (AuNPs) has been proposed. Anticancer activity of the stabilized AuNPs studied against MCF-7 breast cancer cell line revealed that the stabilized AuNPs were highly effective for the apoptosis of cancer cells selectively. The antioxidant activity of the stem bark extract of Nerium oleander has also been studied against a long lived 2,2-diphenylpicrylhydrazyl radical at room temperature. Moreover, the utilization of the stabilized AuNPs as a catalyst has also been demonstrated. [Figure not available: see fulltext.

Green synthesis of Nerium oleander-conjugated gold nanoparticles and study of its in vitro anticancer activity on MCF-7 cell lines and catalytic activity.

PubMed

Barai, Abir Chandan; Paul, Koushik; Dey, Aditi; Manna, Subhankar; Roy, Somenath; Bag, Braja Gopal; Mukhopadhyay, Chiradeep

2018-01-01

The phytochemicals present in the stem bark extract of Nerium oleander (commonly known as Karabi) have been utilized for the green synthesis of stable gold-conjugated nanoparticles at room temperature under very mild conditions. The green synthesized gold-conjugated nanoparticles were characterized by surface plasmon resonance spectroscopy, High resolution transmission electron microscopy, X-ray diffraction studies and dynamic light scattering. A mechanism for the synthesis and stabilization of gold-conjugated nanoparticles (AuNPs) has been proposed. Anticancer activity of the stabilized AuNPs studied against MCF-7 breast cancer cell line revealed that the stabilized AuNPs were highly effective for the apoptosis of cancer cells selectively. The antioxidant activity of the stem bark extract of Nerium oleander has also been studied against a long lived 2,2-diphenylpicrylhydrazyl radical at room temperature. Moreover, the utilization of the stabilized AuNPs as a catalyst has also been demonstrated.

Large horizontal axis wind turbine development

NASA Technical Reports Server (NTRS)

Robbins, W. H.; Thomas, R. L.

1979-01-01

An overview of the NASA activities concerning ongoing wind systems oriented toward utility application is presented. First-generation-technology large wind turbines were designed and are in operation at selected utility sites. In order to make a significant energy impact, costs of 2 to 3 cents per kilowatt hour must be achieved. The federal program continues to fund the development by industry of wind turbines which can meet the cost goals of 2 to 3 cents per kilowatt hour. Lower costs are achieved through the incorporation of new technology and innovative system design to reduce weight and increase energy capture.

Utilization of Ancillary Data Sets for SMAP Algorithm Development and Product Generation

NASA Technical Reports Server (NTRS)

ONeill, P.; Podest, E.; Njoku, E.

2011-01-01

Algorithms being developed for the Soil Moisture Active Passive (SMAP) mission require a variety of both static and ancillary data. The selection of the most appropriate source for each ancillary data parameter is driven by a number of considerations, including accuracy, latency, availability, and consistency across all SMAP products and with SMOS (Soil Moisture Ocean Salinity). It is anticipated that initial selection of all ancillary datasets, which are needed for ongoing algorithm development activities on the SMAP algorithm testbed at JPL, will be completed within the year. These datasets will be updated as new or improved sources become available, and all selections and changes will be documented for the benefit of the user community. Wise choices in ancillary data will help to enable SMAP to provide new global measurements of soil moisture and freeze/thaw state at the targeted accuracy necessary to tackle hydrologically-relevant societal issues.

Comprehensive assay of kinase catalytic activity reveals features of kinase inhibitor selectivity

PubMed Central

Anastassiadis, Theonie; Deacon, Sean W.; Devarajan, Karthik; Ma, Haiching; Peterson, Jeffrey R.

2011-01-01

Small-molecule protein kinase inhibitors are central tools for elucidating cellular signaling pathways and are promising therapeutic agents. Due to evolutionary conservation of the ATP-binding site, most kinase inhibitors that target this site promiscuously inhibit multiple kinases. Interpretation of experiments utilizing these compounds is confounded by a lack of data on the comprehensive kinase selectivity of most inhibitors. Here we profiled the activity of 178 commercially available kinase inhibitors against a panel of 300 recombinant protein kinases using a functional assay. Quantitative analysis revealed complex and often unexpected kinase-inhibitor interactions, with a wide spectrum of promiscuity. Many off-target interactions occur with seemingly unrelated kinases, revealing how large-scale profiling can be used to identify multi-targeted inhibitors of specific, diverse kinases. The results have significant implications for drug development and provide a resource for selecting compounds to elucidate kinase function and for interpreting the results of experiments that use them. PMID:22037377

Lightweight, durable lead-acid batteries

DOEpatents

Lara-Curzio, Edgar [Lenoir City, TN; An, Ke [Knoxville, TX; Kiggans, Jr., James O.; Dudney, Nancy J [Knoxville, TN; Contescu, Cristian I [Knoxville, TN; Baker, Frederick S [Oak Ridge, TN; Armstrong, Beth L [Clinton, TN

2011-09-13

A lightweight, durable lead-acid battery is disclosed. Alternative electrode materials and configurations are used to reduce weight, to increase material utilization and to extend service life. The electrode can include a current collector having a buffer layer in contact with the current collector and an electrochemically active material in contact with the buffer layer. In one form, the buffer layer includes a carbide, and the current collector includes carbon fibers having the buffer layer. The buffer layer can include a carbide and/or a noble metal selected from of gold, silver, tantalum, platinum, palladium and rhodium. When the electrode is to be used in a lead-acid battery, the electrochemically active material is selected from metallic lead (for a negative electrode) or lead peroxide (for a positive electrode).

Lightweight, durable lead-acid batteries

DOEpatents

Lara-Curzio, Edgar; An, Ke; Kiggans, Jr., James O; Dudney, Nancy J; Contescu, Cristian I; Baker, Frederick S; Armstrong, Beth L

2013-05-21

A lightweight, durable lead-acid battery is disclosed. Alternative electrode materials and configurations are used to reduce weight, to increase material utilization and to extend service life. The electrode can include a current collector having a buffer layer in contact with the current collector and an electrochemically active material in contact with the buffer layer. In one form, the buffer layer includes a carbide, and the current collector includes carbon fibers having the buffer layer. The buffer layer can include a carbide and/or a noble metal selected from of gold, silver, tantalum, platinum, palladium and rhodium. When the electrode is to be used in a lead-acid battery, the electrochemically active material is selected from metallic lead (for a negative electrode) or lead peroxide (for a positive electrode).

Discovery of a highly selective chemical inhibitor of matrix metalloproteinase-9 (MMP-9) that allosterically inhibits zymogen activation.

PubMed

Scannevin, Robert H; Alexander, Richard; Haarlander, Tara Mezzasalma; Burke, Sharon L; Singer, Monica; Huo, Cuifen; Zhang, Yue-Mei; Maguire, Diane; Spurlino, John; Deckman, Ingrid; Carroll, Karen I; Lewandowski, Frank; Devine, Eric; Dzordzorme, Keli; Tounge, Brett; Milligan, Cindy; Bayoumy, Shariff; Williams, Robyn; Schalk-Hihi, Celine; Leonard, Kristi; Jackson, Paul; Todd, Matthew; Kuo, Lawrence C; Rhodes, Kenneth J

2017-10-27

Aberrant activation of matrix metalloproteinases (MMPs) is a common feature of pathological cascades observed in diverse disorders, such as cancer, fibrosis, immune dysregulation, and neurodegenerative diseases. MMP-9, in particular, is highly dynamically regulated in several pathological processes. Development of MMP inhibitors has therefore been an attractive strategy for therapeutic intervention. However, a long history of failed clinical trials has demonstrated that broad-spectrum MMP inhibitors have limited clinical utility, which has spurred the development of inhibitors selective for individual MMPs. Attaining selectivity has been technically challenging because of sequence and structural conservation across the various MMPs. Here, through a biochemical and structural screening paradigm, we have identified JNJ0966, a highly selective compound that inhibited activation of MMP-9 zymogen and subsequent generation of catalytically active enzyme. JNJ0966 had no effect on MMP-1, MMP-2, MMP-3, MMP-9, or MMP-14 catalytic activity and did not inhibit activation of the highly related MMP-2 zymogen. The molecular basis for this activity was characterized as an interaction of JNJ0966 with a structural pocket in proximity to the MMP-9 zymogen cleavage site near Arg-106, which is distinct from the catalytic domain. JNJ0966 was efficacious in reducing disease severity in a mouse experimental autoimmune encephalomyelitis model, demonstrating the viability of this therapeutic approach. This discovery reveals an unprecedented pharmacological approach to MMP inhibition, providing an opportunity to improve selectivity of future clinical drug candidates. Targeting zymogen activation in this manner may also allow for pharmaceutical exploration of other enzymes previously viewed as intractable drug targets. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Application of activated carbon modified by acetic acid in adsorption and separation of CO2 and CH4

NASA Astrophysics Data System (ADS)

Song, Xue; Wang, Li'ao; Zeng, Yunmin; Zhan, Xinyuan; Gong, Jian; Li, Tong

2018-03-01

Compared with the methods to modify the activated carbons by alkalis for gas adsorption, fewer studies of that by organic acids have been reported. The acid modified activated carbons are usually utilized to treat wastewater, whereas the application in the separation of CO2/CH4 has less been studied. In this study, acetic acid was used to modify activated carbon. N2 adsorption/desorption isotherms and FT-IR were adopted to describe the properties of the samples. According to the adsorption data of pure gas component at 298 K, the gas adsorbed amount and the selectivity on the modified samples were larger than that on the raw sample. Besides, the adsorbed amount of CO2 and the selectivity on 15H-AC in the adsorption breakthrough experiments showed better performance. The results confirm that the method to modify the activated carbons with acetic acid is feasible to improve the adsorption capacity and the separation effect of CO2/CH4.

Dockres: a computer program that analyzes the output of virtual screening of small molecules

PubMed Central

2010-01-01

Background This paper describes a computer program named Dockres that is designed to analyze and summarize results of virtual screening of small molecules. The program is supplemented with utilities that support the screening process. Foremost among these utilities are scripts that run the virtual screening of a chemical library on a large number of processors in parallel. Methods Dockres and some of its supporting utilities are written Fortran-77; other utilities are written as C-shell scripts. They support the parallel execution of the screening. The current implementation of the program handles virtual screening with Autodock-3 and Autodock-4, but can be extended to work with the output of other programs. Results Analysis of virtual screening by Dockres led to both active and selective lead compounds. Conclusions Analysis of virtual screening was facilitated and enhanced by Dockres in both the authors' laboratories as well as laboratories elsewhere. PMID:20205801

Discovery of 5-Chloro-1-(5-chloro-2-(methylsulfonyl)benzyl)-2-imino-1,2-dihydropyridine-3-carboxamide (TAK-259) as a Novel, Selective, and Orally Active α1D Adrenoceptor Antagonist with Antiurinary Frequency Effects: Reducing Human Ether-a-go-go-Related Gene (hERG) Liabilities.

PubMed

Sakauchi, Nobuki; Kohara, Yasuhisa; Sato, Ayumu; Suzaki, Tomohiko; Imai, Yumi; Okabe, Yuichi; Imai, Shigemitsu; Saikawa, Reiko; Nagabukuro, Hiroshi; Kuno, Haruhiko; Fujita, Hisashi; Kamo, Izumi; Yoshida, Masato

2016-04-14

A novel structural class of iminopyridine derivative 1 was identified as a potent and selective human α1D adrenoceptor (α1D adrenergic receptor; α1D-AR) antagonist against α1A- and α1B-AR through screening of an in-house compound library. From initial structure-activity relationship studies, we found lead compound 9m with hERG K(+) channel liability. To develop analogues with reduced hERG K(+) channel inhibition, a combination of site-directed mutagenesis and docking studies was employed. Further optimization led to the discovery of (R)-9s and 9u, which showed antagonistic activity by a bladder strip test in rats with bladder outlet obstruction, as well as ameliorated cystitis-induced urinary frequency in rats. Ultimately, 9u was selected as a clinical candidate. This is the first study to show the utility of iminopyridine derivatives as selective α1D-AR antagonists and evaluate their effects in vivo.

Utilization of 2,6-diaminopurine by Salmonella typhimurium.

PubMed Central

Garber, B B; Gots, J S

1980-01-01

The pathway for the utilization of 2,6-diaminopurine (DAP) as an exogenous purine source in Salmonella typhimurium was examined. In strains able to use DAP as a purine source, mutant derivatives lacking either purine nucleoside phosphorylase or adenosine deaminase activity lost the ability to do so. The implied pathway of DAP utilization was via its conversion to DAP ribonucleoside by purine nucleoside phosphorylase, followed by deamination to guanosine by adenosine deaminase. Guanosine can then enter the established purine salvage pathways. In the course of defining this pathway, purine auxotrophs able to utilize DAP as sole purine source were isolated and partially characterized. These mutants fell into several classes, including (i) strains that only required an exogenous source of guanine nucleotides (e.g., guaA and guaB strains); (ii) strains that had a purF genetic lesion (i.e., were defective in alpha-5-phosphoribosyl 1-pyrophosphate amidotransferase activity); and (iii) strains that had constitutive levels of purine nucleoside phosphorylase. Selection among purine auxotrophs blocked in the de novo synthesis of inosine 5'-monophosphate, for efficient growth on DAP as sole source of purine nucleotides, readily yielded mutants which were defective in the regulation of their deoxyribonucleoside-catabolizing enzymes (e.g., deoR mutants). PMID:6782081

Reciprocal and activity-dependent regulation of surface AMPA and NMDA receptors in cultured neurons

PubMed Central

Li, Guo Hua; Jackson, Michael F; Orser, Beverley A; MacDonald, John F

2010-01-01

Activation of NMDA receptors (NMDARs) can modulate excitatory synaptic transmission in the central nervous system by dynamically altering the number of synaptic AMPA receptors (AMPARs). The surface expression of NMDARs themselves is also subject to modulation in an activity-dependent manner. In addition to NMDAR-induced changes in AMPAR expression, AMPARs have also been found to regulate their own surface expression, independently of NMDARs. However, whether or not AMPARs and NMDARs might reciprocally regulate their surface expression has not previously been systematically explored. We utilized surface biotinylation assays and stimulation protocols intended to selectively stimulate various glutamate receptor subpopulations (e.g. AMPARs vs NMDARs; synaptic vs extrasynaptic). We reveal that activation of synaptic NMDARs increases the surface expression of both NMDAR and AMPAR subunits, while activation of extrasynaptic NMDAR produces the opposite effect. Surprisingly, we find that selective activation of AMPARs reduces the surface expression of not only AMPARs but also of NMDARs. These results suggest that both AMPARs and NMDARs at synaptic sites are subject to modulation by multiple signalling pathways in an activity-dependent way. PMID:21383896

Selective separation of pyrite and chalcopyrite by biomodulation.

PubMed

Chandraprabha, M N; Natarajan, K A; Modak, Jayant M

2004-09-01

Selective separation of pyrite from other associated ferrous sulphides at acidic and neutral pH has been a challenging problem. This paper discusses the utility of Acidithiobacillus ferrooxidans for the selective flotation of chalcopyrite from pyrite. Consequent to interaction with bacterial cells, pyrite remained depressed even in the presence of potassium isopropyl xanthate collector while chalcopyrite exhibited significant flotability. However, when the minerals were conditioned together, the selectivity achieved was poor due to the activation of pyrite surface by the copper ions in solution. The selectivity was improved when the sequence of conditioning with bacterial cells and collector was reversed, since the bacterial cells were able to depress collector interacted pyrite effectively, while having negligible effect on chalcopyrite. The observed behaviour is analysed and discussed in detail. The separation obtained was significant both at acidic and alkaline pH. This selectivity achieved was retained when the minerals were interacted with both bacterial cells and collector simultaneously.

A novel mechanism of sugar selection utilized by a human X-family DNA polymerase.

PubMed

Brown, Jessica A; Fiala, Kevin A; Fowler, Jason D; Sherrer, Shanen M; Newmister, Sean A; Duym, Wade W; Suo, Zucai

2010-01-15

During DNA synthesis, most DNA polymerases and reverse transcriptases select against ribonucleotides via a steric clash between the ribose 2'-hydroxyl group and the bulky side chain of an active-site residue. In this study, we demonstrated that human DNA polymerase lambda used a novel sugar selection mechanism to discriminate against ribonucleotides, whereby the ribose 2'-hydroxyl group was excluded mostly by a backbone segment and slightly by the side chain of Y505. Such steric clash was further demonstrated to be dependent on the size and orientation of the substituent covalently attached at the ribonucleotide C2'-position. Copyright 2009 Elsevier Ltd. All rights reserved.

The evolution of colour polymorphism in British winter-active Lepidoptera in response to search image use by avian predators.

PubMed

Weir, Jamie C

2018-05-10

Phenotypic polymorphism in cryptic species is widespread. This may evolve in response to search image use by predators exerting negative frequency-dependent selection on intraspecific colour morphs, 'apostatic selection'. Evidence exists to indicate search image formation by predators and apostatic selection operating on wild prey populations, though not to demonstrate search image use directly resulting in apostatic selection. The present study attempted to address this deficiency, using British Lepidoptera active in winter as a model system. It has been proposed that the typically polymorphic wing colouration of these species represents an anti-search image adaptation against birds. To test (a) for search image-driven apostatic selection, dimorphic populations of artificial moth-like models were established in woodland at varying relative morph frequencies and exposed to predation by natural populations of birds. In addition, to test (b) whether abundance and degree of polymorphism are correlated across British winter-active moths, as predicted where search image use drives apostatic selection, a series of phylogenetic comparative analyses were conducted. There was a positive relationship between artificial morph frequency and probability of predation, consistent with birds utilizing search images and exerting apostatic selection. Abundance and degree of polymorphism were found to be positively correlated across British Lepidoptera active in winter, though not across all taxonomic groups analysed. This evidence is consistent with polymorphism in this group having evolved in response to search image-driven apostatic selection and supports the viability of this mechanism as a means by which phenotypic and genetic variation may be maintained in natural populations. © 2018 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2018 European Society For Evolutionary Biology.

Engineering an Antibiotic to Fight Cancer: Optimization of the Novobiocin Scaffold to Produce Anti-Proliferative Agents

PubMed Central

Zhao, Huiping; Donnelly, Alison C.; Kusuma, Bhaskar R.; Brandt, Gary E. L.; Brown, Douglas; Rajewski, Roger A.; Vielhauer, George; Holzbeierlein, Jeffrey; Cohen, Mark S.; Blagg, Brian S. J.

2011-01-01

Development of the DNA gyrase inhibitor, novobiocin, into a selective Hsp90 inhibitor was accomplished through structural modifications to the amide side chain, coumarin ring, and sugar moiety. These species exhibit ~700-fold improved anti-proliferative activity versus the natural product as evaluated by cellular efficacies against breast, colon, prostate, lung, and other cancer cell lines. Utilization of structure–activity relationships established for three novobiocin synthons produced optimized scaffolds, which manifest mid-nanomolar activity against a panel of cancer cell lines and serve as lead compounds that manifest their activities through Hsp90 inhibition. PMID:21553822

Care and Service at Home for Persons With Dementia in Europe.

PubMed

Bökberg, Christina; Ahlström, Gerd; Leino-Kilpi, Helena; Soto-Martin, Maria E; Cabrera, Esther; Verbeek, Hilde; Saks, Kai; Stephan, Astrid; Sutcliffe, Caroline; Karlsson, Staffan

2015-09-01

To describe available and utilized formal care and service at home for persons with dementia, from diagnosis to end-of-life stage, in eight European countries. A descriptive cross-country design concerning eight European countries as a part of the European research project RightTimePlaceCare. The research team in each country used a mapping system to collect country-specific information concerning dementia care and service system. The mapping system consists of 50 types of care and service activities. Sixteen of the 50 predefined activities concerning care and service at home were selected for this study and subdivided into three categories, following the stages of dementia. Availability was reported to be higher than utilization, and the findings indicated more similarities than differences among the eight countries involved. Even though there were several available activities of "basic care and services" and "healthcare interventions," they were utilized by few in most countries. Furthermore, "specialized dementia care and services" were sparsely available and even more sparsely utilized in the participating countries. The findings indicated that persons with dementia in Europe received formal care and service on a general, basic level but seldom adjusted to their specific needs. This study describes the gap between service provision and utilization enabling nurses to develop individually adjusted care plans for persons with dementia during the progress of the disease. The findings do not include matters of quality of care or how to best organize effective care and services. However, the activities of care and services presented here should shed light on what room there is for improvement when it comes to enabling persons with dementia to go on living at home. © 2015 Sigma Theta Tau International.

School Sites: Selection, Development and Utilization. Educational Facilities Series: A Guide to Planning.

ERIC Educational Resources Information Center

New Jersey State Dept. of Education, Trenton. Bureau of Facility Planning.

School sites are an integral part of educational facilities. Modern educational programs emphasize the discovery approach to learning where pupils do more than just read about the world around them. For example, they become active explorers and participate in discovering nature and how best to enjoy it and care for it. Thus, there is a curricular…

Estimating sawmill processing capacity for Tongass timber: 2005 and 2006 update

Treesearch

Allen M. Brackley; Lisa K. Crone

2009-01-01

In spring 2006 and 2007, sawmill capacity and wood utilization information was collected for selected mills in southeast Alaska. The collected information is required to prepare information for compliance with Section 705(a) of the Tongass Timber Reform Act. The total estimated design capacity in the region (active and inactive mills) was 289,850 thousand board feet (...

Estimating sawmill processing capacity for Tongass timber: 2003 and 2004 update.

Treesearch

Allen M. Brackley; Daniel J. Parrent; Thomas D. Rojas

2006-01-01

In spring 2004 and 2005, sawmill capacity and wood utilization information was collected for selected mills in southeast Alaska. The collected information is required to prepare information for compliance with Section 705(a) of the Tongass Timber Reform Act. The total capacity in the region (active and inactive mills) was 370,350 thousand board feet (mbf) Scribner log...

Research Objectives for Human Missions in the Proving Ground of Cis-Lunar Space

NASA Technical Reports Server (NTRS)

Niles, P. B.; Eppler, D. B.; Kennedy, K. J.; Lewis, R.; Spann, J. F.; Sullivan, T. A.

2016-01-01

Beginning in as early as 2023, crewed missions beyond low Earth orbit will begin enabled by the new capabilities of the SLS and Orion vehicles. This will initiate the "Proving Ground" phase of human exploration with Mars as an ultimate destination. The primary goal of the Proving Ground is to demonstrate the capability of suitably long duration spaceflight without need of continuous support from Earth, i.e. become Earth Independent. A major component of the Proving Ground phase is to conduct research activities aimed at accomplishing major objectives selected from a wide variety of disciplines including but not limited to: Astronomy, Heliophysics, Fundamental Physics, Planetary Science, Earth Science, Human Systems, Fundamental Space Biology, Microgravity, and In A major component of the Proving Ground phase is to conduct research activities aimed at accomplishing major objectives selected from a wide variety of disciplines including but not limited to: Astronomy, Heliophysics, Fundamental Physics, Planetary Science, Earth Science, Human Systems, Fundamental Space Biology, Microgravity, and In Situ Resource Utilization. Mapping and prioritizing the most important objectives from these disciplines will provide a strong foundation for establishing the architecture to be utilized in the Proving Ground.

Confirmation of high-throughput screening data and novel mechanistic insights into VDR-xenobiotic interactions by orthogonal assays.

PubMed

Mahapatra, Debabrata; Franzosa, Jill A; Roell, Kyle; Kuenemann, Melaine Agnes; Houck, Keith A; Reif, David M; Fourches, Denis; Kullman, Seth W

2018-06-11

High throughput screening (HTS) programs have demonstrated that the Vitamin D receptor (VDR) is activated and/or antagonized by a wide range of structurally diverse chemicals. In this study, we examined the Tox21 qHTS data set generated against VDR for reproducibility and concordance and elucidated functional insights into VDR-xenobiotic interactions. Twenty-one potential VDR agonists and 19 VDR antagonists were identified from a subset of >400 compounds with putative VDR activity and examined for VDR functionality utilizing select orthogonal assays. Transient transactivation assay (TT) using a human VDR plasmid and Cyp24 luciferase reporter construct revealed 20/21 active VDR agonists and 18/19 active VDR antagonists. Mammalian-2-hybrid assay (M2H) was then used to evaluate VDR interactions with co-activators and co-regulators. With the exception of a select few compounds, VDR agonists exhibited significant recruitment of co-regulators and co-activators whereas antagonists exhibited considerable attenuation of recruitment by VDR. A unique set of compounds exhibiting synergistic activity in antagonist mode and no activity in agonist mode was identified. Cheminformatics modeling of VDR-ligand interactions were conducted and revealed selective ligand VDR interaction. Overall, data emphasizes the molecular complexity of ligand-mediated interactions with VDR and suggest that VDR transactivation may be a target site of action for diverse xenobiotics.

Designing highly active siRNAs for therapeutic applications.

PubMed

Walton, S Patrick; Wu, Ming; Gredell, Joseph A; Chan, Christina

2010-12-01

The discovery of RNA interference (RNAi) generated considerable interest in developing short interfering RNAs (siRNAs) for understanding basic biology and as the active agents in a new variety of therapeutics. Early studies showed that selecting an active siRNA was not as straightforward as simply picking a sequence on the target mRNA and synthesizing the siRNA complementary to that sequence. As interest in applying RNAi has increased, the methods for identifying active siRNA sequences have evolved from focusing on the simplicity of synthesis and purification, to identifying preferred target sequences and secondary structures, to predicting the thermodynamic stability of the siRNA. As more specific details of the RNAi mechanism have been defined, these have been incorporated into more complex siRNA selection algorithms, increasing the reliability of selecting active siRNAs against a single target. Ultimately, design of the best siRNA therapeutics will require design of the siRNA itself, in addition to design of the vehicle and other components necessary for it to function in vivo. In this minireview, we summarize the evolution of siRNA selection techniques with a particular focus on one issue of current importance to the field, how best to identify those siRNA sequences likely to have high activity. Approaches to designing active siRNAs through chemical and structural modifications will also be highlighted. As the understanding of how to control the activity and specificity of siRNAs improves, the potential utility of siRNAs as human therapeutics will concomitantly grow. © 2010 The Authors Journal compilation © 2010 FEBS.

Measurement properties of self-report physical activity assessment tools in stroke: a protocol for a systematic review.

PubMed

Martins, Júlia Caetano; Aguiar, Larissa Tavares; Nadeau, Sylvie; Scianni, Aline Alvim; Teixeira-Salmela, Luci Fuscaldi; Faria, Christina Danielli Coelho de Morais

2017-02-13

Self-report physical activity assessment tools are commonly used for the evaluation of physical activity levels in individuals with stroke. A great variety of these tools have been developed and widely used in recent years, which justify the need to examine their measurement properties and clinical utility. Therefore, the main objectives of this systematic review are to examine the measurement properties and clinical utility of self-report measures of physical activity and discuss the strengths and limitations of the identified tools. A systematic review of studies that investigated the measurement properties and/or clinical utility of self-report physical activity assessment tools in stroke will be conducted. Electronic searches will be performed in five databases: Medical Literature Analysis and Retrieval System Online (MEDLINE) (PubMed), Excerpta Medica Database (EMBASE), Physiotherapy Evidence Database (PEDro), Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) and Scientific Electronic Library Online (SciELO), followed by hand searches of the reference lists of the included studies. Two independent reviewers will screen all retrieve titles, abstracts, and full texts, according to the inclusion criteria and will also extract the data. A third reviewer will be referred to solve any disagreement. A descriptive summary of the included studies will contain the design, participants, as well as the characteristics, measurement properties, and clinical utility of the self-report tools. The methodological quality of the studies will be evaluated using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklist and the clinical utility of the identified tools will be assessed considering predefined criteria. This systematic review will follow the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) statement. This systematic review will provide an extensive review of the measurement properties and clinical utility of self-report physical activity assessment tools used in individuals with stroke, which would benefit clinicians and researchers. PROSPERO CRD42016037146. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Printable enzyme-embedded materials for methane to methanol conversion

DOE PAGES

Blanchette, Craig D.; Knipe, Jennifer M.; Stolaroff, Joshuah K.; ...

2016-06-15

An industrial process for the selective activation of methane under mild conditions would be highly valuable for controlling emissions to the environment and for utilizing vast new sources of natural gas. The only selective catalysts for methane activation and conversion to methanol under mild conditions are methane monooxygenases (MMOs) found in methanotrophic bacteria; however, these enzymes are not amenable to standard enzyme immobilization approaches. Using particulate methane monooxygenase (pMMO), we create a biocatalytic polymer material that converts methane to methanol. We demonstrate embedding the material within a silicone lattice to create mechanically robust, gas-permeable membranes, and direct printing of micron-scalemore » structures with controlled geometry. Remarkably, the enzymes retain up to 100% activity in the polymer construct. The printed enzyme-embedded polymer motif is highly flexible for future development and should be useful in a wide range of applications, especially those involving gas–liquid reactions.« less

Printable enzyme-embedded materials for methane to methanol conversion

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

Blanchette, Craig D.; Knipe, Jennifer M.; Stolaroff, Joshuah K.

An industrial process for the selective activation of methane under mild conditions would be highly valuable for controlling emissions to the environment and for utilizing vast new sources of natural gas. The only selective catalysts for methane activation and conversion to methanol under mild conditions are methane monooxygenases (MMOs) found in methanotrophic bacteria; however, these enzymes are not amenable to standard enzyme immobilization approaches. Using particulate methane monooxygenase (pMMO), we create a biocatalytic polymer material that converts methane to methanol. We demonstrate embedding the material within a silicone lattice to create mechanically robust, gas-permeable membranes, and direct printing of micron-scalemore » structures with controlled geometry. Remarkably, the enzymes retain up to 100% activity in the polymer construct. The printed enzyme-embedded polymer motif is highly flexible for future development and should be useful in a wide range of applications, especially those involving gas–liquid reactions.« less

Printable enzyme-embedded materials for methane to methanol conversion

PubMed Central

Blanchette, Craig D.; Knipe, Jennifer M.; Stolaroff, Joshuah K.; DeOtte, Joshua R.; Oakdale, James S.; Maiti, Amitesh; Lenhardt, Jeremy M.; Sirajuddin, Sarah; Rosenzweig, Amy C.; Baker, Sarah E.

2016-01-01

An industrial process for the selective activation of methane under mild conditions would be highly valuable for controlling emissions to the environment and for utilizing vast new sources of natural gas. The only selective catalysts for methane activation and conversion to methanol under mild conditions are methane monooxygenases (MMOs) found in methanotrophic bacteria; however, these enzymes are not amenable to standard enzyme immobilization approaches. Using particulate methane monooxygenase (pMMO), we create a biocatalytic polymer material that converts methane to methanol. We demonstrate embedding the material within a silicone lattice to create mechanically robust, gas-permeable membranes, and direct printing of micron-scale structures with controlled geometry. Remarkably, the enzymes retain up to 100% activity in the polymer construct. The printed enzyme-embedded polymer motif is highly flexible for future development and should be useful in a wide range of applications, especially those involving gas–liquid reactions. PMID:27301270

A novel strategy for selection of allosteric ribozymes yields RiboReporter™ sensors for caffeine and aspartame

PubMed Central

Ferguson, Alicia; Boomer, Ryan M.; Kurz, Markus; Keene, Sara C.; Diener, John L.; Keefe, Anthony D.; Wilson, Charles; Cload, Sharon T.

2004-01-01

We have utilized in vitro selection technology to develop allosteric ribozyme sensors that are specific for the small molecule analytes caffeine or aspartame. Caffeine- or aspartame-responsive ribozymes were converted into fluorescence-based RiboReporter™ sensor systems that were able to detect caffeine or aspartame in solution over a concentration range from 0.5 to 5 mM. With read-times as short as 5 min, these caffeine- or aspartame-dependent ribozymes function as highly specific and facile molecular sensors. Interestingly, successful isolation of allosteric ribozymes for the analytes described here was enabled by a novel selection strategy that incorporated elements of both modular design and activity-based selection methods typically used for generation of catalytic nucleic acids. PMID:15026535

Diallyl Polysulfides from Allium sativum as Immunomodulators, Hepatoprotectors, and Antimycobacterial Agents.

PubMed

Oosthuizen, Carel; Arbach, Miriam; Meyer, Debra; Hamilton, Chris; Lall, Namrita

2017-07-01

Mycobacterium tuberculosis remains one of the world's deadliest killers, with an annual death rate of ∼1.5 million. The medicinal effects of garlic have been well documented, and natural products have been shown to have antimycobacterial activity. The current study evaluated the efficacy of six Allium sativum L. polysulfide mixtures as antimycobacterial agents together with their cytotoxic, immunomodulatory, and hepatoprotective activities. The microtitre PrestoBlue assay was used to determine the minimum inhibitory concentrations (MIC). Cytotoxicity was evaluated by using peripheral blood mononuclear cells (PBMC). Excreted cytokine levels were determined by utilizing an enzyme-linked immunosorbent assay (ELISA), by exposing isolated PBMCs to varying concentrations of polysulfide mixtures. Human C3A liver cells were utilized in the hepatoprotective study, to assess the protective effect against the toxicity induced by acetaminophen. Samples with higher amounts of diallyl trisulfide (Sample G4) showed the highest antimycobacterial activity, exhibiting an MIC of 2.5 μg/mL against M. tuberculosis H37Rv. Five samples showed moderate toxicity in PBMC, with G1 showing no toxicity. The selective index of G4 was the highest, with a selectivity index close to one. Two samples, G3 and G6 containing higher amounts of diallyl tetrasulfide and lower amounts of diallyl trisulfide, showed >50% hepatoprotection. This is comparable to a hepatoprotective agent, Silymarin, which showed a hepatoprotective effect of 30% at the tested concentration. Diallyl tetrasulfide showed significant antimycobacterial activity. A combination of higher diallyl tetrasulfide and lower diallyl trisulfide was indicative of hepatoprotective activity.

Bioorthogonal Diversification of Peptides through Selective Ruthenium(II)-Catalyzed C-H Activation.

PubMed

Schischko, Alexandra; Ren, Hongjun; Kaplaneris, Nikolaos; Ackermann, Lutz

2017-02-01

Methods for the chemoselective modification of amino acids and peptides are powerful techniques in biomolecular chemistry. Among other applications, they enable the total synthesis of artificial peptides. In recent years, significant momentum has been gained by exploiting palladium-catalyzed cross-coupling for peptide modification. Despite major advances, the prefunctionalization elements on the coupling partners translate into undesired byproduct formation and lengthy synthetic operations. In sharp contrast, we herein illustrate the unprecedented use of versatile ruthenium(II)carboxylate catalysis for the step-economical late-stage diversification of α- and β-amino acids, as well as peptides, through chemo-selective C-H arylation under racemization-free reaction conditions. The ligand-accelerated C-H activation strategy proved water-tolerant and set the stage for direct fluorescence labelling as well as various modes of peptide ligation with excellent levels of positional selectivity in a bioorthogonal fashion. The synthetic utility of our approach is further demonstrated by twofold C-H arylations for the complexity-increasing assembly of artificial peptides within a multicatalytic C-H activation manifold. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

An electrostatic selection mechanism controls sequential kinase signaling downstream of the T cell receptor

PubMed Central

Shah, Neel H; Wang, Qi; Yan, Qingrong; Karandur, Deepti; Kadlecek, Theresa A; Fallahee, Ian R; Russ, William P; Ranganathan, Rama; Weiss, Arthur; Kuriyan, John

2016-01-01

The sequence of events that initiates T cell signaling is dictated by the specificities and order of activation of the tyrosine kinases that signal downstream of the T cell receptor. Using a platform that combines exhaustive point-mutagenesis of peptide substrates, bacterial surface-display, cell sorting, and deep sequencing, we have defined the specificities of the first two kinases in this pathway, Lck and ZAP-70, for the T cell receptor ζ chain and the scaffold proteins LAT and SLP-76. We find that ZAP-70 selects its substrates by utilizing an electrostatic mechanism that excludes substrates with positively-charged residues and favors LAT and SLP-76 phosphosites that are surrounded by negatively-charged residues. This mechanism prevents ZAP-70 from phosphorylating its own activation loop, thereby enforcing its strict dependence on Lck for activation. The sequence features in ZAP-70, LAT, and SLP-76 that underlie electrostatic selectivity likely contribute to the specific response of T cells to foreign antigens. DOI: http://dx.doi.org/10.7554/eLife.20105.001 PMID:27700984

Coding of visual object features and feature conjunctions in the human brain.

PubMed

Martinovic, Jasna; Gruber, Thomas; Müller, Matthias M

2008-01-01

Object recognition is achieved through neural mechanisms reliant on the activity of distributed coordinated neural assemblies. In the initial steps of this process, an object's features are thought to be coded very rapidly in distinct neural assemblies. These features play different functional roles in the recognition process--while colour facilitates recognition, additional contours and edges delay it. Here, we selectively varied the amount and role of object features in an entry-level categorization paradigm and related them to the electrical activity of the human brain. We found that early synchronizations (approx. 100 ms) increased quantitatively when more image features had to be coded, without reflecting their qualitative contribution to the recognition process. Later activity (approx. 200-400 ms) was modulated by the representational role of object features. These findings demonstrate that although early synchronizations may be sufficient for relatively crude discrimination of objects in visual scenes, they cannot support entry-level categorization. This was subserved by later processes of object model selection, which utilized the representational value of object features such as colour or edges to select the appropriate model and achieve identification.

Engineering a Cell-surface Aptamer Circuit for Targeted and Amplified Photodynamic Cancer Therapy

PubMed Central

Han, Da; Zhu, Guizhi; Wu, Cuichen; Zhu, Zhi; Chen, Tao; Zhang, Xiaobing

2013-01-01

Photodynamic therapy (PDT) is one of the most promising and noninvasive methods for clinical treatment of different malignant diseases. Here, we present a novel strategy of designing an aptamer-based DNA nanocircuit capable of the selective recognition of cancer cells, controllable activation of photosensitizer and amplification of photodynamic therapeutic effect. The aptamers can selectively recognize target cancer cells and bind to the specific proteins on cell membranes. Then the overhanging catalyst sequence on aptamer can trigger a toehold-mediated catalytic strand displacement to activate photosensitizer and achieve amplified therapeutic effect. The specific binding-induced activation allows the DNA circuit to distinguish diseased cells from healthy cells, reducing damage to nearby healthy cells. Moreover, the catalytic amplification reaction will only take place close to the target cancer cells, resulting in a high local concentration of singlet oxygen to selectively kill the target cells. The principle employed in this study demonstrated the feasibility of assembling a DNA circuit on cell membranes and could further broaden the utility of DNA circuits for applications in biology, biotechnology, and biomedicine. PMID:23397942

Utilizing Antecedent Manipulations and Reinforcement in the Treatment of Food Selectivity by Texture

ERIC Educational Resources Information Center

Najdowski, Adel C.; Tarbox, Jonathan; Wilke, Arthur E.

2012-01-01

Food selectivity by texture is relatively common in children. Treatments for food selectivity by texture have included components such as stimulus fading, reinforcement, and escape extinction. The purpose of the current study was to attempt to treat food selectivity by texture utilizing antecedent manipulations and reinforcement in the absence of…

Impact of Medicare SELECT on Cost and Utilization in 11 States

PubMed Central

Lee, A. James; Garfinkel, Steven A.; Khandker, Rezaul K.; Norton, Edward C.

1997-01-01

In this article, the authors evaluate the cost and utilization effects of the SELECT implementations in 11 States. In particular they compare the before-and-after enrollment experiences of Medicare beneficiaries newly enrolled in SELECT plans with the experiences of those newly enrolled in traditional medigap plans. Using Medicare claims data for 1991 through 1994, the authors find that Medicare SELECT increased costs in five States, decreased costs in three States, and had no effect in three States. Cost increases were generally related to Part B utilization. PMID:10179998

Theoretical Insights into Direct Methane to Methanol Conversion over Supported Dicopper Oxo Nanoclusters

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

Doan, Hieu A.; Li, Zhanyong; Farha, Omar K.

In this study, the prospect of using copper oxide nanoclusters grown by atomic layer deposition on a porphyrin support for selective oxidation of methane to methanol was examined by means of density functional theory (DFT) calculations. Ab initio thermodynamic analysis indicates that an active site in the form of Cu(μ-O)Cu can be stabilized by activation in O2 at 465K. Furthermore, a moderate methane activation energy barrier (Ea=54kJ/mol) is predicted, and the hydrogen abstraction activity of the active site could be attributed to the radical character of the bridging oxygen. Methanol extraction in this system is limited by a thermodynamic barriermore » to desorption of ΔG=57kJ/mol at 473K; however, desorption can be facilitated by the addition of water in a “stepped conversion” process. Overall, our results indicate similar activity between porphyrin-supported copper oxide nanoclusters and existing Cu-exchanged zeolites and provide a computational proof-of-concept for utilizing functionalized organic linkers in metal-organic frameworks (MOFs) for selective oxidation of methane to methanol.« less

Theoretical Insights into Direct Methane to Methanol Conversion over Supported Dicopper Oxo Nanoclusters

DOE PAGES

Doan, Hieu A.; Li, Zhanyong; Farha, Omar K.; ...

2018-04-08

In this study, the prospect of using copper oxide nanoclusters grown by atomic layer deposition on a porphyrin support for selective oxidation of methane to methanol was examined by means of density functional theory (DFT) calculations. Ab initio thermodynamic analysis indicates that an active site in the form of Cu(μ-O)Cu can be stabilized by activation in O2 at 465K. Furthermore, a moderate methane activation energy barrier (Ea=54kJ/mol) is predicted, and the hydrogen abstraction activity of the active site could be attributed to the radical character of the bridging oxygen. Methanol extraction in this system is limited by a thermodynamic barriermore » to desorption of ΔG=57kJ/mol at 473K; however, desorption can be facilitated by the addition of water in a “stepped conversion” process. Overall, our results indicate similar activity between porphyrin-supported copper oxide nanoclusters and existing Cu-exchanged zeolites and provide a computational proof-of-concept for utilizing functionalized organic linkers in metal-organic frameworks (MOFs) for selective oxidation of methane to methanol.« less

The impact of functional imaging on radiation medicine.

PubMed

Sharma, Nidhi; Neumann, Donald; Macklis, Roger

2008-09-15

Radiation medicine has previously utilized planning methods based primarily on anatomic and volumetric imaging technologies such as CT (Computerized Tomography), ultrasound, and MRI (Magnetic Resonance Imaging). In recent years, it has become apparent that a new dimension of non-invasive imaging studies may hold great promise for expanding the utility and effectiveness of the treatment planning process. Functional imaging such as PET (Positron Emission Tomography) studies and other nuclear medicine based assays are beginning to occupy a larger place in the oncology imaging world. Unlike the previously mentioned anatomic imaging methodologies, functional imaging allows differentiation between metabolically dead and dying cells and those which are actively metabolizing. The ability of functional imaging to reproducibly select viable and active cell populations in a non-invasive manner is now undergoing validation for many types of tumor cells. Many histologic subtypes appear amenable to this approach, with impressive sensitivity and selectivity reported. For clinical radiation medicine, the ability to differentiate between different levels and types of metabolic activity allows the possibility of risk based focal treatments in which the radiation doses and fields are more tightly connected to the perceived risk of recurrence or progression at each location. This review will summarize many of the basic principles involved in the field of functional PET imaging for radiation oncology planning and describe some of the major relevant published data behind this expanding trend.

Linear and non-linear quantitative structure-activity relationship models on indole substitution patterns as inhibitors of HIV-1 attachment.

PubMed

Nirouei, Mahyar; Ghasemi, Ghasem; Abdolmaleki, Parviz; Tavakoli, Abdolreza; Shariati, Shahab

2012-06-01

The antiviral drugs that inhibit human immunodeficiency virus (HIV) entry to the target cells are already in different phases of clinical trials. They prevent viral entry and have a highly specific mechanism of action with a low toxicity profile. Few QSAR studies have been performed on this group of inhibitors. This study was performed to develop a quantitative structure-activity relationship (QSAR) model of the biological activity of indole glyoxamide derivatives as inhibitors of the interaction between HIV glycoprotein gp120 and host cell CD4 receptors. Forty different indole glyoxamide derivatives were selected as a sample set and geometrically optimized using Gaussian 98W. Different combinations of multiple linear regression (MLR), genetic algorithms (GA) and artificial neural networks (ANN) were then utilized to construct the QSAR models. These models were also utilized to select the most efficient subsets of descriptors in a cross-validation procedure for non-linear log (1/EC50) prediction. The results that were obtained using GA-ANN were compared with MLR-MLR and MLR-ANN models. A high predictive ability was observed for the MLR, MLR-ANN and GA-ANN models, with root mean sum square errors (RMSE) of 0.99, 0.91 and 0.67, respectively (N = 40). In summary, machine learning methods were highly effective in designing QSAR models when compared to statistical method.

Scaling law in free walking of mice in circular open fields of various diameters.

PubMed

Shoji, Hiroto

2016-03-01

Open-field tests are routinely used to study locomotor activity in rodents. I studied the effects of apparatus size on rodent locomotor activity, specifically with respect to how resting and walking periods are interwoven. I explored the open-field behavior of mice utilizing circular open fields of various diameters. When the diameter of the test apparatus was greater than 75 cm, the durations of the resting and moving periods of free walking behavior obeyed bounded power-law distribution functions. I found that the properties of the scaling exponents and model selection became similar for test apparatus diameters greater than 75 cm. These results can provide a guide for the selection of the size of the test apparatus for use in the study of the open-field behavior of rodents.

Exercise motivation of college students in online, face-to-face, and blended basic studies physical activity and wellness course delivery formats.

PubMed

Sidman, Cara Lynn; Fiala, Kelly Ann; D'Abundo, Michelle Lee

2011-01-01

The purpose of this study was to assess exercise motivation among college students self-selected into 4 online (OL) and face-to-face (F2F) basic studies' physical activity and wellness course delivery formats. Out of 1,037 enrolled students during the Spring 2009 semester, 602 responded online to demographic questions and to the Behavioural Regulation in Exercise Questionnaire, which assessed exercise motivation on 5 subscales. There were no significant differences (p > .05) in exercise motivation for students across course delivery formats, but there was a significant difference in age and employment status between the completely OL and F2F course formats. Health and physical educators can utilize these findings to better understand that physical activity and wellness students are not necessarily trying to avoid physical activity when selecting the OL course format, but are more likely trying to balance work and school responsibilities and need greater flexibility in time and location.

syn-Selective crotylation of aldehydes using bismuth-crotyl bromide-(1-butyl-3-methylimidazolium bromide) combination: some synthetic applications.

PubMed

Goswami, Dibakar; Koli, Mrunesh R; Chatterjee, Sucheta; Chattopadhyay, Subrata; Sharma, Anubha

2017-05-03

The Bi-[bmim][Br] combination has been found to offer high syn-selectivity in the crotylation of aldehydes with crotyl bromide using practically stoichiometric amounts of the reagents. The room temperature ionic liquid (RTIL), [bmim][Br], activated Bi metal in the presence of oxygen to produce crotylbismuthdibromide, which reacted with the aldehydes at room temperature. The major anti-syn diastereomeric product obtained from the crotylation of (R)-cyclohexylideneglyceraldehyde was utilized for the synthesis of dictyostatin and cryptophycin segments, and (+)-cis-aerangis lactone, using standard synthetic protocols.

Selective and non-selective OT receptor agonists induce different locomotor behaviors in male rats via central OT receptors and peripheral V1a receptors.

PubMed

Wolfe, Monica; Wisniewska, Halina; Tariga, Hiroe; Ibanez, Gerardo; Collins, James C; Wisniewski, Kazimierz; Qi, Steve; Srinivasan, Karthik; Hargrove, Diane; Lindstrom, Beatriz Fioravanti

2018-05-21

Oxytocin (OT) continues to inspire much research due to its diverse physiological effects. While the best-understood actions of OT are uterine contraction and milk ejection, OT is also implicated in maternal and bonding behaviors, and potentially in CNS disorders such as autism, schizophrenia, and pain. The dissection of the mechanism of action of OT is complicated by the fact that this peptide activates not only its cognate receptor but also vasopressin type 1a (V1a) receptors. In this study, we evaluated OT and a selective OT receptor (OTR) agonist, FE 204409, in an automated assay that measures rat locomotor activity. The results showed: 1) Subcutaneous (sc) administration of OT decreased locomotor behavior (distance traveled, stereotypy, and rearing). This effect was reversed by a V1a receptor (V1aR) antagonist ([Pmp1,Tyr(ME)2]AVP, sc), suggesting that OT acts through peripheral V1aR to inhibit locomotor activity. 2) A selective OTR agonist (FE 204409, sc) increased stereotypy. This effect was reversed by an OTR antagonist dosed icv, suggesting a central OTR site of action. Our findings identify distinct behavioral effects for OT and the selective agonist FE 204409, adding to the growing body of evidence that the V1aR mediates many effects attributed to OT and that peptides administered systemically at supra-physiological doses may activate receptors in the brain. Our studies further emphasize the importance of utilizing selective agonists and antagonists to assess therapeutic indications. Copyright © 2018 Elsevier Ltd. All rights reserved.

Design study of wind turbines, 50 kW to 3000 kW for electric utility applications: Executive summary

NASA Technical Reports Server (NTRS)

1977-01-01

Preliminary designs of low power (50 to 500 kW) and high power (500 to 3000 kW) wind generator systems (WGS) for electric utility applications were developed. These designs provide the bases for detail design, fabrication, and experimental demonstration testing of these units at selected utility sites. Several feasible WGS configurations were evaluated, and the concept offering the lowest energy cost potential and minimum technical risk for utility applications was selected. The selected concept was optimized utilizing a parametric computer program prepared for this purpose. The utility requirements evaluation task examined the economic, operational and institutional factors affecting the WGS in a utility environment, and provided additional guidance for the preliminary design effort. Results of the conceptual design task indicated that a rotor operating at constant speed, driving an AC generator through a gear transmission is the most cost effective WGS configuration.

Defect in the GTPase activating protein (GAP) function of eIF5 causes repression of GCN4 translation.

PubMed

Antony A, Charles; Alone, Pankaj V

2017-05-13

In eukaryotes, the eIF5 protein plays an important role in translation start site selection by providing the GAP (GTPase activating protein) function. However, in yeast translation initiation fidelity defective eIF5 G31R mutant causes preferential utilization of UUG as initiation codon and is termed as Suppressor of initiation codon (Sui - ) phenotype due to its hyper GTPase activity. The eIF5 G31R mutant dominantly represses GCN4 expression and confers sensitivity to 3-Amino-1,2,4-Trizole (3AT) induced starvation. The down-regulation of the GCN4 expression (Gcn - phenotype) in the eIF5 G31R mutant was not because of leaky scanning defects; rather was due to the utilization of upUUG initiation codons at the 5' regulatory region present between uORF1 and the main GCN4 ORF. Copyright © 2017 Elsevier Inc. All rights reserved.

Research-based care on an acute inpatient psychiatric unit.

PubMed

Bartholomew, David; Collier, Elizabeth

Many studies of research-based practice in nursing highlight factors that impede the development of practice. With the aim of adding to this body of knowledge, a modified grounded theory approach was used in order to understand more about these barriers and how individual nurses utilize research in their practice. A selective sample of five staff nurses from one acute inpatient psychiatric unit took part in semi-structured interviews. Three main themes were identified, each with two sub-themes. These were (a) activities to utilize research with (i) a 'systematic' model and (ii) a 'latent' model of research utilization (b) enhancing research utilization with (i) organizational culture and (ii) individual attitude and knowledge and (c) impeding research utilization with (i) resources (ii) resistance to change. It is suggested that for these nurses research utilization occurs through their individual knowledge, skill and motivation coupled with organizational commitment. Recommendation is made that further investigation of the 'systematic' and 'latent' models should be carried out. Additionally, it is suggested that these research findings might be used to inform future training, further research-based initiatives and to raise managerial awareness of the impeding factors of research utilization.

Engineering human T cells for resistance to methotrexate and mycophenolate mofetil as an in vivo cell selection strategy.

PubMed

Jonnalagadda, Mahesh; Brown, Christine E; Chang, Wen-Chung; Ostberg, Julie R; Forman, Stephen J; Jensen, Michael C

2013-01-01

Gene transfer and drug selection systems that enforce ongoing transgene expression in vitro and in vivo which are compatible with human pharmaceutical drugs are currently underdeveloped. Here, we report on the utility of incorporating human enzyme muteins that confer resistance to the lymphotoxic/immunosuppressive drugs methotrexate (MTX) and mycophenolate mofetil (MMF) in a multicistronic lentiviral vector for in vivo T lymphocyte selection. We found that co-expression of human dihydrofolate reductase (DHFR(FS); L22F, F31S) and inosine monophosphate dehydrogenase II (IMPDH2(IY); T333I, S351Y) conferred T cell resistance to the cytocidal and anti-proliferative effects of these drugs at concentrations that can be achieved clinically (up to 0.1 µM MTX and 1.0 µM MPA). Furthermore, using a immunodeficient mouse model that supports the engraftment of central memory derived human T cells, in vivo selection studies demonstrate that huEGFRt(+)DHFR(FS+)IMPDH2(IY+) T cells could be enriched following adoptive transfer either by systemic administration of MTX alone (4.4 -fold), MMF alone (2.9-fold), or combined MTX and MMF (4.9-fold). These findings demonstrate the utility of both DHFR(FS)/MTX and IMPDH2(IY)/MMF for in vivo selection of lentivirally transduced human T cells. Vectors incorporating these muteins in combination with other therapeutic transgenes may facilitate the selective engraftment of therapeutically active cells in recipients.

Selective imaging of cathepsin L in breast cancer by fluorescent activity-based probes† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c7sc04303a

PubMed Central

Rut, Wioletta; Vizovisek, Matej; Groborz, Katarzyna; Kasperkiewicz, Paulina; Finlay, Darren; Vuori, Kristiina; Turk, Dusan; Turk, Boris; Salvesen, Guy S.

2018-01-01

Cysteine cathepsins normally function in the lysosomal degradation system where they are critical for the maintenance of cellular homeostasis and the MHC II immune response, and have been found to have major roles in several diseases and in tumor progression. Selective visualization of individual protease activity within a complex proteome is of major importance to establish their roles in both normal and tumor cells, thereby facilitating our understanding of the regulation of proteolytic networks. A generally accepted means to monitor protease activity is the use of small molecule substrates and activity-based probes. However, there are eleven human cysteine cathepsins, with a few of them displaying overlapping substrate specificity, making the development of small molecules that selectively target a single cathepsin very challenging. Here, we utilized HyCoSuL, a positional scanning substrate approach, to develop a highly-selective fluorogenic substrate and activity-based probe for monitoring cathepsin L activity in the breast cancer cell line MDA-MB-231. Use of this probe enabled us to distinguish the activity of cathepsin L from that of other cathepsins, particularly cathepsin B, which is abundant and ubiquitously expressed in normal and transformed cell types. We found that cathepsin L localization in MDA-MB-231 cells greatly overlaps with that of cathepsin B, however, several cathepsin L-rich lysosomes lacked cathepsin B activity. Overall, these studies demonstrate that HyCoSuL-derived small molecule probes are valuable tools to image cathepsin L activity in living cells. This approach thus enables evaluation of cathepsin L function in tumorigenesis and is applicable to other cysteine cathepsins. PMID:29719685

Catalyst recognition of cis-1,2-diols enables site-selective functionalization of complex molecules

NASA Astrophysics Data System (ADS)

Sun, Xixi; Lee, Hyelee; Lee, Sunggi; Tan, Kian L.

2013-09-01

Carbohydrates and natural products serve essential roles in nature, and also provide core scaffolds for pharmaceutical agents and vaccines. However, the inherent complexity of these molecules imposes significant synthetic hurdles for their selective functionalization and derivatization. Nature has, in part, addressed these issues by employing enzymes that are able to orient and activate substrates within a chiral pocket, which increases dramatically both the rate and selectivity of organic transformations. In this article we show that similar proximity effects can be utilized in the context of synthetic catalysts to achieve general and predictable site-selective functionalization of complex molecules. Unlike enzymes, our catalysts apply a single reversible covalent bond to recognize and bind to specific functional group displays within substrates. By combining this unique binding selectivity and asymmetric catalysis, we are able to modify the less reactive axial positions within monosaccharides and natural products.

