System among the corticosteroids: specificity and molecular dynamics

PubMed Central

Brookes, Jennifer C.; Galigniana, Mario D.; Harker, Anthony H.; Stoneham, A. Marshall; Vinson, Gavin P.

2012-01-01

Understanding how structural features determine specific biological activities has often proved elusive. With over 161 000 steroid structures described, an algorithm able to predict activity from structural attributes would provide manifest benefits. Molecular simulations of a range of 35 corticosteroids show striking correlations between conformational mobility and biological specificity. Thus steroid ring A is important for glucocorticoid action, and is rigid in the most specific (and potent) examples, such as dexamethasone. By contrast, ring C conformation is important for the mineralocorticoids, and is rigid in aldosterone. Other steroids that are less specific, or have mixed functions, or none at all, are more flexible. One unexpected example is 11-deoxycorticosterone, which the methods predict (and our activity studies confirm) is not only a specific mineralocorticoid, but also has significant glucocorticoid activity. These methods may guide the design of new corticosteroid agonists and antagonists. They will also have application in other examples of ligand–receptor interactions. PMID:21613285

Large-scale cortical correlation structure of spontaneous oscillatory activity

PubMed Central

Hipp, Joerg F.; Hawellek, David J.; Corbetta, Maurizio; Siegel, Markus; Engel, Andreas K.

2013-01-01

Little is known about the brain-wide correlation of electrophysiological signals. Here we show that spontaneous oscillatory neuronal activity exhibits frequency-specific spatial correlation structure in the human brain. We developed an analysis approach that discounts spurious correlation of signal power caused by the limited spatial resolution of electrophysiological measures. We applied this approach to source estimates of spontaneous neuronal activity reconstructed from magnetoencephalography (MEG). Overall, correlation of power across cortical regions was strongest in the alpha to beta frequency range (8–32 Hz) and correlation patterns depended on the underlying oscillation frequency. Global hubs resided in the medial temporal lobe in the theta frequency range (4–6 Hz), in lateral parietal areas in the alpha to beta frequency range (8–23 Hz), and in sensorimotor areas for higher frequencies (32–45 Hz). Our data suggest that interactions in various large-scale cortical networks may be reflected in frequency specific power-envelope correlations. PMID:22561454

Confused ionic liquid ions--a "liquification" and dosage strategy for pharmaceutically active salts.

PubMed

Bica, Katharina; Rogers, Robin D

2010-02-28

We present a strategy to expand the liquid and compositional ranges of ionic liquids, specifically pharmaceutically active ionic liquids, by simple mixing with a solid acid or base to form oligomeric ions.

Dissecting the functional significance of non-catalytic carbohydrate binding modules in the deconstruction of plant cell walls

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

Hahn, Michael G.

The project seeks to investigate the mechanism by which CBMs potentiate the activity of glycoside hydrolases against complete plant cell walls. The project is based on the hypothesis that the wide range of CBMs present in bacterial enzymes maximize the potential target substrates by directing the cognate enzymes not only to different regions of a specific plant cell wall, but also increases the range of plant cell walls that can be degraded. In addition to maximizing substrate access, it was also proposed that CBMs can target specific subsets of hydrolases with complementary activities to the same region of the plantmore » cell wall, thereby maximizing the synergistic interactions between these enzymes. This synergy is based on the premise that the hydrolysis of a specific polysaccharide will increase the access of closely associated polymers to enzyme attack. In addition, it is unclear whether the catalytic module and appended CBM of modular enzymes have evolved unique complementary activities.« less

Spatial distribution and vertical migration of (137)Cs in soils of Belgrade (Serbia) 25 years after the Chernobyl accident.

PubMed

Petrović, Jelena; Ćujić, Mirjana; Đorđević, Milan; Dragović, Ranko; Gajić, Boško; Miljanić, Šćepan; Dragović, Snežana

2013-06-01

In this study, the specific activity of (137)Cs was determined by gamma-ray spectrometry in 72 surface soil samples and 11 soil profiles collected from the territory of Belgrade 25 years after the Chernobyl accident. Based on the data obtained the external effective gamma dose rates due to (137)Cs were assessed and geographically mapped. The influence of pedogenic factors (pH, specific electrical conductivity, cation exchange capacity, organic matter content, soil particle size and carbonate content) on the spatial and vertical distribution of (137)Cs in soil was estimated through Pearson correlations. The specific activity of (137)Cs in surface soil samples ranged from 1.00 to 180 Bq kg(-1), with a mean value of 29.9 Bq kg(-1), while in soil profiles they ranged from 0.90 to 58.0 Bq kg(-1), with a mean value of 15.3 Bq kg(-1). The mean external effective gamma dose at 1 m above the ground due to (137)Cs in the soil was calculated to be 1.96 nSv h(-1). Geographic mapping of the external effective gamma dose rates originating from (137)Cs revealed much higher dose rates in southern parts of Belgrade city and around the confluence of the Sava and Danube. Negative Pearson correlation coefficients were found between pH, cation exchange capacity and (137)Cs specific activity in surface soil. There were positive correlations between organic matter and (137)Cs specific activity in surface soil; and between specific electrical conductivity, organic matter, silt content and (137)Cs specific activity in soil profiles.

Calibration of context-specific survey items to assess youth physical activity behaviour.

PubMed

Saint-Maurice, Pedro F; Welk, Gregory J; Bartee, R Todd; Heelan, Kate

2017-05-01

This study tests calibration models to re-scale context-specific physical activity (PA) items to accelerometer-derived PA. A total of 195 4th-12th grades children wore an Actigraph monitor and completed the Physical Activity Questionnaire (PAQ) one week later. The relative time spent in moderate-to-vigorous PA (MVPA % ) obtained from the Actigraph at recess, PE, lunch, after-school, evening and weekend was matched with a respective item score obtained from the PAQ's. Item scores from 145 participants were calibrated against objective MVPA % using multiple linear regression with age, and sex as additional predictors. Predicted minutes of MVPA for school, out-of-school and total week were tested in the remaining sample (n = 50) using equivalence testing. The results showed that PAQ β-weights ranged from 0.06 (lunch) to 4.94 (PE) MVPA % (P < 0.05) and models root mean square error ranged from 4.2% (evening) to 20.2% (recess). When applied to an independent sample, differences between PAQ and accelerometer MVPA at school and out-of-school ranged from -15.6 to +3.8 min and the PAQ was within 10-15% of accelerometer measured activity. This study demonstrated that context-specific items can be calibrated to predict minutes of MVPA in groups of youth during in- and out-of-school periods.

Different specificities of two aldehyde dehydrogenases from Saccharomyces cerevisiae var. boulardii.

PubMed

Datta, Suprama; Annapure, Uday S; Timson, David J

2017-04-30

Aldehyde dehydrogenases play crucial roles in the detoxification of exogenous and endogenous aldehydes by catalysing their oxidation to carboxylic acid counterparts. The present study reports characterization of two such isoenzymes from the yeast Saccharomyces cerevisiae var. boulardii (NCYC 3264), one mitochondrial (Ald4p) and one cytosolic (Ald6p). Both Ald4p and Ald6p were oligomeric in solution and demonstrated positive kinetic cooperativity towards aldehyde substrates. Wild-type Ald6p showed activity only with aliphatic aldehydes. Ald4p, on the contrary, showed activity with benzaldehyde along with a limited range of aliphatic aldehydes. Inspection of modelled structure of Ald6p revealed that a bulky amino acid residue (Met 177 , compared with the equivalent residue Leu 196 in Ald4p) might cause steric hindrance of cyclic substrates. Therefore, we hypothesized that specificities of the two isoenzymes towards aldehyde substrates were partly driven by steric hindrance in the active site. A variant of wild-type Ald6p with the Met 177 residue replaced by a valine was also characterized to address to the hypothesis. It showed an increased specificity range and a gain of activity towards cyclohexanecarboxaldehyde. It also demonstrated an increased thermal stability when compared with both the wild-types. These data suggest that steric bulk in the active site of yeast aldehyde dehydrogenases is partially responsible for controlling specificity. © 2017 The Author(s).

Analysis of the Effects of Cell Stress and Cytotoxicity on In ...

EPA Pesticide Factsheets

Chemical toxicity can arise from disruption of specific biomolecular functions or through more generalized cell stress and cytotoxicity-mediated processes. Here, concentration-dependent responses of 1063 chemicals including pharmaceuticals, natural products, pesticidals, consumer, and industrial chemicals across a diverse battery of 821 in vitro assay endpoints from 7 high-throughput assay technology platforms were analyzed in order to better distinguish between these types of activities. Both cell-based and cell-free assays showed a rapid increase in the frequency of responses at concentrations where cell stress / cytotoxicity responses were observed in cell-based assays. Chemicals that were positive on at least two viability/cytotoxicity assays within the concentration range tested (typically up to 100 M) activated a median of 12% of assay endpoints while those that were not cytotoxic in this concentration range activated 1.3% of the assays endpoints. The results suggest that activity can be broadly divided into: (1) specific biomolecular interactions against one or more targets (e.g., receptors or enzymes) at concentrations below which overt cytotoxicity-associated activity is observed; and (2) activity associated with cell stress or cytotoxicity, which may result from triggering of specific cell stress pathways, chemical reactivity, physico-chemical disruption of proteins or membranes, or broad low-affinity non-covalent interactions. Chemicals showing a g

Long-range electrostatic complementarity governs substrate recognition by human chymotrypsin C, a key regulator of digestive enzyme activation.

PubMed

Batra, Jyotica; Szabó, András; Caulfield, Thomas R; Soares, Alexei S; Sahin-Tóth, Miklós; Radisky, Evette S

2013-04-05

Human chymotrypsin C (CTRC) is a pancreatic serine protease that regulates activation and degradation of trypsinogens and procarboxypeptidases by targeting specific cleavage sites within their zymogen precursors. In cleaving these regulatory sites, which are characterized by multiple flanking acidic residues, CTRC shows substrate specificity that is distinct from that of other isoforms of chymotrypsin and elastase. Here, we report the first crystal structure of active CTRC, determined at 1.9-Å resolution, revealing the structural basis for binding specificity. The structure shows human CTRC bound to the small protein protease inhibitor eglin c, which binds in a substrate-like manner filling the S6-S5' subsites of the substrate binding cleft. Significant binding affinity derives from burial of preferred hydrophobic residues at the P1, P4, and P2' positions of CTRC, although acidic P2' residues can also be accommodated by formation of an interfacial salt bridge. Acidic residues may also be specifically accommodated in the P6 position. The most unique structural feature of CTRC is a ring of intense positive electrostatic surface potential surrounding the primarily hydrophobic substrate binding site. Our results indicate that long-range electrostatic attraction toward substrates of concentrated negative charge governs substrate discrimination, which explains CTRC selectivity in regulating active digestive enzyme levels.

The study of Cutaneous Lupus Erythematosus Disease Area and Severity Index in Indian patients with systemic lupus erythematosus.

PubMed

Salphale, P; Danda, D; Chandrashekar, L; Peter, D; Jayaseeli, N; George, R

2011-12-01

The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) is a newly described tool used to assess the activity of and damage caused by cutaneous lupus erythematosus (CLE). There is a paucity of data on CLASI from the Indian subcontinent. We sought to determine the applicability of CLASI in specific lesions of CLE in patients with systemic lupus erythematosus (SLE) attending a tertiary care hospital in India. In this prospective, cross-sectional study, 93 patients of SLE with cutaneous lesions were recruited. CLASI activity and damage scores of lupus erythematosus (LE)-specific skin lesions were done in 75 patients with SLE. The mean CLASI activity score was 15.4 ± 9.4 (range 0-39) and the mean damage score was 6.87 ± 7.75 (range 0-30). Higher mean CLASI activity scores were seen in patients with a combination of acute, subacute and chronic CLE and in those with widespread lesions. Patients with longstanding disease and long duration of skin lesions had higher damage scores. This study shows that CLASI is an effective tool to assess cutaneous activity of LE-specific lesions, and the damage caused by them, in Indian patients.

A Measure of the Broad Substrate Specificity of Enzymes Based on ‘Duplicate’ Catalytic Residues

PubMed Central

Chakraborty, Sandeep; Ásgeirsson, Bjarni; Rao, Basuthkar J.

2012-01-01

The ability of an enzyme to select and act upon a specific class of compounds with unerring precision and efficiency is an essential feature of life. Simultaneously, these enzymes often catalyze the reaction of a range of similar substrates of the same class, and also have promiscuous activities on unrelated substrates. Previously, we have established a methodology to quantify promiscuous activities in a wide range of proteins. In the current work, we quantitatively characterize the active site for the ability to catalyze distinct, yet related, substrates (BRASS). A protein with known structure and active site residues provides the framework for computing ‘duplicate’ residues, each of which results in slightly modified replicas of the active site scaffold. Such spatial congruence is supplemented by Finite difference Poisson Boltzmann analysis which filters out electrostatically unfavorable configurations. The congruent configurations are used to compute an index (BrassIndex), which reflects the broad substrate profile of the active site. We identify an acetylhydrolase and a methyltransferase as having the lowest and highest BrassIndex, respectively, from a set of non-homologous proteins extracted from the Catalytic Site Atlas. The acetylhydrolase, a regulatory enzyme, is known to be highly specific for platelet-activating factor. In the methyltransferase (PDB: 1QAM), various combinations of glycine (Gly38/40/42), asparagine (Asn101/11) and glutamic acid (Glu59/36) residues having similar spatial and electrostatic profiles with the specified scaffold (Gly38, Asn101 and Glu59) exemplifies the broad substrate profile such an active site may provide. ‘Duplicate’ residues identified by relaxing the spatial and/or electrostatic constraints can be the target of directed evolution methodologies, like saturation mutagenesis, for modulating the substrate specificity of proteins. PMID:23166637

Radiological study of soils in oil and gas producing areas in Delta State, Nigeria.

PubMed

Tchokossa, P; Olomo, J B; Balogun, F A; Adesanmi, C A

2013-01-01

Measurements of radioactivity concentrations in soils around the oil and gas producing areas in Delta State of Nigeria were carried out using a high-purity germanium detector gamma-ray spectrometer. Soil samples were collected from 20 locations from the study area and analysed. The radionuclides detected are traceable to the primordial series of (238)U and(232)Th as well as (40)K and traces of globally released (137)Cs. The specific activity values ranged between 7 and 60 Bq kg(-1) with a mean of 24±2 Bq kg(-1) for (238)U; while for (232)Th the range was 7-73 Bq kg(-1) with a mean of 29±3 Bq kg(-1). Relatively higher specific activity values were recorded in (40)K with a range of 15-696 Bq kg(-1), while the mean was 256±37 Bq kg(-1). However, a relatively low-specific radioactivity was obtained from(137)Cs with a range of 1-25 Bq kg(-1) and a mean of 7±1 Bq kg(-1). The estimated dose equivalent obtainable per year from these levels of radioactivity is <5 % of the recommended safe level of 1 mSv per annum. Therefore, the area and the use of the soils as building materials may be considered safe.

Activities and impairments in the early stage of rehabilitation after Colles' fracture.

PubMed

Dekkers, Merete; Søballe, Kjeld

2004-06-03

The purpose of this study was to investigate problems in performing activities after Colles' fracture, and to correlate activity limitations with impairments in the early stage of rehabilitation. Assessments were performed 1 and 5 weeks after removing plaster casts. A client-specific instrument, The Canadian Occupational Performance Measure, and a disease-specific dichotomous scale of 10 activities of daily living were used. Range of motion, grip strength, pain and dexterity were also assessed according to standardized methods. Thirty-three women, aged 51-87 years, with Colles' fracture treated with closed reduction and a plaster cast participated. Highly significant statistical and clinical improvements were found in the capacity, number and performance of activities. Problems were mainly classified as self-care activities at 1 week, and as productivity activities at 5 weeks, while problems in leisure activities were practically the same. However, one-third of the patients were not able to perform all basic activities of daily living at 5 weeks. Improvements in pain frequency, range of motion, grip strength and dexterity did not correlate very well with improvements in performance or the patients' satisfaction with the performance of their activities. The importance of assessing both impairments and activities in patients with Colles' fracture must be stressed.

Diversity of the Arabidopsis mitochondrial genome occurs via nuclear-controlled recombination activity.

PubMed

Arrieta-Montiel, Maria P; Shedge, Vikas; Davila, Jaime; Christensen, Alan C; Mackenzie, Sally A

2009-12-01

The plant mitochondrial genome is recombinogenic, with DNA exchange activity controlled to a large extent by nuclear gene products. One nuclear gene, MSH1, appears to participate in suppressing recombination in Arabidopsis at every repeated sequence ranging in size from 108 to 556 bp. Present in a wide range of plant species, these mitochondrial repeats display evidence of successful asymmetric DNA exchange in Arabidopsis when MSH1 is disrupted. Recombination frequency appears to be influenced by repeat sequence homology and size, with larger size repeats corresponding to increased DNA exchange activity. The extensive mitochondrial genomic reorganization of the msh1 mutant produced altered mitochondrial transcription patterns. Comparison of mitochondrial genomes from the Arabidopsis ecotypes C24, Col-0, and Ler suggests that MSH1 activity accounts for most or all of the polymorphisms distinguishing these genomes, producing ecotype-specific stoichiometric changes in each line. Our observations suggest that MSH1 participates in mitochondrial genome evolution by influencing the lineage-specific pattern of mitochondrial genetic variation in higher plants.

36 CFR 1260.2 - Definitions.

Code of Federal Regulations, 2011 CFR

2011-07-01

... means a distinct component of a file series, as defined in this section, that should be maintained as a... of records covering either a specific topic or a range of time such as presidential administration or a 5-year retirement schedule within a specific file series that is retired from active use as a...

36 CFR 1260.2 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... means a distinct component of a file series, as defined in this section, that should be maintained as a... of records covering either a specific topic or a range of time such as presidential administration or a 5-year retirement schedule within a specific file series that is retired from active use as a...

A novel serine protease from strawberry (Fragaria ananassa): Purification and biochemical characterization.

PubMed

Alici, Esma Hande; Arabaci, Gulnur

2018-03-27

In this study, a protease enzyme was purified from strawberry by using Sepharose-4B-l-tyrosine-p-amino benzoic acid affinity chromatography. The molecular weight of pure protease was determined 65.8 kDa by SDS-PAGE. The single band observed on the gel showed that the enzyme had a single polypeptide chain and was successfully purified. Purification of the protease by the chromatographic method resulted in a 395.6-fold increase in specific activity (3600 U/mg). Optimum pH and temperature for the enzyme were 6 and 40 °C, respectively. The protease was stable at a wide temperature range of 40 to 70 °C and a pH range of 3.0 to 9.0. Co 2+ ions stimulated protease activity very strongly. Cu 2+ , Hg 2+ , Cd 2+ and Mn 2+ ions significantly inhibited protease activity. While 2-propanol completely inhibited the enzyme, the enzyme maintained its activity better in the presence of ethanol and methanol. The strawberry protease showed the highest specificity towards hemoglobin among all the natural substrates tested. The specificity of the enzyme towards synthetic substrates was also investigated and it was concluded that it has broad substrate specificity. The obtained results indicated that this purified protease was highly-likely a serine protease and its activity was significantly affected by the presence of metal ions. Copyright © 2018. Published by Elsevier B.V.

Long-range Electrostatic Complementarity Governs Substrate Recognition by Human Chymotrypsin C, a Key Regulator of Digestive Enzyme Activation*

PubMed Central

Batra, Jyotica; Szabó, András; Caulfield, Thomas R.; Soares, Alexei S.; Sahin-Tóth, Miklós; Radisky, Evette S.

2013-01-01

Human chymotrypsin C (CTRC) is a pancreatic serine protease that regulates activation and degradation of trypsinogens and procarboxypeptidases by targeting specific cleavage sites within their zymogen precursors. In cleaving these regulatory sites, which are characterized by multiple flanking acidic residues, CTRC shows substrate specificity that is distinct from that of other isoforms of chymotrypsin and elastase. Here, we report the first crystal structure of active CTRC, determined at 1.9-Å resolution, revealing the structural basis for binding specificity. The structure shows human CTRC bound to the small protein protease inhibitor eglin c, which binds in a substrate-like manner filling the S6-S5′ subsites of the substrate binding cleft. Significant binding affinity derives from burial of preferred hydrophobic residues at the P1, P4, and P2′ positions of CTRC, although acidic P2′ residues can also be accommodated by formation of an interfacial salt bridge. Acidic residues may also be specifically accommodated in the P6 position. The most unique structural feature of CTRC is a ring of intense positive electrostatic surface potential surrounding the primarily hydrophobic substrate binding site. Our results indicate that long-range electrostatic attraction toward substrates of concentrated negative charge governs substrate discrimination, which explains CTRC selectivity in regulating active digestive enzyme levels. PMID:23430245

Body-part-specific representations of semantic noun categories.

PubMed

Carota, Francesca; Moseley, Rachel; Pulvermüller, Friedemann

2012-06-01

Word meaning processing in the brain involves ventrolateral temporal cortex, but a semantic contribution of the dorsal stream, especially frontocentral sensorimotor areas, has been controversial. We here examine brain activation during passive reading of object-related nouns from different semantic categories, notably animal, food, and tool words, matched for a range of psycholinguistic features. Results show ventral stream activation in temporal cortex along with category-specific activation patterns in both ventral and dorsal streams, including sensorimotor systems and adjacent pFC. Precentral activation reflected action-related semantic features of the word categories. Cortical regions implicated in mouth and face movements were sparked by food words, and hand area activation was seen for tool words, consistent with the actions implicated by the objects the words are used to speak about. Furthermore, tool words specifically activated the right cerebellum, and food words activated the left orbito-frontal and fusiform areas. We discuss our results in the context of category-specific semantic deficits in the processing of words and concepts, along with previous neuroimaging research, and conclude that specific dorsal and ventral areas in frontocentral and temporal cortex index visual and affective-emotional semantic attributes of object-related nouns and action-related affordances of their referent objects.

The Relationship between Fundamental Movement Skills and Self-Reported Physical Activity during Finnish Junior High School

ERIC Educational Resources Information Center

Jaakkola, Timo; Washington, Tracy

2013-01-01

Background: Previous studies have shown that fundamental movement skills (FMS) and physical activity are related. Specifically, earlier studies have demonstrated that the ability to perform a variety of FMS increases the likelihood of children participating in a range of physical activities throughout their lives. To date, however, there have not…

Thermophysical properties of enzyme clarified Lime (Citrus aurantifolia L) juice at different moisture contents.

PubMed

Manjunatha, S S; Raju, P S; Bawa, A S

2014-11-01

Thermophysical properties of enzyme clarified lime (Citrus aurantifolia L.) juice were evaluated at different moisture contents ranging from 30.37 % to 89.30 % (wet basis) corresponding to a water activity range of 0.835 to 0.979. The thermophysical properties evaluated were density, Newtonian viscosity, thermal conductivity, specific heat and thermal diffusivity. The investigation showed that density and Newtonian viscosity of enzyme clarified lime juice decreased significantly (p < 0.05) with increase in moisture content and water activity, whereas thermal conductivity and specific heat increased significantly (p < 0.05) with increase in moisture content and water activity and the thermal diffusivity increased marginally. Empirical mathematical models were established relating to thermophysical properties of enzyme clarified lime juice with moisture content/water activity employing regression analysis by the method of least square approximation. Results indicated the existence of strong correlation between thermophysical properties and moisture content/water activity of enzyme clarified lime juice, a significant (p < 0.0001) negative correlation between physical and thermal properties was observed.

A Haloalkane Dehalogenase from a Marine Microbial Consortium Possessing Exceptionally Broad Substrate Specificity.

PubMed

Buryska, Tomas; Babkova, Petra; Vavra, Ondrej; Damborsky, Jiri; Prokop, Zbynek

2018-01-15

The haloalkane dehalogenase enzyme DmmA was identified by marine metagenomic screening. Determination of its crystal structure revealed an unusually large active site compared to those of previously characterized haloalkane dehalogenases. Here we present a biochemical characterization of this interesting enzyme with emphasis on its structure-function relationships. DmmA exhibited an exceptionally broad substrate specificity and degraded several halogenated environmental pollutants that are resistant to other members of this enzyme family. In addition to having this unique substrate specificity, the enzyme was highly tolerant to organic cosolvents such as dimethyl sulfoxide, methanol, and acetone. Its broad substrate specificity, high overexpression yield (200 mg of protein per liter of cultivation medium; 50% of total protein), good tolerance to organic cosolvents, and a broad pH range make DmmA an attractive biocatalyst for various biotechnological applications. IMPORTANCE We present a thorough biochemical characterization of the haloalkane dehalogenase DmmA from a marine metagenome. This enzyme with an unusually large active site shows remarkably broad substrate specificity, high overexpression, significant tolerance to organic cosolvents, and activity under a broad range of pH conditions. DmmA is an attractive catalyst for sustainable biotechnology applications, e.g., biocatalysis, biosensing, and biodegradation of halogenated pollutants. We also report its ability to convert multiple halogenated compounds to corresponding polyalcohols. Copyright © 2018 American Society for Microbiology.

Engineered Cpf1 variants with altered PAM specificities increase genome targeting range

PubMed Central

Gao, Linyi; Cox, David B.T.; Yan, Winston X.; Manteiga, John C.; Schneider, Martin W.; Yamano, Takashi; Nishimasu, Hiroshi; Nureki, Osamu; Crosetto, Nicola; Zhang, Feng

2017-01-01

The RNA-guided endonuclease Cpf1 is a promising tool for genome editing in eukaryotic cells1–7. However, the utility of the commonly used Acidaminococcus sp. BV3L6 Cpf1 (AsCpf1) and Lachnospiraceae bacterium ND2006 Cpf1 (LbCpf1) is limited by their requirement of a TTTV protospacer adjacent motif (PAM) in the DNA substrate. To address this limitation, we performed a structure-guided mutagenesis screen to increase the targeting range of Cpf1. We engineered two AsCpf1 variants carrying the mutations S542R/K607R and S542R/K548V/N552R, which recognize TYCV and TATV PAMs, respectively, with enhanced activities in vitro and in human cells. Genome-wide assessment of off-target activity using BLISS7 assay indicated that these variants retain high DNA targeting specificity, which we further improved by introducing an additional non-PAM-interacting mutation. Introducing the identified mutations at their corresponding positions in LbCpf1 similarly altered its PAM specificity. Together, these variants increase the targeting range of Cpf1 by approximately three-fold in human coding sequences to one cleavage site per ~11 bp. PMID:28581492

A Review of Activity Implementation in Out-of-School Time Programs. Out-of-School Time Evaluation Snapshot.

ERIC Educational Resources Information Center

Bouffard, Suzanne; Little, Priscilla M. D.

Noting that most evaluations of out-of-school (OST) programs have examined the programs as a whole without taking into account the specific activities offered, this issue of "Out-of-School Time Evaluation Snapshots" surveys the range of activities being implemented in OST settings across the country to better understand and promote…

Automation and uncertainty analysis of a method for in-vivo range verification in particle therapy.

PubMed

Frey, K; Unholtz, D; Bauer, J; Debus, J; Min, C H; Bortfeld, T; Paganetti, H; Parodi, K

2014-10-07

We introduce the automation of the range difference calculation deduced from particle-irradiation induced β(+)-activity distributions with the so-called most-likely-shift approach, and evaluate its reliability via the monitoring of algorithm- and patient-specific uncertainty factors. The calculation of the range deviation is based on the minimization of the absolute profile differences in the distal part of two activity depth profiles shifted against each other. Depending on the workflow of positron emission tomography (PET)-based range verification, the two profiles under evaluation can correspond to measured and simulated distributions, or only measured data from different treatment sessions. In comparison to previous work, the proposed approach includes an automated identification of the distal region of interest for each pair of PET depth profiles and under consideration of the planned dose distribution, resulting in the optimal shift distance. Moreover, it introduces an estimate of uncertainty associated to the identified shift, which is then used as weighting factor to 'red flag' problematic large range differences. Furthermore, additional patient-specific uncertainty factors are calculated using available computed tomography (CT) data to support the range analysis. The performance of the new method for in-vivo treatment verification in the clinical routine is investigated with in-room PET images for proton therapy as well as with offline PET images for proton and carbon ion therapy. The comparison between measured PET activity distributions and predictions obtained by Monte Carlo simulations or measurements from previous treatment fractions is performed. For this purpose, a total of 15 patient datasets were analyzed, which were acquired at Massachusetts General Hospital and Heidelberg Ion-Beam Therapy Center with in-room PET and offline PET/CT scanners, respectively. Calculated range differences between the compared activity distributions are reported in a 2D map in beam-eye-view. In comparison to previously proposed approaches, the new most-likely-shift method shows more robust results for assessing in-vivo the range from strongly varying PET distributions caused by differing patient geometry, ion beam species, beam delivery techniques, PET imaging concepts and counting statistics. The additional visualization of the uncertainties and the dedicated weighting strategy contribute to the understanding of the reliability of observed range differences and the complexity in the prediction of activity distributions. The proposed method promises to offer a feasible technique for clinical routine of PET-based range verification.

Automation and uncertainty analysis of a method for in-vivo range verification in particle therapy

NASA Astrophysics Data System (ADS)

Frey, K.; Unholtz, D.; Bauer, J.; Debus, J.; Min, C. H.; Bortfeld, T.; Paganetti, H.; Parodi, K.

2014-10-01

We introduce the automation of the range difference calculation deduced from particle-irradiation induced β+-activity distributions with the so-called most-likely-shift approach, and evaluate its reliability via the monitoring of algorithm- and patient-specific uncertainty factors. The calculation of the range deviation is based on the minimization of the absolute profile differences in the distal part of two activity depth profiles shifted against each other. Depending on the workflow of positron emission tomography (PET)-based range verification, the two profiles under evaluation can correspond to measured and simulated distributions, or only measured data from different treatment sessions. In comparison to previous work, the proposed approach includes an automated identification of the distal region of interest for each pair of PET depth profiles and under consideration of the planned dose distribution, resulting in the optimal shift distance. Moreover, it introduces an estimate of uncertainty associated to the identified shift, which is then used as weighting factor to ‘red flag’ problematic large range differences. Furthermore, additional patient-specific uncertainty factors are calculated using available computed tomography (CT) data to support the range analysis. The performance of the new method for in-vivo treatment verification in the clinical routine is investigated with in-room PET images for proton therapy as well as with offline PET images for proton and carbon ion therapy. The comparison between measured PET activity distributions and predictions obtained by Monte Carlo simulations or measurements from previous treatment fractions is performed. For this purpose, a total of 15 patient datasets were analyzed, which were acquired at Massachusetts General Hospital and Heidelberg Ion-Beam Therapy Center with in-room PET and offline PET/CT scanners, respectively. Calculated range differences between the compared activity distributions are reported in a 2D map in beam-eye-view. In comparison to previously proposed approaches, the new most-likely-shift method shows more robust results for assessing in-vivo the range from strongly varying PET distributions caused by differing patient geometry, ion beam species, beam delivery techniques, PET imaging concepts and counting statistics. The additional visualization of the uncertainties and the dedicated weighting strategy contribute to the understanding of the reliability of observed range differences and the complexity in the prediction of activity distributions. The proposed method promises to offer a feasible technique for clinical routine of PET-based range verification.

Heterologous expression of lipases YLIP4, YLIP5, YLIP7, YLIP13, and YLIP15 from Yarrowia lipolytica MSR80 in Escherichia coli: Substrate specificity, kinetic comparison, and enantioselectivity.

PubMed

Syal, Poonam; Gupta, Rani

2017-11-01

Five lipase genes, ylip4, ylip5, ylip7, ylip13, and ylip15, from Yarrowia lipolytica MSR80 were cloned and expressed in the pEZZ18-HB101 system. The lipases shared maximum sequence identity with Candida galli lipase, whereas they shared structural similarity with YLIP2 of Y. lipolytica CLIB122. The enzymes, purified using IgG sepharose, had specific activities in the range of 7-25 U mg -1 . Biochemical characteristics of all the lipases varied with respect to thermostability, substrate specificity, and enantioselectivity. All the enzymes were most active at neutral or slightly alkaline pH and were stable in the pH range 3.0-8.0, except YLIP4, which showed 50% stability at pH 10.0. Temperature optima of all the lipases varied from 30 to 50 ºC. YLIP15 and YLIP13 were most thermostable with a t 1/2 of 138 and 112 Min, respectively, at 60 °C. The lipases exhibited varied substrate specificity on p-nitrophenyl esters ranging from short-chain specificity (YLIP15), mid-chain specificity (YLIP4, YLIP5, YLIP7), and long-chain specificity (YLIP13). Catalytic efficiency on p-nitrophenylcaprate was highest for YLIP13 (67 × 10 3 mM -1 min -1 ) and lowest for YLIP15 (6.7 × 10 3 mM -1 min -1 ). YLIP13 was S-enantioselective, and YLIP15 was R-enantioselective with enantiomeric excess of 53 and 36%, respectively. Of all five lipases, YLIP13 and YLIP15 could be considered as industrially important enzymes as they were thermostable and enantioselective. © 2016 International Union of Biochemistry and Molecular Biology, Inc.

Neutron spectrum determination in a sub-critical assembly using the multi-disc neutron activation technique

NASA Astrophysics Data System (ADS)

Koseoglou, P.; Vagena, E.; Stoulos, S.; Manolopoulou, M.

2016-09-01

Neutron spectrum of the sub-critical nuclear assembly-reactor of Aristotle University of Thessaloniki was measured at three radial distances from the reactor core. The neutron activation technique was applied irradiating 15 thick foils - disc of various elements at each position. The data of 38 (n, γ), (n, p) and (n, α) reactions were analyzed for specific activity determination. Discs instead of foils were used due to the relevant low neutron flux, so the gamma self-absorption as well as the neutron self-shielding factors has been calculated using GEANT simulations in order to determine the activity induced. The specific activities calculated for all isotopes studied were the input to the SANDII code, which was built specifically for the neutron spectrum de-convolution when the neutron activation technique is used. For the optimization of the results a technique was applied in order to minimize the influence of the initial-"guessed" spectrum shape SANDII uses. The neutron spectrum estimated presents a peak in the regions of (i) thermal neutrons ranged between 0.001 and 1 eV peaking at neutron energy ∼0.1 eV and (ii) fast neutrons ranged between 0.1 and 20 MeV peaking at neutron energy ∼1.2 MeV. The reduction of thermal neutrons is higher than the fast one as the distance from the reactor core increases since thermal neutrons capture by natural U-fuel has higher cross section than the fast neutrons.

A dynamic model for generating actuator specifications for small arms barrel active stabilization

NASA Astrophysics Data System (ADS)

Pathak, Anupam; Brei, Diann; Luntz, Jonathan; Lavigna, Chris

2006-03-01

Due to stresses encountered in combat, it is known that soldier marksmanship noticeably decreases regardless of prior training. Active stabilization systems in small arms have potential to address this problem to increase soldier survivability and mission effectiveness. The key to success is proper actuator design, but this is highly dependent on proper specification which is challenging due to the human/weapon interaction. This paper presents a generic analytical dynamic model which is capable of defining the necessary actuation specifications for a wide range of small arms platforms. The model is unique because it captures the human interface--shoulder and arm--that introduces the jitter disturbance in addition to the geometry, inertial properties and active stabilization stiffness of the small arms platform. Because no data to date is available for actual shooter-induced disturbance in field conditions, a method is given using the model to back-solve from measured shooting range variability data the disturbance amplitude information relative to the input source (arm or shoulder). As examples of the applicability of the model to various small arms systems, two different weapon systems were investigated: the M24 sniper weapon and the M16 assault rifle. In both cases, model based simulations provided valuable insight into impact on the actuation specifications (force, displacement, phase, frequency) due to the interplay of the human-weapon-active stabilization interface including the effect of shooter-disturbance frequency, disturbance location (shoulder vs. arm), and system parameters (stiffness, barrel rotation).

A study on pore-opening behaviors of graphite nanofibers by a chemical activation process.

PubMed

Kim, Byung-Joo; Lee, Young-Seak; Park, Soo-Jin

2007-02-15

In this work, porous graphite nanofibers (GNFs) were prepared by a KOH activation method in order to manufacture porous carbon nanofibers. The process was conducted in the activation temperature range of 900-1100 degrees C, and the KOH:GNFs ratio was fixed at 3.5:1. The textural properties of the porous carbons were analyzed using N2 adsorption isotherms at 77 K. The BET, D-R, and BJH equations were used to observe the specific surface areas and the micro- and mesopore structures, respectively. From the results, it was found that the textural properties, including the specific surface area and the pore volumes, were proportionally enhanced with increasing activation temperatures. However, the activation mechanisms showed quite significant differences between the samples activated at low and high temperatures.

Total lactate dehydrogenase activity of tail muscle is not cold-adapted in nocturnal lizards from cool-temperate habitats.

PubMed

Hare, K M; Miller, J H; Clark, A G; Daugherty, C H

2005-12-01

The dependence of metabolic processes on temperature constrains the behavior, physiology and ecology of many ectothermic animals. The evolution of nocturnality in lizards, especially in temperate regions, requires adaptations for activity at low temperatures when optimal body temperatures are unlikely to be obtained. We examined whether nocturnal lizards have cold-adapted lactate dehydrogenase (LDH). LDH was chosen as a representative metabolic enzyme. We measured LDH activity of tail muscle in six lizard species (n=123: three nocturnal, two diurnal and one crepuscular) between 5 and 35 degrees C and found no differences in LDH-specific activity or thermal sensitivity among the species. Similarly, the specific activity and thermal sensitivity of LDH were similar between skinks and geckos. Similar enzyme activities among nocturnal and diurnal lizards indicate that there is no selection of temperature specific LDH enzyme activity at any temperature. As many nocturnal lizards actively thermoregulate during the day, LDH may be adapted for a broad range of temperatures rather than adapted specifically for the low temperatures encountered when the animals are active. The total activity of LDH in tropical and temperate lizards is not cold-adapted. More data are required on biochemical adaptations and whole animal thermal preferences before trends can be established.

Mechanism of Mediator recruitment by tandem Gcn4 activation domains and three Gal11 activator-binding domains.

PubMed

Herbig, Eric; Warfield, Linda; Fish, Lisa; Fishburn, James; Knutson, Bruce A; Moorefield, Beth; Pacheco, Derek; Hahn, Steven

2010-05-01

Targets of the tandem Gcn4 acidic activation domains in transcription preinitiation complexes were identified by site-specific cross-linking. The individual Gcn4 activation domains cross-link to three common targets, Gal11/Med15, Taf12, and Tra1, which are subunits of four conserved coactivator complexes, Mediator, SAGA, TFIID, and NuA4. The Gcn4 N-terminal activation domain also cross-links to the Mediator subunit Sin4/Med16. The contribution of the two Gcn4 activation domains to transcription was gene specific and varied from synergistic to less than additive. Gcn4-dependent genes had a requirement for Gal11 ranging from 10-fold dependence to complete Gal11 independence, while the Gcn4-Taf12 interaction did not significantly contribute to the expression of any gene studied. Complementary methods identified three conserved Gal11 activator-binding domains that bind each Gcn4 activation domain with micromolar affinity. These Gal11 activator-binding domains contribute additively to transcription activation and Mediator recruitment at Gcn4- and Gal11-dependent genes. Although we found that the conserved Gal11 KIX domain contributes to Gal11 function, we found no evidence of specific Gcn4-KIX interaction and conclude that the Gal11 KIX domain does not function by specific interaction with Gcn4. Our combined results show gene-specific coactivator requirements, a surprising redundancy in activator-target interactions, and an activator-coactivator interaction mediated by multiple low-affinity protein-protein interactions.

Notch signalling coordinates tissue growth and wing fate specification in Drosophila.

PubMed

Rafel, Neus; Milán, Marco

2008-12-01

During the development of a given organ, tissue growth and fate specification are simultaneously controlled by the activity of a discrete number of signalling molecules. Here, we report that these two processes are extraordinarily coordinated in the Drosophila wing primordium, which extensively proliferates during larval development to give rise to the dorsal thoracic body wall and the adult wing. The developmental decision between wing and body wall is defined by the opposing activities of two secreted signalling molecules, Wingless and the EGF receptor ligand Vein. Notch signalling is involved in the determination of a variety of cell fates, including growth and cell survival. We present evidence that growth of the wing primordium mediated by the activity of Notch is required for wing fate specification. Our data indicate that tissue size modulates the activity range of the signalling molecules Wingless and Vein. These results highlight a crucial role of Notch in linking proliferation and fate specification in the developing wing primordium.

Alternative Nucleophilic Substrates for the Endonuclease Activities of Human Immunodeficiency Virus Type 1 Integrase

PubMed Central

Ealy, Julie B.; Sudol, Malgorzata; Krzeminski, Jacek; Amin, Shantu; Katzman, Michael

2012-01-01

Retroviral integrase can use water or some small alcohols as the attacking nucleophile to nick DNA. To characterize the range of compounds that human immunodeficiency virus type 1 integrase can accommodate for its endonuclease activities, we tested 45 potential electron donors (having varied size and number or spacing of nucleophilic groups) as substrates during site-specific nicking at viral DNA ends and during nonspecific nicking reactions. We found that integrase used 22 of the 45 compounds to nick DNA, but not all active compounds were used for both activities. In particular, 13 compounds were used for site-specific and nonspecific nicking, 5 only for site-specific nicking, and 4 only for nonspecific nicking; 23 other compounds were not used for either activity. Thus, integrase can accommodate a large number of nucleophilic substrates but has selective requirements for its different activities, underscoring its dynamic properties and providing new information for modeling and understanding integrase. PMID:22910593

Single-Cell Analysis Reveals that Insulation Maintains Signaling Specificity between Two Yeast MAPK Pathways with Common Components

PubMed Central

Patterson, Jesse C.; Klimenko, Evguenia S.; Thorner, Jeremy

2014-01-01

Eukaryotic cells use multiple mitogen-activated protein kinase (MAPK) cascades to evoke appropriate responses to external stimuli. In Saccharomyces cerevisiae, the MAPK Fus3 is activated by pheromone-binding G protein-coupled receptors to promote mating, whereas the MAPK Hog1 is activated by hyperosmotic stress to elicit the high osmolarity glycerol (HOG) response. Although these MAPK pathways share several upstream components, exposure to either pheromone or osmolyte alone triggers only the appropriate response. We used fluorescent localization- and transcription-specific reporters to assess activation of these pathways in individual cells on the minute and hour timescale, respectively. Dual activation of these two MAPK pathways occurred over a broad range of stimulant concentrations and temporal regimes in wild-type cells subjected to co-stimulation. Thus, signaling specificity is achieved through an “insulation” mechanism, not a “cross-inhibition” mechanism. Furthermore, we showed that there was a critical period during which Hog1 activity had to occur for proper insulation of the HOG pathway. PMID:20959523

Selective inhibition of Erwinia amylovora by the herbicidally-active Germination-Arrest Factor (GAF) produced by Pseudomonas bacteria

USDA-ARS?s Scientific Manuscript database

Aims: The Germination-Arrest Factor (GAF) produced by Pseudomonas fluorescens WH6, and identified as 4-formylaminooxyvinylglycine, specifically inhibits the germination of a wide range of grassy weeds. The present study was undertaken to determine if GAF has antimicrobial activity in addition to it...

Leveling the Playing Field: First Generation Korean American Males and School Based Extracurricular Activities

ERIC Educational Resources Information Center

Levy, Corey

2010-01-01

This study examined the manner in which extracurricular activities impacted the acculturation of first-generation adolescent males. Specifically, the project focused on the influence of organized high school soccer on the development of first-generation adolescent Korean American males. Eight adolescent participants, ranging in age from fourteen…

Tissue-Specific Chromatin Modifications at a Multigene Locus Generate Asymmetric Transcriptional Interactions

PubMed Central

Yoo, Eung Jae; Cajiao, Isabela; Kim, Jeong-Seon; Kimura, Atsushi P.; Zhang, Aiwen; Cooke, Nancy E.; Liebhaber, Stephen A.

2006-01-01

Random assortment within mammalian genomes juxtaposes genes with distinct expression profiles. This organization, along with the prevalence of long-range regulatory controls, generates a potential for aberrant transcriptional interactions. The human CD79b/GH locus contains six tightly linked genes with three mutually exclusive tissue specificities and interdigitated control elements. One consequence of this compact organization is that the pituitarycell-specific transcriptional events that activate hGH-N also trigger ectopic activation of CD79b. However, the B-cell-specific events that activate CD79b do not trigger reciprocal activation of hGH-N. Here we utilized DNase I hypersensitive site mapping, chromatin immunoprecipitation, and transgenic models to explore the basis for this asymmetric relationship. The results reveal tissue-specific patterns of chromatin structures and transcriptional controls at the CD79b/GH locus in B cells distinct from those in the pituitary gland and placenta. These three unique transcriptional environments suggest a set of corresponding gene expression pathways and transcriptional interactions that are likely to be found juxtaposed at multiple sites within the eukaryotic genome. PMID:16847312

Review of cyclotron production and quality control of ``High specific activity'' radionuclides for biomedical, biological, industrial and environmental applications at INFN-LASA

NASA Astrophysics Data System (ADS)

Birattari, C.; Bonardi, M.; Groppi, F.; Gini, L.

2001-12-01

At the "Radiochemistry Laboratory" of Accelerators and Applied Superconductivity Laboratory, LASA, a wide range of high specific activity radionuclides, RNs, have been produced in No Carrier Added form, for both basic research and application purposes. Use was made of the AVF proton cyclotron (K=45) of Milan University (up to 1987). More recently, the irradiations were carried out at the Scanditronix MC40 cyclotron (K=38; p, d, He-4 and He-3) of JRC-Ispra, Italy, of the European Community. In order to optimize the irradiation conditions for radioisotope production, a series of thin- and thick-target excitation functions have been experimentally determined. For each RN, a specific radiochemical separation has been developed in order to obtain GBq (mCi) amounts of the radiotracers in "high specific activity" No Carrier Added form (NCA).

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

Klug, Victoria; Lobscheid, Agnes; Singer, Brett

Cooking of food and use of natural gas cooking burners generate pollutants that can have substantial impacts on residential indoor air quality. The extent of these impacts depends on cooking frequency, duration and specific food preparation activities in addition to the extent to which exhaust fans or other ventilation measures (e.g. windows) are used during cooking. With the intent of improving our understanding of indoor air quality impacts of cooking-related pollutants, we created, posted and advertised a web-based survey about cooking activities in residences. The survey included questions similar to those in California's Residential Appliance Saturation Survey (RASS), relating tomore » home, household and cooking appliance characteristics and weekly patterns of meals cooked. Other questions targeted the following information not captured in the RASS: (1) oven vs. cooktop use, the number of cooktop burners used and the duration of burner use when cooking occurs, (2) specific cooking activities, (3) the use of range hood or window to increase ventilation during cooking, and (4) occupancy during cooking. Specific cooking activity questions were asked about the prior 24 hours with the assumption that most people are able to recollect activities over this time period. We examined inter-relationships among cooking activities and patterns and relationships of cooking activities to household demographics. We did not seek to obtain a sample of respondents that is demographically representative of the California population but rather to inexpensively gather information from homes spanning ranges of relevant characteristics including the number of residents and presence or absence of children. This report presents the survey, the responses obtained, and limited analysis of the results.« less

Behavioural Risk Factors in Mid-Life Associated with Successful Ageing, Disability, Dementia and Frailty in Later Life: A Rapid Systematic Review

PubMed Central

Lafortune, Louise; Martin, Steven; Kelly, Sarah; Kuhn, Isla; Remes, Olivia; Cowan, Andy; Brayne, Carol

2016-01-01

Background Smoking, alcohol consumption, poor diet and low levels of physical activity significantly contribute to the burden of illness in developed countries. Whilst the links between specific and multiple risk behaviours and individual chronic conditions are well documented, the impact of these behaviours in mid-life across a range of later life outcomes has yet to be comprehensively assessed. This review aimed to provide an overview of behavioural risk factors in mid-life that are associated with successful ageing and the primary prevention or delay of disability, dementia, frailty and non-communicable chronic conditions. Methods A literature search was conducted to identify cohort studies published in English since 2000 up to Dec 2014. Multivariate analyses and a minimum follow-up of five years were required for inclusion. Two reviewers screened titles, abstracts and papers independently. Studies were assessed for quality. Evidence was synthesised by mid-life behavioural risk for a range of late life outcomes. Findings This search located 10,338 individual references, of which 164 are included in this review. Follow-up data ranged from five years to 36 years. Outcomes include dementia, frailty, disability and cardiovascular disease. There is consistent evidence of beneficial associations between mid-life physical activity, healthy ageing and disease outcomes. Across all populations studied there is consistent evidence that mid-life smoking has a detrimental effect on health. Evidence specific to alcohol consumption was mixed. Limited, but supportive, evidence was available relating specifically to mid-life diet, leisure and social activities or health inequalities. Conclusions There is consistent evidence of associations between mid-life behaviours and a range of late life outcomes. The promotion of physical activity, healthy diet and smoking cessation in all mid-life populations should be encouraged for successful ageing and the prevention of disability and chronic disease. PMID:26845035

A Range Finding Protocol to Support Design for Transcriptomics Experimentation: Examples of In-Vitro and In-Vivo Murine UV Exposure

PubMed Central

van Oostrom, Conny T.; Jonker, Martijs J.; de Jong, Mark; Dekker, Rob J.; Rauwerda, Han; Ensink, Wim A.; de Vries, Annemieke; Breit, Timo M.

2014-01-01

In transcriptomics research, design for experimentation by carefully considering biological, technological, practical and statistical aspects is very important, because the experimental design space is essentially limitless. Usually, the ranges of variable biological parameters of the design space are based on common practices and in turn on phenotypic endpoints. However, specific sub-cellular processes might only be partially reflected by phenotypic endpoints or outside the associated parameter range. Here, we provide a generic protocol for range finding in design for transcriptomics experimentation based on small-scale gene-expression experiments to help in the search for the right location in the design space by analyzing the activity of already known genes of relevant molecular mechanisms. Two examples illustrate the applicability: in-vitro UV-C exposure of mouse embryonic fibroblasts and in-vivo UV-B exposure of mouse skin. Our pragmatic approach is based on: framing a specific biological question and associated gene-set, performing a wide-ranged experiment without replication, eliminating potentially non-relevant genes, and determining the experimental ‘sweet spot’ by gene-set enrichment plus dose-response correlation analysis. Examination of many cellular processes that are related to UV response, such as DNA repair and cell-cycle arrest, revealed that basically each cellular (sub-) process is active at its own specific spot(s) in the experimental design space. Hence, the use of range finding, based on an affordable protocol like this, enables researchers to conveniently identify the ‘sweet spot’ for their cellular process of interest in an experimental design space and might have far-reaching implications for experimental standardization. PMID:24823911

Functional and topological characteristics of mammalian regulatory domains

PubMed Central

Symmons, Orsolya; Uslu, Veli Vural; Tsujimura, Taro; Ruf, Sandra; Nassari, Sonya; Schwarzer, Wibke; Ettwiller, Laurence; Spitz, François

2014-01-01

Long-range regulatory interactions play an important role in shaping gene-expression programs. However, the genomic features that organize these activities are still poorly characterized. We conducted a large operational analysis to chart the distribution of gene regulatory activities along the mouse genome, using hundreds of insertions of a regulatory sensor. We found that enhancers distribute their activities along broad regions and not in a gene-centric manner, defining large regulatory domains. Remarkably, these domains correlate strongly with the recently described TADs, which partition the genome into distinct self-interacting blocks. Different features, including specific repeats and CTCF-binding sites, correlate with the transition zones separating regulatory domains, and may help to further organize promiscuously distributed regulatory influences within large domains. These findings support a model of genomic organization where TADs confine regulatory activities to specific but large regulatory domains, contributing to the establishment of specific gene expression profiles. PMID:24398455

Acupuncture inhibits cue-induced heroin craving and brain activation.

PubMed

Cai, Xinghui; Song, Xiaoge; Li, Chuanfu; Xu, Chunsheng; Li, Xiliang; Lu, Qi

2012-11-25

Previous research using functional MRI has shown that specific brain regions associated with drug dependence and cue-elicited heroin craving are activated by environmental cues. Craving is an important trigger of heroin relapse, and acupuncture may inhibit craving. In this study, we performed functional MRI in heroin addicts and control subjects. We compared differences in brain activation between the two groups during heroin cue exposure, heroin cue exposure plus acupuncture at the Zusanli point (ST36) without twirling of the needle, and heroin cue exposure plus acupuncture at the Zusanli point with twirling of the needle. Heroin cue exposure elicited significant activation in craving-related brain regions mainly in the frontal lobes and callosal gyri. Acupuncture without twirling did not significantly affect the range of brain activation induced by heroin cue exposure, but significantly changed the extent of the activation in the heroin addicts group. Acupuncture at the Zusanli point with twirling of the needle significantly decreased both the range and extent of activation induced by heroin cue exposure compared with heroin cue exposure plus acupuncture without twirling of the needle. These experimental findings indicate that presentation of heroin cues can induce activation in craving-related brain regions, which are involved in reward, learning and memory, cognition and emotion. Acupuncture at the Zusanli point can rapidly suppress the activation of specific brain regions related to craving, supporting its potential as an intervention for drug craving.

Protective effects of buckwheat honey on DNA damage induced by hydroxyl radicals.

PubMed

Zhou, Juan; Li, Peng; Cheng, Ni; Gao, Hui; Wang, Bini; Wei, Yahui; Cao, Wei

2012-08-01

To understand the antioxidant properties of buckwheat honeys, we investigated their antioxidant effects on hydroxyl radical-induced DNA breaks in the non-site-specific and site-specific systems, the physicochemical properties, antioxidant activities (1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl radical scavenging activity, chelating, and reducing power assays), total phenolic content and individual phenolic acids were also determined. Total phenolic content of buckwheat honeys ranged from 774 to 1694 mg PA/kg, and p-hydroxybenzoic and p-coumaric acids proved to be the main components in buckwheat honeys. All the buckwheat honey samples possess stronger capability to protect DNA in the non-site-specific systems than in the site-specific systems from being damaged by hydroxyl radicals. In the non-site-specific and site-specific system, buckwheat honeys samples prevented ()OH-induced DNA breaks by 21-78% and 5-31% over control value, respectively. Copyright © 2012 Elsevier Ltd. All rights reserved.

Engineering Neprilysin Activity and Specificity to Create a Novel Therapeutic for Alzheimer’s Disease

PubMed Central

Webster, Carl I.; Burrell, Matthew; Olsson, Lise-Lotte; Fowler, Susan B.; Digby, Sarah; Sandercock, Alan; Snijder, Arjan; Tebbe, Jan; Haupts, Ulrich; Grudzinska, Joanna; Jermutus, Lutz; Andersson, Christin

2014-01-01

Neprilysin is a transmembrane zinc metallopeptidase that degrades a wide range of peptide substrates. It has received attention as a potential therapy for Alzheimer’s disease due to its ability to degrade the peptide amyloid beta. However, its broad range of peptide substrates has the potential to limit its therapeutic use due to degradation of additional peptides substrates that tightly regulate many physiological processes. We sought to generate a soluble version of the ectodomain of neprilysin with improved activity and specificity towards amyloid beta as a potential therapeutic for Alzheimer’s disease. Extensive amino acid substitutions were performed at positions surrounding the active site and inner surface of the enzyme and variants screened for activity on amyloid beta 1–40, 1–42 and a variety of other physiologically relevant peptides. We identified several mutations that modulated and improved both enzyme selectivity and intrinsic activity. Neprilysin variant G399V/G714K displayed an approximately 20-fold improved activity on amyloid beta 1–40 and up to a 3,200-fold reduction in activity on other peptides. Along with the altered peptide substrate specificity, the mutant enzyme produced a markedly altered series of amyloid beta cleavage products compared to the wild-type enzyme. Crystallisation of the mutant enzyme revealed that the amino acid substitutions result in alteration of the shape and size of the pocket containing the active site compared to the wild-type enzyme. The mutant enzyme offers the potential for the more efficient degradation of amyloid beta in vivo as a therapeutic for the treatment of Alzheimer’s disease. PMID:25089527

Structure-activity relationships of 4-hydroxyalkenals in the conjugation catalysed by mammalian glutathione transferases.

PubMed Central

Danielson, U H; Esterbauer, H; Mannervik, B

1987-01-01

The substrate specificities of 15 cytosolic glutathione transferases from rat, mouse and man have been explored by use of a homologous series of 4-hydroxyalkenals, extending from 4-hydroxypentenal to 4-hydroxypentadecenal. Rat glutathione transferase 8-8 is exceptionally active with the whole range of 4-hydroxyalkenals, from C5 to C15. Rat transferase 1-1, although more than 10-fold less efficient than transferase 8-8, is the second most active transferase with the longest chain length substrates. Other enzyme forms showing high activities with these substrates are rat transferase 4-4 and human transferase mu. The specificity constants, kcat./Km, for the various enzymes have been determined with the 4-hydroxyalkenals. From these constants the incremental Gibbs free energy of binding to the enzyme has been calculated for the homologous substrates. The enzymes responded differently to changes in the length of the hydrocarbon side chain and could be divided into three groups. All glutathione transferases displayed increased binding energy in response to increased hydrophobicity of the substrate. For some of the enzymes, steric limitations of the active site appear to counteract the increase in binding strength afforded by increased chain length of the substrate. Comparison of the activities with 4-hydroxyalkenals and other activated alkenes provides information about the active-site properties of certain glutathione transferases. The results show that the ensemble of glutathione transferases in a given species may serve an important physiological role in the conjugation of the whole range of 4-hydroxyalkenals. In view of its high catalytic efficiency with all the homologues, rat glutathione transferase 8-8 appears to have evolved specifically to serve in the detoxication of these reactive compounds of oxidative metabolism. PMID:3426557

Thermodynamics-Based Models of Transcriptional Regulation by Enhancers: The Roles of Synergistic Activation, Cooperative Binding and Short-Range Repression

PubMed Central

He, Xin; Samee, Md. Abul Hassan; Blatti, Charles; Sinha, Saurabh

2010-01-01

Quantitative models of cis-regulatory activity have the potential to improve our mechanistic understanding of transcriptional regulation. However, the few models available today have been based on simplistic assumptions about the sequences being modeled, or heuristic approximations of the underlying regulatory mechanisms. We have developed a thermodynamics-based model to predict gene expression driven by any DNA sequence, as a function of transcription factor concentrations and their DNA-binding specificities. It uses statistical thermodynamics theory to model not only protein-DNA interaction, but also the effect of DNA-bound activators and repressors on gene expression. In addition, the model incorporates mechanistic features such as synergistic effect of multiple activators, short range repression, and cooperativity in transcription factor-DNA binding, allowing us to systematically evaluate the significance of these features in the context of available expression data. Using this model on segmentation-related enhancers in Drosophila, we find that transcriptional synergy due to simultaneous action of multiple activators helps explain the data beyond what can be explained by cooperative DNA-binding alone. We find clear support for the phenomenon of short-range repression, where repressors do not directly interact with the basal transcriptional machinery. We also find that the binding sites contributing to an enhancer's function may not be conserved during evolution, and a noticeable fraction of these undergo lineage-specific changes. Our implementation of the model, called GEMSTAT, is the first publicly available program for simultaneously modeling the regulatory activities of a given set of sequences. PMID:20862354

Specific cerebellar regions are related to force amplitude and rate of force development

PubMed Central

Spraker, M.B.; Corcos, D.M.; Kurani, A.S.; Prodoehl, J.; Swinnen, S.P.; Vaillancourt, D.E.

2011-01-01

The human cerebellum has been implicated in the control of a wide variety of motor control parameters, such as force amplitude, movement extent, and movement velocity. These parameters often covary in both movement and isometric force production tasks, so it is difficult to resolve whether specific regions of the cerebellum relate to specific parameters. In order to address this issue, the current study used two experiments and SUIT normalization to determine whether BOLD activation in the cerebellum scales with the amplitude or rate of change of isometric force production or both. In the first experiment, subjects produced isometric pinch-grip force over a range of force amplitudes without any constraints on the rate of force development. In the second experiment, subjects varied the rate of force production, but the target force amplitude remained constant. The data demonstrate that BOLD activation in separate sub-areas of cerebellar regions lobule VI and Crus I/II scale with both force amplitude and force rate. In addition, BOLD activation in cerebellar lobule V and vermis VI was specific to force amplitude, whereas BOLD activation in lobule VIIb was specific to force rate. Overall, cerebellar activity related to force amplitude was located superior and medial, whereas activity related to force rate was inferior and lateral. These findings suggest that specific circuitry in the cerebellum may be dedicated to specific motor control parameters such as force amplitude and force rate. PMID:21963915

Learning Objectives for Shooting Sports Instruction. 554A: Using Measurable Criteria To Evaluate Performance.

ERIC Educational Resources Information Center

Benson, Delwin E.; Manning, Jan

This publication contains objectives that range from basic shooting sports safety and proficiency to more specialized activities. They can be applied to hunter safety education, 4-H shooting sports, scouting, and club or community activities for youth or adults. The specific learning objectives in each list have been grouped into learning…

Make It Relevant: A Guide to Using "The Morning Call" in the Classroom.

ERIC Educational Resources Information Center

Haggerty, Donna

A wide range of classroom activities employing daily newspapers can be found in this teaching guide, and there are suggestions for teachers of kindergarten children through high school seniors. Each chapter deals with a different content area, and is further subdivided into specific topics, with many suggested activities for each. After an…

Acupuncture inhibits cue-induced heroin craving and brain activation★

PubMed Central

Cai, Xinghui; Song, Xiaoge; Li, Chuanfu; Xu, Chunsheng; Li, Xiliang; Lu, Qi

2012-01-01

Previous research using functional MRI has shown that specific brain regions associated with drug dependence and cue-elicited heroin craving are activated by environmental cues. Craving is an important trigger of heroin relapse, and acupuncture may inhibit craving. In this study, we performed functional MRI in heroin addicts and control subjects. We compared differences in brain activation between the two groups during heroin cue exposure, heroin cue exposure plus acupuncture at the Zusanli point (ST36) without twirling of the needle, and heroin cue exposure plus acupuncture at the Zusanli point with twirling of the needle. Heroin cue exposure elicited significant activation in craving-related brain regions mainly in the frontal lobes and callosal gyri. Acupuncture without twirling did not significantly affect the range of brain activation induced by heroin cue exposure, but significantly changed the extent of the activation in the heroin addicts group. Acupuncture at the Zusanli point with twirling of the needle significantly decreased both the range and extent of activation induced by heroin cue exposure compared with heroin cue exposure plus acupuncture without twirling of the needle. These experimental findings indicate that presentation of heroin cues can induce activation in craving-related brain regions, which are involved in reward, learning and memory, cognition and emotion. Acupuncture at the Zusanli point can rapidly suppress the activation of specific brain regions related to craving, supporting its potential as an intervention for drug craving. PMID:25368637

Production of activated carbon from rice husk Vietnam

NASA Astrophysics Data System (ADS)

Korobochkin, V. V.; Tu, N. V.; Hieu, N. M.

2016-09-01

This work is dedicated to the production of activated carbon from rice husk from Delta of the Red River in Viet Nam. At the first stage, carbonization of a rice husk was carried out to obtain material containing 43.1% carbon and 25 % silica with a specific surface area of 51.5 m2/g. After separating of silica (the second stage), the specific surface area of the product increased to 204 m2/g and the silica content decreased to 1.23% by weight as well. The most important stage in the formation of the porous structure of the material is the activation. The products with the high specific surface area in the range of 800-1345 m2/g were obtained by activation of carbonized product with water vapour or carbon dioxide at temperatures of 700 °C and 850 °C, with varying the flow rate of the activating agent and activation time. The best results were achieved by activation of carbon material with water vapour at the flow rate of 0.08 dm3/min per 500 g of material and the temperature of 850 °C.

Structural Principles in the Development of Cyclic Peptidic Enzyme Inhibitors

PubMed Central

Xu, Peng; Andreasen, Peter A.; Huang, Mingdong

2017-01-01

This review summarizes our studies in the development of small cyclic peptides for specifically modulating enzyme activity. Serine proteases share highly similar active sites but perform diverse physiological and pathological functions. From a phage-display peptide library, we isolated two mono-cyclic peptides, upain-1 (CSWRGLENHRMC) and mupain-1 (CPAYSRYLDC), which inhibit the activity of human and murine urokinase-type plasminogen activators (huPA and muPA) with Ki values in the micromolar or sub-micromolar range, respectively. The following affinity maturations significantly enhanced the potencies of the two peptides, 10-fold and >250-fold for upain-1 and mupain-1, respectively. The most potent muPA inhibitor has a potency (Ki = 2 nM) and specificity comparable to mono-clonal antibodies. Furthermore, we also found an unusual feature of mupain-1 that its inhibitory potency can be enhanced by increasing the flexibility, which challenges the traditional viewpoint that higher rigidity leading to higher affinity. Moreover, by changing a few key residues, we converted mupain-1 from a uPA inhibitor to inhibitors of other serine proteases, including plasma kallikrein (PK) and coagulation factor XIa (fXIa). PK and fXIa inhibitors showed Ki values in the low nanomolar range and high specificity. Our studies demonstrate the versatility of small cyclic peptides to engineer inhibitory potency against serine proteases and to provide a new strategy for generating peptide inhibitors of serine proteases. PMID:29104489

Neural field model to reconcile structure with function in primary visual cortex.

PubMed

Rankin, James; Chavane, Frédéric

2017-10-01

Voltage-sensitive dye imaging experiments in primary visual cortex (V1) have shown that local, oriented visual stimuli elicit stable orientation-selective activation within the stimulus retinotopic footprint. The cortical activation dynamically extends far beyond the retinotopic footprint, but the peripheral spread stays non-selective-a surprising finding given a number of anatomo-functional studies showing the orientation specificity of long-range connections. Here we use a computational model to investigate this apparent discrepancy by studying the expected population response using known published anatomical constraints. The dynamics of input-driven localized states were simulated in a planar neural field model with multiple sub-populations encoding orientation. The realistic connectivity profile has parameters controlling the clustering of long-range connections and their orientation bias. We found substantial overlap between the anatomically relevant parameter range and a steep decay in orientation selective activation that is consistent with the imaging experiments. In this way our study reconciles the reported orientation bias of long-range connections with the functional expression of orientation selective neural activity. Our results demonstrate this sharp decay is contingent on three factors, that long-range connections are sufficiently diffuse, that the orientation bias of these connections is in an intermediate range (consistent with anatomy) and that excitation is sufficiently balanced by inhibition. Conversely, our modelling results predict that, for reduced inhibition strength, spurious orientation selective activation could be generated through long-range lateral connections. Furthermore, if the orientation bias of lateral connections is very strong, or if inhibition is particularly weak, the network operates close to an instability leading to unbounded cortical activation.

Cytomegalovirus Infection Leads to Development of High Frequencies of Cytotoxic Virus-Specific CD4+ T Cells Targeted to Vascular Endothelium

PubMed Central

Begum, Jusnara; Lal, Neeraj; Zuo, Jianmin; Beggs, Andrew; Moss, Paul

2016-01-01

Cytomegalovirus (CMV) infection elicits a very strong and sustained intravascular T cell immune response which may contribute towards development of accelerated immune senescence and vascular disease in older people. Virus-specific CD8+ T cell responses have been investigated extensively through the use of HLA-peptide tetramers but much less is known regarding CMV-specific CD4+ T cells. We used a range of HLA class II-peptide tetramers to investigate the phenotypic and transcriptional profile of CMV-specific CD4+ T cells within healthy donors. We show that such cells comprise an average of 0.45% of the CD4+ T cell pool and can reach up to 24% in some individuals (range 0.01–24%). CMV-specific CD4+ T cells display a highly differentiated effector memory phenotype and express a range of cytokines, dominated by dual TNF-α and IFN-γ expression, although substantial populations which express IL-4 were seen in some donors. Microarray analysis and phenotypic expression revealed a profile of unique features. These include the expression of CX3CR1, which would direct cells towards fractalkine on activated endothelium, and the β2-adrenergic receptor, which could permit rapid response to stress. CMV-specific CD4+ T cells display an intense cytotoxic profile with high level expression of granzyme B and perforin, a pattern which increases further during aging. In addition CMV-specific CD4+ T cells demonstrate strong cytotoxic activity against antigen-loaded target cells when isolated directly ex vivo. PD-1 expression is present on 47% of cells but both the intensity and distribution of the inhibitory receptor is reduced in older people. These findings reveal the marked accumulation and unique phenotype of CMV-specific CD4+ T cells and indicate how such T cells may contribute to the vascular complications associated with CMV in older people. PMID:27606804

International Laser Ranging Service (ILRS): Terms of Reference

NASA Technical Reports Server (NTRS)

Husson, Van; Noll, Carey

2000-01-01

The International Laser Ranging Service (ILRS) is an established Service within Section II , Advanced Space Technology, of the International Association of Geodesy (IAG). The primary objective of the ILRS is to provide a service to support, through Satellite and Lunar Laser Ranging data and related products, geodetic and geophysical research activities as well as International Earth Rotation Service (IERS) products important to the maintenance of an accurate International Terrestrial Reference Frame (ITRF). The service also develops the necessary standards/specifications and encourages international adherence to its conventions.

2012 NASA Range Safety Annual Report

NASA Technical Reports Server (NTRS)

Dumont, Alan G.

2012-01-01

This report provides a NASA Range Safety (NRS) overview for current and potential range users. This report contains articles which cover a variety of subject areas, summaries of various NASA Range Safety Program (RSP) activities performed during the past year, links to past reports, and information on several projects that may have a profound impact on the way business will be conducted in the future. Specific topics discussed in the 2012 NASA Range Safety Annual Report include a program overview and 2012 highlights; Range Safety Training; Independent Assessments; Support to Program Operations at all ranges conducting NASA launch/flight operations; a continuing overview of emerging range safety-related technologies; and status reports from all of the NASA Centers that have Range Safety responsibilities.

High-performance super capacitors based on activated anthracite with controlled porosity

NASA Astrophysics Data System (ADS)

Lee, Hyun-Chul; Byamba-Ochir, Narandalai; Shim, Wang-Geun; Balathanigaimani, M. S.; Moon, Hee

2015-02-01

Mongolian anthracite is chemically activated using potassium hydroxide as an activation agent to make activated carbon materials. Prior to the chemical activation, the chemical agent is introduced by two different methods as follows, (1) simple physical mixing, (2) impregnation. The physical properties such as specific surface area, pore volume, pore size distribution, and adsorption energy distribution are measured to assess them as carbon electrode materials for electric double-layer capacitors (EDLC). The surface functional groups and morphology are also characterized by X-ray photoelectron spectroscopy (XPS) and transmission electron microscopy (TEM) analyses respectively. The electrochemical results for the activated carbon electrodes in 3 M sulfuric acid electrolyte solution indicate that the activated Mongolian anthracite has relatively large specific capacitances in the range of 120-238 F g-1 and very high electrochemical stability, as they keep more than 98% of initial capacitances until 1000 charge/discharge cycles.

Impact of a product-specific reference standard for the measurement of a PEGylated rFVIII activity: the Swiss Multicentre Field Study.

PubMed

Bulla, O; Poncet, A; Alberio, L; Asmis, L M; Gähler, A; Graf, L; Nagler, M; Studt, J-D; Tsakiris, D A; Fontana, P

2017-07-01

Measuring factor VIII (FVIII) activity can be challenging when it has been modified, such as when FVIII is pegylated to increase its circulating half-life. Use of a product-specific reference standard may help avoid this issue. Evaluate the impact of using a product-specific reference standard for measuring the FVIII activity of BAX 855 - a pegylated FVIII - in eight of Switzerland's main laboratories. Factor VIII-deficient plasma, spiked with five different concentrations of BAX 855, plus a control FVIII sample, was sent to the participating laboratories. They measured FVIII activity by using either with a one-stage (OSA) or the chromogenic assay (CA) against their local or a product-specific reference standard. When using a local reference standard, there was an overestimation of BAX 855 activity compared to the target concentrations, both with the OSA and CA. The use of a product-specific reference standard reduced this effect: mean recovery ranged from 127.7% to 213.5% using the OSA with local reference standards, compared to 110% to 183.8% with a product-specific reference standard, and from 146.3% to 182.4% using the CA with local reference standards compared to 72.7% to 103.7% with a product-specific reference standard. In this in vitro study, the type of reference standard had a major impact on the measurement of BAX 855 activity. Evaluation was more accurate and precise when using a product-specific reference standard. © 2017 John Wiley & Sons Ltd.

Sustainable Range Management of RDX and TNT by Phytoremediation with Engineered Plants

DTIC Science & Technology

2016-04-01

transformation products in the environment. Dinitrotoluenes are often co- contaminants at TNT- manufacturing sites, and dinitrotoluene-mineralizing bacteria...specific commercial product, process, or service by trade name, trademark, manufacturer , or otherwise, does not necessarily constitute or imply its...Distribution A 13. SUPPLEMENTARY NOTES 14. ABSTRACT Decades of military activity on live-fire training ranges have resulted in the contamination of

Opening wedge and anatomic-specific plates in foot and ankle applications.

PubMed

Kluesner, Andrew J; Morris, Jason B

2011-08-01

As surgeons continually push to improve techniques and outcomes, anatomic-specific and procedure-specific fixation options are becoming increasingly available. The unique size, shape, and function of the foot provide an ideal framework for the use of anatomic-specific plates. These distinctive plate characteristics range from anatomic contouring and screw placements to incorporated step-offs and wedges. By optimizing support, compression, and stabilization, patients may return to weight bearing and activity sooner, improving outcomes. This article discusses anatomic-specific plates and their use in forefoot and rearfoot surgical procedures. Copyright © 2011 Elsevier Inc. All rights reserved.

Analysis of the restricting factors of laser countermeasure active detection technology

NASA Astrophysics Data System (ADS)

Zhang, Yufa; Sun, Xiaoquan

2016-07-01

The detection effect of laser active detection system is affected by various kinds of factors. In view of the application requirement of laser active detection, the influence factors for laser active detection are analyzed. The mathematical model of cat eye target detection distance has been built, influence of the parameters of laser detection system and the environment on detection range and the detection efficiency are analyzed. Various parameters constraint detection performance is simulated. The results show that the discovery distance of laser active detection is affected by the laser divergence angle, the incident angle and the visibility of the atmosphere. For a given detection range, the laser divergence angle and the detection efficiency are mutually restricted. Therefore, in view of specific application environment, it is necessary to select appropriate laser detection parameters to achieve optimal detection effect.

Perfect mixing of immiscible macromolecules at fluid interfaces

NASA Astrophysics Data System (ADS)

Sheiko, Sergei S.; Zhou, Jing; Arnold, Jamie; Neugebauer, Dorota; Matyjaszewski, Krzysztof; Tsitsilianis, Constantinos; Tsukruk, Vladimir V.; Carrillo, Jan-Michael Y.; Dobrynin, Andrey V.; Rubinstein, Michael

2013-08-01

The difficulty of mixing chemically incompatible substances—in particular macromolecules and colloidal particles—is a canonical problem limiting advances in fields ranging from health care to materials engineering. Although the self-assembly of chemically different moieties has been demonstrated in coordination complexes, supramolecular structures, and colloidal lattices among other systems, the mechanisms of mixing largely rely on specific interfacing of chemically, physically or geometrically complementary objects. Here, by taking advantage of the steric repulsion between brush-like polymers tethered to surface-active species, we obtained long-range arrays of perfectly mixed macromolecules with a variety of polymer architectures and a wide range of chemistries without the need of encoding specific complementarity. The net repulsion arises from the significant increase in the conformational entropy of the brush-like polymers with increasing distance between adjacent macromolecules at fluid interfaces. This entropic-templating assembly strategy enables long-range patterning of thin films on sub-100 nm length scales.

Antimicrobial activity of commercial Olea europaea (olive) leaf extract.

PubMed

Sudjana, Aurelia N; D'Orazio, Carla; Ryan, Vanessa; Rasool, Nooshin; Ng, Justin; Islam, Nabilah; Riley, Thomas V; Hammer, Katherine A

2009-05-01

The aim of this research was to investigate the activity of a commercial extract derived from the leaves of Olea europaea (olive) against a wide range of microorganisms (n=122). Using agar dilution and broth microdilution techniques, olive leaf extract was found to be most active against Campylobacter jejuni, Helicobacter pylori and Staphylococcus aureus [including meticillin-resistant S. aureus (MRSA)], with minimum inhibitory concentrations (MICs) as low as 0.31-0.78% (v/v). In contrast, the extract showed little activity against all other test organisms (n=79), with MICs for most ranging from 6.25% to 50% (v/v). In conclusion, olive leaf extract was not broad-spectrum in action, showing appreciable activity only against H. pylori, C. jejuni, S. aureus and MRSA. Given this specific activity, olive leaf extract may have a role in regulating the composition of the gastric flora by selectively reducing levels of H. pylori and C. jejuni.

[Recording and data processing of electrical signals of the specific atrioventricular conduction pathways in man].

PubMed

Héron, F; Mialet, G; Schuller, C; Breton, D; Perrin, J; Degeorges, M

1979-01-01

Signals of the electrical activity of the specific atrioventricular conduction pathways were recorded with an unipolar lead to obtain an exact time reference. The amplifier used had special characteristics: high gain settings (up to 300,000), very low noise levels, and wide filter range (2 Hz - 1,600 Hz). The low amplitude of the signals under study, of the order of a microvolt, and the wide filter range of the amplifier necessitated placing the patient in a Faraday cage. The signals recorded on magnetic tape were treated by a system of analysis for signal treatment. The method of averaging was used to extract the signal from background noise especially that arising from somatic muscle. The amplitude of the Hisian signal was much larger than that usually obtained with other methods. The intervals were determined with precision of the order of 1 millisecond. Frequential analysis of the signals gave another representation of the information contained in the time signals. This new representation seems to give better discrimination of the different zones of activation of the specific atrioventricular conduction pathways.

Multichannel brain recordings in behaving Drosophila reveal oscillatory activity and local coherence in response to sensory stimulation and circuit activation

PubMed Central

Paulk, Angelique C.; Zhou, Yanqiong; Stratton, Peter; Liu, Li

2013-01-01

Neural networks in vertebrates exhibit endogenous oscillations that have been associated with functions ranging from sensory processing to locomotion. It remains unclear whether oscillations may play a similar role in the insect brain. We describe a novel “whole brain” readout for Drosophila melanogaster using a simple multichannel recording preparation to study electrical activity across the brain of flies exposed to different sensory stimuli. We recorded local field potential (LFP) activity from >2,000 registered recording sites across the fly brain in >200 wild-type and transgenic animals to uncover specific LFP frequency bands that correlate with: 1) brain region; 2) sensory modality (olfactory, visual, or mechanosensory); and 3) activity in specific neural circuits. We found endogenous and stimulus-specific oscillations throughout the fly brain. Central (higher-order) brain regions exhibited sensory modality-specific increases in power within narrow frequency bands. Conversely, in sensory brain regions such as the optic or antennal lobes, LFP coherence, rather than power, best defined sensory responses across modalities. By transiently activating specific circuits via expression of TrpA1, we found that several circuits in the fly brain modulate LFP power and coherence across brain regions and frequency domains. However, activation of a neuromodulatory octopaminergic circuit specifically increased neuronal coherence in the optic lobes during visual stimulation while decreasing coherence in central brain regions. Our multichannel recording and brain registration approach provides an effective way to track activity simultaneously across the fly brain in vivo, allowing investigation of functional roles for oscillations in processing sensory stimuli and modulating behavior. PMID:23864378

Frequency distribution of specific activities and radiological hazard assessment in surface beach sand samples collected in Bangsaen beach in Chonburi province, Thailand

NASA Astrophysics Data System (ADS)

Changkit, N.; Boonkrongcheep, R.; Youngchauy, U.; Polthum, S.; Kessaratikoon, P.

2017-09-01

The specific activities of natural radionuclides (40K, 226Ra and 232Th) in 50 surface beach sand samples collected from Bangsaen beach in Chonburi province in the easthern region of Thailand, were measured and evaluated. Experimental results were obtained by using a high-purity germanium (HPGe) detector and gamma spectrometry analysis system in the special laboratory at Thailand Institute of Nuclear Technology (Public Organization). The IAEA-SOIL-375 reference material was used to analyze the concentration of 40K, 226Ra and 232Th in all samples. It was found that the specific activities of 40K, 226Ra and 232Th were ranged from 510.85 - 771.35, 8.17 - 17.06 and 4.25 - 15.68 Bq/kg. Furthermore, frequency distribution of the specific activities were studied, analyzed and found to be the asymmetrical distribution by using a statistical computer program. Moreover, four radiological hazard indices for the investigated area were also calculated by using the median values of specific activities of 40K, 226Ra and 232Th. The results were also compared with the Office of Atoms for Peace (OAP) annual report data, Thailand and global radioactivity measurement and evaluations.

Use of boron nitride for neutron spectrum characterization and cross-section validation in the epithermal range through integral activation measurements

NASA Astrophysics Data System (ADS)

Radulović, Vladimir; Trkov, Andrej; Jaćimović, Radojko; Gregoire, Gilles; Destouches, Christophe

2016-12-01

A recent experimental irradiation and measurement campaign using containers made from boron nitride (BN) at the Jožef Stefan Institute (JSI) TRIGA Mark II reactor in Ljubljana, Slovenia, has shown the applicability of BN for neutron spectrum characterization and cross-section validation in the epithermal range through integral activation measurements. The first part of the paper focuses on the determination of the transmission function of a BN container through Monte Carlo calculations and experimental measurements. The second part presents the process of tayloring the sensitivity of integral activation measurements to specific needs and a selection of suitable radiative capture reactions for neutron spectrum characterization in the epithermal range. A BN container used in our experiments and its qualitative effect on the neutron spectrum in the irradiation position employed is displayed in the Graphical abstract.

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.

Whatever Happened to the Jock, the Brain, and the Princess? Young Adult Pathways Linked to Adolescent Activity Involvement and Social Identity.

ERIC Educational Resources Information Center

Barber, Bonnie L.; Eccles, Jacquelynne S.; Stone, Margaret R.

2001-01-01

Examined young adult participation in high school activities and identity group as predictors of later substance use, psychological adjustment, and educational and occupational outcomes. Found both participation and identity may consolidate specific skills, attitudes, values, and social networks that have a far-ranging impact on the transition to…

Research activities at the Australian Bureau of Meteorology for the regional ionospheric specification and forecasting

NASA Astrophysics Data System (ADS)

Bouya, Zahra; Terkildsen, Michael

2016-07-01

The Australian Space Forecast Centre (ASFC) provides space weather forecasts to a diverse group of customers. Space Weather Services (SWS) within the Australian Bureau of Meteorology is focussed both on developing tailored products and services for the key customer groups, and supporting ASFC operations. Research in SWS is largely centred on the development of data-driven models using a range of solar-terrestrial data. This paper will cover some data requirements , approaches and recent SWS activities for data driven modelling with a focus on the regional Ionospheric specification and forecasting.

LOGO Bibliography.

ERIC Educational Resources Information Center

Proud, Jim

This bibliography lists 168 articles, books, and instructional materials for anyone interested in learning more about the LOGO programming language. Items listed range from research reports and program descriptions to lesson plans and activities. Specific titles include "A Beginner's Guide to LOGO"; "LOGO Music"; "Printing…

NASA Information Resources Management Long Range Plan, FY 1994-1998

NASA Technical Reports Server (NTRS)

1993-01-01

Table of Contents: Introduction; Agency 5-Year IRM Investment Projections; Program Specific IRM Activities by Program Office; Major IRM Program Accomplishments for FY 1992; Information Collection Budget; Summary of Computer Security Plans; and Appendix: Acronym List.

Re-examination of the Pt Particle Size Effect on the Oxygen Reduction Reaction for Ultrathin Uniform Pt/C Catalyst Layers without Influence from Nafion

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

Shinozaki, Kazuma; Morimoto, Yu; Pivovar, Bryan S.

The platinum 'particle size effect' on the oxygen reduction reaction (ORR) has been re-evaluated using commercial Pt/C catalysts (2-10 nm Pt particle) and polycrystalline Pt (poly-Pt) in 0.1 M HClO4 with a rotating disk electrode method. Nafion-free catalyst layers were employed to obtain specific activities (SA) that were not perturbed (suppressed) by sulfonate anion adsorption/blocking. By using ultrathin uniform catalyst layers, O2 diffusion limitation was minimized as confirmed from the high SAs of our supported catalysts that were comparable to unsupported sputtered Pt having controlled sizes. The specific activity (SA) steeply increased for the particle sizes in the range -2-10more » nm (0.8-1.8 mA/cm2Pt at 0.9 V vs. RHE) and plateaued over -10 nm to 2.7 mA/cm2Pt for bulk poly-Pt. On the basis of the activity trend for the range of particle sizes studied, it appears that the effect of carbon support on activity is negligible. The experimental results and the concomitant profile of SA vs. particle size was found to be in an agreement to a truncated octahedral particle model that assumes active terrace sites.« less

Lab-based validation of different data processing methods for wrist-worn ActiGraph accelerometers in young adults.

PubMed

Ellingson, Laura D; Hibbing, Paul R; Kim, Youngwon; Frey-Law, Laura A; Saint-Maurice, Pedro F; Welk, Gregory J

2017-06-01

The wrist is increasingly being used as the preferred site for objectively assessing physical activity but the relative accuracy of processing methods for wrist data has not been determined. This study evaluates the validity of four processing methods for wrist-worn ActiGraph (AG) data against energy expenditure (EE) measured using a portable metabolic analyzer (OM; Oxycon mobile) and the Compendium of physical activity. Fifty-one adults (ages 18-40) completed 15 activities ranging from sedentary to vigorous in a laboratory setting while wearing an AG and the OM. Estimates of EE and categorization of activity intensity were obtained from the AG using a linear method based on Hildebrand cutpoints (HLM), a non-linear modification of this method (HNLM), and two methods developed by Staudenmayer based on a Linear Model (SLM) and using random forest (SRF). Estimated EE and classification accuracy were compared to the OM and Compendium using Bland-Altman plots, equivalence testing, mean absolute percent error (MAPE), and Kappa statistics. Overall, classification agreement with the Compendium was similar across methods ranging from a Kappa of 0.46 (HLM) to 0.54 (HNLM). However, specificity and sensitivity varied by method and intensity, ranging from a sensitivity of 0% (HLM for sedentary) to a specificity of ~99% for all methods for vigorous. None of the methods was significantly equivalent to the OM (p  >  0.05). Across activities, none of the methods evaluated had a high level of agreement with criterion measures. Additional research is needed to further refine the accuracy of processing wrist-worn accelerometer data.

Is it meaningful to distinguish between generalized and specific Internet addiction? Evidence from a cross-cultural study from Germany, Sweden, Taiwan and China.