The relationship between activity specialization and preferences for setting and route attributes of selected rock climbers

Treesearch

Kurt Merrill; Alan Graefe

1998-01-01

Many natural areas are now in the process of developing climbing management plans in order to control management factors associated with the growth of rock climbing. These factors may include limiting areas of use and limiting the type of climber utilizing the resource. The purpose of this study was to further develop and operationalize the concept of recreation...

Pseudomonas oleovorans strain KBPF-004 culture supernatants reduced seed transmission of Cucumber green mottle mosaic virus and Pepper mild mottle virus, and remodeled aggregation of 126 kDa and subcellular localization......

USDA-ARS?s Scientific Manuscript database

Efforts to control viral diseases in crop production include several types of physical or chemical treatments; antiviral extracts from a number of plants have also been examined to inhibit plant viral infection. However, treatments utilizing naturally selected microorganisms with activity against pl...

An Analysis of the Space Transportation System Launch Rate Capability Utilizing Q-GERT Simulation Techniques.

DTIC Science & Technology

1982-12-01

VAPE was modeled to determine this launch rate and to determine the processing times for an Orbiter at VAPe . This informa- 21 tion was then used in the...year (node 79 and activity ?1). ETa are then selected to be sent to either KSC or VAPE (node 80). This decision is made (using Ur 8) on the basis of

Cloning and characterization of a Candida albicans maltase gene involved in sucrose utilization.

PubMed Central

Geber, A; Williamson, P R; Rex, J H; Sweeney, E C; Bennett, J E

1992-01-01

In order to isolate the structural gene involved in sucrose utilization, we screened a sucrose-induced Candida albicans cDNA library for clones expressing alpha-glucosidase activity. The C. albicans maltase structural gene (CAMAL2) was isolated. No other clones expressing alpha-glucosidase activity. were detected. A genomic CAMAL2 clone was obtained by screening a size-selected genomic library with the cDNA clone. DNA sequence analysis reveals that CAMAL2 encodes a 570-amino-acid protein which shares 50% identity with the maltase structural gene (MAL62) of Saccharomyces carlsbergensis. The substrate specificity of the recombinant protein purified from Escherichia coli identifies the enzyme as a maltase. Northern (RNA) analysis reveals that transcription of CAMAL2 is induced by maltose and sucrose and repressed by glucose. These results suggest that assimilation of sucrose in C. albicans relies on an inducible maltase enzyme. The family of genes controlling sucrose utilization in C. albicans shares similarities with the MAL gene family of Saccharomyces cerevisiae and provides a model system for studying gene regulation in this pathogenic yeast. Images PMID:1400249

Green Power Marketing in the United States: A Status Report (Eighth Edition)

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

Bird, L.; Swezey, B.

Voluntary consumer decisions to purchase electricity supplied by renewable energy sources represent a powerful market support mechanism for renewable energy development. Beginning in the early 1990s, a small number of U.S. utilities began offering "green power" options to their customers. Since then, these products have become more prevalent, both from utilities and in states that have introduced competition into their retail electricity markets. Today, more than 50% of all U.S. consumers have an option to purchase some type of green power product from a retail electricity provider. This report provides an overview of green power marketing activity in the Unitedmore » States. The first section provides an overview of green power markets, consumer response, and recent industry trends. The second section provides brief descriptions of utility green pricing programs. The third section describes companies that actively market green power in competitive markets and those that market renewable energy certificates nationally or regionally. The final section provides information on a select number of large, nonresidential green power purchasers, including businesses, universities, and government agencies.« less

Green Power Marketing in the United States: A Status Report; Seventh Edition

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

Bird, L.; Swezey, B.

Voluntary consumer decisions to purchase electricity supplied from renewable energy sources represent a powerful market support mechanism for renewable energy development. Beginning in the early 1990s, a small number of U.S. utilities began offering ''green power'' options to their customers. Since then, these products have become more prevalent both from utilities and in states that have introduced competition into their retail electricity markets. Today, more than 50% of all U.S. consumers have an option to purchase some type of green power product from a retail electricity provider. This report provides an overview of green power marketing activity in the Unitedmore » States. The first section provides an overview of green power markets, consumer response, and recent industry trends. Section 2 provides brief descriptions of the utility green pricing programs available nationally. Section 3 describes companies that actively market green power in competitive markets and those that market renew able energy certificates nationally or regionally. The last section provides information on a select number of large, nonresidential green power purchasers, including governmental agencies, universities, and businesses.« less

Inertial navigation sensor integrated obstacle detection system

NASA Technical Reports Server (NTRS)

Bhanu, Bir (Inventor); Roberts, Barry A. (Inventor)

1992-01-01

A system that incorporates inertial sensor information into optical flow computations to detect obstacles and to provide alternative navigational paths free from obstacles. The system is a maximally passive obstacle detection system that makes selective use of an active sensor. The active detection typically utilizes a laser. Passive sensor suite includes binocular stereo, motion stereo and variable fields-of-view. Optical flow computations involve extraction, derotation and matching of interest points from sequential frames of imagery, for range interpolation of the sensed scene, which in turn provides obstacle information for purposes of safe navigation.

Beyond small molecule SAR – using the dopamine D3 receptor crystal structure to guide drug design

PubMed Central

Keck, Thomas M.; Burzynski, Caitlin; Shi, Lei; Newman, Amy Hauck

2016-01-01

The dopamine D3 receptor is a target of pharmacotherapeutic interest in a variety of neurological disorders including schizophrenia, restless leg syndrome, and drug addiction. The high protein sequence homology between the D3 and D2 receptors has posed a challenge to developing D3 receptor-selective ligands whose behavioral actions can be attributed to D3 receptor engagement, in vivo. However, through primarily small molecule structure-activity relationship (SAR) studies, a variety of chemical scaffolds have been discovered over the past two decades that have resulted in several D3 receptor-selective ligands with high affinity and in vivo activity. Nevertheless, viable clinical candidates remain limited. The recent determination of the high-resolution crystal structure of the D3 receptor has invigorated structure-based drug design, providing refinements to the molecular dynamic models and testable predictions about receptor-ligand interactions. This review will highlight recent preclinical and clinical studies demonstrating potential utility of D3 receptor-selective ligands in the treatment of addiction. In addition, new structure-based rational drug design strategies for D3 receptor-selective ligands that complement traditional small molecule SAR to improve the selectivity and directed efficacy profiles are examined. PMID:24484980

Highly efficient temperature-induced visible light photocatalytic hydrogen production

NASA Astrophysics Data System (ADS)

Han, Bing

Photocatalysis is the acceleration of photoreaction in presence of a photocatalyst. Semiconductor photocatalysis has obtained much attention as a potential solution to the worldwide energy storage due to its promising ability to directly convert solar energy into chemical fuels. This dissertation research mainly employ three approaches to enhance photocatalytic activities, which includes (I) Modifying semiconductor nanomaterials for visible and near-IR light absorption; (II) Synthesis of light-diffuse-reflection-surface of SiO2 substrate to utilize scattered light; and (III) design of a hybrid system that combines light and heat to enhance visible light photocatalytic activity. Those approaches were applied to two systems: (1) hydrogen production from water; (2) carbon dioxide reforming of methane. The activity of noble metals such as platinum were investigated as co-catalysts and cheap earth abundant catalysts as alternatives to reduce cost were also developed. Stability, selectivity, mechanism were investigated. Great enhancement of visible light activity over a series of semiconductors/heterostructures were observed. Such extraordinary performance of artificial photosynthetic hydrogen production system would provide a novel approach for the utilization of solar energy for chemical fuel production.

More complete gene silencing by fewer siRNAs: transparent optimized design and biophysical signature

PubMed Central

Ladunga, Istvan

2007-01-01

Highly accurate knockdown functional analyses based on RNA interference (RNAi) require the possible most complete hydrolysis of the targeted mRNA while avoiding the degradation of untargeted genes (off-target effects). This in turn requires significant improvements to target selection for two reasons. First, the average silencing activity of randomly selected siRNAs is as low as 62%. Second, applying more than five different siRNAs may lead to saturation of the RNA-induced silencing complex (RISC) and to the degradation of untargeted genes. Therefore, selecting a small number of highly active siRNAs is critical for maximizing knockdown and minimizing off-target effects. To satisfy these needs, a publicly available and transparent machine learning tool is presented that ranks all possible siRNAs for each targeted gene. Support vector machines (SVMs) with polynomial kernels and constrained optimization models select and utilize the most predictive effective combinations from 572 sequence, thermodynamic, accessibility and self-hairpin features over 2200 published siRNAs. This tool reaches an accuracy of 92.3% in cross-validation experiments. We fully present the underlying biophysical signature that involves free energy, accessibility and dinucleotide characteristics. We show that while complete silencing is possible at certain structured target sites, accessibility information improves the prediction of the 90% active siRNA target sites. Fast siRNA activity predictions can be performed on our web server at . PMID:17169992

Comparison of the Deacylase and Deacetylase Activity of Zinc-Dependent HDACs.

PubMed

McClure, Jesse J; Inks, Elizabeth S; Zhang, Cheng; Peterson, Yuri K; Li, Jiaying; Chundru, Kalyan; Lee, Bradley; Buchanan, Ashley; Miao, Shiqin; Chou, C James

2017-06-16

The acetylation status of lysine residues on histone proteins has long been attributed to a balance struck between the catalytic activity of histone acetyl transferases and histone deacetylases (HDAC). HDACs were identified as the sole removers of acetyl post-translational modifications (PTM) of histone lysine residues. Studies into the biological role of HDACs have also elucidated their role as removers of acetyl PTMs from lysine residues of nonhistone proteins. These findings, coupled with high-resolution mass spectrometry studies that revealed the presence of acyl-group PTMs on lysine residues of nonhistone proteins, brought forth the possibility of HDACs acting as removers of both acyl- and acetyl-based PTMs. We posited that HDACs fulfill this dual role and sought to investigate their specificity. Utilizing a fluorescence-based assay and biologically relevant acyl-substrates, the selectivities of zinc-dependent HDACs toward these acyl-based PTMs were identified. These findings were further validated using cellular models and molecular biology techniques. As a proof of principal, an HDAC3 selective inhibitor was designed using HDAC3's substrate preference. This resulting inhibitor demonstrates nanomolar activity and >30 fold selectivity toward HDAC3 compared to the other class I HDACs. This inhibitor is capable of increasing p65 acetylation, attenuating NF-κB activation, and thereby preventing downstream nitric oxide signaling. Additionally, this selective HDAC3 inhibition allows for control of HMGB-1 secretion from activated macrophages without altering the acetylation status of histones or tubulin.

Do You See What I See? Exploring the Consequences of Luminosity Limits in Black Hole-Galaxy Evolution Studies

NASA Astrophysics Data System (ADS)

Jones, Mackenzie L.; Hickox, Ryan C.; Mutch, Simon J.; Croton, Darren J.; Ptak, Andrew F.; DiPompeo, Michael A.

2017-07-01

In studies of the connection between active galactic nuclei (AGNs) and their host galaxies, there is widespread disagreement on some key aspects of the connection. These disagreements largely stem from a lack of understanding of the nature of the full underlying AGN population. Recent attempts to probe this connection utilize both observations and simulations to correct for a missed population, but presently are limited by intrinsic biases and complicated models. We take a simple simulation for galaxy evolution and add a new prescription for AGN activity to connect galaxy growth to dark matter halo properties and AGN activity to star formation. We explicitly model selection effects to produce an “observed” AGN population for comparison with observations and empirically motivated models of the local universe. This allows us to bypass the difficulties inherent in models that attempt to infer the AGN population by inverting selection effects. We investigate the impact of selecting AGNs based on thresholds in luminosity or Eddington ratio on the “observed” AGN population. By limiting our model AGN sample in luminosity, we are able to recreate the observed local AGN luminosity function and specific star formation-stellar mass distribution, and show that using an Eddington ratio threshold introduces less bias into the sample by selecting the full range of growing black holes, despite the challenge of selecting low-mass black holes. We find that selecting AGNs using these various thresholds yield samples with different AGN host galaxy properties.

Multi-Modal Active Perception for Autonomously Selecting Landing Sites on Icy Moons

NASA Technical Reports Server (NTRS)

Arora, A.; Furlong, P. M.; Wong, U.; Fong, T.; Sukkarieh, S.

2017-01-01

Selecting suitable landing sites is fundamental to achieving many mission objectives in planetary robotic lander missions. However, due to sensing limitations, landing sites which are both safe and scientifically valuable often cannot be determined reliably from orbit, particularly, in icy moon missions where orbital sensing data is noisy and incomplete. This paper presents an active perception approach to Entry Descent and Landing (EDL) which enables the lander to autonomously plan informative descent trajectories, acquire high quality sensing data during descent and exploit this additional information to select higher utility landing sites. Our approach consists of two components: probabilistic modeling of landing site features and approximate trajectory planning using a sampling based planner. The proposed framework allows the lander to plan long horizons paths and remain robust to noisy data. Results in simulated environments show large performance improvements over alternative approaches and show promise that our approach has strong potential to improve science return of not only icy moon missions but EDL systems in general.

In Vitro Selection of a Single-Stranded DNA Molecular Recognition Element against the Pesticide Fipronil and Sensitive Detection in River Water

PubMed Central

Sooter, Letha J.

2017-01-01

Fipronil is a commonly used insecticide that has been shown to have environmental and human health risks. The current standard methods of detection for fipronil and its metabolites, such as GC-MS, are time consuming and labor intensive. In this study, a variant of systematic evolution of ligands by exponential enrichment (SELEX), was utilized to identify the first single-stranded DNA (ssDNA) molecular recognition element (MRE) that binds to fipronil with high affinity (Kd = 48 ± 8 nM). The selected MRE displayed low cross binding activity on various environmentally relevant, structurally unrelated herbicides and pesticides, in addition to broad-spectrum binding activity on major metabolites of fipronil and a structurally similar pesticide in prepared river samples. Additionally, a proof-of-principle fluorescent detection assay was developed by using the selected ssDNA MRE as a signal-reporting element, with a limit of detection of 105 nM in a prepared river water sample. PMID:29283416

Deoxygenation of glycolaldehyde and furfural on Mo2C/Mo(100)

NASA Astrophysics Data System (ADS)

McManus, Jesse R.; Vohs, John M.

2014-12-01

The desire to produce fuels and chemicals in an energy conscious, environmentally sympathetic approach has motivated considerable research on the use of cellulosic biomass feedstocks. One of the major challenges facing the utilization of biomass is finding effective catalysts for the efficient and selective removal of oxygen from the highly-oxygenated, biomass-derived platform molecules. Herein, a study of the reaction pathways for the biomass-derived platform molecule furfural and biomass-derived sugar model compound glycolaldehyde provides insight into the mechanisms of hydrodeoxygenation (HDO) on a model molybdenum carbide catalyst, Mo2C/Mo(100). Using temperature programmed desorption (TPD) and high resolution electron energy loss spectroscopy (HREELS), it was found that the Mo2C/Mo(100) catalyst was active for selective deoxygenation of the aldehyde carbonyl by facilitating adsorption of the aldehyde in an η2(C,O) bonding configuration. Furthermore, the catalyst showed no appreciable activity for furanic ring hydrogenation, highlighting the promise of relatively inexpensive Mo2C catalysts for selective HDO chemistry.

Assessment of US industry's technology trends and new technology requirements

NASA Technical Reports Server (NTRS)

1984-01-01

The utility and effectiveness of a novel approach (the Applications Development, or AD approach), intended to augment the efficiency of NASA's technology utilization (TU) through dissemination of NASA technologies and joint technology development efforts with U.S. industry is tested. The innovative AD approach consists of the following key elements: selection of NASA technologies appearing to have leading edge attributes; interaction with NASA researchers to assess the characteristics and quality of each selected technology; identification of industry's needs in the selected technology areas; structuring the selected technologies in terms of specifications and standards familiar to industry (industrial Spec. Sheets); identification and assessment of industry's interest in the specific selected NASA technologies, utilizing the greatly facilitated communication made possible by the availability of the industrial Spec. Sheets; and matching selected NASA technologies with the needs of selected industries.

Measuring benefits of opioid misuse treatment for economic evaluation: health related quality of life of opioid dependent individuals and their spouses as assessed by a sample of the US population

PubMed Central

Wittenberg, Eve; Bray, Jeremy W.; Aden, Brandon; Gebremariam, Achamyeleh; Nosyk, Bohdan; Schackman, Bruce R.

2016-01-01

Aims To understand how the general public views the quality of life effects of opioid misuse and opioid use disorder on an individual and his/her spouse, measured in terms used in economic evaluations. Design Cross-sectional internet survey of a US-population-representative respondent panel conducted December 2013-January 2014. Setting USA. Participants 2,054 randomly-selected adults; 51% male (before weighting). Measurements Mean (95% CI) and median health “utility” for 6 opioid misuse and treatment outcomes: active injection misuse; active prescription misuse; methadone maintenance therapy at initiation, and when stabilized in treatment; and buprenorphine therapy at initiation, and when stabilized. Utility is a numerical representation of health-related quality of life used in economic evaluations to “adjust” estimated survival to include peoples' preferences for health states. Utilities are determined by surveying the general population to estimate the value they assign to particular health states—on a scale where 0=the value of being dead, and 1.0=the value of being in perfect health. Spouse spillover utility is assigned to a spouse of an individual who is in a particular health state. Findings Mean individual utility ranged from 0.574 (95%CI: 0.538, 0.611) for active injection opioid misuse to 0.766 for stabilized buprenorphine therapy (95%CI: 0.738, 0.795), with other states in between. Female respondents assigned higher utility to the active prescription misuse and buprenorphine therapy at initiation states than did males (p<0.05); all other states did not differ by respondent gender. Mean spousal utilities were significantly lower than 1.0 but mostly higher than individual utility, and were similar between male and female respondents. Conclusions In the opinion of the US public, injection opioid misuse results in worse health-related quality of life than prescription misuse, and methadone therapy results in worse health-related quality of life than buprenorphine therapy. Spouses are negatively affected by their partner's opioid misuse and early treatment. PMID:26498740

Spectral characterization of a pteridine derivative from cyanide-utilizing bacterium Bacillus subtilis - JN989651.

PubMed

Durairaju Nisshanthini, S; Teresa Infanta S, Antony K; Raja, Duraisamy Senthil; Natarajan, Karuppannan; Palaniswamy, M; Angayarkanni, Jayaraman

2015-04-01

Soil and water samples were collected from various regions of SIPCOT and nearby Vanappadi Lake, Ranipet, Tamilnadu, India. Based on their colony morphology and their stability during subculturing, 72 bacteria were isolated, of which 14 isolates were actinomycetes. Preliminary selection was carried out to exploit the ability of the microorganisms to utilize sodium cyanate as nitrogen source. Those organisms that were able to utilize cyanate were subjected to secondary screening viz., utilization of sodium cyanide as the nitrogen source. The oxygenolytic cleavage of cyanide is dependent on cyanide monooxygenase which obligately requires pterin cofactor for its activity. Based on this, the organisms capable of utilizing sodium cyanide were tested for the presence of pterin. Thin layer chromatography (TLC) of the cell extracts using n-butanol: 5 N glacial acetic acid (4:1) revealed that 10 out of 12 organisms that were able to utilize cyanide had the pterin-related blue fluorescent compound in the cell extract. The cell extracts of these 10 organisms were subjected to high performance thin layer chromatography (HPTLC) for further confirmation using a pterin standard. Based on the incubation period, cell biomass yield, peak height and area, strain VPW3 was selected and was identified as Bacillus subtilis. The Rf value of the cell extract was 0.73 which was consistent with the 0.74 Rf value of the pterin standard when scanned at 254 nm. The compound was extracted and purified by preparative High Performance Liquid Chromatography (HPLC). Characterization of the compound was performed by ultraviolet spectrum, fluorescence spectrum, Electrospray Ionization-Mass Spectrometry (ESI-MS), and Nuclear Magnetic Resonance spectroscopy (NMR). The compound is proposed to be 6-propionyl pterin (2-amino-6-propionyl-3H-pteridin-4-one).

Mammalian genomic regulatory regions predicted by utilizing human genomics, transcriptomics, and epigenetics data

PubMed Central

Nguyen, Quan H; Tellam, Ross L; Naval-Sanchez, Marina; Porto-Neto, Laercio R; Barendse, William; Reverter, Antonio; Hayes, Benjamin; Kijas, James; Dalrymple, Brian P

2018-01-01

Abstract Genome sequences for hundreds of mammalian species are available, but an understanding of their genomic regulatory regions, which control gene expression, is only beginning. A comprehensive prediction of potential active regulatory regions is necessary to functionally study the roles of the majority of genomic variants in evolution, domestication, and animal production. We developed a computational method to predict regulatory DNA sequences (promoters, enhancers, and transcription factor binding sites) in production animals (cows and pigs) and extended its broad applicability to other mammals. The method utilizes human regulatory features identified from thousands of tissues, cell lines, and experimental assays to find homologous regions that are conserved in sequences and genome organization and are enriched for regulatory elements in the genome sequences of other mammalian species. Importantly, we developed a filtering strategy, including a machine learning classification method, to utilize a very small number of species-specific experimental datasets available to select for the likely active regulatory regions. The method finds the optimal combination of sensitivity and accuracy to unbiasedly predict regulatory regions in mammalian species. Furthermore, we demonstrated the utility of the predicted regulatory datasets in cattle for prioritizing variants associated with multiple production and climate change adaptation traits and identifying potential genome editing targets. PMID:29618048

Mammalian genomic regulatory regions predicted by utilizing human genomics, transcriptomics, and epigenetics data.

PubMed

Nguyen, Quan H; Tellam, Ross L; Naval-Sanchez, Marina; Porto-Neto, Laercio R; Barendse, William; Reverter, Antonio; Hayes, Benjamin; Kijas, James; Dalrymple, Brian P

2018-03-01

Genome sequences for hundreds of mammalian species are available, but an understanding of their genomic regulatory regions, which control gene expression, is only beginning. A comprehensive prediction of potential active regulatory regions is necessary to functionally study the roles of the majority of genomic variants in evolution, domestication, and animal production. We developed a computational method to predict regulatory DNA sequences (promoters, enhancers, and transcription factor binding sites) in production animals (cows and pigs) and extended its broad applicability to other mammals. The method utilizes human regulatory features identified from thousands of tissues, cell lines, and experimental assays to find homologous regions that are conserved in sequences and genome organization and are enriched for regulatory elements in the genome sequences of other mammalian species. Importantly, we developed a filtering strategy, including a machine learning classification method, to utilize a very small number of species-specific experimental datasets available to select for the likely active regulatory regions. The method finds the optimal combination of sensitivity and accuracy to unbiasedly predict regulatory regions in mammalian species. Furthermore, we demonstrated the utility of the predicted regulatory datasets in cattle for prioritizing variants associated with multiple production and climate change adaptation traits and identifying potential genome editing targets.

Oncogenic activation of JAK3-STAT signaling confers clinical sensitivity to PRN371, a novel selective and potent JAK3 inhibitor, in natural killer/T-cell lymphoma.

PubMed

Nairismägi, M -L; Gerritsen, M E; Li, Z M; Wijaya, G C; Chia, B K H; Laurensia, Y; Lim, J Q; Yeoh, K W; Yao, X S; Pang, W L; Bisconte, A; Hill, R J; Bradshaw, J M; Huang, D; Song, T L L; Ng, C C Y; Rajasegaran, V; Tang, T; Tang, Q Q; Xia, X J; Kang, T B; Teh, B T; Lim, S T; Ong, C K; Tan, J

2018-05-01

Aberrant activation of the JAK3-STAT signaling pathway is a characteristic feature of many hematological malignancies. In particular, hyperactivity of this cascade has been observed in natural killer/T-cell lymphoma (NKTL) cases. Although the first-in-class JAK3 inhibitor tofacitinib blocks JAK3 activity in NKTL both in vitro and in vivo, its clinical utilization in cancer therapy has been limited by the pan-JAK inhibition activity. To improve the therapeutic efficacy of JAK3 inhibition in NKTL, we have developed a highly selective and durable JAK3 inhibitor PRN371 that potently inhibits JAK3 activity over the other JAK family members JAK1, JAK2, and TYK2. PRN371 effectively suppresses NKTL cell proliferation and induces apoptosis through abrogation of the JAK3-STAT signaling. Moreover, the activity of PRN371 has a more durable inhibition on JAK3 compared to tofacitinib in vitro, leading to significant tumor growth inhibition in a NKTL xenograft model harboring JAK3 activating mutation. These findings provide a novel therapeutic approach for the treatment of NKTL.

A Negative Selection Immune System Inspired Methodology for Fault Diagnosis of Wind Turbines.

PubMed

Alizadeh, Esmaeil; Meskin, Nader; Khorasani, Khashayar

2017-11-01

High operational and maintenance costs represent as major economic constraints in the wind turbine (WT) industry. These concerns have made investigation into fault diagnosis of WT systems an extremely important and active area of research. In this paper, an immune system (IS) inspired methodology for performing fault detection and isolation (FDI) of a WT system is proposed and developed. The proposed scheme is based on a self nonself discrimination paradigm of a biological IS. Specifically, the negative selection mechanism [negative selection algorithm (NSA)] of the human body is utilized. In this paper, a hierarchical bank of NSAs are designed to detect and isolate both individual as well as simultaneously occurring faults common to the WTs. A smoothing moving window filter is then utilized to further improve the reliability and performance of the FDI scheme. Moreover, the performance of our proposed scheme is compared with another state-of-the-art data-driven technique, namely the support vector machines (SVMs) to demonstrate and illustrate the superiority and advantages of our proposed NSA-based FDI scheme. Finally, a nonparametric statistical comparison test is implemented to evaluate our proposed methodology with that of the SVM under various fault severities.

The utility of postmortem computed tomography selective coronary angiography in parallel with autopsy.

PubMed

Inokuchi, Go; Yajima, Daisuke; Hayakawa, Mutsumi; Motomura, Ayumi; Chiba, Fumiko; Torimitsu, Suguru; Makino, Yohsuke; Iwase, Hirotaro

2013-12-01

Historically, coronary angiography of the isolated heart has played an important role in the detection of stenotic or occlusive lesions that are difficult to identify by autopsy alone. Meanwhile, although the application of multidetector computed tomography (MDCT) to forensic fields has accelerated recently, isolated single organ angiography with MDCT is rarely performed. In this article, we present an evaluation of postmortem selective coronary CT angiography of the isolated heart with MDCT and discuss its utility for autopsy. First, in a preliminary experiment using pig coronary artery, we examined the behavior of water soluble contrast material on postmortem computed tomography angiography (PMCTA) and found that better angiographic images were acquired when the viscosity of the contrast material was increased and CT was performed under conditions of sustained perfusion. Based on these results, we devised a selective coronary angiography procedure using a pressurized bag for drip infusion that can be performed easily, quickly, and at low cost. The angiographic images obtained provided useful supportive evidence of autopsy findings suggestive of ischemic heart disease. With active discussions underway in forensic fields on the proper use of postmortem computed tomography, PMCTA has also naturally attracted attention as it compensates for some of the shortcomings of CT alone. Although PMCTA typically involves whole-body angiography, if we view PMCTA as one of the many useful and supplementary tools available for autopsy, then isolated heart angiography continues to have utility in autopsy today.

Therapeutics targeting Bcl-2 in hematological malignancies.

PubMed

Ruefli-Brasse, Astrid; Reed, John C

2017-10-23

Members of the B-cell lymphoma 2 ( BCL-2 ) gene family are attractive targets for cancer therapy as they play a key role in promoting cell survival, a long-since established hallmark of cancer. Clinical utility for selective inhibition of specific anti-apoptotic Bcl-2 family proteins has recently been realized with the Food and Drug Administration (FDA) approval of venetoclax (formerly ABT-199/GDC-0199) in relapsed chronic lymphocytic leukemia (CLL) with 17p deletion. Despite the impressive monotherapy activity in CLL, such responses have rarely been observed in other B-cell malignancies, and preclinical data suggest that combination therapies will be needed in other indications. Additional selective antagonists of Bcl-2 family members, including Bcl-X L and Mcl-1, are in various stages of preclinical and clinical development and hold the promise of extending clinical utility beyond CLL and overcoming resistance to venetoclax. In addition to direct targeting of Bcl-2 family proteins with BH3 mimetics, combination therapies that aim at down-regulating expression of anti-apoptotic BCL-2 family members or restoring expression of pro-apoptotic BH3 family proteins may provide a means to deepen responses to venetoclax and extend the utility to additional indications. Here, we review recent progress in direct and selective targeting of Bcl-2 family proteins for cancer therapy and the search for rationale combinations. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Covalent Docking of Large Libraries for the Discovery of Chemical Probes

PubMed Central

London, Nir; Miller, Rand M.; Krishnan, Shyam; Uchida, Kenji; Irwin, John J.; Eidam, Oliv; Gibold, Lucie; Cimermančič, Peter; Bonnet, Richard; Shoichet, Brian K.; Taunton, Jack

2014-01-01

Chemical probes that form a covalent bond with a protein target often show enhanced selectivity, potency, and utility for biological studies. Despite these advantages, protein-reactive compounds are usually avoided in high-throughput screening campaigns. Here we describe a general method (DOCKovalent) for screening large virtual libraries of electrophilic small molecules. We apply this method prospectively to discover reversible covalent fragments that target distinct protein nucleophiles, including the catalytic serine of AmpC β-lactamase and noncatalytic cysteines in RSK2, MSK1, and JAK3 kinases. We identify submicromolar to low-nanomolar hits with high ligand efficiency, cellular activity and selectivity, including the first reported reversible covalent inhibitors of JAK3. Crystal structures of inhibitor complexes with AmpC and RSK2 confirm the docking predictions and guide further optimization. As covalent virtual screening may have broad utility for the rapid discovery of chemical probes, we have made the method freely available through an automated web server (http://covalent.docking.org). PMID:25344815

Covalent docking of large libraries for the discovery of chemical probes.

PubMed

London, Nir; Miller, Rand M; Krishnan, Shyam; Uchida, Kenji; Irwin, John J; Eidam, Oliv; Gibold, Lucie; Cimermančič, Peter; Bonnet, Richard; Shoichet, Brian K; Taunton, Jack

2014-12-01

Chemical probes that form a covalent bond with a protein target often show enhanced selectivity, potency and utility for biological studies. Despite these advantages, protein-reactive compounds are usually avoided in high-throughput screening campaigns. Here we describe a general method (DOCKovalent) for screening large virtual libraries of electrophilic small molecules. We apply this method prospectively to discover reversible covalent fragments that target distinct protein nucleophiles, including the catalytic serine of AmpC β-lactamase and noncatalytic cysteines in RSK2, MSK1 and JAK3 kinases. We identify submicromolar to low-nanomolar hits with high ligand efficiency, cellular activity and selectivity, including what are to our knowledge the first reported reversible covalent inhibitors of JAK3. Crystal structures of inhibitor complexes with AmpC and RSK2 confirm the docking predictions and guide further optimization. As covalent virtual screening may have broad utility for the rapid discovery of chemical probes, we have made the method freely available through an automated web server (http://covalent.docking.org/).

Stereocomplexes Formed From Select Oligomers of Polymer d-lactic Acid (PDLA) and l-lactate May Inhibit Growth of Cancer Cells and Help Diagnose Aggressive Cancers-Applications of the Warburg Effect.

PubMed

Goldberg, Joel S

2011-02-15

It is proposed that select oligomers of polymer d-lactic acid (PDLA) will form a stereocomplex with l-lactate in vivo, producing lactate deficiency in tumor cells. Those cancer cells that utilize transport of lactate to maintain electrical neutrality may cease to multiply or die because of lactate trapping, and those cancer cells that benefit from utilization of extracellular lactate may be impaired. Intracellular trapping of lactate produces a different physiology than inhibition of LDH because the cell loses the option of shuttling pyruvate to an alternative pathway to produce an anion. Conjugated with stains or fluorescent probes, PDLA oligomers may be an agent for the diagnosis of tissue lactate and possibly cell differentiation in biopsy specimens. Preliminary experimental evidence is presented confirming that PDLA in high concentrations is cytotoxic and that l-lactate forms a presumed stereocomplex with PDLA. Future work should be directed at isolation of biologically active oligomers of PDLA.

Optimization-based sale transactions and hydrothermal scheduling

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

Prasannan, B.; Luh, P.B.; Yan, H.

1995-12-31

Selling and purchasing power are important activities for utilities because of potential savings. When a selling utility presents an offer including prices, power levels and durations, a purchasing utility selects power levels and durations within the offered range subject to relevant constraints. The decisionmaking process is complicated because transactions are coupled with system demand and reserve, therefore decisions have to be made in conjunction with the commitment and dispatching of units. Furthermore, transaction decisions have to be made in almost real time in view of the competitiveness of the power market caused by deregulation. In this paper, transactions are analyzedmore » from a selling utility`s viewpoint for a system consisting of thermal, hydro and pumped-storage units. To effectively solve the problem, linear sale revenues are approximated by nonlinear functions, and non-profitable options are identified and eliminated from consideration. The multipliers are then updated at the high level by using a modified subgradient method to obtain near optimal solutions quickly. Testing results show that the algorithm produces good sale offers efficiently.« less

Optimization-based sale transactions and hydrothermal scheduling

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

Prasannan, B.; Luh, P.B.; Yan, H.

1996-05-01

Selling and purchasing power are important activities for utilities because of potential savings. When a selling utility presents an offer including prices, power levels and durations, a purchasing utility selects power levels and durations within the offered range subject to relevant constraints. The decisionmaking process is complicated because transactions are coupled with system demand and reserve, therefore decisions have to be made in conjunction with the commitment and dispatching of units. Furthermore, transaction decisions have to be made in almost real time in view of the competitiveness of the power market caused by deregulation. In this paper, transactions are analyzedmore » from a selling utility`s viewpoint for a system consisting of thermal, hydro and pumped-storage units. To effectively solve the problem, linear sale revenues are approximated by nonlinear functions, and non-profitable options are identified and eliminated from consideration. The multipliers are then updated at the high level by using a modified subgradient method to obtain near optimal solutions quickly. Testing results show that the algorithm produces good sale offers efficiently.« less

Increasing Health Portal Utilization in Cardiac Ambulatory Patients: A Pilot Project.

PubMed

Shaw, Carmen L; Casterline, Gayle L; Taylor, Dennis; Fogle, Maureen; Granger, Bradi

2017-10-01

Increasing health portal participation actively engages patients in their care and improves outcomes. The primary aim for this project was to increase patient health portal utilization. Nurses used a tablet-based demo to teach patients how to navigate the health portal. Assigning health videos to the portal was a tactic used to increase utilization. Each patient participant was surveyed about health portal utilization at initial nurse navigator appointment, day of procedure, and 30 days after discharge. Seventy-three percent (n = 14) of the 19 selected patients received the intervention; 36% (n = 4) of patients reported using a health portal feature; meaningful use metric preintervention increased from 12% to 16% after the intervention; 16% and 18% of patients viewed assigned videos in their health portal prior to procedure and after hospital discharge. Patients need a reason to access their health portal. Education alone is not enough to motivate patient portal use. Further research is needed to specify what tactics are required to motivate patients to use their health portals.

NASA Space Engineering Research Center for utilization of local planetary resources

NASA Technical Reports Server (NTRS)

1992-01-01

In 1987, responding to widespread concern about America's competitiveness and future in the development of space technology and the academic preparation of our next generation of space professionals, NASA initiated a program to establish Space Engineering Research Centers (SERC's) at universities with strong doctoral programs in engineering. The goal was to create a national infrastructure for space exploration and development, and sites for the Centers would be selected on the basis of originality of proposed research, the potential for near-term utilization of technologies developed, and the impact these technologies could have on the U.S. space program. The Centers would also be charged with a major academic mission: the recruitment of topnotch students and their training as space professionals. This document describes the goals, accomplishments, and benefits of the research activities of the University of Arizona/NASA SERC. This SERC has become recognized as the premier center in the area known as In-Situ Resource Utilization or Indigenous Space Materials Utilization.

A discrete event modelling framework for simulation of long-term outcomes of sequential treatment strategies for ankylosing spondylitis.

PubMed

Tran-Duy, An; Boonen, Annelies; van de Laar, Mart A F J; Franke, Angelinus C; Severens, Johan L

2011-12-01

To develop a modelling framework which can simulate long-term quality of life, societal costs and cost-effectiveness as affected by sequential drug treatment strategies for ankylosing spondylitis (AS). Discrete event simulation paradigm was selected for model development. Drug efficacy was modelled as changes in disease activity (Bath Ankylosing Spondylitis Disease Activity Index (BASDAI)) and functional status (Bath Ankylosing Spondylitis Functional Index (BASFI)), which were linked to costs and health utility using statistical models fitted based on an observational AS cohort. Published clinical data were used to estimate drug efficacy and time to events. Two strategies were compared: (1) five available non-steroidal anti-inflammatory drugs (strategy 1) and (2) same as strategy 1 plus two tumour necrosis factor α inhibitors (strategy 2). 13,000 patients were followed up individually until death. For probability sensitivity analysis, Monte Carlo simulations were performed with 1000 sets of parameters sampled from the appropriate probability distributions. The models successfully generated valid data on treatments, BASDAI, BASFI, utility, quality-adjusted life years (QALYs) and costs at time points with intervals of 1-3 months during the simulation length of 70 years. Incremental cost per QALY gained in strategy 2 compared with strategy 1 was €35,186. At a willingness-to-pay threshold of €80,000, it was 99.9% certain that strategy 2 was cost-effective. The modelling framework provides great flexibility to implement complex algorithms representing treatment selection, disease progression and changes in costs and utilities over time of patients with AS. Results obtained from the simulation are plausible.

Selective Hydrogen Atom Abstraction through Induced Bond Polarization: Direct α-Arylation of Alcohols through Photoredox, HAT, and Nickel Catalysis.

PubMed

Twilton, Jack; Christensen, Melodie; DiRocco, Daniel A; Ruck, Rebecca T; Davies, Ian W; MacMillan, David W C

2018-05-04

The combination of nickel metallaphotoredox catalysis, hydrogen atom transfer catalysis, and a Lewis acid activation mode, has led to the development of an arylation method for the selective functionalization of alcohol α-hydroxy C-H bonds. This approach employs zinc-mediated alcohol deprotonation to activate α-hydroxy C-H bonds while simultaneously suppressing C-O bond formation by inhibiting the formation of nickel alkoxide species. The use of Zn-based Lewis acids also deactivates other hydridic bonds such as α-amino and α-oxy C-H bonds. This approach facilitates rapid access to benzylic alcohols, an important motif in drug discovery. A 3-step synthesis of the drug Prozac exemplifies the utility of this new method. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Analysis of differential secondary effects of novel rexinoids: select rexinoid X receptor ligands demonstrate differentiated side effect profiles

PubMed Central

Marshall, Pamela A; Jurutka, Peter W; Wagner, Carl E; van der Vaart, Arjan; Kaneko, Ichiro; Chavez, Pedro I; Ma, Ning; Bhogal, Jaskaran S; Shahani, Pritika; Swierski, Johnathon C; MacNeill, Mairi

2015-01-01

In order to determine the feasibility of utilizing novel rexinoids for chemotherapeutics and as potential treatments for neurological conditions, we undertook an assessment of the side effect profile of select rexinoid X receptor (RXR) analogs that we reported previously. We assessed pharmacokinetic profiles, lipid and thyroid-stimulating hormone (TSH) levels in rats, and cell culture activity of rexinoids in sterol regulatory element-binding protein (SREBP) induction and thyroid hormone inhibition assays. We also performed RNA sequencing of the brain tissues of rats that had been dosed with the compounds. We show here for the first time that potent rexinoid activity can be uncoupled from drastic lipid changes and thyroid axis variations, and we propose that rexinoids can be developed with improved side effect profiles than the parent compound, bexarotene (1). PMID:26038698

Identification of Uncultured Bacterial Species from Firmicutes, Bacteroidetes and CANDIDATUS Saccharibacteria as Candidate Cellulose Utilizers from the Rumen of Beef Cows

PubMed Central

Opdahl, Lee James; Gonda, Michael G.

2018-01-01

The ability of ruminants to utilize cellulosic biomass is a result of the metabolic activities of symbiotic microbial communities that reside in the rumen. To gain further insight into this complex microbial ecosystem, a selection-based batch culturing approach was used to identify candidate cellulose-utilizing bacterial consortia. Prior to culturing with cellulose, rumen contents sampled from three beef cows maintained on a forage diet shared 252 Operational Taxonomic Units (OTUs), accounting for 41.6–50.0% of bacterial 16S rRNA gene sequences in their respective samples. Despite this high level of overlap, only one OTU was enriched in cellulose-supplemented cultures from all rumen samples. Otherwise, each set of replicate cellulose supplemented cultures originating from a sampled rumen environment was found to have a distinct bacterial composition. Two of the seven most enriched OTUs were closely matched to well-established rumen cellulose utilizers (Ruminococcus flavefaciens and Fibrobacter succinogenes), while the others did not show high nucleotide sequence identity to currently defined bacterial species. The latter were affiliated to Prevotella (1 OTU), Ruminococcaceae (3 OTUs), and the candidate phylum Saccharibacteria (1 OTU), respectively. While further investigations will be necessary to elucidate the metabolic function(s) of each enriched OTU, these results together further support cellulose utilization as a ruminal metabolic trait shared across vast phylogenetic distances, and that the rumen is an environment conducive to the selection of a broad range of microbial adaptations for the digestion of plant structural polysaccharides. PMID:29495256

Identification of Uncultured Bacterial Species from Firmicutes, Bacteroidetes and CANDIDATUS Saccharibacteria as Candidate Cellulose Utilizers from the Rumen of Beef Cows.

PubMed

Opdahl, Lee James; Gonda, Michael G; St-Pierre, Benoit

2018-02-24

The ability of ruminants to utilize cellulosic biomass is a result of the metabolic activities of symbiotic microbial communities that reside in the rumen. To gain further insight into this complex microbial ecosystem, a selection-based batch culturing approach was used to identify candidate cellulose-utilizing bacterial consortia. Prior to culturing with cellulose, rumen contents sampled from three beef cows maintained on a forage diet shared 252 Operational Taxonomic Units (OTUs), accounting for 41.6-50.0% of bacterial 16S rRNA gene sequences in their respective samples. Despite this high level of overlap, only one OTU was enriched in cellulose-supplemented cultures from all rumen samples. Otherwise, each set of replicate cellulose supplemented cultures originating from a sampled rumen environment was found to have a distinct bacterial composition. Two of the seven most enriched OTUs were closely matched to well-established rumen cellulose utilizers ( Ruminococcus flavefaciens and Fibrobacter succinogenes ), while the others did not show high nucleotide sequence identity to currently defined bacterial species. The latter were affiliated to Prevotella (1 OTU), Ruminococcaceae (3 OTUs), and the candidate phylum Saccharibacteria (1 OTU), respectively. While further investigations will be necessary to elucidate the metabolic function(s) of each enriched OTU, these results together further support cellulose utilization as a ruminal metabolic trait shared across vast phylogenetic distances, and that the rumen is an environment conducive to the selection of a broad range of microbial adaptations for the digestion of plant structural polysaccharides.

Design study of wind turbines 50 kW to 3000 kW for electric utility applications: Analysis and design

NASA Technical Reports Server (NTRS)

1976-01-01

In the conceptual design task, several feasible wind generator systems (WGS) configurations were evaluated, and the concept offering the lowest energy cost potential and minimum technical risk for utility applications was selected. In the optimization task, the selected concept was optimized utilizing a parametric computer program prepared for this purpose. In the preliminary design task, the optimized selected concept was designed and analyzed in detail. The utility requirements evaluation task examined the economic, operational, and institutional factors affecting the WGS in a utility environment, and provided additional guidance for the preliminary design effort. Results of the conceptual design task indicated that a rotor operating at constant speed, driving an AC generator through a gear transmission is the most cost effective WGS configuration. The optimization task results led to the selection of a 500 kW rating for the low power WGS and a 1500 kW rating for the high power WGS.

The practical operational-amplifier gyrator circuit for inductorless filter synthesis

NASA Technical Reports Server (NTRS)

Sutherland, W. C.

1976-01-01

A literature is reported for gyrator circuits utilizing operational amplifiers as the active device. A gyrator is a two port nonreciprocal device with the property that the input impedance is proportional to the reciprocal of the load impedance. Following an experimental study, the gyrator circuit with optimum properties was selected for additional testing. A theoretical analysis was performed and compared to the experimental results for excellent agreement.

Satellite remote sensing of the ocean

NASA Technical Reports Server (NTRS)

Fu, Lee-Lueng; Liu, W. T.; Abbott, Mark R.

1990-01-01

A concise description of the principles and applications of several selected instruments that have been utilized most frequently in remote sensing of the ocean from satellites is presented. Emphasis is placed on the current progress in oceanographic applications and the outlook of the instruments in future oceanographic satellite missions is discussed. The instruments under discussion are placed into three groups: active microwave sensors, passive ocean color and infrared sensors, and passive microwave sensors.

Dimensions of flow during an experiential wilderness science program

NASA Astrophysics Data System (ADS)

Wang, Robert

Over the past twenty-five years, there has been an alarming decline in academic performance among American students. This trend is seen in failing test scores, poor attendance, and low first-year retention rates at post-secondary institutions. There have been numerous studies that have examined this issue but few to offer solutions. Mihalyi Csikszentmihalyi, the originator of flow theory, suggests that poor academic performance might be best explained in terms of lack of student motivation and engagement (flow) rather than a lack of cognitive abilities. This study was designed to examine a series of activities conducted during an Experiential Wilderness Science Program at a college located in the Rocky Mountain region. Specifically, this study measured student engagement for each activity and described the dimensions (phenomenological, instructional, etc.) that were present when there was a high frequency of engagement among program participants. A combined quantitative and qualitative research methodology was utilized. The Experience Sampling Form (ESF) was administered to 41 freshman students participating in a 3-day wilderness science program to measure the frequency of engagement (flow) for nine different activities. A qualitative investigation using journals, participant interviews, and focus groups was used to describe the dimensions that were present when a high frequency of engagement among program participants was observed. Results revealed that engagement (flow) was highest during two challenge education activities and during a river sampling activity. Dimensions common among these activities included: an environment dimension, a motivation dimension, and an instruction dimension. The environment dimension included: incorporating novel learning activities, creating student interests, and introducing an element of perceived risk. The motivation dimension included: developing internal loci of control, facilitating high levels of self-efficacy, and developing intrinsic and extrinsic motivation. The instructional dimension included: selecting appropriate subject matter, using proper instructional methods, utilizing appropriate activity levels, and selecting proper goals.

Effects of activity, genetic selection and their interaction on muscle metabolic capacities and organ masses in mice.

PubMed

Kelly, Scott A; Gomes, Fernando R; Kolb, Erik M; Malisch, Jessica L; Garland, Theodore

2017-03-15

Chronic voluntary exercise elevates total daily energy expenditure and food consumption, potentially resulting in organ compensation supporting nutrient extraction/utilization. Additionally, species with naturally higher daily energy expenditure often have larger processing organs, which may represent genetic differences and/or phenotypic plasticity. We tested for possible adaptive changes in organ masses of four replicate lines of house mice selected (37 generations) for high running (HR) compared with four non-selected control (C) lines. Females were housed with or without wheel access for 13-14 weeks beginning at 53-60 days of age. In addition to organ compensation, chronic activity may also require an elevated aerobic capacity. Therefore, we also measured hematocrit and both citrate synthase activity and myoglobin concentration in heart and gastrocnemius. Both selection (HR versus C) and activity (wheels versus no wheels) significantly affected morphological and biochemical traits. For example, with body mass as a covariate, mice from HR lines had significantly higher hematocrit and larger ventricles, with more myoglobin. Wheel access lengthened the small intestine, increased relative ventricle and kidney size, and increased skeletal muscle citrate synthase activity and myoglobin concentration. As compared with C lines, HR mice had greater training effects for ventricle mass, hematocrit, large intestine length and gastrocnemius citrate synthase activity. For ventricle and gastrocnemius citrate synthase activity, the greater training was quantitatively explainable as a result of greater wheel running (i.e. 'more pain, more gain'). For hematocrit and large intestine length, differences were not related to amount of wheel running and instead indicate inherently greater adaptive plasticity in HR lines. © 2017. Published by The Company of Biologists Ltd.

3D-Pharmacophore Identification for κ-Opioid Agonists Using Ligand-Based Drug-Design Techniques

NASA Astrophysics Data System (ADS)

Yamaotsu, Noriyuki; Hirono, Shuichi

A selective κ-opioid receptor (KOR) agonist might act as a powerful analgesic without the side effects of μ-opioid receptor-selective drugs such as morphine. The eight classes of known KOR agonists have different chemical structures, making it difficult to construct a pharmacophore model that takes them all into account. Here, we summarize previous efforts to identify the pharmacophore for κ-opioid agonists and propose a new three-dimensional pharmacophore model that encompasses the κ-activities of all classes. This utilizes conformational sampling of agonists by high-temperature molecular dynamics and pharmacophore extraction through a series of molecular superpositions.

Method For Selective Catalytic Reduction Of Nitrogen Oxides

DOEpatents

Mowery-Evans, Deborah L.; Gardner, Timothy J.; McLaughlin, Linda I.

2005-02-15

A method for catalytically reducing nitrogen oxide compounds (NO.sub.x, defined as nitric oxide, NO, +nitrogen dioxide, NO.sub.2) in a gas by a material comprising a base metal consisting essentially of CuO and Mn, and oxides of Mn, on an activated metal hydrous metal oxide support, such as HMO:Si. A promoter, such as tungsten oxide or molybdenum oxide, can be added and has been shown to increase conversion efficiency. This method provides good conversion of NO.sub.x to N.sub.2, good selectivity, good durability, resistance to SO.sub.2 aging and low toxicity compared with methods utilizing vanadia-based catalysts.

Method for selective catalytic reduction of nitrogen oxides

DOEpatents

Mowery-Evans, Deborah L [Broomfield, CO; Gardner, Timothy J [Albuquerque, NM; McLaughlin, Linda I [Albuquerque, NM

2005-02-15

A method for catalytically reducing nitrogen oxide compounds (NO.sub.x, defined as nitric oxide, NO, +nitrogen dioxide, NO.sub.2) in a gas by a material comprising a base metal consisting essentially of CuO and Mn, and oxides of Mn, on an activated metal hydrous metal oxide support, such as HMO:Si. A promoter, such as tungsten oxide or molybdenum oxide, can be added and has been shown to increase conversion efficiency. This method provides good conversion of NO.sub.x to N.sub.2, good selectivity, good durability, resistance to SO.sub.2 aging and low toxicity compared with methods utilizing vanadia-based catalysts.

Color flat panel display for the Bradley Fighting Vehicle

NASA Astrophysics Data System (ADS)

Prince, J. Colin; Martin, A. J.

1996-05-01

The modernization program for the Bradley Fighting Vehicle, M2 A3, represents the first deployment of an active matrix liquid crystal display, AMLCD, in a military ground vehicle. In many respects the selection of AMLCD was determined according to the familiar metrics which have resulted in AMLCD being broadly selected for modern air vehicle installations. In fact, there is considerable similarities between the Bradley AMLCD and its recent forbearers in the avionic industry. In the Bradley, the AMLCD unit is referred to as a color flat panel display, CFPD and the features of this unit, as well as its environment and utilization are described in this paper.

Superfund explanation of significant difference for the Record of Decision (EPA Region 10): Umatilla Army Depot (Lagoons), Hermiston, OR, September 30, 1997

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

NONE

1998-10-01

This document presents an Explanation of Significant Difference (ESD) from the Record of Decision (ROD) for the Umatilla Depot Activity (UMDA) Explosives Washout Lagoons Soils Operable Unit issued September 25, 1992 (PB93-964610). This ESD documents the significant differences to the selected remedy outlined in the ROD. In summary, the significant difference from the selected remedy in the ROD is the utilization of the treated soil as the organic component in the re-vegetation of several designated sites on the installation rather than backfilling the former Explosive Washout Lagoons with the compost.

Prediction and selection of vocabulary for two leisure activities.

PubMed

Dark, Leigha; Balandin, Susan

2007-01-01

People who use augmentative or alternative communication (AAC) need access to a relevant, socially valid vocabulary if they are to communicate successfully in a variety of contexts. Many people with complex communication needs who utilize some form of high technology or low technology AAC rely on others to predict and select vocabulary for them. In this study the ability of one speech pathologist, nine leisure support workers, and six people with cerebral palsy to accurately predict context-specific vocabulary was explored. Participants predicted vocabulary for two leisure activities - sailing session and Internet café - using the blank page method of vocabulary selection to identify the vocabulary items they considered important for each activity. This predicted vocabulary was then compared with the actual vocabulary used in each of the activities. A total of 187 (68%) of the words predicted for the sailing session were used during recorded conversations, with 88 words (32%) not appearing in the recorded samples. During the visit to the Internet café only 104 (47%) of the words predicted occurred in the recorded samples, with 117 words (53%) not occurring at all. These results support the need to socially validate any vocabulary in order to ensure that it is relevant and useful for the person using the AAC system.

Visualization of proteolytic activity associated with the apoptotic response in cancer cells

NASA Astrophysics Data System (ADS)

Tice, Brian George

Caspases execute programmed cell death, where low levels of caspase activity are linked to cancer. Chemotherapies utilize induction of apoptosis as a key mechanism for cancer treatment, where caspase-3 is a major player involved in dismantling these aberrant cells. The ability to sensitively measure the initial caspase-3 cleavage events during apoptosis is important for understanding the initiation of this complex cellular process, however, current ensemble methods are not sensitive enough to measure single cleavage events in cells. By utilizing the optical properties of plasmon coupling, peptide-linked gold nanoparticles were developed to enable single molecule imaging of caspase-3 activity in two different cancer systems. Au crown nanoparticles were assembled in a multimeric fashion to overcome the high and heterogeneous background scattering of live cells. In a colon cancer (SW620) cell line challenged with tumor necrosis factor-alpha (TNF-alpha), single molecule trajectories show early stage caspase-3 activation within minutes, which was not detectable by ensemble assays until 23 hours. Variability in caspase-3 activation among the population of cells was identified and likely a result of each cell's specific resistance to death receptor-induced apoptosis. Following these studies, improvements by way of sensitivity and selectivity were tailored into an improved nanosensor construct. Au nanoshell dimers were prepared as a comparably bright construct with 1) reduced heterogeneity compared to the synthesis of the crown nanoparticles and 2) a peptide sequence highly selective for caspase-3. Chronic myeloid leukemia (CML) K562 cells were assessed for their early apoptotic response upon treatment with dasatinib, a clinically approved tyrosine kinase inhibitor that specifically targets BCR-ABL. It has been demonstrated that inhibition of BCR-ABL by dasatinib commits K562 cells to apoptosis. Single molecule experiments with Au nanoshell dimers show caspase-3 activation as early as 8 hours than previously reported. This suggests an early commitment to apoptosis that precedes the competing fate of growth factor mediated survival in CML patient-derived BCR-ABL cells. These nanosensors are sensitive and selective in observing caspase-3 activation compared to ensemble methods; and allow the possibility to detect caspase-3 activity for use as a drug screening or diagnostic tool for personalized care in the treatment of cancer.

The impact of persistent visually disabling vitreous floaters on health status utility values.