PubMed

Montag, Christian; Bey, Katharina; Sha, Peng; Li, Mei; Chen, Ya-Fei; Liu, Wei-Yin; Zhu, Yi-Kang; Li, Chun-Bo; Markett, Sebastian; Keiper, Julia; Reuter, Martin

2015-03-01

It has been hypothesized that two distinctive forms of Internet addiction exist. Here, generalized Internet addiction refers to the problematic use of the Internet covering a broad range of Internet-related activities. In contrast, specific forms of Internet addiction target the problematic use of distinct online activities such as excessive online video gaming or activities in social networks. The present study investigates the relationship between generalized and specific Internet addiction in a cross-cultural study encompassing data from China, Taiwan, Sweden and Germany in n = 636 participants. In this study, we assessed - besides generalized Internet addiction - addictive behavior in the domains of online video gaming, online shopping, online social networks and online pornography. The results confirm the existence of distinct forms of specific Internet addiction. One exception, however, was established in five of the six samples under investigation: online social network addiction correlates in large amounts with generalized Internet addiction. In general, it is of importance to distinguish between generalized and specific Internet addiction. Copyright © 2014 Wiley Publishing Asia Pty Ltd.

Sedentary behavior and residual-specific mortality

PubMed Central

Loprinzi, Paul D.; Edwards, Meghan K.; Sng, Eveleen; Addoh, Ovuokerie

2016-01-01

Background: The purpose of this study was to examine the association of accelerometer-assessed sedentary behavior and residual-specific mortality. Methods: Data from the 2003-2006 National Health and Nutrition Examination Survey (NHANES) were used (N = 5536), with follow-up through 2011. Sedentary behavior was objectively measured over 7 days via accelerometry. Results: When expressing sedentary behavior as a 60 min/day increase, the hazard ratio across the models ranged from 1.07-1.40 (P < 0.05). There was evidence of an interaction effect between sedentary behavior and total physical activity on residual-specific mortality (Hazard ratiointeraction [HR] = 0.9989; 95% CI: 0.9982-0.9997; P = 0.008). Conclusion: Sedentary behavior was independently associated with residual-specific mortality. However, there was evidence to suggest that residual-specific mortality risk was a function of sedentary behavior and total physical activity. These findings highlight the need for future work to not only examine the association between sedentary behavior and health independent of total physical activity, but evaluate whether there is a joint effect of these two parameters on health. PMID:27766237

Regulation of Dpp activity by tissue-specific cleavage of an upstream site within the prodomain

PubMed Central

Sopory, Shailaja; Kwon, Sunjong; Wehrli, Marcel; Christian, Jan L.

2010-01-01

BMP4 is synthesized as an inactive precursor that is cleaved at two sites during maturation: initially at a site (S1) adjacent to the ligand domain, and then at an upstream site (S2) within the prodomain. Cleavage at the second site regulates the stability of mature BMP4 and this in turn influences its signaling intensity and range of action. The Drosophila ortholog of BMP4, Dpp, functions as a long- or short-range signaling molecule in the wing disc or embryonic midgut, respectively but mechanisms that differentially regulate its bioactivity in these tissues have not been explored. In the current studies we demonstrate, by dpp mutant rescue, that cleavage at the S2 site of proDpp is required for development of the wing and leg imaginal discs, whereas cleavage at the S1 site is sufficient to rescue Dpp function in the midgut. Both the S1 and S2 site of proDpp are cleaved in the wing disc, and S2-cleavage is essential to generate sufficient ligand to exceed the threshold for pMAD activation at both short- and long-range in most cells. By contrast, proDpp is cleaved at the S1 site alone in the embryonic mesoderm and this generates sufficient ligand to activate physiological target genes in neighboring cells. These studies provide the first biochemical and genetic evidence that that selective cleavage of the S2 site of proDPP provides a tissue-specific mechanism for regulating Dpp activity, and that differential cleavage can contribute to, but is not an absolute determinant of signaling range. PMID:20659445

Generalized extracellular molecule sensor platform for programming cellular behavior.

PubMed

Scheller, Leo; Strittmatter, Tobias; Fuchs, David; Bojar, Daniel; Fussenegger, Martin

2018-04-23

Strategies for expanding the sensor space of designer receptors are urgently needed to tailor cell-based therapies to respond to any type of medically relevant molecules. Here, we describe a universal approach to designing receptor scaffolds that enables antibody-specific molecular input to activate JAK/STAT, MAPK, PLCG or PI3K/Akt signaling rewired to transgene expression driven by synthetic promoters. To demonstrate its scope, we equipped the GEMS (generalized extracellular molecule sensor) platform with antibody fragments targeting a synthetic azo dye, nicotine, a peptide tag and the PSA (prostate-specific antigen) biomarker, thereby covering inputs ranging from small molecules to proteins. These four GEMS devices provided robust signaling and transgene expression with high signal-to-noise ratios in response to their specific ligands. The sensitivity of the nicotine- and PSA-specific GEMS devices matched the clinically relevant concentration ranges, and PSA-specific GEMS were able to detect pathological PSA levels in the serum of patients diagnosed with prostate cancer.

Developing a Vocational Index for Adults with Autism Spectrum Disorders

PubMed Central

Seltzer, Marsha Mailick

2012-01-01

Existing methods of indexing the vocational activities of adults with autism spectrum disorders (ASD) have made significant contributions to research. Nonetheless, they are limited by problems with sensitivity and reliability. We developed an index of vocational and educational outcomes that captures the full range of activities experienced by adults with ASD, and that can be reliably coded across studies using specific decision rules. To develop this index, we used employment, vocational, and educational data collected from nearly 350 adults with ASD at 6 times over 12 years, as part of a larger longitudinal study. The resulting index consists of 11 categories coded on a 9-point scale, ranging from competitive employment and/or postsecondary educational program to no vocational/educational activities. PMID:22466690

Formaldehyde activation of mitoxantrone yields CpG and CpA specific DNA adducts

PubMed Central

Parker, Belinda S.; Cutts, Suzanne M.; Cullinane, Carleen; Phillips, Don R.

2000-01-01

Recently we have found that mitoxantrone, like Adriamycin, can be activated by formaldehyde and subsequently form adducts which stabilise double-stranded DNA in vitro. This activation by formaldehyde may be biologically relevant since formaldehyde levels are elevated in those tumours in which mitoxantrone is most cytotoxic. In vitro transcription analysis revealed that these adducts block the progression of RNA polymerase during transcription and cause truncated RNA transcripts. There was an absolute requirement for both mitoxantrone and formaldehyde in transcriptional blockage formation and the activated complex was found to exhibit site specificity, with blockage occurring prior to CpG and CpA sites in the DNA (non-template strand). The stability of the adduct at 37°C was site dependent. The half-lives ranged from 45 min to ~5 h and this was dependent on both the central 2 bp blockage site as well as flanking sequences. The CpG specificity of mitoxantrone adduct sites was also confirmed independently by a λ exonuclease digestion assay. PMID:10648792

The development and characterization of an ELISA specifically detecting the active form of cathepsin K.

PubMed

Sun, S; Karsdal, M A; Bay-Jensen, A C; Sørensen, M G; Zheng, Q; Dziegiel, M H; Maksymowych, W P; Henriksen, K

2013-10-01

Cathepsin K plays essential roles in bone resorption and is intensely investigated as a therapeutic target for the treatment of osteoporosis. Hence an assessment of the active form of cathepsin K may provide important biological information in metabolic bone diseases, such as osteoporosis or ankylosing spondylitis. Presently there are no robust assays for the assessment of active cathepsin K in serum, and therefore an ELISA specifically detecting the N-terminal of the active form of cathepsin K was developed. The assay was technically robust, with a lowest limit of detection (LOD) of 0.085 ng/mL. The average intra- and inter-assay CV% were 6.60% and 8.56% respectively. The dilution recovery and spike recovery tests in human serum were within 100±20% within the range of the assay. A comparison of latent and active cathepsin K confirmed specificity towards the active form. Quantification of the levels of active cathepsin K in supernatants of purified human osteoclasts compared to corresponding macrophages showed a 30-fold induction (p<0.001). In contrast, in serum samples from osteoporotic women on estrogen or bisphosphonate therapy and from ankylosing spondylitis patients no clinically relevant differences were observed. In summary, we have developed a robust and sensitive assay specifically detecting the active form of cathepsin K; however, while it monitors osteoclasts with high specificity in vitro, it appears that circulating levels of active cathepsin K do not reflect bone changes under these circumstances. Copyright © 2013 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Curriculum Guides for SSSQ.

ERIC Educational Resources Information Center

McCarron, Lawrence; And Others

The curriculum guide was designed to teach prevocational and independent living skills to students with a wide range of handicapping conditions. The SSSQ (Street Survival Skills Questionnaire) curriculum presents information on objectives, materials, suggested performance criteria, teacher strategies, and specific students activities for the…

Neuroserpin Differentiates Between Forms of Tissue Type Plasminogen Activator via pH Dependent Deacylation

PubMed Central

Carlson, Karen-Sue B.; Nguyen, Lan; Schwartz, Kat; Lawrence, Daniel A.; Schwartz, Bradford S.

2016-01-01

Tissue-type plasminogen activator (t-PA), initially characterized for its critical role in fibrinolysis, also has key functions in both physiologic and pathologic processes in the CNS. Neuroserpin (NSP) is a t-PA specific serine protease inhibitor (serpin) found almost exclusively in the CNS that regulates t-PA’s proteolytic activity and protects against t-PA mediated seizure propagation and blood–brain barrier disruption. This report demonstrates that NSP inhibition of t-PA varies profoundly as a function of pH within the biologically relevant pH range for the CNS, and reflects the stability, rather than the formation of NSP: t-PA acyl-enzyme complexes. Moreover, NSP differentiates between the zymogen-like single chain form (single chain t-PA, sct-PA) and the mature protease form (two chain t-PA, tct-PA) of t-PA, demonstrating different pH profiles for protease inhibition, different pH ranges over which catalytic deacylation occurs, and different pH dependent profiles of deacylation rates for each form of t-PA. NSP’s pH dependent inhibition of t-PA is not accounted for by differential acylation, and is specific for the NSP-t-PA serpin-protease pair. These results demonstrate a novel mechanism for the differential regulation of the two forms of t-PA in the CNS, and suggest a potential specific regulatory role for CNS pH in controlling t-PA proteolytic activity. PMID:27378851

The biological function of antibodies induced by the RTS,S/AS01 malaria vaccine candidate is determined by their fine specificity.

PubMed

Chaudhury, Sidhartha; Ockenhouse, Christian F; Regules, Jason A; Dutta, Sheetij; Wallqvist, Anders; Jongert, Erik; Waters, Norman C; Lemiale, Franck; Bergmann-Leitner, Elke

2016-05-31

Recent vaccine studies have shown that the magnitude of an antibody response is often insufficient to explain efficacy, suggesting that characteristics regarding the quality of the antibody response, such as its fine specificity and functional activity, may play a major role in protection. Previous studies of the lead malaria vaccine candidate, RTS,S, have shown that circumsporozoite protein (CSP)-specific antibodies and CD4(+) T cell responses are associated with protection, however the role of fine specificity and biological function of CSP-specific antibodies remains to be elucidated. Here, the relationship between fine specificity, opsonization-dependent phagocytic activity and protection in RTS,S-induced antibodies is explored. A new method for measuring the phagocytic activity mediated by CSP-specific antibodies in THP-1 cells is presented and applied to samples from a recently completed phase 2 RTS,S/AS01 clinical trial. The fine specificity of the antibody response was assessed using ELISA against three antigen constructs of CSP: the central repeat region, the C-terminal domain and the full-length protein. A multi-parameter analysis of phagocytic activity and fine-specificity data was carried out to identify potential correlates of protection in RTS,S. Results from the newly developed assay revealed that serum samples from RTS,S recipients displayed a wide range of robust and repeatable phagocytic activity. Phagocytic activity was correlated with full-length CSP and C-terminal specific antibody titres, but not to repeat region antibody titres, suggesting that phagocytic activity is primarily driven by C-terminal antibodies. Although no significant difference in overall phagocytic activity was observed with respect to protection, phagocytic activity expressed as 'opsonization index', a relative measure that normalizes phagocytic activity with CS antibody titres, was found to be significantly lower in protected subjects than non-protected subjects. Opsonization index was identified as a surrogate marker of protection induced by the RTS,S/AS01 vaccine and determined how antibody fine specificity is linked to opsonization activity. These findings suggest that the role of opsonization in protection in the RTS,S vaccine may be more complex than previously thought, and demonstrate how integrating multiple immune measures can provide insight into underlying mechanisms of immunity and protection.

Long-range comparison of human and mouse Sprr loci to identify conserved noncoding sequences involved in coordinate regulation

PubMed Central

Martin, Natalia; Patel, Satyakam; Segre, Julia A.

2004-01-01

Mammalian epidermis provides a permeability barrier between an organism and its environment. Under homeostatic conditions, epidermal cells produce structural proteins, which are cross-linked in an orderly fashion to form a cornified envelope (CE). However, under genetic or environmental stress, specific genes are induced to rapidly build a temporary barrier. Small proline-rich (SPRR) proteins are the primary constituents of the CE. Under stress the entire family of 14 Sprr genes is upregulated. The Sprr genes are clustered within the larger epidermal differentiation complex on mouse chromosome 3, human chromosome 1q21. The clustering of the Sprr genes and their upregulation under stress suggest that these genes may be coordinately regulated. To identify enhancer elements that regulate this stress response activation of the Sprr locus, we utilized bioinformatic tools and classical biochemical dissection. Long-range comparative sequence analysis identified conserved noncoding sequences (CNSs). Clusters of epidermal-specific DNaseI-hypersensitive sites (HSs) mapped to specific CNSs. Increased prevalence of these HSs in barrier-deficient epidermis provides in vivo evidence of the regulation of the Sprr locus by these conserved sequences. Individual components of these HSs were cloned, and one was shown to have strong enhancer activity specific to conditions when the Sprr genes are coordinately upregulated. PMID:15574822

Memory Retrieval Re-Activates Erk1/2 Signaling in the Same Set of CA1 Neurons Recruited During Conditioning.

PubMed

Zamorano, Cristina; Fernández-Albert, Jordi; Storm, Daniel R; Carné, Xavier; Sindreu, Carlos

2018-02-01

The hippocampus enables a range of behaviors through its intrinsic circuits and concerted actions with other brain regions. One such important function is the retrieval of episodic memories. How hippocampal cells support retrieval of contextual fear memory remains largely unclear. Here we monitored phospho-activation of extracellular-regulated kinase (Erk1/2) across neuronal populations of the hippocampus to find that CA1 pyramidal neurons, but not cells in CA3 or dentate gyrus, specifically respond to retrieval of an aversive context. In contrast, retrieval of a neutral context that fails to elicit a threat response did not activate Erk1/2. Moreover, retrieval preferentially re-activated Erk1/2 in the same set of CA1 neurons previously activated during conditioning in a context-specific manner. By confining drug inhibition within dorsal CA1, we established the crucial role for Erk1/2 activity in retrieval of long-term memory, as well as in amygdala activation associated with fear expression. These data provide functional evidence that Erk1/2 signaling in CA1 encodes a specific neural representation of contextual memory with emotional value. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

A Youth Compendium of Physical Activities: Activity Codes and Metabolic Intensities

PubMed Central

BUTTE, NANCY F.; WATSON, KATHLEEN B.; RIDLEY, KATE; ZAKERI, ISSA F.; MCMURRAY, ROBERT G.; PFEIFFER, KARIN A.; CROUTER, SCOTT E.; HERRMANN, STEPHEN D.; BASSETT, DAVID R.; LONG, ALEXANDER; BERHANE, ZEKARIAS; TROST, STEWART G.; AINSWORTH, BARBARA E.; BERRIGAN, DAVID; FULTON, JANET E.

2018-01-01

ABSTRACT Purpose A Youth Compendium of Physical Activities (Youth Compendium) was developed to estimate the energy costs of physical activities using data on youth only. Methods On the basis of a literature search and pooled data of energy expenditure measurements in youth, the energy costs of 196 activities were compiled in 16 activity categories to form a Youth Compendium of Physical Activities. To estimate the intensity of each activity, measured oxygen consumption (V˙O2) was divided by basal metabolic rate (Schofield age-, sex-, and mass-specific equations) to produce a youth MET (METy). A mixed linear model was developed for each activity category to impute missing values for age ranges with no observations for a specific activity. Results This Youth Compendium consists of METy values for 196 specific activities classified into 16 major categories for four age-groups, 6–9, 10–12, 13–15, and 16–18 yr. METy values in this Youth Compendium were measured (51%) or imputed (49%) from youth data. Conclusion This Youth Compendium of Physical Activities uses pediatric data exclusively, addresses the age dependency of METy, and imputes missing METy values and thus represents advancement in physical activity research and practice. This Youth Compendium will be a valuable resource for stakeholders interested in evaluating interventions, programs, and policies designed to assess and encourage physical activity in youth. PMID:28938248

Versatile illumination platform and fast optical switch to give standard observation camera gated active imaging capacity

NASA Astrophysics Data System (ADS)

Grasser, R.; Peyronneaudi, Benjamin; Yon, Kevin; Aubry, Marie

2015-10-01

CILAS, subsidiary of Airbus Defense and Space, develops, manufactures and sales laser-based optronics equipment for defense and homeland security applications. Part of its activity is related to active systems for threat detection, recognition and identification. Active surveillance and active imaging systems are often required to achieve identification capacity in case for long range observation in adverse conditions. In order to ease the deployment of active imaging systems often complex and expensive, CILAS suggests a new concept. It consists on the association of two apparatus working together. On one side, a patented versatile laser platform enables high peak power laser illumination for long range observation. On the other side, a small camera add-on works as a fast optical switch to select photons with specific time of flight only. The association of the versatile illumination platform and the fast optical switch presents itself as an independent body, so called "flash module", giving to virtually any passive observation systems gated active imaging capacity in NIR and SWIR.

RSPOs facilitated HSC activation and promoted hepatic fibrogenesis

PubMed Central

Yin, Xinguang; Yi, Huixing; Wang, Linlin; Wu, Wanxin; Wu, Xiaojun; Yu, Linghua

2016-01-01

Roof plate-specific spondin (RSPO) proteins are potent Wnt pathway agonists and involve in a broad range of developmental and physiological processes. This study investigated the activities and mechanisms of RSPOs in liver fibrogenesis, especially in hepatic stellate cell (HSC) activation. HSC activation was assessed by fibrosis biomarker (α-smooth muscle actin and Collagen-I), phenotypic change (accumulation of lipid droplets), and increased proliferation. Similarly, Wnt pathway activity was evaluated by the expression of nuclear β-catenin and T cell-specific transcription factors (TCF) activity. We found RSPOs were overexpressed in human fibrotic liver tissue and the expressions were correlated with liver fibrosis stages. In vitro studies showed RSPOs level increased during HSC activation, and stimuli with RSPOs enhanced Wnt pathway activity and promoted HSC activation subsequently. Furthermore, in vivo experiments demonstrated that the knockdown of RSPOs suppressed both Wnt pathway activity and HSC activation. Interestingly, the inhibitor of the Wnt signaling pathway Dickkopf1 impairs RSPOs effects on HSCs. Taken together, our results revealed that RSPOs facilitated HSC activation and promote liver fibrogenesis by enhancing the Wnt pathway. PMID:27572318

RSPOs facilitated HSC activation and promoted hepatic fibrogenesis.

PubMed

Yin, Xinguang; Yi, Huixing; Wang, Linlin; Wu, Wanxin; Wu, Xiaojun; Yu, Linghua

2016-09-27

Roof plate-specific spondin (RSPO) proteins are potent Wnt pathway agonists and involve in a broad range of developmental and physiological processes. This study investigated the activities and mechanisms of RSPOs in liver fibrogenesis, especially in hepatic stellate cell (HSC) activation. HSC activation was assessed by fibrosis biomarker (α-smooth muscle actin and Collagen-I), phenotypic change (accumulation of lipid droplets), and increased proliferation. Similarly, Wnt pathway activity was evaluated by the expression of nuclear β-catenin and T cell-specific transcription factors (TCF) activity. We found RSPOs were overexpressed in human fibrotic liver tissue and the expressions were correlated with liver fibrosis stages. In vitro studies showed RSPOs level increased during HSC activation, and stimuli with RSPOs enhanced Wnt pathway activity and promoted HSC activation subsequently. Furthermore, in vivo experiments demonstrated that the knockdown of RSPOs suppressed both Wnt pathway activity and HSC activation. Interestingly, the inhibitor of the Wnt signaling pathway Dickkopf1 impairs RSPOs effects on HSCs. Taken together, our results revealed that RSPOs facilitated HSC activation and promote liver fibrogenesis by enhancing the Wnt pathway.

The role of the local environment and epigenetics in shaping macrophage identity and their effect on tissue homeostasis.

PubMed

Amit, Ido; Winter, Deborah R; Jung, Steffen

2016-01-01

Macrophages provide a critical systemic network cells of the innate immune system. Emerging data suggest that in addition, they have important tissue-specific functions that range from clearance of surfactant from the lungs to neuronal pruning and establishment of gut homeostasis. The differentiation and tissue-specific activation of macrophages require precise regulation of gene expression, a process governed by epigenetic mechanisms such as DNA methylation, histone modification and chromatin structure. We argue that epigenetic regulation of macrophages is determined by lineage- and tissue-specific transcription factors controlled by the built-in programming of myeloid development in combination with signaling from the tissue environment. Perturbation of epigenetic mechanisms of tissue macrophage identity can affect normal macrophage tissue function and contribute to pathologies ranging from obesity and autoimmunity to neurodegenerative diseases.

A Long-Chain Secondary Alcohol Dehydrogenase from Rhodococcus erythropolis ATCC 4277

PubMed Central

Ludwig, B.; Akundi, A.; Kendall, K.

1995-01-01

A NAD-dependent secondary alcohol dehydrogenase has been purified from the alkane-degrading bacterium, Rhodococcus erythropolis ATCC 4277. The enzyme was found to be active against a broad range of substrates, particularly long-chain secondary aliphatic alcohols. Although optimal activity was observed with linear 2-alcohols containing between 6 and 11 carbon atoms, secondary alcohols as long as 2-tetradecanol were oxidized at 25% of the rate seen with mid-range alcohols. The purified enzyme was specific for the S-(+) stereoisomer of 2-octanol and had a specific activity for 2-octanol of over 200 (mu)mol/min/mg of protein at pH 9 and 37(deg)C, 25-fold higher than that of any previously reported S-(+) secondary alcohol dehydrogenase. Linear primary alcohols containing between 3 and 13 carbon atoms were utilized 20- to 40-fold less efficiently than the corresponding secondary alcohols. The apparent K(infm) value for NAD(sup+) with 2-octanol as the substrate was 260 (mu)M, whereas the apparent K(infm) values for the 2-alcohols ranged from over 5 mM for 2-pentanol to less than 2 (mu)M for 2-tetradecanol. The enzyme showed moderate thermostability (half-life of 4 h at 60(deg)C) and could potentially be useful for the synthesis of optically pure stereoisomers of secondary alcohols. PMID:16535152

Antigen-specific antibody response in juvenile-onset SLE patients following routine immunization with tetanus toxoid.

PubMed

Kashef, Sara; Ghazizadeh, Farid; Derakhshan, Ali; Farjadian, Shirin; Alyasin, Soheila

2008-09-01

Infection is now the most common cause of morbidity in Systemic Lupus Erythematosus (SLE). There is lack of information regarding the specific antibody formation in response to vaccines in young SLE patients. To determine the efficacy of anti-tetanus antibody response in young patients with SLE. Forty SLE patients with mean age of 14.1 years (range: 7-21) and 60 age and sex matched normal controls were enrolled in this study over a period of one year. Diagnosis was made according to the ACR criteria and disease activity was determined based on SLE Disease Activity Index (SLEDAI). All patients and controls had received the complete schedule of tetanus vaccinations consisting of three primary doses and two boosters by the age of six. Serum immunoglobulins and anti-tetanus antibody titers were determined by Nephelometry and ELISA. Anti-tetanus antibody levels greater than 0.1 IU/ml have been suggested as protective. In all of the patients and controls anti-tetanus antibody titer was > 0.1 IU/ml. IgG, IgA, and IgM levels were in the normal range for their age. Mean disease activity score was 4.9 (range: 0-16). There was no association between SLEDAI score and anti-tetanus antibody response. School age onset and immunosuppressive therapy does not seem to interfere with development of consistent immunity to tetanus vaccine in young SLE patients.

Effects of pore structure and electrolyte on the capacitive characteristics of steam- and KOH-activated carbons for supercapacitors

NASA Astrophysics Data System (ADS)

Wu, Feng-Chin; Tseng, Ru-Ling; Hu, Chi-Chang; Wang, Chen-Ching

Four kinds of activated carbons (denoted as ACs) with specific surface area of ca. 1050 m 2 g -1 were fabricated from fir wood and pistachio shell by means of steam activation or chemical activation with KOH. Pore structures of ACs were characterized by a t-plot method based on N 2 adsorption isotherms. The amount of mesopores within KOH-activated carbons ranged from 9.2 to 15.3% while 33.3-49.5% of mesopores were obtained for the steam-activated carbons. The pore structure, surface functional groups, and raw materials of ACs, as well as pH and the supporting electrolyte were also found to be significant factors determining the capacitive characteristics of ACs. The excellent capacitive characteristics in both acidic and neutral media and the weak dependence of the specific capacitance on the scan rate of cyclic voltammetry (CV) for the ACs derived from the pistachio shell with steam activation (denoted as P-H 2O-AC) revealed their promising potential in the application of supercapacitors. The ACs derived from fir wood with KOH activation (denoted as F-KOH-AC), on the other hand, showed the best capacitive performance in H 2SO 4 due to excellent reversibility and high specific capacitance (180 F g -1 measured at 10 mV s -1), which is obviously larger than 100 F g -1 (a typical value of activated carbons with specific surface areas equal to/above 1000 m 2 g -1).

Evaluation of radioisotope tracer and activation analysis techniques for contamination monitoring in space environment simulation chambers

NASA Technical Reports Server (NTRS)

Smathers, J. B.; Kuykendall, W. E., Jr.; Wright, R. E., Jr.; Marshall, J. R.

1973-01-01

Radioisotope measurement techniques and neutron activation analysis are evaluated for use in identifying and locating contamination sources in space environment simulation chambers. The alpha range method allows the determination of total contaminant concentration in vapor state and condensate state. A Cf-252 neutron activation analysis system for detecting oils and greases tagged with stable elements is described. While neutron activation analysis of tagged contaminants offers specificity, an on-site system is extremely costly to implement and provides only marginal detection sensitivity under even the most favorable conditions.

Controlled ecological evaluation of an implemented exercise training programme to prevent lower limb injuries in sport: differences in implementation activity.

PubMed

Donaldson, Alex; Gabbe, Belinda J; Lloyd, David G; Cook, Jill; Finch, Caroline F

2018-04-24

The public health benefits of injury prevention programmes are maximised when programmes are widely adopted and adhered to. Therefore, these programmes require appropriate implementation support. This study evaluated implementation activity outcomes associated with the implementation of FootyFirst, an exercise training injury prevention programme for community Australian football, both with (FootyFirst+S) and without (FootyFirst+NS) implementation support. An evaluation plan based on the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) Sports Setting Matrix was applied in a controlled ecological evaluation of the implementation of FootyFirst. RE-AIM dimension-specific (range: 0-2) and total RE-AIM scores (range: 0-10) were derived by triangulating data from a number of sources (including surveys, interviews, direct observations and notes) describing FootyFirst implementation activities. The mean dimension-specific and total scores were compared for clubs in regions receiving FootyFirst+S and FootyFirst+NS, through analysis of variance. The mean total RE-AIM score forclubs in the FootyFirst+S regions was 2.4 times higher than for clubs in the FootyFirst+NS region (4.73 vs 1.94; 95% CI for the difference: 1.64 to 3.74). Similarly, all dimension-specific scores were significantly higher for clubs in the FootyFirst+S regions compared with clubs in the FootyFirst+NS region. In all regions, the dimension-specific scores were highest for reach and adoption, and lowest for implementation. Implementing exercise training injury prevention programmes in community sport is challenging. Delivering programme content supported by a context-specific and evidence-informed implementation plan leads to greater implementation activity, which is an important precursor to injury reductions. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Cleavage Specificity of Mycobacterium tuberculosis ClpP1P2 Protease and Identification of Novel Peptide Substrates and Boronate Inhibitors with Anti-bacterial Activity*

PubMed Central

Akopian, Tatos; Kandror, Olga; Tsu, Christopher; Lai, Jack H.; Wu, Wengen; Liu, Yuxin; Zhao, Peng; Park, Annie; Wolf, Lisa; Dick, Lawrence R.; Rubin, Eric J.; Bachovchin, William; Goldberg, Alfred L.

2015-01-01

The ClpP1P2 protease complex is essential for viability in Mycobacteria tuberculosis and is an attractive drug target. Using a fluorogenic tripeptide library (Ac-X3X2X1-aminomethylcoumarin) and by determining specificity constants (kcat/Km), we show that ClpP1P2 prefers Met ≫ Leu > Phe > Ala in the X1 position, basic residues or Trp in the X2 position, and Pro ≫ Ala > Trp in the X3 position. We identified peptide substrates that are hydrolyzed up to 1000 times faster than the standard ClpP substrate. These positional preferences were consistent with cleavage sites in the protein GFPssrA by ClpXP1P2. Studies of ClpP1P2 with inactive ClpP1 or ClpP2 indicated that ClpP1 was responsible for nearly all the peptidase activity, whereas both ClpP1 and ClpP2 contributed to protein degradation. Substrate-based peptide boronates were synthesized that inhibit ClpP1P2 peptidase activity in the submicromolar range. Some of them inhibited the growth of Mtb cells in the low micromolar range indicating that cleavage specificity of Mtb ClpP1P2 can be used to design novel anti-bacterial agents. PMID:25759383

Analysis of Tobyhanna Army Depot’s Radio Frequency Identification (RFID) Pilot Program: RFID as an Asset Management Tool

DTIC Science & Technology

2005-06-01

each has advantages and disadvantages. 1. Active Tags The main difference between the two types of RFID tags is that active tags have an internal...battery source and passive tags do not. The advantage of the active tag is that it transmits its own signal, which increases the read range of the...applications provide a stand-alone solution that employs a specific usage application of RFID and has clear economic advantages over supply chain

Electrode-active material for electrochemical batteries and method of preparation

DOEpatents

Varma, R.

1983-11-07

A battery electrode material comprises a non-stoichiometric electrode-active material which forms a redox pair with the battery electrolyte, an electrically conductive polymer present in the range of from about 2% by weight to about 5% by weight of the electrode-active material, and a binder. The conductive polymer provides improved proton or ion conductivity and is a ligand resulting in metal ion or negative ion vacancies of less than about 0.1 atom percent. Specific electrodes of nickel and lead are disclosed.

Electrode-active material for electrochemical batteries and method of preparation

DOEpatents

Varma, Ravi

1987-01-01

A battery electrode material comprising a non-stoichiometric electrode-active material which forms a redox pair with the battery electrolyte, an electrically conductive polymer present in the range of from about 2% by weight to about 5% by weight of the electrode-active material, and a binder. The conductive polymer provides improved proton or ion conductivity and is a ligand resulting in metal ion or negative ion vacancies of less than about 0.1 atom percent. Specific electrodes of nickel and lead are disclosed.

Report on Active and Planned Spacecraft and Experiments

NASA Technical Reports Server (NTRS)

Vostreys, R. W. (Editor); Maitson, H. H. (Editor)

1981-01-01

Active and planned spacecraft activity and experiments between June 1, 1980 and May 31, 1981 known to the National Space Science Data Center are described. The information covers a wide range of disciplines: astronomy, Earth sciences, meteorology, planetary sciences, aeronomy, particles and fields, solar physics, life sciences, and material sciences. Each spacecraft and experiment is described and its current status presented. Descriptions of navigational and communications satellites and of spacecraft that contain only continuous radio beacons used for ionospheric studies are specifically excluded.

Generation of dTALEs and Libraries of Synthetic TALE-Activated Promoters for Engineering of Gene Regulatory Networks in Plants.

PubMed

Schreiber, Tom; Tissier, Alain

2017-01-01

Transcription factors with programmable DNA-binding specificity constitute valuable tools for the design of orthogonal gene regulatory networks for synthetic biology. Transcription activator-like effectors (TALEs), as natural transcription regulators, were used to design, build, and test libraries of synthetic TALE-activated promoters (STAPs) that show a broad range of expression levels in plants. In this chapter, we present protocols for the construction of artificial TALEs and corresponding STAPs.

Electromagnetized gold nanoparticles mediate direct lineage reprogramming into induced dopamine neurons in vivo for Parkinson's disease therapy

NASA Astrophysics Data System (ADS)

Yoo, Junsang; Lee, Euiyeon; Kim, Hee Young; Youn, Dong-Ho; Jung, Junghyun; Kim, Hongwon; Chang, Yujung; Lee, Wonwoong; Shin, Jaein; Baek, Soonbong; Jang, Wonhee; Jun, Won; Kim, Soochan; Hong, Jongki; Park, Hi-Joon; Lengner, Christopher J.; Moh, Sang Hyun; Kwon, Youngeun; Kim, Jongpil

2017-10-01

Electromagnetic fields (EMF) are physical energy fields generated by electrically charged objects, and specific ranges of EMF can influence numerous biological processes, which include the control of cell fate and plasticity. In this study, we show that electromagnetized gold nanoparticles (AuNPs) in the presence of specific EMF conditions facilitate an efficient direct lineage reprogramming to induced dopamine neurons in vitro and in vivo. Remarkably, electromagnetic stimulation leads to a specific activation of the histone acetyltransferase Brd2, which results in histone H3K27 acetylation and a robust activation of neuron-specific genes. In vivo dopaminergic neuron reprogramming by EMF stimulation of AuNPs efficiently and non-invasively alleviated symptoms in mouse Parkinson's disease models. This study provides a proof of principle for EMF-based in vivo lineage conversion as a potentially viable and safe therapeutic strategy for the treatment of neurodegenerative disorders.

A novel mammal-specific three partite enhancer element regulates node and notochord-specific Noto expression.

PubMed

Alten, Leonie; Schuster-Gossler, Karin; Eichenlaub, Michael P; Wittbrodt, Beate; Wittbrodt, Joachim; Gossler, Achim

2012-01-01

The vertebrate organizer and notochord have conserved, essential functions for embryonic development and patterning. The restricted expression of developmental regulators in these tissues is directed by specific cis-regulatory modules (CRMs) whose sequence conservation varies considerably. Some CRMs have been conserved throughout vertebrates and likely represent ancestral regulatory networks, while others have diverged beyond recognition but still function over a wide evolutionary range. Here we identify and characterize a mammalian-specific CRM required for node and notochord specific (NNC) expression of NOTO, a transcription factor essential for node morphogenesis, nodal cilia movement and establishment of laterality in mouse. A 523 bp enhancer region (NOCE) upstream the Noto promoter was necessary and sufficient for NNC expression from the endogenous Noto locus. Three subregions in NOCE together mediated full activity in vivo. Binding sites for known transcription factors in NOCE were functional in vitro but dispensable for NOCE activity in vivo. A FOXA2 site in combination with a novel motif was necessary for NOCE activity in vivo. Strikingly, syntenic regions in non-mammalian vertebrates showed no recognizable sequence similarities. In contrast to its activity in mouse NOCE did not drive NNC expression in transgenic fish. NOCE represents a novel, mammal-specific CRM required for the highly restricted Noto expression in the node and nascent notochord and thus regulates normal node development and function.

Crystal structure of isoflavone reductase from alfalfa (Medicago sativa L.).

PubMed

Wang, Xiaoqiang; He, Xianzhi; Lin, Jianqiao; Shao, Hui; Chang, Zhenzhan; Dixon, Richard A

2006-05-19

Isoflavonoids play important roles in plant defense and exhibit a range of mammalian health-promoting activities. Isoflavone reductase (IFR) specifically recognizes isoflavones and catalyzes a stereospecific NADPH-dependent reduction to (3R)-isoflavanone. The crystal structure of Medicago sativa IFR with deletion of residues 39-47 has been determined at 1.6A resolution. Structural analysis, molecular modeling and docking, and comparison with the structures of other NADPH-dependent enzymes, defined the putative binding sites for co-factor and substrate and potential key residues for enzyme activity and substrate specificity. Further mutagenesis has confirmed the role of Lys144 as a catalytic residue. This study provides a structural basis for understanding the enzymatic mechanism and substrate specificity of IFRs as well as the functions of IFR-like proteins.

[Species specificity, age factors, and various neurochemical correlates of the animal spontaneous behavior after exposure to electromagnetic field of the ultralow intensity].

PubMed

Shtemberg, A S; Uzbekov, M G; Shikhov, S N; Bazian, A S; Cherniakov, G M

2000-01-01

Behavioral and neurochemical reactions of small laboratory animals (mice and rats of different age) under exposure to ultralow-intensity electromagnetic fields (EMF, frequency of 4200 and 970 MHz, modulated by a quasistochastic signal in the range of 20-20,000 Hz, power density 15 microW/cm2, specific body absorption rate up to 4.5 mJ/kg) were studied. The EMF basically inhibited the locomotor and exploratory activity in the "open-field" test. The species- and age-specific features rather than radiation conditions dominated. However, decrease in the EMF frequency considerably intensified the observed effect. Change in animal behavior was accompanied by shifts in neurochemical processes, i.e., sharp activation of serotoninergic and inhibition of morepinephrinergic system.

Chaperones in maturation of molybdoenzymes: Why specific is better than general?

PubMed

Lemaire, Olivier N; Bouillet, Sophie; Méjean, Vincent; Iobbi-Nivol, Chantal; Genest, Olivier

2017-03-04

Molybdoenzymes play essential functions in living organisms and, as a result, in various geochemical cycles. It is thus crucial to understand how these complex proteins become highly efficient enzymes able to perform a wide range of catalytic activities. It has been established that specific chaperones are involved during their maturation process. Here, we raise the question of the involvement of general chaperones acting in concert with dedicated chaperones or not.

A wedge-based approach to estimating health co-benefits of climate change mitigation activities in the United States

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

Balbus, John M.; Greenblatt, Jeffery B.; Chari, Ramya

While it has been recognized that actions reducing greenhouse gas (GHG) emissions can have significant positive and negative impacts on human health through reductions in ambient fine particulate matter (PM2.5) concentrations, these impacts are rarely taken into account when analyzing specific policies. This study presents a new framework for estimating the change in health outcomes resulting from implementation of specific carbon dioxide (CO 2) reduction activities, allowing comparison of different sectors and options for climate mitigation activities. Our estimates suggest that in the year 2020, the reductions in adverse health outcomes from lessened exposure to PM2.5 would yield economic benefitsmore » in the range of $6 to $14 billion (in 2008 USD), depending on the specific activity. This equates to between $40 and $93 per metric ton of CO 2 in health benefits. Specific climate interventions will vary in the health co-benefits they provide as well as in potential harms that may result from their implementation. Rigorous assessment of these health impacts is essential for guiding policy decisions as efforts to reduce GHG emissions increase in scope and intensity.« less

Evaluation of the catalytic specificity, biochemical properties, and milk clotting abilities of an aspartic peptidase from Rhizomucor miehei.

PubMed

da Silva, Ronivaldo Rodrigues; Souto, Tatiane Beltramini; de Oliveira, Tássio Brito; de Oliveira, Lilian Caroline Gonçalves; Karcher, Daniel; Juliano, Maria Aparecida; Juliano, Luiz; de Oliveira, Arthur H C; Rodrigues, André; Rosa, Jose C; Cabral, Hamilton

2016-08-01

In this study, we detail the specificity of an aspartic peptidase from Rhizomucor miehei and evaluate the effects of this peptidase on clotting milk using the peptide sequence of k-casein (Abz-LSFMAIQ-EDDnp) and milk powder. Molecular mass of the peptidase was estimated at 37 kDa, and optimum activity was achieved at pH 5.5 and 55 °C. The peptidase was stable at pH values ranging from 3 to 5 and temperatures of up 45 °C for 60 min. Dramatic reductions in proteolytic activity were observed with exposure to sodium dodecyl sulfate, and aluminum and copper (II) chloride. Peptidase was inhibited by pepstatin A, and mass spectrometry analysis identified four peptide fragments (TWSISYGDGSSASGILAK, ASNGGGGEYIFGGYDSTK, GSLTTVPIDNSR, and GWWGITVDRA), similar to rhizopuspepsin. The analysis of catalytic specificity showed that the coagulant activity of the peptidase was higher than the proteolytic activity and that there was a preference for aromatic, basic, and nonpolar amino acids, particularly methionine, with specific cleavage of the peptide bond between phenylalanine and methionine. Thus, this peptidase may function as an important alternative enzyme in milk clotting during the preparation of cheese.

Engineered Cpf1 variants with altered PAM specificities.

PubMed

Gao, Linyi; Cox, David B T; Yan, Winston X; Manteiga, John C; Schneider, Martin W; Yamano, Takashi; Nishimasu, Hiroshi; Nureki, Osamu; Crosetto, Nicola; Zhang, Feng

2017-08-01

The RNA-guided endonuclease Cpf1 is a promising tool for genome editing in eukaryotic cells. However, the utility of the commonly used Acidaminococcus sp. BV3L6 Cpf1 (AsCpf1) and Lachnospiraceae bacterium ND2006 Cpf1 (LbCpf1) is limited by their requirement of a TTTV protospacer adjacent motif (PAM) in the DNA substrate. To address this limitation, we performed a structure-guided mutagenesis screen to increase the targeting range of Cpf1. We engineered two AsCpf1 variants carrying the mutations S542R/K607R and S542R/K548V/N552R, which recognize TYCV and TATV PAMs, respectively, with enhanced activities in vitro and in human cells. Genome-wide assessment of off-target activity using BLISS indicated that these variants retain high DNA-targeting specificity, which we further improved by introducing an additional non-PAM-interacting mutation. Introducing the identified PAM-interacting mutations at their corresponding positions in LbCpf1 similarly altered its PAM specificity. Together, these variants increase the targeting range of Cpf1 by approximately threefold in human coding sequences to one cleavage site per ∼11 bp.

Intralaminar stimulation of the inferior colliculus facilitates frequency-specific activation in the auditory cortex

NASA Astrophysics Data System (ADS)

Allitt, B. J.; Benjaminsen, C.; Morgan, S. J.; Paolini, A. G.

2013-08-01

Objective. Auditory midbrain implants (AMI) provide inadequate frequency discrimination for open set speech perception. AMIs that can take advantage of the tonotopic laminar of the midbrain may be able to better deliver frequency specific perception and lead to enhanced performance. Stimulation strategies that best elicit frequency specific activity need to be identified. This research examined the characteristic frequency (CF) relationship between regions of the auditory cortex (AC), in response to stimulated regions of the inferior colliculus (IC), comparing monopolar, and intralaminar bipolar electrical stimulation. Approach. Electrical stimulation using multi-channel micro-electrode arrays in the IC was used to elicit AC responses in anaesthetized male hooded Wistar rats. The rate of activity in AC regions with CFs within 3 kHz (CF-aligned) and unaligned CFs was used to assess the frequency specificity of responses. Main results. Both monopolar and bipolar IC stimulation led to CF-aligned neural activity in the AC. Altering the distance between the stimulation and reference electrodes in the IC led to changes in both threshold and dynamic range, with bipolar stimulation with 400 µm spacing evoking the lowest AC threshold and widest dynamic range. At saturation, bipolar stimulation elicited a significantly higher mean spike count in the AC at CF-aligned areas than at CF-unaligned areas when electrode spacing was 400 µm or less. Bipolar stimulation using electrode spacing of 400 µm or less also elicited a higher rate of elicited activity in the AC in both CF-aligned and CF-unaligned regions than monopolar stimulation. When electrodes were spaced 600 µm apart no benefit over monopolar stimulation was observed. Furthermore, monopolar stimulation of the external cortex of the IC resulted in more localized frequency responses than bipolar stimulation when stimulation and reference sites were 200 µm apart. Significance. These findings have implications for the future development of AMI, as a bipolar stimulation strategy may improve the ability of implant users to discriminate between frequencies.

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.

Mechanisms of specificity in neuronal activity-regulated gene transcription

PubMed Central

Lyons, Michelle R.; West, Anne E.

2011-01-01

The brain is a highly adaptable organ that is capable of converting sensory information into changes in neuronal function. This plasticity allows behavior to be accommodated to the environment, providing an important evolutionary advantage. Neurons convert environmental stimuli into long-lasting changes in their physiology in part through the synaptic activity-regulated transcription of new gene products. Since the neurotransmitter-dependent regulation of Fos transcription was first discovered nearly 25 years ago, a wealth of studies have enriched our understanding of the molecular pathways that mediate activity-regulated changes in gene transcription. These findings show that a broad range of signaling pathways and transcriptional regulators can be engaged by neuronal activity to sculpt complex programs of stimulus-regulated gene transcription. However, the shear scope of the transcriptional pathways engaged by neuronal activity raises the question of how specificity in the nature of the transcriptional response is achieved in order to encode physiologically relevant responses to divergent stimuli. Here we summarize the general paradigms by which neuronal activity regulates transcription while focusing on the molecular mechanisms that confer differential stimulus-, cell-type-, and developmental-specificity upon activity-regulated programs of neuronal gene transcription. In addition, we preview some of the new technologies that will advance our future understanding of the mechanisms and consequences of activity-regulated gene transcription in the brain. PMID:21620929

Lymphocyte-conditioned medium in combination with interleukin-2 effectively induces antitumour autoimmunity by adoptive transfer of short activated killer (SHAK) cells.

PubMed

Buer, J; Hilse, R; Dallmann, I; Grosse, J; Kirchner, H; Zorn, U; Hänninen, E L; Franzke, A; Duensing, S; Poliwoda, H

1995-03-01

In this study, effective antitumour immunity was transferred by autologous short activated killer (SHAK) cells induced over four hours with lymphocyte conditioned medium (LCM) and recombinant interleukin-2 (rIL-2). Among eight patients with progressive metastatic renal cell carcinoma refractory to standard therapy, there were six objective tumour responses to SHAKs. Progression-free survival ranged from 0 to 8+ months, and overall survival ranged from 2 to 14+ months, with a median of 9+ months. Systemic toxicity of SHAKs was limited to flulike symptoms. Patient SHAKs provided a tumour-specific immunity, both cellular and humoral (expression and secretion of secondary cytokines, including IL-2, GM-CSF, INF-gamma and TNF-alpha), far superior to rIL-2 activated killer cells.

An activated form of ADAM10 is tumor selective and regulates cancer stem-like cells and tumor growth

PubMed Central

Saha, Nayanendu; Eissman, Moritz F.; Xu, Kai; Llerena, Carmen; Kusebauch, Ulrike; Ding, Bi-Sen; Cao, Zhongwei; Rafii, Shahin; Ernst, Matthias; Scott, Andrew M.; Nikolov, Dimitar B.; Lackmann, Martin

2016-01-01

The transmembrane metalloprotease ADAM10 sheds a range of cell surface proteins, including ligands and receptors of the Notch, Eph, and erbB families, thereby activating signaling pathways critical for tumor initiation and maintenance. ADAM10 is thus a promising therapeutic target. Although widely expressed, its activity is normally tightly regulated. We now report prevalence of an active form of ADAM10 in tumors compared with normal tissues, in mouse models and humans, identified by our conformation-specific antibody mAb 8C7. Structure/function experiments indicate mAb 8C7 binds an active conformation dependent on disulfide isomerization and oxidative conditions, common in tumors. Moreover, this active ADAM10 form marks cancer stem-like cells with active Notch signaling, known to mediate chemoresistance. Importantly, specific targeting of active ADAM10 with 8C7 inhibits Notch activity and tumor growth in mouse models, particularly regrowth after chemotherapy. Our results indicate targeted inhibition of active ADAM10 as a potential therapy for ADAM10-dependent tumor development and drug resistance. PMID:27503072

An activated form of ADAM10 is tumor selective and regulates cancer stem-like cells and tumor growth.

PubMed

Atapattu, Lakmali; Saha, Nayanendu; Chheang, Chanly; Eissman, Moritz F; Xu, Kai; Vail, Mary E; Hii, Linda; Llerena, Carmen; Liu, Zhanqi; Horvay, Katja; Abud, Helen E; Kusebauch, Ulrike; Moritz, Robert L; Ding, Bi-Sen; Cao, Zhongwei; Rafii, Shahin; Ernst, Matthias; Scott, Andrew M; Nikolov, Dimitar B; Lackmann, Martin; Janes, Peter W

2016-08-22

The transmembrane metalloprotease ADAM10 sheds a range of cell surface proteins, including ligands and receptors of the Notch, Eph, and erbB families, thereby activating signaling pathways critical for tumor initiation and maintenance. ADAM10 is thus a promising therapeutic target. Although widely expressed, its activity is normally tightly regulated. We now report prevalence of an active form of ADAM10 in tumors compared with normal tissues, in mouse models and humans, identified by our conformation-specific antibody mAb 8C7. Structure/function experiments indicate mAb 8C7 binds an active conformation dependent on disulfide isomerization and oxidative conditions, common in tumors. Moreover, this active ADAM10 form marks cancer stem-like cells with active Notch signaling, known to mediate chemoresistance. Importantly, specific targeting of active ADAM10 with 8C7 inhibits Notch activity and tumor growth in mouse models, particularly regrowth after chemotherapy. Our results indicate targeted inhibition of active ADAM10 as a potential therapy for ADAM10-dependent tumor development and drug resistance. © 2016 Atapattu et al.

MOLECULAR EPIDEMIOLOGY: POTENTIAL IMPACTS ON THE ASSESSMENT OF PUBLIC HEALTH

EPA Science Inventory

Introduction

The term "molecular epidemiology" has been used to cover a broad range of scientific activities, often without specific reference to epidemiology. In fact, as noted by Foxman and Riley [1],molecular epidemiology has often been described almost exclusively in...

45 CFR 1614.3 - Range of activities.

Code of Federal Regulations, 2010 CFR

2010-10-01

... legal research systems or other resources. (c) The specific methods to be undertaken by a recipient to... bono basis through the provision of community legal education, training, technical assistance, research..., computer-assisted legal research systems or other resources; and (2) Support provided by the recipient in...

Geochemistry of uranium and thorium and natural radioactivity levels of the western Anatolian plutons, Turkey

NASA Astrophysics Data System (ADS)

Papadopoulos, Argyrios; Altunkaynak, Şafak; Koroneos, Antonios; Ünal, Alp; Kamaci, Ömer

2017-10-01

Seventy samples from major plutons (mainly granitic) of Western Anatolia (Turkey) have been analyzed by γ-ray spectrometry to determine the specific activities of 238U, 226Ra, 232Th and 40K (Bq/kg). Τhe natural radioactivity ranged up to 264 Bq/kg for 238U, 229.62 Bq/kg for 226Ra, up to 207.32 Bq/kg for 232Th and up to 2541.95 Bq/kg for 40K. Any possible relationship between the specific activities of 226Ra, 238U, 232Th and 40K and some characteristics of the studied samples (age, rock-type, colour, grain size, occurrence, chemical and mineralogical composition) was investigated. Age, major and trace element geochemistry, color, pluton location and mineralogical composition are likely to affect the concentrations of the measured radionuclides. The range of the Th/U ratio was large (0.003-11.374). The latter, along with 226Ra/238U radioactive secular disequilibrium, is also discussed and explained by magmatic processes during differentiation.

Selective Impairment in Frequency Discrimination in a Mouse Model of Tinnitus

PubMed Central

Mwilambwe-Tshilobo, Laetitia; Davis, Andrew J. O.; Aizenberg, Mark; Geffen, Maria N.

2015-01-01

Tinnitus is an auditory disorder, which affects millions of Americans, including active duty service members and veterans. It is manifested by a phantom sound that is commonly restricted to a specific frequency range. Because tinnitus is associated with hearing deficits, understanding how tinnitus affects hearing perception is important for guiding therapies to improve the quality of life in this vast group of patients. In a rodent model of tinnitus, prolonged exposure to a tone leads to a selective decrease in gap detection in specific frequency bands. However, whether and how hearing acuity is affected for sounds within and outside those frequency bands is not well understood. We induced tinnitus in mice by prolonged exposure to a loud mid-range tone, and behaviorally assayed whether mice exhibited a change in frequency discrimination acuity for tones embedded within the mid-frequency range and high-frequency range at 1, 4, and 8 weeks post-exposure. A subset of tone-exposed mice exhibited tinnitus-like symptoms, as demonstrated by selective deficits in gap detection, which were restricted to the high frequency range. These mice exhibited impaired frequency discrimination both for tones in the mid-frequency range and high-frequency range. The remaining tone exposed mice, which did not demonstrate behavioral evidence of tinnitus, showed temporary deficits in frequency discrimination for tones in the mid-frequency range, while control mice remained unimpaired. Our findings reveal that the high frequency-specific deficits in gap detection, indicative of tinnitus, are associated with impairments in frequency discrimination at the frequency of the presumed tinnitus. PMID:26352864

Dipole source localization of event-related brain activity indicative of an early visual selective attention deficit in ADHD children.

PubMed

Jonkman, L M; Kenemans, J L; Kemner, C; Verbaten, M N; van Engeland, H

2004-07-01

This study was aimed at investigating whether attention-deficit hyperactivity disorder (ADHD) children suffer from specific early selective attention deficits in the visual modality with the aid of event-related brain potentials (ERPs). Furthermore, brain source localization was applied to identify brain areas underlying possible deficits in selective visual processing in ADHD children. A two-channel visual color selection task was administered to 18 ADHD and 18 control subjects in the age range of 7-13 years and ERP activity was derived from 30 electrodes. ADHD children exhibited lower perceptual sensitivity scores resulting in poorer target selection. The ERP data suggested an early selective-attention deficit as manifested in smaller frontal positive activity (frontal selection positivity; FSP) in ADHD children around 200 ms whereas later occipital and fronto-central negative activity (OSN and N2b; 200-400 ms latency) appeared to be unaffected. Source localization explained the FSP by posterior-medial equivalent dipoles in control subjects, which may reflect the contribution of numerous surrounding areas. ADHD children have problems with selective visual processing that might be caused by a specific early filtering deficit (absent FSP) occurring around 200 ms. The neural sources underlying these problems have to be further identified. Source localization also suggested abnormalities in the 200-400 ms time range, pertaining to the distribution of attention-modulated activity in lateral frontal areas.

The impact of Dupuytren disease on patient activity and quality of life.

PubMed

Wilburn, J; McKenna, S P; Perry-Hinsley, D; Bayat, A

2013-06-01

To explore the impact of Dupuytren disease (DD) from the patients' perspective. Audio-recorded interviews were conducted for patients with Dupuytren disease (DD) attending outpatient clinics. The interviews were transcribed and subjected to content analysis. This analysis highlighted key impact areas and common themes in individuals' personal experiences. These were then allocated to categories specified by the World Health Organization International Classification of Functioning, Disability, and Health (impairments and activity limitations) and the needs-based model of quality of life (QoL). Qualitative unstructured interviews were conducted with 34 patients (74% men; age, 41-80 y; mean [SD], 64 [13] y). The sample had a wide range of severity and duration of DD (range, 0.5-40; mean [SD], 13 [10] y). Nine hundred fifty-three statements relating to the impact of DD were identified from the interview transcripts. These statements fell into 2 major categories of impact: activity limitations (10 themes including problems with dressing, gripping, and personal care) and QoL (6 need categories: physiological, safety and security, social, affection, esteem, and cognitive needs). Findings from the interviews suggest that DD affects both performance of activities and QoL. To determine accurately the effectiveness of DD interventions from the patients' perspective, it is important to determine their impacts on both activity limitations and QoL. We intend to develop valid, reproducible, and responsive DD-specific scales for this purpose. The study identifies key issues specific to DD that influence patients' functioning and QoL. The information reported will form the basis of DD-specific patient-reported outcomes measures for use in clinical practice and evaluations of interventions. Copyright © 2013 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

The purification and characterisation of novel dipeptidyl peptidase IV-like activity from bovine serum.

PubMed

Buckley, Seamus J; Collins, Patrick J; O'Connor, Brendan F

2004-07-01

The discovery of a potentially novel proline-specific peptidase from bovine serum is presented which is capable of cleaving the dipeptidyl peptidase IV (DPIV) substrate Gly-Pro-MCA. The enzyme was isolated and purified with the use of Phenyl Sepharose Hydrophobic Interaction, Sephacryl S-300 Gel Filtration, and Q-Sephacryl Anion Exchange, producing an overall purification factor of 257. SDS PAGE resulted in a monomeric molecular mass of 158kDa while size exclusion chromatography generated a native molecular mass of 328kDa. The enzyme remained active over a broad pH range with a distinct preference for a neutral pH range of 7-8.5. Chromatofocusing and isoelectric focusing (IEF) revealed the enzyme's isoelectric point to be 4.74. DPIV-like activity was not inhibited by serine protease inhibitors but was by the metallo-protease inhibitors, the phenanthrolines. The enzyme was also partially inhibited by bestatin. Substrate specificity studies proved that the enzyme is capable of sequential cleavage of bovine beta-Casomorphin and Substance P. The peptidase cleaved the standard DPIV substrate, Gly-Pro-MCA with a K(M) of 38.4 microM, while Lys-Pro-MCA was hydrolysed with a K(M) of 103 microM. The DPIV-like activity was specifically inhibited by both Diprotin A and B, non-competitively, generating a K(i) of 1.4 x 10(-4) M for both inhibitors. Ile-Thiazolidide and Ile-Pyrrolidide both inhibited competitively with an inhibition constant of 3.7 x 10(-7) and 7.5 x 10(-7) M, respectively. It is concluded that bovine serum DPIV-like activity share many biochemical properties with DPIV and DPIV-like enzymes but not exclusively, suggesting that the purified peptidase may play an important novel role in bioactive oligopeptide degradation.

Theta dynamics reveal domain-specific control over stimulus and response conflict.

PubMed

Nigbur, Roland; Cohen, Michael X; Ridderinkhof, K Richard; Stürmer, Birgit

2012-05-01

Cognitive control allows us to adjust to environmental changes. The medial frontal cortex (MFC) is thought to detect conflicts and recruit additional resources from other brain areas including the lateral prefrontal cortices. Here we investigated how the MFC acts in concert with visual, motor, and lateral prefrontal cortices to support adaptations of goal-directed behavior. Physiologically, these interactions may occur through local and long-range synchronized oscillation dynamics, particularly in the theta range (4-8 Hz). A speeded flanker task allowed us to investigate conflict-type-specific control networks for perceptual and response conflicts. Theta power over MFC was sensitive to both perceptual and response conflict. Interareal theta phase synchrony, however, indicated a selective enhancement specific for response conflicts between MFC and left frontal cortex as well as between MFC and the presumed motor cortex contralateral to the response hand. These findings suggest that MFC theta-band activity is both generally involved in conflict processing and specifically involved in linking a neural network controlling response conflict.

Genomic characterization of Ralstonia solanacearum phage phiRSB1, a T7-like wide-host-range phage.

PubMed

Kawasaki, Takeru; Shimizu, Mio; Satsuma, Hideki; Fujiwara, Akiko; Fujie, Makoto; Usami, Shoji; Yamada, Takashi

2009-01-01

PhiRSB1 is a wide-host-range, T7-like bacteriophage that infects and efficiently lyses the phytopathogenic bacterium Ralstonia solanacearum. The phiRSB1 genome comprises 43,079 bp of double-stranded DNA (61.7% G+C) with 325-bp terminal repeats and contains 47 open reading frames. Strong activity of tandem early promoters and wide specificity of phage promoters of phiRSB1 were demonstrated.

A sensitive electrochemical biosensor for detection of protein kinase A activity and inhibitors based on Phos-tag and enzymatic signal amplification.

PubMed

Yin, Huanshun; Wang, Mo; Li, Bingchen; Yang, Zhiqing; Zhou, Yunlei; Ai, Shiyun

2015-01-15

A simple, highly sensitive and selective electrochemical assay is developed for the detection of protein kinase A (PKA) activity based on the specific recognition utility of Phos-tag for kinase-induced phosphopeptides and enzymatic signal amplification. When the substrate peptide was phosphorylated by PKA reaction, they could specifically bind with Phos-tag-biotin in the presence of Zn(2+) through the formation of a specific noncovalent complex with the phosphomonoester dianion in phosphorylated peptides. Through the further specific interaction between biotin and avidin, avidin functionalized horseradish peroxidase (HRP) can be captured on the electrode surface. Under the catalytic effect of HRP, a sensitive electrochemical signal for benzoquinone was obtained, which was related to PKA activity. Under the optimal experiment conditions, the proposed electrochemical method presented dynamic range from 0.5 to 25 unit/mL with low detection limit of 0.15 unit/mL. This new detection strategy was also successfully applied to analyze the inhibition effect of inhibitors (ellagic acid and H-89) on PKA activity and monitored the PKA activity in cell lysates. Therefore, this Phos-tag-based electrochemical assay offers an alternative platform for PKA activity assay and inhibitor screening, and thus it might be a valuable tool for development of targeted therapy and clinical diagnosis. Copyright © 2014 Elsevier B.V. All rights reserved.

Layer-specific optogenetic activation of pyramidal neurons causes beta–gamma entrainment of neonatal networks

PubMed Central

Bitzenhofer, Sebastian H; Ahlbeck, Joachim; Wolff, Amy; Wiegert, J. Simon; Gee, Christine E.; Oertner, Thomas G.; Hanganu-Opatz, Ileana L.

2017-01-01

Coordinated activity patterns in the developing brain may contribute to the wiring of neuronal circuits underlying future behavioural requirements. However, causal evidence for this hypothesis has been difficult to obtain owing to the absence of tools for selective manipulation of oscillations during early development. We established a protocol that combines optogenetics with electrophysiological recordings from neonatal mice in vivo to elucidate the substrate of early network oscillations in the prefrontal cortex. We show that light-induced activation of layer II/III pyramidal neurons that are transfected by in utero electroporation with a high-efficiency channelrhodopsin drives frequency-specific spiking and boosts network oscillations within beta–gamma frequency range. By contrast, activation of layer V/VI pyramidal neurons causes nonspecific network activation. Thus, entrainment of neonatal prefrontal networks in fast rhythms relies on the activation of layer II/III pyramidal neurons. This approach used here may be useful for further interrogation of developing circuits, and their behavioural readout. PMID:28216627

Discovery of core-structurally novel PTP1B inhibitors with specific selectivity containing oxindole-fused spirotetrahydrofurochroman by one-pot reaction.

PubMed

Dong, Suzhen; Lei, Yubing; Jia, Shikun; Gao, Lixin; Li, Jia; Zhu, Tong; Liu, Shunying; Hu, Wenhao

2017-02-15

Protein tyrosine phosphatase 1B (PTP1B) has been proposed to be an ideal target for treatment of type II diabetes and obesity. However, no druggable PTP1B inhibitor has been established and there is still an urgent demand for the development of structurally novel PTPIB inhibitor. Herein, we reported core-structurally novel PTP1B inhibitors with low micromole-ranged inhibitory activity by one-pot reaction from simple starting materials. Further studies demonstrated some of these active compounds had a specific selectivity over other PTPs. The structure and activity relationship was also described. The best active and selective compound 5e inhibited PTP1B activity with an IC 50 of 4.53μM. Molecular docking analysis further demonstrated that compound 5e bound to the active pocket of PTP1B. The results might provide some insights for further development of new drugs for type II diabetes and obesity. Copyright © 2016 Elsevier Ltd. All rights reserved.

Consolidated fuel reprocessing program

NASA Astrophysics Data System (ADS)

1985-02-01

Improved processes and components for the Breeder Reprocessing Engineering Test (BRET) were identified and developed as well as the design, procurement and development of prototypic equipment. The integrated testing of process equipment and flowsheets prototypical of a pilot scale full reprocessing plant, and also for testing prototypical remote features of specific complex components in the system are provided. Information to guide the long range activities of the Consolidated Fuel Reprocessing Program (CERP), a focal point for foreign exchange activities, and support in specialized technical areas are described. Research and development activities in HTGR fuel treatment technology are being conducted. Head-end process and laboratory scale development efforts, as well as studies specific to HTGR fuel, are reported. The development of off-gas treatment processes has generic application to fuel reprocessing, progress in this work is also reported.

Neuronal and Cardiovascular Potassium Channels as Therapeutic Drug Targets

PubMed Central

Humphries, Edward S. A.

2015-01-01

Potassium (K+) channels, with their diversity, often tissue-defined distribution, and critical role in controlling cellular excitability, have long held promise of being important drug targets for the treatment of dysrhythmias in the heart and abnormal neuronal activity within the brain. With the exception of drugs that target one particular class, ATP-sensitive K+ (KATP) channels, very few selective K+ channel activators or inhibitors are currently licensed for clinical use in cardiovascular and neurological disease. Here we review what a range of human genetic disorders have told us about the role of specific K+ channel subunits, explore the potential of activators and inhibitors of specific channel populations as a therapeutic strategy, and discuss possible reasons for the difficulty in designing clinically relevant K+ channel modulators. PMID:26303307

Outcomes of hip resurfacing in a professional dancer: a case report.

PubMed

Dunleavy, Kim

2012-02-01

A new surgical option (hip resurfacing arthroplasty) is now available for younger patients with hip osteoarthritis. A more aggressive rehabilitation program than the typical total hip arthroplasty protocol is needed for active individuals. This case report describes interventions used to maximize function in a 46-year-old professional dancer after hip resurfacing with a progressive therapeutic exercise program. Exercise choices were selected to address dance-specific requirements while respecting healing of the posterior capsular incision. Strengthening focused on hip abduction, extension, and external rotation. Precautions included avoiding gluteal stretching until 6 months. Pelvic alignment and weight-bearing distribution were emphasized. The patient was able to return to rehearsal by 7 months, at which time strength was equivalent to the unaffected leg. Range of motion reached unaffected side values at week 8 for internal rotation, week 11 for extension, week 13 for adduction, and week 28 for flexion. External rotation and abduction were still limited at 1 year, which influenced pelvic alignment with resultant pain on the unaffected side. Functional and impairment outcomes are presented with timelines to provide a basis for postoperative benchmarks for active clients after hip resurfacing. Although this case report presents a dance-specific program, exercise progressions for other active individuals may benefit from similar exercise intensity and sports-specific focus. Future rehabilitation programs should take into account possible flexion and external rotation range limitations and the need for gluteal muscle strengthening along with symmetry and pelvic alignment correction. Long-term studies investigating intensity of rehabilitation are warranted for patients intending to participate in higher level athletic activity.

Which Factors Can Protect Against Range Stress in Everyday Usage of Battery Electric Vehicles? Toward Enhancing Sustainability of Electric Mobility Systems.

PubMed

Franke, Thomas; Rauh, Nadine; Günther, Madlen; Trantow, Maria; Krems, Josef F

2016-02-01

The objective of the present research was to advance understanding of factors that can protect against range anxiety, specifically range stress in everyday usage of battery electric vehicles (BEVs). Range anxiety is a major barrier to the broad adoption of sustainable electric mobility systems. To develop strategies aimed at overcoming range anxiety, a clear understanding of this phenomenon and influencing factors is needed. We examined range anxiety in the form of everyday range stress (ERS) in a field study setting. Seventy-two customers leased a BEV for 3 months. The field study was specifically designed to enable examination of factors that can contribute to lower ERS. In particular, study design and sample recruitment were targeted at generating vehicle usage profiles that would lead to relatively frequent experience of situations requiring active management of range resources and thereby potentially leading to experienced range stress. Less frequent encounter with critical range situations, higher practical experience, subjective range competence, tolerance of low range, and experienced trustworthiness of the range estimation system were related to lower ERS. Moreover, range stress was found to be related to range satisfaction and BEV acceptance. The results underline the importance of the human factors perspective to overcome range anxiety and enhance sustainability of electric mobility systems. Trustworthiness should be employed as a key benchmark variable in the design of range estimation systems, and assistance systems should target increasing drivers' adaptive capacity (i.e., resilience) to cope with critical range situations. © 2015, Human Factors and Ergonomics Society.

Influence of footwear and equipment on stride length and range of motion of ankle, knee and hip joint.

PubMed

Schulze, Christoph; Lindner, Tobias; Woitge, Sandra; Schulz, Katharina; Finze, Susanne; Mittelmeier, Wolfram; Bader, Rainer

2014-01-01

Footwear and equipment worn by military personnel is of importance for them to be able to meet the physical demands specific to their profession daily activities. The aim of the present study was to investigate by means of gait analysis how army-provided footwear and equipment influence the range of motion of hip, knee and ankle joints as well as stride length. Thirty-two soldiers were subjected to gait analysis on a treadmill by way of video recordings and goniometric measurements. The stride length increased when military shoes are worn. We found no influence on stride length in connection to increased loading. The weight of the shoes represents the decisive factor. Neither shoes nor equipment changed the range of motion of the knee joint. Weight of equipment affected range of motion of the hip joint. The range of motion of the upper and lower ankle joints was mainly influenced by the properties of the shoes. Military footwear and weight of equipment influence stride length and range of motion of joints of the lower extremities in a specific way. Shape of material is the decisive factor.

Different mechanisms for Arabidopsis thaliana hybrid necrosis cases inferred from temperature responses.

PubMed

Muralidharan, S; Box, M S; Sedivy, E L; Wigge, P A; Weigel, D; Rowan, B A

2014-11-01

Temperature is a major determinant of plant growth, development and success. Understanding how plants respond to temperature is particularly relevant in a warming climate. Plant immune responses are often suppressed above species-specific critical temperatures. This is also true for intraspecific hybrids of Arabidopsis thaliana that express hybrid necrosis due to inappropriate activation of the immune system caused by epistatic interactions between alleles from different genomes. The relationship between temperature and defence is unclear, largely due to a lack of studies that assess immune activation over a wide range of temperatures. To test whether the temperature-based suppression of ectopic immune activation in hybrids exhibits a linear or non-linear relationship, we characterised the molecular and morphological phenotypes of two different necrotic A. thaliana hybrids over a range of ecologically relevant temperatures. We found both linear and non-linear responses for expression of immunity markers and for morphological defects depending on the underlying genetic cause. This suggests that the influence of temperature on the trade-off between immunity and growth depends on the specific defence components involved. © 2014 German Botanical Society and The Royal Botanical Society of the Netherlands.

Statistical Model of Dynamic Markers of the Alzheimer's Pathological Cascade.

PubMed

Balsis, Steve; Geraci, Lisa; Benge, Jared; Lowe, Deborah A; Choudhury, Tabina K; Tirso, Robert; Doody, Rachelle S

2018-05-05

Alzheimer's disease (AD) is a progressive disease reflected in markers across assessment modalities, including neuroimaging, cognitive testing, and evaluation of adaptive function. Identifying a single continuum of decline across assessment modalities in a single sample is statistically challenging because of the multivariate nature of the data. To address this challenge, we implemented advanced statistical analyses designed specifically to model complex data across a single continuum. We analyzed data from the Alzheimer's Disease Neuroimaging Initiative (ADNI; N = 1,056), focusing on indicators from the assessments of magnetic resonance imaging (MRI) volume, fluorodeoxyglucose positron emission tomography (FDG-PET) metabolic activity, cognitive performance, and adaptive function. Item response theory was used to identify the continuum of decline. Then, through a process of statistical scaling, indicators across all modalities were linked to that continuum and analyzed. Findings revealed that measures of MRI volume, FDG-PET metabolic activity, and adaptive function added measurement precision beyond that provided by cognitive measures, particularly in the relatively mild range of disease severity. More specifically, MRI volume, and FDG-PET metabolic activity become compromised in the very mild range of severity, followed by cognitive performance and finally adaptive function. Our statistically derived models of the AD pathological cascade are consistent with existing theoretical models.

Extending enzyme molecular recognition with an expanded amino acid alphabet

PubMed Central

Windle, Claire L.; Simmons, Katie J.; Ault, James R.; Trinh, Chi H.; Nelson, Adam

2017-01-01

Natural enzymes are constructed from the 20 proteogenic amino acids, which may then require posttranslational modification or the recruitment of coenzymes or metal ions to achieve catalytic function. Here, we demonstrate that expansion of the alphabet of amino acids can also enable the properties of enzymes to be extended. A chemical mutagenesis strategy allowed a wide range of noncanonical amino acids to be systematically incorporated throughout an active site to alter enzymic substrate specificity. Specifically, 13 different noncanonical side chains were incorporated at 12 different positions within the active site of N-acetylneuraminic acid lyase (NAL), and the resulting chemically modified enzymes were screened for activity with a range of aldehyde substrates. A modified enzyme containing a 2,3-dihydroxypropyl cysteine at position 190 was identified that had significantly increased activity for the aldol reaction of erythrose with pyruvate compared with the wild-type enzyme. Kinetic investigation of a saturation library of the canonical amino acids at the same position showed that this increased activity was not achievable with any of the 20 proteogenic amino acids. Structural and modeling studies revealed that the unique shape and functionality of the noncanonical side chain enabled the active site to be remodeled to enable more efficient stabilization of the transition state of the reaction. The ability to exploit an expanded amino acid alphabet can thus heighten the ambitions of protein engineers wishing to develop enzymes with new catalytic properties. PMID:28196894

Synthesis of iron based hydrocracking catalysts

DOEpatents

Farcasiu, Malvina; Eldredge, Patricia A.; Ladner, Edward P.

1993-01-01

A method of preparing a fine particle iron based hydrocracking catalyst and the catalyst prepared thereby. An iron (III) oxide powder and elemental sulfur are reacted with a liquid hydrogen donor having a hydroaromatic structure present in the range of from about 5 to about 50 times the weight of iron (III) oxide at a temperature in the range of from about 180.degree. C. to about 240.degree. C. for a time in the range of from about 0 to about 8 hours. Various specific hydrogen donors are disclosed. The catalysts are active at low temperature (<350.degree. C.) and low pressure.

Mycobacterium tuberculosis Lipolytic Enzymes as Potential Biomarkers for the Diagnosis of Active Tuberculosis

PubMed Central

Brust, Belinda; Lecoufle, Mélanie; Tuaillon, Edouard; Dedieu, Luc; Canaan, Stéphane; Valverde, Viviane; Kremer, Laurent

2011-01-01

Background New diagnosis tests are urgently needed to address the global tuberculosis (TB) burden and to improve control programs especially in resource-limited settings. An effective in vitro diagnostic of TB based on serological methods would be regarded as an attractive progress because immunoassays are simple, rapid, inexpensive, and may offer the possibility to detect cases missed by standard sputum smear microscopy. However, currently available serology tests for TB are highly variable in sensitivity and specificity. Lipolytic enzymes have recently emerged as key factors in lipid metabolization during dormancy and/or exit of the non-replicating growth phase, a prerequisite step of TB reactivation. The focus of this study was to analyze and compare the potential of four Mycobacterium tuberculosis lipolytic enzymes (LipY, Rv0183, Rv1984c and Rv3452) as new markers in the serodiagnosis of active TB. Methods Recombinant proteins were produced and used in optimized ELISA aimed to detect IgG and IgM serum antibodies against the four lipolytic enzymes. The capacity of the assays to identify infection was evaluated in patients with either active TB or latent TB and compared with two distinct control groups consisting of BCG-vaccinated blood donors and hospitalized non-TB individuals. Results A robust humoral response was detected in patients with active TB whereas antibodies against lipolytic enzymes were infrequently detected in either uninfected groups or in subjects with latent infection. High specifity levels, ranging from 93.9% to 97.5%, were obtained for all four antigens with sensitivity values ranging from 73.4% to 90.5%, with Rv3452 displaying the highest performances. Patients with active TB usually exhibited strong IgG responses but poor IgM responses. Conclusion These results clearly indicate that the lipolytic enzymes tested are strongly immunogenic allowing to distinguish active from latent TB infections. They appear as potent biomarkers providing high sensitivity and specificity levels for the immunodiagnosis of active TB. PMID:21966416

Contributions of non-occupational activities to total noise exposure of construction workers.

PubMed

Neitzel, Richard; Seixas, Noah; Goldman, Bryan; Daniell, William

2004-07-01

This paper describes how exposures received during routine and episodic non-occupational activities contribute to total noise exposure in a group of occupationally exposed workers. Two-hundred and sixty-six construction apprentices enrolled in a longitudinal hearing loss study and completed questionnaires at 1 yr of follow-up to determine their episodic activities (e.g. concert attendance, power tool use, firearms exposure). Noise exposure levels for these episodic exposures were determined from the published literature. Routine activities were assessed using activity cards filled out over 530 subject-days, along with noise dosimetry measurements made over 124 subject-days of measurement. Equivalent Leq exposure levels were then calculated for specific activities. These activity-specific Leq values were combined into estimated individual annual Leq exposure levels for the 6760 nominal annual non-occupational hours in a year (LAeq6760h), which were then transformed into equivalent levels for a 2000 h exposure period (LA2000hn) for comparison with occupational noise exposure risk criteria. The mean non-occupational LAeq6760h exposure values for the cohort ranged from 56 to 87 dBA (equivalent LA2000hn 62-93 dBA). At the mid range of the routine and episodic activity exposure level distribution, the mean LAeq6760h was 73 dBA (LA2000hn 78 dBA). Nineteen percent of the LA2000hn non-occupational exposures exceeded 85 dBA, the generally recommended occupational limit for a 2000 h workyear, at the mid-range of exposure levels. Due to a lack of available data, firearms use could not be incorporated into the total noise exposure estimates. However, firearms users reported more exposure to other noisy non-occupational activities and had statistically significantly higher estimated exposure levels even without including their firearms exposure than did non-shooters. When compared with the high levels of occupational noise found in construction, non-occupational noise exposures generally present little additional exposure for most workers. However, they may contribute significantly to overall exposure in the subset of workers who frequently participate in selected noisy activities.

RE-DEFINING THE ROLES OF SENSORS IN OBJECTIVE PHYSICAL ACTIVITY MONITORING

PubMed Central

Chen, Kong Y.; Janz, Kathleen F.; Zhu, Weimo; Brychta, Robert J.

2011-01-01

Background As physical activity researchers are increasingly using objective portable devices, this review describes current state of the technology to assess physical activity, with a focus on specific sensors and sensor properties currently used in monitors and their strengths and weakness. Additional sensors and sensor properties desirable for activity measurement and best practices for users and developers also are discussed. Best Practices We grouped current sensors into three broad categories for objectively measuring physical activity: associated body movement, physiology, and context. Desirable sensor properties for measuring physical activity and the importance of these properties in relationship to specific applications are addressed, and the specific roles of transducers and data acquisition systems within the monitoring devices are defined. Technical advancements in sensors, microcomputer processors, memory storage, batteries, wireless communication, and digital filters have made monitors more usable for subjects (smaller, more stable, and longer running time) and for researchers (less costly, higher time resolution and memory storage, shorter download time, and user-defined data features). Future Directions Users and developers of physical activity monitors should learn about the basic properties of their sensors, such as range, accuracy, precision, while considering the data acquisition/filtering steps that may be critical to data quality and may influence the desirable measurement outcome(s). PMID:22157770

Electrophysiological characteristics of task-specific tremor in 22 instrumentalists.

PubMed

Lee, André; Tominaga, Kenta; Furuya, Shinichi; Miyazaki, Fumio; Altenmüller, Eckart

2015-03-01

Our aim was to address three characteristics of task-specific tremor in musicians (TSTM): First, we quantified muscular activity of flexor and extensor muscles, of coactivation as well as tremor acceleration. Second, we compared muscular activity between task-dependent and position-dependent tremor. Third, we investigated, whether there is an overflow of muscular activity to muscles adjacent to the affected muscles in TSTM. Tremor acceleration and muscular activity were measured in the affected muscles and the muscles adjacent to the affected muscles in 22 patients aged 51.5 ± 11.4 years with a task-specific tremor. We assessed power of muscular oscillatory activity and calculated the coherence between EMG activity of affected muscles and tremor acceleration as well as between adjacent muscles and tremor acceleration. This was done for task-dependent and position-dependent tremor. We found the highest power and coherence of muscular oscillatory activity in the frequency range of 3-8 Hz for affected and adjacent muscles. No difference was found between task-dependent and position-dependent tremor in neither power nor coherence measures. Our results generalize previous results of a relation between coactivation and tremor among a variety of musicians. Furthermore, we found coherence of adjacent muscles and TSTM. This indicates that overflow exists in TSTM and suggests an association of TST with dystonia.

The regulatory mechanism of fungal elicitor-induced secondary metabolite biosynthesis in medical plants.

PubMed

Zhai, Xin; Jia, Min; Chen, Ling; Zheng, Cheng-Jian; Rahman, Khalid; Han, Ting; Qin, Lu-Ping

2017-03-01

A wide range of external stress stimuli trigger plant cells to undergo complex network of reactions that ultimately lead to the synthesis and accumulation of secondary metabolites. Accumulation of such metabolites often occurs in plants subjected to stresses including various elicitors or signal molecules. Throughout evolution, endophytic fungi, an important constituent in the environment of medicinal plants, have known to form long-term stable and mutually beneficial symbiosis with medicinal plants. The endophytic fungal elicitor can rapidly and specifically induce the expression of specific genes in medicinal plants which can result in the activation of a series of specific secondary metabolic pathways resulting in the significant accumulation of active ingredients. Here we summarize the progress made on the mechanisms of fungal elicitor including elicitor signal recognition, signal transduction, gene expression and activation of the key enzymes and its application. This review provides guidance on studies which may be conducted to promote the efficient synthesis and accumulation of active ingredients by the endogenous fungal elicitor in medicinal plant cells, and provides new ideas and methods of studying the regulation of secondary metabolism in medicinal plants.

Digital micromirror based near-infrared illumination system for plasmonic photothermal neuromodulation.

PubMed

Jung, Hyunjun; Kang, Hongki; Nam, Yoonkey

2017-06-01

Light-mediated neuromodulation techniques provide great advantages to investigate neuroscience due to its high spatial and temporal resolution. To generate a spatial pattern of neural activity, it is necessary to develop a system for patterned-light illumination to a specific area. Digital micromirror device (DMD) based patterned illumination system have been used for neuromodulation due to its simple configuration and design flexibility. In this paper, we developed a patterned near-infrared (NIR) illumination system for region specific photothermal manipulation of neural activity using NIR-sensitive plasmonic gold nanorods (GNRs). The proposed system had high power transmission efficiency for delivering power density up to 19 W/mm 2 . We used a GNR-coated microelectrode array (MEA) to perform biological experiments using E18 rat hippocampal neurons and showed that it was possible to inhibit neural spiking activity of specific area in neural circuits with the patterned NIR illumination. This patterned NIR illumination system can serve as a promising neuromodulation tool to investigate neuroscience in a wide range of physiological and clinical applications.

Characterization of a bacterial tannase from Streptococcus gallolyticus UCN34 suitable for tannin biodegradation.

PubMed

Jiménez, Natalia; Barcenilla, José María; de Felipe, Félix López; de Las Rivas, Blanca; Muñoz, Rosario

2014-01-01

The gene in the locus GALLO_1609 from Streptococcus gallolyticus UCN34 was cloned and expressed as an active protein in Escherichia coli BL21 (DE3). The protein was named TanSg1 since it shows similarity to bacterial tannases previously described. The recombinant strain produced His-tagged TanSg1 which was purified by affinity chromatography. Purified TanSg1 protein showed tannase activity, having a specific activity of 577 U/mg which is 41 % higher than the activity of Lactobacillus plantarum tannase. Remarkably, TanSg1 displayed optimum catalytic activity at pH 6-8 and 50-70 °C and showed high stability over a broad range of temperatures. It retained 25 % of its relative activity after prolonged incubation at 45 °C. The specific activity of TanSg1 is enhanced by the divalent cation Ca(2+) and is dramatically reduced by Zn(2+) and Hg(2+). The enzyme was highly specific for gallate and protocatechuate esters and showed no catalytic activity against other phenolic esters. The protein TanSg1 hydrolyzes efficiently tannic acid, a complex and polymeric gallotanin, allowing its complete conversion to gallic acid, a potent antioxidant. From its biochemical properties, TanSg1 is a tannase with potential industrial interest regarding the biodegradation of tannin waste or its bioconversion into biologically active products.

Site-Specific RNase A Activity Was Dramatically Reduced in Serum from Multiple Types of Cancer Patients

PubMed Central

Huang, Weiyan; Zhao, Mei; Wei, Na; Wang, Xiaoxia; Cao, Huqing; Du, Quan; Liang, Zicai

2014-01-01

Potent RNase activities were found in the serum of mammals but the physiological function of the RNases was never well illustrated, largely due to the caveats in methods of RNase activity measurement. None of the existing methods can distinguish between RNases with different target specificities. A systematic study was recently carried out in our lab to investigate the site-specificity of serum RNases on double-stranded RNA substrates, and found that serum RNases cleave double-stranded RNAs predominantly at 5′-U/A-3′ and 5′-C/A-3′ dinucleotide sites, in a manner closely resembling RNase A. Based on this finding, a FRET assay was developed in the current study to measure this site-specific serum RNase activity in human samples using a double stranded RNA substrate. We demonstrated that the method has a dynamic range of 10−5 mg/ml- 10−1 mg/ml using serial dilution of RNase A. The sera of 303 cancer patients were subjected to comparison with 128 healthy controls, and it was found that serum RNase activities visualized with this site-specific double stranded probe were found to be significantly reduced in patients with gastric cancer, liver cancer, pancreatic cancer, esophageal cancer, ovary cancer, cervical cancer, bladder cancer, kidney cancer and lung cancer, while only minor changes were found in breast and colon cancer patients. This is the first report using double stranded RNA as probe to quantify site-specific activities of RNase A in a serum. The results illustrated that RNase A might be further evaluated to determine if it can serve as a new class of biomarkers for certain cancer types. PMID:24805924

Cytochrome c oxidase loses catalytic activity and structural integrity during the aging process in Drosophila melanogaster

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

Ren, Jian-Ching; Rebrin, Igor; Klichko, Vladimir

2010-10-08

Research highlights: {yields} Cytochrome c oxidase loses catalytic activity during the aging process. {yields} Abundance of seven nuclear-encoded subunits of cytochrome c oxidase decreased with age in Drosophila. {yields} Cytochrome c oxidase is specific intra-mitochondrial site of age-related deterioration. -- Abstract: The hypothesis, that structural deterioration of cytochrome c oxidase (CcO) is a causal factor in the age-related decline in mitochondrial respiratory activity and an increase in H{sub 2}O{sub 2} generation, was tested in Drosophila melanogaster. CcO activity and the levels of seven different nuclear DNA-encoded CcO subunits were determined at three different stages of adult life, namely, young-, middle-,more » and old-age. CcO activity declined progressively with age by 33%. Western blot analysis, using antibodies specific to Drosophila CcO subunits IV, Va, Vb, VIb, VIc, VIIc, and VIII, indicated that the abundance these polypeptides decreased, ranging from 11% to 40%, during aging. These and previous results suggest that CcO is a specific intra-mitochondrial site of age-related deterioration, which may have a broad impact on mitochondrial physiology.« less

Cross-modal integration of lexical-semantic features during word processing: evidence from oscillatory dynamics during EEG.