PubMed

Zou, Haidong; Liu, Haiyun; Xu, Xun; Zhang, Xi

2013-08-01

To assess the time trade-off (TTO) utility values in patients with persistent visually disabling vitreous floaters (DVF) and to determine the reliability and validity of TTO methods in DVF patients. Prospective cross-sectional questionnaire survey: Eligible patients with persistent DVF referred to the Shanghai First People's Hospital outpatient service between January 2006 and February 2010, and randomly selected normal vision general population residents, were enrolled. All participants underwent TTO utility value evaluation. After 4-5 weeks, the patients were asked to undergo second TTO utility value evaluation during the follow-up interview. The mean initial utility values of the 107 persistent DVF patients were 0.904 ± 0.054. Regression analyses revealed that length of education, visual acuity in the poorer-vision eye and employment status were associated with utility values (all P < 0.01). All patients took part in the follow-up interview; the intra-class correlation coefficient for TTO utility values at the initial and follow-up interviews was 0.855. In the 91 general population residents, the mean utility value was 0.923 ± 0.032, which was statistically higher than that of active study patients (t = 3.01, P < 0.01). Persistent DVF can substantially diminish the patients' perception of their life, and can be measured by TTO utility values with high reliability and construct validity.

Functionalized active-nucleus complex sensor

DOEpatents

Pines, Alexander; Wemmer, David E.; Spence, Megan; Rubin, Seth

2003-11-25

A functionalized active-nucleus complex sensor that selectively associates with one or more target species, and a method for assaying and screening for one or a plurality of target species utilizing one or a plurality of functionalized active-nucleus complexes with at least two of the functionalized active-nucleus complexes having an attraction affinity to different corresponding target species. The functionalized active-nucleus complex has an active-nucleus and a targeting carrier. The method involves functionalizing an active-nucleus, for each functionalized active-nucleus complex, by incorporating the active-nucleus into a macromolucular or molecular complex that is capable of binding one of the target species and then bringing the macromolecular or molecular complexes into contact with the target species and detecting the occurrence of or change in a nuclear magnetic resonance signal from each of the active-nuclei in each of the functionalized active-nucleus complexes.

Active link selection for efficient semi-supervised community detection

NASA Astrophysics Data System (ADS)

Yang, Liang; Jin, Di; Wang, Xiao; Cao, Xiaochun

2015-03-01

Several semi-supervised community detection algorithms have been proposed recently to improve the performance of traditional topology-based methods. However, most of them focus on how to integrate supervised information with topology information; few of them pay attention to which information is critical for performance improvement. This leads to large amounts of demand for supervised information, which is expensive or difficult to obtain in most fields. For this problem we propose an active link selection framework, that is we actively select the most uncertain and informative links for human labeling for the efficient utilization of the supervised information. We also disconnect the most likely inter-community edges to further improve the efficiency. Our main idea is that, by connecting uncertain nodes to their community hubs and disconnecting the inter-community edges, one can sharpen the block structure of adjacency matrix more efficiently than randomly labeling links as the existing methods did. Experiments on both synthetic and real networks demonstrate that our new approach significantly outperforms the existing methods in terms of the efficiency of using supervised information. It needs ~13% of the supervised information to achieve a performance similar to that of the original semi-supervised approaches.

Active link selection for efficient semi-supervised community detection

PubMed Central

Yang, Liang; Jin, Di; Wang, Xiao; Cao, Xiaochun

2015-01-01

Several semi-supervised community detection algorithms have been proposed recently to improve the performance of traditional topology-based methods. However, most of them focus on how to integrate supervised information with topology information; few of them pay attention to which information is critical for performance improvement. This leads to large amounts of demand for supervised information, which is expensive or difficult to obtain in most fields. For this problem we propose an active link selection framework, that is we actively select the most uncertain and informative links for human labeling for the efficient utilization of the supervised information. We also disconnect the most likely inter-community edges to further improve the efficiency. Our main idea is that, by connecting uncertain nodes to their community hubs and disconnecting the inter-community edges, one can sharpen the block structure of adjacency matrix more efficiently than randomly labeling links as the existing methods did. Experiments on both synthetic and real networks demonstrate that our new approach significantly outperforms the existing methods in terms of the efficiency of using supervised information. It needs ~13% of the supervised information to achieve a performance similar to that of the original semi-supervised approaches. PMID:25761385

Utilization of healthcare services and renewal of health insurance membership: evidence of adverse selection in Ghana.

PubMed

Duku, Stephen Kwasi Opoku; Asenso-Boadi, Francis; Nketiah-Amponsah, Edward; Arhinful, Daniel Kojo

2016-12-01

Utilization of healthcare in Ghana's novel National Health Insurance Scheme (NHIS) has been increasing since inception with associated high claims bill which threatens the scheme's financial sustainability. This paper investigates the presence of adverse selection by assessing the effect of healthcare utilization and frequency of use on NHIS renewal. Routine enrolment and utilization data from 2008 to 2013 in two regions in Ghana was analyzed. Pearson Chi-square test was performed to test if the proportion of insured who utilize healthcare in a particular year and renew membership the following year is significantly different from those who utilize healthcare and drop-out. Logistic regressions were estimated to examine the relationship between healthcare utilization and frequency of use in previous year and NHIS renewal in current year. We found evidence suggestive of the presence of adverse selection in the NHIS. Majority of insured who utilized healthcare renewed their membership whiles most of those who did not utilize healthcare dropped out. The likelihood of renewal was significantly higher for those who utilize healthcare than those who did not and also higher for those who make more health facility visits. The NHIS claims bill is high because high risk individuals who self-select into the scheme makes more health facility visits and creates financial sustainability problems. Policy makers should adopt pragmatic ways of enforcing mandatory enrolment so that low risk individuals remain enrolled; and sustainable ways of increasing revenue whiles ensuring that the societal objectives of the scheme are not compromised.

Rhodium-Catalyzed C-C Bond Formation via Heteroatom-Directed C-H Bond Activation

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

Colby, Denise; Bergman, Robert; Ellman, Jonathan

2010-05-13

Once considered the 'holy grail' of organometallic chemistry, synthetically useful reactions employing C-H bond activation have increasingly been developed and applied to natural product and drug synthesis over the past decade. The ubiquity and relative low cost of hydrocarbons makes C-H bond functionalization an attractive alternative to classical C-C bond forming reactions such as cross-coupling, which require organohalides and organometallic reagents. In addition to providing an atom economical alternative to standard cross - coupling strategies, C-H bond functionalization also reduces the production of toxic by-products, thereby contributing to the growing field of reactions with decreased environmental impact. In the areamore » of C-C bond forming reactions that proceed via a C-H activation mechanism, rhodium catalysts stand out for their functional group tolerance and wide range of synthetic utility. Over the course of the last decade, many Rh-catalyzed methods for heteroatom-directed C-H bond functionalization have been reported and will be the focus of this review. Material appearing in the literature prior to 2001 has been reviewed previously and will only be introduced as background when necessary. The synthesis of complex molecules from relatively simple precursors has long been a goal for many organic chemists. The ability to selectively functionalize a molecule with minimal pre-activation can streamline syntheses and expand the opportunities to explore the utility of complex molecules in areas ranging from the pharmaceutical industry to materials science. Indeed, the issue of selectivity is paramount in the development of all C-H bond functionalization methods. Several groups have developed elegant approaches towards achieving selectivity in molecules that possess many sterically and electronically similar C-H bonds. Many of these approaches are discussed in detail in the accompanying articles in this special issue of Chemical Reviews. One approach that has seen widespread success involves the use of a proximal heteroatom that serves as a directing group for the selective functionalization of a specific C-H bond. In a survey of examples of heteroatom-directed Rh catalysis, two mechanistically distinct reaction pathways are revealed. In one case, the heteroatom acts as a chelator to bind the Rh catalyst, facilitating reactivity at a proximal site. In this case, the formation of a five-membered metallacycle provides a favorable driving force in inducing reactivity at the desired location. In the other case, the heteroatom initially coordinates the Rh catalyst and then acts to stabilize the formation of a metal-carbon bond at a proximal site. A true test of the utility of a synthetic method is in its application to the synthesis of natural products or complex molecules. Several groups have demonstrated the applicability of C-H bond functionalization reactions towards complex molecule synthesis. Target-oriented synthesis provides a platform to test the effectiveness of a method in unique chemical and steric environments. In this respect, Rh-catalyzed methods for C-H bond functionalization stand out, with several syntheses being described in the literature that utilize C-H bond functionalization in a key step. These syntheses are highlighted following the discussion of the method they employ.« less

Mimicking Heme Enzymes in the Solid State: Metal-Organic Materials with Selectively Encapsulated Heme

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

Larsen, Randy W; Wojtas, Lukasz; Perman, Jason

2011-06-13

To carry out essential life processes, nature has had to evolve heme enzymes capable of synthesizing and manipulating complex molecules. These proteins perform a plethora of chemical reactions utilizing a single iron porphyrin active site embedded within an evolutionarily designed protein pocket. We herein report the first class of metal–organic materials (MOMs) that mimic heme enzymes in terms of both structure and reactivity. The MOMzyme-1 class is based upon a prototypal MOM, HKUST-1, into which catalytically active metalloporphyrins are selectively encapsulated in a “ship-in-a-bottle” fashion within one of the three nanoscale cages that exist in HKUST-1. MOMs offer unparalleled levelsmore » of permanent porosity and their modular nature affords enormous diversity of structures and properties. The MOMzyme-1 class could therefore represent a new paradigm for heme biomimetic catalysis since it combines the activity of a homogeneous catalyst with the stability and recyclability of heterogeneous catalytic systems within a single material.« less

Potential Application of NASA Aerospace Technology to Ground-Based Power System

NASA Technical Reports Server (NTRS)

Povinelli, Louis A.; Welch, Gerard E.; Bakhle, Milind A.; Brown, Gerald V.

2000-01-01

A review of some of the basic gas turbine technology being developed at the NASA John H. Glenn Research Center at Lewis Field, which may have the potential to be applied to ground-based systems, is presented in this paper. Only a sampling of the large number of research activities underway at the Glenn Research Center can be represented here. The items selected for presentation are those that may lead to increased power and efficiency, reduced cycle design time and cost, improved thermal design, reduced fatigue and fracture, reduced mechanical friction and increased operating margin. The topic of improved material will be presented in this conference and shall not be discussed here. The topics selected for presentation are key research activities at the Glenn Center of Excellence on Turbo-machinery. These activities should be of interest and utility to this ISABE (International Symposium on Air Breathing Engines) Special Forum on Aero-Derivative Land-Based Gas Turbines and to the power industry.

Mimicking heme enzymes in the solid state: metal-organic materials with selectively encapsulated heme.

PubMed

Larsen, Randy W; Wojtas, Lukasz; Perman, Jason; Musselman, Ronald L; Zaworotko, Michael J; Vetromile, Carissa M

2011-07-13

To carry out essential life processes, nature has had to evolve heme enzymes capable of synthesizing and manipulating complex molecules. These proteins perform a plethora of chemical reactions utilizing a single iron porphyrin active site embedded within an evolutionarily designed protein pocket. We herein report the first class of metal-organic materials (MOMs) that mimic heme enzymes in terms of both structure and reactivity. The MOMzyme-1 class is based upon a prototypal MOM, HKUST-1, into which catalytically active metalloporphyrins are selectively encapsulated in a "ship-in-a-bottle" fashion within one of the three nanoscale cages that exist in HKUST-1. MOMs offer unparalleled levels of permanent porosity and their modular nature affords enormous diversity of structures and properties. The MOMzyme-1 class could therefore represent a new paradigm for heme biomimetic catalysis since it combines the activity of a homogeneous catalyst with the stability and recyclability of heterogeneous catalytic systems within a single material.

Novel series of potent, nonsteroidal, selective androgen receptor modulators based on 7H-[1,4]oxazino[3,2-g]quinolin-7-ones.

PubMed

Higuchi, Robert I; Arienti, Kristen L; López, Francisco J; Mani, Neelakhanda S; Mais, Dale E; Caferro, Thomas R; Long, Yun Oliver; Jones, Todd K; Edwards, James P; Zhi, Lin; Schrader, William T; Negro-Vilar, Andrés; Marschke, Keith B

2007-05-17

Recent interest in orally available androgens has fueled the search for new androgens for use in hormone replacement therapy and as anabolic agents. In pursuit of this, we have discovered a series of novel androgen receptor modulators derived from 7H-[1,4]oxazino[3,2-g]quinolin-7-ones. These compounds were synthesized and evaluated in competitive binding assays and an androgen receptor transcriptional activation assay. A number of compounds from the series demonstrated single-digit nanomolar agonist activity in vitro. In addition, lead compound (R)-16e was orally active in established rodent models that measure androgenic and anabolic properties of these agents. In this assay, (R)-16e demonstrated full efficacy in muscle and only partially stimulated the prostate at 100 mg/kg. These data suggest that these compounds may be utilized as selective androgen receptor modulators or SARMs. This series represents a novel class of compounds for use in androgen replacement therapy.

An assessment of schoolyard renovation strategies to encourage children's physical activity

PubMed Central

2011-01-01

Background Children in poor and minority neighborhoods often lack adequate environmental support for healthy physical development and community interventions designed to improve physical activity resources serve as an important approach to addressing obesity. In Denver, the Learning Landscapes (LL) program has constructed over 98 culturally-tailored schoolyard play spaces at elementary schools with the goal to encourage utilization of play spaces and physical activity. In spite of enthusiasm about such projects to improve urban environments, little work has evaluated their impact or success in achieving their stated objectives. This study evaluates the impacts of LL construction and recency of renovation on schoolyard utilization and the physical activity rates of children, both during and outside of school, using an observational study design. Methods This study employs a quantitative method for evaluating levels of physical activity of individuals and associated environmental characteristics in play and leisure environments. Schools were selected on the basis of their participation in the LL program, the recency of schoolyard renovation, the size of the school, and the social and demographic characteristics of the school population. Activity in the schoolyards was measured using the System for Observing Play and Leisure Activity (SOPLAY), a validated quantitative method for evaluating levels of physical activity of individuals in play and leisure environments. Trained observers collected measurements before school, during school recess, after school, and on weekends. Overall utilization (the total number of children observed on the grounds) and the rate of activity (the percentage of children observed who were physically active) were analyzed. Observations were compared using t-tests and the data were stratified by gender for further analysis. In order to assess the impacts of LL renovation, recently-constructed LL schoolyards were compared to LL schoolyards with older construction, as well as un-renovated schoolyards. Results Overall utilization was significantly higher at LL schools than at un-renovated schools for most observation periods. Notably, LL renovation had no impact on girl's utilization on the weekends, although differences were observed for all other periods. There were no differences in rates of activity for any comparison. With the exception of the number of boys observed, there was no statistically significant difference in activity when recently-constructed LL schools are compared to LL schools with older construction dates and there was no difference observed in comparisons of older LL with unrenovated sites. Conclusions While we observed greater utilization and physical activity in schools with LL, the impact of specific features of LL renovation is not clear. However, schoolyard renovation and programs to encourage schoolyard use before and after school may offer a means to encourage greater physical activity among children, and girls in particular. Additional study of schoolyard renovation may shed light on the specific reasons for these findings or suggest effective policies to improve the physical activity resources of poor and minority neighborhoods. PMID:21477325

Beyond diagnoses: family medicine core themes in student reflective writing.

PubMed

Bradner, Melissa K; Crossman, Steven H; Gary, Judy; Vanderbilt, Allison A; VanderWielen, Lynn

2015-03-01

We share qualitative study results of third-year medical student writings during their family medicine clerkship utilizing a reflective writing exercise from 2005 and 2013. For this paper, 50 student writings were randomly selected from the 2005 cohort in addition to 50 student writings completed by the 2013 cohort. Deductive thematic analysis utilizing Atlas.ti software was completed utilizing the Future of Family Medicine core attributes of family physicians as the a priori coding template. Student writings actively reflect key attributes of family physicians as described by the Future of Family Medicine Report: a deep understanding of the dynamics of the whole person, a generative impact on patients' lives, a talent for humanizing the health care experience, and a natural command of complexity and multidimensional access to care. We discuss how to lead the writing exercise and provide suggestions for facilitating the discussion to bring out these important aspects of family medicine care.

25 CFR 1000.69 - How can a Tribe/Consortium obtain comments or selection documents received or utilized after OSG...

Code of Federal Regulations, 2010 CFR

2010-04-01

...-DETERMINATION AND EDUCATION ACT Other Financial Assistance for Planning and Negotiation Grants for Non-BIA... documents received or utilized after OSG has made a decision on a planning grant application? 1000.69... selection documents received or utilized after OSG has made a decision on a planning grant application? A...

Utilization of Selected Vitality Staple Foods by Low Income Households in Ebonyi State

ERIC Educational Resources Information Center

Igba, Chimezie Elizabeth; Okoro, M. O.

2015-01-01

The study focused on the utilization of selected vitality foods among low income household in Ebonyi State. Specifically the study aimed at identifying vitality foods that are available, accessible and utilized by low income household in state. Descriptive survey design was used for the study. The population of the study is 2,173,501 households…

Selection, application, and validation of a set of molecular descriptors for nuclear receptor ligands.

PubMed

Stewart, Eugene L; Brown, Peter J; Bentley, James A; Willson, Timothy M

2004-08-01

A methodology for the selection and validation of nuclear receptor ligand chemical descriptors is described. After descriptors for a targeted chemical space were selected, a virtual screening methodology utilizing this space was formulated for the identification of potential NR ligands from our corporate collection. Using simple descriptors and our virtual screening method, we are able to quickly identify potential NR ligands from a large collection of compounds. As validation of the virtual screening procedure, an 8, 000-membered NR targeted set and a 24, 000-membered diverse control set of compounds were selected from our in-house general screening collection and screened in parallel across a number of orphan NR FRET assays. For the two assays that provided at least one hit per set by the established minimum pEC(50) for activity, the results showed a 2-fold increase in the hit-rate of the targeted compound set over the diverse set.

Highly photoresponsive and wavelength-selective circularly-polarized-light detector based on metal-oxides hetero-chiral thin film.

PubMed

Lee, Seung Hee; Singh, Dhruv Pratap; Sung, Ji Ho; Jo, Moon-Ho; Kwon, Ki Chang; Kim, Soo Young; Jang, Ho Won; Kim, Jong Kyu

2016-01-22

A highly efficient circularly-polarized-light detector with excellent wavelength selectivity is demonstrated with an elegant and simple microelectronics-compatible way. The circularly-polarized-light detector based on a proper combination of the geometry-controlled TiO2-SnO2 hetero-chiral thin film as an effective chiroptical filter and the Si active layer shows excellent chiroptical response with external quantum efficiency as high as 30% and high helicity selectivity of ~15.8% in an intended wavelength range. Furthermore, we demonstrated the ability of manipulating both bandwidth and responsivity of the detector simultaneously in whole visible wavelength range by a precise control over the geometry and materials constituting hetero-chiral thin film. The high efficiency, wavelength selectivity and compatibility with conventional microelectronics processes enabled by the proposed device can result in remarkable developments in highly integrated photonic platforms utilizing chiroptical responses.

Highly photoresponsive and wavelength-selective circularly-polarized-light detector based on metal-oxides hetero-chiral thin film

PubMed Central

Lee, Seung Hee; Singh, Dhruv Pratap; Sung, Ji Ho; Jo, Moon-Ho; Kwon, Ki Chang; Kim, Soo Young; Jang, Ho Won; Kim, Jong Kyu

2016-01-01

A highly efficient circularly-polarized-light detector with excellent wavelength selectivity is demonstrated with an elegant and simple microelectronics-compatible way. The circularly-polarized-light detector based on a proper combination of the geometry-controlled TiO2-SnO2 hetero-chiral thin film as an effective chiroptical filter and the Si active layer shows excellent chiroptical response with external quantum efficiency as high as 30% and high helicity selectivity of ~15.8% in an intended wavelength range. Furthermore, we demonstrated the ability of manipulating both bandwidth and responsivity of the detector simultaneously in whole visible wavelength range by a precise control over the geometry and materials constituting hetero-chiral thin film. The high efficiency, wavelength selectivity and compatibility with conventional microelectronics processes enabled by the proposed device can result in remarkable developments in highly integrated photonic platforms utilizing chiroptical responses. PMID:26795601

Highly photoresponsive and wavelength-selective circularly-polarized-light detector based on metal-oxides hetero-chiral thin film

NASA Astrophysics Data System (ADS)

Lee, Seung Hee; Singh, Dhruv Pratap; Sung, Ji Ho; Jo, Moon-Ho; Kwon, Ki Chang; Kim, Soo Young; Jang, Ho Won; Kim, Jong Kyu

2016-01-01

A highly efficient circularly-polarized-light detector with excellent wavelength selectivity is demonstrated with an elegant and simple microelectronics-compatible way. The circularly-polarized-light detector based on a proper combination of the geometry-controlled TiO2-SnO2 hetero-chiral thin film as an effective chiroptical filter and the Si active layer shows excellent chiroptical response with external quantum efficiency as high as 30% and high helicity selectivity of ~15.8% in an intended wavelength range. Furthermore, we demonstrated the ability of manipulating both bandwidth and responsivity of the detector simultaneously in whole visible wavelength range by a precise control over the geometry and materials constituting hetero-chiral thin film. The high efficiency, wavelength selectivity and compatibility with conventional microelectronics processes enabled by the proposed device can result in remarkable developments in highly integrated photonic platforms utilizing chiroptical responses.

Diversity of actions of GnRHs mediated by ligand-induced selective signaling

PubMed Central

Millar, Robert P.; Pawson, Adam J.; Morgan, Kevin; Rissman, Emilie F.; Lu, Zhi-Liang

2009-01-01

Geoffrey Wingfield Harris’ demonstration of hypothalamic hormones regulating pituitary function led to their structural identification and therapeutic utilization in a wide spectrum of diseases. Amongst these, Gonadotropin Releasing Hormone (GnRH) and its analogs are widely employed in modulating gonadotropin and sex steroid secretion to treat infertility, precocious puberty and many hormone-dependent diseases including endometriosis, uterine fibroids and prostatic cancer. While these effects are all mediated via modulation of the pituitary gonadotrope GnRH receptor and the Gq signaling pathway, it has become increasingly apparent that GnRH regulates many extrapituitary cells in the nervous system and periphery. This review focuses on two such examples, namely GnRH analog effects on reproductive behaviors and GnRH analog effects on the inhibition of cancer cell growth. For both effects the relative activities of a range of GnRH analogs is distinctly different from their effects on the pituitary gonadotrope and different signaling pathways are utilized. As there is only a single functional GnRH receptor type in man we have proposed that the GnRH receptor can assume different conformations which have different selectivity for GnRH analogs and intracellular signaling proteins complexes. This ligand-induced selective-signaling recruits certain pathways while by-passing others and has implications in developing more selective GnRH analogs for highly specific therapeutic intervention. PMID:17976709

Renewable energy recovery through selected industrial wastes

NASA Astrophysics Data System (ADS)

Zhang, Pengchong

Typically, industrial waste treatment costs a large amount of capital, and creates environmental concerns as well. A sound alternative for treating these industrial wastes is anaerobic digestion. This technique reduces environmental pollution, and recovers renewable energy from the organic fraction of those selected industrial wastes, mostly in the form of biogas (methane). By applying anaerobic technique, selected industrial wastes could be converted from cash negative materials into economic energy feed stocks. In this study, three kinds of industrial wastes (paper mill wastes, brown grease, and corn-ethanol thin stillage) were selected, their performance in the anaerobic digestion system was studied and their applicability was investigated as well. A pilot-scale system, including anaerobic section (homogenization, pre-digestion, and anaerobic digestion) and aerobic section (activated sludge) was applied to the selected waste streams. The investigation of selected waste streams was in a gradually progressive order. For paper mill effluents, since those effluents contain a large amount of recalcitrant or toxic compounds, the anaerobic-aerobic system was used to check its treatability, including organic removal efficiency, substrate utilization rate, and methane yield. The results showed the selected effluents were anaerobically treatable. For brown grease, as it is already well known as a treatable substrate, a high rate anaerobic digester were applied to check the economic effect of this substrate, including methane yield and substrate utilization rate. These data from pilot-scale experiment have the potential to be applied to full-scale plant. For thin stillage, anaerobic digestion system has been incorporated to the traditional ethanol making process as a gate-to-gate process. The performance of anaerobic digester was applied to the gate-to-gate life-cycle analysis to estimate the energy saving and industrial cost saving in a typical ethanol plant.

Discovery of a Potent, Dual Serotonin and Norepinephrine Reuptake Inhibitor

PubMed Central

2013-01-01

The objective of the described research effort was to identify a novel serotonin and norepinephrine reuptake inhibitor (SNRI) with improved norepinephrine transporter activity and acceptable metabolic stability and exhibiting minimal drug–drug interaction. We describe herein the discovery of a series of 3-substituted pyrrolidines, exemplified by compound 1. Compound 1 is a selective SNRI in vitro and in vivo, has favorable ADME properties, and retains inhibitory activity in the formalin model of pain behavior. Compound 1 thus represents a potential new probe to explore utility of SNRIs in central nervous system disorders, including chronic pain conditions. PMID:24900709

Structure-activity relationships amongst 4-position quinoline methanol antimalarials that inhibit the growth of drug sensitive and resistant strains of Plasmodium falciparum.

PubMed

Milner, Erin; McCalmont, William; Bhonsle, Jayendra; Caridha, Diana; Carroll, Dustin; Gardner, Sean; Gerena, Lucia; Gettayacamin, Montip; Lanteri, Charlotte; Luong, Thulan; Melendez, Victor; Moon, Jay; Roncal, Norma; Sousa, Jason; Tungtaeng, Anchalee; Wipf, Peter; Dow, Geoffrey

2010-02-15

Utilizing mefloquine as a scaffold, a next generation quinoline methanol (NGQM) library was constructed to identify early lead compounds that possess biological properties consistent with the target product profile for malaria chemoprophylaxis while reducing permeability across the blood-brain barrier. The library of 200 analogs resulted in compounds that inhibit the growth of drug sensitive and resistant strains of Plasmodium falciparum. Herein we report selected chemotypes and the emerging structure-activity relationship for this library of quinoline methanols. Published by Elsevier Ltd.

Transition to subthreshold activity with the use of phase shifting in a model thalamic network

NASA Astrophysics Data System (ADS)

Thomas, Elizabeth; Grisar, Thierry

1997-05-01

Absence epilepsy involves a state of low frequency synchronous oscillations by the involved neuronal networks. These oscillations may be either above or subthreshold. In this investigation, we studied the methods which could be utilized to transform the threshold activity of neurons in the network to a subthreshold state. A model thalamic network was constructed using the Hodgkin Huxley framework. Subthreshold activity was achieved by the application of stimuli to the network which caused phase shifts in the oscillatory activity of selected neurons in the network. In some instances the stimulus was a periodic pulse train of low frequency to the reticular thalamic neurons of the network while in others, it was a constant hyperpolarizing current applied to the thalamocortical neurons.

Utilities and the Issue of Fairness in a Decision Theoretic Model for Selection

ERIC Educational Resources Information Center

Sawyer, Richard L.; And Others

1976-01-01

This article examines some of the values that might be considered in a selection situation within the context of a decision theoretic model also described here. Several alternate expressions of fair selection are suggested in the form of utility statements in which these values can be understood and compared. (Author/DEP)

Screening of transporters to improve xylodextrin utilization in the yeast Saccharomyces cerevisiae.

PubMed

Zhang, Chenlu; Acosta-Sampson, Ligia; Yu, Vivian Yaci; Cate, Jamie H D

2017-01-01

The economic production of cellulosic biofuel requires efficient and full utilization of all abundant carbohydrates naturally released from plant biomass by enzyme cocktails. Recently, we reconstituted the Neurospora crassa xylodextrin transport and consumption system in Saccharomyces cerevisiae, enabling growth of yeast on xylodextrins aerobically. However, the consumption rate of xylodextrin requires improvement for industrial applications, including consumption in anaerobic conditions. As a first step in this improvement, we report analysis of orthologues of the N. crassa transporters CDT-1 and CDT-2. Transporter ST16 from Trichoderma virens enables faster aerobic growth of S. cerevisiae on xylodextrins compared to CDT-2. ST16 is a xylodextrin-specific transporter, and the xylobiose transport activity of ST16 is not inhibited by cellobiose. Other transporters identified in the screen also enable growth on xylodextrins including xylotriose. Taken together, these results indicate that multiple transporters might prove useful to improve xylodextrin utilization in S. cerevisiae. Efforts to use directed evolution to improve ST16 from a chromosomally-integrated copy were not successful, due to background growth of yeast on other carbon sources present in the selection medium. Future experiments will require increasing the baseline growth rate of the yeast population on xylodextrins, to ensure that the selective pressure exerted on xylodextrin transport can lead to isolation of improved xylodextrin transporters.

L-Asparaginase Activity of Fungal Endophytes from Tabernaemontana heyneana Wall. (Apocynaceae), Endemic to the Western Ghats (India)

PubMed Central

Manasa, Chandramouli; Nalini, Monnanda Somaiah

2014-01-01

“Endophytes,” the microbes residing within the plant tissues, are important sources of secondary metabolites. Tabernaemontana heyneana Wall., a medicinal tree, endemic to the Western Ghats with rich ethnobotanical history and unique chemical diversity, was selected to study fungal endophytes and evaluate them for L-asparaginase activity. Healthy plant parts were selected for the isolation of endophytes following standard isolation protocols. A total of 727 isolates belonging to 20 taxa were obtained. The isolates comprised of bark (11%), twig (22%), leaf (43%), fruit (12.0%), and seeds (12%). Endophytes such as Colletotrichum, Curvularia, Fusarium, Phomopsis, Verticillium, and Volutella colonized T. heyneana plant parts. Fusarium sp., Phomopsis spp., isolate Thlf01, and Fusarium solani were the dominant genera of bark, twig, leaf, fruits, and seed samples, respectively. The endophytes were screened for their ability to utilize L-asparagine by plate assay method. Fusarium spp. exhibited a high level of activity among the nine endophytes tested positive for L-asparaginase activity. Studies underline the potentials of endophyte-derived fungal L-asparaginases as sources of chemotherapeutic agents. PMID:27382605

Managing the SOS Response for Enhanced CRISPR-Cas-Based Recombineering in E. coli through Transient Inhibition of Host RecA Activity.

PubMed

Moreb, Eirik Adim; Hoover, Benjamin; Yaseen, Adam; Valyasevi, Nisakorn; Roecker, Zoe; Menacho-Melgar, Romel; Lynch, Michael D

2017-12-15

Phage-derived "recombineering" methods are utilized for bacterial genome editing. Recombineering results in a heterogeneous population of modified and unmodified chromosomes, and therefore selection methods, such as CRISPR-Cas9, are required to select for edited clones. Cells can evade CRISPR-Cas-induced cell death through recA-mediated induction of the SOS response. The SOS response increases RecA dependent repair as well as mutation rates through induction of the umuDC error prone polymerase. As a result, CRISPR-Cas selection is more efficient in recA mutants. We report an approach to inhibiting the SOS response and RecA activity through the expression of a mutant dominant negative form of RecA, which incorporates into wild type RecA filaments and inhibits activity. Using a plasmid-based system in which Cas9 and recA mutants are coexpressed, we can achieve increased efficiency and consistency of CRISPR-Cas9-mediated selection and recombineering in E. coli, while reducing the induction of the SOS response. To date, this approach has been shown to be independent of recA genotype and host strain lineage. Using this system, we demonstrate increased CRISPR-Cas selection efficacy with over 10 000 guides covering the E. coli chromosome. The use of dominant negative RecA or homologues may be of broad use in bacterial CRISPR-Cas-based genome editing where the SOS pathways are present.

Do You See What I See? Exploring the Consequences of Luminosity Limits in Black Hole–Galaxy Evolution Studies

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

Jones, Mackenzie L.; Hickox, Ryan C.; DiPompeo, Michael A.

In studies of the connection between active galactic nuclei (AGNs) and their host galaxies, there is widespread disagreement on some key aspects of the connection. These disagreements largely stem from a lack of understanding of the nature of the full underlying AGN population. Recent attempts to probe this connection utilize both observations and simulations to correct for a missed population, but presently are limited by intrinsic biases and complicated models. We take a simple simulation for galaxy evolution and add a new prescription for AGN activity to connect galaxy growth to dark matter halo properties and AGN activity to starmore » formation. We explicitly model selection effects to produce an “observed” AGN population for comparison with observations and empirically motivated models of the local universe. This allows us to bypass the difficulties inherent in models that attempt to infer the AGN population by inverting selection effects. We investigate the impact of selecting AGNs based on thresholds in luminosity or Eddington ratio on the “observed” AGN population. By limiting our model AGN sample in luminosity, we are able to recreate the observed local AGN luminosity function and specific star formation-stellar mass distribution, and show that using an Eddington ratio threshold introduces less bias into the sample by selecting the full range of growing black holes, despite the challenge of selecting low-mass black holes. We find that selecting AGNs using these various thresholds yield samples with different AGN host galaxy properties.« less

p21-activated kinase inhibitors.

PubMed

Rudolph, Joachim; Crawford, James J; Hoeflich, Klaus P; Chernoff, Jonathan

2013-01-01

The p21-activated kinases (PAKs) are Ser/Thr kinases in the STE20 kinase family with important roles in regulating cytoskeletal organization, cell migration, and signaling. The PAK enzyme family comprises six members subdivided into two groups: Group I, represented by PAK1, 2, and 3, and Group II, represented by PAK 4, 5, and 6, based on sequence and structural homology. Individual PAK isoforms were found to be overexpressed and amplified in a variety of human cancers, and in vitro and in vivo studies using genetically engineered systems as well as small-molecule tool compounds have suggested therapeutic utility of PAKs as oncology targets. The identification of potent and kinome-selective ATP-competitive PAK inhibitors has proven challenging, likely caused by the openness and unique plasticity of the ATP-binding site of PAK enzymes. Progress in achieving increased kinase selectivity has been achieved with certain inhibitors but at the expense of increased molecular weight. Allosteric inhibitors, such as IPA-3, leverage the unique Group I PAK autoregulatory domain for selective inhibition, and this approach might provide an outlet to evade the kinase selectivity challenges observed with ATP-competitive PAK inhibitors. © 2013 Elsevier Inc. All rights reserved.

Indomethacin causes prostaglandin D(2)-like and eotaxin-like selective responses in eosinophils and basophils.

PubMed

Stubbs, Victoria E L; Schratl, Petra; Hartnell, Adele; Williams, Timothy J; Peskar, Bernhard A; Heinemann, Akos; Sabroe, Ian

2002-07-19

We investigated the actions of a panel of nonsteroidal anti-inflammatory drugs on eosinophils, basophils, neutrophils, and monocytes. Indomethacin alone was a potent and selective inducer of eosinophil and basophil shape change. In eosinophils, indomethacin induced chemotaxis, CD11b up-regulation, respiratory burst, and L-selectin shedding but did not cause up-regulation of CD63 expression. Pretreatment of eosinophils with indomethacin also enhanced subsequent eosinophil shape change induced by eotaxin, although treatment with higher concentrations of indomethacin resulted in a decrease in the expression of the major eosinophil chemokine receptor, CCR3. Indomethacin activities and cell selectivity closely resembled those of prostaglandin D(2) (PGD(2)). Eosinophil shape change in response to eotaxin was inhibited by pertussis toxin, but indomethacin- and PGD(2)-induced shape change responses were not. Treatment of eosinophils with specific inhibitors of phospholipase C (U-73122), phosphatidylinositol 3-kinase (LY-294002), and p38 mitogen-activated protein kinase (SB-202190) revealed roles for these pathways in indomethacin signaling. Indomethacin and its analogues may therefore provide a structural basis from which selective PGD(2) receptor small molecule antagonists may be designed and which may have utility in the treatment of allergic inflammatory disease.

In silico identification of novel and selective monoamine oxidase B inhibitors.

PubMed

Yelekçi, Kemal; Büyüktürk, Bora; Kayrak, Nurdan

2013-06-01

Monoamine oxidases (MAO) A and B are flavin adenine dinucleotides containing enzymes bound to the mitochondrial outer membranes of the cells of the brain, liver, intestine, and placenta, as well as platelets. Recently, selective MAO-B inhibitors have received increasing attention due to their neuroprotective properties and the multiple roles they can play in the therapy of neurodegenerative disorders. This study was based on 10 scaffolds that were selected from more than a million lead compounds in the ZINCv12 lead library for their structural and physicochemical properties which inhibit MAO-B. Utilizing ZINC and Accelrys 3.1 fragment-based libraries, which contain about 400 thousand fragments, we generated 200 potential candidates. GOLD, LibDock, and AutoDock 4.02 were used to identify the inhibition constants and their position in the active sites of both MAO isozymes. The dispositions of the candidate molecules within the organism were checked with ADMET PSA 2D (polar surface area) against ADMET AlogP98 (the logarithm of the partition coefficient between n-octanol and water). The MAO-B inhibition activities of the candidates were compared with the properties of rasagiline which is known to be a selective inhibitor of MAO-B.

Development of Selective Androgen Receptor Modulators (SARMs)

PubMed Central

Narayanan, Ramesh; Coss, Christopher C.; Dalton, James T.

2018-01-01

The Androgen Receptor (AR), a member of the steroid hormone receptor family, plays important roles in the physiology and pathology of diverse tissues. AR ligands, which include circulating testosterone and locally synthesized dihydrotestosterone, bind to and activate the AR to elicit their effects. Ubiquitous expression of the AR, metabolism and cross reactivity with other receptors limit broad therapeutic utilization of steroidal androgens. However, the discovery of selective androgen receptor modulators (SARMs) and other tissue-selective nuclear hormone receptor modulators that activate their cognate receptors in a tissue-selective manner provides an opportunity to promote the beneficial effects of androgens and other hormones in target tissues with greatly reduced unwanted side-effects. In the last two decades, significant resources have been dedicated to the discovery and biological characterization of SARMs in an effort to harness the untapped potential of the AR. SARMs have been proposed as treatments of choice for various diseases, including muscle-wasting, breast cancer, and osteoporosis. This review provides insight into the evolution of SARMs from proof-of-concept agents to the cusp of therapeutic use in less than two decades, while covering contemporary views of their mechanisms of action and therapeutic benefits. PMID:28624515

The roles of selective attention and desensitization in the association between video gameplay and aggression: An ERP investigation.

PubMed

Jabr, Mejdy M; Denke, Greg; Rawls, Eric; Lamm, Connie

2018-04-01

A number of studies have indicated that violent video gameplay is associated with higher levels of aggression and that desensitization and selective attention to violent content may contribute to this association. Utilizing an emotionally-charged rapid serial visual presentation (RSVP) task, the current study used two event-related potentials (ERPs) - the N1 and P3 - that have been associated with selective attention and desensitization as neurocognitive mechanisms potentially underlying the connection between gameplay and higher levels of aggression. Results indicated that video game players and non-players differed in N1 and P3 activation when engaged with emotionally-charged imagery. Additionally, P3 amplitudes moderated the association between video gameplay and aggression, indicating that players who display small P3 amplitudes also showed heightened levels of aggression. Follow-up moderational analyses revealed that individuals who play games for many hours and show more negative N1 amplitudes show smaller P3 activation. Together, our results suggest that selective attention to violent content and desensitization both play key roles in the association between video gameplay and aggression. Copyright © 2018 Elsevier Ltd. All rights reserved.

Monolithic Gallium Arsenide Superheterodyne Front End.

DTIC Science & Technology

1982-06-01

which also provides a con - venient heat sink (not of primary importance in this application due to the low power dissipation of the monolithic...components utilized in the receiver front end). The thickness of the GaAs is then selected as a compromise between con - flicting requirements. A thick...International ERC41014.2FR 2.4 Analysis and Design for Low Noise The design of monolithic amplifiers for low noise must take into con - sideration active

Assessment of multi-wildfire occurrence data for machine learning based risk modelling

NASA Astrophysics Data System (ADS)

Lim, C. H.; Kim, M.; Kim, S. J.; Yoo, S.; Lee, W. K.

2017-12-01

The occurrence of East Asian wildfires is mainly caused by human-activities, but the extreme drought increased due to the climate change caused wildfires and they spread to large-scale fires. Accurate occurrence location data is required for modelling wildfire probability and risk. In South Korea, occurrence data surveyed through KFS (Korea Forest Service) and MODIS (MODerate-resolution Imaging Spectroradiometer) satellite-based active fire data can be utilized. In this study, two sorts of wildfire occurrence data were applied to select suitable occurrence data for machine learning based wildfire risk modelling. MaxEnt (Maximum Entropy) model based on machine learning is used for wildfire risk modelling, and two types of occurrence data and socio-economic and climate-environment data are applied to modelling. In the results with KFS survey based data, the low relationship was shown with climate-environmental factors, and the uncertainty of coordinate information appeared. The MODIS-based active fire data were found outside the forests, and there were a lot of spots that did not match the actual wildfires. In order to utilize MODIS-based active fire data, it was necessary to extract forest area and utilize only high-confidence level data. In KFS data, it was necessary to separate the analysis according to the damage scale to improve the modelling accuracy. Ultimately, it is considered to be the best way to simulate the wildfire risk by constructing more accurate information by combining two sorts of wildfire occurrence data.

Predicting the performance of fingerprint similarity searching.

PubMed

Vogt, Martin; Bajorath, Jürgen

2011-01-01

Fingerprints are bit string representations of molecular structure that typically encode structural fragments, topological features, or pharmacophore patterns. Various fingerprint designs are utilized in virtual screening and their search performance essentially depends on three parameters: the nature of the fingerprint, the active compounds serving as reference molecules, and the composition of the screening database. It is of considerable interest and practical relevance to predict the performance of fingerprint similarity searching. A quantitative assessment of the potential that a fingerprint search might successfully retrieve active compounds, if available in the screening database, would substantially help to select the type of fingerprint most suitable for a given search problem. The method presented herein utilizes concepts from information theory to relate the fingerprint feature distributions of reference compounds to screening libraries. If these feature distributions do not sufficiently differ, active database compounds that are similar to reference molecules cannot be retrieved because they disappear in the "background." By quantifying the difference in feature distribution using the Kullback-Leibler divergence and relating the divergence to compound recovery rates obtained for different benchmark classes, fingerprint search performance can be quantitatively predicted.

Surface Texture-Induced Enhancement of Optical and Photoelectrochemical Activity of Cu2ZnSnS4 Photocathodes

NASA Astrophysics Data System (ADS)

Sarswat, Prashant K.; Deka, Nipon; Jagan Mohan Rao, S.; Free, Michael L.; Kumar, Gagan

2017-08-01

The objective of this work is to understand and improve the photocatalytic activity of Cu2ZnSnS4 (CZTS) through postgrowth modification techniques to create surface textures. This objective can be achieved using a combination of solvents, etching agents, and anodization techniques. One of the most effective surface treatments for enhancing the surface properties of photovoltaic materials is formation of nanoscale flakes, although other surface modifications were also evaluated. The superior performance of textured films can be attributed to enhanced surface area of absorber material exposed to electrolyte, ZnS deficiency, and high catalytic activity due to reduced charge-transfer resistance. Fine-tuning of ion flux and electrolyte stoichiometry can be used to create a controlled growth algorithm for CZTS thin films. The resulting information can be utilized to optimize film properties. The utility of nanostructured or engineered surfaces was evaluated using photoelectrochemical measurements. Finite-difference time-domain (FDTD)-assisted simulations were conducted for selected texturing, revealing enhanced surface area of absorbing medium that ultimately resulted in greater power loss of light in the medium.

A Sensitive and Versatile Fluorescent Activity Assay for ABHD12.

PubMed

Savinainen, Juha R; Navia-Paldanius, Dina; Laitinen, Jarmo T

2016-01-01

Despite great progress in identifying and deorphanizing members of the human metabolic serine hydrolase (mSH) family, the fundamental role of numerous enzymes in this large protein class has remained unclear. One recently found mSH is α/β-hydrolase domain containing 12 (ABHD12) enzyme, whose natural substrate in vivo appears to be the lysophospholipid lysophosphatidylserine (LPS). In vitro, ABHD12 together with monoacylglycerol lipase (MAGL) and ABHD6 hydrolyzes also monoacylglycerols (MAGs) such as the primary endocannabinoid 2-arachidonoyl glycerol (2-AG). Traditional approaches for determining 2-AG hydrolase activity are rather laborious, and often utilize unnatural substrates. Here, we describe a sensitive fluorescent assay of ABHD12 activity in a 96-well-plate format that allows simultaneous testing of inhibitor activities of up to 40 compounds in a single assay. The method utilizes lysates of HEK293 cells transiently overexpressing human ABHD12 as the enzymatic source, and kinetically monitors glycerol liberated in the hydrolysis of 1(3)-AG, the preferred MAG substrate of this enzyme. Glycerol output is coupled to an enzymatic cascade generating the fluorescent end-product resorufin. This methodology has helped to identify the first class of inhibitors showing selectivity for ABHD12 over the other mSHs.

Active Semi-Supervised Community Detection Based on Must-Link and Cannot-Link Constraints

PubMed Central

Cheng, Jianjun; Leng, Mingwei; Li, Longjie; Zhou, Hanhai; Chen, Xiaoyun

2014-01-01

Community structure detection is of great importance because it can help in discovering the relationship between the function and the topology structure of a network. Many community detection algorithms have been proposed, but how to incorporate the prior knowledge in the detection process remains a challenging problem. In this paper, we propose a semi-supervised community detection algorithm, which makes full utilization of the must-link and cannot-link constraints to guide the process of community detection and thereby extracts high-quality community structures from networks. To acquire the high-quality must-link and cannot-link constraints, we also propose a semi-supervised component generation algorithm based on active learning, which actively selects nodes with maximum utility for the proposed semi-supervised community detection algorithm step by step, and then generates the must-link and cannot-link constraints by accessing a noiseless oracle. Extensive experiments were carried out, and the experimental results show that the introduction of active learning into the problem of community detection makes a success. Our proposed method can extract high-quality community structures from networks, and significantly outperforms other comparison methods. PMID:25329660

Versatile de novo enzyme activity in capsid proteins from an engineered M13 bacteriophage library.

PubMed

Casey, John P; Barbero, Roberto J; Heldman, Nimrod; Belcher, Angela M

2014-11-26

Biocatalysis has grown rapidly in recent decades as a solution to the evolving demands of industrial chemical processes. Mounting environmental pressures and shifting supply chains underscore the need for novel chemical activities, while rapid biotechnological progress has greatly increased the utility of enzymatic methods. Enzymes, though capable of high catalytic efficiency and remarkable reaction selectivity, still suffer from relative instability, high costs of scaling, and functional inflexibility. Herein, we developed a biochemical platform for engineering de novo semisynthetic enzymes, functionally modular and widely stable, based on the M13 bacteriophage. The hydrolytic bacteriophage described in this paper catalyzes a range of carboxylic esters, is active from 25 to 80 °C, and demonstrates greater efficiency in DMSO than in water. The platform complements biocatalysts with characteristics of heterogeneous catalysis, yielding high-surface area, thermostable biochemical structures readily adaptable to reactions in myriad solvents. As the viral structure ensures semisynthetic enzymes remain linked to the genetic sequences responsible for catalysis, future work will tailor the biocatalysts to high-demand synthetic processes by evolving new activities, utilizing high-throughput screening technology and harnessing M13's multifunctionality.

Defining RNA motif-aminoglycoside interactions via two-dimensional combinatorial screening and structure-activity relationships through sequencing.

PubMed

Velagapudi, Sai Pradeep; Disney, Matthew D

2013-10-15

RNA is an extremely important target for the development of chemical probes of function or small molecule therapeutics. Aminoglycosides are the most well studied class of small molecules to target RNA. However, the RNA motifs outside of the bacterial rRNA A-site that are likely to be bound by these compounds in biological systems is largely unknown. If such information were known, it could allow for aminoglycosides to be exploited to target other RNAs and, in addition, could provide invaluable insights into potential bystander targets of these clinically used drugs. We utilized two-dimensional combinatorial screening (2DCS), a library-versus-library screening approach, to select the motifs displayed in a 3×3 nucleotide internal loop library and in a 6-nucleotide hairpin library that bind with high affinity and selectivity to six aminoglycoside derivatives. The selected RNA motifs were then analyzed using structure-activity relationships through sequencing (StARTS), a statistical approach that defines the privileged RNA motif space that binds a small molecule. StARTS allowed for the facile annotation of the selected RNA motif-aminoglycoside interactions in terms of affinity and selectivity. The interactions selected by 2DCS generally have nanomolar affinities, which is higher affinity than the binding of aminoglycosides to a mimic of their therapeutic target, the bacterial rRNA A-site. Copyright © 2013 Elsevier Ltd. All rights reserved.

Defining RNA motif–aminoglycoside interactions via two-dimensional combinatorial screening and structure–activity relationships through sequencing

PubMed Central

Velagapudi, Sai Pradeep; Disney, Matthew D.

2013-01-01

RNA is an extremely important target for the development of chemical probes of function or small molecule therapeutics. Aminoglycosides are the most well studied class of small molecules to target RNA. However, the RNA motifs outside of the bacterial rRNA A-site that are likely to be bound by these compounds in biological systems is largely unknown. If such information were known, it could allow for aminoglycosides to be exploited to target other RNAs and, in addition, could provide invaluable insights into potential bystander targets of these clinically used drugs. We utilized two-dimensional combinatorial screening (2DCS), a library-versus-library screening approach, to select the motifs displayed in a 3 × 3 nucleotide internal loop library and in a 6-nucleotide hairpin library that bind with high affinity and selectivity to six aminoglycoside derivatives. The selected RNA motifs were then analyzed using structure–activity relationships through sequencing (StARTS), a statistical approach that defines the privileged RNA motif space that binds a small molecule. StARTS allowed for the facile annotation of the selected RNA motif–aminoglycoside interactions in terms of affinity and selectivity. The interactions selected by 2DCS generally have nanomolar affinities, which is higher affinity than the binding of aminoglycosides to a mimic of their therapeutic target, the bacterial rRNA A-site. PMID:23719281

Influence of harvest season on antioxidant activity and constituents of rabbiteye blueberry ( Vaccinium ashei ) leaves.

PubMed

Zhu, Liancai; Liu, Xi; Tan, Jun; Wang, Bochu

2013-11-27

To select rabbiteye blueberry leaves from an appropriate harvest season to develop functional foods, this paper studied the bioactive secondary metabolites and the antioxidant capacity of rabbiteye blueberry leaves from May, September, and November. The results showed the leaves from May had the highest content of total flavonoids (114.21 mg/g) and the leaves from November had the highest content of total polyphenols and proanthocyanidins (425.24 and 243.29 mg/g, respectively). It was further found that blueberry leaves from different seasons have similar bioactive constituents, but their contents are obviously different by HPLC. The rabbiteye blueberry leaves from November had the highest antioxidant capacity, which was well correlated with their highest proanthocyanidin content. The results clarify that the blueberry leaves from different seasons have different contents of bioactive secondary metabolites and different antioxidant activities, which implied that leaves from November should be selected first for utilization in functional foods.

Informing the Selection of Screening Hit Series with in Silico Absorption, Distribution, Metabolism, Excretion, and Toxicity Profiles.

PubMed

Sanders, John M; Beshore, Douglas C; Culberson, J Christopher; Fells, James I; Imbriglio, Jason E; Gunaydin, Hakan; Haidle, Andrew M; Labroli, Marc; Mattioni, Brian E; Sciammetta, Nunzio; Shipe, William D; Sheridan, Robert P; Suen, Linda M; Verras, Andreas; Walji, Abbas; Joshi, Elizabeth M; Bueters, Tjerk

2017-08-24

High-throughput screening (HTS) has enabled millions of compounds to be assessed for biological activity, but challenges remain in the prioritization of hit series. While biological, absorption, distribution, metabolism, excretion, and toxicity (ADMET), purity, and structural data are routinely used to select chemical matter for further follow-up, the scarcity of historical ADMET data for screening hits limits our understanding of early hit compounds. Herein, we describe a process that utilizes a battery of in-house quantitative structure-activity relationship (QSAR) models to generate in silico ADMET profiles for hit series to enable more complete characterizations of HTS chemical matter. These profiles allow teams to quickly assess hit series for desirable ADMET properties or suspected liabilities that may require significant optimization. Accordingly, these in silico data can direct ADMET experimentation and profoundly impact the progression of hit series. Several prospective examples are presented to substantiate the value of this approach.

Promysalin Elicits Species-Selective Inhibition of Pseudomonas aeruginosa by Targeting Succinate Dehydrogenase.

PubMed

Keohane, Colleen E; Steele, Andrew D; Fetzer, Christian; Khowsathit, Jittasak; Van Tyne, Daria; Moynié, Lucile; Gilmore, Michael S; Karanicolas, John; Sieber, Stephan A; Wuest, William M

2018-02-07

Natural products have served as an inspiration to scientists both for their complex three-dimensional architecture and exquisite biological activity. Promysalin is one such Pseudomonad secondary metabolite that exhibits narrow-spectrum antibacterial activity, originally isolated from the rhizosphere. We herein utilize affinity-based protein profiling (AfBPP) to identify succinate dehydrogenase (Sdh) as the biological target of the natural product. The target was further validated in silico, in vitro, in vivo, and through the selection, and sequencing, of a resistant mutant. Succinate dehydrogenase plays an essential role in primary metabolism of Pseudomonas aeruginosa as the only enzyme that is involved both in the tricarboxylic acid cycle (TCA) and in respiration via the electron transport chain. These findings add credence to other studies that suggest that the TCA cycle is an understudied target in the development of novel therapeutics to combat P. aeruginosa, a significant pathogen in clinical settings.

The total antioxidant capacity and fluorescence imaging of selected plant leaves commonly consumed in Brunei Darussalam

NASA Astrophysics Data System (ADS)

Watu, Aswani; Metussin, Nurzaidah; Yasin, Hartini M.; Usman, Anwar

2018-02-01

We investigated the total antioxidant capacity and fluorescence imaging of several selected plants, namely Centella asiatica, Aidia borneensis and Anacardium occidentale, which are grown and traditionally consumed in Brunei Darussalam. The total antioxidant capacities of aqueous-methanolic infusions of their leaves were measured by 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging activity, and microscopic fluorescence images were measured to identify the fluorescent substances bound in the leaves. We found that the total antioxidant capacity of their infusions is estimated to be 150, 25, 15 folds, respectively, lower compared with that of the standard gallic acid. Accordingly, we demonstrated that the relative antioxidant activity of young and matured leaves agrees with the intensity of red light emission of their fresh leaves upon UV excitation. Thus, this non-invasive spectroscopic method can be potentially utilized to indicate the antioxidants in plant leaves qualitatively.

Selection Bias and Utilization of the Dual Eligibles in Medicare and Medicaid HMOs

PubMed Central

Zhang, Hui; Kane, Robert L; Dowd, Bryan; Feldman, Roger

2008-01-01

Objective To examine the existence of selection bias in the first 3 years of the Minnesota Senior Health Options (MSHO) demonstration and to estimate the MSHO effects on medical services utilization after adjusting for selection bias. Data Sources Monthly dual eligibility data and MSHO encounter data of March 1997–December 2000 and Medicaid encounter data of January 1995–December 2000 from the Minnesota Department of Human Services; Medicare fee-for-service claims data of January 1995–December 2000 from the Centers for Medicare and Medicaid Services. Study Design Quasi-experimental design comparing utilization between MSHO and control groups; multiple econometric and statistical models were estimated with time-invariant and time-varying covariates. Principal Findings Favorable MSHO selection was found in the nursing home (NH) and community populations, but selection bias did not substantially affect the findings. Enrollment in MSHO for more than 1 year reduced inpatient hospital admissions and days, emergency room and physician visits for NH residents, and lowered physician visits for community residents. Conclusions There was favorable selection in the first 3 years of the MSHO program. Enrollment in MSHO reduced several types of utilization for the NH group and physician visits for community enrollees. PMID:18479403

Activity recognition from minimal distinguishing subsequence mining

NASA Astrophysics Data System (ADS)

Iqbal, Mohammad; Pao, Hsing-Kuo

2017-08-01

Human activity recognition is one of the most important research topics in the era of Internet of Things. To separate different activities given sensory data, we utilize a Minimal Distinguishing Subsequence (MDS) mining approach to efficiently find distinguishing patterns among different activities. We first transform the sensory data into a series of sensor triggering events and operate the MDS mining procedure afterwards. The gap constraints are also considered in the MDS mining. Given the multi-class nature of most activity recognition tasks, we modify the MDS mining approach from a binary case to a multi-class one to fit the need for multiple activity recognition. We also study how to select the best parameter set including the minimal and the maximal support thresholds in finding the MDSs for effective activity recognition. Overall, the prediction accuracy is 86.59% on the van Kasteren dataset which consists of four different activities for recognition.