PubMed

van Ackeren, Markus J; Rueschemeyer, Shirley-Ann

2014-01-01

In recent years, numerous studies have provided converging evidence that word meaning is partially stored in modality-specific cortical networks. However, little is known about the mechanisms supporting the integration of this distributed semantic content into coherent conceptual representations. In the current study we aimed to address this issue by using EEG to look at the spatial and temporal dynamics of feature integration during word comprehension. Specifically, participants were presented with two modality-specific features (i.e., visual or auditory features such as silver and loud) and asked to verify whether these two features were compatible with a subsequently presented target word (e.g., WHISTLE). Each pair of features described properties from either the same modality (e.g., silver, tiny  =  visual features) or different modalities (e.g., silver, loud  =  visual, auditory). Behavioral and EEG data were collected. The results show that verifying features that are putatively represented in the same modality-specific network is faster than verifying features across modalities. At the neural level, integrating features across modalities induces sustained oscillatory activity around the theta range (4-6 Hz) in left anterior temporal lobe (ATL), a putative hub for integrating distributed semantic content. In addition, enhanced long-range network interactions in the theta range were seen between left ATL and a widespread cortical network. These results suggest that oscillatory dynamics in the theta range could be involved in integrating multimodal semantic content by creating transient functional networks linking distributed modality-specific networks and multimodal semantic hubs such as left ATL.

Correlations between human mobility and social interaction reveal general activity patterns.

PubMed

Mollgaard, Anders; Lehmann, Sune; Mathiesen, Joachim

2017-01-01

A day in the life of a person involves a broad range of activities which are common across many people. Going beyond diurnal cycles, a central question is: to what extent do individuals act according to patterns shared across an entire population? Here we investigate the interplay between different activity types, namely communication, motion, and physical proximity by analyzing data collected from smartphones distributed among 638 individuals. We explore two central questions: Which underlying principles govern the formation of the activity patterns? Are the patterns specific to each individual or shared across the entire population? We find that statistics of the entire population allows us to successfully predict 71% of the activity and 85% of the inactivity involved in communication, mobility, and physical proximity. Surprisingly, individual level statistics only result in marginally better predictions, indicating that a majority of activity patterns are shared across our sample population. Finally, we predict short-term activity patterns using a generalized linear model, which suggests that a simple linear description might be sufficient to explain a wide range of actions, whether they be of social or of physical character.

Intuitive visual impressions (cogs) for identifying clusters of diversity within potato species

USDA-ARS?s Scientific Manuscript database

One of the basic research activities of genebanks is to partition stocks into groups that facilitate the efficient preservation and evaluation of the full range of useful phenotype diversity. We sought to test the usefulness of making of infra-specific groups by replicated rapid visual intuitive imp...

Internationalising Professional Skill Development: Are the Rich Getting Richer?

ERIC Educational Resources Information Center

Soontiens, Werner

2004-01-01

Internationalisation of education, and more specifically tertiary education, all over the world has contributed to a significant overhaul in student composition. Parallel to this runs the need for graduates to leave university with a range of professional skills. In response to this, universities actively encourage the development of such skills…

Evaluation of fungicides for control of Phytophthora ramorum

Treesearch

S. Wagner; K. Kaminski; S. Werres

2008-01-01

As part of the project European Phytophthora ramorum Pest Risk Analysis (RAPRA) a wide range of fungicides was tested for in vitro activity against mycelial growth and zoospore germination of P. ramorum. A preliminary set of experiments was performed to study the effect of nine common fungicides specific for

Integrated arrays of air-dielectric graphene transistors as transparent active-matrix pressure sensors for wide pressure ranges.

PubMed

Shin, Sung-Ho; Ji, Sangyoon; Choi, Seiho; Pyo, Kyoung-Hee; Wan An, Byeong; Park, Jihun; Kim, Joohee; Kim, Ju-Young; Lee, Ki-Suk; Kwon, Soon-Yong; Heo, Jaeyeong; Park, Byong-Guk; Park, Jang-Ung

2017-03-31

Integrated electronic circuitries with pressure sensors have been extensively researched as a key component for emerging electronics applications such as electronic skins and health-monitoring devices. Although existing pressure sensors display high sensitivities, they can only be used for specific purposes due to the narrow range of detectable pressure (under tens of kPa) and the difficulty of forming highly integrated arrays. However, it is essential to develop tactile pressure sensors with a wide pressure range in order to use them for diverse application areas including medical diagnosis, robotics or automotive electronics. Here we report an unconventional approach for fabricating fully integrated active-matrix arrays of pressure-sensitive graphene transistors with air-dielectric layers simply formed by folding two opposing panels. Furthermore, this realizes a wide tactile pressure sensing range from 250 Pa to ∼3 MPa. Additionally, fabrication of pressure sensor arrays and transparent pressure sensors are demonstrated, suggesting their substantial promise as next-generation electronics.

Integrated arrays of air-dielectric graphene transistors as transparent active-matrix pressure sensors for wide pressure ranges

NASA Astrophysics Data System (ADS)

Shin, Sung-Ho; Ji, Sangyoon; Choi, Seiho; Pyo, Kyoung-Hee; Wan An, Byeong; Park, Jihun; Kim, Joohee; Kim, Ju-Young; Lee, Ki-Suk; Kwon, Soon-Yong; Heo, Jaeyeong; Park, Byong-Guk; Park, Jang-Ung

2017-03-01

Integrated electronic circuitries with pressure sensors have been extensively researched as a key component for emerging electronics applications such as electronic skins and health-monitoring devices. Although existing pressure sensors display high sensitivities, they can only be used for specific purposes due to the narrow range of detectable pressure (under tens of kPa) and the difficulty of forming highly integrated arrays. However, it is essential to develop tactile pressure sensors with a wide pressure range in order to use them for diverse application areas including medical diagnosis, robotics or automotive electronics. Here we report an unconventional approach for fabricating fully integrated active-matrix arrays of pressure-sensitive graphene transistors with air-dielectric layers simply formed by folding two opposing panels. Furthermore, this realizes a wide tactile pressure sensing range from 250 Pa to ~3 MPa. Additionally, fabrication of pressure sensor arrays and transparent pressure sensors are demonstrated, suggesting their substantial promise as next-generation electronics.

Integrated arrays of air-dielectric graphene transistors as transparent active-matrix pressure sensors for wide pressure ranges

PubMed Central

Shin, Sung-Ho; Ji, Sangyoon; Choi, Seiho; Pyo, Kyoung-Hee; Wan An, Byeong; Park, Jihun; Kim, Joohee; Kim, Ju-Young; Lee, Ki-Suk; Kwon, Soon-Yong; Heo, Jaeyeong; Park, Byong-Guk; Park, Jang-Ung

2017-01-01

Integrated electronic circuitries with pressure sensors have been extensively researched as a key component for emerging electronics applications such as electronic skins and health-monitoring devices. Although existing pressure sensors display high sensitivities, they can only be used for specific purposes due to the narrow range of detectable pressure (under tens of kPa) and the difficulty of forming highly integrated arrays. However, it is essential to develop tactile pressure sensors with a wide pressure range in order to use them for diverse application areas including medical diagnosis, robotics or automotive electronics. Here we report an unconventional approach for fabricating fully integrated active-matrix arrays of pressure-sensitive graphene transistors with air-dielectric layers simply formed by folding two opposing panels. Furthermore, this realizes a wide tactile pressure sensing range from 250 Pa to ∼3 MPa. Additionally, fabrication of pressure sensor arrays and transparent pressure sensors are demonstrated, suggesting their substantial promise as next-generation electronics. PMID:28361867

Understanding in an instant: neurophysiological evidence for mechanistic language circuits in the brain.

PubMed

Pulvermüller, Friedemann; Shtyrov, Yury; Hauk, Olaf

2009-08-01

How long does it take the human mind to grasp the idea when hearing or reading a sentence? Neurophysiological methods looking directly at the time course of brain activity indexes of comprehension are critical for finding the answer to this question. As the dominant cognitive approaches, models of serial/cascaded and parallel processing, make conflicting predictions on the time course of psycholinguistic information access, they can be tested using neurophysiological brain activation recorded in MEG and EEG experiments. Seriality and cascading of lexical, semantic and syntactic processes receives support from late (latency approximately 1/2s) sequential neurophysiological responses, especially N400 and P600. However, parallelism is substantiated by early near-simultaneous brain indexes of a range of psycholinguistic processes, up to the level of semantic access and context integration, emerging already 100-250ms after critical stimulus information is present. Crucially, however, there are reliable latency differences of 20-50ms between early cortical area activations reflecting lexical, semantic and syntactic processes, which are left unexplained by current serial and parallel brain models of language. We here offer a mechanistic model grounded in cortical nerve cell circuits that builds upon neuroanatomical and neurophysiological knowledge and explains both near-simultaneous activations and fine-grained delays. A key concept is that of discrete distributed cortical circuits with specific inter-area topographies. The full activation, or ignition, of specifically distributed binding circuits explains the near-simultaneity of early neurophysiological indexes of lexical, syntactic and semantic processing. Activity spreading within circuits determined by between-area conduction delays accounts for comprehension-related regional activation differences in the millisecond range.

Overview on NASA's Advanced Electric Propulsion Concepts Activities

NASA Technical Reports Server (NTRS)

Frisbee, Robert H.

1999-01-01

Advanced electric propulsion research activities are currently underway that seek to addresses feasibility issues of a wide range of advanced concepts, and may result in the development of technologies that will enable exciting new missions within our solar system and beyond. Each research activity is described in terms of the present focus and potential future applications. Topics include micro-electric thrusters, electrodynamic tethers, high power plasma thrusters and related applications in materials processing, variable specific impulse plasma thrusters, pulsed inductive thrusters, computational techniques for thruster modeling, and advanced electric propulsion missions and systems studies.

Detailed Structural Analyses of KOH Activated Carbon from Waste Coffee Beans

NASA Astrophysics Data System (ADS)

Takahata, Tomokazu; Toda, Ikumi; Ono, Hiroki; Ohshio, Shigeo; Akasaka, Hiroki; Himeno, Syuji; Kokubu, Toshinori; Saitoh, Hidetoshi

2009-11-01

The relationship of the detailed structural change of KOH activated carbon and hydrogen storage ability was investigated in activated carbon materials fabricated from waste coffee beans. The specific surface area of porous carbon materials calculated from N2 adsorption isotherms stood at 2070 m2/g when the weight ratio of KOH to carbon materials was 5:1, and pore size was in the range of approximately 0.6 to 1.1 nm as micropores. In the structural analysis, X-ray diffraction analysis and Raman spectroscopy indicated structural change in these carbon materials through KOH activation. The order of the graphite structure changed to a smaller scale with this activation. It is theorized that specific surface area increased using micropores provided by carbon materials developed from the descent of the graphite structure. Hydrogen storage ability improved with these structural changes, and reached 0.6 wt % at 2070 m2/g. These results suggest that hydrogen storage ability is conferred by the chemical effect on graphite of carbon materials.

Angiotensin-I converting enzyme (ACE): structure, biological roles, and molecular basis for chloride ion dependence.

PubMed

Masuyer, Geoffrey; Yates, Christopher J; Sturrock, Edward D; Acharya, K Ravi

2014-10-01

Somatic angiotensin-I converting enzyme (sACE) has an essential role in the regulation of blood pressure and electrolyte fluid homeostasis. It is a zinc protease that cleaves angiotensin-I (AngI), bradykinin, and a broad range of other signalling peptides. The enzyme activity is provided by two homologous domains (N- and C-), which display clear differences in substrate specificities and chloride activation. The presence of chloride ions in sACE and its unusual role in activity was identified early on in the characterisation of the enzyme. The molecular mechanisms of chloride activation have been investigated thoroughly through mutagenesis studies and shown to be substrate-dependent. Recent results from X-ray crystallography structural analysis have provided the basis for the intricate interactions between ACE, its substrate and chloride ions. Here we describe the role of chloride ions in human ACE and its physiological consequences. Insights into the chloride activation of the N- and C-domains could impact the design of improved domain-specific ACE inhibitors.

A mixed-method analysis of free-time involvement and motivation among adolescents in Cape Town, South Africa

PubMed Central

Palen, Lori-Ann; Caldwell, Linda L.; Smith, Edward A.; Gleeson, Sarah L.; Patrick, Megan E.

2012-01-01

Using focus group (N = 114) and survey (N = 946) data, this study employed Self-Determination Theory (SDT) as an organizing framework to examine free-time use and motivation among predominantly mixed-race adolescents from one area in South Africa. Adolescents reported participating in a broad range of activities, with socializing, media use, sports, risk behaviour, and performing arts being most frequently mentioned. All of the motivation types proposed by SDT were spontaneously mentioned by focus group participants. Free time was most strongly characterized by intrinsic motivations, such as competence, relatedness, and positive affect. Activities were also seen as a way to achieve outside goals. With few exceptions, multiple motivations were identified for the same activities, and specific motivations were reported across multiple activity types. The findings suggest that positive motivational experiences were not limited to a specific subset of activities. However, future longitudinal research on participation, motivation, and outcomes is needed to determine the developmental implications of different forms of free-time motivation. PMID:23055820

Brief review: Preparation techniques of biomass based activated carbon monolith electrode for supercapacitor applications

NASA Astrophysics Data System (ADS)

Taer, Erman; Taslim, Rika

2018-02-01

The synthesis of activated carbon monolith electrode made from a biomass material using the hydrolytic pressure or the pelletization technique of pre-carbonized materials is one of standard reported methods. Several steps such as pre-carbonization, milling, chemical activation, hydraulic press, carbonization, physical activation, polishing and washing need to be accomplished in the production of electrodes by this method. This is relatively a long process that need to be simplified. In this paper we present the standard method and proceed with the introduction to several alternative methods in the synthesis of activated carbon monolith electrodes. The alternative methods were emphasized on the selection of suitable biomass materials. All of carbon electrodes prepared by different methods will be analyzed for physical and electrochemical properties. The density, degree of crystallinity, surface morphology are examples for physical study and specific capacitance was an electrochemical properties that has been analysed. This alternative method has offered a specific capacitance in the range of 10 to 171 F/g.

Voluntary control of intracortical oscillations for reconfiguration of network activity

PubMed Central

Corlier, Juliana; Valderrama, Mario; Navarrete, Miguel; Lehongre, Katia; Hasboun, Dominique; Adam, Claude; Belaid, Hayat; Clémenceau, Stéphane; Baulac, Michel; Charpier, Stéphane; Navarro, Vincent; Le Van Quyen, Michel

2016-01-01

Voluntary control of oscillatory activity represents a key target in the self-regulation of brain function. Using a real-time closed-loop paradigm and simultaneous macro- and micro-electrode recordings, we studied the effects of self-induced intracortical oscillatory activity (4–8 Hz) in seven neurosurgical patients. Subjects learned to robustly and specifically induce oscillations in the target frequency, confirmed by increased oscillatory event density. We have found that the session-to-session variability in performance was explained by the functional long-range decoupling of the target area suggesting a training-induced network reorganization. Downstream effects on more local activities included progressive cross-frequency-coupling with gamma oscillations (30–120 Hz), and the dynamic modulation of neuronal firing rates and spike timing, indicating an improved temporal coordination of local circuits. These findings suggest that effects of voluntary control of intracortical oscillations can be exploited to specifically target plasticity processes to reconfigure network activity, with a particular relevance for memory function or skill acquisition. PMID:27808225

Platform-dependent optimization considerations for mHealth applications

NASA Astrophysics Data System (ADS)

Kaghyan, Sahak; Akopian, David; Sarukhanyan, Hakob

2015-03-01

Modern mobile devices contain integrated sensors that enable multitude of applications in such fields as mobile health (mHealth), entertainment, sports, etc. Human physical activity monitoring is one of such the emerging applications. There exists a range of challenges that relate to activity monitoring tasks, and, particularly, exploiting optimal solutions and architectures for respective mobile software application development. This work addresses mobile computations related to integrated inertial sensors for activity monitoring, such as accelerometers, gyroscopes, integrated global positioning system (GPS) and WLAN-based positioning, that can be used for activity monitoring. Some of the aspects will be discussed in this paper. Each of the sensing data sources has its own characteristics such as specific data formats, data rates, signal acquisition durations etc., and these specifications affect energy consumption. Energy consumption significantly varies as sensor data acquisition is followed by data analysis including various transformations and signal processing algorithms. This paper will address several aspects of more optimal activity monitoring implementations exploiting state-of-the-art capabilities of modern platforms.

Data communications in a parallel active messaging interface of a parallel computer

DOEpatents

Davis, Kristan D.; Faraj, Daniel A.

2014-07-22

Algorithm selection for data communications in a parallel active messaging interface (`PAMI`) of a parallel computer, the PAMI composed of data communications endpoints, each endpoint including specifications of a client, a context, and a task, endpoints coupled for data communications through the PAMI, including associating in the PAMI data communications algorithms and ranges of message sizes so that each algorithm is associated with a separate range of message sizes; receiving in an origin endpoint of the PAMI a data communications instruction, the instruction specifying transmission of a data communications message from the origin endpoint to a target endpoint, the data communications message characterized by a message size; selecting, from among the associated algorithms and ranges, a data communications algorithm in dependence upon the message size; and transmitting, according to the selected data communications algorithm from the origin endpoint to the target endpoint, the data communications message.

Data communications in a parallel active messaging interface of a parallel computer

DOEpatents

Davis, Kristan D; Faraj, Daniel A

2013-07-09

Algorithm selection for data communications in a parallel active messaging interface (`PAMI`) of a parallel computer, the PAMI composed of data communications endpoints, each endpoint including specifications of a client, a context, and a task, endpoints coupled for data communications through the PAMI, including associating in the PAMI data communications algorithms and ranges of message sizes so that each algorithm is associated with a separate range of message sizes; receiving in an origin endpoint of the PAMI a data communications instruction, the instruction specifying transmission of a data communications message from the origin endpoint to a target endpoint, the data communications message characterized by a message size; selecting, from among the associated algorithms and ranges, a data communications algorithm in dependence upon the message size; and transmitting, according to the selected data communications algorithm from the origin endpoint to the target endpoint, the data communications message.

Neighborhood Environment Walkability Scale for Youth (NEWS-Y): reliability and relationship with physical activity.

PubMed

Rosenberg, Dori; Ding, Ding; Sallis, James F; Kerr, Jacqueline; Norman, Gregory J; Durant, Nefertiti; Harris, Sion K; Saelens, Brian E

2009-01-01

To examine the psychometric properties of the Neighborhood Environment Walkability Scale-Youth (NEWS-Y) and explore its associations with context-specific and overall physical activity (PA) among youth. In 2005, parents of children ages 5-11 (n=116), parents of adolescents ages 12-18 (n=171), and adolescents ages 12-18 (n=171) from Boston, Cincinnati, and San Diego, completed NEWS-Y surveys regarding perceived land use mix-diversity, recreation facility availability, pedestrian/automobile traffic safety, crime safety, aesthetics, walking/cycling facilities, street connectivity, land use mix-access, and residential density. A standardized neighborhood environment score was derived. Self-reported activity in the street and in parks, and walking to parks, shops, school, and overall physical activity were assessed. The NEWS-Y subscales had acceptable test-retest reliability (ICC range .56-.87). Being active in a park, walking to a park, walking to shops, and walking to school were related to multiple environmental attributes in all three participant groups. Total neighborhood environment, recreation facilities, walking and cycling facilities, and land use mix-access had the most consistent relationships with specific types of activity. The NEWS-Y has acceptable reliability and subscales were significantly correlated with specific types of youth PA. The NEWS-Y can be used to examine neighborhood environment correlates of youth PA.

Meat and poultry consumption contribution to the natural radionuclide intake of the inhabitants of the Obafemi Awolowo University, Ile-Ife, Nigeria

NASA Astrophysics Data System (ADS)

Akinloye, M. K.; Olomo, J. B.; Olubunmi, P. A.

1999-02-01

The mean activity concentrations of the naturally occurring radionuclides ( 226Ra, 228Ra and 40K) in three types of meat (goat meat, beef and pork) from stock animals as well as free-range and intensive poultry raised within the OAU environment of the Obafemi Awolowo University (OAU), Ile-Ife, were measured by means of a well-calibrated high-purity germanium detector. The specific activities of 226Ra in the three types of meat ranged from 1.11 to 5.83 Bq kg -1 with a mean of 3.10±1.52 Bq kg -1. 228Ra was not detectable in both beef and pork but had a range of 1.53-1.63 Bq kg -1 with a mean of 1.58±0.30 Bq kg -1 in goat meat while 40K recorded an average specific activity of 360.00±54.20 Bq kg -1 for the various samples of meat. The mean activity values of 226Ra, 228Ra and 40K for the poultry were 2.59±0.48, 0.78±0.13 and 265.01±15.90 Bq kg -1, respectively. The results obtained for the daily radionuclide intake of the various meat types showed that those of 226Ra ranged from 0.4 to 8.1 mBq d -1 with a mean of 4.9±0.4 mBq d -1. Since 228Ra was not detectable in beef and pork its daily intake could not be estimated. However, a mean value of intake of 2.2±0.4 mBq d -1 was obtained for goat meat. The values of 40K intake ranged from 150.0 to 672.7 mBq d -1 with an average of 455.5±19.0 mBq d -1. The mean daily intakes of 226Ra, 228Ra and 40K for the two types of poultry were 6.15±0.70, 1.9±0.3 and 633.4±38.0 mBq d -1, respectively.

Chlorophyll-Derivative Modulation of Rhodopsin Signaling Properties through Evolutionarily Conserved Interaction Pathways

PubMed Central

Woods, Kristina N.; Pfeffer, Jürgen; Klein-Seetharaman, Judith

2017-01-01

Retinal is the light-absorbing chromophore that is responsible for the activation of visual pigments and light-driven ion pumps. Evolutionary changes in the intermolecular interactions of the retinal with specific amino acids allow for adaptation of the spectral characteristics, referred to as spectral tuning. However, it has been proposed that a specific species of dragon fish has bypassed the adaptive evolutionary process of spectral tuning and replaced it with a single evolutionary event: photosensitization of rhodopsin by chlorophyll derivatives. Here, by using a combination of experimental measurements and computational modeling to probe retinal-receptor interactions in rhodopsin, we show how the binding of the chlorophyll derivative, chlorin-e6 (Ce6) in the intracellular domain (ICD) of the receptor allosterically excites G-protein coupled receptor class A (GPCR-A) conserved long-range correlated fluctuations that connect distant parts of the receptor. These long-range correlated motions are associated with regulating the dynamics and intermolecular interactions of specific amino acids in the retinal ligand-binding pocket that have been associated with shifts in the absorbance peak maximum (λmax) and hence, spectral sensitivity of the visual system. Moreover, the binding of Ce6 affects the overall global properties of the receptor. Specifically, we find that Ce6-induced dynamics alter the thermal stability of rhodopsin by adjusting hydrogen-bonding interactions near the receptor active-site that consequently also influences the intrinsic conformational equilibrium of the receptor. Due to the conservation of the ICD residues amongst different receptors in this class and the fact that all GPCR-A receptors share a common mechanism of activation, it is possible that the allosteric associations excited in rhodopsin with Ce6 binding are a common feature in all class A GPCRs. PMID:29312953

Do site-specific radiocarbon measurements reflect localized distributions of 14C in biota inhabiting a wetland with point contamination sources?

PubMed

Yankovich, T; King-Sharp, K J; Benz, M L; Carr, J; Killey, R W D; Beresford, N A; Wood, M D

2013-12-01

Duke Swamp is a wetland ecosystem that receives (14)C via a groundwater pathway originating from a waste management area on Atomic Energy Canada Limited's Chalk River Laboratories site. This groundwater reaches the surface of the swamp, resulting in relatively high (14)C levels over an area of 146 m(2). The objective of this study was to quantify (14)C concentrations in flora and fauna inhabiting areas of Duke Swamp over the gradient of (14)C activity concentrations in moss to determine whether (14)C specific activities in receptor biota reflect the localized nature of the groundwater source in the swamp. Representative receptor plants and animals, and corresponding air and soil samples were collected at six sites in Duke Swamp with (14)C specific activities in air that ranged from 1140 to 45,900 Bq/kg C. In general, it was found that specific activities of (14)C in biota tissues reflected those measured in environmental media collected from the same sampling site. The findings demonstrate that mosses could be used in monitoring programs to ensure protection of biota in areas with elevated (14)C, negating the need to capture and euthanize higher organisms. Copyright © 2013 Elsevier Ltd. All rights reserved.

Measurement and Analysis of Specific Activities of Natural Radionuclides (40K, 226Ra and 232Th) in Beach Sand Samples from Talo Kapo Beach of Yaring District in Pattani Province using Gamma Ray Spectrometry

NASA Astrophysics Data System (ADS)

Daoh, M.; Masae, R. N.; Po-oh, S.; Boonkrongcheep; Kessaratikoon, P.

2017-09-01

The Specific Activities of 40K, 226Ra and 232Th were studied and determinate for 30 beach sand samples collected from Talo Kapo beach of Yaring district in Pattani province. Experimental results were obtained by using a high-purity germanium (HPGe) detector and gamma spectrometry analysis system. The IAEA-SOIL-6 reference materials obtained from the International Atomic Energy Agency were also used to analyze and compute the 40K, 226Ra and 232Th specific activity in all 30 beach sand samples. The measuring time of each sample is 10,000 seconds. It was found that specific activity range from 1805.37 - 3323.05, 40.96 - 2137.36 38.63 - 4329.28 Bq/kg for with mean values of 2242.79 ± 117.40, 250.18 ± 8.21 and 458.42 ± 7.68 Bq/kg for 40K, 226Ra and 232Th, respectively. Moreover, the results were also compared with research data in the south of Thailand, the Office of Atoms for Peace (OAP) annual report data and the recommended values which were proposed by United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR,)

The effectiveness of isometric exercises as compared to general exercises in the management of chronic non-specific neck pain.

PubMed

Khan, Muhammad; Soomro, Rabail Rani; Ali, Syed Shahzad

2014-09-01

To evaluate the effectiveness of isometric exercises as compared to general exercises in chronic non-specific neck pain. For this randomised controlled trial total 68 patients (34 each group) with chronic non-specific neck pain were recruited from Alain Poly Clinic and Institute of Physical Medicine & Rehabilitation Dow University of Health Sciences, Karachi between May, 2012 and August, 2012. Simple randomisation method was used to assign participants into isometric exercise group and general exercise groups. The isometric exercise group performed exercises for neck muscle groups with a rubber band and general exercises group performed active range of movement exercises for all neck movements. Patients in both groups received 3 supervised treatment sessions per week for 12 weeks. Visual Analogue Scale (VAS), North wick Park Neck Pain Questionnaire and goniometer were used to assess pain, disability and neck range of movements at baseline and after 12 weeks. Both interventions showed statistically significant improvements in pain, function and range of movement p = 0.001f or isometric exercise group, p = 0.04 for general exercises group and p = 0.001 for range of movement. However, mean improvements in post intervention VAS score and North wick Park Neck Pain Questionnaire score was better in isometric exercises group as compared to general exercise group. In conclusion, both interventions are effective in the treatment of chronic non-specific neck pain however; isometric exercises are clinically more effective than general exercises.

Micro-mesoporous carbon spheres derived from carrageenan as electrode material for supercapacitors

NASA Astrophysics Data System (ADS)

Fan, Yang; Yang, Xin; Zhu, Bing; Liu, Pei-Fang; Lu, Hai-Ting

2014-12-01

The polysaccharide carrageenan is used as a natural precursor to prepare micro-mesoporous carbon spheres. The carbon spheres were synthesized by hydrothermal carbonization of carrageenan, and subsequent chemical activation by KOH at different temperatures. The obtained micro-mesoporous carbon spheres have high surface area (up to 2502 m2 g-1) and large pore volume (up to 1.43 cm3 g-1). Moreover, the micro- and mesoporosity can be finely tuned be modifying the activation temperatures in the range of 700-900 °C. The carbon spheres activated at 900 °C present high specific capacitance of 230 F g-1 at a current density of 1 A g-1 and good ion transport kinetics. The good capacitive performance can be ascribed to the high specific surface area, well-controlled micro- and mesoporosity and narrow pore size distribution.

Characteristics of Lower Leg Muscle Activity in Patients with Cerebral Palsy during Cycling on an Ergometer.

PubMed

Roy, Susmita; Alves-Pinto, Ana; Lampe, Renée

2018-01-01

Cycling on ergometer is often part of rehabilitation programs for patients with cerebral palsy (CP). The present study analyzed activity patterns of individual lower leg muscle during active cycling on ergometer in patients with CP and compared them to similar recordings in healthy participants. Electromyographic (EMG) recordings of lower leg muscle activity were collected from 14 adult patients and 10 adult healthy participants. Activity of the following muscles was recorded: Musculus tibialis anterior, Musculus gastrocnemius, Musculus rectus femoris, and Musculus biceps femoris. Besides qualitative analysis also quantitative analysis of individual muscle activity was performed by computing the coefficient of variation of EMG signal amplitude. More irregular EMG patterns were observed in patients in comparison to healthy participants: agonist-antagonist cocontractions were more frequent, muscle activity measured at specific points of the cycle path was more variable, and dynamic range of muscle activity along the cycle path was narrower in patients. Hypertonicity was also more frequent in patients. Muscle activity patterns during cycling differed substantially across patients. It showed irregular nature and occasional sharp high peaks. Dynamic range was also narrower than in controls. Observations underline the need for individualized cycling training to optimize rehabilitation effects.

The effect of CO2 activation temperature on the physical and electrochemical properties of activated carbon monolith from banana stem waste

NASA Astrophysics Data System (ADS)

Taer, E.; Susanti, Y.; Awitdrus, Sugianto, Taslim, R.; Setiadi, R. N.; Bahri, S.; Agustino, Dewi, P.; Kurniasih, B.

2018-02-01

The effect of CO2 activation on the synthesis of activated carbon monolith from banana stem waste has been studied. Physical characteristics such as density, degree of crystallinity, surface morphology and elemental content has been analyzed, supporting the finding of an excellent electrochemical properties for the supercapacitor. The synthesis of activated carbon electrode began with pre-carbonization process at temperature of 250°C for 2.5 h. Then the process was continued by chemical activation using KOH as activating agent with a concentration of 0.4 M. The pellets were formed with 8 ton hydrolic pressure. All the samples were carbonized at a temperature of 600°C, followed by physical activation using CO2 gas at a various temperatures ranging from 800°C, 850°C, 900°C and 950°C for 2 h. The carbon content was increased with increasing temperature and the optimum temperature was 900°C. The specific capacitance depends on the activation temperature with the highest specific capacitance of 104.2 F/g at the activation temperature of 900°C.

Purification and Partial Characterization of Trypsin-Specific Proteinase Inhibitors from Pigeonpea Wild Relative Cajanus platycarpus L. (Fabaceae) Active against Gut Proteases of Lepidopteran Pest Helicoverpa armigera

PubMed Central

Swathi, Marri; Mishra, Prashant K.; Lokya, Vadthya; Swaroop, Vanka; Mallikarjuna, Nalini; Dutta-Gupta, Aparna; Padmasree, Kollipara

2016-01-01

Proteinase inhibitors (PIs) are natural defense proteins of plants found to be active against gut proteases of various insects. A pigeonpea wild relative Cajanus platycarpus was identified as a source of resistance against Helicoverpa armigera, a most devastating pest of several crops including pigeonpea. In the light of earlier studies, trypsin-specific PIs (CpPI 63) were purified from mature dry seeds of C. platycarpus (ICPW-63) and characterized their biochemical properties in contributing to H. armigera resistance. CpPI 63 possessed significant H. armigera gut trypsin-like proteinase inhibitor (HGPI) activity than trypsin inhibitor (TI) activity. Analysis of CpPI 63 using two-dimensional (2-D) electrophoresis and matrix assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry revealed that it contained several isoinhibitors and small oligomers with masses ranging between 6 and 58 kDa. The gelatin activity staining studies suggest that these isoinhibitors and oligomers possessed strong inhibitory activity against H. armigera gut trypsin-like proteases (HGPs). The N-terminal sequence of the isoinhibitors (pI 6.6 and pI 5.6) of CpPI 63 exhibited 80% homology with several Kunitz trypsin inhibitors (KTIs) as well as miraculin-like proteins (MLPs). Further, modification of lysine residue(s) lead to 80% loss in both TI and HGPI activities of CpPI 63. In contrast, the TI and HGPI activities of CpPI 63 were stable over a wide range of temperature and pH conditions. The reported results provide a biochemical basis for pod borer resistance in C. platycarpus. PMID:27656149

Chromatography of blood-clotting factors and serum proteins on columns of diatomaceous earth.

PubMed

MILSTONE, J H

1955-07-20

1. In batch adsorptions with prothrombin solutions, hyflo was the weakest adsorbent, standard super-cel intermediate, and filter-cel strongest. Of these three grades of diatomaceous earth, hyflo has the smallest surface area per gram and filter-cel the largest. In parallel breakthrough experiments, a column of standard super-cel had a capacity almost six times that of a hyflo column. 2. After partial removal of impurities by diatomaceous earth, prothrombin preparations contained less thrombokinase, were more stable, and displayed less tendency to form thrombin "spontaneously." Thrombokinase (or its precursor) was removed from a preparation of prothrombin by passage through a filter cake of standard super-cel. The specific activity of the prothrombin was increased; and 62 per cent of the activity was recovered. 3. Prothrombin was adsorbed from an ammonium sulfate solution at pH 5.26 by columns of hyflo or standard super-cel. When eluted by phosphate solutions, the protein moved down the columns more readily at higher pH and higher concentration of phosphate salts, within the pH range 5.0 to 6.6, and within the phosphate range 0.1 to 1.0 M. 4. Thrombin was adsorbed on a column of standard super-cel at pH 5.11. As successive eluents passed through the column, the thrombin emerged between two bands of impurities. The specific activity of the thrombin was raised; and 83 per cent of the activity was recovered. 5. With a column of standard super-cel, and with a series of eluents within the pH range 5.1 to 6.3, total serum proteins were separated into four major bands. About 94 per cent of the protein was recovered.

CHROMATOGRAPHY OF BLOOD-CLOTTING FACTORS AND SERUM PROTEINS ON COLUMNS OF DIATOMACEOUS EARTH

PubMed Central

Milstone, J. H.

1955-01-01

1. In batch adsorptions with prothrombin solutions, hyflo was the weakest adsorbent, standard super-cel intermediate, and filter-cel strongest. Of these three grades of diatomaceous earth, hyflo has the smallest surface area per gram and filter-cel the largest. In parallel breakthrough experiments, a column of standard super-cel had a capacity almost six times that of a hyflo column. 2. After partial removal of impurities by diatomaceous earth, prothrombin preparations contained less thrombokinase, were more stable, and displayed less tendency to form thrombin "spontaneously." Thrombokinase (or its precursor) was removed from a preparation of prothrombin by passage through a filter cake of standard super-cel. The specific activity of the prothrombin was increased; and 62 per cent of the activity was recovered. 3. Prothrombin was adsorbed from an ammonium sulfate solution at pH 5.26 by columns of hyflo or standard super-cel. When eluted by phosphate solutions, the protein moved down the columns more readily at higher pH and higher concentration of phosphate salts, within the pH range 5.0 to 6.6, and within the phosphate range 0.1 to 1.0 M. 4. Thrombin was adsorbed on a column of standard super-cel at pH 5.11. As successive eluents passed through the column, the thrombin emerged between two bands of impurities. The specific activity of the thrombin was raised; and 83 per cent of the activity was recovered. 5. With a column of standard super-cel, and with a series of eluents within the pH range 5.1 to 6.3, total serum proteins were separated into four major bands. About 94 per cent of the protein was recovered. PMID:13242761

Differentiating high priority pathway-based toxicity from non ...

EPA Pesticide Factsheets

The ToxCast chemical screening approach enables the rapid assessment of large numbers of chemicals for biological effects, primarily at the molecular level. Adverse outcome pathways (AOPs) offer a means to link biomolecular effects with potential adverse outcomes at the level of the individual or population, thus enhancing the utility of the ToxCast effort for hazard assessment. Thus, efforts are underway to develop AOPs relevant to the pathway perturbations detected in ToxCast assays. However, activity (?‘hits’) determined for chemical-assay pairs may reflect target-specific activity relevant to a molecular initiating event of an AOP, or more generalized cell stress and cytotoxicity-mediated effects. Previous work identified a ?‘cytotoxic burst’ phenomenon wherein large numbers of assays begin to respond at or near concentrations that elicit cytotoxicity. The concentration range at which the “burst” occurs is definable, statistically. Consequently, in order to focus AOP development on the ToxCast assay targetswhich are most sensitive and relevant to pathway-specific effects, we conducted a meta-analysis to identify which assays were frequently responding at concentrations well below the cytotoxic burst. Assays were ranked by the fraction of chemical hits below the burst concentration range compared to the number of chemicals tested, resulting in a preliminary list of potentially important, target-specific assays. After eliminating cytotoxicity a

Serum Amyloid P Is a Sialylated Glycoprotein Inhibitor of Influenza A Viruses

PubMed Central

Job, Emma R.; Bottazzi, Barbara; Gilbertson, Brad; Edenborough, Kathryn M.; Brown, Lorena E.; Mantovani, Alberto; Brooks, Andrew G.; Reading, Patrick C.

2013-01-01

Members of the pentraxin family, including PTX3 and serum amyloid P component (SAP), have been reported to play a role in innate host defence against a range of microbial pathogens, yet little is known regarding their antiviral activities. In this study, we demonstrate that human SAP binds to human influenza A virus (IAV) strains and mediates a range of antiviral activities, including inhibition of IAV-induced hemagglutination (HA), neutralization of virus infectivity and inhibition of the enzymatic activity of the viral neuraminidase (NA). Characterization of the anti-IAV activity of SAP after periodate or bacterial sialidase treatment demonstrated that α(2,6)-linked sialic acid residues on the glycosidic moiety of SAP are critical for recognition by the HA of susceptible IAV strains. Other proteins of the innate immune system, namely human surfactant protein A and porcine surfactant protein D, have been reported to express sialylated glycans which facilitate inhibition of particular IAV strains, yet the specific viral determinants for recognition of these inhibitors have not been defined. Herein, we have selected virus mutants in the presence of human SAP and identified specific residues in the receptor-binding pocket of the viral HA which are critical for recognition and therefore susceptibility to the antiviral activities of SAP. Given the widespread expression of α(2,6)-linked sialic acid in the human respiratory tract, we propose that SAP may act as an effective receptor mimic to limit IAV infection of airway epithelial cells. PMID:23544079

Purification an α-galactosidase from Coriolus versicolor with acid-resistant and good degradation ability on raffinose family oligosaccharides.

PubMed

Du, Fang; Liu, Qin; Wang, Hexiang; Ng, TziBin

2014-04-01

An acid-tolerant α-galactosidase (CVGI) was isolated from the fruiting bodies of Coriolus versicolor with a 229-fold of purification and a specific activity of 398.6 units mg⁻¹. It was purified to electrophoretic homogeneity by ion exchange chromatography and gel filtration chromatography. The purified enzyme gave a single band corresponding to a molecular mass of 40 kDa in SDS-PAGE and gel filtration. The α-galactosidase was identified by MALDI-TOF-MS and its inner peptides were sequenced by ESI-MS/MS. The optimum temperature and pH of the enzyme were determined as 60 °C and 3.0, respectively. The enzyme was very stable at a temperature range of 4-50 °C and at a pH range of 2-5. Among the metal ions tested, Cu²⁺, Cd²⁺ and Hg²⁺ ions have been shown to partially inhibit the activity of α-galactosidase, while the activity of CVGI was completely inactivated by Ag⁺ ions. N-bromosuccinamide inhibited enzyme activity by 100 %, indicating the importance of tryptophan residue(s) at or near the active site. CVGI had wide substrate specificity (p-nitrophenyl galactoside, melidiose, raffinose and stachyose). After treatment with CVGI, raffinose family oligosaccharide was hydrolyzed effectively to yield galactose and sucrose. The results showed that the general properties of the enzyme offer potential for use of this α-galactosidase in several production processes.

A concept analysis of voluntary active euthanasia.

PubMed

Guo, Fenglin

2006-01-01

Euthanasia has a wide range of classifications. Confusion exists in the application of specific concepts to various studies. To analyze the concept of voluntary active euthanasia using Walker and Avant's concept analysis method. A comprehensive literature review from various published literature and bibliographies. Clinical, ethical, and policy differences and similarities of euthanasia need to be debated openly, both within the medical profession and publicly. Awareness of the classifications about euthanasia may help nurses dealing with "end of life issues" properly.

Resonance energy transfer between the active sites of creatine kinase from rabbit brain.

PubMed

Grossman, S H

1990-09-03

Resonance energy transfer was measured between the active site domains of the brain isozyme of creatine kinase (CK-BB). The reactive thiol near the active sites, one on each subunit of the dimeric protein, was derivatized using 5-[2-[iodoacetyl)amino)ethyl]aminonaphthalene-1-sulfonic acid (AED), 2-[4'-iodoacetamidoanilino]naphthalene-6-sulfonic acid (AANS) and 5-iodoacetamidofluorescein (AF). Suitable donor/acceptor protein conjugated hybrids were prepared by controlled kinetics producing CK-BB-AED/AF and CK-BB-AANS/AF. Transfer efficiencies, measured from the quenching of the donor lifetime and steady-state sensitized acceptor emission, ranged from 0.10 to 0.17. From determination of the donor/acceptor overlap integrals, donor quantum yields and attempts to delimit the orientation factor using steady-state and phase-resolved anisotropy measurements, it was found that a suitable estimate of the range between the active sites was between 45 and 57 A. This range is similar to that reported previously for the muscle isozyme of creatine kinase (Grossman, S.H. (1989) Biochemistry 28, 4894-4902) but is a significantly greater distance than detected for the hybrid, myocardial specific isozyme (Grossman, S.H. (1983) Biochemistry 22, 5369-5375).

In vivo bacterial imaging without engineering; A novel probe-based strategy facilitated by endogenous nitroreductase enzymes.

PubMed

Stanton, Michael; Cronin, Michelle; Lehouritis, Panos; Tangney, Mark

2015-01-01

The feasibility of utilising bacteria as vectors for gene therapy is becoming increasingly recognised. This is primarily due to a number of intrinsic properties of bacteria such as their tumour targeting capabilities, their ability to carry large genetic or protein loads and the availability of well-established genetic engineering tools for a range of common lab strains. However, a number of issues relating to the use of bacteria as vectors for gene therapy need to be addressed in order for the field to progress. Amongst these is the need for the development of non-invasive detection/imaging systems for bacteria within a living host. In vivo optical imaging has advanced preclinical research greatly, and typically involves engineering of bacteria with genetic expression constructs for luminescence (e.g. the lux operon) or fluorescent proteins (GFP etc.). This requirement for genetic modification can be restrictive, where engineering is not experimentally appropriate or technologically feasible (e.g. due to lack of suitable engineering tools). We describe a novel strategy exploiting endogenous bacterial enzymatic activity to specifically activate an exogenously administered fluorescent imaging probe. The red shifted, quenched fluorophore CytoCy5S is reduced to a fluorescent form by bacterial-specific nitroreductase (NTR) enzymes. NTR enzymes are present in a wide range of bacterial genera and absent in mammalian systems, permitting highly specific detection of Gram-negative and Gram-positive bacteria in vivo. In this study, dose-responsive bacterial-specific signals were observed in vitro from all genera examined - E. coli, Salmonella, Listeria, Bifidobacterium and Clostridium difficile. Examination of an NTR-knockout strain validated the enzyme specificity of the probe. In vivo whole-body imaging permitted specific, dose-responsive monitoring of bacteria over time in various infection models, and no toxicity to bacteria or host was observed. This study demonstrates the concept of exploiting innate NTR activity as a reporting strategy for wild-type bacteria using optical imaging, while the concept may also be extended to NTR-specific probes for use with other imaging modalities.

Segregated and integrated coding of reward and punishment in the cingulate cortex.

PubMed

Fujiwara, Juri; Tobler, Philippe N; Taira, Masato; Iijima, Toshio; Tsutsui, Ken-Ichiro

2009-06-01

Reward and punishment have opposite affective value but are both processed by the cingulate cortex. However, it is unclear whether the positive and negative affective values of monetary reward and punishment are processed by separate or common subregions of the cingulate cortex. We performed a functional magnetic resonance imaging study using a free-choice task and compared cingulate activations for different levels of monetary gain and loss. Gain-specific activation (increasing activation for increasing gain, but no activation change in relation to loss) occurred mainly in the anterior part of the anterior cingulate and in the posterior cingulate cortex. Conversely, loss-specific activation (increasing activation for increasing loss, but no activation change in relation to gain) occurred between these areas, in the middle and posterior part of the anterior cingulate. Integrated coding of gain and loss (increasing activation throughout the full range, from biggest loss to biggest gain) occurred in the dorsal part of the anterior cingulate, at the border with the medial prefrontal cortex. Finally, unspecific activation increases to both gains and losses (increasing activation to increasing gains and increasing losses, possibly reflecting attention) occurred in dorsal and middle regions of the cingulate cortex. Together, these results suggest separate and common coding of monetary reward and punishment in distinct subregions of the cingulate cortex. Further meta-analysis suggested that the presently found reward- and punishment-specific areas overlapped with those processing positive and negative emotions, respectively.

Purification and characterization of endo-beta-1,4 mannanase from Aspergillus niger gr for application in food processing industry.

PubMed

Naganagouda, K; Salimath, P V; Mulimani, V H

2009-10-01

A thermostable extracellular beta-mannanase from the culture supernatant of a fungus Aspergillus niger gr was purified to homogeneity. SDS-PAGE of the purified enzyme showed a single protein band of molecular mass 66 kDa. The beta- mannanase exhibited optimum catalytic activity at pH 5.5 and 55 degrees C. It was thermostable at 55 degrees C, and retained 50% activity after 6 h at 55 degrees C. The enzyme was stable at a pH range of 3.0 to 7.0. The metal ions Hg(2+), Cu(2+), and Ag(2+) inhibited complete enzyme activity. The inhibitors tested, EDTA, PMSF, and 1,10-phenanthroline, did not inhibit the enzyme activity. N-Bromosuccinimide completely inhibited enzyme activity. The relative substrate specificity of enzyme towards the various mannans is in the order of locust bean gum>guar gum>copra mannan, with K(m) of 0.11, 0.28, and 0.33 mg/ml, respectively. Since the enzyme is active over a wide range of pH and temperature, it could find potential use in the food-processing industry.

Human neutral brush border endopeptidase EC 3.4.24.11 in urine, its isolation, characterisation and activity in renal diseases.

PubMed

Vlaskou, D; Hofmann, W; Guder, W G; Siskos, P A; Dionyssiou-Asteriou, A

2000-07-01

Human neutral brush border endopeptidase (NEP) was purified from the urine of patients suffering from acute toxic tubulointerstitial nephropathy. An enzyme preparation with specific activity of 102 Ug(-1) protein was obtained. The urinary activities of neutral endopeptidase and alanine aminopeptidase were measured in patients with renal disease and in 30 control patients, resulting in a reference range from 0.1 to 0.7 Ug(-1) creatinine and 1.4-14.1 Ug(-1) creatinine, respectively. Urine enzyme activities were highest in patients with acute tubulotoxic renal diseases. Neutral endopeptidase and alanine aminopeptidase activities were found to be 6.5- and 10-fold higher than the upper value of the reference range, respectively. Smaller increases in the rate of excretion of these enzymes (2.5- and 3.5-fold), respectively, were observed in patients suffering from acute tubular insufficiency and even lower increases, 2- and 1.5-fold, respectively, were observed in patients with chronic renal diseases. In diabetics and kidney transplant patients the enzyme excretion rates were within the reference range. Assay of both transmembrane metalloproteinases in urine may prove valuable in serving as markers for renal toxicity. Together with beta-NAG these enzymes could be employed as differentiation markers between acute and chronic tubular insufficiency.

Overcoming non-specific binding to measure the active concentration and kinetics of serum anti-HLA antibodies by surface plasmon resonance.

PubMed

Visentin, Jonathan; Couzi, Lionel; Dromer, Claire; Neau-Cransac, Martine; Guidicelli, Gwendaline; Veniard, Vincent; Coniat, Karine Nubret-le; Merville, Pierre; Di Primo, Carmelo; Taupin, Jean-Luc

2018-06-07

Human leukocyte antigen (HLA) donor-specific antibodies are key serum biomarkers for assessing the outcome of transplanted patients. Measuring their active concentration, i.e. the fraction that really interacts with donor HLA, and their affinity could help deciphering their pathogenicity. Surface plasmon resonance (SPR) is recognized as the gold-standard for measuring binding kinetics but also active concentrations, without calibration curves. SPR-based biosensors often suffer from non-specific binding (NSB) occurring with the sensor chip surface and the immobilized targets, especially for complex media such as human serum. In this work we show that several serum treatments such as dialysis or IgG purification reduce NSB but insufficiently for SPR applications. We then demonstrate that the NSB contribution to the SPR signal can be eliminated to determine precisely and reliably the active concentration and the affinity of anti-HLA antibodies from patients' sera. This was achieved even at concentrations close to the limit of quantification of the method, in the 0.5-1 nM range. The robustness of the assay was demonstrated by using a wide range of artificially generated NSB and by varying the density of the targets captured onto the surface. The assay is of general interest and can be used with molecules generating strong NSB, as far as a non-cognate target structurally close to the target can be captured on the same flow cell, in a different binding cycle. Compared with current fluorescence-based methods that are semi-quantitative, we expect this SPR-based assay to help better understanding anti-HLA antibodies pathogenicity and improving organ recipients' management. Copyright © 2018 Elsevier B.V. All rights reserved.

Decoupling the Effects of High Crystallinity and Surface Area on the Photocatalytic Overall Water Splitting over β-Ga2 O3 Nanoparticles by Chemical Vapor Synthesis.

PubMed

Lukic, Sasa; Menze, Jasper; Weide, Philipp; Busser, G Wilma; Winterer, Markus; Muhler, Martin

2017-09-11

Chemical vapor synthesis (CVS) is a unique method to prepare well-defined photocatalyst materials with both large specific surface area and a high degree of crystallinity. The obtained β-Ga 2 O 3 nanoparticles were optimized for photocatalysis by reductive photodeposition of the Rh/CrO x co-catalyst system. The influence of the degree of crystallinity and the specific surface area on photocatalytic aqueous methanol reforming and overall water splitting (OWS) was investigated by synthesizing β-Ga 2 O 3 samples in the temperature range from 1000 °C to 1500 °C. With increasing temperature, the specific surface area and the microstrain were found to decrease, whereas the degree of crystallinity and the crystallite size increased. Whereas the photocatalyst with the highest specific surface area showed the highest aqueous methanol reforming activity, the highest OWS activity was that for the sample with an optimum ratio between high degree of crystallinity and specific surface area. Thus, it was possible to show that the facile aqueous methanol reforming and the demanding OWS have different requirements for high photocatalytic activity. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Examining Physical Activity Service Provision to Culturally and Linguistically Diverse (CALD) Communities in Australia: A Qualitative Evaluation

PubMed Central

Caperchione, Cristina M.; Kolt, Gregory S.; Mummery, W. Kerry

2013-01-01

Strong evidence exists for the role of physical activity in preventing and managing a range of chronic health conditions. A particular challenge in promoting physical activity as a health strategy exists in culturally and linguistically diverse (CALD) groups, as such groups demonstrate high risk for a range of non-communicable diseases. The aim of this research was to examine the perspective of multicultural health service providers for CALD groups with respect to the physical activity services/initiatives on offer, access barriers to these services, and ideas for future service delivery in this area. Semi-structured interviews were conducted with 15 multicultural health service providers across the capital cities of the three most populous states in Australia (New South Wales, Queensland, and Victoria), and thematic content analysis was used to examine the data. Findings indicated that the majority of physical activity initiatives were associated with organizations offering other social services for CALD communities but were greatly restrained by resources. As well, it was found that most services were not designed by taking into account specific cultural requirements for CALD communities or their cultural expectations. Common barriers identified to service uptake were classified as socio-cultural (e.g., gender, language, context of health) and environmental (e.g., transportation) in nature. These findings should be utilized when planning future physical activity and health promotion initiatives for increasing CALD participation. In particular, programs need to be culturally tailored to the specific expectations of CALD groups, addressing cultural safety and sensitivity, and should be in partnership with other organizations to extend the reach and capacity. PMID:23638145

2010 NASA Range Safety Annual Report

NASA Technical Reports Server (NTRS)

Dumont, Alan G.

2010-01-01

this report provides a NASA Range Safety overview for current and potential range users. This report contains articles which cover a variety of subject areas, summaries of various NASA Range Safety Program activities conducted during the past year, links to past reports, and information on several projects that may have a profound impact on the way business will be done in the future. Specific topics discussed in the 2010 NASA Range Safety Annual Report include a program overview and 2010 highlights; Range Safety Training; Range Safety Policy revision; Independent Assessments; Support to Program Operations at all ranges conducting NASA launch/flight operations; a continuing overview of emerging range safety-related technologies; and status reports from all of the NASA Centers that have Range Safety responsibilities. Every effort has been made to include the most current information available. We recommend this report be used only for guidance and that the validity and accuracy of all articles be verified for updates. Once again, the web-based format was used to present the annual report.

Substrate Specificity and Inhibitor Sensitivity of Plant UDP-Sugar Producing Pyrophosphorylases.

PubMed

Decker, Daniel; Kleczkowski, Leszek A

2017-01-01

UDP-sugars are essential precursors for glycosylation reactions producing cell wall polysaccharides, sucrose, glycoproteins, glycolipids, etc. Primary mechanisms of UDP sugar formation involve the action of at least three distinct pyrophosphorylases using UTP and sugar-1-P as substrates. Here, substrate specificities of barley and Arabidopsis (two isozymes) UDP-glucose pyrophosphorylases (UGPase), Arabidopsis UDP-sugar pyrophosphorylase (USPase) and Arabidopsis UDP- N -acetyl glucosamine pyrophosphorylase2 (UAGPase2) were investigated using a range of sugar-1-phosphates and nucleoside-triphosphates as substrates. Whereas all the enzymes preferentially used UTP as nucleotide donor, they differed in their specificity for sugar-1-P. UGPases had high activity with D-Glc-1-P, but could also react with Fru-1-P and Fru-2-P ( K m values over 10 mM). Contrary to an earlier report, their activity with Gal-1-P was extremely low. USPase reacted with a range of sugar-1-phosphates, including D-Glc-1-P, D-Gal-1-P, D-GalA-1-P ( K m of 1.3 mM), β-L-Ara-1-P and α-D-Fuc-1-P ( K m of 3.4 mM), but not β-L-Fuc-1-P. In contrast, UAGPase2 reacted only with D-GlcNAc-1-P, D-GalNAc-1-P ( K m of 1 mM) and, to some extent, D-Glc-1-P ( K m of 3.2 mM). Generally, different conformations/substituents at C2, C4, and C5 of the pyranose ring of a sugar were crucial determinants of substrate specificity of a given pyrophosphorylase. Homology models of UDP-sugar binding to UGPase, USPase and UAGPase2 revealed more common amino acids for UDP binding than for sugar binding, reflecting differences in substrate specificity of these proteins. UAGPase2 was inhibited by a salicylate derivative that was earlier shown to affect UGPase and USPase activities, consistent with a common structural architecture of the three pyrophosphorylases. The results are discussed with respect to the role of the pyrophosphorylases in sugar activation for glycosylated end-products.

Substrate Specificity and Inhibitor Sensitivity of Plant UDP-Sugar Producing Pyrophosphorylases

PubMed Central

Decker, Daniel; Kleczkowski, Leszek A.

2017-01-01

UDP-sugars are essential precursors for glycosylation reactions producing cell wall polysaccharides, sucrose, glycoproteins, glycolipids, etc. Primary mechanisms of UDP sugar formation involve the action of at least three distinct pyrophosphorylases using UTP and sugar-1-P as substrates. Here, substrate specificities of barley and Arabidopsis (two isozymes) UDP-glucose pyrophosphorylases (UGPase), Arabidopsis UDP-sugar pyrophosphorylase (USPase) and Arabidopsis UDP-N-acetyl glucosamine pyrophosphorylase2 (UAGPase2) were investigated using a range of sugar-1-phosphates and nucleoside-triphosphates as substrates. Whereas all the enzymes preferentially used UTP as nucleotide donor, they differed in their specificity for sugar-1-P. UGPases had high activity with D-Glc-1-P, but could also react with Fru-1-P and Fru-2-P (Km values over 10 mM). Contrary to an earlier report, their activity with Gal-1-P was extremely low. USPase reacted with a range of sugar-1-phosphates, including D-Glc-1-P, D-Gal-1-P, D-GalA-1-P (Km of 1.3 mM), β-L-Ara-1-P and α-D-Fuc-1-P (Km of 3.4 mM), but not β-L-Fuc-1-P. In contrast, UAGPase2 reacted only with D-GlcNAc-1-P, D-GalNAc-1-P (Km of 1 mM) and, to some extent, D-Glc-1-P (Km of 3.2 mM). Generally, different conformations/substituents at C2, C4, and C5 of the pyranose ring of a sugar were crucial determinants of substrate specificity of a given pyrophosphorylase. Homology models of UDP-sugar binding to UGPase, USPase and UAGPase2 revealed more common amino acids for UDP binding than for sugar binding, reflecting differences in substrate specificity of these proteins. UAGPase2 was inhibited by a salicylate derivative that was earlier shown to affect UGPase and USPase activities, consistent with a common structural architecture of the three pyrophosphorylases. The results are discussed with respect to the role of the pyrophosphorylases in sugar activation for glycosylated end-products. PMID:28970843

NoteCards: A Multimedia Idea Processing Environment.

ERIC Educational Resources Information Center

Halasz, Frank G.

1986-01-01

Notecards is a computer environment designed to help people work with ideas by providing a set of tools for a variety of specific activities, which can range from sketching on the back of an envelope to formally representing knowledge. The basic framework of this hypermedia system is a semantic network of electronic notecards connected by…

Building Conservation Capacity in Southeast Asia: Outcomes of the ATBC 2015 Asia-Pacific Chapter Meeting Conservation Education Symposium

ERIC Educational Resources Information Center

Souter, Nicholas J.; Hughes, Alice C.; Savini, Tommaso; Rao, Madhu; Goodale, Eben; Van Nice, Amy; Huang, Natalia; Liu, Jing-Xin; Hunt, Matt P.; O'Connor, David A.; Heung-Lam, Anny Li; Gnuen, Gneb; Sun, Yoeung; Silva, Inês

2017-01-01

The "Building Capacity for Conservation in Southeast Asia" symposium was held at the 2015 Association for Tropical Biology and Conservation, Asia-Pacific Chapter meeting. The range of programs discussed fell into three categories: career development, project-specific activities and outreach, and delivering conservation information to…

Education in Emergencies: The Gender Implications. Advocacy Brief

ERIC Educational Resources Information Center

Kirk, Jackie

2006-01-01

"Education in emergencies" refers to a broad range of education activities, both formal and non-formal, which are life saving and sustaining. They are critical for children, youth and their families in times of crisis. Programmes for emergency education are often designed according to a specific environmental context and sometimes as temporary…

Canopy gap dynamics of second-growth red spruce-northern hardwood stands in West Virginia

Treesearch

James S. Rentch; Thomas M. Schuler; Gregory J. Nowacki; Nathan R. Beane; W. Mark Ford

2010-01-01

Forest restoration requires an understanding of the natural disturbance regime of the target community and estimates of the historic range of variability of ecosystem components (composition, structure, and disturbance processes). Management prescriptions that support specific restoration activities should be consistent with these parameters. In this study, we describe...

Outcomes of Mixed-Age Groupings. Research Highlights.

ERIC Educational Resources Information Center

Stegelin, Dolores A.

1997-01-01

A review of the literature on mixed-age settings reveals benefits in the areas of social and cognitive development. Research on the psychosocial advantages of mixed-age groupings is less consistent. Factors such as group size, age range, time together, and context-specific curriculum activities may have a relationship to the level of success and…

Steps Toward Understanding Rapid Culture Change in Native Rural Alaska.

ERIC Educational Resources Information Center

Davis, Nancy Yaw

To increase understanding of culture change in rural Alaska as it specifically pertains to selected policy-related issues outlined by the Federal-State Land Use Planning Commission staff, four general areas are addressed: traditional subsistence use and effects of changing access and availability of those activities, apparent long-range effects of…

77 FR 58383 - Agency Information Collection Activities: Proposed Collection; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-20

...) The Kids' Inpatient Database (KID) is the only all-payer inpatient care database for children in the United States. The KID was specifically designed to permit researchers to study a broad range of conditions and procedures related to child health issues. The KID contains a sample of over 3 million...

The Past, Present, and Future of the Consortium and Foreign Language Instruction.

ERIC Educational Resources Information Center

Paine, Ruth

The proportion of active foreign language teachers working in cooperative or collaborative efforts is very small. Foreign languages have lagged behind other disciplines in this area. Consortia, or groups of postsecondary institutions agreeing to work together toward specific, long-range goals, date back to medieval times, but few have emerged over…

Histolocalization and physico-chemical characterization of dihydrochalcones: Insight into the role of apple major flavonoids.

PubMed

Gaucher, Matthieu; Dugé de Bernonville, Thomas; Lohou, David; Guyot, Sylvain; Guillemette, Thomas; Brisset, Marie-Noëlle; Dat, James F

2013-06-01

Flavonoids, like other metabolites synthesized via the phenylpropanoid pathway, possess a wide range of biological activities including functions in plant development and its interaction with the environment. Dihydrochalcones (mainly phloridzin, sieboldin, trilobatin, phloretin) represent the major flavonoid subgroup in apple green tissues. Although this class of phenolic compounds is found in very large amounts in some tissues (≈200mg/g of leaf DW), their physiological significance remains unclear. In the present study, we highlight their tissue-specific localization in young growing shoots suggesting a specific role in important physiological processes, most notably in response to biotic stress. Indeed, dihydrochalcones could constitute a basal defense, in particular phloretin which exhibits a strong broad-range bactericidal and fungicidal activity. Our results also indicate that sieboldin forms complexes with iron with strong affinity, reinforcing its antioxidant properties and conferring to this dihydrochalcone a potential for iron seclusion and/or storage. The importance of localization and biochemical properties of dihydrochalcones are discussed in view of the apple tree defense strategy against both biotic and abiotic stresses. Copyright © 2013 Elsevier Ltd. All rights reserved.

Dense range map reconstruction from a versatile robotic sensor system with an active trinocular vision and a passive binocular vision.

PubMed

Kim, Min Young; Lee, Hyunkee; Cho, Hyungsuck

2008-04-10

One major research issue associated with 3D perception by robotic systems is the creation of efficient sensor systems that can generate dense range maps reliably. A visual sensor system for robotic applications is developed that is inherently equipped with two types of sensor, an active trinocular vision and a passive stereo vision. Unlike in conventional active vision systems that use a large number of images with variations of projected patterns for dense range map acquisition or from conventional passive vision systems that work well on specific environments with sufficient feature information, a cooperative bidirectional sensor fusion method for this visual sensor system enables us to acquire a reliable dense range map using active and passive information simultaneously. The fusion algorithms are composed of two parts, one in which the passive stereo vision helps active vision and the other in which the active trinocular vision helps the passive one. The first part matches the laser patterns in stereo laser images with the help of intensity images; the second part utilizes an information fusion technique using the dynamic programming method in which image regions between laser patterns are matched pixel-by-pixel with help of the fusion results obtained in the first part. To determine how the proposed sensor system and fusion algorithms can work in real applications, the sensor system is implemented on a robotic system, and the proposed algorithms are applied. A series of experimental tests is performed for a variety of configurations of robot and environments. The performance of the sensor system is discussed in detail.

High infrasonic goniometry applied to the detection of a helicopter in a high activity environment

NASA Astrophysics Data System (ADS)

Chritin, Vincent; Van Lancker, Eric; Wellig, Peter; Ott, Beat

2016-10-01

A current concern of armasuisse is the feasibility of a fixed or mobile acoustic surveillance and recognition network of sensors allowing to permanently monitor the noise immissions of a wide range of aerial activities such as civil or military aviation, and other possible acoustic events such as transient events, subsonic or sonic booms or other. This objective requires an ability to detect, localize and recognize a wide range of potential acoustic events of interest, among others possibly parasitic acoustic events (natural and industrial events on the ground for example), and possibly high background noise (for example close to urban or high activity areas). This article presents a general discussion and conclusion about this problem, based on 20 years of experience totalizing a dozen of research programs or internal researches by IAV, with an illustration through one central specific experimental case-study carried out within the framework of an armasuisse research program.

Purification and characterization of an extracellular cellulase from Anoxybacillus gonensis O9 isolated from geothermal area in Turkey.

PubMed

Genc, Berna; Nadaroglu, Hayrunnisa; Adiguzel, Ahmet; Baltaci, Ozkan

2015-11-01

In the present study, cellulase was purified and characterized from Anoxybacillus gonensis (Gen bank Number: KM596794) which was isolated and characterized from Agri Diyadin Hot spring. It was found to synthesize cellulase which had a wide range of industrial applications. Twenty four-hour-cultured bacteria induced cellulase production and specific activities during the purification steps were 1.47, 81.06 and 109.4 EU mg(-1) protein at crude extract, ammonium sulphate precipitated and DEAE-Sephadex purification steps. The highest enzyme activity was observed at 50°C and the optimum range of pH was 3-10. Molecular weight of enzyme was determined approximately 40kDa. The kinetic parameters of cellulase against carboxymethylcellulose (CMC) were 153.4 pmol min(-1) mg for Vmax and 0.46mM for Km. Among effectors of the enzyme, Zn2+, Ca2+, Co2+ and EDTA decreased enzyme activity.

Validation of the VitaBit Sit–Stand Tracker: Detecting Sitting, Standing, and Activity Patterns

PubMed Central

Plasqui, Guy

2018-01-01

Sedentary behavior (SB) has detrimental consequences and cannot be compensated for through moderate-to-vigorous physical activity (PA). In order to understand and mitigate SB, tools for measuring and monitoring SB are essential. While current direct-to-customer wearables focus on PA, the VitaBit validated in this study was developed to focus on SB. It was tested in a laboratory and in a free-living condition, comparing it to direct observation and to a current best-practice device, the ActiGraph, on a minute-by-minute basis. In the laboratory, the VitaBit yielded specificity and negative predictive rates (NPR) of above 91.2% for sitting and standing, while sensitivity and precision ranged from 74.6% to 85.7%. For walking, all performance values exceeded 97.3%. In the free-living condition, the device revealed performance of over 72.6% for sitting with the ActiGraph as criterion. While sensitivity and precision for standing and walking ranged from 48.2% to 68.7%, specificity and NPR exceeded 83.9%. According to the laboratory findings, high performance for sitting, standing, and walking makes the VitaBit eligible for SB monitoring. As the results are not transferrable to daily life activities, a direct observation study in a free-living setting is recommended. PMID:29543766

Dampened hippocampal oscillations and enhanced spindle activity in an asymptomatic model of developmental cortical malformations

PubMed Central

Cid, Elena; Gomez-Dominguez, Daniel; Martin-Lopez, David; Gal, Beatriz; Laurent, François; Ibarz, Jose M.; Francis, Fiona; Menendez de la Prida, Liset

2014-01-01

Developmental cortical malformations comprise a large spectrum of histopathological brain abnormalities and syndromes. Their genetic, developmental and clinical complexity suggests they should be better understood in terms of the complementary action of independently timed perturbations (i.e., the multiple-hit hypothesis). However, understanding the underlying biological processes remains puzzling. Here we induced developmental cortical malformations in offspring, after intraventricular injection of methylazoxymethanol (MAM) in utero in mice. We combined extensive histological and electrophysiological studies to characterize the model. We found that MAM injections at E14 and E15 induced a range of cortical and hippocampal malformations resembling histological alterations of specific genetic mutations and transplacental mitotoxic agent injections. However, in contrast to most of these models, intraventricularly MAM-injected mice remained asymptomatic and showed no clear epilepsy-related phenotype as tested in long-term chronic recordings and with pharmacological manipulations. Instead, they exhibited a non-specific reduction of hippocampal-related brain oscillations (mostly in CA1); including theta, gamma and HFOs; and enhanced thalamocortical spindle activity during non-REM sleep. These data suggest that developmental cortical malformations do not necessarily correlate with epileptiform activity. We propose that the intraventricular in utero MAM approach exhibiting a range of rhythmopathies is a suitable model for multiple-hit studies of associated neurological disorders. PMID:24782720

Dampened hippocampal oscillations and enhanced spindle activity in an asymptomatic model of developmental cortical malformations.

PubMed

Cid, Elena; Gomez-Dominguez, Daniel; Martin-Lopez, David; Gal, Beatriz; Laurent, François; Ibarz, Jose M; Francis, Fiona; Menendez de la Prida, Liset

2014-01-01

Developmental cortical malformations comprise a large spectrum of histopathological brain abnormalities and syndromes. Their genetic, developmental and clinical complexity suggests they should be better understood in terms of the complementary action of independently timed perturbations (i.e., the multiple-hit hypothesis). However, understanding the underlying biological processes remains puzzling. Here we induced developmental cortical malformations in offspring, after intraventricular injection of methylazoxymethanol (MAM) in utero in mice. We combined extensive histological and electrophysiological studies to characterize the model. We found that MAM injections at E14 and E15 induced a range of cortical and hippocampal malformations resembling histological alterations of specific genetic mutations and transplacental mitotoxic agent injections. However, in contrast to most of these models, intraventricularly MAM-injected mice remained asymptomatic and showed no clear epilepsy-related phenotype as tested in long-term chronic recordings and with pharmacological manipulations. Instead, they exhibited a non-specific reduction of hippocampal-related brain oscillations (mostly in CA1); including theta, gamma and HFOs; and enhanced thalamocortical spindle activity during non-REM sleep. These data suggest that developmental cortical malformations do not necessarily correlate with epileptiform activity. We propose that the intraventricular in utero MAM approach exhibiting a range of rhythmopathies is a suitable model for multiple-hit studies of associated neurological disorders.

Specific Calpain Inhibition by Calpastatin Prevents Tauopathy and Neurodegeneration and Restores Normal Lifespan in Tau P301L Mice

PubMed Central

McBrayer, Mary Kate; Campbell, Jabbar; Kumar, Asok; Hashim, Audrey; Sershen, Henry; Stavrides, Philip H.; Ohno, Masuo; Hutton, Michael; Nixon, Ralph A.

2014-01-01

Tau pathogenicity in Alzheimer's disease and other tauopathies is thought to involve the generation of hyperphosphorylated, truncated, and oligomeric tau species with enhanced neurotoxicity, although the generative mechanisms and the implications for disease therapy are not well understood. Here, we report a striking rescue from mutant tau toxicity in the JNPL3 mouse model of tauopathy. We show that pathological activation of calpains gives rise to a range of potentially toxic forms of tau, directly, and by activating cdk5. Calpain overactivation in brains of these mice is accelerated as a result of the marked depletion of the endogenous calpain inhibitor, calpastatin. When levels of this inhibitor are restored in neurons of JNPL3 mice by overexpressing calpastatin, tauopathy is prevented, including calpain-mediated breakdown of cytoskeletal proteins, cdk5 activation, tau hyperphosphorylation, formation of potentially neurotoxic tau fragments by either calpain or caspase-3, and tau oligomerization. Calpastatin overexpression also prevents loss of motor axons, delays disease onset, and extends survival of JNPL3 mice by 3 months to within the range of normal lifespan. Our findings support the therapeutic promise of highly specific calpain inhibition in the treatment of tauopathies and other neurodegenerative states. PMID:25009256

Non-antigenic and low allergic gelatin produced by specific digestion with an enzyme-coupled matrix.

PubMed

Sakai, Y; Yamato, R; Onuma, M; Kikuta, T; Watanabe, M; Nakayama, T

1998-04-01

Porcine gelatin (heat-denatured collagen) was digested with a bioreactor using an enzyme-coupled matrix (ECM) with purified collagenase. The digested gelatin, FreAlagin type R (M.W. range 200-10000 Da), was further purified by an HPLC system depending upon molecular size. The molecular weight range of the purified fractions, FreAlagin type P and type AD, were 200-500 and 2000-10000 Da, respectively, and glycine was the N-terminal amino acid of both types (> or =93%). ECM has the capability of digesting gelatin at a specific point in the sequence before glycine, and it was determined that FreAlagin type P consists of a tri-peptide fraction with the amino acid sequence Gly-X-Y. No types of FreAlagin exhibited any reactivity with gelatin-specific IgG antibody raised in guinea pigs, and they also possessed an extremely low reactivity with gelatin-specific IgE antibody from the sera of patients who had experienced an anaphylactic reaction against gelatin after vaccination or after eating gelatin-containing foods. From these results, it was determined that FreAlagin types R and AD were non-antigenic, low-allergic gelatins. FreAlagin type R, and especially type AD, had strong adsorption-blocking activity comparable to the level of bovine serum albumin, whereas type P and glycine had virtually no adsorption-blocking activity. Therefore, the new types of gelatin, FreAlagin types R and AD, are suitable for pharmaceutical use to avoid gelatin allergy.

Specific cognitive functions and depressive symptoms as predictors of activities of daily living in older adults with heterogeneous cognitive backgrounds

PubMed Central

de Paula, Jonas J.; Diniz, Breno S.; Bicalho, Maria A.; Albuquerque, Maicon Rodrigues; Nicolato, Rodrigo; de Moraes, Edgar N.; Romano-Silva, Marco A.; Malloy-Diniz, Leandro F.

2015-01-01

Cognitive functioning influences activities of daily living (ADL). However, studies reporting the association between ADL and neuropsychological performance show inconsistent results regarding what specific cognitive domains are related to each specific functional domains. Additionally, whether depressive symptoms are associated with a worse functional performance in older adults is still under explored. We investigated if specific cognitive domains and depressive symptoms would affect different aspects of ADL. Participants were 274 older adults (96 normal aging participants, 85 patients with mild cognitive impairment, and 93 patients probable with mild Alzheimer’s disease dementia) with low formal education (∼4 years). Measures of ADL included three complexity levels: Self-care, Instrumental-Domestic, and Instrumental-Complex. The specific cognitive functions were evaluated through a factorial strategy resulting in four cognitive domains: Executive Functions, Language/Semantic Memory, Episodic Memory, and Visuospatial Abilities. The Geriatric Depression Scale measured depressive symptoms. Multiple linear regression analysis showed executive functions and episodic memory as significant predictors of Instrumental-Domestic ADL, and executive functions, episodic memory and language/semantic memory as predictors of Instrumental-Complex ADL (22 and 28% of explained variance, respectively). Ordinal regression analysis showed the influence of specific cognitive functions and depressive symptoms on each one of the instrumental ADL. We observed a heterogeneous pattern of association with explained variance ranging from 22 to 38%. Different instrumental ADL had specific cognitive predictors and depressive symptoms were predictive of ADL involving social contact. Our results suggest a specific pattern of influence depending on the specific instrumental daily living activity. PMID:26257644

Oxidation of Wine Polyphenols by Secretomes of Wild Botrytis cinerea Strains from White and Red Grape Varieties and Determination of Their Specific Laccase Activity.

PubMed

Zimdars, Sabrina; Hitschler, Julia; Schieber, Andreas; Weber, Fabian

2017-12-06

Processing of Botrytis cinerea-infected grapes leads to enhanced enzymatic browning reactions mainly caused by the enzyme laccase which is able to oxidize a wide range of phenolic compounds. The extent of color deterioration depends on the activity of the enzymes secreted by the fungus. The present study revealed significant differences in the oxidative properties of secretomes of several B. cinerea strains isolated from five grape varieties. The presumed laccase-containing secretomes varied in their catalytic activity toward six phenolic compounds present in grapes. All strains led to identical product profiles for five of six substrates, but two strains showed deviating product profiles during gallic acid oxidation. Fast oxidation of caffeic acid, ferulic acid, and malvidin 3-O-glucoside was observed. Product formation rates and relative product concentrations were determined. The results reflect the wide range of enzyme activity and the corresponding different impact on color deterioration by B. cinerea.

Measurement of natural radionuclides in phosphgypsum using an anti-cosmic gamma-ray spectrometer.

PubMed

Ferreux, Laurent; Moutard, Gérard; Branger, Thierry

2009-05-01

Gamma-ray spectrometry measurements have been carried out to determine the activity of natural radionuclides in a phosphogypsum sample included in a specific tight container. The gamma spectrometer includes an N-type coaxial high-purity germanium (HPGe) detector equipped with an anti-cosmic system. This measurement required the determination of linear attenuation coefficients of phosphogypsum to calculate self-absorption correction between efficiency calibration conditions and measurement ones. The results are given for the three natural chains and for (40)K, in term of specific activity/g of dry material, ranging from a few Bq kg(-1) to a few hundreds Bq kg(-1). The equilibrium within the different families and the (235)U/(238)U ratio are discussed.

Biochemical characterisation of the esterase activities of wine lactic acid bacteria.

PubMed

Matthews, Angela; Grbin, Paul R; Jiranek, Vladimir

2007-11-01

Esters are an important group of volatile compounds that can contribute to wine flavour. Wine lactic acid bacteria (LAB) have been shown to produce esterases capable of hydrolysing ester substrates. This study aims to characterise the esterase activities of nine LAB strains under important wine conditions, namely, acidic conditions, low temperature (to 10 degrees C) and in the presence of ethanol (2-18% v/v). Esterase substrate specificity was also examined using seven different ester substrates. The bacteria were generally found to have a broad pH activity range, with the majority of strains showing maximum activity close to pH 6.0. Exceptions included an Oenococcus oeni strain that retained most activity even down to a pH of 4.0. Most strains exhibited highest activity across the range 30-40 degrees C. Increasing ethanol concentration stimulated activity in some of the strains. In particular, O. oeni showed an increase in activity up to a maximum ethanol concentration of around 16%. Generally, strains were found to have greater activity towards short-chained esters (C2-C8) compared to long-chained esters (C10-C18). Even though the optimal physicochemical conditions for enzyme activity differed from those found in wine, these findings are of potential importance to oenology because significant activities remained under wine-like conditions.

Functionality based detection of airborne engineered nanoparticles in quasi real time: a new type of detector and a new metric.

PubMed

Neubauer, Nicole; Seipenbusch, Martin; Kasper, Gerhard

2013-08-01

A new type of detector which we call the Catalytic Activity Aerosol Monitor (CAAM) was investigated towards its capability to detect traces of commonly used industrial catalysts in ambient air in quasi real time. Its metric is defined as the catalytic activity concentration (CAC) expressed per volume of sampled workplace air. We thus propose a new metric which expresses the presence of nanoparticles in terms of their functionality - in this case a functionality of potential relevance for damaging effects - rather than their number, surface, or mass concentration in workplace air. The CAAM samples a few micrograms of known or anticipated airborne catalyst material onto a filter first and then initiates a chemical reaction which is specific to that catalyst. The concentration of specific gases is recorded using an IR sensor, thereby giving the desired catalytic activity. Due to a miniaturization effort, the laboratory prototype is compact and portable. Sensitivity and linearity of the CAAM response were investigated with catalytically active palladium and nickel nano-aerosols of known mass concentration and precisely adjustable primary particle size in the range of 3-30 nm. With the miniature IR sensor, the smallest detectable particle mass was found to be in the range of a few micrograms, giving estimated sampling times on the order of minutes for workplace aerosol concentrations typically reported in the literature. Tests were also performed in the presence of inert background aerosols of SiO2, TiO2, and Al2O3. It was found that the active material is detectable via its catalytic activity even when the particles are attached to a non-active background aerosol.

Cell-Specific Production and Antimicrobial Activity of Naphthoquinones in Roots of Lithospermum erythrorhizon1

PubMed Central

Brigham, Lindy A.; Michaels, Paula J.; Flores, Hector E.

1999-01-01

Pigmented naphthoquinone derivatives of shikonin are produced at specific times and in specific cells of Lithospermum erythrorhizon roots. Normal pigment development is limited to root hairs and root border cells in hairy roots grown on “noninducing” medium, whereas induction of additional pigment production by abiotic (CuSO4) or biotic (fungal elicitor) factors increases the amount of total pigment, changes the ratios of derivatives produced, and initiates production of pigment de novo in epidermal cells. When the biological activity of these compounds was tested against soil-borne bacteria and fungi, a wide range of sensitivity was recorded. Acetyl-shikonin and β-hydroxyisovaleryl-shikonin, the two most abundant derivatives in both Agrobacterium rhizogenes-transformed “hairy-root” cultures and greenhouse-grown plant roots, were the most biologically active of the seven compounds tested. Hyphae of the pathogenic fungi Rhizoctonia solani, Pythium aphanidermatum, and Nectria hematococca induced localized pigment production upon contact with the roots. Challenge by R. solani crude elicitor increased shikonin derivative production 30-fold. We have studied the regulation of this suite of related, differentially produced, differentially active compounds to understand their role(s) in plant defense at the cellular level in the rhizosphere. PMID:9952436

Mirror movements in unilateral spastic cerebral palsy: Specific negative impact on bimanual activities of daily living.

PubMed

Adler, Caroline; Berweck, Steffen; Lidzba, Karen; Becher, Thomas; Staudt, Martin

2015-09-01

Mirror movements are involuntary movements of the other hand during voluntary unimanual movements. Some, but not all children with unilateral spastic cerebral palsy (USCP) show this phenomenon. In this observational study, we investigated whether these mirror movements have a specific negative impact on bimanual activities of daily living. Eighteen children (six girls; age range, 6-16 years; mean age, 12 years 1 month; SD, 3 years 3 month) with USCP, nine with and nine without mirror movements, underwent the Jebsen Taylor Hand Function Test (unimanual capacity) and the Assisting Hand Assessment (bimanual performance). In addition, we measured the time the participants needed for the completion of five activities we had identified as particularly difficult for children with mirror movements. Multivariate analysis demonstrated that mirror movements indeed have a specific negative impact on bimanual performance (Assisting Hand Assessment) and on the time needed for the completion of these five particularly difficult activities. This effect was independent from unimanual capacity. Functional therapies in children with USCP and mirror movements should address this phenomenon. Copyright © 2015 European Paediatric Neurology Society. Published by Elsevier Ltd. All rights reserved.

Coexistence of coyotes (Canis latrans) and red foxes (Vulpes vulpes) in an urban landscape.

PubMed

Mueller, Marcus A; Drake, David; Allen, Maximilian L

2018-01-01

Urban environments are increasing worldwide and are inherently different than their rural counterparts, with a variety of effects on wildlife due to human presence, increased habitat fragmentation, movement barriers, and access to anthropogenic food sources. Effective management of urban wildlife requires an understanding of how urbanization affects their behavior and ecology. The spatial activity and interactions of urban wildlife, however, have not been as rigorously researched as in rural areas. From January 2015 to December 2016, we captured, radio-collared, and tracked 11 coyotes and 12 red foxes in Madison, WI. Within our study area, coyotes strongly selected home ranges with high proportions of natural areas; conversely, red foxes selected home ranges with open space and moderately developed areas. Use of highly developed areas best explained variation among individual home range sizes and inversely affected home range size for coyotes and red foxes. Coyote and red fox home ranges showed some degree of spatial and temporal overlap, but generally appeared partitioned by habitat type within our study area. Coyotes and red foxes were both active at similar times of the day, but their movement patterns differed based on species-specific habitat use. This spatial partitioning may promote positive co-existence between these sympatric canids in urban areas, and our findings of spatial activity and interactions will better inform wildlife managers working in urban areas.

Coexistence of coyotes (Canis latrans) and red foxes (Vulpes vulpes) in an urban landscape

PubMed Central

Drake, David; Allen, Maximilian L.

2018-01-01

Urban environments are increasing worldwide and are inherently different than their rural counterparts, with a variety of effects on wildlife due to human presence, increased habitat fragmentation, movement barriers, and access to anthropogenic food sources. Effective management of urban wildlife requires an understanding of how urbanization affects their behavior and ecology. The spatial activity and interactions of urban wildlife, however, have not been as rigorously researched as in rural areas. From January 2015 to December 2016, we captured, radio-collared, and tracked 11 coyotes and 12 red foxes in Madison, WI. Within our study area, coyotes strongly selected home ranges with high proportions of natural areas; conversely, red foxes selected home ranges with open space and moderately developed areas. Use of highly developed areas best explained variation among individual home range sizes and inversely affected home range size for coyotes and red foxes. Coyote and red fox home ranges showed some degree of spatial and temporal overlap, but generally appeared partitioned by habitat type within our study area. Coyotes and red foxes were both active at similar times of the day, but their movement patterns differed based on species-specific habitat use. This spatial partitioning may promote positive co-existence between these sympatric canids in urban areas, and our findings of spatial activity and interactions will better inform wildlife managers working in urban areas. PMID:29364916

Successful outcome of modified quad surgical procedure in preteen and teen patients with brachial plexus birth palsy.

PubMed

Nath, Rahul K; Somasundaram, Chandra

2012-01-01

To evaluate the outcome of modified Quad procedure in preteen and teen patients with brachial plexus birth palsy. We have previously demonstrated a significant improvement in shoulder abduction, resulting from the modified Quad procedure in children (mean age 2.5 years; range, 0.5-9 years) with obstetric brachial plexus injury. We describe in this report the outcome of 16 patients (6 girls and 10 boys; 7 preteen and 9 teen) who have undergone the modified Quad procedure for the correction of the shoulder function, specifically abduction. The patients underwent transfer of the latissimus dorsi and teres major muscles, release of contractures of subscapularis pectoralis major and minor, and axillary nerve decompression and neurolysis (the modified Quad procedure). Mean age of these patients at surgery was 13.5 years (range, 10.1-17.9 years). The mean preoperative total Mallet score was 14.8 (range, 10-20), and active abduction was 84° (range, 20°-140°). At a mean follow-up of 1.5 years, the mean postoperative total Mallet score increased to 19.7 (range, 13-25, P < .0001), and the mean active abduction improved to 132° (range, 40°-180°, P < .0003). The modified Quad procedure greatly improves not only the active abduction but also other shoulder functions in preteen and teen patients, as this outcome is the combined result of decompression and neurolysis of the axillary nerve and the release of the contracted internal rotators of the shoulder.

Influences of internal resistance and specific surface area of electrode materials on characteristics of electric double layer capacitors

NASA Astrophysics Data System (ADS)

Suda, Yoshiyuki; Mizutani, Akitaka; Harigai, Toru; Takikawa, Hirofumi; Ue, Hitoshi; Umeda, Yoshito

2017-01-01

We fabricated electric double layer capacitors (EDLCs) using particulate and fibrous types of carbon nanomaterials with a wide range of specific surface areas and resistivity as an active material. The carbon nanomaterials used in this study are carbon nanoballoons (CNBs), onion-like carbon (OLC), and carbon nanocoils (CNCs). A commercially used activated carbon (AC) combined with a conductive agent was used as a comparison. We compared the EDLC performance using cyclic voltammetry (CV), galvanostatic charge/discharge testing, and electrochemical impedance spectroscopy (EIS). OLC showed a poor EDLC performance, although it has the lowest resistivity among the carbon nanomaterials. CNB, which has a 1/16 lower specific surface area than AC but higher specific surface area than CNC and OLC, had a higher specific capacitance than CNC and OLC. Moreover, at current densities of 1.5 Ag-1 and larger, the specific capacitance of the EDLC using CNB was almost the same as that using AC. Electrochemical impedance spectroscopy of the EDLCs revealed that the CNB and CNC electrodes had a much lower internal resistance than the AC electrode, which correlated with a low capacitance maintenance factor as the current density increased.