Activation of remote meta-C-H bonds assisted by an end-on template.

PubMed

Leow, Dasheng; Li, Gang; Mei, Tian-Sheng; Yu, Jin-Quan

2012-06-27

Functionalization of unactivated carbon-hydrogen (C-H) single bonds is an efficient strategy for rapid generation of complex molecules from simpler ones. However, it is difficult to achieve selectivity when multiple inequivalent C-H bonds are present in the target molecule. The usual approach is to use σ-chelating directing groups, which lead to ortho-selectivity through the formation of a conformationally rigid six- or seven-membered cyclic pre-transition state. Despite the broad utility of this approach, proximity-driven reactivity prevents the activation of remote C-H bonds. Here we report a class of easily removable nitrile-containing templates that direct the activation of distal meta-C-H bonds (more than ten bonds away) of a tethered arene. We attribute this new mode of C-H activation to a weak 'end-on' interaction between the linear nitrile group and the metal centre. The 'end-on' coordination geometry relieves the strain of the cyclophane-like pre-transition state of the meta-C-H activation event. In addition, this template overrides the intrinsic electronic and steric biases as well as ortho-directing effects with two broadly useful classes of arene substrates (toluene derivatives and hydrocinnamic acids).

Molecular analysis of maltotriose active transport and fermentation by Saccharomyces cerevisiae reveals a determinant role for the AGT1 permease.

PubMed

Alves, Sergio L; Herberts, Ricardo A; Hollatz, Claudia; Trichez, Debora; Miletti, Luiz C; de Araujo, Pedro S; Stambuk, Boris U

2008-03-01

Incomplete and/or sluggish maltotriose fermentation causes both quality and economic problems in the ale-brewing industry. Although it has been proposed previously that the sugar uptake must be responsible for these undesirable phenotypes, there have been conflicting reports on whether all the known alpha-glucoside transporters in Saccharomyces cerevisiae (MALx1, AGT1, and MPH2 and MPH3 transporters) allow efficient maltotriose utilization by yeast cells. We characterized the kinetics of yeast cell growth, sugar consumption, and ethanol production during maltose or maltotriose utilization by several S. cerevisiae yeast strains (both MAL constitutive and MAL inducible) and by their isogenic counterparts with specific deletions of the AGT1 gene. Our results clearly showed that yeast strains carrying functional permeases encoded by the MAL21, MAL31, and/or MAL41 gene in their plasma membranes were unable to utilize maltotriose. While both high- and low-affinity transport activities were responsible for maltose uptake from the medium, in the case of maltotriose, the only low-affinity (K(m), 36 +/- 2 mM) transport activity was mediated by the AGT1 permease. In conclusion, the AGT1 transporter is required for efficient maltotriose fermentation by S. cerevisiae yeasts, highlighting the importance of this permease for breeding and/or selection programs aimed at improving sluggish maltotriose fermentations.

Discrimination of Swiss cheese from 5 different factories by high impact volatile organic compound profiles determined by odor activity value using selected ion flow tube mass spectrometry and odor threshold.

PubMed

Taylor, Kaitlyn; Wick, Cheryl; Castada, Hardy; Kent, Kyle; Harper, W James

2013-10-01

Swiss cheese contains more than 200 volatile organic compounds (VOCs). Gas chromatography-mass spectrometry has been utilized for the analysis of volatile compounds in food products; however, it is not sensitive enough to measure VOCs directly in the headspace of a food at low concentrations. Selected ion flow tube mass spectrometry (SIFT-MS) provides a basis for determining the concentrations of VOCs in the head space of the sample in real time at low concentration levels of parts per billion/trillion by volume. Of the Swiss cheese VOCs, relatively few have a major impact on flavor quality. VOCs with odor activity values (OAVs) (concentration/odor threshold) greater than one are considered high-impact flavor compounds. The objective of this study was to utilize SIFT-MS concentrations in conjunction with odor threshold values to determine OAVs thereby identifying high-impact VOCs to use for differentiating Swiss cheese from five factories and identify the factory variability. Seventeen high-impact VOCs were identified for Swiss cheese based on an OAV greater than one in at least 1 of the 5 Swiss cheese factories. Of these, 2,3-butanedione was the only compound with significantly different OAVs in all factories; however, cheese from any pair of factories had multiple statistically different compounds based on OAV. Principal component analysis using soft independent modeling of class analogy statistical differentiation plots, with all of the OAVs, showed differentiation between the 5 factories. Overall, Swiss cheese from different factories was determined to have different OAV profiles utilizing SIFT-MS to determine OAVs of high impact compounds. © 2013 Institute of Food Technologists®

Oxygen Reduction Reaction Measurements on Platinum Electrocatalysts Utilizing Rotating Disk Electrode Technique: I. Impact of Impurities, Measurement Protocols and Applied Corrections

DOE PAGES

Shinozaki, Kazuma; Zack, Jason W.; Richards, Ryan M.; ...

2015-07-22

The rotating disk electrode (RDE) technique is being extensively used as a screening tool to estimate the activity of novel PEMFC electrocatalysts synthesized in lab-scale (mg) quantities. Discrepancies in measured activity attributable to glassware and electrolyte impurity levels, as well as conditioning, protocols and corrections are prevalent in the literature. Moreover, the electrochemical response to a broad spectrum of commercially sourced perchloric acid and the effect of acid molarity on impurity levels and solution resistance were also assessed. Our findings reveal that an area specific activity (SA) exceeding 2.0 mA/cm 2 (20 mV/s, 25°C, 100 kPa, 0.1 M HClO 4)more » for polished poly-Pt is an indicator of impurity levels that do not impede the accurate measurement of the ORR activity of Pt based catalysts. After exploring various conditioning protocols to approach maximum utilization of the electrochemical area (ECA) and peak ORR activity without introducing catalyst degradation, an investigation of measurement protocols for ECA and ORR activity was conducted. Down-selected protocols were based on the criteria of reproducibility, duration of experiments, impurity effects and magnitude of pseudo-capacitive background correction. In sum, statistical reproducibility of ORR activity for poly-Pt and Pt supported on high surface area carbon was demonstrated.« less

New trends in the development of opioid peptide analogues as advanced remedies for pain relief.

PubMed

Gentilucci, Luca

2004-01-01

The search for new peptides to be used as analgesics in place of morphine has been mainly directed to develop peptide analogues or peptidomimetics having higher biological stability and receptor selectivity. Indeed, most of the alkaloid opioid counterindications are due to the scarce stability and the contemporary activation of different receptor types. However, the development of several extremely stable and selective peptide ligands for the different opioid receptors, and the recent discovery of the micro-receptor selective endomorphins, rendered this search less fundamental. In recent years, other opioid peptide properties have been investigated in the search for new pharmacological tools. The utility of a drug depends on its ability to reach appropriate receptors at the target tissue and to remain metabolically stable in order to produce the desired effect. This review deals with the recent investigations on peptide bioavailability, in particular barrier penetration and resistance against enzymatic degradation; with the development of peptides having activity at different receptors; with chimeric peptides, with propeptides, and with non-conventional peptides, lacking basic pharmacophoric features.

Criteria for selecting a CO/sub 2//climate change region of study

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

Edmonds, J.; Cushman, R.; Easterling, W.

One of the most important research issues active today is the greenhouse issue. Progress has been made in exploring the relationship between human activities and the accumulation of CO/sub 2/ and other radiatively important gases in the atmosphere. While significant research remains in refining our understanding of the timing of possible CO/sub 2//climate change, the examination of the nature and magnitude of consequences of CO/sub 2//climate change remains in a relatively early stage of development. While the accumulation of greenhouse gases in the atmosphere may be a global problem, the consequences of CO/sub 2//climate change will be experienced regionally. Itmore » is therefore critical that methods be developed to address the regional examination of CO/sub 2//climate change. An analytical framework is described and a ''cookie cutter'' technique is utilized to deal with multiple resource sectors in selecting a Region of Study. The result leads to the selection of the four midwestern states of Kansas, Nebraska, Iowa, and Missouri. The role of information systems, uncertainty analysis, and knowledge transfer is discussed. 19 refs., 2 figs.« less

Method and apparatus for synthesis of arrays of DNA probes

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

Cerrina, Francesco; Sussman, Michael R.; Blattner, Frederick R.

The synthesis of arrays of DNA probes sequences, polypeptides, and the like is carried out using a patterning process on an active surface of a substrate. An image is projected onto the active surface of the substrate utilizing an image former that includes a light source that provides light to a micromirror device comprising an array of electronically addressable micromirrors, each of which can be selectively tilted between one of at least two positions. Projection optics receives the light reflected from the micromirrors along an optical axis and precisely images the micromirrors onto the active surface of the substrate, whichmore » may be used to activate the surface of the substrate. The first level of bases may then be applied to the substrate, followed by development steps, and subsequent exposure of the substrate utilizing a different pattern of micromirrors, with further repeats until the elements of a two dimensional array on the substrate surface have an appropriate base bound thereto. The micromirror array can be controlled in conjunction with a DNA synthesizer supplying appropriate reagents to a flow cell containing the active substrate to control the sequencing of images presented by the micromirror array in coordination of the reagents provided to the substrate.« less

AH-1S communication switch integration program

NASA Technical Reports Server (NTRS)

Haworth, Loran; Szoboszlay, Zoltan; Shively, Robert; Bick, Frank J.

1989-01-01

The C-6533/ARC communication system as installed on the test AH-1E Cobra helicopter was modified to allow discrete radio selection of all aircraft radios at the cyclic radio/intercommunication system switch. The current Cobra-fleet use of the C-6533 system is cumbersome, particularly during low-altitude operations. Operationally, the current system C-6533 configuration and design requires the pilot to estimate when he can safely remove his hand from an active flight control to select radios during low-altitude flight. The pilot must then physically remove his hand from the flight control, look inside the cockpit to select and verify the radio selection and then effect the selected radio transmission by activating the radio/ICS switch on the cyclic. This condition is potentially hazardous, especially during low-level flight at night in degraded weather. To improve pilot performance, communications effectiveness, and safety, manprint principles were utilized in the selection of a design modification. The modified C-6533 design was kept as basic as possible for potential Cobra-fleet modification. The communications system was modified and the design was subsequently flight-tested by the U.S. Army Aeroflightdynamics Directorate and NASA at the NASA Ames Research Center, Mountain View, California. The design modification enables the Cobra pilot to maintain hands-on flight controls while selecting radios during nap-of-the-Earth (NOE) flight without looking inside the cockpit which resulted in reduced pilot workload ratings, better pilot handling quality ratings and increased flight safety for the NOE flight environment.

Exploiting selective BCL-2 family inhibitors to dissect cell survival dependencies and define improved strategies for cancer therapy.

PubMed

Leverson, Joel D; Phillips, Darren C; Mitten, Michael J; Boghaert, Erwin R; Diaz, Dolores; Tahir, Stephen K; Belmont, Lisa D; Nimmer, Paul; Xiao, Yu; Ma, Xiaoju Max; Lowes, Kym N; Kovar, Peter; Chen, Jun; Jin, Sha; Smith, Morey; Xue, John; Zhang, Haichao; Oleksijew, Anatol; Magoc, Terrance J; Vaidya, Kedar S; Albert, Daniel H; Tarrant, Jacqueline M; La, Nghi; Wang, Le; Tao, Zhi-Fu; Wendt, Michael D; Sampath, Deepak; Rosenberg, Saul H; Tse, Chris; Huang, David C S; Fairbrother, Wayne J; Elmore, Steven W; Souers, Andrew J

2015-03-18

The BCL-2/BCL-XL/BCL-W inhibitor ABT-263 (navitoclax) has shown promising clinical activity in lymphoid malignancies such as chronic lymphocytic leukemia. However, its efficacy in these settings is limited by thrombocytopenia caused by BCL-XL inhibition. This prompted the generation of the BCL-2-selective inhibitor venetoclax (ABT-199/GDC-0199), which demonstrates robust activity in these cancers but spares platelets. Navitoclax has also been shown to enhance the efficacy of docetaxel in preclinical models of solid tumors, but clinical use of this combination has been limited by neutropenia. We used venetoclax and the BCL-XL-selective inhibitors A-1155463 and A-1331852 to assess the relative contributions of inhibiting BCL-2 or BCL-XL to the efficacy and toxicity of the navitoclax-docetaxel combination. Selective BCL-2 inhibition suppressed granulopoiesis in vitro and in vivo, potentially accounting for the exacerbated neutropenia observed when navitoclax was combined with docetaxel clinically. By contrast, selectively inhibiting BCL-XL did not suppress granulopoiesis but was highly efficacious in combination with docetaxel when tested against a range of solid tumors. Therefore, BCL-XL-selective inhibitors have the potential to enhance the efficacy of docetaxel in solid tumors and avoid the exacerbation of neutropenia observed with navitoclax. These studies demonstrate the translational utility of this toolkit of selective BCL-2 family inhibitors and highlight their potential as improved cancer therapeutics. Copyright © 2015, American Association for the Advancement of Science.

Spatiotemporal Patterns of the Use of Urban Green Spaces and External Factors Contributing to Their Use in Central Beijing

PubMed Central

Li, Fangzheng; Zhang, Fen; Li, Xiong; Wang, Peng; Liang, Junhui; Mei, Yuting; Cheng, Wenwen; Qian, Yun

2017-01-01

Urban green spaces encourage outdoor activity and social communication that contribute to the health of local residents. Examining the relationship between the use of urban green spaces and factors influencing their utilization can provide essential references for green space site selection in urban planning. In contrast to previous studies that focused on internal factors, this study highlights the external factors (traffic convenience, population density and commercial facilities) contributing to the use of urban green spaces. We conducted a spatiotemporal analysis of the distribution of visitors in 208 selected green spaces in central Beijing. We examined the relationship between the spatial pattern of visitor distribution within urban green spaces and external factors, using the Gini coefficient, kernel density estimation, and geographical detectors. The results of the study were as follows. The spatial distribution of visitors within central Beijing’s green spaces was concentrated, forming different agglomerations. The three examined external factors are all associated with the use of green spaces. Among them, commercial facilities are the important external factor associated with the use of green spaces. For the selection of sites for urban green spaces, we recommend consideration of external factors in order to balance urban green space utilization. PMID:28264451

Ion-Specific Nutrient Management in Closed Systems: The Necessity for Ion-Selective Sensors in Terrestrial and Space-Based Agriculture and Water Management Systems

PubMed Central

Bamsey, Matthew; Graham, Thomas; Thompson, Cody; Berinstain, Alain; Scott, Alan; Dixon, Michael

2012-01-01

The ability to monitor and control plant nutrient ions in fertigation solutions, on an ion-specific basis, is critical to the future of controlled environment agriculture crop production, be it in traditional terrestrial settings (e.g., greenhouse crop production) or as a component of bioregenerative life support systems for long duration space exploration. Several technologies are currently available that can provide the required measurement of ion-specific activities in solution. The greenhouse sector has invested in research examining the potential of a number of these technologies to meet the industry's demanding requirements, and although no ideal solution yet exists for on-line measurement, growers do utilize technologies such as high-performance liquid chromatography to provide off-line measurements. An analogous situation exists on the International Space Station where, technological solutions are sought, but currently on-orbit water quality monitoring is considerably restricted. This paper examines the specific advantages that on-line ion-selective sensors could provide to plant production systems both terrestrially and when utilized in space-based biological life support systems and how similar technologies could be applied to nominal on-orbit water quality monitoring. A historical development and technical review of the various ion-selective monitoring technologies is provided. PMID:23201999

Spatiotemporal Patterns of the Use of Urban Green Spaces and External Factors Contributing to Their Use in Central Beijing.

PubMed

Li, Fangzheng; Zhang, Fen; Li, Xiong; Wang, Peng; Liang, Junhui; Mei, Yuting; Cheng, Wenwen; Qian, Yun

2017-02-27

Urban green spaces encourage outdoor activity and social communication that contribute to the health of local residents. Examining the relationship between the use of urban green spaces and factors influencing their utilization can provide essential references for green space site selection in urban planning. In contrast to previous studies that focused on internal factors, this study highlights the external factors (traffic convenience, population density and commercial facilities) contributing to the use of urban green spaces. We conducted a spatiotemporal analysis of the distribution of visitors in 208 selected green spaces in central Beijing. We examined the relationship between the spatial pattern of visitor distribution within urban green spaces and external factors, using the Gini coefficient, kernel density estimation, and geographical detectors. The results of the study were as follows. The spatial distribution of visitors within central Beijing's green spaces was concentrated, forming different agglomerations. The three examined external factors are all associated with the use of green spaces. Among them, commercial facilities are the important external factor associated with the use of green spaces. For the selection of sites for urban green spaces, we recommend consideration of external factors in order to balance urban green space utilization.

Ion-specific nutrient management in closed systems: the necessity for ion-selective sensors in terrestrial and space-based agriculture and water management systems.

PubMed

Bamsey, Matthew; Graham, Thomas; Thompson, Cody; Berinstain, Alain; Scott, Alan; Dixon, Michael

2012-10-01

The ability to monitor and control plant nutrient ions in fertigation solutions, on an ion-specific basis, is critical to the future of controlled environment agriculture crop production, be it in traditional terrestrial settings (e.g., greenhouse crop production) or as a component of bioregenerative life support systems for long duration space exploration. Several technologies are currently available that can provide the required measurement of ion-specific activities in solution. The greenhouse sector has invested in research examining the potential of a number of these technologies to meet the industry's demanding requirements, and although no ideal solution yet exists for on-line measurement, growers do utilize technologies such as high-performance liquid chromatography to provide off-line measurements. An analogous situation exists on the International Space Station where, technological solutions are sought, but currently on-orbit water quality monitoring is considerably restricted. This paper examines the specific advantages that on-line ion-selective sensors could provide to plant production systems both terrestrially and when utilized in space-based biological life support systems and how similar technologies could be applied to nominal on-orbit water quality monitoring. A historical development and technical review of the various ion-selective monitoring technologies is provided.

Identification of a novel phospholipase D with high transphosphatidylation activity and its application in synthesis of phosphatidylserine and DHA-phosphatidylserine.

PubMed

Mao, Xiangzhao; Liu, Qianqian; Qiu, Yongqian; Fan, Xiaoqin; Han, Qingqing; Liu, Yanjun; Zhang, Lujia; Xue, Changhu

2017-05-10

Phosphatidylserine (PS) and docosahexaenoic acid-phosphatidylserine (DHA-PS) have significant nutritional and biological functions, which are extensively used in functional food industries. Phospholipase D (PLD)-mediated transphosphatidylation of phosphatidylcholine (PC) or DHA-PC with l-serine, is an effective method for PS and DHA-PS preparation. However, because of the hydrolysis activity of PLD, PC and DHA-PC would be converted to the undesirable byproduct, phosphatidic acid (PA) and DHA-PA. In this study, a novel phospholipase D (PLD a2 ) was firstly cloned from Acinetobacter radioresistens a2 with high transphosphatidylation activity and no hydrolysis activity. In the PLD-catalyzed synthesis process (12h), both the transphosphatidylation conversion rate and selectivity of PS and DHA-PS were about 100%, which is the only PLD enzyme reported with this superiority up till now. In comparison with the majority of other known PLDs, PLD a2 exerted the highest activity at neutral pH, and it was stable from pH 4.0 to pH 9.0. In addition, PLD a2 had excellent thermal stability, with an optimum reaction temperature of 40°C and keeping more than 80% activity from 20°C to 60°C. The high catalytic selectivity mechanism of PLD a2 was explained by utilizing homology modeling, two-step docking, and binding energy and conformation analysis. PLD a2 ensured a stable supply of the biocatalyst with its most preponderant transphosphatidylation activity and PS selectivity, and had great potential in phospholipids industrial production. Copyright © 2017 Elsevier B.V. All rights reserved.

A Comparative Study of Students' Access to and Utilization of Learning Resources in Selected Public and Private Universities in Southwest, Nigeria

ERIC Educational Resources Information Center

Lawal, B. O.; Viatonu, Olumuyiwa

2017-01-01

The study investigated students' access to and utilization of some learning resources in selected public and private universities in southwest Nigeria. Stratified random sampling technique was used to select 585 (295 public and 290 private) students from 12 (six public and six private) universities in southwest Nigeria. Two instruments--Cost and…

Measurements of carbon utilization by single bacterial species in sterile soil: insights into Rhizobium spp.

PubMed

Wigley, K; Wakelin, S A; Moot, D J; Hammond, S; Ridgway, H J

2016-08-01

The aim of this work was to develop a tool to investigate the influence of soil factors on carbon utilization activity of single micro-organisms. The assay for Rhizobium leguminosarum bv. trifolii in γ-irradiated soil, using the MicroResp(™) system, was optimized for sterility, incubation time, and moisture level. The optimized method was validated with experiments that assessed (i) differences in C utilization of different rhizobia strains and (ii) how this was affected by soil type. Carbon utilization differed among strains of the same species (and symbiovar), but some strains were more responsive to the soil environment than others. This novel modification of the MicroResp(™) has enabled the scope of carbon-utilization patterns of single strains of bacteria, such as Rh. leguminosarum bv. trifolii, to be studied in soil. The system is a new tool with applications in microbial ecology adaptable to the study of many culturable bacterial and fungal soil-borne taxa. It will allow measurement of a micro-organism's ability to utilize common C sources released in rhizosphere exudates to be measured in a physical soil background. This knowledge may improve selection efficiency and deployment of commercial microbial inoculants. © 2016 The Society for Applied Microbiology.

Utilization of turkey manure as granular activated carbon: physical, chemical and adsorptive properties.

PubMed

Lima, Isabel; Marshall, Wayne E

2005-01-01

The high availability of large quantities of turkey manure generated from turkey production makes it an attractive feedstock for carbon production. Pelletized samples of turkey litter and cake were converted to granular activated carbons (GACs) by steam activation. Water flow rate and activation time were changed to produce a range of activation conditions. The GACs were characterized for select physical (yield, surface area, bulk density, attrition), chemical (pH, surface charge) and adsorptive properties (copper ion uptake). Carbon physical and adsorptive properties were dependent on activation time and quantity of steam used as activant. Yields varied from 23% to 37%, surface area varied from 248 to 472 m(2)/g and copper ion adsorption varied from 0.72 to 1.86 mmol Cu(2+)/g carbon. Copper ion adsorption greatly exceeded the values for two commercial GACs. GACs from turkey litter and cake show considerable potential to remove metal ions from water.

Improvement of Toluene Selectivity via the Application of an Ethanol Oxidizing Catalytic Cell Upstream of a YSZ-Based Sensor for Air Monitoring Applications

PubMed Central

Sato, Tomoaki; Breedon, Michael; Miura, Norio

2012-01-01

The sensing characteristics of a yttria-stabilized zirconia (YSZ)-based sensor utilizing a NiO sensing-electrode (SE) towards toluene (C7H8) and interfering gases (C3H6, H2, CO, NO2 and C2H5OH) were evaluated with a view to selective C7H8 monitoring in indoor atmospheres. The fabricated YSZ-based sensor showed preferential responses toward 480 ppb C2H5OH, rather than the target 50 ppb C7H8 at an operational temperature of 450 °C under humid conditions (RH ≃ 32%). To overcome this limitation, the catalytic activity of Cr2O3, SnO2, Fe2O3 and NiO powders were evaluated for their selective ethanol oxidation ability. Among these oxides, SnO2 was found to selectively oxidize C2H5OH, thus improving C7H8 selectivity. An inline pre-catalytic cell loaded with SnO2 powder was installed upstream of the YSZ-based sensor utilizing NiO-SE, which enabled the following excellent abilities by selectively catalyzing common interfering gases; sensitive ppb level detection of C7H8 lower than the established Japanese Guideline value; low interferences from 50 ppb C3H6, 500 ppb H2, 100 ppb CO, 40 ppb NO2, as well as 480 ppb C2H5OH. These operational characteristics are all indicative that the developed sensor may be suitable for real-time C7H8 concentration monitoring in indoor environments. PMID:22666053

Cryogenic Model Materials

NASA Technical Reports Server (NTRS)

Kimmel, W. M.; Kuhn, N. S.; Berry, R. F.; Newman, J. A.

2001-01-01

An overview and status of current activities seeking alternatives to 200 grade 18Ni Steel CVM alloy for cryogenic wind tunnel models is presented. Specific improvements in material selection have been researched including availability, strength, fracture toughness and potential for use in transonic wind tunnel testing. Potential benefits from utilizing damage tolerant life-prediction methods, recently developed fatigue crack growth codes and upgraded NDE methods are also investigated. Two candidate alloys are identified and accepted for cryogenic/transonic wind tunnel models and hardware.

Iodine in foods. February 1974-December 1979 (citations from the Food Science and Technology Abstracts data base). Report for February 1974-December 1979

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

Young, C.G.

The bibliography cites reports dealing with determination, content and effects of iodine in foods and beverages such as milk and water. Methods of determination include utilization of ion-selective electrodes, gas chromatography and neutron activation analysis. I values of fats and oils are reported, as well as effects of iodophor preparations used for washing udders and milk equipment. (Contains 188 abstracts)

Regression Equations for Estimating Flood Flows at Selected Recurrence Intervals for Ungaged Streams in Pennsylvania

USGS Publications Warehouse

Roland, Mark A.; Stuckey, Marla H.

2008-01-01

Regression equations were developed for estimating flood flows at selected recurrence intervals for ungaged streams in Pennsylvania with drainage areas less than 2,000 square miles. These equations were developed utilizing peak-flow data from 322 streamflow-gaging stations within Pennsylvania and surrounding states. All stations used in the development of the equations had 10 or more years of record and included active and discontinued continuous-record as well as crest-stage partial-record stations. The state was divided into four regions, and regional regression equations were developed to estimate the 2-, 5-, 10-, 50-, 100-, and 500-year recurrence-interval flood flows. The equations were developed by means of a regression analysis that utilized basin characteristics and flow data associated with the stations. Significant explanatory variables at the 95-percent confidence level for one or more regression equations included the following basin characteristics: drainage area; mean basin elevation; and the percentages of carbonate bedrock, urban area, and storage within a basin. The regression equations can be used to predict the magnitude of flood flows for specified recurrence intervals for most streams in the state; however, they are not valid for streams with drainage areas generally greater than 2,000 square miles or with substantial regulation, diversion, or mining activity within the basin. Estimates of flood-flow magnitude and frequency for streamflow-gaging stations substantially affected by upstream regulation are also presented.

Facile fabrication of efficient organic CMOS circuits.

PubMed

Dzwilewski, Andrzej; Matyba, Piotr; Edman, Ludvig

2010-01-14

Organic electronic circuits based on a combination of n- and p-type transistors (so-called CMOS circuits) are attractive, since they promise the realization of a manifold of versatile and low-cost electronic devices. Here, we report a novel photoinduced transformation method, which allows for a particularly straightforward fabrication of highly functional organic CMOS circuits. A solution-deposited single-layer film, comprising a mixture of the n-type semiconductor [6,6]-phenyl-C(61)-butyric acid methyl ester (PCBM) and the p-type semiconductor poly-3-hexylthiophene (P3HT) in a 3:1 mass ratio, was utilized as the common active material in an array of transistors. Selected film areas were exposed to laser light, with the result that the irradiated PCBM monomers were photochemically transformed into a low-solubility and high-mobility dimeric state. Thereafter, the entire film was developed via immersion into a developer solution, which selectively removed the nonexposed, and monomeric, PCBM component. The end result was that the transistors in the exposed film areas are n-type, as dimeric PCBM is the majority component in the active material, while the transistors in the nonexposed film areas are p-type, as P3HT is the sole remaining material. We demonstrate the merit of the method by utilizing the resulting combination of n-type and p-type transistors for the realization of CMOS inverters with a high gain of approximately 35.

Photocatalytic conversion of CO2 into value-added and renewable fuels

NASA Astrophysics Data System (ADS)

Yuan, Lan; Xu, Yi-Jun

2015-07-01

The increasing energy crisis and the worsening global climate caused by the excessive utilization of fossil fuel have boosted tremendous research activities about CO2 capture, storage and utilization. Artificial photosynthesis that uses solar light energy to convert CO2 to form value-added and renewable fuels such as methane or methanol has been consistently drawing increasing attention. It is like killing two birds with one stone since it can not only reduce the greenhouse effects caused by CO2 emission but also produce value added chemicals for alternative energy supplying. This review provides a brief introduction about the basic principles of artificial photosynthesis of CO2 and the progress made in exploring more efficient photocatalysts from the viewpoint of light harvesting and photogenerated charge carriers boosting. Moreover, the undergoing mechanisms of CO2 photoreduction are discussed with selected examples, in terms of adsorption of reactants, CO2 activation as well as the possible reaction pathways. Finally, perspectives on future research directions and open issues in CO2 photoreduction are outlined.

Super Spy variants implicate flexibility in chaperone action.

PubMed

Quan, Shu; Wang, Lili; Petrotchenko, Evgeniy V; Makepeace, Karl At; Horowitz, Scott; Yang, Jianyi; Zhang, Yang; Borchers, Christoph H; Bardwell, James Ca

2014-01-01

Experimental study of the role of disorder in protein function is challenging. It has been proposed that proteins utilize disordered regions in the adaptive recognition of their various binding partners. However apart from a few exceptions, defining the importance of disorder in promiscuous binding interactions has proven to be difficult. In this paper, we have utilized a genetic selection that links protein stability to antibiotic resistance to isolate variants of the newly discovered chaperone Spy that show an up to 7 fold improved chaperone activity against a variety of substrates. These "Super Spy" variants show tighter binding to client proteins and are generally more unstable than is wild type Spy and show increases in apparent flexibility. We establish a good relationship between the degree of their instability and the improvement they show in their chaperone activity. Our results provide evidence for the importance of disorder and flexibility in chaperone function. DOI: http://dx.doi.org/10.7554/eLife.01584.001.

Super Spy variants implicate flexibility in chaperone action

PubMed Central

Quan, Shu; Wang, Lili; Petrotchenko, Evgeniy V; Makepeace, Karl AT; Horowitz, Scott; Yang, Jianyi; Zhang, Yang; Borchers, Christoph H; Bardwell, James CA

2014-01-01

Experimental study of the role of disorder in protein function is challenging. It has been proposed that proteins utilize disordered regions in the adaptive recognition of their various binding partners. However apart from a few exceptions, defining the importance of disorder in promiscuous binding interactions has proven to be difficult. In this paper, we have utilized a genetic selection that links protein stability to antibiotic resistance to isolate variants of the newly discovered chaperone Spy that show an up to 7 fold improved chaperone activity against a variety of substrates. These “Super Spy” variants show tighter binding to client proteins and are generally more unstable than is wild type Spy and show increases in apparent flexibility. We establish a good relationship between the degree of their instability and the improvement they show in their chaperone activity. Our results provide evidence for the importance of disorder and flexibility in chaperone function. DOI: http://dx.doi.org/10.7554/eLife.01584.001 PMID:24497545

Superhydrophobic Materials for Biomedical Applications

PubMed Central

Colson, Yolonda L.; Grinstaff, Mark W.

2016-01-01

Superhydrophobic surfaces are actively studied across a wide range of applications and industries, and are now finding increased use in the biomedical arena as substrates to control protein adsorption, cellular interaction, and bacterial growth, as well as platforms for drug delivery devices and for diagnostic tools. The commonality in the design of these materials is to create a stable or metastable air state at the material surface, which lends itself to a number of unique properties. These activities are catalyzing the development of new materials, applications, and fabrication techniques, as well as collaborations across material science, chemistry, engineering, and medicine given the interdisciplinary nature of this work. The review begins with a discussion of superhydrophobicity, and then explores biomedical applications that are utilizing superhydrophobicity in depth including material selection characteristics, in vitro performance, and in vivo performance. General trends are offered for each application in addition to discussion of conflicting data in the literature, and the review concludes with the authors’ future perspectives on the utility of superhydrophobic surfaces for biomedical applications. PMID:27449946

Stereocomplexes Formed From Select Oligomers of Polymer d-lactic Acid (PDLA) and l-lactate May Inhibit Growth of Cancer Cells and Help Diagnose Aggressive Cancers—Applications of the Warburg Effect

PubMed Central

Goldberg, Joel S.

2011-01-01

It is proposed that select oligomers of polymer d-lactic acid (PDLA) will form a stereocomplex with l-lactate in vivo, producing lactate deficiency in tumor cells. Those cancer cells that utilize transport of lactate to maintain electrical neutrality may cease to multiply or die because of lactate trapping, and those cancer cells that benefit from utilization of extracellular lactate may be impaired. Intracellular trapping of lactate produces a different physiology than inhibition of LDH because the cell loses the option of shuttling pyruvate to an alternative pathway to produce an anion. Conjugated with stains or fluorescent probes, PDLA oligomers may be an agent for the diagnosis of tissue lactate and possibly cell differentiation in biopsy specimens. Preliminary experimental evidence is presented confirming that PDLA in high concentrations is cytotoxic and that l-lactate forms a presumed stereocomplex with PDLA. Future work should be directed at isolation of biologically active oligomers of PDLA. PMID:21487535

Use of Polyamine Derivatives as Selective Histone Deacetylase Inhibitors

PubMed Central

Woster, Patrick M.

2014-01-01

Histone acetylation and deacetylation, mediated by histone acetyltransferase and the 11 isoforms of histone deacetylase, play an important role in gene expression. Histone deacetylase inhibitors have found utility in the treatment of cancer by promoting the reexpression of aberrantly silenced genes that code for tumor suppressor factors. It is unclear which of the 11 histone deacetylase isoforms are important in human cancer. We have designed a series of polyaminohydroxamic acid (PAHA) and polyaminobenzamide (PABA) histone deacetylase inhibitors that exhibit selectivity among four histone deacetylase isoforms. Although all of the active inhibitors promote reexpression of tumor suppressor factors, they produce variable cellular effects ranging from stimulation of growth to cytostasis and cytotoxicity. This chapter describes the procedures used to quantify the global and isoform-specific inhibition caused by these inhibitors, and techniques used to measure cellular effects such as reexpression of tumor suppressor proteins and hyperacetylation of histones H3 and H4. Procedures are also described to examine the ability of PAHAs and PABAs to utilize the polyamine transport system and to induce overexpression of the early apoptotic factor annexin A1. PMID:21318894

[Physiological basis of survival and rehabilitation of the residents of blockaded Leningrad].

PubMed

Magaeva, S V; Simonenko, V B

2012-01-01

The authors attribute survival of certain residents of blockaded Leningrad under conditions ofcomplete starvation to activation of natural sanologic mechanisms of the body. Physiological psychoemotional stress is supposed to contribute to the formation of prerequisites for survival during subsequent starvation. Also, the survival is believed to be related to selected activation of apoptosis of renewable cells and utilization of their constituents in endogenous nutrition. The role of priority energetic and trophic support of brain and kidneys and the contribution of the psychosomatic factor are postulated. The mechanisms of rehabilitation after upset of vital activity involve partial reversibility of atrophic and metabolic processes and neural regulation of organs and their systems. The importance of the study of activation of natural sanologic mechanisms in extreme conditions is discussed

Spatial Niche Segregation of Sympatric Stone Marten and Pine Marten--Avoidance of Competition or Selection of Optimal Habitat?

PubMed

Wereszczuk, Anna; Zalewski, Andrzej

2015-01-01

Coexistence of ecologically similar species relies on differences in one or more dimensions of their ecological niches, such as space, time and resources in diel and/or seasonal scales. However, niche differentiation may result from other mechanisms such as avoidance of high predation pressure, different adaptations or requirements of ecologically similar species. Stone marten (Martes foina) and pine marten (Martes martes) occur sympatrically over a large area in Central Europe and utilize similar habitats and food, therefore it is expected that their coexistence requires differentiation in at least one of their niche dimensions or the mechanisms through which these dimensions are used. To test this hypothesis, we used differences in the species activity patterns and habitat selection, estimated with a resource selection function (RSF), to predict the relative probability of occurrence of the two species within a large forest complex in the northern geographic range of the stone marten. Stone martens were significantly heavier, have a longer body and a better body condition than pine martens. We found weak evidence for temporal niche segregation between the species. Stone and pine martens were both primarily nocturnal, but pine martens were active more frequently during the day and significantly reduced the duration of activity during autumn-winter. Stone and pine martens utilized different habitats and almost completely separated their habitat niches. Stone marten strongly preferred developed areas and avoided meadows and coniferous or deciduous forests. Pine marten preferred deciduous forest and small patches covered by trees, and avoided developed areas and meadows. We conclude that complete habitat segregation of the two marten species facilitates sympatric coexistence in this area. However, spatial niche segregation between these species was more likely due to differences in adaptation to cold climate, avoidance of high predator pressure and/or food preferences by both species than competitive interaction between them.

Expected Utility Distributions for Flexible, Contingent Execution

NASA Technical Reports Server (NTRS)

Bresina, John L.; Washington, Richard

2000-01-01

This paper presents a method for using expected utility distributions in the execution of flexible, contingent plans. A utility distribution maps the possible start times of an action to the expected utility of the plan suffix starting with that action. The contingent plan encodes a tree of possible courses of action and includes flexible temporal constraints and resource constraints. When execution reaches a branch point, the eligible option with the highest expected utility at that point in time is selected. The utility distributions make this selection sensitive to the runtime context, yet still efficient. Our approach uses predictions of action duration uncertainty as well as expectations of resource usage and availability to determine when an action can execute and with what probability. Execution windows and probabilities inevitably change as execution proceeds, but such changes do not invalidate the cached utility distributions, thus, dynamic updating of utility information is minimized.

Demand-Side Management and Integrated Resource Planning: Findings from a Survey of 24 Electric Utilities

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

Schweitzer, M.

1991-01-01

Integrated resource planning differs from traditional utility planning practices primarily in its increased attention to demand-side management (DSM) programs and its integration of supply- and demand-side resources into a combined resource portfolio. This report details the findings from an Oak Ridge National Laboratory (ORNL) survey of 24 electric utilities that have well-developed integrated planning processes. These utilities account for roughly one-third of total capacity, electricity generation, and DSM-program expenditures nationwide. The ORNL survey was designed to obtain descriptive data on a national sample of utilities and to test a number of hypothesized relationships between selected utility characteristics and the mixmore » of resources selected for the integrated plan, with an emphasis on the use of DSM resources and the processes by which they are chosen. The survey solicited information on each utility's current and projected resource mix, operating environment, procedures used to screen potential DSM resources, techniques used to obtain public input and to integrate supply- and demand-side options into a unified plan, and procedures used in the final selection of resources for the plan.« less

Halogenase engineering and its utility in medicinal chemistry.

PubMed

Fraley, Amy E; Sherman, David H

2018-06-15

Halogenation is commonly used in medicinal chemistry to improve the potency of pharmaceutical leads. While synthetic methods for halogenation present selectivity and reactivity challenges, halogenases have evolved over time to perform selective reactions under benign conditions. The optimization of halogenation biocatalysts has utilized enzyme evolution and structure-based engineering alongside biotransformation in a variety of systems to generate stable site-selective variants. The recent improvements in halogenase-catalyzed reactions has demonstrated the utility of these biocatalysts for industrial purposes, and their ability to achieve a broad substrate scope implies a synthetic tractability with increasing relevance in medicinal chemistry. Copyright © 2018 Elsevier Ltd. All rights reserved.

Double Blind Test For Bio-Stimulation Effects On Pain Relief By Diode Laser

NASA Astrophysics Data System (ADS)

Saeki, Norio; Sembokuya, Iwajiro; Arakawa, Kazuo; Fujimasa, Iwao; Mabuchi, Kunihiko; Abe, Yuusuke; Atsumi, Kazuhiko

1989-09-01

The bio-stimulation effect of semiconductor laser on therapeutic pain relief was investigated by conducting a double blind test performed on more than one hundred patient subjects suffering from various neualgia. A compact laser therapeutic equipment with two laser probes each having 60 mW power was developed and utilized for the experiment. Each probe was driven by either the active or the dummy source selected randomly, and its results were stored in the memory for statistical processing. The therapeutic treatments including active and dummy treatments were performed on 102 subjects. The pain relief effects were confirmed for 85.5% of the subjects.

Computer aided drug discovery of highly ligand efficient, low molecular weight imidazopyridine analogs as FLT3 inhibitors

PubMed Central

Frett, Brendan; McConnell, Nick; Smith, Catherine C.; Wang, Yuanxiang; Shah, Neil P.; Li, Hong-yu

2015-01-01

The FLT3 kinase represents an attractive target to effectively treat AML. Unfortunately, no FLT3 targeted therapeutic is currently approved. In line with our continued interests in treating kinase related disease for anti-FLT3 mutant activity, we utilized pioneering synthetic methodology in combination with computer aided drug discovery and identified low molecular weight, highly ligand efficient, FLT3 kinase inhibitors. Compounds were analyzed for biochemical inhibition, their ability to selectively inhibit cell proliferation, for FLT3 mutant activity, and preliminary aqueous solubility. Validated hits were discovered that can serve as starting platforms for lead candidates. PMID:25765758

Contaminant removal from enclosed atmospheres by regenerable adsorbents

NASA Technical Reports Server (NTRS)

Goldsmith, R. L.; Mcnulty, K. J.; Freedland, G. M.; Turk, A.; Nwankwo, J.

1974-01-01

A system for removing contaminants from spacecraft atmospheres was studied, which utilizes catalyst-impregnated activated carbon followed by in-situ regeneration by low-temperature catalytic oxidation of the adsorbed contaminants. Platinum was deposited on activated carbon by liquid phase impregnation with chloroplatinic acid, followed by drying and high-temperature reduction. Results were obtained for the seven selected spacecraft contaminants by means of three experimental test systems. The results indicate that the contaminants could be removed by oxidation with very little loss in adsorptive capacity. The advantages of a catalyst-impregnated carbon for oxidative regeneration are found to be significant enough to warrent its use.

Service Demand Discovery Mechanism for Mobile Social Networks.

PubMed

Wu, Dapeng; Yan, Junjie; Wang, Honggang; Wang, Ruyan

2016-11-23

In the last few years, the service demand for wireless data over mobile networks has continually been soaring at a rapid pace. Thereinto, in Mobile Social Networks (MSNs), users can discover adjacent users for establishing temporary local connection and thus sharing already downloaded contents with each other to offload the service demand. Due to the partitioned topology, intermittent connection and social feature in such a network, the service demand discovery is challenging. In particular, the service demand discovery is exploited to identify the best relay user through the service registration, service selection and service activation. In order to maximize the utilization of limited network resources, a hybrid service demand discovery architecture, such as a Virtual Dictionary User (VDU) is proposed in this paper. Based on the historical data of movement, users can discover their relationships with others. Subsequently, according to the users activity, VDU is selected to facilitate the service registration procedure. Further, the service information outside of a home community can be obtained through the Global Active User (GAU) to support the service selection. To provide the Quality of Service (QoS), the Service Providing User (SPU) is chosen among multiple candidates. Numerical results show that, when compared with other classical service algorithms, the proposed scheme can improve the successful service demand discovery ratio by 25% under reduced overheads.

Structure-based optimization of a series of selective BET inhibitors containing aniline or indoline groups.

PubMed

Hu, Jianping; Wang, Yingqing; Li, Yanlian; Cao, Danyan; Xu, Lin; Song, ShanShan; Damaneh, Mohammadali Soleimani; Li, Jian; Chen, Yuelei; Wang, Xin; Chen, Lin; Shen, Jingkang; Miao, Zehong; Xiong, Bing

2018-04-25

Recently, several kinase inhibitors were found to also inhibit bromodomains, providing a new strategy for the discovery of bromodomain inhibitors. Along this line, starting from PLK1-BRD4 dual inhibitor BI-2536, we discovered a new series of dihydroquinoxalin-2(1H)-one with aniline and indoline WPF binders as selective BRD4 inhibitors. They showed better BRD4-BD1 potency and negligible PLK1 kinase activity comparing with BI-2536. Additionally, dihydroquinoxalin-2(1H)-ones containing indoline group showed profound activities in molecular and cellular based assays. Throughout the study, compounds 9, 28 and 37 showed significant inhibitory activity for c-Myc or PD-L1 protein expression and mRNA transcription both at concentration of 0.2 and 1 μM. Compound 9 was found possessing the best balance of binding affinity, in vitro metabolic stability and in vivo pharmacokinetic properties. Therefore, it was selected for in vivo pharmacological study. By using MM.1S cell derived xenograft model, we confirmed compound 9 showed comparable in vivo tumor inhibition to phase II investigation drug I-BET762, which, together with the novel WPF binder, further indicated the utility of this series of BRD4 inhibitors. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Manifold Regularized Experimental Design for Active Learning.

PubMed

Zhang, Lining; Shum, Hubert P H; Shao, Ling

2016-12-02

Various machine learning and data mining tasks in classification require abundant data samples to be labeled for training. Conventional active learning methods aim at labeling the most informative samples for alleviating the labor of the user. Many previous studies in active learning select one sample after another in a greedy manner. However, this is not very effective because the classification models has to be retrained for each newly labeled sample. Moreover, many popular active learning approaches utilize the most uncertain samples by leveraging the classification hyperplane of the classifier, which is not appropriate since the classification hyperplane is inaccurate when the training data are small-sized. The problem of insufficient training data in real-world systems limits the potential applications of these approaches. This paper presents a novel method of active learning called manifold regularized experimental design (MRED), which can label multiple informative samples at one time for training. In addition, MRED gives an explicit geometric explanation for the selected samples to be labeled by the user. Different from existing active learning methods, our method avoids the intrinsic problems caused by insufficiently labeled samples in real-world applications. Various experiments on synthetic datasets, the Yale face database and the Corel image database have been carried out to show how MRED outperforms existing methods.

Cost-effectiveness methodology for computer systems selection

NASA Technical Reports Server (NTRS)

Vallone, A.; Bajaj, K. S.

1980-01-01

A new approach to the problem of selecting a computer system design has been developed. The purpose of this methodology is to identify a system design that is capable of fulfilling system objectives in the most economical way. The methodology characterizes each system design by the cost of the system life cycle and by the system's effectiveness in reaching objectives. Cost is measured by a 'system cost index' derived from an analysis of all expenditures and possible revenues over the system life cycle. Effectiveness is measured by a 'system utility index' obtained by combining the impact that each selection factor has on the system objectives and it is assessed through a 'utility curve'. A preestablished algorithm combines cost and utility and provides a ranking of the alternative system designs from which the 'best' design is selected.

Effective Sensor Selection and Data Anomaly Detection for Condition Monitoring of Aircraft Engines

PubMed Central

Liu, Liansheng; Liu, Datong; Zhang, Yujie; Peng, Yu

2016-01-01

In a complex system, condition monitoring (CM) can collect the system working status. The condition is mainly sensed by the pre-deployed sensors in/on the system. Most existing works study how to utilize the condition information to predict the upcoming anomalies, faults, or failures. There is also some research which focuses on the faults or anomalies of the sensing element (i.e., sensor) to enhance the system reliability. However, existing approaches ignore the correlation between sensor selecting strategy and data anomaly detection, which can also improve the system reliability. To address this issue, we study a new scheme which includes sensor selection strategy and data anomaly detection by utilizing information theory and Gaussian Process Regression (GPR). The sensors that are more appropriate for the system CM are first selected. Then, mutual information is utilized to weight the correlation among different sensors. The anomaly detection is carried out by using the correlation of sensor data. The sensor data sets that are utilized to carry out the evaluation are provided by National Aeronautics and Space Administration (NASA) Ames Research Center and have been used as Prognostics and Health Management (PHM) challenge data in 2008. By comparing the two different sensor selection strategies, the effectiveness of selection method on data anomaly detection is proved. PMID:27136561

Effective Sensor Selection and Data Anomaly Detection for Condition Monitoring of Aircraft Engines.

PubMed

Liu, Liansheng; Liu, Datong; Zhang, Yujie; Peng, Yu

2016-04-29

In a complex system, condition monitoring (CM) can collect the system working status. The condition is mainly sensed by the pre-deployed sensors in/on the system. Most existing works study how to utilize the condition information to predict the upcoming anomalies, faults, or failures. There is also some research which focuses on the faults or anomalies of the sensing element (i.e., sensor) to enhance the system reliability. However, existing approaches ignore the correlation between sensor selecting strategy and data anomaly detection, which can also improve the system reliability. To address this issue, we study a new scheme which includes sensor selection strategy and data anomaly detection by utilizing information theory and Gaussian Process Regression (GPR). The sensors that are more appropriate for the system CM are first selected. Then, mutual information is utilized to weight the correlation among different sensors. The anomaly detection is carried out by using the correlation of sensor data. The sensor data sets that are utilized to carry out the evaluation are provided by National Aeronautics and Space Administration (NASA) Ames Research Center and have been used as Prognostics and Health Management (PHM) challenge data in 2008. By comparing the two different sensor selection strategies, the effectiveness of selection method on data anomaly detection is proved.

Time-Dependent Trapping of Pollinators Driven by the Alignment of Floral Phenology with Insect Circadian Rhythms

PubMed Central

Lau, Jenny Y. Y.; Guo, Xing; Pang, Chun-Chiu; Tang, Chin Cheung; Thomas, Daniel C.; Saunders, Richard M. K.

2017-01-01

Several evolutionary lineages in the early divergent angiosperm family Annonaceae possess flowers with a distinctive pollinator trapping mechanism, in which floral phenological events are very precisely timed in relation with pollinator activity patterns. This contrasts with previously described angiosperm pollinator traps, which predominantly function as pitfall traps. We assess the circadian rhythms of pollinators independently of their interactions with flowers, and correlate these data with detailed assessments of floral phenology. We reveal a close temporal alignment between patterns of pollinator activity and the floral phenology driving the trapping mechanism (termed ‘circadian trapping’ here). Non-trapping species with anthesis of standard duration (c. 48 h) cannot be pollinated effectively by pollinators with a morning-unimodal activity pattern; non-trapping species with abbreviated anthesis (23–27 h) face limitations in utilizing pollinators with a bimodal circadian activity; whereas species that trap pollinators (all with short anthesis) can utilize a broader range of potential pollinators, including those with both unimodal and bimodal circadian rhythms. In addition to broadening the range of potential pollinators based on their activity patterns, circadian trapping endows other selective advantages, including the possibility of an extended staminate phase to promote pollen deposition, and enhanced interfloral movement of pollinators. The relevance of the alignment of floral phenological changes with peaks in pollinator activity is furthermore evaluated for pitfall trap pollination systems. PMID:28713403

Carbon Dioxide Methanation for Human Exploration of Mars: A Look at Catalyst Longevity and Activity Using Supported Ruthenium

NASA Technical Reports Server (NTRS)

Petersen, Elspeth M.; Meier, Anne J.; Tessonnier, Jean-Philippe

2018-01-01

Overarching Purpose: To design a carbon dioxide methanation/Sabatier reaction catalyst able to withstand variable conditions including fluctuations in bed temperature and feed flow rates for 480 days of remote operation to produce seven tons of methane. Current Study Purpose: Examine supported Ruthenium as a carbon dioxide methanation catalyst to determine the effects support properties have on the active phase by studying activity and selectivity. Objective: The remote operation of the Mars ISRU (In Situ Resources Utilization) lander to produce rocket fuel prior to crew arrival on the planet to power an ascent vehicle. Constraints: Long-term operation (480 days); Variable conditions: Feed gas flow rates, Feed gas flow ratios, Reactor bed temperature.

Utility of multi-channel surface electromyography in assessment of focal hand dystonia.

PubMed

Sivadasan, Ajith; Sanjay, M; Alexander, Mathew; Devasahayam, Suresh R; Srinivasa, Babu K

2013-09-01

Surface electromyography (SEMG) allows objective assessment and guides selection of appropriate treatment in focal hand dystonia (FHD). Sixteen-channel SEMG obtained during different phases of a writing task was used to study timing, activation patterns, and spread of muscle contractions in FHD compared with normal controls. Customized software was developed to acquire and analyze EMG signals. SEMG of FHD subjects (20) showed "early onset" during motor imagery, rapid proximal muscle recruitment, agonist-antagonist co-contraction involving proximal muscle groups, "delayed offset" after stopping writing, higher rectified mean amplitudes, and mirror activity in contralateral limb compared with controls (16). Muscle activation latencies were heterogenous in FHD. Anticipation, delayed relaxation, and mirror EMG activation were noted in FHD. A clear pattern of muscle activation cannot be ascertained. Multi-channel SEMG can aid in objective assessment of temporal-spatial distribution of activity and can refine targeted therapies like chemodenervation and biofeedback. Copyright © 2013 Wiley Periodicals, Inc.

Regional differences in mu and kappa opioid receptor G-protein activation in brain in male and female prairie voles.

PubMed

Martin, T J; Sexton, T; Kim, S A; Severino, A L; Peters, C M; Young, L J; Childers, S R

2015-12-17

Prairie voles are unusual mammals in that, like humans, they are capable of forming socially monogamous pair bonds, display biparental care, and engage in alloparental behaviors. Both mu and kappa opioid receptors are involved in behaviors that either establish and maintain, or result from pair bond formation in these animals. Mu and kappa opioid receptors both utilize inhibitory G-proteins in signal transduction mechanisms, however the efficacy by which these receptor subtypes stimulate G-protein signaling across the prairie vole neuraxis is not known. Utilizing [(35)S]GTPγS autoradiography, we characterized the efficacy of G-protein stimulation in coronal sections throughout male and female prairie vole brains by [D-Ala2,NMe-Phe4,Gly-ol5]-enkephalin (DAMGO) and U50,488H, selective mu and kappa opioid agonists, respectively. DAMGO stimulation was highest in the forebrain, similar to that found with other rodent species. U-50,488H produced greater stimulation in prairie voles than is typically seen in mice and rats, particularly in select forebrain areas. DAMGO produced higher stimulation in the core versus the shell of the nucleus accumbens (NAc) in females, while the distribution of U-50,488H stimulation was the opposite. There were no gender differences for U50,488H stimulation of G-protein activity across the regions examined, while DAMGO stimulation was greater in sections from females compared to those from males for NAc core, entopeduncular nucleus, and hippocampus. These data suggest that the kappa opioid system may be more sensitive to manipulation in prairie voles compared to mice and rats, and that female prairie voles may be more sensitive to mu agonists in select brain regions than males. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

Relationship of nutrition and physical activity behaviors and fitness measures to academic performance for sixth graders in a midwest city school district.

PubMed

Edwards, Jane U; Mauch, Lois; Winkelman, Mark R

2011-02-01

To support curriculum and policy, a midwest city school district assessed the association of selected categories of nutrition and physical activity (NUTR/PA) behaviors, fitness measures, and body mass index (BMI) with academic performance (AP) for 800 sixth graders. Students completed an adapted Youth Risk Behavior Surveillance Survey (NUTR/PA behaviors), fitness assessments (mile run, curl-ups, push-ups, height, and weight) with results matched to standardized scores (Measures of Academic Progress [MAP]), meal price status, and gender. Differences in mean MAP scores (math and reading) were compared by selected categories of each variable utilizing 1-way analysis of variance. Associations were determined by stepwise multiple regression utilizing mean MAP scores (for math and for reading) as the dependent variable and NUTR/PA behaviors, fitness, and BMI categories as independent variables. Significance was set at α = 0.05. Higher MAP math scores were associated with NUTR (more milk and breakfast; less 100% fruit juice and sweetened beverages [SB]) and PA (increased vigorous PA and sports teams; reduced television), and fitness (higher mile run performance). Higher MAP reading scores were associated with NUTR (fewer SB) and PA (increased vigorous PA, reduced television). Regression analysis indicated about 11.1% of the variation in the mean MAP math scores and 6.7% of the mean MAP reading scores could be accounted for by selected NUTR/PA behaviors, fitness, meal price status, and gender. Many positive NUTR/PA behaviors and fitness measures were associated with higher MAP scores supporting the school district focus on healthy lifestyles. Additional factors, including meal price status and gender, contribute to AP. © 2011, Fargo Public School.

Exploring the anti-cancer activity of novel thiosemicarbazones generated through the combination of retro-fragments: dissection of critical structure-activity relationships.