Configuration management issues and objectives for a real-time research flight test support facility

NASA Technical Reports Server (NTRS)

Yergensen, Stephen; Rhea, Donald C.

1988-01-01

An account is given of configuration management activities for the Western Aeronautical Test Range (WATR) at NASA-Ames, whose primary function is the conduct of aeronautical research flight testing through real-time processing and display, tracking, and communications systems. The processing of WATR configuration change requests for specific research flight test projects must be conducted in such a way as to refrain from compromising the reliability of WATR support to all project users. Configuration management's scope ranges from mission planning to operations monitoring and performance trend analysis.

Rapid Debris Analysis Project Task 3 Final Report - Sensitivity of Fallout to Source Parameters, Near-Detonation Environment Material Properties, Topography, and Meteorology

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

Goldstein, Peter

2014-01-24

This report describes the sensitivity of predicted nuclear fallout to a variety of model input parameters, including yield, height of burst, particle and activity size distribution parameters, wind speed, wind direction, topography, and precipitation. We investigate sensitivity over a wide but plausible range of model input parameters. In addition, we investigate a specific example with a relatively narrow range to illustrate the potential for evaluating uncertainties in predictions when there are more precise constraints on model parameters.

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.

Biodesulfurization of refractory organic sulfur compounds in fossil fuels.

PubMed

Soleimani, Mehran; Bassi, Amarjeet; Margaritis, Argyrios

2007-01-01

The stringent new regulations to lower sulfur content in fossil fuels require new economic and efficient methods for desulfurization of recalcitrant organic sulfur. Hydrodesulfurization of such compounds is very costly and requires high operating temperature and pressure. Biodesulfurization is a non-invasive approach that can specifically remove sulfur from refractory hydrocarbons under mild conditions and it can be potentially used in industrial desulfurization. Intensive research has been conducted in microbiology and molecular biology of the competent strains to increase their desulfurization activity; however, even the highest activity obtained is still insufficient to fulfill the industrial requirements. To improve the biodesulfurization efficiency, more work is needed in areas such as increasing specific desulfurization activity, hydrocarbon phase tolerance, sulfur removal at higher temperature, and isolating new strains for desulfurizing a broader range of sulfur compounds. This article comprehensively reviews and discusses key issues, advances and challenges for a competitive biodesulfurization process.

Neurotransmitters couple brain activity to subventricular zone neurogenesis

PubMed Central

Young, Stephanie Z.; Taylor, M. Morgan; Bordey, Angélique

2011-01-01

Adult neurogenesis occurs in two privileged microenvironments, the hippocampal subgranular zone of the dentate gyrus and the subventricular zone (SVZ) along the lateral ventricle. This review focuses on accumulating evidence suggesting that the activity of specific brain regions or bodily states influences SVZ cell proliferation and neurogenesis. Neuromodulators such as dopamine and serotonin have been shown to have long-range effects through neuronal projections into the SVZ. Local GABA and glutamate signaling have demonstrated effects on SVZ proliferation and neurogenesis, but an extra-niche source of these neurotransmitters remains to be explored and options will be discussed. There is also accumulating evidence that diseases and bodily states such as Alzheimer's disease, seizures, sleep, and pregnancy influence SVZ cell proliferation. With such complex behavior and environmentally-driven factors that control subregion-specific activity, it will become necessary to account for overlapping roles of multiple neurotransmitter systems on neurogenesis when developing cell therapies or drug treatments. PMID:21395856

Neurochemistry of neurons in the ventrolateral medulla activated by hypotension: Are the same neurons activated by glucoprivation?

PubMed

Parker, Lindsay M; Le, Sheng; Wearne, Travis A; Hardwick, Kate; Kumar, Natasha N; Robinson, Katherine J; McMullan, Simon; Goodchild, Ann K

2017-06-15

Previous studies have demonstrated that a range of stimuli activate neurons, including catecholaminergic neurons, in the ventrolateral medulla. Not all catecholaminergic neurons are activated and other neurochemical content is largely unknown hence whether stimulus specific populations exist is unclear. Here we determine the neurochemistry (using in situ hybridization) of catecholaminergic and noncatecholaminergic neurons which express c-Fos immunoreactivity throughout the rostrocaudal extent of the ventrolateral medulla, in Sprague Dawley rats treated with hydralazine or saline. Distinct neuronal populations containing PPCART, PPPACAP, and PPNPY mRNAs, which were largely catecholaminergic, were activated by hydralazine but not saline. Both catecholaminergic and noncatecholaminergic neurons containing preprotachykinin and prepro-enkephalin (PPE) mRNAs were also activated, with the noncatecholaminergic population located in the rostral C1 region. Few GlyT2 neurons were activated. A subset of these data was then used to compare the neuronal populations activated by 2-deoxyglucose evoked glucoprivation (Brain Structure and Function (2015) 220:117). Hydralazine activated more neurons than 2-deoxyglucose but similar numbers of catecholaminergic neurons. Commonly activated populations expressing PPNPY and PPE mRNAs were defined. These likely include PPNPY expressing catecholaminergic neurons projecting to vasopressinergic and corticotrophin releasing factor neurons in the paraventricular nucleus, which when activated result in elevated plasma vasopressin and corticosterone. Stimulus specific neurons included noncatecholaminergic neurons and a few PPE positive catecholaminergic neuron but neurochemical codes were largely unidentified. Reasons for the lack of identification of stimulus specific neurons, readily detectable using electrophysiology in anaesthetized preparations and for which neural circuits can be defined, are discussed. © 2017 Wiley Periodicals, Inc.

Predictors of participation in sports after hip and knee arthroplasty.

PubMed

Williams, Daniel H; Greidanus, Nelson V; Masri, Bassam A; Duncan, Clive P; Garbuz, Donald S

2012-02-01

While the primary objective of joint arthroplasty is to improve patient quality of life, pain, and function, younger active patients often demand a return to higher function that includes sporting activity. Knowledge of rates and predictors of return to sports will help inform expectations in patients anticipating return to sports after joint arthroplasty. We measured the rate of sports participation at 1 year using the UCLA activity score and explored 11 variables, including choice of procedure/prosthesis, that might predict return to a high level of sporting activity, when controlling for potential confounding variables. We retrospectively evaluated 736 patients who underwent primary metal-on-polyethylene THA, metal-on-metal THA, hip resurfacing arthroplasty, revision THA, primary TKA, unicompartmental knee arthroplasty, and revision TKA between May 2005 and June 2007. We obtained UCLA activity scores on all patients; we defined high activity as a UCLA score of 7 or more. We evaluated patient demographics (age, sex, BMI, comorbidity), quality of life (WOMAC score, Oxford Hip Score, SF-12 score), and surgeon- and procedural/implant-specific variables to identify factors associated with postoperative activity score. Minimum followup was 11 months (mean, 12.1 months; range, 11-13 months). Preoperative UCLA activity score, age, male sex, and BMI predicted high activity scores. The type of operation and implant characteristics did not predict return to high activity sports. Our data suggest patient-specific factors predict postoperative activity rather than factors specific to type of surgery, implant, or surgeon factors. Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Foot kinematics and loading of professional athletes in American football-specific tasks.

PubMed

Riley, Patrick O; Kent, Richard W; Dierks, Tracy A; Lievers, W Brent; Frimenko, Rebecca E; Crandall, Jeff R

2013-09-01

The purpose of this study was to describe stance foot and ankle kinematics and the associated ground reaction forces at the upper end of human performance in professional football players during commonly performed football-specific tasks. Nine participants were recruited from the spring training squad of a professional football team. In a motion analysis laboratory setting, participants performed three activities used at the NFL Scouting Combine to assess player speed and agility: the 3-cone drill, the shuttle run, and the standing high jump. The talocrural and first metatarsophalangial joint dorsiflexion, subtalar joint inversion, and the ground reaction forces were determined for the load bearing portions of each activity. We documented load-bearing foot and ankle kinematics of elite football players performing competition-simulating activities, and confirmed our hypothesis that the talocrural, subtalar, and metatarsophalangeal joint ranges of motion for the activities studied approached or exceeded reported physiological limits. Copyright © 2012 Elsevier B.V. All rights reserved.

Casein Hydrolysates by Lactobacillus brevis and Lactococcus lactis Proteases: Peptide Profile Discriminates Strain-Dependent Enzyme Specificity.

PubMed

Bounouala, Fatima Zohra; Roudj, Salima; Karam, Nour-Eddine; Recio, Isidra; Miralles, Beatriz

2017-10-25

Casein from ovine and bovine milk were hydrolyzed with two extracellular protease preparations from Lactobacillus brevis and Lactococcus lactis. The hydrolysates were analyzed by HPLC-MS/MS for peptide identification. A strain-dependent peptide profile could be observed, regardless of the casein origin, and the specificity of these two proteases could be computationally ascribed. The cleavage pattern yielding phenylalanine, leucine, or tyrosine at C-terminal appeared both at L. lactis and Lb. brevis hydrolysates. However, the cleavage C-terminal to lysine was favored with Lb. brevis protease. The hydrolysates showed ACE-inhibitory activity with IC 50 in the 16-70 μg/mL range. Ovine casein hydrolysates yielded greater ACE-inhibitory activity. Previously described antihypertensive and opioid peptides were found in these ovine and bovine casein hydrolysates and prediction of the antihypertensive activity of the sequences based on quantitative structure and activity relationship (QSAR) was performed. This approach might represent a useful classification tool regarding health-related properties prior to further purification.

Digital micromirror based near-infrared illumination system for plasmonic photothermal neuromodulation

PubMed Central

Jung, Hyunjun; Kang, Hongki; Nam, Yoonkey

2017-01-01

Light-mediated neuromodulation techniques provide great advantages to investigate neuroscience due to its high spatial and temporal resolution. To generate a spatial pattern of neural activity, it is necessary to develop a system for patterned-light illumination to a specific area. Digital micromirror device (DMD) based patterned illumination system have been used for neuromodulation due to its simple configuration and design flexibility. In this paper, we developed a patterned near-infrared (NIR) illumination system for region specific photothermal manipulation of neural activity using NIR-sensitive plasmonic gold nanorods (GNRs). The proposed system had high power transmission efficiency for delivering power density up to 19 W/mm2. We used a GNR-coated microelectrode array (MEA) to perform biological experiments using E18 rat hippocampal neurons and showed that it was possible to inhibit neural spiking activity of specific area in neural circuits with the patterned NIR illumination. This patterned NIR illumination system can serve as a promising neuromodulation tool to investigate neuroscience in a wide range of physiological and clinical applications. PMID:28663912

Unnatural amino acids increase activity and specificity of synthetic substrates for human and malarial cathepsin C.

PubMed

Poreba, Marcin; Mihelic, Marko; Krai, Priscilla; Rajkovic, Jelena; Krezel, Artur; Pawelczak, Malgorzata; Klemba, Michael; Turk, Dusan; Turk, Boris; Latajka, Rafal; Drag, Marcin

2014-04-01

Mammalian cathepsin C is primarily responsible for the removal of N-terminal dipeptides and activation of several serine proteases in inflammatory or immune cells, while its malarial parasite ortholog dipeptidyl aminopeptidase 1 plays a crucial role in catabolizing the hemoglobin of its host erythrocyte. In this report, we describe the systematic substrate specificity analysis of three cathepsin C orthologs from Homo sapiens (human), Bos taurus (bovine) and Plasmodium falciparum (malaria parasite). Here, we present a new approach with a tailored fluorogenic substrate library designed and synthesized to probe the S1 and S2 pocket preferences of these enzymes with both natural and a broad range of unnatural amino acids. Our approach identified very efficiently hydrolyzed substrates containing unnatural amino acids, which resulted in the design of significantly better substrates than those previously known. Additionally, in this study significant differences in terms of the structures of optimal substrates for human and malarial orthologs are important from the therapeutic point of view. These data can be also used for the design of specific inhibitors or activity-based probes.

Quantifying space use of breeders and floaters of a long-lived species using individual movement data.

PubMed

Penteriani, Vincenzo; del Mar Delgado, Maria; Campioni, Letizia

2015-06-01

To date, animal movement studies have mostly analysed the movement behaviours of individuals at specific times of their lives, but we lack detailed information on how individual movements may be affected by the various and different changes that individuals experience throughout their life (e.g. life history phases, experience, age). Here, we attempt to identify differences in home range and movement behaviour between two different statuses, disperser vs. breeder, of a long-lived species (the eagle owl Bubo bubo). Information on home range and movement behaviour between different stages of an individual life are crucial for species conservation and management, as well as for basic knowledge on space use and rhythm of activity. Does the transition from an exploratory stage to moving within more familiar surroundings call for changes in the movement behaviour? We observed notable differences during the two stages of the owls' lives, with individuals having different home range behaviours and rhythms of activity depending on their social status. Significant differences in home range behaviour between the sexes began only with the acquisition of a breeding site. Breeders showed larger home ranges than dispersing individuals, although nightly variation of home ranges size was higher for dispersers than for breeders. Finally, dispersers were active throughout the night, whereas breeders displayed a less active movement phase at both the beginning and end of the night. Our results demonstrate it is important to consider individual variations in space use and movement behaviour due to the different life history phases that they attain during their lifetime. The knowledge of the different needs of a species across life stages may represent an important tool for species conservation because each phase of an individual life may need different requirements.

Quantifying space use of breeders and floaters of a long-lived species using individual movement data

NASA Astrophysics Data System (ADS)

Penteriani, Vincenzo; del Mar Delgado, Maria; Campioni, Letizia

2015-06-01

To date, animal movement studies have mostly analysed the movement behaviours of individuals at specific times of their lives, but we lack detailed information on how individual movements may be affected by the various and different changes that individuals experience throughout their life (e.g. life history phases, experience, age). Here, we attempt to identify differences in home range and movement behaviour between two different statuses, disperser vs. breeder, of a long-lived species (the eagle owl Bubo bubo). Information on home range and movement behaviour between different stages of an individual life are crucial for species conservation and management, as well as for basic knowledge on space use and rhythm of activity. Does the transition from an exploratory stage to moving within more familiar surroundings call for changes in the movement behaviour? We observed notable differences during the two stages of the owls' lives, with individuals having different home range behaviours and rhythms of activity depending on their social status. Significant differences in home range behaviour between the sexes began only with the acquisition of a breeding site. Breeders showed larger home ranges than dispersing individuals, although nightly variation of home ranges size was higher for dispersers than for breeders. Finally, dispersers were active throughout the night, whereas breeders displayed a less active movement phase at both the beginning and end of the night. Our results demonstrate it is important to consider individual variations in space use and movement behaviour due to the different life history phases that they attain during their lifetime. The knowledge of the different needs of a species across life stages may represent an important tool for species conservation because each phase of an individual life may need different requirements.

Sexual division of labor: energetic and evolutionary scenarios.

PubMed

Panter-Brick, Catherine

2002-01-01

This article examines comparative energetic data on hunter-gatherers in the context of evolutionary scenarios of the sexual division of labor, with respect to both specific task allocation and overall levels of daily physical activity. The division of labor between men and women, well marked in contemporary foraging societies, was once posited as the "true watershed" for the evolution of the genus Homo. Some research on brain-wiring even links sex differences in cognitive and spatial abilities to sex-specific foraging activities. Most recent evolutionary arguments posit that men focus on hunting and women on gathering activities to realize potentially conflicting mating and parenting goals. A range of cooperative strategies (male/female and female/female) for child provisioning is also under investigation. Attention to energetic and reproductive trade-offs has usefully challenged the proposition that women are excluded from big-game hunting due to constraints of foraging ecology and reproduction. Simplistic assumptions about gender roles are thus increasingly questioned in anthropology, as well as in archaeology. Current models in behavioral ecology explore ways in which foraging practices vary with ecological circumstances, aiming to derive testable hypotheses from fine-grained data on the behavior of contemporary hunter-gatherers. Data on overall physical activity levels (PAL) can also serve to evaluate relative male/female workloads in modern groups, reconstruct hominid energy requirements and activity profiles, and examine changes with subsistence intensification. Male/female PAL ratios show that a task-specific division of labor does not readily extrapolate to 24-hour energy expenditure and that male/female differences in workloads were not necessarily reduced with the transition to agriculture. With respect to gender roles and PAL, a shift away from facile stereotypes of human behavior is evident. The challenge is to incorporate a range of behavioral responses to ecological circumstances in reconstructions of our evolutionary past. Copyright 2002 Wiley-Liss, Inc.

Measurement of natural radioactivity and assessment of radiation hazard indices in soil samples at Pengerang, Kota Tinggi, Johor

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

Hassan, Nur Nazihah; Khoo, Kok Siong

Pengerang area consists of a mix of private plantation, individual residential lots and state land, which is leased for agriculture related activities. The analysis was conducted to determine the specific activity of the initial value and the radiation hazard indices in the surrounding area in Pengerang. This area will be developed into a major downstream for oil and gas. The aims of this preliminary study were 1) to determine the specific activities of {sup 238}U, {sup 232}Th, {sup 226}Ra and {sup 40}K of soil samples at six selected areas by Gamma-ray spectrometry and 2) to calculate the radiation hazard indices.more » The specific activities (Bq/kg) of the samples ranged from 7.08±5.01 to 36.29±25.72 Bq/kg, 5.62±3.98 to 34.53±24.07 Bq/kg, 4.75±3.42 to 24.76±17.66 Bq/kg and 10.58±7.51 to 101.25±72.00 Bq/kg for {sup 238}U, {sup 232}Th, {sup 226}Ra and {sup 40}K, respectively. These values were well within the range that reported by UNSCEAR. The study also examined the radiation hazard indices, the mean values obtained were 48.49±28.06 Bq/kg for Radium Equivalent Activity (Raeq), 0.34 Bq/kg for Representative Level Index (I{sub γ}), 21.83 nGy/h for Absorbed dose rates (D), 0.27 mSv/y for Annual Effective Dose Rates (Deff), 0.13 and 0.18 for External Hazards Index (H{sub ex}) and Internal Hazard Index (H{sub in}), respectively. These calculated hazard indices were used to estimate the potential radiological health risk in soil and the dose rates associated with it were well below their permissible limit. The overall findings show that no radiological threat to the health of the population in the study area.« less

The Diagnostic Role of Magnetic Resonance Enterography as a Complementary Test to Colonoscopy in Active Crohn's Disease.

PubMed

Aryan, Arvin; Azizi, Zahra; Teimouri, Azam; Ebrahimi Daryani, Nasser; Aletaha, Najme; Jahanbakhsh, Ali; Nouritaromlou, Mohammad Kazem; Alborzi, Forough; Mami, Masoud; Basirat, Vahid; Javid Anbardan, Sanam

2016-04-01

BACKGROUND According to recent studies comparing magnetic resonance enterography (MRE) with ileocolonoscopy for assessing inflammation of small bowel and colonic segments in adults with active Crohn's disease (CD), we aimed to compare the accuracy of these two diagnostic methods in Iranian population. METHODS During 2013-2014 a follow-up study was done on 30 patients with active CD in a gastroenterology clinic affiliated to Tehran University of Medical Sciences. MRE and ileocolonoscopy were performed for all the patients. All statistical analyses were performed using SPSS (version 18) and p-value<0.05 was considered as statistically significant. RESULTS Of the 30 patients with active CD, 11(36.7%) were men and 19 (63.3%) were women with mean age of 37.30±13.66 years (range: 19-67 years). MRE had sensitivity and specificity of 50% and 90% with positive predictive value (PPV) and negative predictive value (NPV) of 71.43 and 78.26, respectively for localizing sigmoid lesions and ileum had sensitivity and specificity of 84.21 and 45.45 with PPV and NPV of 72.73 and 62.50, respectively. CONCLUSION While moderate sensitivity and high specificity of MRE in localizing colonic lesions makes it an appropriate confirmatory test after colonoscopy, the reported high sensitivity and moderate specificity of MRE versus colonoscopy in detecting ileal lesions makes it a suitable screening test for ileal lesions. Finally we can conclude that MRE can be an important complementary test to colonoscopy in detecting active disease.

Antiviral Effects of Small Interfering RNA Simultaneously Inducing RNA Interference and Type 1 Interferon in Coxsackievirus Myocarditis

PubMed Central

Ahn, Jeonghyun; Ko, Ara; Jun, Eun Jung; Won, Minah; Kim, Yoo Kyum; Ju, Eun-Seon

2012-01-01

Antiviral therapeutics are currently unavailable for treatment of coxsackievirus B3, which can cause life-threatening myocarditis. A modified small interfering RNA (siRNA) containing 5′-triphosphate, 3p-siRNA, was shown to induce RNA interference and interferon activation. We aimed to develop a potent antiviral treatment using CVB3-specific 3p-siRNA and to understand its underlying mechanisms. Virus-specific 3p-siRNA was superior to both conventional virus-specific siRNA with an empty hydroxyl group at the 5′ end (OH-siRNA) and nonspecific 3p-siRNA in decreasing viral replication and subsequent cytotoxicity. A single administration of 3p-siRNA dramatically attenuated virus-associated pathological symptoms in mice with no signs of toxicity, and their body weights eventually reached the normal range. Myocardial inflammation and fibrosis were rare, and virus production was greatly reduced. A nonspecific 3p-siRNA showed relatively less protective effect under identical conditions, and a virus-specific OH-siRNA showed no protective effects. We confirmed that virus-specific 3p-siRNA simultaneously activated target-specific gene silencing and type I interferon signaling. We provide a clear proof of concept that coxsackievirus B3-specific 3p-siRNA has 2 distinct modes of action, which significantly enhance antiviral activities with minimal organ damage. This is the first direct demonstration of improved antiviral effects with an immunostimulatory virus-specific siRNA in coxsackievirus myocarditis, and this method could be applied to many virus-related diseases. PMID:22508300

Phenology of the Hemlock Woolly Adelgid (Hemiptera: Adelgidae) in Northern Georgia

Treesearch

Shimar V. Joseph; Albert E. Mayfield; Mark J. Dalusky; Christopher Asaro; C. Wayne. Berisford

2011-01-01

Understanding the seasonal phenology of an insect pest in a specific geographic region is essential for optimizing the timing of management actions or research activities. We examined the phenology of hemlock woolly adelgid, Adelges tsugae Annand, near the southern limit of the range of eastern hemlock, Tsuga canadensis (L.) Carriere, in the Appalachians of northern...

Federal fire managers' perceptions of the importance, scarcity and substitutability of suppression resources

Treesearch

Crystal S. Stonesifer; David E. Calkin; Michael S. Hand

2017-01-01

Wildland firefighting in the United States is a complex and costly enterprise. While there are strong seasonal signatures for fire occurrence in specific regions of the United States, spatiotemporal occurrence of wildfire activity can have high inter-annual variability. Suppression resources come from a variety of jurisdictions and provide a wide range of skills,...

Increasing Children's Positive Connection to, Orientation toward, and Knowledge of Nature through Nature Camp Experiences

ERIC Educational Resources Information Center

San Jose, Alyssa L.; Nelson, Keith E.

2017-01-01

What do children actually carry away from participating in planned activities in natural areas such as those in outdoor camps and schools? Prior research has seldom been rigorous in establishing participants' connection to, knowledge of, and orientation toward nature before intervention, followed by a clear specification of what range of…

Assessing herbivore foraging behavior with GPS collars in a semiarid grassland.

PubMed

Augustine, David J; Derner, Justin D

2013-03-15

Advances in global positioning system (GPS) technology have dramatically enhanced the ability to track and study distributions of free-ranging livestock. Understanding factors controlling the distribution of free-ranging livestock requires the ability to assess when and where they are foraging. For four years (2008-2011), we periodically collected GPS and activity sensor data together with direct observations of collared cattle grazing semiarid rangeland in eastern Colorado. From these data, we developed classification tree models that allowed us to discriminate between grazing and non-grazing activities. We evaluated: (1) which activity sensor measurements from the GPS collars were most valuable in predicting cattle foraging behavior, (2) the accuracy of binary (grazing, non-grazing) activity models vs. models with multiple activity categories (grazing, resting, traveling, mixed), and (3) the accuracy of models that are robust across years vs. models specific to a given year. A binary classification tree correctly removed 86.5% of the non-grazing locations, while correctly retaining 87.8% of the locations where the animal was grazing, for an overall misclassification rate of 12.9%. A classification tree that separated activity into four different categories yielded a greater misclassification rate of 16.0%. Distance travelled in a 5 minute interval and the proportion of the interval with the sensor indicating a head down position were the two most important variables predicting grazing activity. Fitting annual models of cattle foraging activity did not improve model accuracy compared to a single model based on all four years combined. This suggests that increased sample size was more valuable than accounting for interannual variation in foraging behavior associated with variation in forage production. Our models differ from previous assessments in semiarid rangeland of Israel and mesic pastures in the United States in terms of the value of different activity sensor measurements for identifying grazing activity, suggesting that the use of GPS collars to classify cattle grazing behavior will require calibrations specific to the environment and vegetation being studied.

The Colorado front range: anatomy of a Laramide uplift

USGS Publications Warehouse

Kellogg, Karl; Bryant, Bruce; Reed, John C.

2004-01-01

Along a transect across the Front Range from Denver to the Blue River valley near Dillon, the trip explores the geologic framework and Laramide (Late Cretaceous to early Eocene) uplift history of this basement-cored mountain range. Specific items for discussion at various stops are (1) the sedimentary and structural record along the upturned eastern margin of the range, which contains several discontinuous, east-directed reverse faults; (2) the western structural margin of the range, which contains a minimum of 9 km of thrust overhang and is significantly different in structural style from the eastern margin; (3) mid- to late-Tertiary modifications to the western margin of the range from extensional faulting along the northern Rio Grande rift trend; (4) the thermal and uplift history of the range as revealed by apatite fission track analysis; (5) the Proterozoic basement of the range, including the significance of northeast-trending shear zones; and (6) the geologic setting of the Colorado mineral belt, formed during Laramide and mid-Tertiary igneous activity.

Characterisation of a detergent-stable alkaline protease from a novel thermophilic strain Paenibacillus tezpurensis sp. nov. AS-S24-II.

PubMed

Rai, Sudhir K; Roy, Jetendra K; Mukherjee, Ashis K

2010-02-01

An alkaline-protease-producing bacterial strain (AS-S24-II) isolated from a soil sample in Assam is a Gram-stain-positive, catalase-positive, endospore-forming rod and grows at temperatures ranging from 30 degrees C to 60 degrees C and salinity ranging from 0% to 7% (w/v) NaCl. Phenotypic characterisation, chemotaxonomic properties, presence of Paenibacillus-specific signature sequences, and ribotyping data suggested that the strain AS-S24-II represents a novel species of the genus Paenibacillus, for which the name Paenibacillus tezpurensis sp. nov. (MTCC 8959) is proposed. Phylogenetic analysis revealed that P. lentimorbus strain DNG-14 and P. lentimorbus strain DNG-16 represent the closest phylogenetic neighbour of this novel strain. Alkaline protease production (598 x 10(3) U l(-1)) by P. tezpurensis sp. nov. in SmF was optimised by response surface method. A laundry-detergent-stable, Ca(2+)-independent, 43-kDa molecular weight alkaline serine protease from this strain was purified with a 1.7-fold increase in specific activity. The purified protease displayed optimum activity at pH 9.5 and 45-50 degrees C temperature range and exhibited a significant stability and compatibility with surfactants and most of the tested commercial laundry detergents at room temperature. Further, the protease improved the wash performance of detergents, thus demonstrating its feasibility for inclusion in laundry detergent formulations.

Occurrence and Trends of Selected Chemical Constituents in Bottom Sediment, Grand Lake O' the Cherokees, Northeast Oklahoma, 1940-2008

USGS Publications Warehouse

Juracek, Kyle E.; Becker, Mark F.

2009-01-01

After over 100 years of continuous activity, lead and zinc mining in the Tri-State Mining District (hereafter referred to as the TSMD) in parts of southeast Kansas, southwest Missouri, and northeast Oklahoma ended in the 1970s. The mining activity resulted in substantial historical and ongoing input of cadmium, lead, and zinc to the environment including Grand Lake O' the Cherokees (hereafter referred to as Grand Lake), a large reservoir in northeast Oklahoma. To help determine the extent and magnitude of contamination in Grand Lake, a one-year study was conducted by the U.S. Geological Survey in cooperation with the U.S. Fish and Wildlife Service. Bottom-sediment coring at five sites was used to investigate the occurrence of cadmium, lead, zinc, and other selected constituents in the bottom sediment of Grand Lake. Cadmium concentrations in the bottom sediment of Grand Lake ranged from 2.3 to 3.6 mg/kg (milligrams per kilogram) with a median of 3.5 mg/kg (5 samples). Compared to an estimated local background concentration of 0.6 mg/kg, the historical mining activity increased cadmium concentrations by about 280 to 500 percent. Lead concentrations ranged from 35 to 102 mg/kg with a median of 59 mg/kg (50 samples). Compared to an estimated local background concentration of 20 mg/kg, the historical mining activity increased lead concentrations by about 75 to 410 percent. The range in zinc concentrations was 380 to 986 mg/kg with a median of 765 mg/kg (50 samples). Compared to an estimated local background concentration of 100 mg/kg, the historical mining activity increased zinc concentrations by about 280 to 890 percent. With the exception of the most upstream coring site, the lead and zinc depositional profiles generally were similar in terms of the range in concentrations measured and the temporal pattern observed. Depositional profiles for lead and zinc indicated mid-core peaks followed by concentrations that decreased since about the 1980s. The depositional profiles reflect the complex interaction of several factors including historical mining and related activities, mine drainage, remediation, landscape stabilization, precipitation and associated runoff, and the erosion and transport of contaminated and clean sediments within the basin. Compared to sediment-quality guidelines, the Grand Lake samples had cadmium concentrations that were substantially less than the general probable-effects concentration (PEC) (4.98 mg/kg) and a TSMD-specific PEC (11.1 mg/kg). The PECs represent the concentration above which toxic biological effects are likely to occur. Likewise, all sediment samples had lead concentrations that were substantially less than the general PEC (128 mg/kg) and a TSMD-specific PEC (150 mg/kg). Zinc concentrations typically exceeded the general PEC (459 mg/kg), but were substantially less than a TSMD-specific PEC (2,083 mg/kg). Throughout the history of Grand Lake, lead and zinc concentrations in the deposited sediment did not approach or exceed the TSMD-specific PECs. As of 2008, legacy effects of mining still included the delivery of contaminated sediment to Grand Lake by the Spring and Neosho Rivers. The Neosho River, with its larger flows and less-contaminated sediment, likely dilutes the load of contaminated sediment delivered to Grand Lake by the Spring River. The information contained in this report provides a baseline of Grand Lake conditions with which to compare future conditions that may represent a response to changes in mining-related activity in the Grand Lake Basin.

Tactical swimming activity and heart rate aspects of youth water polo game.

PubMed

Lupo, Corrado; Capranica, Laura; Cugliari, Giovanni; Gomez, Miguel A; Tessitore, Antonio

2016-09-01

Although physical demands could differently occur during particular phases of the youth water polo game, at present, literature lacks of time-motion and heart rate data referred to specific tactical situation. Therefore, the present study aimed to analyze a youth water polo game, specifying heart rate, and swimming activity aspects in relation to game situations. Twenty-six youth male players (15.6±0.5 years old) voluntary played a friendly game, which was tactically analyzed (offensive and defensive Even and Counterattack situation, and Power-play, Inferiority and Game Breaks) using notational analysis procedures. Successively, the heart rate (aerobic, anaerobic) and time motion (horizontal, vertical, and duel swimming patterns, with and without ball possession, backstroke) analyses were applied only to six (3 for team) players because they performed at list half of the total game duration. The tactical scenarios were mainly characterized by offensive (33%) and defensive (33%) even possessions, and game breaks (23%). No effect emerged between situations in terms of heart rate distribution, because it principally resulted as aerobic (range: 58-97%). The swimming activity analysis mainly showed differences (P≤0.05) between offensive counterattack and power-play in terms of distance (1 min of game, single pattern), time duration (1 min of game), and speed (single pattern) related to the horizontal activity. Repeated high intensity activities were performed 3.0±2.8 (range: 1-7) during the game. The findings of the present study provide important information for the planning of youth water polo training, with specific reference to playing situations.

Return to sport after total or unicompartmental knee arthroplasty

PubMed Central

Dagneaux, Louis; Bourlez, Julien; Degeorge, Benjamin; Canovas, François

2017-01-01

Knee arthroplasty survival rate — either UKA or TKA — is currently 95%, greater than it was ten years ago, but has not been specifically evaluated in very active patients practicing sport at a high intensity. The terms and conditions of return to physical activities are decided by the surgeon, the rehabilitation or Sports Medicine doctor, who needs to make sure that postoperative rehabilitation has been conducted optimally. Specifically, range of movement must be complete, muscular strengthening has to be sufficient and balance must be recovered by proprioception. Only after this stage (i.e. three to six months after surgery) can physical activities be resumed. Return to sport must be gentle and progressive, with moderate activities limited to short sessions. Progressively the patient will be able to return to intermediate activities, provided that he/she possesses the adequate level of technique for the sport. This up-to-date review for young surgeons and residents aims to provide an informative guide for patients regarding sport following knee arthroplasty. Cite this article: EFORT Open Rev 2017;2:496–501. DOI: 10.1302/2058-5241.2.170037 PMID:29387472

Biomimetic approaches to modulate cellular adhesion in biomaterials: A review.

PubMed

Rahmany, Maria B; Van Dyke, Mark

2013-03-01

Natural extracellular matrix (ECM) proteins possess critical biological characteristics that provide a platform for cellular adhesion and activation of highly regulated signaling pathways. However, ECM-based biomaterials can have several limitations, including poor mechanical properties and risk of immunogenicity. Synthetic biomaterials alleviate the risks associated with natural biomaterials but often lack the robust biological activity necessary to direct cell function beyond initial adhesion. A thorough understanding of receptor-mediated cellular adhesion to the ECM and subsequent signaling activation has facilitated development of techniques that functionalize inert biomaterials to provide a biologically active surface. Here we review a range of approaches used to modify biomaterial surfaces for optimal receptor-mediated cell interactions, as well as provide insights into specific mechanisms of downstream signaling activation. In addition to a brief overview of integrin receptor-mediated cell function, so-called "biomimetic" techniques reviewed here include (i) surface modification of biomaterials with bioadhesive ECM macromolecules or specific binding motifs, (ii) nanoscale patterning of the materials and (iii) the use of "natural-like" biomaterials. Copyright © 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Organic emissions from coal pyrolysis: mutagenic effects.

PubMed Central

Braun, A G; Wornat, M J; Mitra, A; Sarofim, A F

1987-01-01

Four different types of coal have been pyrolyzed in a laminar flow, drop tube furnace in order to establish a relationship between polycyclic aromatic compound (PAC) evolution and mutagenicity. Temperatures of 900K to 1700K and particle residence times up to 0.3 sec were chosen to best simulate conditions of rapid rate pyrolysis in pulverized (44-53 microns) coal combustion. The specific mutagenic activity (i.e., the activity per unit sample weight) of extracts from particulates and volatiles captured on XAD-2 resin varied with coal type according to the order: subbituminous greater than high volatile bituminous greater than lignite greater than anthracite. Total mutagenic activity (the activity per gram of coal pyrolyzed), however, varied with coal type according to the order: high volatile bituminous much greater than subbituminous = lignite much greater than anthracite, due primarily to high organic yield during high volatile bituminous coal pyrolysis. Specific mutagenic activity peaked in a temperature range of 1300K to 1500K and generally appeared at higher temperatures and longer residence times than peak PAC production. PMID:3311724

Phosphorylation and activation of ubiquitin-specific protease-14 by Akt regulates the ubiquitin-proteasome system

PubMed Central

Xu, Daichao; Shan, Bing; Lee, Byung-Hoon; Zhu, Kezhou; Zhang, Tao; Sun, Huawang; Liu, Min; Shi, Linyu; Liang, Wei; Qian, Lihui; Xiao, Juan; Wang, Lili; Pan, Lifeng; Finley, Daniel; Yuan, Junying

2015-01-01

Regulation of ubiquitin-proteasome system (UPS), which controls the turnover of short-lived proteins in eukaryotic cells, is critical in maintaining cellular proteostasis. Here we show that USP14, a major deubiquitinating enzyme that regulates the UPS, is a substrate of Akt, a serine/threonine-specific protein kinase critical in mediating intracellular signaling transducer for growth factors. We report that Akt-mediated phosphorylation of USP14 at Ser432, which normally blocks its catalytic site in the inactive conformation, activates its deubiquitinating activity in vitro and in cells. We also demonstrate that phosphorylation of USP14 is critical for Akt to regulate proteasome activity and consequently global protein degradation. Since Akt can be activated by a wide range of growth factors and is under negative control by phosphoinosotide phosphatase PTEN, we suggest that regulation of UPS by Akt-mediated phosphorylation of USP14 may provide a common mechanism for growth factors to control global proteostasis and for promoting tumorigenesis in PTEN-negative cancer cells. DOI: http://dx.doi.org/10.7554/eLife.10510.001 PMID:26523394

A serendipitous discovery of antifreeze protein-specific activity in C-linked antifreeze glycoprotein analogs.

PubMed

Eniade, Adewale; Purushotham, Madhusudhan; Ben, Robert N; Wang, J B; Horwath, Kathleen

2003-01-01

Structurally diverse carbon-linked (C-linked) analogs of antifreeze glycoprotein (AFGP) have been prepared via linear or convergent solid phase synthesis. These analogs range in molecular weight from approx 1.5-4.1 KDa and do not possess the beta-D-galactose-1,3-alpha-D-N-acetylgalactosamine carbohydrate moiety or the L-threonine-L-alanine-L-alanine polypeptide backbone native to the AFGP wild-type. Despite these dramatic structural modifications, the 2.7-KDa and 4.1-KDa analogs possess antifreeze protein-specific activity as determined by recrystallization-inhibition (RI) and thermal hysteresis (TH) assays. These analogs are weaker than the wild-type in their activity, but nanoliter osmometry indicates that these compounds are binding to ice and affecting a localized freezing point depression. This is the first example of a C-linked AFGP analog that possesses TH and RI activity and suggests that the rational design and synthesis of chemically and biologically stable AFGP analogs is a feasible and worthwhile endeavor. Given the low degree of TH activity, these compounds may prove useful for the protection of cells during freezing and thawing cycles.

The GLAMA (Girls! Lead! Achieve! Mentor! Activate!) physical activity and peer leadership intervention pilot project: a process evaluation using the RE-AIM framework.

PubMed

Jenkinson, Kate A; Naughton, Geraldine; Benson, Amanda C

2012-01-19

Implementing new initiatives and physical activity interventions in schools represents a myriad of challenges that if overcome can potentially facilitate a range of behavioural changes. The aim of this paper is to describe the process evaluation of specific design constructs used in the GLAMA (Girls! Lead! Achieve! Mentor! Activate!) peer leadership and physical activity pilot project. Conducted in a state secondary school in Australia, the intervention was designed to provide students with opportunities to develop leadership skills, school and social connectedness in addition to a range of physical activity experiences. This process evaluation used the RE-AIM (Reach, Efficacy, Adoption, Implementation and Maintenance) health promotion evaluation framework to assess three design constructs of the intervention: the effectiveness of leadership training and leader preparedness, activity suitability and participation, and the barriers to implementation of the intervention and potential solutions to overcome these barriers. As it was not the specific aim of this pilot, no behavioural change data were collected from students. Data were collected using a mixed methods approach including student questionnaires, teachers and researchers reporting on their own observations and feedback from students. There were three main considerations evident across more than one RE-AIM dimension that need to be addressed to assist with future GLAMA dissemination. Firstly, the development of teacher, school and student participation. This needs to be through a variety of professional development opportunities for teachers, integration of the program within timetabled classes within the school and promoting the program to students as an opportunity to develop a range of skills to apply to future learning and workplace environments. Secondly, the successful translation of leadership training to practice is necessary to ensure that leaders are effectively able to motivate, facilitate and activate their teams. Finally, the need for consistent activity implementation requires sequential, competitive elements, purposeful team selection and clearly defined scoring and time periods for team 'challenges'. Factors that have the greatest impact on intervention success are those that come from within the school setting including: the structure of the curriculum, pressure to meet curriculum and assessment content, lack of support for new initiatives, multiple programs already running within the school, time allowances for teachers, appropriate training for teachers, and support for students to participate. These barriers need to be considered when developing all secondary school interventions.

Transcriptional Dynamics Driving MAMP-Triggered Immunity and Pathogen Effector-Mediated Immunosuppression in Arabidopsis Leaves Following Infection with Pseudomonas syringae pv tomato DC3000[OPEN

PubMed Central

Lewis, Laura A.; Polanski, Krzysztof; de Torres-Zabala, Marta; Bowden, Laura; Jenkins, Dafyd J.; Hill, Claire; Baxter, Laura; Truman, William; Prusinska, Justyna; Hickman, Richard; Wild, David L.; Ott, Sascha; Buchanan-Wollaston, Vicky; Beynon, Jim

2015-01-01

Transcriptional reprogramming is integral to effective plant defense. Pathogen effectors act transcriptionally and posttranscriptionally to suppress defense responses. A major challenge to understanding disease and defense responses is discriminating between transcriptional reprogramming associated with microbial-associated molecular pattern (MAMP)-triggered immunity (MTI) and that orchestrated by effectors. A high-resolution time course of genome-wide expression changes following challenge with Pseudomonas syringae pv tomato DC3000 and the nonpathogenic mutant strain DC3000hrpA- allowed us to establish causal links between the activities of pathogen effectors and suppression of MTI and infer with high confidence a range of processes specifically targeted by effectors. Analysis of this information-rich data set with a range of computational tools provided insights into the earliest transcriptional events triggered by effector delivery, regulatory mechanisms recruited, and biological processes targeted. We show that the majority of genes contributing to disease or defense are induced within 6 h postinfection, significantly before pathogen multiplication. Suppression of chloroplast-associated genes is a rapid MAMP-triggered defense response, and suppression of genes involved in chromatin assembly and induction of ubiquitin-related genes coincide with pathogen-induced abscisic acid accumulation. Specific combinations of promoter motifs are engaged in fine-tuning the MTI response and active transcriptional suppression at specific promoter configurations by P. syringae. PMID:26566919

Transcriptional Dynamics Driving MAMP-Triggered Immunity and Pathogen Effector-Mediated Immunosuppression in Arabidopsis Leaves Following Infection with Pseudomonas syringae pv tomato DC3000.