PubMed

Serda, Maciej; Kalinowski, Danuta S; Rasko, Nathalie; Potůčková, Eliška; Mrozek-Wilczkiewicz, Anna; Musiol, Robert; Małecki, Jan G; Sajewicz, Mieczysław; Ratuszna, Alicja; Muchowicz, Angelika; Gołąb, Jakub; Simůnek, Tomáš; Richardson, Des R; Polanski, Jaroslaw

2014-01-01

Thiosemicarbazones (TSCs) are an interesting class of ligands that show a diverse range of biological activity, including anti-fungal, anti-viral and anti-cancer effects. Our previous studies have demonstrated the potent in vivo anti-tumor activity of novel TSCs and their ability to overcome resistance to clinically used chemotherapeutics. In the current study, 35 novel TSCs of 6 different classes were designed using a combination of retro-fragments that appear in other TSCs. Additionally, di-substitution at the terminal N4 atom, which was previously identified to be critical for potent anti-cancer activity, was preserved through the incorporation of an N4-based piperazine or morpholine ring. The anti-proliferative activity of the novel TSCs were examined in a variety of cancer and normal cell-types. In particular, compounds 1d and 3c demonstrated the greatest promise as anti-cancer agents with potent and selective anti-proliferative activity. Structure-activity relationship studies revealed that the chelators that utilized "soft" donor atoms, such as nitrogen and sulfur, resulted in potent anti-cancer activity. Indeed, the N,N,S donor atom set was crucial for the formation of redox active iron complexes that were able to mediate the oxidation of ascorbate. This further highlights the important role of reactive oxygen species generation in mediating potent anti-cancer activity. Significantly, this study identified the potent and selective anti-cancer activity of 1d and 3c that warrants further examination.

A behavioural and neural evaluation of prospective decision-making under risk

PubMed Central

Symmonds, Mkael; Bossaerts, Peter; Dolan, Raymond J.

2010-01-01

Making the best choice when faced with a chain of decisions requires a person to judge both anticipated outcomes and future actions. Although economic decision-making models account for both risk and reward in single choice contexts there is a dearth of similar knowledge about sequential choice. Classical utility-based models assume that decision-makers select and follow an optimal pre-determined strategy, irrespective of the particular order in which options are presented. An alternative model involves continuously re-evaluating decision utilities, without prescribing a specific future set of choices. Here, using behavioral and functional magnetic resonance imaging (fMRI) data, we studied human subjects in a sequential choice task and use these data to compare alternative decision models of valuation and strategy selection. We provide evidence that subjects adopt a model of re-evaluating decision utilities, where available strategies are continuously updated and combined in assessing action values. We validate this model by using simultaneously-acquired fMRI data to show that sequential choice evokes a pattern of neural response consistent with a tracking of anticipated distribution of future reward, as expected in such a model. Thus, brain activity evoked at each decision point reflects the expected mean, variance and skewness of possible payoffs, consistent with the idea that sequential choice evokes a prospective evaluation of both available strategies and possible outcomes. PMID:20980595

ToHajiilee Economic Development, Inc.(TEDI) Feasibility Study for Utility-Scale Solar

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

Burpo, Rob

2012-02-29

To Hajiilee Economic Development, Inc. (TEDI) is the economic development entity representing the ToHajiilee Chapter of the Navajo Nation, also known as the Caoncito Band of Navajo (CBN). Using DOE funding, TEDI assembled a team of qualified advisors to conduct a feasibility study for a utility-scale 30 MW Photovoltaic (PV) solar power generation facility on TEDI trust lands. The goal for this project has been to gather information and practical business commitments to successfully complete the feasibility analysis. The TEDI approach was to successively make informed decisions to select an appropriate technology best suited to the site, determine environmental viabilitymore » of the site, secure options for the sale of generated power, determine practicality of transmission and interconnection of power to the local grid, and secure preliminary commitments on project financing. The feasibility study has been completed and provides TEDI with a practical understanding of its business options in moving forward with developing a solar project on CBN tribal lands. Funding from DOE has allowed TEDI and its team of professional advisors to carefully select technology and business partners and build a business model to develop this utility-scale solar project. As a result of the positive feasibility findings, TEDI is moving forward with finalizing all pre-construction activities for its major renewable energy project.« less

A behavioral and neural evaluation of prospective decision-making under risk.

PubMed

Symmonds, Mkael; Bossaerts, Peter; Dolan, Raymond J

2010-10-27

Making the best choice when faced with a chain of decisions requires a person to judge both anticipated outcomes and future actions. Although economic decision-making models account for both risk and reward in single-choice contexts, there is a dearth of similar knowledge about sequential choice. Classical utility-based models assume that decision-makers select and follow an optimal predetermined strategy, regardless of the particular order in which options are presented. An alternative model involves continuously reevaluating decision utilities, without prescribing a specific future set of choices. Here, using behavioral and functional magnetic resonance imaging (fMRI) data, we studied human subjects in a sequential choice task and use these data to compare alternative decision models of valuation and strategy selection. We provide evidence that subjects adopt a model of reevaluating decision utilities, in which available strategies are continuously updated and combined in assessing action values. We validate this model by using simultaneously acquired fMRI data to show that sequential choice evokes a pattern of neural response consistent with a tracking of anticipated distribution of future reward, as expected in such a model. Thus, brain activity evoked at each decision point reflects the expected mean, variance, and skewness of possible payoffs, consistent with the idea that sequential choice evokes a prospective evaluation of both available strategies and possible outcomes.

An FDA oncology analysis of immune activating products and first-in-human dose selection.

PubMed

Saber, Haleh; Gudi, Ramadevi; Manning, Michael; Wearne, Emily; Leighton, John K

2016-11-01

As sub-therapeutic doses are not medically justifiable in patients with cancer, we retrospectively analyzed data on immune activating products, to assess approaches used in first-in-human (FIH) dose selection, the utility of animal toxicology studies in dose selection, and the length of time to complete FIH trials. The information collected included pharmacology and toxicology data, FIH dose and rationale, and dose-finding trial design. We used the principles of the Hill equation to estimate the FIH doses for antibodies and compared them to the doses administered to patients with acceptable toxicities. For approximately half the antibodies (44%) examined, the FIH doses were at least a hundred-fold lower than the doses safely administered to patients, indicating optimization of FIH dose selection and/or optimization of dose-finding trial design is needed to minimize patient exposure to sub-therapeutic doses. However, selection of the FIH dose for antibodies based on animal toxicology studies using 1/6th the HNSTD or 1/10th the NOAEL resulted in human doses that were unsafe for several antibodies examined. We also concluded that antibodies with Fc-modifications for increased effector function may be less tolerated, resulting in toxicities at lower doses than those without such modifications. There was insufficient information to evaluate CD3 bispecific products. Published by Elsevier Inc.

Taste Receptor Signaling-- From Tongues to Lungs

PubMed Central

Kinnamon, Sue C.

2013-01-01

Taste buds are the transducing endorgans of gustation. Each taste bud comprises 50–100 elongated cells, which extend from the basal lamina to the surface of the tongue, where their apical microvilli encounter taste stimuli in the oral cavity. Salts and acids utilize apically located ion channels for transduction, while bitter, sweet and umami (glutamate) stimuli utilize G protein coupled receptors (GPCRs) and second messenger signaling mechanisms. This review will focus on GPCR signaling mechanisms. Two classes of taste GPCRs have been identified, the T1Rs for sweet and umami (glutamate) stimuli, and the T2Rs for bitter stimuli. These low affinity GPCRs all couple to the same downstream signaling effectors that include Gβγ activation of PLCβ2, IP3-mediated release of Ca2+ from intracellular stores, and Ca2+-dependent activation of the monovalent selective cation channel, TrpM5. These events lead to membrane depolarization, action potentials, and release of ATP as a transmitter to activate gustatory afferents. The Gα subunit, α-gustducin, activates a phosphodiesterase to decrease intracellular cAMP levels, although the precise targets of cAMP have not been identified. With the molecular identification of the taste GPCRs, it has become clear that taste signaling is not limited to taste buds, but occurs in many cell types of the airways. These include solitary chemosensory cells, ciliated epithelial cells, and smooth muscle cells. Bitter receptors are most abundantly expressed in the airways, where they respond to irritating chemicals and promote protective airway reflexes, utilizing the same downstream signaling effectors as taste cells. PMID:21481196

Paternity testing a non-linkage based marker assisted selection scheme for outbred forage species

USDA-ARS?s Scientific Manuscript database

In many major perennial forage species, genomic tools and infrastructure development has advanced enough that their utilization in marker assisted selection (MAS) can be cheaply explored. This paper presents a paternity testing MAS in diploid red clover (Trifolium pratense L.). Utilizing individual ...

The impact of utilizing mobile phones to promote physical activity among post-secondary students: a scoping review

PubMed Central

2016-01-01

A commitment to regular physical activity may reduce the risks of chronic diseases for young adults. Internationally, the majority of post-secondary students are insufficiently active for health benefits. Novel health strategies and interventions utilizing mobiles phones could increase post-secondary students’ physical activity levels. However, there is contradictory evidence to support the use of mobile phones to promote physical activity, and a scoping review could provide further insights into this topic. The purpose of this study was to conduct a scoping review to explore the existing literature and investigate what is currently known about the use of mobile phones to enhance physical activity levels among post-secondary students. A total of 84 articles were identified from the literature search, and six studies were selected for data analysis. Two major themes were supported by the evidence, which included: (I) the relationship between mobile phones and physical activity levels; and (II) students’ perceptions of mobile phones. Goal setting principles combined with text message interventions were reported to have significant influences on students’ physical activity levels. Students expressed mixed feelings about coaching elements of apps and posting personal results on social networking websites. No studies reported the use of objective physical activity measurements. In conclusion, mobile phone technologies such as text message reminders could be included in health interventions to enhance post-secondary students’ physical activity levels. There is limited evidence available on this topic and additional research is warranted to establish a clearer understanding of the relationship between mobile phones and post-secondary students’ physical activity. PMID:28293617

The impact of utilizing mobile phones to promote physical activity among post-secondary students: a scoping review.

PubMed

Ly, Hieu

2016-01-01

A commitment to regular physical activity may reduce the risks of chronic diseases for young adults. Internationally, the majority of post-secondary students are insufficiently active for health benefits. Novel health strategies and interventions utilizing mobiles phones could increase post-secondary students' physical activity levels. However, there is contradictory evidence to support the use of mobile phones to promote physical activity, and a scoping review could provide further insights into this topic. The purpose of this study was to conduct a scoping review to explore the existing literature and investigate what is currently known about the use of mobile phones to enhance physical activity levels among post-secondary students. A total of 84 articles were identified from the literature search, and six studies were selected for data analysis. Two major themes were supported by the evidence, which included: (I) the relationship between mobile phones and physical activity levels; and (II) students' perceptions of mobile phones. Goal setting principles combined with text message interventions were reported to have significant influences on students' physical activity levels. Students expressed mixed feelings about coaching elements of apps and posting personal results on social networking websites. No studies reported the use of objective physical activity measurements. In conclusion, mobile phone technologies such as text message reminders could be included in health interventions to enhance post-secondary students' physical activity levels. There is limited evidence available on this topic and additional research is warranted to establish a clearer understanding of the relationship between mobile phones and post-secondary students' physical activity.

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

Pihl, Josh A.; Toops, Todd J.; Fisher, Galen B.

Lean gasoline engines running on ethanol/gasoline blends and equipped with a silver/alumina catalyst for selective catalytic reduction (SCR) of NO by ethanol provide a pathway to reduced petroleum consumption through both increased biofuel utilization and improved engine efficiency relative to the current stoichiometric gasoline engines that dominate the U.S. light duty vehicle fleet. A pre-commercial silver/alumina catalyst demonstrated high NO x conversions over a moderate temperature window with both neat ethanol and ethanol/gasoline blends containing at least 50% ethanol. Selectivity to NH 3 increases with HC dosing and ethanol content in gasoline blends, but appears to saturate at around 45%.more » NO 2 and acetaldehyde behave like intermediates in the ethanol SCR of NO. NH 3 SCR of NO x does not appear to play a major role in the ethanol SCR reaction mechanism. Ethanol is responsible for the low temperature SCR activity observed with the ethanol/gasoline blends. In conclusion, the gasoline HCs do not deactivate the catalyst ethanol SCR activity, but they also do not appear to be significantly activated by the presence of ethanol.« less

High voltage power supply with modular series resonant inverters

DOEpatents

Dreifuerst, Gary R.; Merritt, Bernard T.

1995-01-01

A relatively small and compact high voltage, high current power supply for a laser utilizes a plurality of modules containing series resonant half bridge inverters. A pair of reverse conducting thyristors are incorporated in each series resonant inverter module such that the series resonant inverter modules are sequentially activated in phases 360.degree./n apart, where n=number of modules for n>2. Selective activation of the modules allows precise output control reducing ripple and improving efficiency. Each series resonant half bridge inverter module includes a transformer which has a cooling manifold for actively circulating a coolant such as water, to cool the transformer core as well as selected circuit elements. Conductors connecting and forming various circuit components comprise hollow, electrically conductive tubes such as copper. Coolant circulates through the tubes to remove heat. The conductive tubes act as electrically conductive lines for connecting various components of the power supply. Where it is desired to make electrical isolation breaks, tubes comprised of insulating material such as nylon are used to provide insulation and continue the fluid circuit.

High voltage power supply with modular series resonant inverters

DOEpatents

Dreifuerst, G.R.; Merritt, B.T.

1995-07-18

A relatively small and compact high voltage, high current power supply for a laser utilizes a plurality of modules containing series resonant half bridge inverters. A pair of reverse conducting thyristors are incorporated in each series resonant inverter module such that the series resonant inverter modules are sequentially activated in phases 360{degree}/n apart, where n=number of modules for n>2. Selective activation of the modules allows precise output control reducing ripple and improving efficiency. Each series resonant half bridge inverter module includes a transformer which has a cooling manifold for actively circulating a coolant such as water, to cool the transformer core as well as selected circuit elements. Conductors connecting and forming various circuit components comprise hollow, electrically conductive tubes such as copper. Coolant circulates through the tubes to remove heat. The conductive tubes act as electrically conductive lines for connecting various components of the power supply. Where it is desired to make electrical isolation breaks, tubes comprised of insulating material such as nylon are used to provide insulation and continue the fluid circuit. 11 figs.

Physical therapists' perceptions of the roles of the physical therapist assistant.

PubMed

Robinson, A J; McCall, M; DePalma, M T; Clayton-Krasinski, D; Tingley, S; Simoncelli, S; Harnish, L

1994-06-01

This longitudinal study investigated physical therapists' perceptions of the roles of physical therapist assistants (PTAs). In 1986, a questionnaire describing 79 physical therapy activities was distributed to a random sample (n = 400) of physical therapists derived from the American Physical Therapy Association (APTA) membership. In 1992, a similar questionnaire was distributed to a representative sample (n = 400) of physical therapists derived from the APTA membership. Response rates were 53% and 55% in 1986 and 1992, respectively. Respondents indicated whether each activity was included in the documentation describing PTA roles. Results revealed considerable agreement between therapists' perceptions of PTA roles and those outlined by PTA practice guidelines, and these perceptions changed little over time. Discriminant analyses suggested that therapists' perceptions of PTA roles were, in general, not predicted by supervisory experience with PTAs, therapist experience, or content of entry-level professional education curricula. Generally, therapists' perceptions of PTA roles are consistent with published practice guidelines. Therapists' perceptions on selected activities, however, were incongruent with PTA practice guidelines, suggesting the potential for inefficient or inappropriate utilization of the PTA in the delivery of selected services.

Isolation and identification of a bacterium from marine shrimp digestive tract: A new degrader of starch and protein

NASA Astrophysics Data System (ADS)

Li, Jiqiu; Tan, Beiping; Mai, Kangsen

2011-09-01

It is a practical approach to select candidate probiotic bacterial stains on the basis of their special traits. Production of digestive enzyme was used as a trait to select a candidate probiotic bacterial strain in this study. In order to select a bacterium with the ability to degrade both starch and protein, an ideal bacterial strain STE was isolated from marine shrimp ( Litopenaeus vannamei) intestines by using multiple selective media. The selected isolate STE was identified on the basis of its morphological, physiological, and biochemical characteristics as well as molecular analyses. Results of degradation experiments confirmed the ability of the selected isolate to degrade both starch and casein. The isolate STE was aerobic, Gram-negative, rod-shaped, motile and non-spore-forming, and had catalase and oxidase activities but no glucose fermentation activity. Among the tested carbon/nitrogen sources, only Tween40, alanyl-glycine, aspartyl-glycine, and glycyl-l-glutamic acid were utilized by the isolate STE. Results of homology comparison analyses of the 16S rDNA sequences showed that the isolate STE had a high similarity to several Pseudoalteromonas species and, in the phylogenetic tree, grouped with P. ruthenica with maximum bootstrap support (100%). In conclusion, the isolate STE was characterized as a novel strain belonging to the genus Pseudoalteromonas. This study provides a further example of a probiotic bacterial strain with specific characteristics isolated from the host gastrointestinal tract.

A Feature Selection Algorithm to Compute Gene Centric Methylation from Probe Level Methylation Data.

PubMed

Baur, Brittany; Bozdag, Serdar

2016-01-01

DNA methylation is an important epigenetic event that effects gene expression during development and various diseases such as cancer. Understanding the mechanism of action of DNA methylation is important for downstream analysis. In the Illumina Infinium HumanMethylation 450K array, there are tens of probes associated with each gene. Given methylation intensities of all these probes, it is necessary to compute which of these probes are most representative of the gene centric methylation level. In this study, we developed a feature selection algorithm based on sequential forward selection that utilized different classification methods to compute gene centric DNA methylation using probe level DNA methylation data. We compared our algorithm to other feature selection algorithms such as support vector machines with recursive feature elimination, genetic algorithms and ReliefF. We evaluated all methods based on the predictive power of selected probes on their mRNA expression levels and found that a K-Nearest Neighbors classification using the sequential forward selection algorithm performed better than other algorithms based on all metrics. We also observed that transcriptional activities of certain genes were more sensitive to DNA methylation changes than transcriptional activities of other genes. Our algorithm was able to predict the expression of those genes with high accuracy using only DNA methylation data. Our results also showed that those DNA methylation-sensitive genes were enriched in Gene Ontology terms related to the regulation of various biological processes.

SAGA complex and Gcn5 are necessary for respiration in budding yeast.

PubMed

Canzonetta, Claudia; Leo, Manuela; Guarino, Salvatore Rocco; Montanari, Arianna; Francisci, Silvia; Filetici, Patrizia

2016-12-01

In budding yeast, growth through fermentation and/or respiration is dependent on the type of carbon source present in the medium. SAGA complex is the main acetylation complex and is required, together with Rtg factors, for nucleus-mitochondria communication and transcriptional activation of specific nuclear genes. Even though acetylation is necessary for mitochondria activity and respiratory pathways the direct role of histone acetyltransferases and SAGA complex has never been investigated directly. In this study we demonstrate, for the first time, that Gcn5 and SAGA are needed for respiratory metabolism and oxygen consumption. According to a central role for acetylation in respiration we find that the Gcn5 inhibitor CPTH2 had higher efficacy on cells grown in glycerol containing media. We also demonstrated that the opposing activities of Gcn5 and Hda1 modify selectively H3-AcK18 and are essential for respiration. Taken together our results suggest a novel paradigm coupling acetyltransferase activity to respiratory metabolism. Correspondingly we propose the selective utilization of KAT inhibitor CPTH2, combined to the modulation of the respiratory metabolism of the cell, as a promising novel tool of intervention in cancer cells. Copyright © 2016 Elsevier B.V. All rights reserved.

Improving the Selection, Classification, and Utilization of Army Enlisted Personnel: Final Report on Project A

DTIC Science & Technology

1991-08-01

being used in both current and long-range research programs that are expected to make the Army more effective in matching the requirements for first- and... make substantial improvements to the existing selection and classifi- cation system. xi IMPROVING THE SELECTION, CLASSIFICATION, AND UTILIZATION OF...basis for new methods of allocating personnel, and making near-real-time decisions on the best match between characteristics of an individual enlistee

Utilization of xylose for growth by the eukaryotic alga, Chlorella.

PubMed

Hawkins, R L

1999-06-01

A green alga, Chlorella, was found to be capable of utilizing xylose or other pentose sugars (xylitol, arabinose) for enhanced growth rates when grown in the light, but not when grown heterotrophically in the dark. With selection for growth in xylose-containing medium, it was possible to improve dramatically the ability of selected Chlorella strains to grow on xylose mixotrophically. Growth on arabinose or xylitol was not changed in the xylose-selected strains.

Domestic & International Air Cargo Activity: National and Selected Hub Forecasts.

DTIC Science & Technology

1979-11-01

111371 1991 1887811 2?. 768 :297968 Forecast utilizes 1972 dollar GNP from Wharton’s annual model, December 6, 1978, Post-Meeting Control Solution...mile based on 1973 revenue ton-miles reported in the DOT/CAB, Air Carrier Traffic Statistics. South America - RSA - simple average of American (Latin...9518 F (2/11) = 129.347 DW = 1.41 (b) South America (ESA) 4 = 11.8926 + 18.2908* (GDPSA.C) - 8.94307* ( RSA ) 4 (0.14) (6.08) (-0.46) R2 .8717 F (2/11

Payload system tradeoffs for mobile communications satellites

NASA Technical Reports Server (NTRS)

Moody, H. J.

1990-01-01

System level trade-offs carried out during Mobile Satellite (M-SAT) design activities are described. These trade-offs relate to the use of low level beam forming, flexible power and spectrum distribution, and selection of the number of beams to cover the service area. It is shown that antenna performance can be improved by sharing horns between beams using a low level beam forming network (BFN). Additionally, greatly increased power utilization is possible using a hybrid matrix concept to share power between beams.

Neural Mechanisms of the Transformation from Objective Value to Subjective Utility: Converting from Count to Worth.

PubMed

Kurnianingsih, Yoanna A; Mullette-Gillman, O'Dhaniel A

2016-01-01

When deciding, we aim to choose the "best" possible outcome. This is not just selection of the option that is the most numerous or physically largest, as options are translated from objective value (count) to subjective value (worth or utility). We localized the neural instantiation of the value-to-utility transformation to the dorsal anterior midcingulate cortex (daMCC), with independent replication. The daMCC encodes the context-specific information necessary to convert from count to worth. This encoding is not simply a representation of utility or preference, but the interaction of the two. Specifically, the relationship of brain activation to value is dependent on individual preference, with both positive and negative slopes across the population depending on whether each individual's preference results in enhancement or diminishment of the valuation. For a given value, across participants, enhanced daMCC activation corresponds to diminished subjective valuation, deactivation to enhanced subjective valuation, and non-modulated activation with non-modulated subjective valuation. Further, functional connectivity analyses identified brain regions (positive connectivity with the inferior frontal gyrus and negative connectivity with the nucleus accumbens) through which contextual information may be integrated into the daMCC and allow for outputs to modulate valuation signals. All analyses were replicated through an independent within-study replication, with initial testing in the gains domain and replication in the intermixed and mirrored losses trials. We also present and discuss an ancillary finding: we were unable to identify parametric value signals for losses through whole-brain analyses, and ROI analyses of the vmPFC presented non-modulation across loss value levels. These results identify the neural locus of the value-to-utility transformation, and provide a specific computational function for the daMCC in the production of subjective valuation through the integration of value, context, and preferences.

Neural Mechanisms of the Transformation from Objective Value to Subjective Utility: Converting from Count to Worth

PubMed Central

Kurnianingsih, Yoanna A.; Mullette-Gillman, O'Dhaniel A.

2016-01-01

When deciding, we aim to choose the “best” possible outcome. This is not just selection of the option that is the most numerous or physically largest, as options are translated from objective value (count) to subjective value (worth or utility). We localized the neural instantiation of the value-to-utility transformation to the dorsal anterior midcingulate cortex (daMCC), with independent replication. The daMCC encodes the context-specific information necessary to convert from count to worth. This encoding is not simply a representation of utility or preference, but the interaction of the two. Specifically, the relationship of brain activation to value is dependent on individual preference, with both positive and negative slopes across the population depending on whether each individual's preference results in enhancement or diminishment of the valuation. For a given value, across participants, enhanced daMCC activation corresponds to diminished subjective valuation, deactivation to enhanced subjective valuation, and non-modulated activation with non-modulated subjective valuation. Further, functional connectivity analyses identified brain regions (positive connectivity with the inferior frontal gyrus and negative connectivity with the nucleus accumbens) through which contextual information may be integrated into the daMCC and allow for outputs to modulate valuation signals. All analyses were replicated through an independent within-study replication, with initial testing in the gains domain and replication in the intermixed and mirrored losses trials. We also present and discuss an ancillary finding: we were unable to identify parametric value signals for losses through whole-brain analyses, and ROI analyses of the vmPFC presented non-modulation across loss value levels. These results identify the neural locus of the value-to-utility transformation, and provide a specific computational function for the daMCC in the production of subjective valuation through the integration of value, context, and preferences. PMID:27881949

Studies of the fate of sulfur trioxide in coal-fired utility boilers based on modified selected condensation methods.

PubMed

Cao, Yan; Zhou, Hongcang; Jiang, Wu; Chen, Chien-Wei; Pan, Wei-Ping

2010-05-01

The formation of sulfur trioxide (SO(3)) in coal-fired utility boilers can have negative effects on boiler performance and operation, such as fouling and corrosion of equipment, efficiency loss in the air preheater (APH), increase in stack opacity, and the formation of PM(2.5). Sulfur trioxide can also compete with mercury when bonding with injected activated carbons. Tests in a lab-scale reactor confirmed there are major interferences between fly ash and SO(3) during SO(3) sampling. A modified SO(3) procedure to maximize the elimination of measurement biases, based on the inertial-filter-sampling and the selective-condensation-collecting of SO(3), was applied in SO(3) tests in three full-scale utility boilers. For the two units burning bituminous coal, SO(3) levels starting at 20 to 25 ppmv at the inlet to the selective catalytic reduction (SCR), increased slightly across the SCR, owing to catalytic conversion of SO(2) to SO(3,) and then declined in other air pollutant control device (APCD) modules downstream to approximately 5 ppmv and 15 ppmv at the two sites, respectively. In the unit burning sub-bituminous coal, the much lower initial concentration of SO(3) estimated to be approximately 1.5 ppmv at the inlet to the SCR was reduced to about 0.8 ppmv across the SCR and to about 0.3 ppmv at the exit of the wet flue gas desulfurization (WFGD). The SO(3) removal efficiency across the WFGD scrubbers at the three sites was generally 35% or less. Reductions in SO(3) across either the APH or the dry electrostatic precipitator (ESP) in units burning high-sulfur bituminous coal were attributed to operating temperatures being below the dew point of SO(3).

Consortium for health and military performance and American College of Sports Medicine Summit: utility of functional movement assessment in identifying musculoskeletal injury risk.

PubMed

Teyhen, Deydre; Bergeron, Michael F; Deuster, Patricia; Baumgartner, Neal; Beutler, Anthony I; de la Motte, Sarah J; Jones, Bruce H; Lisman, Peter; Padua, Darin A; Pendergrass, Timothy L; Pyne, Scott W; Schoomaker, Eric; Sell, Timothy C; O'Connor, Francis

2014-01-01

Prevention of musculoskeletal injuries (MSKI) is critical in both civilian and military populations to enhance physical performance, optimize health, and minimize health care expenses. Developing a more unified approach through addressing identified movement impairments could result in improved dynamic balance, trunk stability, and functional movement quality while potentially minimizing the risk of incurring such injuries. Although the evidence supporting the utility of injury prediction and return-to-activity readiness screening tools is encouraging, considerable additional research is needed regarding improving sensitivity, specificity, and outcomes, and especially the implementation challenges and barriers in a military setting. If selected current functional movement assessments can be administered in an efficient and cost-effective manner, utilization of the existing tools may be a beneficial first step in decreasing the burden of MSKI, with a subsequent focus on secondary and tertiary prevention via further assessments on those with prior injury history.

Relations between Municipal Water Use and Selected Meteorological Parameters and Drought Indices, East-Central and Northeast Florida

USGS Publications Warehouse

Murray, Louis C.

2009-01-01

Water-use data collected between 1992 and 2006 at eight municipal water-supply utilities in east-central and northeast Florida were analyzed to identify seasonal trends in use and to quantify monthly variations. Regression analyses were applied to identify significant correlations between water use and selected meteorological parameters and drought indices. Selected parameters and indices include precipitation (P), air temperature (T), potential evapotranspiration (PET), available water (P-PET), monthly changes in these parameters (Delta P, Delta T, Delta PET, Delta(P-PET), the Palmer Drought Severity Index (PDSI), and the Standardized Precipitation Index (SPI). Selected utilities include the City of Daytona Beach (Daytona), the City of Eustis (Eustis), Gainesville Regional Utilities (GRU), Jacksonville Electric Authority (JEA), Orange County Utilities (OCU), Orlando Utilities Commission (OUC), Seminole County Utilities (SCU), and the City of St. Augustine (St. Augustine). Water-use rates at these utilities in 2006 ranged from about 3.2 million gallons per day at Eustis to about 131 million gallons per day at JEA. Total water-use rates increased at all utilities throughout the 15-year period of record, ranging from about 4 percent at Daytona to greater than 200 percent at OCU and SCU. Metered rates, however, decreased at six of the eight utilities, ranging from about 2 percent at OCU and OUC to about 17 percent at Eustis. Decreases in metered rates occurred because the number of metered connections increased at a greater rate than did total water use, suggesting that factors other than just population growth may play important roles in water-use dynamics. Given the absence of a concurrent trend in precipitation, these decreases can likely be attributed to changes in non-climatic factors such as water-use type, usage of reclaimed water, water-use restrictions, demographics, and so forth. When averaged for the eight utilities, metered water-use rates depict a clear seasonal pattern in which rates were lowest in the winter and greatest in the late spring. Averaged water-use rates ranged from about 9 percent below the 15-year daily mean in January to about 11 percent above the daily mean in May. Water-use rates were found to be statistically correlated to meteorological parameters and drought indices, and to be influenced by system memory. Metered rates (in gallons per day per active metered connection) were consistently found to be influenced by P, T, PET, and P-PET and changes in these parameters that occurred in prior months. In the single-variant analyses, best correlations were obtained by fitting polynomial functions to plots of metered rates versus moving-averaged values of selected parameters (R2 values greater than 0.50 at three of eight sites). Overall, metered water-use rates were best correlated with the 3- to 4-month moving average of Delta T or Delta PET (R2 values up to 0.66), whereas the full suite of meteorological parameters was best correlated with metered rates at Daytona and least correlated with rates at St. Augustine. Similarly, metered rates were substantially better correlated with moving-averaged values of precipitation (significant at all eight sites) than with single (current) monthly values (significant at only three sites). Total and metered water-use rates were positively correlated with T, PET, Delta P, Delta T, and Delta PET, and negatively correlated with P, P-PET, Delta (P-PET), PDSI, and SPI. The drought indices were better correlated with total water-use rates than with metered rates, whereas metered rates were better correlated with meteorological parameters. Multivariant analyses produced fits of the data that explained a greater degree of the variance in metered rates than did the single-variant analyses. Adjusted R2 values for the 'best' models ranged from 0.79 at JEA to 0.29 at St. Augustine and exceeded 0.60 at five of eight sites. The amount of available water (P-PET) was the si

Microsystems for the Capture of Low-Abundance Cells

NASA Astrophysics Data System (ADS)

Dharmasiri, Udara; Witek, Małgorzata A.; Adams, Andre A.; Soper, Steven A.

2010-07-01

Efficient selection and enumeration of low-abundance biological cells are highly important in a variety of applications. For example, the clinical utility of circulating tumor cells (CTCs) in peripheral blood is recognized as a viable biomarker for the management of various cancers, in which the clinically relevant number of CTCs per 7.5 ml of blood is two to five. Although there are several methods for isolating rare cells from a variety of heterogeneous samples, such as immunomagnetic-assisted cell sorting and fluorescence-activated cell sorting, they are fraught with challenges. Microsystem-based technologies are providing new opportunities for selecting and isolating rare cells from complex, heterogeneous samples. Such approaches involve reductions in target-cell loss, process automation, and minimization of contamination issues. In this review, we introduce different application areas requiring rare cell analysis, conventional techniques for their selection, and finally microsystem approaches for low-abundance-cell isolation and enumeration.

DNA-Catalyzed Amide Hydrolysis.

PubMed

Zhou, Cong; Avins, Joshua L; Klauser, Paul C; Brandsen, Benjamin M; Lee, Yujeong; Silverman, Scott K

2016-02-24

DNA catalysts (deoxyribozymes) for a variety of reactions have been identified by in vitro selection. However, for certain reactions this identification has not been achieved. One important example is DNA-catalyzed amide hydrolysis, for which a previous selection experiment instead led to DNA-catalyzed DNA phosphodiester hydrolysis. Subsequent efforts in which the selection strategy deliberately avoided phosphodiester hydrolysis led to DNA-catalyzed ester and aromatic amide hydrolysis, but aliphatic amide hydrolysis has been elusive. In the present study, we show that including modified nucleotides that bear protein-like functional groups (any one of primary amino, carboxyl, or primary hydroxyl) enables identification of amide-hydrolyzing deoxyribozymes. In one case, the same deoxyribozyme sequence without the modifications still retains substantial catalytic activity. Overall, these findings establish the utility of introducing protein-like functional groups into deoxyribozymes for identifying new catalytic function. The results also suggest the longer-term feasibility of deoxyribozymes as artificial proteases.

A model for plant lighting system selection.

PubMed

Ciolkosz, D E; Albright, L D; Sager, J C; Langhans, R W

2002-01-01

A decision model is presented that compares lighting systems for a plant growth scenario and chooses the most appropriate system from a given set of possible choices. The model utilizes a Multiple Attribute Utility Theory approach, and incorporates expert input and performance simulations to calculate a utility value for each lighting system being considered. The system with the highest utility is deemed the most appropriate system. The model was applied to a greenhouse scenario, and analyses were conducted to test the model's output for validity. Parameter variation indicates that the model performed as expected. Analysis of model output indicates that differences in utility among the candidate lighting systems were sufficiently large to give confidence that the model's order of selection was valid.

Selection, management and utilization of biosphere reserves.

Treesearch

Jerry F. Franklin; Stanley L. Krugman

1979-01-01

This publication is directed to the analysis of the selection, management, and utilization of Biosphere Reserves as viewed by scientists from the United States and the Union of Soviet Socialist Republics. Soviet papers focus on types of research and monitoring programs that should be developed on Biosphere Reserves, with emphasis on their use in pollutant monitoring....

Selection and Performance in a Gas Utility Company. Final Report.

ERIC Educational Resources Information Center

Joseph, Myron L.

A study of employment procedures at an unnamed gas utility company was made, examining selection procedures, white and blue collar employee performance, promotion rates, and turnover. The data is based on application files, interviews with management personnel, and employee records. The company relied primarily on walk-ins and employee referrals…

Utilization Deficiencies and Transfer of Strategies in Preschoolers

ERIC Educational Resources Information Center

Clerc, Jerome; Miller, Patricia H.

2013-01-01

Three studies examined whether strategy utilization deficiencies emerge during transfer to two tasks that differ superficially from the main task but have the same underlying structural logic. In Experiment 1, children aged 4, 4 1/2, and 5 spontaneously produced selective attention strategies (or were prompted to do so) on a selective memory task.…

Developing Age Models to Utilize High Arctic Coastal Sediments for Paleoclimate Research: Results from the Colville Delta and Simpson Lagoon, Alaska

NASA Astrophysics Data System (ADS)

Miller, A. J.; Allison, M. A.; Bianchi, T. S.; Marcantonio, F.

2012-12-01

Sediment cores collected from Simpson Lagoon on the inner Beaufort Sea shelf adjacent to the Colville River delta, AK are being utilized to develop new, high-resolution (sub-decadal scale) archives of the 0-3,000 year Arctic paleoclimate record necessary to assess natural and anthropogenic climate variability. An imperative first step for developing a new paleoclimate archive is to establish methodologies for constraining the age-depth relationship. Naturally occurring and bomb-produced radioisotopes have been utilized in sediments to constrain downcore variability of accumulation rates on 100-103 y timescales, but this methodology is complicated by low activities of many of these tracers at high latitudes. The present study utilizes the combination of a (1) multi-tracer approach and a (2) tailored measurement strategy to overcome this limitation. 210Pb and 137Cs analyses were conducted on the fine (<32μm) sediment fraction to maximize measurable activity and to minimize radioisotope activity variability resulting from changes in grain size: 137Cs geochronologies proved more reliable in this setting and revealed mm/y sediment accumulation in the lagoon. To corroborate the 137Cs results, 239,240Pu activities were analyzed for selected sites using ICP-MS which has ultra-low detection limits, and yielded accumulation rates that matched the Cs geochronology. Age model development for the remainder of the core lengths (>~100 y in age) were completed using radiocarbon dating of benthic foraminifera tests, which proved the only datable in situ carbon available in this sediment archive. These dates have been used to constrain the ages of acoustic reflectors in CHIRP subbottom seismic records collected from the lagoon. Using this age control, spatial patterns of lagoonal sediment accumulation over the last ~3 ky were derived from the CHIRP data. Two depocenters are identified and validate combining age-dated coring with high-resolution seismic profiling to identify areas of the highest temporal resolution for Arctic paleoclimate research in coastal sediments.

Can fast-twitch muscle fibres be selectively recruited during lengthening contractions? Review and applications to sport movements.

PubMed

Chalmers, Gordon R

2008-01-01

Literature examining the recruitment order of motor units during lengthening (eccentric) contractions was reviewed to determine if fast-twitch motor units can be active while lower threshold slow-twitch motor units are not active. Studies utilizing surface electromyogram (EMG) amplitude, single motor unit activity, spike amplitude-frequency analyses, EMG power spectrum, mechanomyographic, and phosphocreatine-to-creatine ratio (PCr/Cr) techniques were reviewed. Only single motor unit and PCr/Cr data were found to be suitable to address the goals of this review. Nine of ten single motor unit studies, examining joint movement velocities up to 225 degrees/s and forces up to 53% of a maximum voluntary contraction, found that the size principle of motor unit recruitment applied during lengthening contractions. Deviation from the size principle was demonstrated by one study examining movements within a small range of low velocities and modest forces, although other studies examining similar low forces and lengthening velocities reported size-ordered recruitment. The PCr/Cr data demonstrated the activation of all fibre types in lengthening maximal contractions. Most evidence indicates that for lengthening contractions of a wide range of efforts and speeds, fast-twitch muscle fibres cannot be selectively recruited without activity of the slow-twitch fibres of the same muscle.

Phyto-SERM Constitutes from Flemingia macrophylla

PubMed Central

Lai, Wan-Chun; Tsui, Ya-Ting; Singab, Abdel Nasser B.; El-Shazly, Mohamed; Du, Ying-Chi; Hwang, Tsong-Long; Wu, Chin-Chung; Yen, Ming-Hong; Lee, Ching-Kuo; Hou, Ming-Feng; Wu, Yang-Chang; Chang, Fang-Rong

2013-01-01

The methanolic extract of Flemingia macrophylla roots exhibited significant estrogenic activity in the transgenic plant assay system which was comparable to the activity of soybean extract. Utilizing estrogenic activity-guided fractionation, one new compound, fleminigin, together with 23 known compounds were isolated from F. macrophylla roots’ methanolic extract. The structure of the new compound was identified based on intensive spectroscopic analysis and the full spectral data for one of the isolated compounds, flemichin E, was introduced for the first time in the current investigation. The estrogenic and anti-estrogenic activities of the isolated compounds were evaluated revealing that the isolated isoflavonoids may act as partial estrogen agonists, as well as antagonists. Additionally, the anti-inflammatory and the cytotoxic activities of the isolated compounds were studied. These results suggested the potential applications of F. macrophylla extract and its isolated compounds as selective estrogen receptor modulators (SERMs). PMID:23896592

Optics and Light Activities for Teachers of all Grade Levels from Easily Obtainable Supplies

NASA Astrophysics Data System (ADS)

Lindgren, Richard; Hendricks, Curtis; Lucatorto, Lynn; McNeilus, Thomas; Thornton, Stephen

2010-02-01

Several hands-on activities in light and optics covering selected topics will be discussed in the context of home labs and how such activities can be incorporated into a distance-learning or online web-based course utilizing the latest communication technologies and the Internet. The presentation will focus on activities that can be constructed from easy to obtain supplies as well as a commercially available kit that we are having made available. Activities for teachers at the elementary level will focus on understanding light rays, shadows, and reflection from plane surfaces; at the middle school level will focus on curved mirrors and lenses, dispersion, and drawing ray diagrams; at the high school level will focus on Snell's law, the lens equation, wave interference, polarization, Young's experiment, and diffraction. A distance-learning, web-based course based on these home labs will be described. )

Fluorination utilizing thermodynamically unstable fluorides and fluoride salts thereof

DOEpatents

Bartlett, Neil; Whalen, J. Marc; Chacon, Lisa

2000-12-12

A method for fluorinating a carbon compound or cationic carbon compound utilizes a fluorination agent selected from thermodynamically unstable nickel fluorides and salts thereof in liquid anhydrous hydrogen fluoride. The desired carbon compound or cationic organic compound to undergo fluorination is selected and reacted with the fluorination agent by contacting the selected organic or cationic organic compound and the chosen fluorination agent in a reaction vessel for a desired reaction time period at room temperature or less.

Mechanization for Optimal Landscape Reclamation

NASA Astrophysics Data System (ADS)

Vondráčková, Terezie; Voštová, Věra; Kraus, Michal

2017-12-01

Reclamation is a method of ultimate utilization of land adversely affected by mining or other industrial activity. The paper explains the types of reclamation and the term “optimal reclamation”. Technological options of the long-lasting process of mine dumps reclamation starting with the removal of overlying rocks, transport and backfilling up to the follow-up remodelling of the mine dumps terrain. Technological units and equipment for stripping flow division. Stripping flow solution with respect to optimal reclamation. We recommend that the application of logistic chains and mining simulation with follow-up reclamation to open-pit mines be used for the implementation of optimal reclamation. In addition to a database of local heterogeneities of the stripped soil and reclaimed land, the flow of earths should be resolved in a manner allowing the most suitable soil substrate to be created for the restoration of agricultural and forest land on mine dumps. The methodology under development for the solution of a number of problems, including the geological survey of overlying rocks, extraction of stripping, their transport and backfilling in specified locations with the follow-up deployment of goal-directed reclamation. It will make possible to reduce the financial resources needed for the complex process chain by utilizing GIS, GPS and DGPS technologies, logistic tools and synergistic effects. When selecting machines for transport, moving and spreading of earths, various points of view and aspects must be taken into account. Among such aspects are e.g. the kind of earth to be operated by the respective construction machine, the kind of work activities to be performed, the machine’s capacity, the option to control the machine’s implement and economic aspects and clients’ requirements. All these points of view must be considered in the decision-making process so that the selected machine is capable of executing the required activity and that the use of an unsuitable machine is eliminated as it would result in a delay and increase in the project costs. Therefore, reclamation always includes extensive earth-moving work activities restoring the required relief of the land being reclaimed. Using the earth-moving machine capacity, the kind of soil in mine dumps, the kind of the work activity performed and the machine design, a SW application has been developed that allows the most suitable machine for the respective work technology to be selected with a view to preparing the land intended for reclamation.

Activation of Dioxygen by Iron and Manganese Complexes: A Heme and Nonheme Perspective

PubMed Central

Sahu, Sumit; Goldberg, David P.

2016-01-01

The rational design of well-defined, first-row transition metal complexes that can activate dioxygen has been a challenging goal for the synthetic inorganic chemist. The activation of O2 is important in part because of its central role in the functioning of metalloenzymes, which utilize O2 to perform a number of challenging reactions including the highly selective oxidation of various substrates. There is also great interest in utilizing O2, an abundant and environmentally benign oxidant, in synthetic catalytic oxidation systems. This Perspective brings together recent examples of biomimetic Fe and Mn complexes that can activate O2 in heme or nonheme-type ligand environments. The use of oxidants such as hypervalent iodine (e.g., ArIO), peracids (e.g., m-CPBA), peroxides (e.g., H2O2) or even superoxide is a popular choice for accessing well-characterized metal–superoxo, metal–peroxo, or metal–oxo species, but the instances of biomimetic Fe/Mn complexes that react with dioxygen to yield such observable metal–oxygen species are surprisingly few. This Perspective focuses on mononuclear Fe and Mn complexes that exhibit reactivity with O2 and lead to spectroscopically observable metal–oxygen species, and/or oxidize biologically relevant substrates. Analysis of these examples reveals that solvent, spin state, redox potential, external co-reductants, and ligand architecture can all play important roles in the O2 activation process. PMID:27576170

The peroxisome proliferator-activated receptor beta/delta agonist, GW501516, regulates the expression of genes involved in lipid catabolism and energy uncoupling in skeletal muscle cells.

PubMed

Dressel, Uwe; Allen, Tamara L; Pippal, Jyotsna B; Rohde, Paul R; Lau, Patrick; Muscat, George E O

2003-12-01

Lipid homeostasis is controlled by the peroxisome proliferator-activated receptors (PPARalpha, -beta/delta, and -gamma) that function as fatty acid-dependent DNA-binding proteins that regulate lipid metabolism. In vitro and in vivo genetic and pharmacological studies have demonstrated PPARalpha regulates lipid catabolism. In contrast, PPARgamma regulates the conflicting process of lipid storage. However, relatively little is known about PPARbeta/delta in the context of target tissues, target genes, lipid homeostasis, and functional overlap with PPARalpha and -gamma. PPARbeta/delta, a very low-density lipoprotein sensor, is abundantly expressed in skeletal muscle, a major mass peripheral tissue that accounts for approximately 40% of total body weight. Skeletal muscle is a metabolically active tissue, and a primary site of glucose metabolism, fatty acid oxidation, and cholesterol efflux. Consequently, it has a significant role in insulin sensitivity, the blood-lipid profile, and lipid homeostasis. Surprisingly, the role of PPARbeta/delta in skeletal muscle has not been investigated. We utilize selective PPARalpha, -beta/delta, -gamma, and liver X receptor agonists in skeletal muscle cells to understand the functional role of PPARbeta/delta, and the complementary and/or contrasting roles of PPARs in this major mass peripheral tissue. Activation of PPARbeta/delta by GW501516 in skeletal muscle cells induces the expression of genes involved in preferential lipid utilization, beta-oxidation, cholesterol efflux, and energy uncoupling. Furthermore, we show that treatment of muscle cells with GW501516 increases apolipoprotein-A1 specific efflux of intracellular cholesterol, thus identifying this tissue as an important target of PPARbeta/delta agonists. Interestingly, fenofibrate induces genes involved in fructose uptake, and glycogen formation. In contrast, rosiglitazone-mediated activation of PPARgamma induces gene expression associated with glucose uptake, fatty acid synthesis, and lipid storage. Furthermore, we show that the PPAR-dependent reporter in the muscle carnitine palmitoyl-transferase-1 promoter is directly regulated by PPARbeta/delta, and not PPARalpha in skeletal muscle cells in a PPARgamma coactivator-1-dependent manner. This study demonstrates that PPARs have distinct roles in skeletal muscle cells with respect to the regulation of lipid, carbohydrate, and energy homeostasis. Moreover, we surmise that PPARbeta/delta agonists would increase fatty acid catabolism, cholesterol efflux, and energy expenditure in muscle, and speculate selective activators of PPARbeta/delta may have therapeutic utility in the treatment of hyperlipidemia, atherosclerosis, and obesity.

Adolescents' Knowledge, Attitude and Utilization of Emergency Contraceptive Pills in Nigeria's Niger Delta Region.

PubMed

Onasoga, Olayinka A; Afolayan, Joel Adeleke; Asamabiriowei, Tariebi Florence; Jibril, Umar Nda; Imam, Abubakar Ayinla

2016-01-01

Risky sexual activity among adolescents is on the increase and contraceptive prevalence rate is low which is evidenced by high rate of teenage pregnancy in Bayelsa state, Nigeria. This study assesses the adolescents' knowledge, attitude and utilization of emergency contraceptive pills (ECP) in Amassoma Community, Bayelsa State, in the Niger Delta region of Nigeria. The study was a descriptive cross-sectional research design. A purposive sampling technique was used to select a sample of 220 respondents from the target population. Data were collected using a self-structured questionnaire. Descriptive and inferential statistics were used to analyze the data generated. Majority of the respondents had high level of knowledge and positive attitude towards emergency contraceptive pills but had low level of utilization. Concerns about what others may say, parental attitude, contraceptive availability, contraceptive accessibility, and peer influences were the major factors that influenced the utilization of contraceptive pills. There was no significant relationship between knowledge and utilization of emergency contraceptive pills, as well as level of knowledge and their utilization of emergency contraceptive pills. Adolescents in the study were more likely to use emergency contraceptive pills, if parents and others reaction to adolescents' contraceptive use were positive about those. Health care professionals, especially nurses, should organize enlightenment programs to educate adolescents, parents and the public on the benefits of adolescents' contraceptives use, especially ECP.

Individual determinants of research utilization: a systematic review.

PubMed

Estabrooks, Carole A; Floyd, Judith A; Scott-Findlay, Shannon; O'Leary, Katherine A; Gushta, Matthew

2003-09-01

In order to design interventions that increase research use in nursing, it is necessary to have an understanding of what influences research use. To report findings on a systematic review of studies that examine individual characteristics of nurses and how they influence the utilization of research. A survey of published articles in English that examine the influence of individual factors on the research utilization behaviour of nurses, without restriction of the study design, from selected computerized databases and hand searches. Articles had to measure one or more individual determinants of research utilization, measure the dependent variable (research utilization), and evaluate the relationship between the dependent and independent variables. The studies also had to indicate the direction of the relationship between the independent and dependent variables, report a P-value and the statistic used, and indicate the magnitude of the relationship. Six categories of potential individual determinants were identified: beliefs and attitudes, involvement in research activities, information seeking, professional characteristics, education and other socio-economic factors. Research design, sampling, measurement, and statistical analysis were examined to evaluate methodological quality. Methodological problems surfaced in all of the studies and, apart from attitude to research, there was little to suggest that any potential individual determinant influences research use. Important conceptual and measurement issues with regard to research utilization could be better addressed if research in the area were undertaken longitudinally by multi-disciplinary teams of researchers.

A systematic approach to prioritize drug targets using machine learning, a molecular descriptor-based classification model, and high-throughput screening of plant derived molecules: a case study in oral cancer.

PubMed

Randhawa, Vinay; Kumar Singh, Anil; Acharya, Vishal

2015-12-01

Systems-biology inspired identification of drug targets and machine learning-based screening of small molecules which modulate their activity have the potential to revolutionize modern drug discovery by complementing conventional methods. To utilize the effectiveness of such pipelines, we first analyzed the dysregulated gene pairs between control and tumor samples and then implemented an ensemble-based feature selection approach to prioritize targets in oral squamous cell carcinoma (OSCC) for therapeutic exploration. Based on the structural information of known inhibitors of CXCR4-one of the best targets identified in this study-a feature selection was implemented for the identification of optimal structural features (molecular descriptor) based on which a classification model was generated. Furthermore, the CXCR4-centered descriptor-based classification model was finally utilized to screen a repository of plant derived small-molecules to obtain potential inhibitors. The application of our methodology may assist effective selection of the best targets which may have previously been overlooked, that in turn will lead to the development of new oral cancer medications. The small molecules identified in this study can be ideal candidates for trials as potential novel anti-oral cancer agents. Importantly, distinct steps of this whole study may provide reference for the analysis of other complex human diseases.

Discovery of Highly Selective and Nanomolar Carbamate-Based Butyrylcholinesterase Inhibitors by Rational Investigation into Their Inhibition Mode.

PubMed

Sawatzky, Edgar; Wehle, Sarah; Kling, Beata; Wendrich, Jan; Bringmann, Gerhard; Sotriffer, Christoph A; Heilmann, Jörg; Decker, Michael

2016-03-10

Butyrylcholinesterase (BChE) is a promising target for the treatment of later stage cognitive decline in Alzheimer's disease. A set of pseudo-irreversible BChE inhibitors with high selectivity over hAChE was synthesized based on carbamates attached to tetrahydroquinazoline scaffolds with the 2-thiophenyl compound 2p as the most potent inhibitor of eqBChE (KC = 14.3 nM) and also of hBChE (KC = 19.7 nM). The inhibitors transfer the carbamate moiety onto the active site under release of the phenolic tetrahydroquinazoline scaffolds that themselves act as neuroprotectants. By combination of kinetic data with molecular docking studies, a plausible binding model was probed describing how the tetrahydroquinazoline scaffold guides the carbamate into a close position to the active site. The model explains the influence of the carrier scaffold onto the affinity of an inhibitor just before carbamate transfer. This strategy can be used to utilize the binding mode of other carbamate-based inhibitors.

Escitalopram: a review of its use in the management of major depressive disorder.

PubMed

Murdoch, David; Keam, Susan J

2005-01-01

Escitalopram (Cipralex, Lexapro), the active S-enantiomer of the racemic selective serotonin reuptake inhibitor (SSRI) citalopram (RS-citalopram), is a highly selective inhibitor of the serotonin transporter protein. It possesses a rapid onset of antidepressant activity, and is an effective and generally well tolerated treatment for moderate-to-severe major depressive disorder (MDD). Pooled analyses from an extensive clinical trial database suggest that escitalopram is consistently more effective than citalopram in moderate-to-severe MDD. Preliminary studies suggest that escitalopram is as effective as other SSRIs and the extended-release (XR) formulation of the serotonin/noradrenaline (norepinephrine) reuptake inhibitor venlafaxine, and may have cost-effectiveness and cost-utility advantages. However, additional longer-term, comparative studies evaluating specific efficacy, tolerability, health-related quality of life and economic indices would be helpful in definitively positioning escitalopram relative to these other agents in the treatment of MDD. Nevertheless, available clinical and pharmacoeconomic data indicate that escitalopram is an effective first-line option in the management of patients with MDD.

Transformation of Human Cathelicidin LL-37 into Selective, Stable, and Potent Antimicrobial Compounds

PubMed Central

2015-01-01

This Letter reports a family of novel antimicrobial compounds obtained by combining peptide library screening with structure-based design. Library screening led to the identification of a human LL-37 peptide resistant to chymotrypsin. This d-amino-acid-containing peptide template was active against Escherichia coli but not methicillin-resistant Staphylococcus aureus (MRSA). It possesses a unique nonclassic amphipathic structure with hydrophobic defects. By repairing the hydrophobic defects, the peptide (17BIPHE2) gained activity against the ESKAPE pathogens, including Enterococcus faecium, S. aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter species. In vitro, 17BIPHE2 could disrupt bacterial membranes and bind to DNA. In vivo, the peptide prevented staphylococcal biofilm formation in a mouse model of catheter-associated infection. Meanwhile, it boosted the innate immune response to further combat the infection. Because these peptides are potent, cell-selective, and stable to several proteases, they may be utilized to combat one or more ESKAPE pathogens. PMID:25061850

Adolescents’ Interpretation of the Concept of Wellness: A Qualitative Study

PubMed Central

Ahanonu, Ezihe Loretta; Jooste, Karien

2016-01-01

Introduction: This study sought to explore and describe the interpretation which adolescents ascribe to the term wellness at a selected high school in the Western Cape Province of South Africa. Methods: A qualitative research design was utilized. Nine focus-group discussions were conducted among 58 adolescents. Sample was selected purposefully and collected data was analyzed using open coding. Results: Findings reflected adolescents’ interpretations of the term wellness in the realm of holistic well-being transcending the nonexistence of illness or sickness in the body. The interpretations given include: healthy living which embrace eating enough nutritious foods, exercising regularly and being actively involved in physical activities; practicing self-care habits such as personal hygiene and grooming; well-being of the mind (psychological, emotional); having a balanced personality and interpersonal processes; being focused and goal directed and spiritual well-being. Conclusion: It is imperative to consider adolescents’ understandings of wellness when planning, designing, implementing and evaluating adolescent wellness programs. PMID:28032078

Optogenetic control of contractile function in skeletal muscle

PubMed Central

Bruegmann, Tobias; van Bremen, Tobias; Vogt, Christoph C.; Send, Thorsten; Fleischmann, Bernd K.; Sasse, Philipp

2015-01-01

Optogenetic stimulation allows activation of cells with high spatial and temporal precision. Here we show direct optogenetic stimulation of skeletal muscle from transgenic mice expressing the light-sensitive channel Channelrhodopsin-2 (ChR2). Largest tetanic contractions are observed with 5-ms light pulses at 30 Hz, resulting in 84% of the maximal force induced by electrical stimulation. We demonstrate the utility of this approach by selectively stimulating with a light guide individual intralaryngeal muscles in explanted larynges from ChR2-transgenic mice, which enables selective opening and closing of the vocal cords. Furthermore, systemic injection of adeno-associated virus into wild-type mice provides sufficient ChR2 expression for optogenetic opening of the vocal cords. Thus, direct optogenetic stimulation of skeletal muscle generates large force and provides the distinct advantage of localized and cell-type-specific activation. This technology could be useful for therapeutic purposes, such as restoring the mobility of the vocal cords in patients suffering from laryngeal paralysis. PMID:26035411

Identification and characterization of DNAzymes targeting DNA methyltransferase I for suppressing bladder cancer proliferation

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

Wang, Xiangbo; Zhang, Lu; Ding, Nianhua

2015-05-29

Epigenetic inactivation of genes plays a critical role in many important human diseases, especially in cancer. A core mechanism for epigenetic inactivation of the genes is methylation of CpG islands in genome DNA, which is catalyzed by DNA methyltransferases (DNMTs). The inhibition of DNMTs may lead to demethylation and expression of the silenced tumor suppressor genes. Although DNMT inhibitors are currently being developed as potential anticancer agents, only limited success is achieved due to substantial toxicity. Here, we utilized a multiplex selection system to generate efficient RNA-cleaving DNAzymes targeting DNMT1. The lead molecule from the selection was shown to possessmore » efficient kinetic profiles and high efficiency in inhibiting the enzyme activity. Transfection of the DNAzyme caused significant down-regulation of DNMT1 expression and reactivation of p16 gene, resulting in reduced cell proliferation of bladder cancers. This study provides an alternative for targeting DNMTs for potential cancer therapy. - Highlights: • Identified DNMT1-targeted DNAzymes by multiplex selection system. • Biochemically characterized a lead DNAzyme with high kinetic efficiency. • Validated DNMT1-targeted DNAzyme in its enzymatic and cellular activities.« less

Nurses' perceptions of research utilization in a corporate health care system.

PubMed

McCloskey, Donna Jo

2008-01-01

To explore selected characteristics of nurses based upon educational level (masters, baccalaureate, associate degree/diploma), years of experience, and hospital position (management, advanced practice, staff nurse) that might affect perceived availability of research resources, attitude towards research, support, and research use in practice. A descriptive nonexperimental mailed survey design was used for this study. Nurses in five hospitals within a corporate hospital system were surveyed using the Research Utilization Questionnaire (RUQ). The RUQ was used to measure nurses' perceptions of research utilization in the four dimensions of perceived use of research, attitude toward research, availability of research resources, and perceived support for research activities. ANOVA was used to analyze the data. Statistically significant differences (p<.001) were found in the perceived use of research, attitude toward research, availability of research resources, and perceived support for research activities based on educational level and organizational position. No significant differences were found in the perception of nurses based on years of experience. The results of this study have implications for staff nurses, administrators, advanced practice nurses, and educators working in hospital systems. The different perceptions based upon educational level and hospital position can be integrated and used at all levels of nursing practice to promote research utilization and evidence-based practice initiatives within the organizational structure. The results of this study have nursing implications within administration and for nursing practice. The different perceptions that were found based upon educational level and hospital position can be positively integrated and used by administrators and by nurses all levels of nursing practice to promote research utilization and evidence based practice initiatives within the organizational structure.

Selecting and utilizing Populus and Salix for landfill covers: implications for leachate irrigation.

PubMed

Zalesny, Ronald S; Bauer, Edmund O

2007-01-01

The success of using Populus and Salix for phytoremediation has prompted further use of leachate as a combination of irrigation and fertilization for the trees. A common protocol for such efforts has been to utilize a limited number of readily-available genotypes with decades of deployment in other applications, such as fiber or windbreaks. However, it may be possible to increase phytoremediation success with proper genotypic screening and selection, followed by the field establishment of clones that exhibited favorable potential for cleanup of specific contaminants. There is an overwhelming need for testing and subsequent deployment of diverse Populus and Salix genotypes, given current availability of clonal material and the inherent genetic variation among and within these genera. Therefore, we detail phyto-recurrent selection, a method that consists of revising and combining crop and tree improvement protocols to meet the objective of utilizing superior Populus and Salix clones for remediation applications. Although such information is lacking for environmental clean-up technologies, centuries of plant selection success in agronomy, horticulture, and forestry validate the need for similar approaches in phytoremediation. We bridge the gap between these disciplines by describing project development, clone selection, tree establishment, and evaluation of success metrics in the context of their importance to utilizing trees for phytoremediation.

Integrative functional analyses using rainbow trout selected for tolerance to plant diets reveal nutrigenomic signatures for soy utilization without the concurrence of enteritis.

PubMed

Abernathy, Jason; Brezas, Andreas; Snekvik, Kevin R; Hardy, Ronald W; Overturf, Ken

2017-01-01

Finding suitable alternative protein sources for diets of carnivorous fish species remains a major concern for sustainable aquaculture. Through genetic selection, we created a strain of rainbow trout that outperforms parental lines in utilizing an all-plant protein diet and does not develop enteritis in the distal intestine, as is typical with salmonids on long-term plant protein-based feeds. By incorporating this strain into functional analyses, we set out to determine which genes are critical to plant protein utilization in the absence of gut inflammation. After a 12-week feeding trial with our selected strain and a control trout strain fed either a fishmeal-based diet or an all-plant protein diet, high-throughput RNA sequencing was completed on both liver and muscle tissues. Differential gene expression analyses, weighted correlation network analyses and further functional characterization were performed. A strain-by-diet design revealed differential expression ranging from a few dozen to over one thousand genes among the various comparisons and tissues. Major gene ontology groups identified between comparisons included those encompassing central, intermediary and foreign molecule metabolism, associated biosynthetic pathways as well as immunity. A systems approach indicated that genes involved in purine metabolism were highly perturbed. Systems analysis among the tissues tested further suggests the interplay between selection for growth, dietary utilization and protein tolerance may also have implications for nonspecific immunity. By combining data from differential gene expression and co-expression networks using selected trout, along with ontology and pathway analyses, a set of 63 candidate genes for plant diet tolerance was found. Risk loci in human inflammatory bowel diseases were also found in our datasets, indicating rainbow trout selected for plant-diet tolerance may have added utility as a potential biomedical model.

Larvicidal activity and GC-MS analysis of flavonoids of Vitex negundo and Andrographis paniculata against two vector mosquitoes Anopheles stephensi and Aedes aegypti.

PubMed

Gautam, Keerti; Kumar, Padma; Poonia, Sawitri

2013-09-01

Development of insect resistance to synthetic pesticides, high operational cost and environmental pollution have created the need for developing alternative approaches to control vector-borne diseases. In the present study, larvicidal activity of flavonoid extracts of different parts of Vitex negundo (Linnaeus) and Andrographis paniculata (Nees) have been studied against the late III or early IV instar larvae of Aedes aegypti and Anopheles stephensi (Liston). Flavonoids were extracted from different parts of the selected plants using standard method. Bioassay test was carried out by WHO method for determination of larvicidal activity against mosquitoes. Different compounds of the most active extract were identified by the gas chromatography-mass spectrometry (GC-MS) analysis. Flavonoid extract of whole aerial part of A. paniculata was found to be inactive against the selected larvae of Ae. aegypti even at the concentration of 600 ppm, whereas it caused 70% mortality in An. stephensi at the concentration of 200 ppm. Flavonoid extract of flower-buds produced highest mortality (100%) at the concentration of 600 ppm for the late III or early IV instar larvae of Ae. aegypti and at the concentration of 200 ppm for the larvae of An. stephensi. GC-MS analysis of the most active flavonoid extract from flower-buds of Vitex showed 81 peaks. Phenol (26.83% area), naphthalene (4.95% area), 2,3-dihydrobenzofuran (6.79% area), Phenol-2,4-Bis (1,1-dimethyl) (4.49% area), flavones 4'-OH,5-OH,7-di-O-glucoside (0.25% area) and 5-hydroxy- 3,6,7,3',4'-pentamethoxy flavones (0.80% area) were present in major amount. Flavonoid extracts from different parts of two selected plants possess larvicidal activity against two selected mosquito species, hence, could be utilized for developing flavonoid-based, eco-friendly insecticide as an alternative to synthetic insecticides.

A novel protein factor is required for use of distal alternative 5' splice sites in vitro.

PubMed Central

Harper, J E; Manley, J L

1991-01-01

Adenovirus E1A pre-mRNA was used as a model to examine alternative 5' splice site selection during in vitro splicing reactions. Strong preference for the downstream 13S 5' splice site over the upstream 12S or 9S 5' splice sites was observed. However, the 12S 5' splice site was used efficiently when a mutant pre-mRNA lacking the 13S 5' splice site was processed, and 12S splicing from this substrate was not reduced by 13S splicing from a separate pre-mRNA, demonstrating that 13S splicing reduced 12S 5' splice site selection through a bona fide cis-competition. DEAE-cellulose chromatography of nuclear extract yielded two fractions with different splicing activities. The bound fraction contained all components required for efficient splicing of simple substrates but was unable to utilize alternative 5' splice sites. In contrast, the flow-through fraction, which by itself was inactive, contained an activity required for alternative splicing and was shown to stimulate 12S and 9S splicing, while reducing 13S splicing, when added to reactions carried out by the bound fraction. Furthermore, the activity, which we have called distal splicing factor (DSF), enhanced utilization of an upstream 5' splice site on a simian virus 40 early pre-mRNA, suggesting that the factor acts in a position-dependent, substrate-independent fashion. Several lines of evidence are presented suggesting that DSF is a non-small nuclear ribonucleoprotein protein. Finally, we describe a functional interaction between DSF and ASF, a protein that enhances use of downstream 5' splice sites. Images PMID:1658620

Selective elimination of neuroblastoma cells by synergistic effect of Akt kinase inhibitor and tetrathiomolybdate.

PubMed

Navrátilová, Jarmila; Karasová, Martina; Kohutková Lánová, Martina; Jiráková, Ludmila; Budková, Zuzana; Pacherník, Jiří; Šmarda, Jan; Beneš, Petr

2017-09-01

Neuroblastoma is the most common extracranial solid tumour of infancy. Pathological activation of glucose consumption, glycolysis and glycolysis-activating Akt kinase occur frequently in neuroblastoma cells, and these changes correlate with poor prognosis of patients. Therefore, several inhibitors of glucose utilization and the Akt kinase activity are in preclinical trials as potential anti-cancer drugs. However, metabolic plasticity of cancer cells might undermine efficacy of this approach. In this work, we identified oxidative phosphorylation as compensatory mechanism preserving viability of neuroblastoma cells with inhibited glucose uptake/Akt kinase. It was oxidative phosphorylation that maintained intracellular level of ATP and proliferative capacity of these cells. The oxidative phosphorylation inhibitors (rotenone, tetrathiomolybdate) synergized with inhibitor of the Akt kinase/glucose uptake in down-regulation of both viability of neuroblastoma cells and clonogenic potential of cells forming neuroblastoma spheroids. Interestingly, tetrathiomolybdate acted as highly specific inhibitor of oxygen consumption and activator of lactate production in neuroblastoma cells, but not in normal fibroblasts and neuronal cells. Moreover, the reducing effect of tetrathiomolybdate on cell viability and the level of ATP in the cells with inhibited Akt kinase/glucose uptake was also selective for neuroblastoma cells. Therefore, efficient elimination of neuroblastoma cells requires inhibition of both glucose uptake/Akt kinase and oxidative phosphorylation activities. The use of tetrathiomolybdate as a mitochondrial inhibitor contributes to selectivity of this combined treatment, preferentially targeting neuroblastoma cells. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

Quenching the firefly bioluminescence by various ions.

PubMed

Zhang, Huateng; Bai, Haixiu; Jiang, Tianyu; Ma, Zhao; Cheng, Yanna; Zhou, Yubin; Du, Lupei; Li, Minyong

2016-02-01

The luciferase reporter gene assay system is broadly applied in various biomedical aspects, including signaling pathway dissection, transcriptional activity analysis, and genetic toxicity testing. It significantly improves the experimental accuracy and reduces the experimental error by the addition of an internal control. In the current research, we discovered some specific ions that could selectively inhibit firefly luciferase while having a negligible effect on renilla luciferase in vitro in the dual-reporter gene assay. We showed that these ionic compounds had a high potential of being utilized as quench-and-activate reagents in the dual-reporter assay. Furthermore, results from kinetic studies on ion-mediated quenching effects indicated that different ions have distinct inhibition modes. Our study is anticipated to guide a more affordable design of quench-and-activate reagents in biomedicine and pharmaceutical analysis.

Exploring the utility of organo-polyoxometalate hybrids to inhibit SOX transcription factors

PubMed Central

2014-01-01

Background SOX transcription factors constitute an attractive target class for intervention with small molecules as they play a prominent role in the field of regenerative biomedicine and cancer biology. However, rationally engineering specific inhibitors that interfere with transcription factor DNA interfaces continues to be a monumental challenge in the field of transcription factor chemical biology. Polyoxometalates (POMs) are inorganic compounds that were previously shown to target the high-mobility group (HMG) of SOX proteins at nanomolar concentrations. In continuation of this work, we carried out an assessment of the selectivity of a panel of newly synthesized organo-polyoxometalate hybrids in targeting different transcription factor families to enable the usage of polyoxometalates as specific SOX transcription factor drugs. Results The residual DNA-binding activities of 15 different transcription factors were measured after treatment with a panel of diverse polyoxometalates. Polyoxometalates belonging to the Dawson structural class were found to be more potent inhibitors than the Keggin class. Further, organically modified Dawson polyoxometalates were found to be the most potent in inhibiting transcription factor DNA binding activity. The size of the polyoxometalates and its derivitization were found to be the key determinants of their potency. Conclusion Polyoxometalates are highly potent, nanomolar range inhibitors of the DNA binding activity of the Sox-HMG family. However, binding assays involving a limited subset of structurally diverse polyoxometalates revealed a low selectivity profile against different transcription factor families. Further progress in achieving selectivity and deciphering structure-activity relationship of POMs require the identification of POM binding sites on transcription factors using elaborate approaches like X-ray crystallography and multidimensional NMR. In summary, our report reaffirms that transcription factors are challenging molecular architectures and that future polyoxometalate chemistry must consider further modification strategies, to address the substantial challenges involved in achieving target selectivity. PMID:25678957

Thermogenic effects of sibutramine and its metabolites

PubMed Central

Connoley, Ian P; Liu, Yong-Ling; Frost, Ian; Reckless, Ian P; Heal, David J; Stock, Michael J

1999-01-01

The thermogenic activity of the serotonin and noradrenaline reuptake inhibitor sibutramine (BTS 54524; Reductil) was investigated by measuring oxygen consumption (VO2) in rats treated with sibutramine or its two pharmacologically-active metabolites. Sibutramine caused a dose-dependent rise in VO2, with a dose of 10 mg kg−1 of sibutramine or its metabolites producing increases of up to 30% that were sustained for at least 6 h, and accompanied by significant increases (0.5–1.0°C) in body temperature. Based on the accumulation in vivo of radiolabelled 2-deoxy-[3H]-glucose, sibutramine had little or no effect on glucose utilization in most tissues, but caused an 18 fold increase in brown adipose tissue (BAT). Combined high, non-selective doses (20 mg kg−1) of the β-adrenoceptor antagonists, atenolol and ICI 118551, inhibited completely the VO2 response to sibutramine, but the response was unaffected by low, β1-adrenoceptor-selective (atenolol) or β2-adrenoceptor-selective (ICI 118551) doses (1 mg kg−1). The ganglionic blocking agent, chlorisondamine (15 mg kg−1), inhibited completely the VO2 response to the metabolites of sibutramine, but had no effect on the thermogenic response to the β3-adrenoceptor-selective agonist BRL 35135. Similar thermogenic responses were produced by simultaneous injection of nisoxetine and fluoxetine at doses (30 mg kg−1) that had no effect on VO2 when injected individually. It is concluded that stimulation of thermogenesis by sibutramine requires central reuptake inhibition of both serotonin and noradrenaline, resulting in increased efferent sympathetic activation of BAT thermogenesis via β3-adrenoceptor, and that this contributes to the compound's activity as an anti-obesity agent. PMID:10217544

Structure-activity relationships of phenothiazines and related drugs for inhibition of protein kinase C.

PubMed

Aftab, D T; Ballas, L M; Loomis, C R; Hait, W N

1991-11-01

Phenothiazines are known to inhibit the activity of protein kinase C. To identify structural features that determine inhibitory activity against the enzyme, we utilized a semiautomated assay [Anal. Biochem. 187:84-88 (1990)] to compare the potency of greater than 50 phenothiazines and related compounds. Potency was decreased by trifluoro substitution at position 2 on the phenothiazine nucleus and increased by quinoid structures on the nucleus. An alkyl bridge of at least three carbons connecting the terminal amine to the nucleus was required for activity. Primary amines and unsubstituted piperazines were the most potent amino side chains. We selected 7,8-dihydroxychlorpromazine (DHCP) (IC50 = 8.3 microM) and 2-chloro-9-(3-[1-piperazinyl]propylidene)thioxanthene (N751) (IC50 = 14 microM) for further study because of their potency and distinct structural features. Under standard (vesicle) assay conditions, DHCP was noncompetitive with respect to phosphatidylserine and a mixed-type inhibitor with respect to ATP. N751 was competitive with respect to phosphatidylserine and noncompetitive with respect to ATP. Using the mixed micelle assay, DHCP was a competitive inhibitor with respect to both phosphatidylserine and ATP. DHCP was selective for protein kinase C compared with cAMP-dependent protein kinase, calmodulin-dependent protein kinase type II, and casein kinase. N751 was more potent against protein kinase C compared with cAMP-dependent protein kinase and casein kinase but less potent against protein kinase C compared with calmodulin-dependent protein kinase type II. DHCP was analyzed for its ability to inhibit different isoenzymes of protein kinase C, and no significant isozyme selectivity was detected. These data provide important information for the rational design of more potent and selective inhibitors of protein kinase C.

Wage differences according to health status in France.

PubMed

Ben Halima, Mohamed Ali; Rococo, Emeline

2014-11-01

Many OECD countries have implemented anti-discrimination laws in recent decades. However, according to the annual report published in 2010 by the French High Authority for the Fight against Discrimination and for Equality, the second most commonly cited factor in discrimination claims since 2005 is a handicap or health status. The aim of this research is to estimate the level of unexplained components in the wage gap that can be attributed to wage discrimination based on health status in France in 2010 utilizing data from the Health, Healthcare and Insurance survey among 1594 individuals. Three health indicators are used: self-perceived health status, activity limitations and long-term chronic illness. To measure the wage gap according to an individual's health status, the analysis considers the endogenous selection of health status and unobserved differences in productivity. The results demonstrate that wage discrimination is experienced by individuals in poor health regardless of the health indicator utilized. The hourly wage rate among individuals with poor self-assessed health status is on average 14.2% lower than among individuals with good self-assessed health status. However, for individuals suffering from a long-term chronic illness or an activity limitation, the gap is 6.3% and 4.5%, respectively. The decomposition performed on wage differences according to health status by correcting for health status selection bias and controlling for unobserved differences in productivity indicates that the 'unexplained component' that can be attributed to wage discrimination is equal to 50%. Copyright © 2014 Elsevier Ltd. All rights reserved.

Isolation and characterization of a bacterium that degrades various polyester-based biodegradable plastics.

PubMed

Teeraphatpornchai, T; Nakajima-Kambe, T; Shigeno-Akutsu, Y; Nakayama, M; Nomura, N; Nakahara, T; Uchiyama, H

2003-01-01

Microorganisms isolated from soil samples were screened for their ability to degrade various biodegradable polyester-based plastics. The most active strain, designated as strain TB-13, was selected as the best strain for degrading these plastics. From its phenotypic and genetic characteristics, strain TB-13 was closely related to Paenibacillus amyloyticus. It could degrade poly(lactic acid), poly(butylene succinate), poly(butylene succinate-co-adipate), poly(caprolactone) and poly(ethylene succinate) but not poly(hydroxybutylate-co-valerate). However, it could not utilize these plastics as sole carbon sources. Both protease and esterase activities, which may be involved in the degradation of plastic, were constitutively detected in the culture broth.

Computer aided drug discovery of highly ligand efficient, low molecular weight imidazopyridine analogs as FLT3 inhibitors.

PubMed

Frett, Brendan; McConnell, Nick; Smith, Catherine C; Wang, Yuanxiang; Shah, Neil P; Li, Hong-yu

2015-04-13

The FLT3 kinase represents an attractive target to effectively treat AML. Unfortunately, no FLT3 targeted therapeutic is currently approved. In line with our continued interests in treating kinase related disease for anti-FLT3 mutant activity, we utilized pioneering synthetic methodology in combination with computer aided drug discovery and identified low molecular weight, highly ligand efficient, FLT3 kinase inhibitors. Compounds were analyzed for biochemical inhibition, their ability to selectively inhibit cell proliferation, for FLT3 mutant activity, and preliminary aqueous solubility. Validated hits were discovered that can serve as starting platforms for lead candidates. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Two Catalysts for Selective Oxidation of Contaminant Gases

NASA Technical Reports Server (NTRS)

Wright, John D.

2011-01-01

Two catalysts for the selective oxidation of trace amounts of contaminant gases in air have been developed for use aboard the International Space Station. These catalysts might also be useful for reducing concentrations of fumes in terrestrial industrial facilities especially facilities that use halocarbons as solvents, refrigerant liquids, and foaming agents, as well as facilities that generate or utilize ammonia. The first catalyst is of the supported-precious-metal type. This catalyst is highly active for the oxidation of halocarbons, hydrocarbons, and oxygenates at low concentrations in air. This catalyst is more active for the oxidation of hydrocarbons and halocarbons than are competing catalysts developed in recent years. This catalyst completely converts these airborne contaminant gases to carbon dioxide, water, and mineral acids that can be easily removed from the air, and does not make any chlorine gas in the process. The catalyst is thermally stable and is not poisoned by chlorine or fluorine atoms produced on its surface during the destruction of a halocarbon. In addition, the catalyst can selectively oxidize ammonia to nitrogen at a temperature between 200 and 260 C, without making nitrogen oxides, which are toxic. The temperature of 260 C is higher than the operational temperature of any other precious-metal catalyst that can selectively oxidize ammonia. The purpose of the platinum in this catalyst is to oxidize hydrocarbons and to ensure that the oxidation of halocarbons goes to completion. However, the platinum exhibits little or no activity for initiating the destruction of halocarbons. Instead, the attack on the halocarbons is initiated by the support. The support also provides a high surface area for exposure of the platinum. Moreover, the support resists deactivation or destruction by halogens released during the destruction of halocarbons. The second catalyst is of the supported- metal-oxide type. This catalyst can selectively oxidize ammonia to nitrogen at temperatures up to 400 C, without producing nitrogen oxides. This catalyst converts ammonia completely to nitrogen, even when the concentration of ammonia is very low. No other catalyst is known to oxidize ammonia selectively at such a high temperature and low concentration. Both the metal oxide and the support contribute to the activity and selectivity of this catalyst.

Development and Field Test of the Trial Battery for Project A. Improving the Selection, Classification and Utilization of Army Enlisted Personnel. Project A: Improving the Selection, Classification and Utilization of Army Enlisted Personnel. ARI Technical Report 739.

ERIC Educational Resources Information Center

Peterson, Norman G., Ed.

As part of the United States Army's Project A, research has been conducted to develop and field test a battery of experimental tests to complement the Armed Services Vocational Aptitude Battery in predicting soldiers' job performance. Project A is the United States Army's large-scale manpower effort to improve selection, classification, and…

Directed evolution of stereoselective enzymes based on genetic selection as opposed to screening systems.

PubMed

Acevedo-Rocha, Carlos G; Agudo, Ruben; Reetz, Manfred T

2014-12-10

Directed evolution of stereoselective enzymes provides a means to generate useful biocatalysts for asymmetric transformations in organic chemistry and biotechnology. Almost all of the numerous examples reported in the literature utilize high-throughput screening systems based on suitable analytical techniques. Since the screening step is the bottleneck of the overall procedure, researchers have considered the use of genetic selection systems as an alternative to screening. In principle, selection would be the most elegant and efficient approach because it is based on growth advantage of host cells harboring stereoselective mutants, but devising such selection systems is very challenging. They must be designed so that the host organism profits from the presence of an enantioselective variant. Progress in this intriguing research area is summarized in this review, which also includes some examples of display systems designed for enantioselectivity as assayed by fluorescence-activated cell sorting (FACS). Although the combination of display systems and FACS is a powerful approach, we also envision innovative ideas combining metabolic engineering and genetic selection systems with protein directed evolution for the development of highly selective and efficient biocatalysts. Copyright © 2014 Elsevier B.V. All rights reserved.

Engineering more stable, selectable marker-free autoluminescent mycobacteria by one step.

PubMed

Yang, Feng; Njire, Moses M; Liu, Jia; Wu, Tian; Wang, Bangxing; Liu, Tianzhou; Cao, Yuanyuan; Liu, Zhiyong; Wan, Junting; Tu, Zhengchao; Tan, Yaoju; Tan, Shouyong; Zhang, Tianyu

2015-01-01

In our previous study, we demonstrated that the use of the autoluminescent Mycobacterium tuberculosis as a reporter strain had the potential to drastically reduce the time, effort, animals and costs consumed in evaluation of the activities of drugs and vaccines in live mice. However, the strains were relatively unstable and lost reporter with time without selection. The kanamycin selection marker used wasn't the best choice as it provides resistance to amino glycosides which are an important class of second line drugs used in tuberculosis treatment. In addition, the marker could limit utility of the strains for screening of new potential drugs or evaluating drug combinations for tuberculosis treatment. Limited selection marker genes for mycobacterial genetic manipulation is a major drawback for such a marker-containing strain in many research fields. Therefore, selectable marker-free, more stable autoluminescent mycobacteria are highly needed. After trying several strategies, we created such mycobacterial strains successfully by using an integrative vector and removing both the resistance maker and integrase genes by Xer site-specific recombination in one step. The corresponding plasmid vectors developed in this study could be very convenient in constructing other selectable marker-free, more stable reporter mycobacteria with diverse applications.

Integrative functional analyses using rainbow trout selected for tolerance to plant diets reveal nutrigenomic signatures for soy utilization without the concurrence of enteritis

USDA-ARS?s Scientific Manuscript database

Finding suitable alternative protein sources for diets of carnivorous fish species remains a major concern for sustainable aquaculture. Through genetic selection, we created a strain of rainbow trout that outperforms parental lines in utilizing an all-plant protein diet and does not develop enteriti...

The Availability and Utilization of School Library Resources in Some Selected Secondary Schools (High School) in Rivers State

ERIC Educational Resources Information Center

Owate, C. N.; Iroha, Okpa

2013-01-01

This study investigates the availability and utilization of school library resources by Secondary School (High School) Students. Eight Selected Secondary Schools in Rivers State, Nigeria were chosen based on their performance in external examinations and geographic locations. In carrying out the research, questionnaires were administered to both…

The Selection of Bridge Materials Utilizing the Analytical Hierarchy Process

Treesearch

Robert L. Smith; Robert J. Bush; Daniel L. Schmoldt

1997-01-01

Effective decisions on the use of natural resources often require the input of many individuals. Determining how specific criteria affect the selection of materials can lead to better utilization of raw materials. Concrete, steel, and timber represent over 98% of the materials used for bridge construction in the United States. Highway officials must often consider...

Developing biochemical and molecular markers for cyanobacterial inoculants.

PubMed

Prasanna, R; Madhan, K; Singh, R N; Chauhan, A K; Nain, L

2010-09-01

Markers for evaluating the establishment of cyanobacteria based on their sensitivity or resistance to antibiotics, saccharide utilization patterns and PCR generated fingerprints were developed. Four selected strains (isolates from rhizosphere soils of diverse agro-ecosystems) have shown potential as diazotrophs and exhibited plant growth promoting abilities. Different responses were obtained on screening against 40 antibiotics, which aided in developing selectable antibiotic markers for each strain. Biochemical profiles generated using standardized chromogenic identification system (including saccharide utilization tests) revealed that 53 % of the saccharides tested were not utilized by any strain, while some strains exhibited unique ability for utilization of saccharides such as melibiose, cellobiose, maltose and glucosamine. PCR based amplification profiles developed using a number of primers based on repeat sequences revealed the utility of 3 primers in providing unique fingerprints for the strains.

Mechanism-based screen for G1/S checkpoint activators identifies a selective activator of EIF2AK3/PERK signalling.

PubMed

Stockwell, Simon R; Platt, Georgina; Barrie, S Elaine; Zoumpoulidou, Georgia; Te Poele, Robert H; Aherne, G Wynne; Wilson, Stuart C; Sheldrake, Peter; McDonald, Edward; Venet, Mathilde; Soudy, Christelle; Elustondo, Frédéric; Rigoreau, Laurent; Blagg, Julian; Workman, Paul; Garrett, Michelle D; Mittnacht, Sibylle

2012-01-01

Human cancers often contain genetic alterations that disable G1/S checkpoint control and loss of this checkpoint is thought to critically contribute to cancer generation by permitting inappropriate proliferation and distorting fate-driven cell cycle exit. The identification of cell permeable small molecules that activate the G1/S checkpoint may therefore represent a broadly applicable and clinically effective strategy for the treatment of cancer. Here we describe the identification of several novel small molecules that trigger G1/S checkpoint activation and characterise the mechanism of action for one, CCT020312, in detail. Transcriptional profiling by cDNA microarray combined with reverse genetics revealed phosphorylation of the eukaryotic initiation factor 2-alpha (EIF2A) through the eukaryotic translation initiation factor 2-alpha kinase 3 (EIF2AK3/PERK) as the mechanism of action of this compound. While EIF2AK3/PERK activation classically follows endoplasmic reticulum (ER) stress signalling that sets off a range of different cellular responses, CCT020312 does not trigger these other cellular responses but instead selectively elicits EIF2AK3/PERK signalling. Phosphorylation of EIF2A by EIF2A kinases is a known means to block protein translation and hence restriction point transit in G1, but further supports apoptosis in specific contexts. Significantly, EIF2AK3/PERK signalling has previously been linked to the resistance of cancer cells to multiple anticancer chemotherapeutic agents, including drugs that target the ubiquitin/proteasome pathway and taxanes. Consistent with such findings CCT020312 sensitizes cancer cells with defective taxane-induced EIF2A phosphorylation to paclitaxel treatment. Our work therefore identifies CCT020312 as a novel small molecule chemical tool for the selective activation of EIF2A-mediated translation control with utility for proof-of-concept applications in EIF2A-centered therapeutic approaches, and as a chemical starting point for pathway selective agent development. We demonstrate that consistent with its mode of action CCT020312 is capable of delivering potent, and EIF2AK3 selective, proliferation control and can act as a sensitizer to chemotherapy-associated stresses as elicited by taxanes.

Process cost and facility considerations in the selection of primary cell culture clarification technology.

PubMed

Felo, Michael; Christensen, Brandon; Higgins, John

2013-01-01

The bioreactor volume delineating the selection of primary clarification technology is not always easily defined. Development of a commercial scale process for the manufacture of therapeutic proteins requires scale-up from a few liters to thousands of liters. While the separation techniques used for protein purification are largely conserved across scales, the separation techniques for primary cell culture clarification vary with scale. Process models were developed to compare monoclonal antibody production costs using two cell culture clarification technologies. One process model was created for cell culture clarification by disc stack centrifugation with depth filtration. A second process model was created for clarification by multi-stage depth filtration. Analyses were performed to examine the influence of bioreactor volume, product titer, depth filter capacity, and facility utilization on overall operating costs. At bioreactor volumes <1,000 L, clarification using multi-stage depth filtration offers cost savings compared to clarification using centrifugation. For bioreactor volumes >5,000 L, clarification using centrifugation followed by depth filtration offers significant cost savings. For bioreactor volumes of ∼ 2,000 L, clarification costs are similar between depth filtration and centrifugation. At this scale, factors including facility utilization, available capital, ease of process development, implementation timelines, and process performance characterization play an important role in clarification technology selection. In the case study presented, a multi-product facility selected multi-stage depth filtration for cell culture clarification at the 500 and 2,000 L scales of operation. Facility implementation timelines, process development activities, equipment commissioning and validation, scale-up effects, and process robustness are examined. © 2013 American Institute of Chemical Engineers.

Optimizing the Activation of Chlorin e6 Utilizing Upconversion Energy Transfer

NASA Astrophysics Data System (ADS)

Avalos, Julio C.; Pedraza, Francisco J.; Sardar, Dhiraj K.

2015-03-01

Current cancer therapy techniques, such as chemotherapy and radiation therapy, possess several drawbacks including lack of selectivity resulting in harmful side effects. Photodynamic therapy (PDT) is one of the fastest emerging techniques due to its many advantages, including the use of nonionizing radiation, targeted delivery, and controlled doses. In PDT, photosensitizers (PSs) are activated inside targeted cells to produce irreversible damage inducing cell death. Since most PSs operate in the visible range, it is difficult to activate them due to the high attenuation of soft tissue. Upconverting nanoparticles (UCNP) are able to absorb in the NIR region, where light is less attenuated, and emit in the visible range, resulting in deeper tissue penetration. UCNPs are able to assist with the activation of the PS by energy transfer when the PS is conjugated onto the UCNP. Chlorin e6 (Ce6) is a commonly used PSs due to its ability to release reactive oxygen species (ROS), which is one of the main processes utilized in PDT. The UCNP studied contain a combination of rare earth doped ions including Erbium, Thulium, and Holmium precisely doped into the host nanocrystal to improve upconversion emission and energy transfer. The work presented will focus on exploring the factors that affect the activation of Ce6. The results will include the enhancement of Ce6 activation and ROS release when conjugated onto a rare earth-doped UCNP. This research was funded by NSF-PREM Grant No. DMR -0934218 and RISE Grant No. GM 060655.

[Concept analysis of a participatory approach to occupational safety and health].

PubMed

Yoshikawa, Etsuko

2013-01-01

The purpose of this study was to analyze a participatory approach to occupational safety and health, and to examine the possibility of applying the concept to the practice and research of occupational safety and health. According to Rodger's method, descriptive data concerning antecedents, attributes and consequences were qualitatively analyzed. A total of 39 articles were selected for analysis. Attributes with a participatory approach were: "active involvement of both workers and employers", "focusing on action-oriented low-cost and multiple area improvements based on good practices", "the process of emphasis on consensus building", and "utilization of a local network". Antecedents of the participatory approach were classified as: "existing risks at the workplace", "difficulty of occupational safety and health activities", "characteristics of the workplace and workers", and "needs for the workplace". The derived consequences were: "promoting occupational safety and health activities", "emphasis of self-management", "creation of safety and healthy workplace", and "contributing to promotion of quality of life and productivity". A participatory approach in occupational safety and health is defined as, the process of emphasis on consensus building to promote occupational safety and health activities with emphasis on self-management, which focuses on action-oriented low-cost and multiple area improvements based on good practices with active involvement of both workers and employers through utilization of local networks. We recommend that the role of the occupational health professional be clarified and an evaluation framework be established for the participatory approach to promote occupational safety and health activities by involving both workers and employers.

Shaking table experimentation on adjacent structures controlled by passive and semi-active MR dampers

NASA Astrophysics Data System (ADS)

Basili, M.; De Angelis, M.; Fraraccio, G.

2013-06-01

This paper presents the results of shaking table tests on adjacent structures controlled by passive and semi-active MR dampers. The aim was to demonstrate experimentally the effectiveness of passive and semi-active strategies in reducing structural vibrations due to seismic excitation. The physical model at issue was represented by two adjacent steel structures, respectively of 4 and 2 levels, connected at the second level by a MR damper. When the device operated in semi-active mode, an ON-OFF control algorithm, derived by the Lyapunov stability theory, was implemented and experimentally validated. Since the experimentation concerned adjacent structures, two control objectives have been reached: global and selective protection. In case of global protection, the attention was focused on protecting both structures, whereas, in case of selective protection, the attention was focused on protecting only one structure. For each objective the effectiveness of passive control has been compared with the situation of no control and then the effectiveness of semi-active control has been compared with the passive one. The quantities directly compared have been: measured displacements, accelerations and force-displacement of the MR damper, moreover some global response quantities have been estimated from experimental measures, which are the base share force and the base bending moment, the input energy and the energy dissipated by the device. In order to evaluate the effectiveness of the control action in both passive and semi-active case, an energy index EDI, previously defined and already often applied numerically, has been utilized. The aspects investigated in the experimentation have been: the implementation and validation of the control algorithm for selective and global protection, the MR damper input voltage influence, the kind of seismic input and its intensity.

Rational design of antimicrobial C3a analogues with enhanced effects against Staphylococci using an integrated structure and function-based approach.

PubMed

Pasupuleti, Mukesh; Walse, Björn; Svensson, Bo; Malmsten, Martin; Schmidtchen, Artur

2008-09-02

The anaphylatoxin C3a and its inactivated derivative C3adesArg, generated during complement activation, exert direct antimicrobial effects, mediated via its C-terminal region [Nordahl et al. (2004) Proc. Natl. Acad. Sci. U.S.A. 101, 16879-16884]. During evolution, this region of C3a displays subtle changes in net charge, while preserving a moderate but variable amphipathicity [Pasupuleti et al. (2007) J. Biol. Chem. 282, 2520-2528]. In this study, we mimic these evolutionary changes, employing a design approach utilizing selected amino acid substitutions at strategic and structurally relevant positions in the original human C3a peptide CNYITELRRQHARASHLGLA, followed by structure-activity studies incorporating sequence-dependent QSAR models as tools for generation of C3a peptide variants with enhanced effects. While the native peptide and related amphipathic analogues of moderate positive net charge were active against the Gram-negative Escherichia coli, activity against the Gram-positive Staphylococcus aureus was primarily observed for peptides characterized by a combination of a relatively high net charge (+6-7) and a propensity to adopt an alpha-helical conformation with amphipathic character. Such increased helicity and charge also conferred activity against the fungus Candida albicans. A central histidine residue (H11), evolutionarily conserved among vertebrates, conferred high selectivity toward microbes, while substitutions with leucine rendered the peptides hemolytic. Selected C3a analogues retained their specificity against staphylococci in the presence of human plasma, while showing low cytotoxicity. The work illustrates structure-activity relationships underlying the function and specificity of antimicrobial C3a and related analogues and provides insights into the forces that drive evolution of antimicrobial peptides.

How diverse are diversity assessment methods? A comparative analysis and benchmarking of molecular descriptor space.

PubMed

Koutsoukas, Alexios; Paricharak, Shardul; Galloway, Warren R J D; Spring, David R; Ijzerman, Adriaan P; Glen, Robert C; Marcus, David; Bender, Andreas

2014-01-27

Chemical diversity is a widely applied approach to select structurally diverse subsets of molecules, often with the objective of maximizing the number of hits in biological screening. While many methods exist in the area, few systematic comparisons using current descriptors in particular with the objective of assessing diversity in bioactivity space have been published, and this shortage is what the current study is aiming to address. In this work, 13 widely used molecular descriptors were compared, including fingerprint-based descriptors (ECFP4, FCFP4, MACCS keys), pharmacophore-based descriptors (TAT, TAD, TGT, TGD, GpiDAPH3), shape-based descriptors (rapid overlay of chemical structures (ROCS) and principal moments of inertia (PMI)), a connectivity-matrix-based descriptor (BCUT), physicochemical-property-based descriptors (prop2D), and a more recently introduced molecular descriptor type (namely, "Bayes Affinity Fingerprints"). We assessed both the similar behavior of the descriptors in assessing the diversity of chemical libraries, and their ability to select compounds from libraries that are diverse in bioactivity space, which is a property of much practical relevance in screening library design. This is particularly evident, given that many future targets to be screened are not known in advance, but that the library should still maximize the likelihood of containing bioactive matter also for future screening campaigns. Overall, our results showed that descriptors based on atom topology (i.e., fingerprint-based descriptors and pharmacophore-based descriptors) correlate well in rank-ordering compounds, both within and between descriptor types. On the other hand, shape-based descriptors such as ROCS and PMI showed weak correlation with the other descriptors utilized in this study, demonstrating significantly different behavior. We then applied eight of the molecular descriptors compared in this study to sample a diverse subset of sample compounds (4%) from an initial population of 2587 compounds, covering the 25 largest human activity classes from ChEMBL and measured the coverage of activity classes by the subsets. Here, it was found that "Bayes Affinity Fingerprints" achieved an average coverage of 92% of activity classes. Using the descriptors ECFP4, GpiDAPH3, TGT, and random sampling, 91%, 84%, 84%, and 84% of the activity classes were represented in the selected compounds respectively, followed by BCUT, prop2D, MACCS, and PMI (in order of decreasing performance). In addition, we were able to show that there is no visible correlation between compound diversity in PMI space and in bioactivity space, despite frequent utilization of PMI plots to this end. To summarize, in this work, we assessed which descriptors select compounds with high coverage of bioactivity space, and can hence be used for diverse compound selection for biological screening. In cases where multiple descriptors are to be used for diversity selection, this work describes which descriptors behave complementarily, and can hence be used jointly to focus on different aspects of diversity in chemical space.

Chronic pancreatitis.

PubMed

Gupte, Anand R; Forsmark, Chris E

2014-09-01

We review selected important clinical observations in chronic pancreatitis reported in 2013. Early diagnosis of chronic pancreatitis remains difficult, although newer techniques utilizing endoscopic ultrasonography-elastography and MRI hold promise. Patients with chronic pancreatitis are at risk of nutritional deficiencies. Osteoporosis, osteopenia, and bone fracture are particularly common in these patients, and require active intervention and treatment. Diabetes caused by chronic pancreatitis, type 3c diabetes, has specific characteristics and requires careful management. Antioxidants and neuromodulators may decrease pain in some patients with chronic pancreatitis. Endoscopic treatment is effective and can be utilized in patients with painful chronic pancreatitis, although randomized trials demonstrate that surgical therapy is somewhat more durable and effective. Although surgery has typically been a last resort, some advocate early surgical intervention but the optimal time remains unknown. Early diagnosis of pancreatitis may be improved by newer techniques associated with endoscopic ultrasonography imaging. Treatment of nutritional deficiencies and diabetes is an important aspect of treating chronic pancreatitis. Pain relief with adjunct means of pain modulation should be tried before starting narcotics for pain control. Endoscopic therapy is appropriate for treating chronic pancreatitis and its local complications and surgical intervention can be considered early in carefully selected individuals.

Enhancing empowerment in eating disorder prevention: Another examination of the REbeL peer education model.

PubMed

Breithaupt, Lauren; Eickman, Laura; Byrne, Catherine E; Fischer, Sarah

2017-04-01

Previously validated eating disorder (ED) prevention programs utilize either a targeted or universal approach. While both approaches have shown to be efficacious, implementing either style of program within a school setting remains a challenge. The current study describes an enhanced version of REbeL, a module based, continuous ED prevention program which utilizes a self-selection model of prevention in high school settings. The purpose of this study was to determine if an enhanced empowerment model of REbeL could increase feelings of empowerment and reduce eating disorder risk. We also aimed to assess the feasibility and acceptability of the intervention. High school peer-educators self-selected into the semi-manualized dissonance based intervention. Following feedback from a pilot trailed, enhanced peer-led group activities, designed to critique the thin ideal and designed to empower macro-changes in societal structures that emphasize the thin ideal, were added. The study (N=83) indicates that the program appears to be effective at reducing eating disorder risk factors and increasing empowerment. Participants reported reductions in body checking and internalization of the thin ideal. Copyright © 2016 Elsevier Ltd. All rights reserved.

Schizophrenia: multi-attribute utility theory approach to selection of atypical antipsychotics.

PubMed

Bettinger, Tawny L; Shuler, Garyn; Jones, Donnamaria R; Wilson, James P

2007-02-01

Current guidelines/algorithms recommend atypical antipsychotics as first-line agents for the treatment of schizophrenia. Because there are extensive healthcare costs associated with the treatment of schizophrenia, many institutions and health systems are faced with making restrictive formulary decisions regarding the use of atypical antipsychotics. Often, medication acquisition costs are the driving force behind formulary decisions, while other treatment factors are not considered. To apply a multi-attribute utility theory (MAUT) analysis to aid in the selection of a preferred agent among the atypical antipsychotics for the treatment of schizophrenia. Five atypical antipsychotics (risperidone, olanzapine, quetiapine, ziprasidone, aripiprazole) were selected as the alternative agents to be included in the MAUT analysis. The attributes identified for inclusion in the analysis were efficacy, adverse effects, cost, and adherence, with relative weights of 35%, 35%, 20%, and 10%, respectively. For each agent, attribute scores were calculated, weighted, and then summed to generate a total utility score. The agent with the highest total utility score was considered the preferred agent. Aripiprazole, with a total utility score of 75.8, was the alternative agent with the highest total utility score in this model. This was followed by ziprasidone, risperidone, and quetiapine, with total utility scores of 71.8, 69.0, and 65.9, respectively. Olanzapine received the lowest total utility score. A sensitivity analysis was performed and failed to displace aripiprazole as the agent with the highest total utility score. This model suggests that aripiprazole should be considered a preferred agent for the treatment of schizophrenia unless found to be otherwise inappropriate.

ECUT (Energy Conversion and Utilization Technologies Program). Biocatalysis Project

NASA Technical Reports Server (NTRS)

1986-01-01

Presented are the FY 1985 accomplishments, activities, and planned research efforts of the Biocatalysis Project of the U.S. Department of Energy, Energy Conversion and Utilization Technologies (ECUT) Program. The Project's technical activities were organized as follows: In the Molecular Modeling and Applied Genetics work element, research focused on (1) modeling and simulation studies to establish the physiological basis of high temperature tolerance in a selected enzyme and the catalytic mechanisms of three species of another enzyme, and (2) determining the degree of plasmid amplification and stability of several DNA bacterial strains. In the Bioprocess Engineering work element, research focused on (1) studies of plasmid propagation and the generation of models, (2) developing methods for preparing immobilized biocatalyst beads, and (3) developing an enzyme encapsulation method. In the Process Design and Analysis work element, research focused on (1) further refinement of a test case simulation of the economics and energy efficiency of alternative biocatalyzed production processes, (2) developing a candidate bioprocess to determine the potential for reduced energy consumption and facility/operating costs, and (3) a techno-economic assessment of potential advancements in microbial ammonia production.

Superhydrophobic materials for biomedical applications.

PubMed

Falde, Eric J; Yohe, Stefan T; Colson, Yolonda L; Grinstaff, Mark W

2016-10-01

Superhydrophobic surfaces are actively studied across a wide range of applications and industries, and are now finding increased use in the biomedical arena as substrates to control protein adsorption, cellular interaction, and bacterial growth, as well as platforms for drug delivery devices and for diagnostic tools. The commonality in the design of these materials is to create a stable or metastable air layer at the material surface, which lends itself to a number of unique properties. These activities are catalyzing the development of new materials, applications, and fabrication techniques, as well as collaborations across material science, chemistry, engineering, and medicine given the interdisciplinary nature of this work. The review begins with a discussion of superhydrophobicity, and then explores biomedical applications that are utilizing superhydrophobicity in depth including material selection characteristics, in vitro performance, and in vivo performance. General trends are offered for each application in addition to discussion of conflicting data in the literature, and the review concludes with the authors' future perspectives on the utility of superhydrophobic biomaterials for medical applications. Copyright © 2016 Elsevier Ltd. All rights reserved.

Synthesis and biological evaluation of glycogen synthase kinase 3 (GSK-3) inhibitors: an fast and atom efficient access to 1-aryl-3-benzylureas.

PubMed

Monte, Fabio Lo; Kramer, Thomas; Boländer, Alexander; Plotkin, Batya; Eldar-Finkelman, Hagit; Fuertes, Ana; Dominguez, Juan; Schmidt, Boris

2011-09-15

The glycogen synthase kinase 3 (GSK-3) is implicated in multiple cellular processes and has been linked to the pathogenesis of Alzheimer's disease (AD). In the course of our research topic we synthesized a library of potent GSK-3 inhibitors. We utilized the urea scaffold present in the potent and highly selective GSK-3 inhibitor AR-A014418 (AstraZeneca). This moiety suits both (a) a convergent approach utilizing readily accessible building blocks and (b) a divergent approach based on a microwave heating assisted Suzuki coupling. We established a chromatography-free purification method to generate products with sufficient purity for the biological assays. The structure-activity relationship of the library provided the rationale for the synthesis of the benzothiazolylurea 66 (IC(50)=140 nM) and the pyridylurea 62 (IC(50)=98 nM), which displayed two to threefold enhanced activity versus the reference compound 18 (AR-A014418: IC(50)=330 nM) in our assays. Copyright © 2011. Published by Elsevier Ltd.

Barriers to Women's Participation: Experiences of Volunteers and Community Healthcare Authorities.

PubMed

Rezakhani Moghaddam, Hamed; Allahverdipour, Hamid; Matlabi, Hossein

2018-01-01

Along with health development in general terms, women's involvement in health programs can be effective in raising their self-confidence and their health promotion. This study was carried out to unveil the barriers to and challenges of the health volunteers and to present the solutions to its promotion using active women participants' experiences and the authorities of the program. The study was carried out using qualitative method along with content analysis in city of Tabriz East-Azerbaijan province, Iran. Data collection was conducted utilizing semistructured individual interviews and focus group discussions with the participation of 29 health volunteers and responsible authorities. The participants were selected using purposive sampling with maximum variation. Data analysis implemented conventional content analysis using MAXODA. Barriers to and challenges of health volunteers were generally categorized into four main themes including volunteers and trainers' inadequate capabilities, inadequate acceptance of the volunteers, restrictive social norms, and organizational problems. It seems that interaction among health system, people, and health volunteers should be improved. Holding training programs about the activities of health volunteers at the society level leads into the better utilization of society sources in health programs.

Wear Analysis in THA Utilizing Oxidized Zirconium and Crosslinked Polyethylene

PubMed Central

Garvin, Kevin L.; Mangla, Jimmi; Murdoch, Nathan; Martell, John M.

2008-01-01

Oxidized zirconium, a material with a ceramic surface on a metal substrate, and highly cross-linked polyethylene are two materials developed to reduce wear. We measured in vivo femoral head penetration in patients with these advanced bearings. We hypothesized the linear wear rates would be lower than those published for cobalt-chrome and standard polyethylene. We retrospectively reviewed a select series of 56 THAs in a relatively young, active patient population utilizing oxidized zirconium femoral heads and highly cross-linked polyethylene acetabular liners. Femoral head penetration was determined using the Martell computerized edge-detection method. All patients were available for 2-year clinical and radiographic followup. True linear wear was 4 μm/year (95% confidence intervals, ± 59 μm/year). The early wear rates in this cohort of relatively young, active patients were low and we believe justify the continued study of these alternative bearing surfaces. Level of Evidence: Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence. PMID:18946711

Ligninolytic basidiomycetes as promising organisms for the mycoremediation of PAH-contaminated Environments

NASA Astrophysics Data System (ADS)

Pozdnyakova, N. N.; Balandina, S. A.; Dubrovskaya, E. V.; Golubev, C. N.; Turkovskaya, O. V.

2018-01-01

Primary screening of ligninolytic fungi belonging to wood- and soil-inhabiting basidiomycetes revealed their ability to degrade three-ringed PAHs with formation of quinone metabolites at the first stage. The degradative activity was both species and strain specific, and some differences in the “chances” for the formed quinones were found. They were the main end metabolites in the degradation of PAHs by Stropharia rugosoannulata and Agaricus bisporus. During PAH degradation by strains of Trametes versicolor, Pleurotus ostreatus, Schizophyllum commune, and Bjerkandera adusta similar metabolites were detected during the cultivation, but they were utilized further. The results supported the hypothesis that the degree of PAH degradation may depend on the composition of the extracellular ligninolytic complex of the fungi: in the presence of a single ligninolytic enzyme, laccase, the accumulation of quinone metabolites takes place; their further utilization is possible with the participation of ligninolytic peroxidases. The data obtained showed the necessity not only to identify the metabolites formed, but also to study the activity of the basic ligninolytic enzymes. It is important for the correct selection of fungal strains for mycoremediation.

Activation of Remote meta-C–H Bonds Assisted by an “End-on” Template

PubMed Central

Leow, Dasheng; Li, Gang; Mei, Tiansheng; Yu, Jin-Quan

2012-01-01

Controlling positional selectivity of C–H activation in molecules possessing multiple inequivalent C–H bonds is one of the most important challenges in developing synthetically useful C–H activation reactions. One widely used approach utilizes σ-chelating directing groups to achieve ortho-selectivity through conformational rigid five- or six-membered cyclic pre-transition states (TS).1–14 We envisioned that an “end-on” chelating template capable of delivering catalysts to previously inaccessible remote meta-C–H bonds via a macrocyclic cyclophane-like pre-TS could overcome the limitations imposed by traditional ortho-directing groups. Herein, we report a class of readily removable nitrile-containing templates that direct the activation of distal meta-C–H bonds (≥ 10 bonds away) of a tethered arene. We attribute this new mode of C–H activation to the weak “end-on” coordination of the linear nitrile group to metal center, as previously observed by Schwarz in the study of remote C–H activation of alkyl nitriles in gas phase.15, 16 The coordination geometry relieves the strain of the cyclophane-like pre-transition state of the meta-C–H activation event. Remarkably, this template overrides electronic and steric biases and ortho-directing effects with two broadly useful classes of arene substrates (toluene derivatives and hydrocinnamic acids), thus constituting a fundamentally new mode of directed C–H activation that is anticipated to be widely adopted. PMID:22739317

Remote Sensing Assessment of Lunar Resources: We Know Where to Go to Find What We Need

NASA Technical Reports Server (NTRS)

Gillis, J. J.; Taylor, G. J.; Lucey, P. G.

2004-01-01

The utilization of space resources is necessary to not only foster the growth of human activities in space, but is essential to the President s vision of a "sustained and affordable human and robotic program to explore the solar system and beyond." The distribution of resources will shape planning permanent settlements by affecting decisions about where to locate a settlement. Mapping the location of such resources, however, is not the limiting factor in selecting a site for a lunar base. It is indecision about which resources to use that leaves the location uncertain. A wealth of remotely sensed data exists that can be used to identify targets for future detailed exploration. Thus, the future of space resource utilization pre-dominantly rests upon developing a strategy for resource exploration and efficient methods of extraction.

Use of Cost-Utility Decision Models in Business Education.

ERIC Educational Resources Information Center

Lewis, Darrell R.

1989-01-01

Explains how cost-utility analysis can be applied to the selection of curriculum and instructional methods. Describes the use of multiattribute utility models of decision making as a tool for more informed judgment in educational administration. (SK)

Active Site Hydrophobicity and the Convergent Evolution of Paraoxonase Activity in Structurally Divergent Enzymes: The Case of Serum Paraoxonase 1

PubMed Central

2016-01-01

Serum paraoxonase 1 (PON1) is a native lactonase capable of promiscuously hydrolyzing a broad range of substrates, including organophosphates, esters, and carbonates. Structurally, PON1 is a six-bladed β-propeller with a flexible loop (residues 70–81) covering the active site. This loop contains a functionally critical Tyr at position 71. We have performed detailed experimental and computational analyses of the role of selected Y71 variants in the active site stability and catalytic activity in order to probe the role of Y71 in PON1’s lactonase and organophosphatase activities. We demonstrate that the impact of Y71 substitutions on PON1’s lactonase activity is minimal, whereas the kcat for the paraoxonase activity is negatively perturbed by up to 100-fold, suggesting greater mutational robustness of the native activity. Additionally, while these substitutions modulate PON1’s active site shape, volume, and loop flexibility, their largest effect is in altering the solvent accessibility of the active site by expanding the active site volume, allowing additional water molecules to enter. This effect is markedly more pronounced in the organophosphatase activity than the lactonase activity. Finally, a detailed comparison of PON1 to other organophosphatases demonstrates that either a similar “gating loop” or a highly buried solvent-excluding active site is a common feature of these enzymes. We therefore posit that modulating the active site hydrophobicity is a key element in facilitating the evolution of organophosphatase activity. This provides a concrete feature that can be utilized in the rational design of next-generation organophosphate hydrolases that are capable of selecting a specific reaction from a pool of viable substrates. PMID:28026940

Active Site Hydrophobicity and the Convergent Evolution of Paraoxonase Activity in Structurally Divergent Enzymes: The Case of Serum Paraoxonase 1.

PubMed

Blaha-Nelson, David; Krüger, Dennis M; Szeler, Klaudia; Ben-David, Moshe; Kamerlin, Shina Caroline Lynn

2017-01-25

Serum paraoxonase 1 (PON1) is a native lactonase capable of promiscuously hydrolyzing a broad range of substrates, including organophosphates, esters, and carbonates. Structurally, PON1 is a six-bladed β-propeller with a flexible loop (residues 70-81) covering the active site. This loop contains a functionally critical Tyr at position 71. We have performed detailed experimental and computational analyses of the role of selected Y71 variants in the active site stability and catalytic activity in order to probe the role of Y71 in PON1's lactonase and organophosphatase activities. We demonstrate that the impact of Y71 substitutions on PON1's lactonase activity is minimal, whereas the k cat for the paraoxonase activity is negatively perturbed by up to 100-fold, suggesting greater mutational robustness of the native activity. Additionally, while these substitutions modulate PON1's active site shape, volume, and loop flexibility, their largest effect is in altering the solvent accessibility of the active site by expanding the active site volume, allowing additional water molecules to enter. This effect is markedly more pronounced in the organophosphatase activity than the lactonase activity. Finally, a detailed comparison of PON1 to other organophosphatases demonstrates that either a similar "gating loop" or a highly buried solvent-excluding active site is a common feature of these enzymes. We therefore posit that modulating the active site hydrophobicity is a key element in facilitating the evolution of organophosphatase activity. This provides a concrete feature that can be utilized in the rational design of next-generation organophosphate hydrolases that are capable of selecting a specific reaction from a pool of viable substrates.

Isoproterenol Acts as a Biased Agonist of the Alpha-1A-Adrenoceptor that Selectively Activates the MAPK/ERK Pathway

PubMed Central

Copik, Alicja. J.; Baldys, Aleksander; Nguyen, Khanh; Sahdeo, Sunil; Ho, Hoangdung; Kosaka, Alan; Dietrich, Paul J.; Fitch, Bill; Raymond, John R.; Ford, Anthony P. D. W.; Button, Donald; Milla, Marcos E.

2015-01-01

The α1A-AR is thought to couple predominantly to the Gαq/PLC pathway and lead to phosphoinositide hydrolysis and calcium mobilization, although certain agonists acting at this receptor have been reported to trigger activation of arachidonic acid formation and MAPK pathways. For several G protein-coupled receptors (GPCRs) agonists can manifest a bias for activation of particular effector signaling output, i.e. not all agonists of a given GPCR generate responses through utilization of the same signaling cascade(s). Previous work with Gαq coupling-defective variants of α1A-AR, as well as a combination of Ca2+ channel blockers, uncovered cross-talk between α1A-AR and β2-AR that leads to potentiation of a Gαq-independent signaling cascade in response to α1A-AR activation. We hypothesized that molecules exist that act as biased agonists to selectively activate this pathway. In this report, isoproterenol (Iso), typically viewed as β-AR-selective agonist, was examined with respect to activation of α1A-AR. α1A-AR selective antagonists were used to specifically block Iso evoked signaling in different cellular backgrounds and confirm its action at α1A-AR. Iso induced signaling at α1A-AR was further interrogated by probing steps along the Gαq /PLC, Gαs and MAPK/ERK pathways. In HEK-293/EBNA cells transiently transduced with α1A-AR, and CHO_α1A-AR stable cells, Iso evoked low potency ERK activity as well as Ca2+ mobilization that could be blocked by α1A-AR selective antagonists. The kinetics of Iso induced Ca2+ transients differed from typical Gαq- mediated Ca2+ mobilization, lacking both the fast IP3R mediated response and the sustained phase of Ca2+ re-entry. Moreover, no inositol phosphate (IP) accumulation could be detected in either cell line after stimulation with Iso, but activation was accompanied by receptor internalization. Data are presented that indicate that Iso represents a novel type of α1A-AR partial agonist with signaling bias toward MAPK/ERK signaling cascade that is likely independent of coupling to Gαq. PMID:25606852

Product-line selection and pricing with remanufacturing under availability constraints

NASA Astrophysics Data System (ADS)

Aras, Necati; Esenduran, G.÷k.‡e.; Altinel, I. Kuban

2004-12-01

Product line selection and pricing are two crucial decisions for the profitability of a manufacturing firm. Remanufacturing, on the other hand, may be a profitable strategy that captures the remaining value in used products. In this paper we develop a mixed-integer nonlinear programming model form the perspective of an original equipment manufacturer (OEM). The objective of the OEM is to select products to manufacture and remanufacture among a set of given alternatives and simultaneously determine their prices so as to maximize its profit. It is assumed that the probability a customer selects a product is proportional to its utility and inversely proportional to its price. The utility of a product is an increasing function of its perceived quality. In our base model, products are discriminated by their unit production costs and utilities. We also analyze a case where remanufacturing is limited by the available quantity of collected remanufacturable products. We show that the resulting problem is decomposed into the pricing and product line selection subproblems. Pricing problem is solved by a variant of the simplex search procedure which can also handle constraints, while complete enumeration and a genetic algorithm are used for the solution of the product line selection problem. A number of experiments are carried out to identify conditions under which it is economically viable for the firm to sell remanufactured products. We also determine the optimal utility and unit production cost values of a remanufactured product, which maximizes the total profit of the OEM.

Selecting essential information for biosurveillance--a multi-criteria decision analysis.

PubMed

Generous, Nicholas; Margevicius, Kristen J; Taylor-McCabe, Kirsten J; Brown, Mac; Daniel, W Brent; Castro, Lauren; Hengartner, Andrea; Deshpande, Alina

2014-01-01

The National Strategy for Biosurveillance defines biosurveillance as "the process of gathering, integrating, interpreting, and communicating essential information related to all-hazards threats or disease activity affecting human, animal, or plant health to achieve early detection and warning, contribute to overall situational awareness of the health aspects of an incident, and to enable better decision-making at all levels." However, the strategy does not specify how "essential information" is to be identified and integrated into the current biosurveillance enterprise, or what the metrics qualify information as being "essential". The question of data stream identification and selection requires a structured methodology that can systematically evaluate the tradeoffs between the many criteria that need to be taken in account. Multi-Attribute Utility Theory, a type of multi-criteria decision analysis, can provide a well-defined, structured approach that can offer solutions to this problem. While the use of Multi-Attribute Utility Theoryas a practical method to apply formal scientific decision theoretical approaches to complex, multi-criteria problems has been demonstrated in a variety of fields, this method has never been applied to decision support in biosurveillance.We have developed a formalized decision support analytic framework that can facilitate identification of "essential information" for use in biosurveillance systems or processes and we offer this framework to the global BSV community as a tool for optimizing the BSV enterprise. To demonstrate utility, we applied the framework to the problem of evaluating data streams for use in an integrated global infectious disease surveillance system.

Prevalence of self-medication and associated factors in an elderly population: a systematic review.

PubMed

Jerez-Roig, Javier; Medeiros, Lucas F B; Silva, Victor A B; Bezerra, Camila L P A M; Cavalcante, Leandro A R; Piuvezam, Grasiela; Souza, Dyego L B

2014-12-01

The aging of the world populat ion together with changes in the epidemiological profile of diseases have led to increases in both the consumption of medicines and health expenses. In this context, self-medication has gained importance as a rapid treatment that bypasses bureaucracy and, in some instances, delays in obtaining medical assistance. Verification of self-medication prevalence and associated factors in the elderly, as well as identification of the main categories of non-prescription drugs utilized. The following databases were utilized: Cochrane, PubMed, Scopus, LILACS, SciELO, PAHO, MedCarib and WHOLIS. Studies on the prevalence of self-medication in community-dwelling elderly were included. Review studies were excluded, as well as MSc dissertations, PhD theses and research with convenience sampling. Community-dwelling individuals aged 60 years or over. A systematic review of population-based articles published up until September 1, 2014, is presented. The STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) Statement was applied for critical assessment of the articles, and those with a minimum score of 60% were selected for inclusion in the review. Thirty-six articles were selected, of which 28 were included after critical reading. The prevalence of self-medication varied between 4 and 87%, and the majority of studies reported values between 20 and 60%. The mean prevalence reported in the articles was 38%, but several criteria were utilized to measure self-medication. The most commonly utilized non-prescription drugs were analgesics and antipyretics, followed by non-hormonal anti-inflammatories, cardiovascular agents, dietary complements and alternative medicine components. The variables that presented positive associations with self-medication were female sex, visits to pharmacists, depression, functional dependency, recent hospitalization, oral pain, restriction of activities and physical inactivity. The variables with negative associations were medical appointments, married status, use of health services, satisfaction with living arrangements, living in institutional settings and private health plans. Different definitions of self-medication were employed in the identified articles, which hindered the comparison between studies and meta-analysis. Only 15 studies analysed associated factors and a minority carried out multivariate data analysis. Self-medication is frequent among the elderly, with different prevalence values found in the selected studies, probably because of heterogeneity in definitions and samples. Future studies are necessary, utilizing a standard self-medication criterion to facilitate comparison and elucidate the factors associated with this behaviour.

Utility of an Error Analysis and Performance Deficit Assessment for Selecting Brief Interventions to Increase Math Fluency

ERIC Educational Resources Information Center

Denison, Aaron

2013-01-01

The purpose of this study was to examine the utility of a brief assessment for the selection of an effective instruction to increase fluency performance on computation math problems. Participants were four general education third-grade students who performed below the median score on a classwide administered multiple math skills probe. Students…

Microbial Electrochemistry and its Application to Energy and Environmental Issues

NASA Astrophysics Data System (ADS)

Hastings, Jason Thomas

Microbial electrochemistry forms the basis of a wide range of topics from microbial fuel cells to fermentation of carbon food sources. The ability to harness microbial electron transfer processes can lead to a greener and cleaner future. This study focuses on microbial electron transfer for liquid fuel production, novel electrode materials, subsurface environments and removal of unwanted byproducts. In the first chapter, exocellular electron transfer through direct contact utilizing passive electrodes for the enhancement of bio-fuel production was tested. Through the application of microbial growth in a 2-cell apparatus on an electrode surface ethanol production was enhanced by 22.7% over traditional fermentation. Ethanol production efficiencies of close to 95% were achieved in a fraction of the time required by traditional fermentation. Also, in this chapter, the effect of exogenous electron shuttles, electrode material selection and resistance was investigated. Power generation was observed using the 2-cell passive electrode system. An encapsulation method, which would also utilize exocellular transfer of electrons through direct contact, was hypothesized for the suspension of viable cells in a conductive polymer substrate. This conductive polymer substrate could have applications in bio-fuel production. Carbon black was added to a polymer solution to test electrospun polymer conductivity and cell viability. Polymer morphology and cell viability were imaged using electron and optical microscopy. Through proper encapsulation, higher fuel production efficiencies would be achievable. Electron transfer through endogenous exocellular protein shuttles was observed in this study. Secretion of a soluble redox active exocellular protein by Clostridium sp. have been shown utilizing a 2-cell apparatus. Cyclic voltammetry and gel electrophoresis were used to show the presence of the protein. The exocellular protein is capable of reducing ferrous iron in a membrane separated chamber. In experiments where the redox active protein was allowed to pass through the permeable membrane, iron dissolution was 14-fold greater than experiments where the protein was held to one chamber by a non-permeable membrane. Confirmation of a redox active protein could reshape or understanding of subsurface redox processes. The final topic in this study discusses electron transfer within the cell for production of fermentation products. Glycerol, which is an unwanted side-product of biodiesel transesterfication, is utilized as a carbon source for fermentation. Bacterial samples harvested from Galena Creek soil (NGC) are shown in this study to be efficient consumers of glycerol. NGC microbe was characterized through 16s rDNA genetic sequencing and determined to belong to genus Clostridium. Clostridium NGC was able to consume glycerol at 29.7gpl within 72hrs grown in a media containing 50gpl glycerol. All observed fermentation metabolites were characterized and quantified through an HPLC. Glycerol consumption rates and metabolite production rates were observed using varying media recipes. This study has found that NGC has higher selectivity for low weight acids at lower yeast extract concentration and higher selectivity for larger acids and alcohols at higher yeast extract concentrations.

Development of selective media for the isolation and enumeration of Alternaria species from soil and plant debris.

PubMed

Hong, Soon Gyu; Pryor, Barry M

2004-07-01

A new semi-selective medium, acidified weak potato-dextrose agar (AWPDA) with Mertect (active ingredient: thiabendazole), was developed for the isolation and enumeration of Alternaria species from samples of soil and plant debris. The medium was selected based on growth inhibition tests against Alternaria and several other commonly encountered saprobic fungi utilizing three antifungal agents, Botran (active ingredient: dichloran), Bayleton (active ingredient: triadimefon), and Mertect, and two basal media, acidified potato-dextrose agar (APDA) and AWPDA. Botran inhibited growth of Rhizopus stolonifer moderately, but had little effect on Cladosporium cladosporoides, Fusarium oxysporum, Penicillium chrysogenum, or Trichoderma harzianum. Bayleton inhibited growth of R. stolonifer and C. cladosporoides severely, and inhibited growth of F. oxysporum, P. chrysogenum, and T. harzianum moderately. Mertect inhibited growth of C. cladosporoides, F. oxysporum, P. chrysogenum, and T. harzianum completely, but had little or moderate effect on R. stolonifer. All three antifungal agents inhibited growth of Alternaria species slightly or moderately. The combination of Bayleton and Mertect inhibited growth of all fungi severely. A comparison of recovery rates of Alternaria from soil and plant debris samples on AWPDA with Mertect and weak potato-dextrose agar (WPDA) revealed that Alternaria spp. accounted for 63.6%-81.0% of recovered fungal isolates on AWPDA with Mertect as compared to 0.6%-2.7% of recovered isolates on WPDA. The AWPDA medium with Mertect exhibited superior selective growth of Alternaria species from samples of soil and plant debris, and will be useful in studies where the recovery and enumeration of Alternaria species is necessary.

FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements) isolates active regulatory elements from human chromatin

PubMed Central

Giresi, Paul G.; Kim, Jonghwan; McDaniell, Ryan M.; Iyer, Vishwanath R.; Lieb, Jason D.

2007-01-01

DNA segments that actively regulate transcription in vivo are typically characterized by eviction of nucleosomes from chromatin and are experimentally identified by their hypersensitivity to nucleases. Here we demonstrate a simple procedure for the isolation of nucleosome-depleted DNA from human chromatin, termed FAIRE (Formaldehyde-Assisted Isolation of Regulatory Elements). To perform FAIRE, chromatin is crosslinked with formaldehyde in vivo, sheared by sonication, and phenol-chloroform extracted. The DNA recovered in the aqueous phase is fluorescently labeled and hybridized to a DNA microarray. FAIRE performed in human cells strongly enriches DNA coincident with the location of DNaseI hypersensitive sites, transcriptional start sites, and active promoters. Evidence for cell-type–specific patterns of FAIRE enrichment is also presented. FAIRE has utility as a positive selection for genomic regions associated with regulatory activity, including regions traditionally detected by nuclease hypersensitivity assays. PMID:17179217

Carbon–hydrogen (C–H) bond activation at PdIV: a Frontier in C–H functionalization catalysis

PubMed Central

Topczewski, Joseph J.

2015-01-01

The direct functionalization of carbon–hydrogen (C–H) bonds has emerged as a versatile strategy for the synthesis and derivatization of organic molecules. Among the methods for C–H bond activation, catalytic processes that utilize a PdII/PdIV redox cycle are increasingly common. The C–H activation step in most of these catalytic cycles is thought to occur at a PdII centre. However, a number of recent reports have suggested the feasibility of C–H cleavage occurring at PdIV complexes. Importantly, these latter processes often result in complementary reactivity and selectivity relative to analogous transformations at PdII. This mini review highlights proposed examples of C–H activation at PdIV centres. Applications of this transformation in catalysis as well as mechanistic details obtained from stoichiometric model studies are discussed. Furthermore, challenges and future perspectives for the field are reviewed. PMID:25544882

Carbon-Hydrogen (C-H) Bond Activation at PdIV: A Frontier in C-H Functionalization Catalysis.

PubMed

Topczewski, Joseph J; Sanford, Melanie S

2015-01-01

The direct functionalization of carbon-hydrogen (C-H) bonds has emerged as a versatile strategy for the synthesis and derivatization of organic molecules. Among the methods for C-H bond activation, catalytic processes that utilize a Pd II /Pd IV redox cycle are increasingly common. The C-H activation step in most of these catalytic cycles is thought to occur at a Pd II centre. However, a number of recent reports have suggested the feasibility of C-H cleavage occurring at Pd IV complexes. Importantly, these latter processes often result in complementary reactivity and selectivity relative to analogous transformations at Pd II . This Mini Review highlights proposed examples of C-H activation at Pd IV centres. Applications of this transformation in catalysis as well as mechanistic details obtained from stoichiometric model studies are discussed. Furthermore, challenges and future perspectives for the field are reviewed.

Photoredox activation of carbon dioxide for amino acid synthesis in continuous flow

NASA Astrophysics Data System (ADS)

Seo, Hyowon; Katcher, Matthew H.; Jamison, Timothy F.

2017-05-01

Although carbon dioxide (CO2) is highly abundant, its low reactivity has limited its use in chemical synthesis. In particular, methods for carbon-carbon bond formation generally rely on two-electron mechanisms for CO2 activation and require highly activated reaction partners. Alternatively, radical pathways accessed via photoredox catalysis could provide new reactivity under milder conditions. Here we demonstrate the direct coupling of CO2 and amines via the single-electron reduction of CO2 for the photoredox-catalysed continuous flow synthesis of α-amino acids. By leveraging the advantages of utilizing gases and photochemistry in flow, a commercially available organic photoredox catalyst effects the selective α-carboxylation of amines that bear various functional groups and heterocycles. The preliminary mechanistic studies support CO2 activation and carbon-carbon bond formation via single-electron pathways, and we expect that this strategy will inspire new perspectives on using this feedstock chemical in organic synthesis.

Bidirectional Active Learning: A Two-Way Exploration Into Unlabeled and Labeled Data Set.

PubMed

Zhang, Xiao-Yu; Wang, Shupeng; Yun, Xiaochun

2015-12-01

In practical machine learning applications, human instruction is indispensable for model construction. To utilize the precious labeling effort effectively, active learning queries the user with selective sampling in an interactive way. Traditional active learning techniques merely focus on the unlabeled data set under a unidirectional exploration framework and suffer from model deterioration in the presence of noise. To address this problem, this paper proposes a novel bidirectional active learning algorithm that explores into both unlabeled and labeled data sets simultaneously in a two-way process. For the acquisition of new knowledge, forward learning queries the most informative instances from unlabeled data set. For the introspection of learned knowledge, backward learning detects the most suspiciously unreliable instances within the labeled data set. Under the two-way exploration framework, the generalization ability of the learning model can be greatly improved, which is demonstrated by the encouraging experimental results.

Phenanthroline-based metal–organic frameworks for Fe-catalyzed C sp3 –H amination

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

Thacker, Nathan C.; Ji, Pengfei; Lin, Zekai

2017-01-01

We report here the synthesis of a robust and highly porous Fe-phenanthroline-based metal–organic framework (MOF) and its application in catalyzing challenging inter- and intramolecular C–H amination reactions. For the intermolecular amination reactions, a FeBr 2-metalated MOF selectively functionalized secondary benzylic and allylic C–H bonds. The intramolecular amination reactions utilizing organic azides as the nitrene source required the reduction of the FeBr 2-metalated MOF with NaBHEt 3to generate the active catalyst. For both reactions, Fe or Zr leaching was less than 0.1%, and MOFs could be recycled and reused with no loss in catalytic activity. Furthermore, MOF catalysts were significantly moremore » active than the corresponding homogeneous analogs. This work demonstrates the great potential of MOFs in generating highly active, recyclable, and reusable earth abundant metal catalysts for challenging organic transformations.« less

13C metabolic flux analysis: optimal design of isotopic labeling experiments.

PubMed

Antoniewicz, Maciek R

2013-12-01

Measuring fluxes by 13C metabolic flux analysis (13C-MFA) has become a key activity in chemical and pharmaceutical biotechnology. Optimal design of isotopic labeling experiments is of central importance to 13C-MFA as it determines the precision with which fluxes can be estimated. Traditional methods for selecting isotopic tracers and labeling measurements did not fully utilize the power of 13C-MFA. Recently, new approaches were developed for optimal design of isotopic labeling experiments based on parallel labeling experiments and algorithms for rational selection of tracers. In addition, advanced isotopic labeling measurements were developed based on tandem mass spectrometry. Combined, these approaches can dramatically improve the quality of 13C-MFA results with important applications in metabolic engineering and biotechnology. Copyright © 2013 Elsevier Ltd. All rights reserved.

AVTA Federal Fleet PEV Readiness Data Logging and Characterization Study: Final Report

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

Schey, Stephen; Francfort, Jim

2015-06-01

Collect and evaluate data on federal fleet operations as part of the Advanced Vehicle Testing Activity’s Federal Fleet Vehicle Data Logging and Characterization Study. The Advanced Vehicle Testing Activity study seeks to collect and evaluate data to validate the utilization of advanced plug-in electric vehicle (PEV) transportation. This report summarizes the fleets studied to identify daily operational characteristics of select vehicles and report findings on vehicle and mission characterizations to support the successful introduction of PEVs into the agencies’ fleets. Individual observations of these selected vehicles provide the basis for recommendations related to electric vehicle adoption and whether a batterymore » electric vehicle or plug-in hybrid electric vehicle (collectively referred to as PEVs) can fulfill the mission requirements.« less

An integrated model for adolescent inpatient group therapy.

PubMed

Garrick, D; Ewashen, C

2001-04-01

This paper proposes an integrated group therapy model to be utilized by psychiatric and mental health nurses; one innovatively designed to meet the therapeutic needs of adolescents admitted to inpatient psychiatric programs. The writers suggest a model of group therapy primarily comprised of interpersonal approaches within a feminist perspective. The proposed group focus is on active therapeutic engagement with adolescents to further interpersonal learning and to critically examine their contextualized lived experiences. Specific client and setting factors relevant to the selection of therapeutic techniques are reviewed. Selected theoretical models of group therapy are critiqued in relation to group therapy with adolescents. This integrated model of group therapy provides a safe and therapeutic forum that enriches clients' personal and interpersonal experiences as well as promotes healthy exploration, change, and empowerment.

Design of a Miniaturized RAD Hard Point-of-Load Converter

NASA Astrophysics Data System (ADS)

Lofgren, Henrik; Landstrom, Sven; Gunnarsson, Marcus; Hagstrom, Maria

2014-08-01

As an ARTES 5.2 activity, a miniaturized radiation hardened Point-Of-Load converter (uPOL) has been developed. Several different design options have been evaluated before the final system level design was selected. The selected topology is a buck regulator with synchronous rectification utilizing peak current mode control. The PWM logic is designed using discrete electronics. Inside the POL converter package, an independent latching current limiter and clamping over- voltage protection are included as protection devices. The converter has an input voltage range of 4.8-6.2V, output voltage range of 1.2-3.5V and an output current of 0-3.5A. The final converter will be a metal packaged hybrid built on LTCC technology with an operating case temperature range of -40 to +85 °C.

Sequence-Specific Targeting of Dosage Compensation in Drosophila Favors an Active Chromatin Context

PubMed Central

Gelbart, Marnie; Tolstorukov, Michael Y.; Plachetka, Annette; Kharchenko, Peter V.; Jung, Youngsook L.; Gorchakov, Andrey A.; Larschan, Erica; Gu, Tingting; Minoda, Aki; Riddle, Nicole C.; Schwartz, Yuri B.; Elgin, Sarah C. R.; Karpen, Gary H.; Pirrotta, Vincenzo; Kuroda, Mitzi I.; Park, Peter J.

2012-01-01

The Drosophila MSL complex mediates dosage compensation by increasing transcription of the single X chromosome in males approximately two-fold. This is accomplished through recognition of the X chromosome and subsequent acetylation of histone H4K16 on X-linked genes. Initial binding to the X is thought to occur at “entry sites” that contain a consensus sequence motif (“MSL recognition element” or MRE). However, this motif is only ∼2 fold enriched on X, and only a fraction of the motifs on X are initially targeted. Here we ask whether chromatin context could distinguish between utilized and non-utilized copies of the motif, by comparing their relative enrichment for histone modifications and chromosomal proteins mapped in the modENCODE project. Through a comparative analysis of the chromatin features in male S2 cells (which contain MSL complex) and female Kc cells (which lack the complex), we find that the presence of active chromatin modifications, together with an elevated local GC content in the surrounding sequences, has strong predictive value for functional MSL entry sites, independent of MSL binding. We tested these sites for function in Kc cells by RNAi knockdown of Sxl, resulting in induction of MSL complex. We show that ectopic MSL expression in Kc cells leads to H4K16 acetylation around these sites and a relative increase in X chromosome transcription. Collectively, our results support a model in which a pre-existing active chromatin environment, coincident with H3K36me3, contributes to MSL entry site selection. The consequences of MSL targeting of the male X chromosome include increase in nucleosome lability, enrichment for H4K16 acetylation and JIL-1 kinase, and depletion of linker histone H1 on active X-linked genes. Our analysis can serve as a model for identifying chromatin and local sequence features that may contribute to selection of functional protein binding sites in the genome. PMID:22570616

Raccoon spatial requirements and multi-scale habitat selection within an intensively managed central Appalachian forest

USGS Publications Warehouse

Owen, Sheldon F.; Berl, Jacob L.; Edwards, John W.; Ford, W. Mark; Wood, Petra Bohall

2015-01-01

We studied a raccoon (Procyon lotor) population within a managed central Appalachian hardwood forest in West Virginia to investigate the effects of intensive forest management on raccoon spatial requirements and habitat selection. Raccoon home-range (95% utilization distribution) and core-area (50% utilization distribution) size differed between sexes with males maintaining larger (2×) home ranges and core areas than females. Home-range and core-area size did not differ between seasons for either sex. We used compositional analysis to quantify raccoon selection of six different habitat types at multiple spatial scales. Raccoons selected riparian corridors (riparian management zones [RMZ]) and intact forests (> 70 y old) at the core-area spatial scale. RMZs likely were used by raccoons because they provided abundant denning resources (i.e., large-diameter trees) as well as access to water. Habitat composition associated with raccoon foraging locations indicated selection for intact forests, riparian areas, and regenerating harvest (stands <10 y old). Although raccoons were able to utilize multiple habitat types for foraging resources, a selection of intact forest and RMZs at multiple spatial scales indicates the need of mature forest (with large-diameter trees) for this species in managed forests in the central Appalachians.

Targeting Histone Deacetylases in Diseases: Where Are We?

PubMed Central

Benedetti, Rosaria; Conte, Mariarosaria

2015-01-01

Abstract Significance: Epigenetic inactivation of pivotal genes involved in cell growth is a hallmark of human pathologies, in particular cancer. Histone acetylation balance obtained through opposing actions of histone deacetylases (HDACs) and histone acetyltransferases is one epigenetic mechanism controlling gene expression and is, thus, associated with disease etiology and progression. Interfering pharmacologically with HDAC activity can correct abnormalities in cell proliferation, migration, vascularization, and death. Recent Advances: Histone deacetylase inhibitors (HDACi) represent a new class of cytostatic agents that interfere with the function of HDACs and are able to increase gene expression by indirectly inducing histone acetylation. Several HDACi, alone or in combination with DNA-demethylating agents, chemopreventive, or classical chemotherapeutic drugs, are currently being used in clinical trials for solid and hematological malignancies, and are, thus, promising candidates for cancer therapy. Critical Issues: (i) Non-specific (off-target) HDACi effects due to activities unassociated with HDAC inhibition. (ii) Advantages/disadvantages of non-selective or isoform-directed HDACi. (iii) Limited number of response-predictive biomarkers. (iv) Toxicity leading to dysfunction of critical biological processes. Future Directions: Selective HDACi could achieve enhanced clinical utility by reducing or eliminating the serious side effects associated with current first-generation non-selective HDACi. Isoform-selective and pan-HDACi candidates might benefit from the identification of biomarkers, enabling better patient stratification and prediction of response to treatment. Antioxid. Redox Signal. 23, 99–126. PMID:24382114

Bicyclic-Capped Histone Deacetylase 6 Inhibitors with Improved Activity in a Model of Axonal Charcot-Marie-Tooth Disease.

PubMed

Shen, Sida; Benoy, Veronick; Bergman, Joel A; Kalin, Jay H; Frojuello, Mariana; Vistoli, Giulio; Haeck, Wanda; Van Den Bosch, Ludo; Kozikowski, Alan P

2016-02-17

Charcot-Marie-Tooth (CMT) disease is a disorder of the peripheral nervous system where progressive degeneration of motor and sensory nerves leads to motor problems and sensory loss and for which no pharmacological treatment is available. Recently, it has been shown in a model for the axonal form of CMT that histone deacetylase 6 (HDAC6) can serve as a target for the development of a pharmacological therapy. Therefore, we aimed at developing new selective and activity-specific HDAC6 inhibitors with improved biochemical properties. By utilizing a bicyclic cap as the structural scaffold from which to build upon, we developed several analogues that showed improved potency compared to tubastatin A while maintaining excellent selectivity compared to HDAC1. Further screening in N2a cells examining both the acetylation of α-tubulin and histones narrowed down the library of compounds to three potent and selective HDAC6 inhibitors. In mutant HSPB1-expressing DRG neurons, serving as an in vitro model for CMT2, these inhibitors were able to restore the mitochondrial axonal transport deficits. Combining structure-based development of HDAC6 inhibitors, screening in N2a cells and in a neuronal model for CMT2F, and preliminary ADMET and pharmacokinetic profiles, resulted in the selection of compound 23d that possesses improved biochemical, functional, and druglike properties compared to tubastatin A.

Long-range transcriptional interference in E. coli used to construct a dual positive selection system for genetic switches

PubMed Central

Hoffmann, Stefan A.; Kruse, Sabrina M.; Arndt, Katja M.

2016-01-01

Abstract We have investigated transcriptional interference between convergent genes in E. coli and demonstrate substantial interference for inter-promoter distances of as far as 3 kb. Interference can be elicited by both strong σ70 dependent and T7 promoters. In the presented design, a strong promoter driving gene expression of a ‘forward’ gene interferes with the expression of a ‘reverse’ gene by a weak promoter. This arrangement allows inversely correlated gene expression without requiring further regulatory components. Thus, modulation of the activity of the strong promoter alters expression of both the forward and the reverse gene. We used this design to develop a dual selection system for conditional operator site binding, allowing positive selection both for binding and for non-binding to DNA. This study demonstrates the utility of this novel system using the Lac repressor as a model protein for conditional DNA binding, and spectinomycin and chloramphenicol resistance genes as positive selection markers in liquid culture. Randomized LacI libraries were created and subjected to subsequent dual selection, but mispairing IPTG and selection cues in respect to the wild-type LacI response, allowing the isolation of a LacI variant with a reversed IPTG response within three rounds of library generation and dual selection. PMID:26932362

Utilizing Ayurvedic literature for the identification of novel phytochemical inhibitors of botulinum neurotoxin A.

PubMed

Yalamanchili, Chinni; Manda, Vamshi K; Chittiboyina, Amar G; Guernieri, Rebecca L; Harrell, William A; Webb, Robert P; Smith, Leonard A; Khan, Ikhlas A

2017-02-02

Ayurveda, an ancient holistic system of health care practiced on the Indian subcontinent, utilizes a number of multi-plant formulations and is considered by many as a potential source for novel treatments, as well as the identification of new drugs. Our aim is to identify novel phytochemicals for the inhibition of bacterial exotoxin, botulinum neurotoxin A (BoNT/A) based on Ayurvedic literature. BoNT/A is released by Clostridium species, which when ingested, inhibits the release of acetylcholine by concentrating at the neuromuscular junction and causes flaccid paralysis, resulting in a condition termed as botulism, and may also lead to death due to respiratory arrest. Fifteen plants were selected from the book 'Diagnosis and treatment of diseases in Ayurveda' by Vaidya Bhagwan Dash and Lalitesh Kashyap, based on their frequency of use in the formulations used for the treatment of six diseases with neuromuscular symptoms similar to botulism. Phytochemicals from these plants were screened using in silico, and in vitro methods. Structures of 570 reported phytochemicals from 14 plants were docked inside six reported BoNT/A light chain crystal structures using ensemble docking module in Maestro (Schrödinger, LLE). From the docking scores and structural diversity, nine compounds including acoric acid 1, three flavonoids, three coumarins derivatives, one kava lactone were selected and screened using an in vitro HPLC-based protease assay. The bioassay results showed that several compounds possess BoNT/A LC inhibition of 50-60% when compared to positive controls NSC 84094 and CB7967495 (80-95%). Further testing of the active compounds identified from Ayurvedic literature and structure-activity studies of acoric acid 1 using more sensitive bioassays is under way. The identification of acoric acid 1, a novel scaffold against BoNT/A, exemplifies the utility of Ayurvedic literature for the discovery of novel drug leads. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Identifying relevant hyperspectral bands using Boruta: a temporal analysis of water hyacinth biocontrol

NASA Astrophysics Data System (ADS)

Agjee, Na'eem Hoosen; Ismail, Riyad; Mutanga, Onisimo

2016-10-01

Water hyacinth plants (Eichhornia crassipes) are threatening freshwater ecosystems throughout Africa. The Neochetina spp. weevils are seen as an effective solution that can combat the proliferation of the invasive alien plant. We aimed to determine if multitemporal hyperspectral data could be utilized to detect the efficacy of the biocontrol agent. The random forest (RF) algorithm was used to classify variable infestation levels for 6 weeks using: (1) all the hyperspectral bands, (2) bands selected by the recursive feature elimination (RFE) algorithm, and (3) bands selected by the Boruta algorithm. Results showed that the RF model using all the bands successfully produced low-classification errors (12.50% to 32.29%) for all 6 weeks. However, the RF model using Boruta selected bands produced lower classification errors (8.33% to 15.62%) than the RF model using all the bands or bands selected by the RFE algorithm (11.25% to 21.25%) for all 6 weeks, highlighting the utility of Boruta as an all relevant band selection algorithm. All relevant bands selected by Boruta included: 352, 754, 770, 771, 775, 781, 782, 783, 786, and 789 nm. It was concluded that RF coupled with Boruta band-selection algorithm can be utilized to undertake multitemporal monitoring of variable infestation levels on water hyacinth plants.

Judging Statistical Models of Individual Decision Making under Risk Using In- and Out-of-Sample Criteria

PubMed Central

Drichoutis, Andreas C.; Lusk, Jayson L.

2014-01-01

Despite the fact that conceptual models of individual decision making under risk are deterministic, attempts to econometrically estimate risk preferences require some assumption about the stochastic nature of choice. Unfortunately, the consequences of making different assumptions are, at present, unclear. In this paper, we compare three popular error specifications (Fechner, contextual utility, and Luce error) for three different preference functionals (expected utility, rank-dependent utility, and a mixture of those two) using in- and out-of-sample selection criteria. We find drastically different inferences about structural risk preferences across the competing functionals and error specifications. Expected utility theory is least affected by the selection of the error specification. A mixture model combining the two conceptual models assuming contextual utility provides the best fit of the data both in- and out-of-sample. PMID:25029467

Judging statistical models of individual decision making under risk using in- and out-of-sample criteria.

PubMed

Drichoutis, Andreas C; Lusk, Jayson L

2014-01-01

Despite the fact that conceptual models of individual decision making under risk are deterministic, attempts to econometrically estimate risk preferences require some assumption about the stochastic nature of choice. Unfortunately, the consequences of making different assumptions are, at present, unclear. In this paper, we compare three popular error specifications (Fechner, contextual utility, and Luce error) for three different preference functionals (expected utility, rank-dependent utility, and a mixture of those two) using in- and out-of-sample selection criteria. We find drastically different inferences about structural risk preferences across the competing functionals and error specifications. Expected utility theory is least affected by the selection of the error specification. A mixture model combining the two conceptual models assuming contextual utility provides the best fit of the data both in- and out-of-sample.

A collaborative university model for employee wellness.

PubMed

Carter, Melondie R; Kelly, Rebecca C; Alexander, Chelley K; Holmes, Lauren M

2011-01-01

Universities are taking a more active approach in understanding and monitoring employees' modifiable health risk factors and chronic care conditions by developing strategies to encourage employees to start and sustain healthy behaviors. WellBama, the University of Alabama's signature health and wellness program, utilizes a collaborative model in partnership with select colleges and departments to implement strategies to improve employees' health status. The program provides onsite health screenings and assessments, timely health advising sessions, assistance in setting and monitoring individual health goals to promote improved health, and preventive examination referrals.

Modeling the Supply Process Using the Application of Selected Methods of Operational Analysis

NASA Astrophysics Data System (ADS)

Chovancová, Mária; Klapita, Vladimír

2017-03-01

Supply process is one of the most important enterprise activities. All raw materials, intermediate products and products, which are moved within enterprise, are the subject of inventory management and by their effective management significant improvement of enterprise position on the market can be achieved. For that reason, the inventory needs to be managed, monitored, evaluated and affected. The paper deals with utilizing the methods of the operational analysis in the field of inventory management in terms of achieving the economic efficiency and ensuring the particular customer's service level as well.

Dual Leucine Zipper Kinase Inhibitors for the Treatment of Neurodegeneration.

PubMed

Siu, Michael; Sengupta Ghosh, Arundhati; Lewcock, Joseph W

2018-06-04

Dual leucine zipper kinase (DLK, MAP3K12) is an essential driver of the neuronal stress response that regulates neurodegeneration in models of acute neuronal injury and chronic neurodegenerative diseases such as Alzheimer's, Parkinson's, and ALS. In this review, we provide an overview of DLK signaling mechanisms and describe selected small molecules that have been utilized to inhibit DLK kinase activity in vivo. These compounds represent valuable tools for understanding the role of DLK signaling and evaluating the potential for DLK inhibition as a therapeutic strategy to prevent neuronal degeneration.

Fiber optic SERS-based plasmonics nanobiosensing in single living cells

NASA Astrophysics Data System (ADS)

Scaffidi, Jonathan P.; Gregas, Molly K.; Seewaldt, Victoria; Vo-Dinh, Tuan

2009-05-01

We describe the development of small molecule-sensitive plasmonics-active fiber-optic nanoprobes suitable for intracellular bioanalysis in single living human cells using surface-enhanced Raman scattering (SERS) detection. The practical utility of SERS-based fiber-optic nanoprobes is illustrated by measurements of intracellular pH in HMEC- 15/hTERT immortalized "normal" human mammary epithelial cells and PC-3 human prostate cancer cells. The results indicate that fiber-optic nanoprobe insertion and interrogation provide a sensitive and selective means to monitor biologically-relevant small molecules at the single cell level.

Progress in wet-coated organic light-emitting devices for lighting

NASA Astrophysics Data System (ADS)

Liu, Jie; Ye, Qing; Lewis, Larry N.; Duggal, Anil R.

2007-09-01

Here we present recent progress in developing efficient wet-coated organic light-emitting devices (OLEDs) for lighting applications. In particular, we describe a novel approach for building efficient wet-coated dye-doped blue phosphorescent devices. Further, a novel approach for achieving arbitrary emission patterning for OLEDs is discussed. This approach utilizes a photo-induced chemical doping strategy for selectively activating charge injection materials, thus enabling devices with arbitrary emission patterning. This approach may provide a simple, low cost path towards specialty lighting and signage applications for OLED technology.

Redox active polymers and colloidal particles for flow batteries

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

Gavvalapalli, Nagarjuna; Moore, Jeffrey S.; Rodriguez-Lopez, Joaquin

The invention provides a redox flow battery comprising a microporous or nanoporous size-exclusion membrane, wherein one cell of the battery contains a redox-active polymer dissolved in the non-aqueous solvent or a redox-active colloidal particle dispersed in the non-aqueous solvent. The redox flow battery provides enhanced ionic conductivity across the electrolyte separator and reduced redox-active species crossover, thereby improving the performance and enabling widespread utilization. Redox active poly(vinylbenzyl ethylviologen) (RAPs) and redox active colloidal particles (RACs) were prepared and were found to be highly effective redox species. Controlled potential bulk electrolysis indicates that 94-99% of the nominal charge on different RAPsmore » is accessible and the electrolysis products are stable upon cycling. The high concentration attainable (>2.0 M) for RAPs in common non-aqueous battery solvents, their electrochemical and chemical reversibility, and their hindered transport across porous separators make them attractive materials for non-aqueous redox flow batteries based on size-selectivity.« less

Purification and characterization of Phaseolus vulgaris alpha-D-galactosidase isozymes.

PubMed

Dhar, M; Mitra, M; Hata, J; Butnariu, O; Smith, D

1994-11-01

A highly purified preparation of alpha-D-galactosidase [E.C. 3.2.1.22] isozymes was obtained from Phaseolus vulgaris (pinto bean) seeds by extraction, salt precipitation, ion exchange, and affinity chromatography. The final preparation was homogeneous by SDS-PAGE but revealed isozymes of relative mass of 38.3 and 39.6 kDa. The N-terminal sequence for both isozymes was identical, LANGLAKT (one letter code for amino acids). Relative native molecular mass was estimated at 149.3 kDa by Sephacryl S-200 chromatography. Activity was unaffected by ionic strength at high enzyme concentrations, and was specific for alpha-D-galactoside conjugates. No protease or hemagglutinin activity was detected, and activity was stable at 4 degrees C. Studies with soluble oligosaccharides demonstrated high activity against the selected straight and branched-chain substrates. The enzyme was active against terminal alpha 1-3 galactosyl residues on human and rabbit erythrocyte membranes. Because of its activity against membrane glycoconjugates, these isozymes may have potential utility for modifying membrane epitopes on native erythrocytes.

Discovery of a new function of curcumin which enhances its anticancer therapeutic potency

NASA Astrophysics Data System (ADS)

Nagahama, Koji; Utsumi, Tomoya; Kumano, Takayuki; Maekawa, Saeko; Oyama, Naho; Kawakami, Junji

2016-08-01

Curcumin has received immense attention over the past decades because of its diverse biological activities and recognized as a promising drug candidate in a large number of diseases. However, its clinical application has been hindered due to extremely low aqueous solubility, chemical stability, and cellular uptake. In this study, we discovered quite a new function of curcumin, i.e. pH-responsive endosomal disrupting activity, derived from curcumin’s self-assembly. We selected anticancer activity as an example of biological activities of curcumin, and investigated the contribution of pH-responsive property to its anticancer activity. As a result, we demonstrated that the pH-responsive property significantly enhances the anticancer activity of curcumin. Furthermore, we demonstrated a utility of the pH-responsive property of curcumin as delivery nanocarriers for doxorubicin toward combination cancer therapy. These results clearly indicate that the smart curcumin assemblies act as promising nanoplatform for development of curcumin-based therapeutics.

Selective vibration sensing: a new concept for activity-sensing rate-responsive pacing.

PubMed

Lau, C P; Stott, J R; Toff, W D; Zetlein, M B; Ward, D E; Camm, A J

1988-09-01

A clinically available model of an activity-sensing, rate-responsive pacemaker (Activitrax, Medtronic) utilizes body vibration during exercise as an indicator of the need for a rate increase. Although having the advantage of rapid onset of rate response, this system lacks specificity and the rate response does not closely correlate with the level of exertion. In addition, this pacemaker is susceptible to the effects of extraneous vibration. In this study involving 20 normal subjects fitted with an external Activitrax pacemaker, the rate responses to a variety of exercises were studied and were compared with the corresponding sinus rates. The vibration generated at the level of the pacemaker was also measured by accelerometers in three axes. Only a fair correlation (r = 0.51) was achieved between the pacemaker rate and the sinus rate. The total root mean square value of acceleration in either the anteroposterior or the vertical axes was found to have a better correlation (r = 0.8). As the main accelerations during physical activities were in the lower frequency range (0.1-4 Hz), a low-pass filter was used to reduce the influence of extraneous vibration. Selective sensing of the acceleration level may be usefully implemented in an algorithm for activity pacing.

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

Prefrontal responses to Stroop tasks in subjects with post-traumatic stress disorder assessed by functional near infrared spectroscopy.

PubMed

Yennu, Amarnath; Tian, Fenghua; Smith-Osborne, Alexa; J Gatchel, Robert; Woon, Fu Lye; Liu, Hanli

2016-07-25

Studies on posttraumatic stress disorder (PTSD) showing attentional deficits have implicated abnormal activities in the frontal lobe. In this study, we utilized multichannel functional near-infrared spectroscopy (fNIRS) to investigate selective attention-related hemodynamic activity in the prefrontal cortex among 15 combat-exposed war-zone veterans with PTSD and 13 age- and gender-matched healthy controls. While performing the incongruent Stroop task, healthy controls showed significant activations in the left lateral prefrontal cortex (LPFC) compared to baseline readings. This observation is consistent with previously reported results. In comparison, subjects with PTSD failed to activate left LPFC during the same Stroop task. Our observations may implicate that subjects with PTSD experienced difficulty in overcoming Stroop interference. We also observed significant negative correlation between task reaction times and hemodynamic responses from left LPFC during the incongruent Stroop task in the PTSD group. Regarding the methodology used in this study, we have learned that an appropriate design of Stroop paradigms is important for meeting an optimal cognitive load which can lead to better brain image contrasts in response to Stroop interference between healthy versus PTSD subjects. Overall, the feasibility of fNIRS for studying and mapping neural correlates of selective attention and interference in subjects with PTSD is reported.

Prefrontal responses to Stroop tasks in subjects with post-traumatic stress disorder assessed by functional near infrared spectroscopy

PubMed Central

Yennu, Amarnath; Tian, Fenghua; Smith-Osborne, Alexa; J. Gatchel, Robert; Woon, Fu Lye; Liu, Hanli

2016-01-01

Studies on posttraumatic stress disorder (PTSD) showing attentional deficits have implicated abnormal activities in the frontal lobe. In this study, we utilized multichannel functional near-infrared spectroscopy (fNIRS) to investigate selective attention-related hemodynamic activity in the prefrontal cortex among 15 combat-exposed war-zone veterans with PTSD and 13 age- and gender-matched healthy controls. While performing the incongruent Stroop task, healthy controls showed significant activations in the left lateral prefrontal cortex (LPFC) compared to baseline readings. This observation is consistent with previously reported results. In comparison, subjects with PTSD failed to activate left LPFC during the same Stroop task. Our observations may implicate that subjects with PTSD experienced difficulty in overcoming Stroop interference. We also observed significant negative correlation between task reaction times and hemodynamic responses from left LPFC during the incongruent Stroop task in the PTSD group. Regarding the methodology used in this study, we have learned that an appropriate design of Stroop paradigms is important for meeting an optimal cognitive load which can lead to better brain image contrasts in response to Stroop interference between healthy versus PTSD subjects. Overall, the feasibility of fNIRS for studying and mapping neural correlates of selective attention and interference in subjects with PTSD is reported. PMID:27452397

Natalizumab in the treatment of Crohn’s disease

PubMed Central

Guagnozzi, Danila; Caprilli, Renzo

2008-01-01

The pathogenesis of Crohn’s disease (CD) is multifactorial and the activation of specific pathways of immunological system is important. In particular, the adhesion molecules (integrins) mediate the selective binding between the leukocytes and the endothelial cells regulating the migration of leukocytes into the normal and inflamed intestine. Selective adhesion molecule inhibitors interfere with the migration of leukocytes to the sites of inflammation by targeting adhesion molecules (α4-integrin or α4β7-integrin). Natalizumab is a humanized IgG4 anti-α4-integrin monoclonal antibody that inhibits both α4β7-integrin/mucosal addressin-cell adhesion molecule-1 (MadCAM-1) interaction and α4β1/vascular-cell adhesion molecule-1 (VCAM-1) binding. Pooled data from the four studies, analyzed in a Cochrane review, suggest that natalizumab is effective for induction of clinical response and remission in patients with moderately to severely active CD. In particular, natalizumab may be beneficial for patients with active inflammation or chronically active disease despite the use of conventional therapies with high level of C-reactive protein values at baseline time. Nevertheless, many problems about the utilization of natalizumab in CD remain unsolved (such as the high placebo response, the final definition of dosage and timing schedule, the definition of outcomes and the development of adverse events). PMID:19707360

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.

Prefrontal responses to Stroop tasks in subjects with post-traumatic stress disorder assessed by functional near infrared spectroscopy

NASA Astrophysics Data System (ADS)

Yennu, Amarnath; Tian, Fenghua; Smith-Osborne, Alexa; J. Gatchel, Robert; Woon, Fu Lye; Liu, Hanli

2016-07-01

Studies on posttraumatic stress disorder (PTSD) showing attentional deficits have implicated abnormal activities in the frontal lobe. In this study, we utilized multichannel functional near-infrared spectroscopy (fNIRS) to investigate selective attention-related hemodynamic activity in the prefrontal cortex among 15 combat-exposed war-zone veterans with PTSD and 13 age- and gender-matched healthy controls. While performing the incongruent Stroop task, healthy controls showed significant activations in the left lateral prefrontal cortex (LPFC) compared to baseline readings. This observation is consistent with previously reported results. In comparison, subjects with PTSD failed to activate left LPFC during the same Stroop task. Our observations may implicate that subjects with PTSD experienced difficulty in overcoming Stroop interference. We also observed significant negative correlation between task reaction times and hemodynamic responses from left LPFC during the incongruent Stroop task in the PTSD group. Regarding the methodology used in this study, we have learned that an appropriate design of Stroop paradigms is important for meeting an optimal cognitive load which can lead to better brain image contrasts in response to Stroop interference between healthy versus PTSD subjects. Overall, the feasibility of fNIRS for studying and mapping neural correlates of selective attention and interference in subjects with PTSD is reported.

Stratified cost-utility analysis of C-Leg versus mechanical knees: Findings from an Italian sample of transfemoral amputees.

PubMed

Cutti, Andrea Giovanni; Lettieri, Emanuele; Del Maestro, Martina; Radaelli, Giovanni; Luchetti, Martina; Verni, Gennero; Masella, Cristina

2017-06-01

The fitting rate of the C-Leg electronic knee (Otto-Bock, D) has increased steadily over the last 15 years. Current cost-utility studies, however, have not considered the patients' characteristics. To complete a cost-utility analysis involving C-Leg and mechanical knee users; "age at the time of enrollment," "age at the time of first prosthesis," and "experience with the current type of prosthesis" are assumed as non-nested stratification parameters. Cohort retrospective. In all, 70 C-Leg and 57 mechanical knee users were selected. For each stratification criteria, we evaluated the cost-utility of C-Leg versus mechanical knees by computing the incremental cost-utility ratio, that is, the ratio of the "difference in cost" and the "difference in utility" of the two technologies. Cost consisted of acquisition, maintenance, transportation, and lodging expenses. Utility was measured in terms of quality-adjusted life years, computed on the basis of participants' answers to the EQ-5D questionnaire. Patients over 40 years at the time of first prosthesis were the only group featuring an incremental cost-utility ratio (88,779 €/quality-adjusted life year) above the National Institute for Health and Care Excellence practical cost-utility threshold (54,120 €/quality-adjusted live year): C-Leg users experience a significant improvement of "mobility," but limited outcomes on "usual activities," "self-care," "depression/anxiety," and reduction of "pain/discomfort." The stratified cost-utility results have relevant clinical implications and provide useful information for practitioners in tailoring interventions. Clinical relevance A cost-utility analysis that considered patients characteristics provided insights on the "affordability" of C-Leg compared to mechanical knees. In particular, results suggest that C-Leg has a significant impact on "mobility" for first-time prosthetic users over 40 years, but implementation of specific low-cost physical/psychosocial interventions is required to retun within cost-utility thresholds.

Building Energy Model Development for Retrofit Homes

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

Chasar, David; McIlvaine, Janet; Blanchard, Jeremy

2012-09-30

Based on previous research conducted by Pacific Northwest National Laboratory and Florida Solar Energy Center providing technical assistance to implement 22 deep energy retrofits across the nation, 6 homes were selected in Florida and Texas for detailed post-retrofit energy modeling to assess realized energy savings (Chandra et al, 2012). However, assessing realized savings can be difficult for some homes where pre-retrofit occupancy and energy performance are unknown. Initially, savings had been estimated using a HERS Index comparison for these homes. However, this does not account for confounding factors such as occupancy and weather. This research addresses a method to moremore » reliably assess energy savings achieved in deep energy retrofits for which pre-retrofit utility bills or occupancy information in not available. A metered home, Riverdale, was selected as a test case for development of a modeling procedure to account occupancy and weather factors, potentially creating more accurate estimates of energy savings. This “true up” procedure was developed using Energy Gauge USA software and post-retrofit homeowner information and utility bills. The 12 step process adjusts the post-retrofit modeling results to correlate with post-retrofit utility bills and known occupancy information. The “trued” post retrofit model is then used to estimate pre-retrofit energy consumption by changing the building efficiency characteristics to reflect the pre-retrofit condition, but keeping all weather and occupancy-related factors the same. This creates a pre-retrofit model that is more comparable to the post-retrofit energy use profile and can improve energy savings estimates. For this test case, a home for which pre- and post- retrofit utility bills were available was selected for comparison and assessment of the accuracy of the “true up” procedure. Based on the current method, this procedure is quite time intensive. However, streamlined processing spreadsheets or incorporation into existing software tools would improve the efficiency of the process. Retrofit activity appears to be gaining market share, and this would be a potentially valuable capability with relevance to marketing, program management, and retrofit success metrics.« less

Resveratrol enhances exercise training responses in rats selectively bred for high running performance.

PubMed

Hart, Nikolett; Sarga, Linda; Csende, Zsolt; Koltai, Erika; Koch, Lauren G; Britton, Steven L; Davies, Kelvin J A; Kouretas, Dimitris; Wessner, Barbara; Radak, Zsolt

2013-11-01

High Capacity Runner (HCR) rats have been developed by divergent artificial selection for treadmill endurance running capacity to explore an aerobic biology-disease connection. The beneficial effects of resveratrol supplementation have been demonstrated in endurance running and the antioxidant capacity of resveratrol is also demonstrated. In this study we examine whether 12 weeks of treadmill exercise training and/or resveratrol can enhance performance in HCR. Indeed, resveratrol increased aerobic performance and strength of upper limbs of these rats. Moreover, we have found that resveratrol activated the AMP-activated protein kinase, SIRT1, and mitochondrial transcription factor A (p<0.05). The changes in mitochondrial fission/fusion and Lon protease/HSP78 levels suggest that exercise training does not significantly induce damage of proteins. Moreover, neither exercise training nor resveratrol supplementation altered the content of protein carbonyls. Changes in the levels of forkhead transcription factor 1 and SIRT4 could suggest increased fat utilization and improved insulin sensitivity. These data indicate, that resveratrol supplementation enhances aerobic performance due to the activation of the AMPK-SIRT1-PGC-1α pathway. Copyright © 2013 Elsevier Ltd. All rights reserved.

Impact of exogenous ascorbic acid on biochemical activities of rice callus treated with salt stress

NASA Astrophysics Data System (ADS)

Alhasnawi, Arshad Naji; Zain, Che Radziah Che Mohd; Kadhimi, Ahsan A.; Isahak, Anizan; Mohamad, Azhar; Ashraf, Mehdi Farshad; Doni, Febri; Yusoff, Wan Mohtar Wan

2016-11-01

The application of in vitro systems can lead to new methods of crop amelioration. This method has been widely utilized for breeding tenacities, particularly for stress tolerance selection. Salinity causes oxidative stress in callus by enhancing the production of Reactive Oxygen Species (ROS), resulting in an efficient antioxidant system. The exogenous application of ascorbic acid (AsA) is an important requirement for tolerance. The present study aimed to examine in vitro selection strategy for callus induction in rice mature embryo culture on MS culture medium and to produce salt-tolerant callus under sodium chloride (NaCl) and AsA conditions in callus rice variety, MR269. This study also highlights changes in the activities of proline and antioxidants peroxidase (POD), catalase (CAT) and superoxide dismutase (SOD) of callus under NaCl stress to understand their possible role in salt tolerance. However, various levels of exogenously applied AsA under saline conditions improved callus, and the antioxidant enzyme activities of AsA are related to resistance to oxidative stress. Our results provide strong support for the hypothesis that AsA-dependent antioxidant enzymes play a significant role in the salinity tolerance of callus rice.

[The evaluation of selected oxidative stress parameters in patients with hyperthyroidism].

PubMed

Andryskowski, Grzegorz; Owczarek, Tomasz

2007-07-01

Hyperthyroidism induces the acceleration of the basic metabolism and increases cellular oxygen utilization, consequently intensifies reactive oxygen species production and disturbs the oxidant-antioxidant balance. The objective of this study was to evaluate the selected oxidative stress parameters in patients with hyperthyroidism by analysis of the reactive oxygen species neutralizing enzymes activity--superoxide dismutase (SOD), glutathione peroxidase (GSHPx) and catalase (CAT), the estimation of free radical processes intensity--concentration of malondialdehyde (MDA), sulfhydryl groups (SH) in proteins and by quantification of the serum total antioxidant status (TAS). . Twenty-seven patients treated for hyperthyroidism and 12 healthy individuals were enrolled in the study. Enzyme activity (SOD, GSHPx, CAT), MDA and concentration of SH groups were analysed in erythrocytes, while TAS was measured in serum. Patients with hyperthyroidism compared with healthy subjects were characterized by a higher GSHPx activity in erythrocytes, lower serum TAS, the lower content of SH groups in proteins and the lower MDA concentration in erythrocytes. Our results suggest that hyperthyroidism increases oxidative stress and disturbs oxidant-antioxidant balance in the body. Thyreostatic treatment, if not leads to whole metabolic compensation, may only reduce oxidant-antioxidant disorders, however is not able to eliminate them entirely.

Development of SH2 probes and pull-down assays to detect pathogen-induced, site-specific tyrosine phosphorylation of the TLR adaptor SCIMP.

PubMed

Luo, Lin; Tong, Samuel J; Wall, Adam A; Khromykh, Tatiana; Sweet, Matthew J; Stow, Jennifer L

2017-07-01

Protein tyrosine phosphorylation guides many molecular interactions for cellular functions. SCIMP is a transmembrane adaptor protein (TRAP) family member that mediates selective proinflammatory cytokine responses generated by pathogen-activated Toll-like receptor (TLR) pathways in macrophages. TLR activation triggers SCIMP phosphorylation and selective phosphorylation of distinct tyrosine residues on this adaptor offers the potential for regulating or biasing inflammatory responses. To analyze site-specific phosphorylation events, we developed three probes based on the SH2 domains of known SCIMP effectors, and used them for pull-downs from macrophage extracts. CRISPR-mediated SCIMP-deficient RAW264.7 macrophage-like cells were reconstituted with various phosphorylation-deficient (Y58F, Y96F, Y120F) SCIMPs, and used to demonstrate the specificity of LPS/TLR4-induced, site-specific phosphorylation of SCIMP for the temporal recruitment of the effectors Grb2, Csk and SLP65. Our findings reveal potential for differential SCIMP phosphorylation and specific effectors to influence TLR signaling and inflammatory programs. Furthermore, the use of Csk-SH2 pull-downs to identify additional known and new Csk targets in LPS-activated macrophages reveals the wider utility of our SH2 probes.

Deep Temporal Nerve Transfer for Facial Reanimation: Anatomic Dissections and Surgical Case Report.

PubMed

Mahan, Mark A; Sivakumar, Walavan; Weingarten, David; Brown, Justin M

2017-09-08

Facial nerve palsy is a disabling condition that may arise from a variety of injuries or insults and may occur at any point along the nerve or its intracerebral origin. To examine the use of the deep temporal branches of the motor division of the trigeminal nerve for neural reconstruction of the temporal branches of the facial nerve for restoration of active blink and periorbital facial expression. Formalin-fixed human cadaver hemifaces were dissected to identify landmarks for the deep temporal branches and the tension-free coaptation lengths. This technique was then utilized in 1 patient with a history of facial palsy due to a brainstem cavernoma. Sixteen hemifaces were dissected. The middle deep temporal nerve could be consistently identified on the deep side of the temporalis, within 9 to 12 mm posterior to the jugal point of the zygoma. From a lateral approach through the temporalis, the middle deep temporal nerve could be directly coapted to facial temporal branches in all specimens. Our patient has recovered active and independent upper facial muscle contraction, providing the first case report of a distinct distal nerve transfer for upper facial function. The middle deep temporal branches can be readily identified and utilized for facial reanimation. This technique provided a successful reanimation of upper facial muscles with independent activation. Utilizing multiple sources for neurotization of the facial muscles, different potions of the face can be selectively reanimated to reduce the risk of synkinesis and improved control. Copyright © 2017 by the Congress of Neurological Surgeons

Ion-pairing HPLC methods to determine EDTA and DTPA in small molecule and biological pharmaceutical formulations.

PubMed

Wang, George; Tomasella, Frank P

2016-06-01

Ion-pairing high-performance liquid chromatography-ultraviolet (HPLC-UV) methods were developed to determine two commonly used chelating agents, ethylenediaminetetraacetic acid (EDTA) in Abilify® (a small molecule drug with aripiprazole as the active pharmaceutical ingredient) oral solution and diethylenetriaminepentaacetic acid (DTPA) in Yervoy® (a monoclonal antibody drug with ipilimumab as the active pharmaceutical ingredient) intravenous formulation. Since the analytes, EDTA and DTPA, do not contain chromophores, transition metal ions (Cu 2+ , Fe 3+ ) which generate highly stable metallocomplexes with the chelating agents were added into the sample preparation to enhance UV detection. The use of metallocomplexes with ion-pairing chromatography provides the ability to achieve the desired sensitivity and selectivity in the development of the method. Specifically, the sample preparation involving metallocomplex formation allowed sensitive UV detection. Copper was utilized for the determination of EDTA and iron was utilized for the determination of DTPA. In the case of EDTA, a gradient mobile phase separated the components of the formulation from the analyte. In the method for DTPA, the active drug substance, ipilimumab, was eluted in the void. In addition, the optimization of the concentration of the ion-pairing reagent was discussed as a means of enhancing the retention of the aminopolycarboxylic acids (APCAs) including EDTA and DTPA and the specificity of the method. The analytical method development was designed based on the chromatographic properties of the analytes, the nature of the sample matrix and the intended purpose of the method. Validation data were presented for the two methods. Finally, both methods were successfully utilized in determining the fate of the chelates.

Extracellular Secretion of Phytase from Transgenic Wheat Roots Allows Utilization of Phytate for Enhanced Phosphorus Uptake.

PubMed

Mohsin, Samreen; Maqbool, Asma; Ashraf, Mehwish; Malik, Kauser Abdulla

2017-08-01

A significant portion of organic phosphorus comprises of phytates which are not available to wheat for uptake. Hence for enabling wheat to utilize organic phosphorus in form of phytate, transgenic wheat expressing phytase from Aspergillus japonicus under barley root-specific promoter was developed. Transgenic events were initially screened via selection media containing BASTA, followed by PCR and BASTA leaf paint assay after hardening. Out of 138 successfully regenerated T o events, only 12 had complete constructs and thus further analyzed. Positive T1 transgenic plants, grown in sand, exhibited 0.08-1.77, 0.02-0.67 and 0.44-2.14 fold increase in phytase activity in root extracts, intact roots and external root solution, respectively, after 4 weeks of phosphorus stress. Based on these results, T2 generation of four best transgenic events was further analyzed which showed up to 1.32, 56.89, and 15.40 fold increase in phytase activity in root extracts, intact roots and external root solution, respectively, while in case of real-time PCR, maximum fold increase of 19.8 in gene expression was observed. Transgenic lines showed 0.01-1.18 fold increase in phosphorus efficiency along with higher phosphorus content when supplied phytate or inorganic phosphorus than control plants. Thus, this transgenic wheat may aid in reducing fertilizer utilization and enhancing wheat yield.

Human-Forest interfaces in Hugumburda-Gratkhassu National Forest Priority Area, North-eastern Ethiopia.

PubMed

Kidane, Leul; Nemomissa, Sileshi; Bekele, Tamrat

2018-02-23

Traditional management regimes and knowledge systems of forest resources have shaped forests throughout the world where materials from individual species are harvested in a sustainable manner. To comprehend this, the vegetation of Hugumburda-Gratkhassu Forest was described and related to anthropogenic factors. Three ethnobotanical research methods were used to collect indigenous knowledge of the local inhabitants related to conservation and utilization of forest resources. Direct matrix ranking was conducted to discover local attitudes on species preference for multiple use. During this work, the 46 most important tree and shrub species were selected based on recommendations of local guides and key informants to determine the range of uses obtained from each species. Through paired comparison, activities supposed to be the major cause of degradation of the forest were adopted. Pairs of activities were then established from the relation n (n-1)/2. Each respondent was then asked to select an activity that he considered being a major problem to management of the forest. Semi-structured interviews were used to obtain information from sixty local informants to address community attitudes towards forest management and utilization. The result obtained from direct matrix ranking showed; that 20 out of 46 plant species compared had the highest scores and rank, indicating that these species are the most important and are exploited by the local communities for multiple purposes. The paired comparison exercise revealed logging for construction materials to be the major threat to the forest due to cutting of large volume of wood for construction of churches, health centers, schools and new houses. Juniperus procera, Olea europaea ssp. cuspidata, Rhus glutinosa, Ficus sur, Hagenia abyssinica, Cassipourea malosana and Acacia etbaica were the most selected and exploited plant species for these purposes. Survival of protected areas depends on the support of local communities, rather than on fences, fines, or even force. The local communities in the study area have a rich indigenous ecological knowledge to suggest appropriate solutions for improvement of the forest resources. Thus the old tradition of isolating forests from the community has to be avoided and the basic needs and traditional rights of the communities over the uses of forest resources should be recognized.

Information Gain Based Dimensionality Selection for Classifying Text Documents

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

Dumidu Wijayasekara; Milos Manic; Miles McQueen

2013-06-01

Selecting the optimal dimensions for various knowledge extraction applications is an essential component of data mining. Dimensionality selection techniques are utilized in classification applications to increase the classification accuracy and reduce the computational complexity. In text classification, where the dimensionality of the dataset is extremely high, dimensionality selection is even more important. This paper presents a novel, genetic algorithm based methodology, for dimensionality selection in text mining applications that utilizes information gain. The presented methodology uses information gain of each dimension to change the mutation probability of chromosomes dynamically. Since the information gain is calculated a priori, the computational complexitymore » is not affected. The presented method was tested on a specific text classification problem and compared with conventional genetic algorithm based dimensionality selection. The results show an improvement of 3% in the true positives and 1.6% in the true negatives over conventional dimensionality selection methods.« less

Isolation and characterization of yeasts capable of efficient utilization of hemicellulosic hydrolyzate as the carbon source.

PubMed

Cassa-Barbosa, L A; Procópio, R E L; Matos, I T S R; Filho, S A

2015-09-28

Few yeasts have shown the potential to efficiently utilize hemicellulosic hydrolyzate as the carbon source. In this study, microorganisms isolated from the Manaus region in Amazonas, Brazil, were characterized based on their utilization of the pentoses, xylose, and arabinose. The yeasts that showed a potential to assimilate these sugars were selected for the better utilization of lignocellulosic biomass. Two hundred and thirty seven colonies of unicellular microorganisms grown on hemicellulosic hydrolyzate, xylose, arabinose, and yeast nitrogen base selective medium were analyzed. Of these, 231 colonies were subjected to sugar assimilation tests. One hundred and twenty five of these were shown to utilize hydrolyzed hemicellulose, xylose, or arabinose as the carbon source for growth. The colonies that showed the best growth (N = 57) were selected, and their internal transcribed spacer-5.8S rDNA was sequenced. The sequenced strains formed four distinct groups in the phylogenetic tree, and showed a high percentage of similarity with Meyerozyma caribbica, Meyerozyma guilliermondii, Trichosporon mycotoxinivorans, Trichosporon loubieri, Pichia kudriavzevii, Candida lignohabitans, and Candida ethanolica. The discovery of these xylose-fermenting yeasts could attract widespread interest, as these can be used in the cost-effective production of liquid fuel from lignocellulosic materials.

Adolescents’ Knowledge, Attitude and Utilization of Emergency Contraceptive Pills in Nigeria’s Niger Delta Region

PubMed Central

Onasoga, Olayinka A.; Afolayan, Joel Adeleke; Asamabiriowei, Tariebi Florence; Jibril, Umar Nda; Imam, Abubakar Ayinla

2016-01-01

Background and Objective: Risky sexual activity among adolescents is on the increase and contraceptive prevalence rate is low which is evidenced by high rate of teenage pregnancy in Bayelsa state, Nigeria. This study assesses the adolescents’ knowledge, attitude and utilization of emergency contraceptive pills (ECP) in Amassoma Community, Bayelsa State, in the Niger Delta region of Nigeria. Methods: The study was a descriptive cross-sectional research design. A purposive sampling technique was used to select a sample of 220 respondents from the target population. Data were collected using a self-structured questionnaire. Descriptive and inferential statistics were used to analyze the data generated. Results: Majority of the respondents had high level of knowledge and positive attitude towards emergency contraceptive pills but had low level of utilization. Concerns about what others may say, parental attitude, contraceptive availability, contraceptive accessibility, and peer influences were the major factors that influenced the utilization of contraceptive pills. There was no significant relationship between knowledge and utilization of emergency contraceptive pills, as well as level of knowledge and their utilization of emergency contraceptive pills. Conclusions and Global Health Implications: Adolescents in the study were more likely to use emergency contraceptive pills, if parents and others reaction to adolescents’ contraceptive use were positive about those. Health care professionals, especially nurses, should organize enlightenment programs to educate adolescents, parents and the public on the benefits of adolescents’ contraceptives use, especially ECP. PMID:28058193

Controlled Synthesis of Pd/Pt Core Shell Nanoparticles Using Area-selective Atomic Layer Deposition

PubMed Central

Cao, Kun; Zhu, Qianqian; Shan, Bin; Chen, Rong

2015-01-01

We report an atomic scale controllable synthesis of Pd/Pt core shell nanoparticles (NPs) via area-selective atomic layer deposition (ALD) on a modified surface. The method involves utilizing octadecyltrichlorosilane (ODTS) self-assembled monolayers (SAMs) to modify the surface. Take the usage of pinholes on SAMs as active sites for the initial core nucleation, and subsequent selective deposition of the second metal as the shell layer. Since new nucleation sites can be effectively blocked by surface ODTS SAMs in the second deposition stage, we demonstrate the successful growth of Pd/Pt and Pt/Pd NPs with uniform core shell structures and narrow size distribution. The size, shell thickness and composition of the NPs can be controlled precisely by varying the ALD cycles. Such core shell structures can be realized by using regular ALD recipes without special adjustment. This SAMs assisted area-selective ALD method of core shell structure fabrication greatly expands the applicability of ALD in fabricating novel structures and can be readily applied to the growth of NPs with other compositions. PMID:25683469

Selecting the Best: Evolutionary Engineering of Chemical Production in Microbes.

PubMed

Shepelin, Denis; Hansen, Anne Sofie Lærke; Lennen, Rebecca; Luo, Hao; Herrgård, Markus J

2018-05-11

Microbial cell factories have proven to be an economical means of production for many bulk, specialty, and fine chemical products. However, we still lack both a holistic understanding of organism physiology and the ability to predictively tune enzyme activities in vivo, thus slowing down rational engineering of industrially relevant strains. An alternative concept to rational engineering is to use evolution as the driving force to select for desired changes, an approach often described as evolutionary engineering. In evolutionary engineering, in vivo selections for a desired phenotype are combined with either generation of spontaneous mutations or some form of targeted or random mutagenesis. Evolutionary engineering has been used to successfully engineer easily selectable phenotypes, such as utilization of a suboptimal nutrient source or tolerance to inhibitory substrates or products. In this review, we focus primarily on a more challenging problem-the use of evolutionary engineering for improving the production of chemicals in microbes directly. We describe recent developments in evolutionary engineering strategies, in general, and discuss, in detail, case studies where production of a chemical has been successfully achieved through evolutionary engineering by coupling production to cellular growth.

Selective electrochemical generation of hydrogen peroxide from water oxidation

DOE PAGES

Viswanathan, Venkatasubramanian; Hansen, Heine A.; Norskov, Jens K.

2015-10-08

Water is a life-giving source, fundamental to human existence, yet over a billion people lack access to clean drinking water. The present techniques for water treatment such as piped, treated water rely on time and resource intensive centralized solutions. In this work, we propose a decentralized device concept that can utilize sunlight to split water into hydrogen and hydrogen peroxide. The hydrogen peroxide can oxidize organics while the hydrogen bubbles out. In enabling this device, we require an electrocatalyst that can oxidize water while suppressing the thermodynamically favored oxygen evolution and form hydrogen peroxide. Using density functional theory calculations, wemore » show that the free energy of adsorbed OH* can be used to determine selectivity trends between the 2e– water oxidation to H 2O 2 and the 4e– oxidation to O 2. We show that materials which bind oxygen intermediates sufficiently weakly, such as SnO 2, can activate hydrogen peroxide evolution. Furthermore, we present a rational design principle for the selectivity in electrochemical water oxidation and identify new material candidates that could perform H 2O 2 evolution selectively.« less

Reducing Conservatism in Aircraft Engine Response Using Conditionally Active Min-Max Limit Regulators

NASA Technical Reports Server (NTRS)

May, Ryan D.; Garg, Sanjay

2012-01-01

Current aircraft engine control logic uses a Min-Max control selection structure to prevent the engine from exceeding any safety or operational limits during transients due to throttle commands. This structure is inherently conservative and produces transient responses that are slower than necessary. In order to utilize the existing safety margins more effectively, a modification to this architecture is proposed, referred to as a Conditionally Active (CA) limit regulator. This concept uses the existing Min-Max architecture with the modification that limit regulators are active only when the operating point is close to a particular limit. This paper explores the use of CA limit regulators using a publicly available commercial aircraft engine simulation. The improvement in thrust response while maintaining all necessary safety limits is demonstrated in a number of cases.

Chemical synthesis and characterization of chitosan/silver nanocomposites films and their potential antibacterial activity.

PubMed

Shah, Aamna; Hussain, Izhar; Murtaza, Ghulam

2018-05-12

This study provides the optimum preparation parameters for functional chitosan silver nanocomposite (CSN) films with promising antibacterial efficacy though prepared with very low silver nitrate (AgNO 3 ) concentration. Chitosan nano‑silver composites were fabricated by In-situ chemical method utilizing the reducing ability of sodium borohydride (NaBH 4 ) and afterward casted into films. Utilization of response surface methodology, NCSS, and SigmaPlot for the optimization of CSN and their predicted antibacterial efficacy assessment of the selected bacterial strains (standard and clinical) was the essential part of the study. The cumulative silver ions released from the CSN films was examined by AAS and was found pH dependent. The developed nanocomposite films exhibited strong antibacterial activity against ATCC strains of Gram-positive Staphylococcus aureus, Gram-negative bacteria (Pseudomonas aeruginosa) and clinically isolated strains of MRSA. The antibacterial activity CSN films were compared with three commercially available dressings (Aquacel Ag®, Bactigras®, and Kaltostat®) and Quench cream. Statistical analysis of the results indicated that the developed CSN films were equally or even more effective than commercial products. Thus the fabricated CSN films may act as a potential candidate to overcome the emerging antibiotic resistance particularly in hospital-acquired skin infections caused by MRSA. Copyright © 2018. Published by Elsevier B.V.

Substrate-specific modifications on magnetic iron oxide nanoparticles as an artificial peroxidase for improving sensitivity in glucose detection.

PubMed

Liu, Yanping; Yu, Faquan

2011-04-08

Magnetic iron oxide nanoparticles (MION) were recently found to act as a peroxidase with intrinsic advantages over natural counterparts. Their limited affinity toward catalysis substrates, however, dramatically reduces their utility. In this paper, some effective groups were screened out and conjugated on MION as substrate-specific modifications for improving MION's affinity to substrates and hence utility. Nanoparticles of four different superficial structures were synthesized and characterized by TEM, size, zeta potential and SQUID, and assayed for peroxidase activity. Glucose detection was selected as an application model system to evaluate the bonus thereof. Catalysis was found to follow Michaelis-Menten kinetics. Sulfhydryl groups incorporated on MION (SH-MION) notably improve the affinity toward a substrate (hydrogen peroxide) and so do amino groups (NH₂-MION) toward another substrate, proved by variation in the determined kinetic parameters. A synergistically positive effect was observed and an apparently elevated detection sensitivity and a significantly lowered detection limit of glucose were achieved when integrated with both sulfhydryl and amino groups (SH-NH₂-MION). Our findings suggest that substrate-specific surface modifications are a straightforward and robust strategy to improve MION peroxidase-like activity. The high activity extends magnetic nanoparticles to wide applications other than glucose detection.

Comprehensive Utilization of Biomass Process Residues Rich in Cellulose

NASA Astrophysics Data System (ADS)

Zhong, Mei; Li, Qiang; Yu, Jian; Dong, Li; Wang, Yin; Xu, Guangwen

2010-11-01

This article investigated the method preparing porous material (PM) with VL and SL. Applications of the prepared material was tested in removal aqueous phenol and COD in tarry water and as the catalyst support for selective catalytic reduction (SCR) of NO in flue gas. The results showed that the optimal activation condition in CO2 for the carbonized VL at 800° C was at 875° C for 1 h, which provided large BET surface area and micropore volume. This material exhibited the highest adsorption to aqueous phenol among all the tested materials including a commercial activated carbon made from coconut shell, showing the potential application of the VL-base porous material in wastewater treatment. The study demonstrated also that the vanadium-base selective catalytic reduction (SCR) catalyst supported on the VL-base porous material (V2O5/VL-PM) provided fairly good activity as well SO2 resistance at temperatures round 200° C for SCR of NO. The activation of the carbonized SL material in H2O was better than that in CO2 for developing the pore structure of the porous material. Steam can improve the formation of mesopore than CO2. This was confirmed by the conclusion that higher COD removal rate was occurred on the PM-1 from SL when H2O was used as an activator.

Oxidation of benzoin catalyzed by oxovanadium(IV) schiff base complexes

PubMed Central

2013-01-01

Background The oxidative transformation of benzoin to benzil has been accomplished by the use of a wide variety of reagents or catalysts and different reaction procedures. The conventional oxidizing agents yielded mainly benzaldehyde or/and benzoic acid and only a trace amount of benzil. The limits of practical utilization of these reagents involves the use of stoichiometric amounts of corrosive acids or toxic metallic reagents, which in turn produce undesirable waste materials and required high reaction temperatures. In recent years, vanadium complexes have attracted much attention for their potential utility as catalysts for various types of reactions. Results Active and selective catalytic systems of new unsymmetrical oxovanadium(IV) Schiff base complexes for the oxidation of benzoin is reported. The Schiff base ligands are derived between 2-aminoethanol and 2-hydroxy-1-naphthaldehyde (H2L1) or 3-ethoxy salicylaldehyde (H2L3); and 2-aminophenol and 3-ethoxysalicylaldehyde (H2L2) or 2-hydroxy-1-naphthaldehyde (H2L4). The unsymmetrical Schiff bases behave as tridentate dibasic ONO donor ligands. Reaction of these Schiff base ligands with oxovanadyl sulphate afforded the mononuclear oxovanadium(IV) complexes (VIVOLx.H2O), which are characterized by various physico-chemical techniques. The catalytic oxidation activities of these complexes for benzoin were evaluated using H2O2 as an oxidant. The best reaction conditions are obtained by considering the effect of solvent, reaction time and temperature. Under the optimized reaction conditions, VOL4 catalyst showed high conversion (>99%) with excellent selectivity to benzil (~100%) in a shorter reaction time compared to the other catalysts considered. Conclusion Four tridentate ONO type Schiff base ligands were synthesized. Complexation of these ligands with vanadyl(IV) sulphate leads to the formation of new oxovanadium(IV) complexes of type VIVOL.H2O. Elemental analyses and spectral data of the free ligands and their oxovanadium(IV) complexes were found to be in good agreement with their structures, indicating high purity of all the compounds. Oxovanadium complexes were screened for the oxidation of benzoin to benzil using H2O2 as oxidant. The effect of time, solvent and temperature were optimized to obtain maximum yield. The catalytic activity results demonstrate that these catalytic systems are both highly active and selective for the oxidation of benzoin under mild reaction conditions. PMID:23294561

Oxidation of benzoin catalyzed by oxovanadium(IV) schiff base complexes.

PubMed

Alsalim, Tahseen A; Hadi, Jabbar S; Ali, Omar N; Abbo, Hanna S; Titinchi, Salam Jj

2013-01-07

The oxidative transformation of benzoin to benzil has been accomplished by the use of a wide variety of reagents or catalysts and different reaction procedures. The conventional oxidizing agents yielded mainly benzaldehyde or/and benzoic acid and only a trace amount of benzil. The limits of practical utilization of these reagents involves the use of stoichiometric amounts of corrosive acids or toxic metallic reagents, which in turn produce undesirable waste materials and required high reaction temperatures.In recent years, vanadium complexes have attracted much attention for their potential utility as catalysts for various types of reactions. Active and selective catalytic systems of new unsymmetrical oxovanadium(IV) Schiff base complexes for the oxidation of benzoin is reported. The Schiff base ligands are derived between 2-aminoethanol and 2-hydroxy-1-naphthaldehyde (H2L1) or 3-ethoxy salicylaldehyde (H2L3); and 2-aminophenol and 3-ethoxysalicylaldehyde (H2L2) or 2-hydroxy-1-naphthaldehyde (H2L4). The unsymmetrical Schiff bases behave as tridentate dibasic ONO donor ligands. Reaction of these Schiff base ligands with oxovanadyl sulphate afforded the mononuclear oxovanadium(IV) complexes (VIVOLx.H2O), which are characterized by various physico-chemical techniques.The catalytic oxidation activities of these complexes for benzoin were evaluated using H2O2 as an oxidant. The best reaction conditions are obtained by considering the effect of solvent, reaction time and temperature. Under the optimized reaction conditions, VOL4 catalyst showed high conversion (>99%) with excellent selectivity to benzil (~100%) in a shorter reaction time compared to the other catalysts considered. Four tridentate ONO type Schiff base ligands were synthesized. Complexation of these ligands with vanadyl(IV) sulphate leads to the formation of new oxovanadium(IV) complexes of type VIVOL.H2O.Elemental analyses and spectral data of the free ligands and their oxovanadium(IV) complexes were found to be in good agreement with their structures, indicating high purity of all the compounds.Oxovanadium complexes were screened for the oxidation of benzoin to benzil using H2O2 as oxidant. The effect of time, solvent and temperature were optimized to obtain maximum yield. The catalytic activity results demonstrate that these catalytic systems are both highly active and selective for the oxidation of benzoin under mild reaction conditions.

Quality of life of persons with severe mental illness living in an intermediate care facility.

PubMed

Anderson, R L; Lewis, D A

2000-04-01

This study examined resident characteristics, clinical factors, and mental health service utilization associated with quality of life (QOL) for residents living in an Intermediate Care Facility (ICF). This study also utilized published literature to compare the QOL of ICF residents to persons with psychiatric disorders living in other residential settings. Chart review and interviews were used to study 100 randomly selected residents living in an ICF with a chart diagnosis of schizophrenia. Multivariate analyses suggest that higher levels of QOL are associated with reports that psychological problems did not interfere with work and activities and with lower levels of being a danger to others. Also, a comparison of the QOL scores reported by ICF residents to other published mentally ill populations suggests that residents of the ICF report somewhat higher QOL scores than state hospital patients, but lower scores as compared to other community samples. Data provide insight into the types of problems faced by residents of an intermediate care facility. These findings have implications for understanding the importance of mental health service utilization on QOL.

Validation of isoleucine utilization targets in Plasmodium falciparum

PubMed Central

Istvan, Eva S.; Dharia, Neekesh V.; Bopp, Selina E.; Gluzman, Ilya; Winzeler, Elizabeth A.; Goldberg, Daniel E.

2011-01-01

Intraerythrocytic malaria parasites can obtain nearly their entire amino acid requirement by degrading host cell hemoglobin. The sole exception is isoleucine, which is not present in adult human hemoglobin and must be obtained exogenously. We evaluated two compounds for their potential to interfere with isoleucine utilization. Mupirocin, a clinically used antibacterial, kills Plasmodium falciparum parasites at nanomolar concentrations. Thiaisoleucine, an isoleucine analog, also has antimalarial activity. To identify targets of the two compounds, we selected parasites resistant to either mupirocin or thiaisoleucine. Mutants were analyzed by genome-wide high-density tiling microarrays, DNA sequencing, and copy number variation analysis. The genomes of three independent mupirocin-resistant parasite clones had all acquired either amplifications encompassing or SNPs within the chromosomally encoded organellar (apicoplast) isoleucyl-tRNA synthetase. Thiaisoleucine-resistant parasites had a mutation in the cytoplasmic isoleucyl-tRNA synthetase. The role of this mutation in thiaisoleucine resistance was confirmed by allelic replacement. This approach is generally useful for elucidation of new targets in P. falciparum. Our study shows that isoleucine utilization is an essential pathway that can be targeted for antimalarial drug development. PMID:21205898

Metal-free g-C{sub 3}N{sub 4} photocatalyst by sulfuric acid activation for selective aerobic oxidation of benzyl alcohol under visible light

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

Zhang, Ligang; University of Chinese Academy of Sciences, Beijing 100049; Liu, Di

2014-11-15

Highlights: • A novel visible-light-driven acid-modified g-C{sub 3}N{sub 4} was prepared. • The texture, electronic and surface property were tuned by acid modification. • Acid-modified g-C{sub 3}N{sub 4} shows much higher activity for photocatalytic activity. • Acid sites on the surface of g-C{sub 3}N{sub 4} favor efficient charge separation. - Abstract: In this work, modification of graphitic carbon nitride photocatalyst with acid was accomplished with a facile method through reflux in different acidic substances. The g-C{sub 3}N{sub 4}-based material was found to be a metal-free photocatalyst useful for the selective oxidation of benzyl alcohol with dioxygen as the oxidant undermore » visible light irradiation. Acid modification had a significant influence on the photocatalytic performance of g-C{sub 3}N{sub 4}. Among all acid tested, sulfuric acid-modified g-C{sub 3}N{sub 4} showed the highest catalytic activity and gave benzaldehyde in 23% yield for 4 h under visible light irradiation, which was about 2.5 times higher than that of g-C{sub 3}N{sub 4}. The acid modification effectively improved surface area, reduced structural size, enlarged band gap, enhanced surface chemical state, and facilitated photoinduced charge separation, contributing to the enhanced photocatalytic activity. It is hoped that our work can open promising prospects for the utilization of metal free g-C{sub 3}N{sub 4}-based semiconductor as visible-light photocatalyst for selective organic transformation.« less

[A Method for Selecting Self-Adoptive Chromaticity of the Projected Markers].

PubMed

Zhao, Shou-bo; Zhang, Fu-min; Qu, Xing-hua; Zheng, Shi-wei; Chen, Zhe

2015-04-01

The authors designed a self-adaptive projection system which is composed of color camera, projector and PC. In detail, digital micro-mirror device (DMD) as a spatial light modulator for the projector was introduced in the optical path to modulate the illuminant spectrum based on red, green and blue light emitting diodes (LED). However, the color visibility of active markers is affected by the screen which has unknown reflective spectrum as well. Here active markers are projected spot array. And chromaticity feature of markers is sometimes submerged in similar spectral screen. In order to enhance the color visibility of active markers relative to screen, a method for selecting self-adaptive chromaticity of the projected markers in 3D scanning metrology is described. Color camera with 3 channels limits the accuracy of device characterization. For achieving interconversion of device-independent color space and device-dependent color space, high-dimensional linear model of reflective spectrum was built. Prior training samples provide additional constraints to yield high-dimensional linear model with more than three degrees of freedom. Meanwhile, spectral power distribution of ambient light was estimated. Subsequently, markers' chromaticity in CIE color spaces was selected via maximization principle of Euclidean distance. The setting values of RGB were easily estimated via inverse transform. Finally, we implemented a typical experiment to show the performance of the proposed approach. An 24 Munsell Color Checker was used as projective screen. Color difference in the chromaticity coordinates between the active marker and the color patch was utilized to evaluate the color visibility of active markers relative to the screen. The result comparison between self-adaptive projection system and traditional diode-laser light projector was listed and discussed to highlight advantage of our proposed method.

Assessment of Scheduling and Plan Execution of Apollo 14 Lunar Surface Operations

NASA Technical Reports Server (NTRS)

Marquez, Jessica J.

2010-01-01

Although over forty years have passed since first landing on the Moon, there is not yet a comprehensive, quantitative assessment of Apollo extravehicular activities (EVAs). Quantitatively evaluating lunar EVAs will provide a better understanding of the challenges involved with surface operations. This first evaluation of a surface EVA centers on comparing the planned and the as-ran timeline, specifically collecting data on discrepancies between durations that were estimated versus executed. Differences were summarized by task categories in order to gain insight as to the type of surface operation activities that were most challenging. One Apollo 14 EVA was assessed utilizing the described methodology. Selected metrics and task categorizations were effective, and limitations to this process were identified.

Spatial Control of Functional Response in 4D-Printed Active Metallic Structures

NASA Astrophysics Data System (ADS)

Ma, Ji; Franco, Brian; Tapia, Gustavo; Karayagiz, Kubra; Johnson, Luke; Liu, Jun; Arroyave, Raymundo; Karaman, Ibrahim; Elwany, Alaa

2017-04-01

We demonstrate a method to achieve local control of 3-dimensional thermal history in a metallic alloy, which resulted in designed spatial variations in its functional response. A nickel-titanium shape memory alloy part was created with multiple shape-recovery stages activated at different temperatures using the selective laser melting technique. The multi-stage transformation originates from differences in thermal history, and thus the precipitate structure, at various locations created from controlled variations in the hatch distance within the same part. This is a first example of precision location-dependent control of thermal history in alloys beyond the surface, and utilizes additive manufacturing techniques as a tool to create materials with novel functional response that is difficult to achieve through conventional methods.

Major Developments in the Design of Inhibitors along the Kynurenine Pathway

PubMed Central

Jacobs, Kelly R.; Castellano-González, Gloria; Guillemin, Gilles J.; Lovejoy, David B.

2017-01-01

Disrupted kynurenine pathway (KP) metabolism has been implicated in the progression of neurodegenerative disease, psychiatric disorders and cancer. Modulation of enzyme activity along this pathway may therefore offer potential new therapeutic strategies for these conditions. Considering their prominent positions in the KP, the enzymes indoleamine 2,3-dioxygenase, kynurenine 3-monooxygenase and kynurenine aminotransferase, appear the most attractive targets. Already, increasing interest in this pathway has led to the identification of a number of potent and selective enzyme inhibitors with promising pre-clinical data and the elucidation of several enzyme crystal structures provides scope to rationalize the molecular mechanisms of inhibitor activity. The field seems poised to yield one or more inhibitors that should find clinical utility. PMID:28464785

Extracellular metalloproteinases in Phytomonas serpens.

PubMed

Vermelho, Alane B; Almeida, Flávia V S; Bronzato, Leandro S; Branquinha, Marta H

2003-03-01

The detection of extracellular proteinases in Phytomonas serpens, a trypanosomatid isolated from tomato fruits, is demonstrated in this paper. Maximal production occurred at the end of the logarithmic phase of growth. These enzymes exhibited selective substrate utilization in SDS-PAGE, being more active with gelatin; hemoglobin and bovine serum albumin were not degraded. Three proteinases were detected in SDS-PAGE-gelatin, with apparent molecular masses between 94 and 70 kDa. The proteolytic activity was completely blocked by 1,10-phenanthroline and strongly inhibited by EDTA, whereas a partial inhibition was observed with trans-epoxysuccinyl-L-leucylamido-(4-guanidino) butane (E-64) and soybean trypsin inhibitor; phenylmethylsulfonyl fluoride weakly inhibited the enzymes. This inhibition profile indicated that these extracellular proteinases belong to the metalloproteinase class.

In-silico evidences for binding of Glucokinase activators to EGFR C797S to overcome EGFR resistance obstacle with mutant-selective allosteric inhibition.

PubMed

Patel, Harun; Pawara, Rahul; Surana, Sanjay

2018-03-29

The tyrosine kinase inhibitors (TKI) against epidermal growth factor receptor (EGFR) are generally utilized as a part of patients with non-small cell lung carcinoma (NSCLC). However, EGFR T790M mutation results in resistance to most clinically available EGFR TKIs. Third-generation EGFR TKIs against the T790M mutation has been in active clinical development to triumph the resistance problem; they covalently bind with conserved Cys797 inside the EGFR active site, offering both potency and kinase-selectivity. Third generation drugs target C797, which makes the C797S resistance mutation more subtle. EGFR C797S mutation was accounted to be a main mechanism of resistance to the third-generation inhibitors. The C797S mutation gives off an impression of being an ideal target for conquering the acquired resistance to the third generation inhibitors. We have performed structure based-virtual screening strategies for binding of glucokinase activator to EGFR C797S, which can overcome EGFR resistance impediment with mutant-selective allosteric inhibition towards all kinds of mutant EGFR (T790M, L858R, TMLR) and WT EGFR. The final filter of Lipinski's Rule of Five, Jargan's Rule of Three and in silico ADME predictions gave 23 hits, which conform to Lipinski's rule and Jorgensen's rule and all their pharmacokinetic parameters are inside the appropriate range characterized for human use, in this manner demonstrating their potential as a drug-like molecule. Copyright © 2018 Elsevier Ltd. All rights reserved.

B lymphocyte selection and age-related changes in VH gene usage in mutant Alicia rabbits.

PubMed

Zhu, X; Boonthum, A; Zhai, S K; Knight, K L

1999-09-15

Young Alicia rabbits use VHa-negative genes, VHx and VHy, in most VDJ genes, and their serum Ig is VHa negative. However, as Alicia rabbits age, VHa2 allotype Ig is produced at high levels. We investigated which VH gene segments are used in the VDJ genes of a2 Ig-secreting hybridomas and of a2 Ig+ B cells from adult Alicia rabbits. We found that 21 of the 25 VDJ genes used the a2-encoding genes, VH4 or VH7; the other four VDJ genes used four unknown VH gene segments. Because VH4 and VH7 are rarely found in VDJ genes of normal or young Alicia rabbits, we investigated the timing of rearrangement of these genes in Alicia rabbits. During fetal development, VH4 was used in 60-80% of nonproductively rearranged VDJ genes, and VHx and VHy together were used in 10-26%. These data indicate that during B lymphopoiesis VH4 is preferentially rearranged. However, the percentage of productive VHx- and VHy-utilizing VDJ genes increased from 38% at day 21 of gestation to 89% at birth (gestation day 31), whereas the percentage of VH4-utilizing VDJ genes remained at 15%. These data suggest that during fetal development, either VH4-utilizing B-lineage cells are selectively eliminated, or B cells with VHx- and VHy-utilizing VDJ genes are selectively expanded, or both. The accumulation of peripheral VH4-utilizing a2 B cells with age indicates that these B cells might be selectively expanded in the periphery. We discuss the possible selection mechanisms that regulate VH gene segment usage in rabbit B cells during lymphopoiesis and in the periphery.

Vessel Classification in Cosmo-Skymed SAR Data Using Hierarchical Feature Selection

NASA Astrophysics Data System (ADS)

Makedonas, A.; Theoharatos, C.; Tsagaris, V.; Anastasopoulos, V.; Costicoglou, S.

2015-04-01

SAR based ship detection and classification are important elements of maritime monitoring applications. Recently, high-resolution SAR data have opened new possibilities to researchers for achieving improved classification results. In this work, a hierarchical vessel classification procedure is presented based on a robust feature extraction and selection scheme that utilizes scale, shape and texture features in a hierarchical way. Initially, different types of feature extraction algorithms are implemented in order to form the utilized feature pool, able to represent the structure, material, orientation and other vessel type characteristics. A two-stage hierarchical feature selection algorithm is utilized next in order to be able to discriminate effectively civilian vessels into three distinct types, in COSMO-SkyMed SAR images: cargos, small ships and tankers. In our analysis, scale and shape features are utilized in order to discriminate smaller types of vessels present in the available SAR data, or shape specific vessels. Then, the most informative texture and intensity features are incorporated in order to be able to better distinguish the civilian types with high accuracy. A feature selection procedure that utilizes heuristic measures based on features' statistical characteristics, followed by an exhaustive research with feature sets formed by the most qualified features is carried out, in order to discriminate the most appropriate combination of features for the final classification. In our analysis, five COSMO-SkyMed SAR data with 2.2m x 2.2m resolution were used to analyse the detailed characteristics of these types of ships. A total of 111 ships with available AIS data were used in the classification process. The experimental results show that this method has good performance in ship classification, with an overall accuracy reaching 83%. Further investigation of additional features and proper feature selection is currently in progress.

Selecting a pharmacy layout design using a weighted scoring system.

PubMed

McDowell, Alissa L; Huang, Yu-Li

2012-05-01

A weighted scoring system was used to select a pharmacy layout redesign. Facilities layout design techniques were applied at a local hospital pharmacy using a step-by-step design process. The process involved observing and analyzing the current situation, observing the current available space, completing activity flow charts of the pharmacy processes, completing communication and material relationship charts to detail which areas in the pharmacy were related to one another and how they were related, researching applications in other pharmacies or in scholarly works that could be beneficial, numerically defining space requirements for areas within the pharmacy, measuring the available space within the pharmacy, developing a set of preliminary designs, and modifying preliminary designs so they were all acceptable to the pharmacy staff. To select a final layout that could be implemented in the pharmacy, those layouts were compared via a weighted scoring system. The weighted aspect further allowed additional emphasis on categories based on their effect on pharmacy performance. The results produced a beneficial layout design as determined through simulated models of the pharmacy operation that more effectively allocated and strategically located space to improve transportation distances and materials handling, employee utilization, and ergonomics. Facilities layout designs for a hospital pharmacy were evaluated using a weighted scoring system to identify a design that was superior to both the current layout and alternative layouts in terms of feasibility, cost, patient safety, employee safety, flexibility, robustness, transportation distance, employee utilization, objective adherence, maintainability, usability, and environmental impact.

Diagnosis of stinging insect allergy: utility of cellular in-vitro tests.

PubMed

Scherer, Kathrin; Bircher, Andreas J; Heijnen, Ingmar Afm

2009-08-01

Diagnosis of stinging insect allergy is based on a detailed history, venom skin tests, and detection of venom-specific IgE. As an additional diagnostic tool, basophil responsiveness to venom allergens has been shown to be helpful in selected patients. This review summarizes the current diagnostic procedures for stinging insect allergy and discusses the latest developments in cellular in-vitro tests. Cellular assays have been evaluated in patients with Hymenoptera venom allergy. The diagnostic performance of the cellular mediator release test is similar to that of the flow cytometric basophil activation test (BAT), but the BAT has been the most intensively studied. BAT offers the possibility to assess basophil reactivity to allergens in their natural environment and to simultaneously analyze surface marker expression and intracellular signaling. It has been demonstrated that BAT represents a valuable additional diagnostic tool in selected patients when used in combination with other well established tests. A major limitation is the current lack of unified, standardized protocols. Flow cytometry offers huge possibilities to enhance knowledge of basophil functions. The BAT may be used as an additional test to confirm the diagnosis of stinging insect allergy in selected patients, provided that it is performed by an experienced laboratory using a validated assay. Test results have to be interpreted by clinicians familiar with the methodological aspects. The utility of the BAT to confirm allergy diagnosis and to predict the risk of subsequent systemic reactions may be improved by combined analysis of multiple surface markers and intracellular signaling pathways.

Association of Inpatient Antimicrobial Utilization Measures with Antimicrobial Stewardship Activities and Facility Characteristics of Veterans Affairs Medical Centers.

PubMed

Graber, Christopher J; Jones, Makoto M; Chou, Ann F; Zhang, Yue; Goetz, Matthew Bidwell; Madaras-Kelly, Karl; Samore, Matthew H; Glassman, Peter A

2017-05-01

Antimicrobial stewardship programs (ASPs) have been advocated to improve antimicrobial utilization, but program implementation is variable. Antimicrobial stewardship programs (ASPs) have been advocated to improve antimicrobial utilization, but program implementation is variable. To determine associations between ASPs and facility characteristics, and inpatient antimicrobial utilization measures in the Veterans Affairs (VA) system in 2012. In 2012, VA administered a survey on antimicrobial stewardship practices to designated ASP contacts at VA acute care hospitals. From the survey, we identified 34 variables across 3 domains (evidence, organizational context, and facilitation) that were assessed using multivariable least absolute shrinkage and selection operator regression against 4 antimicrobial utilization measures from 2012: aggregate acute care antimicrobial use, antimicrobial use in patients with non-infectious primary discharge diagnoses, missed opportunities to convert from parenteral to oral antimicrobial therapy, and double anaerobic coverage. All 130 VA facilities with acute care services. Variables associated with at least 3 favorable changes in antimicrobial utilization included presence of postgraduate physician/pharmacy training programs, number of antimicrobial-specific order sets, frequency of systematic de-escalation review, presence of pharmacists and/or infectious diseases (ID) attendings on acute care ward teams, and formal ID training of the lead ASP pharmacist. Variables associated with 2 unfavorable measures included bed size, the level of engagement with VA Antimicrobial Stewardship Task Force online resources, and utilization of antimicrobial stop orders. Formalization of ASP processes and presence of pharmacy and ID expertise are associated with favorable utilization. Systematic de-escalation review and order set establishment may be high-yield interventions. Journal of Hospital Medicine 2017;12:301-309. © 2017 Society of Hospital Medicine

Gamified physical activation of young men – a Multidisciplinary Population-Based Randomized Controlled Trial (MOPO study)

PubMed Central

2013-01-01

Background Inactive and unhealthy lifestyles are common among adolescent men. The planned intervention examines the effectiveness of an interactive, gamified activation method, based on tailored health information, peer networks and participation, on physical activity, health and wellbeing in young men. We hypothesize that following the intervention the physical activation group will have an improved physical activity, as well as self-determined and measured health compared with the controls. Methods/design Conscription-aged men (18 years) attending compulsory annual call-ups for military service in the city of Oulu in Finland (n = 1500) will be randomized to a 6-months intervention (n = 640) or a control group (n = 640) during the fall 2013. A questionnaire on health, health behaviour, diet and wellbeing is administered in the beginning and end of the intervention. In addition, anthropometric measures (height, weight and waist circumference), body composition, grip strength, heart rate variability and aerobic fitness will be measured. The activation group utilizes an online gamified activation method in combination with communal youth services, objective physical activity measurement, social networking, tailored health information and exercise programs according to baseline activity level and the readiness of changes of each individual. Daily physical activity of the participants is monitored in both the activation and control groups. The activation service rewards improvements in physical activity or reductions in sedentary behaviour. The performance and completion of the military service of the participants will also be followed. Discussion The study will provide new information of physical activity, health and health behaviour of young men. Furthermore, a novel model including methods for increasing physical activity among young people is developed and its effects tested through an intervention. This unique gamified service for activating young men can provide a translational model for community use. It can also be utilized as such or tailored to other selected populations or age groups. Trial registration ClinicalTrials.gov Identifier: NCT01376986 PMID:23311678

Gamified physical activation of young men--a Multidisciplinary Population-Based Randomized Controlled Trial (MOPO study).

PubMed

Ahola, Riikka; Pyky, Riitta; Jämsä, Timo; Mäntysaari, Matti; Koskimäki, Heli; Ikäheimo, Tiina M; Huotari, Maija-Leena; Röning, Juha; Heikkinen, Hannu I; Korpelainen, Raija

2013-01-14

Inactive and unhealthy lifestyles are common among adolescent men. The planned intervention examines the effectiveness of an interactive, gamified activation method, based on tailored health information, peer networks and participation, on physical activity, health and wellbeing in young men. We hypothesize that following the intervention the physical activation group will have an improved physical activity, as well as self-determined and measured health compared with the controls. Conscription-aged men (18 years) attending compulsory annual call-ups for military service in the city of Oulu in Finland (n = 1500) will be randomized to a 6-months intervention (n = 640) or a control group (n = 640) during the fall 2013. A questionnaire on health, health behaviour, diet and wellbeing is administered in the beginning and end of the intervention. In addition, anthropometric measures (height, weight and waist circumference), body composition, grip strength, heart rate variability and aerobic fitness will be measured. The activation group utilizes an online gamified activation method in combination with communal youth services, objective physical activity measurement, social networking, tailored health information and exercise programs according to baseline activity level and the readiness of changes of each individual. Daily physical activity of the participants is monitored in both the activation and control groups. The activation service rewards improvements in physical activity or reductions in sedentary behaviour. The performance and completion of the military service of the participants will also be followed. The study will provide new information of physical activity, health and health behaviour of young men. Furthermore, a novel model including methods for increasing physical activity among young people is developed and its effects tested through an intervention. This unique gamified service for activating young men can provide a translational model for community use. It can also be utilized as such or tailored to other selected populations or age groups. ClinicalTrials.gov Identifier: NCT01376986.

Integrative functional analyses using rainbow trout selected for tolerance to plant diets reveal nutrigenomic signatures for soy utilization without the concurrence of enteritis

PubMed Central

Brezas, Andreas; Snekvik, Kevin R.; Hardy, Ronald W.; Overturf, Ken

2017-01-01

Finding suitable alternative protein sources for diets of carnivorous fish species remains a major concern for sustainable aquaculture. Through genetic selection, we created a strain of rainbow trout that outperforms parental lines in utilizing an all-plant protein diet and does not develop enteritis in the distal intestine, as is typical with salmonids on long-term plant protein-based feeds. By incorporating this strain into functional analyses, we set out to determine which genes are critical to plant protein utilization in the absence of gut inflammation. After a 12-week feeding trial with our selected strain and a control trout strain fed either a fishmeal-based diet or an all-plant protein diet, high-throughput RNA sequencing was completed on both liver and muscle tissues. Differential gene expression analyses, weighted correlation network analyses and further functional characterization were performed. A strain-by-diet design revealed differential expression ranging from a few dozen to over one thousand genes among the various comparisons and tissues. Major gene ontology groups identified between comparisons included those encompassing central, intermediary and foreign molecule metabolism, associated biosynthetic pathways as well as immunity. A systems approach indicated that genes involved in purine metabolism were highly perturbed. Systems analysis among the tissues tested further suggests the interplay between selection for growth, dietary utilization and protein tolerance may also have implications for nonspecific immunity. By combining data from differential gene expression and co-expression networks using selected trout, along with ontology and pathway analyses, a set of 63 candidate genes for plant diet tolerance was found. Risk loci in human inflammatory bowel diseases were also found in our datasets, indicating rainbow trout selected for plant-diet tolerance may have added utility as a potential biomedical model. PMID:28723948

Discovery and Characterization of a Highly Potent and Selective Aminopyrazoline-Based in Vivo Probe (BAY-598) for the Protein Lysine Methyltransferase SMYD2.

PubMed

Eggert, Erik; Hillig, Roman C; Koehr, Silke; Stöckigt, Detlef; Weiske, Jörg; Barak, Naomi; Mowat, Jeffrey; Brumby, Thomas; Christ, Clara D; Ter Laak, Antonius; Lang, Tina; Fernandez-Montalvan, Amaury E; Badock, Volker; Weinmann, Hilmar; Hartung, Ingo V; Barsyte-Lovejoy, Dalia; Szewczyk, Magdalena; Kennedy, Steven; Li, Fengling; Vedadi, Masoud; Brown, Peter J; Santhakumar, Vijayaratnam; Arrowsmith, Cheryl H; Stellfeld, Timo; Stresemann, Carlo

2016-05-26

Protein lysine methyltransferases have recently emerged as a new target class for the development of inhibitors that modulate gene transcription or signaling pathways. SET and MYND domain containing protein 2 (SMYD2) is a catalytic SET domain containing methyltransferase reported to monomethylate lysine residues on histone and nonhistone proteins. Although several studies have uncovered an important role of SMYD2 in promoting cancer by protein methylation, the biology of SMYD2 is far from being fully understood. Utilization of highly potent and selective chemical probes for target validation has emerged as a concept which circumvents possible limitations of knockdown experiments and, in particular, could result in an improved exploration of drug targets with a complex underlying biology. Here, we report the development of a potent, selective, and cell-active, substrate-competitive inhibitor of SMYD2, which is the first reported inhibitor suitable for in vivo target validation studies in rodents.

Vapor Phase Hydrogenolysis of Furanics Utilizing Reduced Cobalt Mixed Metal Oxide Catalysts

DOE PAGES

Sulmonetti, Taylor P.; Hu, Bo; Ifkovits, Zachary; ...

2017-03-21

Vapor phase hydrogenolysis of both furfuryl alcohol and furfural were investigated over reduced Co based mixed metal oxides derived from the calcination of a layered double hydroxide precursor. Although a reduced cobalt aluminate sample displays promising selectivity towards 2-methylfuran (2-MF) production, the addition of an Fe dopant into the oxide matrix significantly enhances the activity and selectivity per gram of catalyst. Approximately 82% 2-MF yield is achieved at high conversion when furfuryl alcohol is fed into the reactor at 180 °C over the reduced 3Co-0.25Fe-0.75Al catalyst. Based on structural characterization studies including TPR, XPS, and in-situ XAS it is suggestedmore » that Fe facilitates the reduction of Co, allowing for formation of more metallic species. Altogether, this study demonstrates that non-precious metal catalysts offer promise for the selective conversion of a key biomass oxygenate to a proposed fuel additive.« less

Selectively Targeting T- and B-Cell Lymphomas: A Benzothiazole Antagonist of α4β1 Integrin

PubMed Central

Carpenter, Richard D.; Andrei, Mirela; Aina, Olulanu H.; Lau, Edmond Y.; Lightstone, Felice C.; Liu, Ruiwu; Lam, Kit S.; Kurth, Mark J.

2011-01-01

Current cancer chemotherapeutic agents clinically deployed today are designed to be indiscriminately cytotoxic, however achieving selective targeting of cancer malignancies would allow for improved diagnostic and chemotherapeutic tools. Integrin α4β1, a heterodimeric cell surface receptor, is believed to have a relaxed conformation in normal cells and an active conformation in cancerous cells, specifically T- and B-cell lymphomas. This highly attractive yet poorly understood receptor has been selectively targeted with the bisaryl urea peptidomimetic antagonist 1. However, concerns regarding its preliminary pharmacokinetic (PK) profile provided an impetus to change the pharmacophore from a bisaryl urea to a 2-arylaminobenzothiazole moiety, resulting in an analog with improved physicochemical properties, solubility and kidney:tumor ratio while maintaining potency (6; IC50 = 53 pM). The results presented herein utilized heterocyclic and solid-phase chemistry, cell adhesion assay, and in vivo optical imaging using the cyanine dye Cy5.5 conjugate. PMID:19072684