PubMed

Lewis, Laura A; Polanski, Krzysztof; de Torres-Zabala, Marta; Jayaraman, Siddharth; Bowden, Laura; Moore, Jonathan; Penfold, Christopher A; Jenkins, Dafyd J; Hill, Claire; Baxter, Laura; Kulasekaran, Satish; Truman, William; Littlejohn, George; Prusinska, Justyna; Mead, Andrew; Steinbrenner, Jens; Hickman, Richard; Rand, David; Wild, David L; Ott, Sascha; Buchanan-Wollaston, Vicky; Smirnoff, Nick; Beynon, Jim; Denby, Katherine; Grant, Murray

2015-11-01

Transcriptional reprogramming is integral to effective plant defense. Pathogen effectors act transcriptionally and posttranscriptionally to suppress defense responses. A major challenge to understanding disease and defense responses is discriminating between transcriptional reprogramming associated with microbial-associated molecular pattern (MAMP)-triggered immunity (MTI) and that orchestrated by effectors. A high-resolution time course of genome-wide expression changes following challenge with Pseudomonas syringae pv tomato DC3000 and the nonpathogenic mutant strain DC3000hrpA- allowed us to establish causal links between the activities of pathogen effectors and suppression of MTI and infer with high confidence a range of processes specifically targeted by effectors. Analysis of this information-rich data set with a range of computational tools provided insights into the earliest transcriptional events triggered by effector delivery, regulatory mechanisms recruited, and biological processes targeted. We show that the majority of genes contributing to disease or defense are induced within 6 h postinfection, significantly before pathogen multiplication. Suppression of chloroplast-associated genes is a rapid MAMP-triggered defense response, and suppression of genes involved in chromatin assembly and induction of ubiquitin-related genes coincide with pathogen-induced abscisic acid accumulation. Specific combinations of promoter motifs are engaged in fine-tuning the MTI response and active transcriptional suppression at specific promoter configurations by P. syringae. © 2015 American Society of Plant Biologists. All rights reserved.

Antimicrobial Activity of a Neem Cake Extract in a Broth Model Meat System

PubMed Central

Del Serrone, Paola; Nicoletti, Marcello

2013-01-01

This work reports on the antimicrobial activity of an ethyl acetate extract of neem (Azadirachta indica) cake (NCE) against bacteria affecting the quality of retail fresh meat in a broth model meat system. NCE (100 µg) was also tested by the agar disc diffusion method. It inhibited the growth of all tested microorganisms. The NCE growth inhibition zone (IZ) ranged 11.33–22.67 mm while the ciprofloxacin (10 µg) IZ ranged from 23.41–32.67 mm. There was no significant difference (p ≤ 0.05) between the antimicrobial activity of NCE and ciprofloxacin vs. C. jejuni and Leuconostoc spp. The NCE antibacterial activity was moreover determined at lower concentrations (1:10–1:100,000) in micro-assays. The percent growth reduction ranged from 61 ± 2.08–92 ± 3.21. The higher bacterial growth reduction was obtained at 10 µg concentration of NCE. Species-specific PCR and multiplex PCR with the DNA dye propidium monoazide were used to directly detect viable bacterial cells from experimentally contaminated meat samples. The numbers of bacterial cells never significantly (p ≤ 0.05) exceeded the inocula concentration used to experimentally contaminate the NCE treated meat. This report represents a screening methodology to evaluate the antimicrobial capability of a herbal extract to preserve meat. PMID:23917814

Determination of 17OHPreg and DHEAS by LC-MS/MS: Impact of Age, Sex, Pubertal Stage, and BMI on the Δ5 Steroid Pathway.

PubMed

Kulle, Alexandra E; Reinehr, Thomas; Simic-Schleicher, Gunter; Hornig, Nadine C; Holterhus, Paul-Martin

2017-01-01

Dehydroepiandrosterone sulfate (DHEAS) and 17-hydroxypregnenolone (17OHPreg) are important for understanding the Δ5 pathway (e.g., in adrenarche and obesity). Although mass spectrometry has become the state-of-the-art method for quantifying steroids, there are few comprehensive age-, sex-, and pubertal stage-specific reference ranges for children. To develop a sensitive and reliable ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for simultaneous quantification of DHEAS and 17OHPreg and to establish entire age-, sex- and pubertal stage-specific reference ranges in children. A total of 684 children, 453 (243 female, 210 male) with normal body mass index (BMI; <90th) and 231 (132 female, 99 male) obese subjects (>97th), were categorized into 11 age groups, and age- and Tanner stage (PH)-specific reference ranges were determined. The limit of detection was 0.05 nmol/L for 17OHPreg and 0.5 nmol/L for DHEAS. Levels of both steroids declined after the neonatal period. Comparisons with RIA assays (Siemens, Munich, Germany) (DHEAS) and an in-house kit (17OHPreg) revealed 0.95 and 0.93, respectively, as coefficients of determination. Although DHEAS-generally higher in boys-increased continuously starting at 3 to 6 years, 17OHPreg remained largely constant. In obese patients, both were significantly elevated, also in part after alignment to Tanner stages (PH). UPLC-MS/MS is sensitive and reliable for quantifying DHEAS and 17OHPreg. Our data support differential maturation of CYP17 during adrenarche with successively increasing 17,20-lyase activity but largely constant 17α-hydroxylation activity. Endocrine interpretation of 17OHPreg and DHEAS must consider differential patterns for age, sex, pubertal stage, and BMI. Copyright © 2017 by the Endocrine Society

Mild neurotrauma indicates a range-specific pressure response to low level shock wave exposure.

PubMed

Vandevord, Pamela J; Bolander, Richard; Sajja, Venkata Siva Sai Sujith; Hay, Kathryn; Bir, Cynthia A

2012-01-01

Identifying the level of overpressure required to create physiological deficits is vital to advance prevention, diagnostic, and treatment strategies for individuals exposed to blasts. In this study, a rodent model of primary blast neurotrauma was employed to determine the pressure at which acute neurological alterations occurred. Rats were exposed to a single low intensity shock wave at a pressure of 0, 97, 117, or 153 kPa. Following exposure, rats were assessed for acute cognitive alterations using the Morris water maze and motor dysfunction using the horizontal ladder test. Subsequently, histological analyses of three brain regions (primary motor cortex, the hippocampal dentate gyrus region, and the posteromedial cortical amygdala) were conducted. Histological parameters included measuring the levels of glial fibrillary acidic protein (GFAP) to identify astrocyte activation, cleaved caspase-3 for early apoptosis identification and Fluoro-Jade B (FJB) which labels degenerating neurons within the brain tissue. The results demonstrated that an exposure to a single 117 kPa shock wave revealed a significant change in overall neurological deficits when compared to controls and the other pressures. The animals showed significant alterations in water maze parameters and a histological increase in the number of GFAP, caspase-3, and FJB-positive cells. It is suggested that when exposed to a low level shock wave, there may be a biomechanical response elicited by a specific pressure range which can cause low level neurological deficits within the rat. These data indicate that neurotrauma induced from a shock wave may lead to cognitive deficits in short-term learning and memory of rats. Additional histological evidence supports significant and diffuse glial activation and cellular damage. Further investigation into the biomechanical aspects of shock wave exposure is required to elucidate this pressure range-specific phenomenon.

Arm position influences the activation patterns of trunk muscles during trunk range-of-motion movements.

PubMed

Siu, Aaron; Schinkel-Ivy, Alison; Drake, Janessa Dm

2016-10-01

To understand the activation patterns of the trunk musculature, it is also important to consider the implications of adjacent structures such as the upper limbs, and the muscles that act to move the arms. This study investigated the effects of arm positions on the activation patterns and co-activation of the trunk musculature and muscles that move the arm during trunk range-of-motion movements (maximum trunk axial twist, flexion, and lateral bend). Fifteen males and fifteen females, asymptomatic for low back pain, performed maximum trunk range-of-motion movements, with three arm positions for axial twist (loose, crossed, abducted) and two positions for flexion and lateral bend (loose, crossed). Electromyographical data were collected for eight muscles bilaterally, and activation signals were cross-correlated between trunk muscles and the muscles that move the arms (upper trapezius, latissimus dorsi). Results revealed consistently greater muscle co-activation (higher cross-correlation coefficients) between the trunk muscles and upper trapezius for the abducted arm position during maximum trunk axial twist, while results for the latissimus dorsi-trunk pairings were more dependent on the specific trunk muscles (either abdominal or back) and latissimus dorsi muscle (either right or left side), as well as the range-of-motion movement. The findings of this study contribute to the understanding of interactions between the upper limbs and trunk, and highlight the influence of arm positions on the trunk musculature. In addition, the comparison of the present results to those of individuals with back or shoulder conditions may ultimately aid in elucidating underlying mechanisms or contributing factors to those conditions. Copyright © 2016 Elsevier B.V. All rights reserved.

Blood SC5b-9 complement levels increase at parturition during term and preterm labor.

PubMed

Segura-Cervantes, Enrique; Mancilla-Ramirez, Javier; Zurita, Luis; Paredes, Yuriria; Arredondo, José Luis; Galindo-Sevilla, Norma

2015-06-01

We explored the hypothesis that complement, an innate and adaptive immune effector, is active in the plasma of parturient women and is deposited on fetal membranes collected after delivery. A cross-sectional study was designed to evaluate complement activity at parturition. Pregnant women (n = 97) between 15 and 41 years of age were enrolled in a hospital protocol during the perinatal period to assess both SC5b-9 complement activity in blood and complement deposition on fetal membranes during parturition. Soluble SC5b-9 complement activity in plasma fractions was measured using a standard enzyme-linked immunosorbent assay (ELISA) that included specific anti-complement antibodies. Complement deposition on membranes was analyzed using immuno-dot blots and immunohistochemistry. Soluble SC5b-9 complement complex levels were increased in the plasma of women during term labor (TL; median 3361; range 1726-5670 ng/mL), preterm labor (PL; median 2958; range 1552-7092 ng/mL), and preterm premature rupture of membranes (PPROM; median 2272; range 167-6540 ng/mL) compared with pregnant women who were not in labor (P; median 1384; range 174-4570 ng/mL; P < 0.001, Kruskal-Wallis test). Active complement, as assessed by the C9 neo-antigen in C5b-9 complexes, was deposited on fetal membranes, with no difference between term and preterm delivery. The deposition of active complement on fetal membranes was confirmed by immunohistochemistry. Women who underwent non-labor-indicated Cesarean sections did not exhibit complement deposition. Soluble SC5b-9 complement complex levels increased in the plasma of women during parturition, and complement C5b-9 complexes were deposited on fetal membranes. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Time-driven activity-based costing: a driver for provider engagement in costing activities and redesign initiatives.

PubMed

McLaughlin, Nancy; Burke, Michael A; Setlur, Nisheeta P; Niedzwiecki, Douglas R; Kaplan, Alan L; Saigal, Christopher; Mahajan, Aman; Martin, Neil A; Kaplan, Robert S

2014-11-01

To date, health care providers have devoted significant efforts to improve performance regarding patient safety and quality of care. To address the lagging involvement of health care providers in the cost component of the value equation, UCLA Health piloted the implementation of time-driven activity-based costing (TDABC). Here, the authors describe the implementation experiment, share lessons learned across the care continuum, and report how TDABC has actively engaged health care providers in costing activities and care redesign. After the selection of pilots in neurosurgery and urology and the creation of the TDABC team, multidisciplinary process mapping sessions, capacity-cost calculations, and model integration were coordinated and offered to engage care providers at each phase. Reviewing the maps for the entire episode of care, varying types of personnel involved in the delivery of care were noted: 63 for the neurosurgery pilot and 61 for the urology pilot. The average cost capacities for care coordinators, nurses, residents, and faculty were $0.70 (range $0.63-$0.75), $1.55 (range $1.28-$2.04), $0.58 (range $0.56-$0.62), and $3.54 (range $2.29-$4.52), across both pilots. After calculating the costs for material, equipment, and space, the TDABC model enabled the linking of a specific step of the care cycle (who performed the step and its duration) and its associated costs. Both pilots identified important opportunities to redesign care delivery in a costconscious fashion. The experimentation and implementation phases of the TDABC model have succeeded in engaging health care providers in process assessment and costing activities. The TDABC model proved to be a catalyzing agent for cost-conscious care redesign.

A Brain System for Auditory Working Memory.

PubMed

Kumar, Sukhbinder; Joseph, Sabine; Gander, Phillip E; Barascud, Nicolas; Halpern, Andrea R; Griffiths, Timothy D

2016-04-20

The brain basis for auditory working memory, the process of actively maintaining sounds in memory over short periods of time, is controversial. Using functional magnetic resonance imaging in human participants, we demonstrate that the maintenance of single tones in memory is associated with activation in auditory cortex. In addition, sustained activation was observed in hippocampus and inferior frontal gyrus. Multivoxel pattern analysis showed that patterns of activity in auditory cortex and left inferior frontal gyrus distinguished the tone that was maintained in memory. Functional connectivity during maintenance was demonstrated between auditory cortex and both the hippocampus and inferior frontal cortex. The data support a system for auditory working memory based on the maintenance of sound-specific representations in auditory cortex by projections from higher-order areas, including the hippocampus and frontal cortex. In this work, we demonstrate a system for maintaining sound in working memory based on activity in auditory cortex, hippocampus, and frontal cortex, and functional connectivity among them. Specifically, our work makes three advances from the previous work. First, we robustly demonstrate hippocampal involvement in all phases of auditory working memory (encoding, maintenance, and retrieval): the role of hippocampus in working memory is controversial. Second, using a pattern classification technique, we show that activity in the auditory cortex and inferior frontal gyrus is specific to the maintained tones in working memory. Third, we show long-range connectivity of auditory cortex to hippocampus and frontal cortex, which may be responsible for keeping such representations active during working memory maintenance. Copyright © 2016 Kumar et al.

Evaluation of Toxic Effects of Aeration and Trichloroethylene Oxidation on Methanotrophic Bacteria Grown with Different Nitrogen Sources

PubMed Central

Chu, Kung-Hui; Alvarez-Cohen, Lisa

1999-01-01

In this study we evaluated specific and nonspecific toxic effects of aeration and trichloroethylene (TCE) oxidation on methanotrophic bacteria grown with different nitrogen sources (nitrate, ammonia, and molecular nitrogen). The specific toxic effects, exerted directly on soluble methane monooxygenase (sMMO), were evaluated by comparing changes in methane uptake rates and naphthalene oxidation rates following aeration and/or TCE oxidation. Nonspecific toxic effects, defined as general cellular damage, were examined by using a combination of epifluorescent cellular stains to measure viable cell numbers based on respiratory activity and measuring formate oxidation activities following aeration and TCE transformation. Our results suggest that aeration damages predominantly sMMO rather than other general cellular components, whereas TCE oxidation exerts a broad range of toxic effects that damage both specific and nonspecific cellular functions. TCE oxidation caused sMMO-catalyzed activity and respiratory activity to decrease linearly with the amount of substrate degraded. Severe TCE oxidation toxicity resulted in total cessation of the methane, naphthalene, and formate oxidation activities and a 95% decrease in the respiratory activity of methanotrophs. The failure of cells to recover even after 7 days of incubation with methane suggests that cellular recovery following severe TCE product toxicity is not always possible. Our evidence suggests that generation of greater amounts of sMMO per cell due to nitrogen fixation may be responsible for enhanced TCE oxidation activities of nitrogen-fixing methanotrophs rather than enzymatic protection mechanisms associated with the nitrogenase enzymes. PMID:9925614

LTR12 promoter activation in a broad range of human tumor cells by HDAC inhibition

PubMed Central

Krönung, Sonja K.; Beyer, Ulrike; Chiaramonte, Maria Luisa; Dolfini, Diletta; Mantovani, Roberto; Dobbelstein, Matthias

2016-01-01

A considerable proportion of the human genome consists of transposable elements, including the long terminal repeats (LTRs) of endogenous retroviruses. During evolution, such LTRs were occasionally inserted upstream of protein-coding genes, contributing to their regulation. We previously identified the LTR12 from endogenous retrovirus 9 (ERV9) as a regulator of proapoptotic genes such as TP63 or TNFRSF10B. The promoter activity of LTR12 is largely confined to the testes, silenced in testicular carcinoma, but reactivated in testicular cancer cells by broad-range histone deacetylase (HDAC) inhibitors. Here we show that inhibition of HDAC1-3 is sufficient for LTR12 activation. Importantly, HDAC inhibitors induce LTR12 activity not only in testicular cancer cells, but also in cells derived from many additional tumor species. Finally, we characterize the transcription factor NF-Y as a mediator of LTR12 promoter activity and HDAC inhibitor-induced apoptosis, in the context of widespread genomic binding of NF-Y to specific LTR12 sequences. Thus, HDAC inhibitor-driven LTR12 activation represents a generally applicable means to induce proapoptotic genes in human cancer cells. PMID:27172897

The effects of electrolyte on the supercapacitive performance of activated calcium carbide-derived carbon

NASA Astrophysics Data System (ADS)

Wu, Hao; Wang, Xianyou; Jiang, Lanlan; Wu, Chun; Zhao, Qinglan; Liu, Xue; Hu, Ben'an; Yi, Lanhua

2013-03-01

Porous calcium carbide-derived carbon (CCDC) has been prepared by one-step route from CaC2 in a freshly prepared chlorine environment at lower temperature, and following activated by ZnCl2 to get activated CCDC. The performances of the supercapacitors based on activated CCDC as electrode active material in aqueous KOH, K2SO4, KCl and KNO3 electrolytes are studied by cyclic voltammetry, constant current charged/discharged, cyclic life and electrochemical impedance spectroscopy. It has been found that the supercapacitor using 6 M KOH as electrolyte shows an energy density of 8.3 Wh kg-1 and a power density of 1992 W kg-1 based on the total weight of the electrode active materials with a voltage range 0 V-1 V. Meanwhile, the specific capacitance of the supercapacitor in 6 M KOH electrolyte is 68 F g-1 at the scan rate of 1 mV s-1 in the voltage range of 0 V-1 V, the charge-transfer resistance is extremely low and the relaxation time is the least of all. The supercapacitor also exhibits a good cycling performance and keeps 95% of initial capacity over 5000 cycles.

Temporal and spatial variation of beaked and sperm whales foraging activity in Hawai'i, as determined with passive acoustics.

PubMed

Giorli, Giacomo; Neuheimer, Anna; Copeland, Adrienne; Au, Whitlow W L

2016-10-01

Beaked and sperm whales are top predators living in the waters off the Kona coast of Hawai'i. Temporal and spatial analyses of the foraging activity of these two species were studied with passive acoustics techniques. Three passive acoustics recorders moored to the ocean floor were used to monitor the foraging activity of these whales in three locations along the Kona coast of the island of Hawaii. Data were analyzed using automatic detector/classification systems: M3R (Marine Mammal Monitoring on Navy Ranges), and custom-designed Matlab programs. The temporal variation in foraging activity was species-specific: beaked whales foraged more at night in the north, and more during the day-time off Kailua-Kona. No day-time/night-time preference was found in the southern end of the sampling range. Sperm whales foraged mainly at night in the north, but no day-time/night-time preference was observed off Kailua-Kona and in the south. A Generalized Linear Model was then applied to assess whether location and chlorophyll concentration affected the foraging activity of each species. Chlorophyll concentration and location influenced the foraging activity of both these species of deep-diving odontocetes.

Social and nonsocial behaviours of sex- and age-matched enclosed and free-ranging rhesus monkeys (Macaca mulatta).

PubMed

Baulu, J; Redmond, D E

1980-01-01

The behavioural profiles (time budgeting of social and nonsocial activities) and the frequencies of major social interactions of corral-enclosed rhesus monkeys were compared with sex- and age-matched free-ranging rhesus monkeys on La Cueva Island, Puerto Rico. All animals (n = 32) were provisioned ad libitum at specific feeder sites. The occurrence of 14 behaviours around feeders was compared with their occurrence away from the feeders by noting the location of each monkey relative to the feeder at the time of observation. An analysis of variance between free-ranging versus corral-enclosed groups and within groups by location (around or away from the feeder) revealed significant differences in several behavioural categories, including foraging, lookout, inactive, dominant, submissive, allogrooming, social contact, social initiative, active, and passive behaviours. When the effect of limited food distribution sites was analyzed by comparing data recorded away from the feeding sites, there were remarkably few differences between the groups.

Different types of theta rhythmicity are induced by social and fearful stimuli in a network associated with social memory.

PubMed

Tendler, Alex; Wagner, Shlomo

2015-02-16

Rhythmic activity in the theta range is thought to promote neuronal communication between brain regions. In this study, we performed chronic telemetric recordings in socially behaving rats to monitor electrophysiological activity in limbic brain regions linked to social behavior. Social encounters were associated with increased rhythmicity in the high theta range (7-10 Hz) that was proportional to the stimulus degree of novelty. This modulation of theta rhythmicity, which was specific for social stimuli, appeared to reflect a brain-state of social arousal. In contrast, the same network responded to a fearful stimulus by enhancement of rhythmicity in the low theta range (3-7 Hz). Moreover, theta rhythmicity showed different pattern of coherence between the distinct brain regions in response to social and fearful stimuli. We suggest that the two types of stimuli induce distinct arousal states that elicit different patterns of theta rhythmicity, which cause the same brain areas to communicate in different modes.

The mathematics of a successful deconvolution: a quantitative assessment of mixture-based combinatorial libraries screened against two formylpeptide receptors.

PubMed

Santos, Radleigh G; Appel, Jon R; Giulianotti, Marc A; Edwards, Bruce S; Sklar, Larry A; Houghten, Richard A; Pinilla, Clemencia

2013-05-30

In the past 20 years, synthetic combinatorial methods have fundamentally advanced the ability to synthesize and screen large numbers of compounds for drug discovery and basic research. Mixture-based libraries and positional scanning deconvolution combine two approaches for the rapid identification of specific scaffolds and active ligands. Here we present a quantitative assessment of the screening of 32 positional scanning libraries in the identification of highly specific and selective ligands for two formylpeptide receptors. We also compare and contrast two mixture-based library approaches using a mathematical model to facilitate the selection of active scaffolds and libraries to be pursued for further evaluation. The flexibility demonstrated in the differently formatted mixture-based libraries allows for their screening in a wide range of assays.

Therapeutic perspectives of epigenetically active nutrients

PubMed Central

Remely, M; Lovrecic, L; de la Garza, A L; Migliore, L; Peterlin, B; Milagro, F I; Martinez, A J; Haslberger, A G

2015-01-01

Many nutrients are known for a wide range of activities in prevention and alleviation of various diseases. Recently, their potential role in regulating human health through effects on epigenetics has become evident, although specific mechanisms are still unclear. Thus, nutriepigenetics/nutriepigenomics has emerged as a new and promising field in current epigenetics research in the past few years. In particular, polyphenols, as part of the central dynamic interaction between the genome and the environment with specificity at physiological concentrations, are well known to affect mechanisms underlying human health. This review summarizes the effects of dietary compounds on epigenetic mechanisms in the regulation of gene expression including expression of enzymes and other molecules responsible for drug absorption, distribution, metabolism and excretion in cancer, metabolic syndrome, neurodegenerative disorders and hormonal dysfunction. PMID:25046997

Coagulation parameters in senior athletes practicing endurance sporting activity.

PubMed

Cerneca, E; Simeone, R; Bruno, G; Gombacci, A

2005-12-01

Physical activity is practiced more and more by middle-aged people. We studied the behavior of the coagulation system before and after near-maximum, specific and standardized exercise tests in 2 groups of senior athletes. The subjects of the study were 2 groups of athletes over 40 years of age (ranging 41 to 60 years): 10 rowers and 10 marathon runners. The data were compared with 10 controls (ranging in age from 40 to 71 years) tested on the cycle ergometer. The first group (rowers) was tested on a rowing machine; the second group (marathon runners) performed a maximal exercise on the treadmill. All subjects were tested to a maximal level of cardiovascular and muscular exertion and cardiac and respiratory parameters were monitored. The following coagulation tests were performed before and after maximal exercise: prothrombin time (PT), partial activated thromboplastin time (PTT), fibrinogen (FBG), antithrombin III (ATIII), protein C (PC), protein S (PS), prothrombin fragment 1+2 (F1+2), tissue activator of plasminogen (t-PA) and its inhibitor (PAI). All subjects performed a complete maximal specific test. The results showed all individuals produced a significant increase of FBG, PT and PTT activities and a lowering trend for PC and PS inhibitors after maximal exercise testing. ATIII levels increased significantly in trained subjects. After the test, data regarding fibrinolysis showed higher t-PA levels in athletes as compared with controls. PAI levels indicated a more marked decrease in athletes. The F1+2 showed a moderate but significant increase in the control group. Coagulative tests showed an increase in procoagulant and fibrinolysis parameters in all the groups but the increased fibrinolytic activity in trained athletes indicates a protective factor and greater vascular efficiency. The results demonstrate that sporting activity practiced by middle-aged people accelerates fibrinolytic activity in conditioned subjects. In conclusion, physical activity benefits the coagulation system particularly as regards fibrinolysis.

Update on Staphylococcal Superantigen-Induced Signaling Pathways and Therapeutic Interventions

PubMed Central

Krakauer, Teresa

2013-01-01

Staphylococcal enterotoxin B (SEB) and related bacterial toxins cause diseases in humans and laboratory animals ranging from food poisoning, acute lung injury to toxic shock. These superantigens bind directly to the major histocompatibility complex class II molecules on antigen-presenting cells and specific Vβ regions of T-cell receptors (TCR), resulting in rapid hyper-activation of the host immune system. In addition to TCR and co-stimulatory signals, proinflammatory mediators activate signaling pathways culminating in cell-stress response, activation of NFκB and mammalian target of rapamycin (mTOR). This article presents a concise review of superantigen-activated signaling pathways and focuses on the therapeutic challenges against bacterial superantigens. PMID:24064719

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

Zhao, Ning; He, Yuqing; Mao, Xun

This paper presents a novel approach to electrochemically determine enzymatically active PSA using ferrocene-functionalized helix peptide (CHSSLKQK). The principle of electrochemical measurement is based on the specific proteolytic cleavage events of the FC-peptide on the gold electrode surface in the presence of PSA, resulting the change of the current signal of the electrode. The percentage of the decreased current is linear with the concentration of active PSA at the range of 0.5-40 ng/mL with a detection limit of 0.2 ng/mL. The direct transduction of peptide cleavage events into an electrical signal provides a simple, sensitive method for detecting the enzymaticmore » activity of PSA and determining the active PSA concentration.« less

Promoting active living in healthy cities of Europe.

PubMed

Faskunger, Johan

2013-10-01

Local governments in Europe have a vital role in promoting physical activity in the daily life of citizens. However, explicit investment in active living has been limited. One of the four core themes for Phase IV (2003-2008) of the World Health Organization (WHO) European Healthy Cities Network (WHO-EHCN) was to encourage local governments and their partners to implement programs in favor of active living. This study analyzes the performance of network cities during this period. Responses to a general evaluation questionnaire are analyzed by content according to a checklist, and categorized into themes and dimensions. Most cities viewed "active living" as an important issue for urban planning; to improve visual appeal, enhance social cohesion, create a more sustainable transport system to promote walkability and cyclability and to reduce inequalities in public health. Almost all member cities reported on existing policies that support the promotion of active living. However, only eight (of the 59) responding cities mentioned an integrated framework specific for active living. Many efforts to promote active living are nested in programs to prevent obesity among adults or children. Future challenges include establishing integrated policies specifically for active living, introducing a larger range of actions, as well as increasing funding and capacity to make a difference at the population level.

Region-dependent hamstrings activity in Nordic hamstring exercise and stiff-leg deadlift defined with high-density electromyography.

PubMed

Hegyi, A; Péter, A; Finni, T; Cronin, N J

2018-03-01

Recent studies suggest region-specific metabolic activity in hamstring muscles during injury prevention exercises, but the neural representation of this phenomenon is unknown. The aim of this study was to examine whether regional differences are evident in the activity of biceps femoris long head (BFlh) and semitendinosus (ST) muscles during two common injury prevention exercises. Twelve male participants without a history of hamstring injury performed the Nordic hamstring exercise (NHE) and stiff-leg deadlift (SDL) while BFlh and ST activities were recorded with high-density electromyography (HD-EMG). Normalized activity was calculated from the distal, middle, and proximal regions in the eccentric phase of each exercise. In NHE, ST overall activity was substantially higher than in BFlh (d = 1.06 ± 0.45), compared to trivial differences between muscles in SDL (d = 0.19 ± 0.34). Regional differences were found in NHE for both muscles, with different proximal-distal patterns: The distal region showed the lowest activity level in ST (regional differences, d range = 0.55-1.41) but the highest activity level in BFlh (regional differences, d range = 0.38-1.25). In SDL, regional differences were smaller in both muscles (d range = 0.29-0.67 and 0.16-0.63 in ST and BFlh, respectively) than in NHE. The use of HD-EMG in hamstrings revealed heterogeneous hamstrings activity during typical injury prevention exercises. High-density EMG might be useful in future studies to provide a comprehensive overview of hamstring muscle activity in other exercises and high-injury risk tasks. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Repurposing Ospemifene for Potentiating an Antigen-Specific Immune Response

PubMed Central

Kao, Chiao-Jung; Wurz, Gregory T.; Lin, Yi-Chen; Vang, Daniel P.; Phong, Brian; DeGregorio, Michael W.

2016-01-01

Objective Ospemifene, an estrogen receptor agonist/antagonist approved for treatment of dyspareunia and vaginal dryness in postmenopausal women, has potential new indications as an immune modulator. The overall objective of the present series of preclinical studies was to evaluate the immunomodulatory activity of ospemifene in combination with a peptide cancer vaccine. Methods Immune regulating effects, mechanism of action and structure activity relationships of ospemifene and related compounds were evaluated by examining expression of T cell activating cytokines in vitro, and antigen-specific immune response and cytotoxic T-lymphocyte activity in vivo. The effects of ospemifene (OSP) on the immune response to a peptide cancer vaccine (PV) were evaluated following chronic [control (n=22); OSP 50 mg/kg (n=16); PV (n=6); OSP+PV (n=11)], intermittent [control (n=10); OSP 10 and 50 mg/kg (n=11); PV (n=11); combination treatment (n=11 each dose)] and pretreatment [control; OSP 100 mg/kg; PV 100 µg; combination treatment (n=8 all groups)] ospemifene oral dosing schedules in a total of 317 mixed-sex tumor-bearing and non-tumor-bearing mice. Results The results showed that ospemifene induced expression of the key TH1 cytokines interferon gamma and interleukin-2 in vitro, which may be mediated by stimulating T cells through phosphoinositide 3-kinase and calmodulin signaling pathways. In combination with an antigen-specific peptide cancer vaccine, ospemifene increased antigen-specific immune response and increased cytotoxic T-lymphocyte activity in tumor-bearing and non-tumor-bearing mice. The pretreatment, intermittent, and chronic dosing schedules of ospemifene activate naïve T cells, modulate antigen-induced tolerance and reduce tumor-associated, pro-inflammatory cytokines, respectively. Conclusions Taken together, ospemifene’s dose response and schedule-dependent immune modulating activity offers a method of tailoring and augmenting the efficacy of previously failed antigen-specific cancer vaccines for a wide range of malignancies. PMID:27922937

An Enzyme-Linked Immunosorbent Spot Assay Measuring Borrelia burgdorferi B31-Specific Interferon Gamma-Secreting T Cells Cannot Discriminate Active Lyme Neuroborreliosis from Past Lyme Borreliosis: a Prospective Study in the Netherlands.

PubMed

van Gorkom, T; Sankatsing, S U C; Voet, W; Ismail, D M; Muilwijk, R H; Salomons, M; Vlaminckx, B J M; Bossink, A W J; Notermans, D W; Bouwman, J J M; Kremer, K; Thijsen, S F T

2018-04-01

Two-tier serology testing is most frequently used for the diagnosis of Lyme borreliosis (LB); however, a positive result is no proof of active disease. To establish a diagnosis of active LB, better diagnostics are needed. Tests investigating the cellular immune system are available, but studies evaluating the utility of these tests on well-defined patient populations are lacking. Therefore, we investigated the utility of an enzyme-linked immunosorbent spot (ELISpot) assay to diagnose active Lyme neuroborreliosis. Peripheral blood mononuclear cells (PBMCs) of various study groups were stimulated by using Borrelia burgdorferi strain B31 and various recombinant antigens, and subsequently, the number of Borrelia -specific interferon gamma (IFN-γ)-secreting T cells was measured. We included 33 active and 37 treated Lyme neuroborreliosis patients, 28 healthy individuals treated for an early manifestation of LB in the past, and 145 untreated healthy individuals. The median numbers of B. burgdorferi B31-specific IFN-γ-secreting T cells/2.5 × 10 5 PBMCs did not differ between active Lyme neuroborreliosis patients (6.0; interquartile range [IQR], 0.5 to 14.0), treated Lyme neuroborreliosis patients (4.5; IQR, 2.0 to 18.6), and treated healthy individuals (7.4; IQR, 2.3 to 14.9) ( P = 1.000); however, the median number of B. burgdorferi B31-specific IFN-γ-secreting T cells/2.5 × 10 5 PBMCs among untreated healthy individuals was lower (2.0; IQR, 0.5 to 3.9) ( P ≤ 0.016). We conclude that the Borrelia ELISpot assay, measuring the number of B. burgdorferi B31-specific IFN-γ-secreting T cells/2.5 × 10 5 PBMCs, correlates with exposure to the Borrelia bacterium but cannot be used for the diagnosis of active Lyme neuroborreliosis. Copyright © 2018 van Gorkom et al.

An Enzyme-Linked Immunosorbent Spot Assay Measuring Borrelia burgdorferi B31-Specific Interferon Gamma-Secreting T Cells Cannot Discriminate Active Lyme Neuroborreliosis from Past Lyme Borreliosis: a Prospective Study in the Netherlands

PubMed Central

van Gorkom, T.; Sankatsing, S. U. C.; Voet, W.; Ismail, D. M.; Muilwijk, R. H.; Salomons, M.; Vlaminckx, B. J. M.; Bossink, A. W. J.; Notermans, D. W.; Bouwman, J. J. M.; Kremer, K.

2018-01-01

ABSTRACT Two-tier serology testing is most frequently used for the diagnosis of Lyme borreliosis (LB); however, a positive result is no proof of active disease. To establish a diagnosis of active LB, better diagnostics are needed. Tests investigating the cellular immune system are available, but studies evaluating the utility of these tests on well-defined patient populations are lacking. Therefore, we investigated the utility of an enzyme-linked immunosorbent spot (ELISpot) assay to diagnose active Lyme neuroborreliosis. Peripheral blood mononuclear cells (PBMCs) of various study groups were stimulated by using Borrelia burgdorferi strain B31 and various recombinant antigens, and subsequently, the number of Borrelia-specific interferon gamma (IFN-γ)-secreting T cells was measured. We included 33 active and 37 treated Lyme neuroborreliosis patients, 28 healthy individuals treated for an early manifestation of LB in the past, and 145 untreated healthy individuals. The median numbers of B. burgdorferi B31-specific IFN-γ-secreting T cells/2.5 × 105 PBMCs did not differ between active Lyme neuroborreliosis patients (6.0; interquartile range [IQR], 0.5 to 14.0), treated Lyme neuroborreliosis patients (4.5; IQR, 2.0 to 18.6), and treated healthy individuals (7.4; IQR, 2.3 to 14.9) (P = 1.000); however, the median number of B. burgdorferi B31-specific IFN-γ-secreting T cells/2.5 × 105 PBMCs among untreated healthy individuals was lower (2.0; IQR, 0.5 to 3.9) (P ≤ 0.016). We conclude that the Borrelia ELISpot assay, measuring the number of B. burgdorferi B31-specific IFN-γ-secreting T cells/2.5 × 105 PBMCs, correlates with exposure to the Borrelia bacterium but cannot be used for the diagnosis of active Lyme neuroborreliosis. PMID:29367297

Detection of trace heavy metal ions in water by nanostructured porous Si biosensors.

PubMed

Shtenberg, Giorgi; Massad-Ivanir, Naama; Segal, Ester

2015-07-07

A generic biosensing platform, based on nanostructured porous Si (PSi), Fabry-Pérot thin films, for label-free monitoring of heavy metal ions in aqueous solutions by enzymatic activity inhibition, is described. First, we show a general detection assay by immobilizing horseradish peroxidase (HRP) within the oxidized PSi nanostructure and monitor its catalytic activity in real time by reflective interferometric Fourier transform spectroscopy. Optical studies reveal the high specificity and sensitivity of the HRP-immobilized PSi towards three metal ions (Ag(+) > Pb(2+) > Cu(2+)), with a detection limit range of 60-120 ppb. Next, we demonstrate the concept of specific detection of Cu(2+) ions (as a model heavy metal) by immobilizing Laccase, a multi-copper oxidase, within the oxidized PSi. The resulting biosensor allows for specific detection and quantification of copper ions in real water samples by monitoring the Laccase relative activity. The optical biosensing results are found to be in excellent agreement with those obtained by the gold standard analytical technique (ICP-AES) for all water samples. The main advantage of the presented biosensing concept is the ability to detect heavy metal ions at environmentally relevant concentrations using a simple and portable experimental setup, while the specific biosensor design can be tailored by varying the enzyme type.

DNA Origami Patterned Colloids for Programmed Design and Chirality

NASA Astrophysics Data System (ADS)

Ben Zion, Matan Yah; He, Xiaojin; Maass, Corinna; Sha, Ruojie; Seeman, Ned; Chaikin, Paul

Micron size colloidal particles are scientifically important as model systems for equilibrium and active systems in physics, chemistry and biology and for technologies ranging from catalysis to photonics. The past decade has seen development of new particles with directional patches, lock and key reactions and specific recognition that guide assembly of structures such as complex crystalline arrays. What remains lacking is the ability to self-assemble structures of arbitrary shape with specific chirality, placement and orientation of neighbors. Here we demonstrate the adaptation of DNA origami nanotechnology to the micron colloidal scale with designed control of neighbor type, placement and dihedral angle. We use DNA origami belts with programmed flexibility, and functionality to pattern colloidal surfaces and bind particles to specific sites at specific angles and make uniquely right handed or left handed structures. The hybrid DNA origami colloid technology should allow the synthesis of designed functional structural and active materials. This work was supported as part of the Center for Bio-Inspired Energy Science, an Energy Frontier Research Center funded by the U.S. Department of Energy, Office of Science, Basic Energy Sciences under Award # DE-SC0000989.

Specificity and disease in the ubiquitin system

PubMed Central

Chaugule, Viduth K.; Walden, Helen

2016-01-01

Post-translational modification (PTM) of proteins by ubiquitination is an essential cellular regulatory process. Such regulation drives the cell cycle and cell division, signalling and secretory pathways, DNA replication and repair processes and protein quality control and degradation pathways. A huge range of ubiquitin signals can be generated depending on the specificity and catalytic activity of the enzymes required for attachment of ubiquitin to a given target. As a consequence of its importance to eukaryotic life, dysfunction in the ubiquitin system leads to many disease states, including cancers and neurodegeneration. This review takes a retrospective look at our progress in understanding the molecular mechanisms that govern the specificity of ubiquitin conjugation. PMID:26862208

A Multiscale Survival Process for Modeling Human Activity Patterns.

PubMed

Zhang, Tianyang; Cui, Peng; Song, Chaoming; Zhu, Wenwu; Yang, Shiqiang

2016-01-01

Human activity plays a central role in understanding large-scale social dynamics. It is well documented that individual activity pattern follows bursty dynamics characterized by heavy-tailed interevent time distributions. Here we study a large-scale online chatting dataset consisting of 5,549,570 users, finding that individual activity pattern varies with timescales whereas existing models only approximate empirical observations within a limited timescale. We propose a novel approach that models the intensity rate of an individual triggering an activity. We demonstrate that the model precisely captures corresponding human dynamics across multiple timescales over five orders of magnitudes. Our model also allows extracting the population heterogeneity of activity patterns, characterized by a set of individual-specific ingredients. Integrating our approach with social interactions leads to a wide range of implications.

The dynamic range of LZ

NASA Astrophysics Data System (ADS)

Yin, J.

2016-02-01

The electronics of the LZ experiment, the 7-tonne dark matter detector to be installed at the Sanford Underground Research Facility (SURF), is designed to permit studies of physics where the energies deposited range from 1 keV of nuclear-recoil energy up to 3,000 keV of electron-recoil energy. The system is designed to provide a 70% efficiency for events that produce three photoelectrons in the photomultiplier tubes (PMTs). This corresponds approximately to the lowest energy threshold achievable in multi-tonne time-projection chambers, and drives the noise specifications for the front end. The upper limit of the LZ dynamic range is defined to accommodate the electroluminescence (S2) signals. The low-energy channels of the LZ amplifiers provide the dynamic range required for the tritium and krypton calibrations. The high-energy channels provide the dynamic range required to measure the activated Xe lines.

Strain screen and haplotype association mapping of wheel running in inbred mouse strains.

PubMed

Lightfoot, J Timothy; Leamy, Larry; Pomp, Daniel; Turner, Michael J; Fodor, Anthony A; Knab, Amy; Bowen, Robert S; Ferguson, David; Moore-Harrison, Trudy; Hamilton, Alicia

2010-09-01

Previous genetic association studies of physical activity, in both animal and human models, have been limited in number of subjects and genetically homozygous strains used as well as number of genomic markers available for analysis. Expansion of the available mouse physical activity strain screens and the recently published dense single-nucleotide polymorphism (SNP) map of the mouse genome (approximately 8.3 million SNPs) and associated statistical methods allowed us to construct a more generalizable map of the quantitative trait loci (QTL) associated with physical activity. Specifically, we measured wheel running activity in male and female mice (average age 9 wk) in 41 inbred strains and used activity data from 38 of these strains in a haplotype association mapping analysis to determine QTL associated with activity. As seen previously, there was a large range of activity patterns among the strains, with the highest and lowest strains differing significantly in daily distance run (27.4-fold), duration of activity (23.6-fold), and speed (2.9-fold). On a daily basis, female mice ran further (24%), longer (13%), and faster (11%). Twelve QTL were identified, with three (on Chr. 12, 18, and 19) in both male and female mice, five specific to males, and four specific to females. Eight of the 12 QTL, including the 3 general QTL found for both sexes, fell into intergenic areas. The results of this study further support the findings of a moderate to high heritability of physical activity and add general genomic areas applicable to a large number of mouse strains that can be further mined for candidate genes associated with regulation of physical activity. Additionally, results suggest that potential genetic mechanisms arising from traditional noncoding regions of the genome may be involved in regulation of physical activity.

Successful Outcome of Modified Quad Surgical Procedure in Preteen and Teen Patients with Brachial Plexus Birth Palsy

PubMed Central

Nath, Rahul K.; Somasundaram, Chandra

2012-01-01

Objective: To evaluate the outcome of modified Quad procedure in preteen and teen patients with brachial plexus birth palsy. Background: We have previously demonstrated a significant improvement in shoulder abduction, resulting from the modified Quad procedure in children (mean age 2.5 years; range, 0.5–9 years) with obstetric brachial plexus injury. Methods: We describe in this report the outcome of 16 patients (6 girls and 10 boys; 7 preteen and 9 teen) who have undergone the modified Quad procedure for the correction of the shoulder function, specifically abduction. The patients underwent transfer of the latissimus dorsi and teres major muscles, release of contractures of subscapularis pectoralis major and minor, and axillary nerve decompression and neurolysis (the modified Quad procedure). Mean age of these patients at surgery was 13.5 years (range, 10.1–17.9 years). Results: The mean preoperative total Mallet score was 14.8 (range, 10–20), and active abduction was 84° (range, 20°–140°). At a mean follow-up of 1.5 years, the mean postoperative total Mallet score increased to 19.7 (range, 13–25, P < .0001), and the mean active abduction improved to 132° (range, 40°–180°, P < .0003). Conclusion: The modified Quad procedure greatly improves not only the active abduction but also other shoulder functions in preteen and teen patients, as this outcome is the combined result of decompression and neurolysis of the axillary nerve and the release of the contracted internal rotators of the shoulder. PMID:23308301

Electrosynthesis of magnetoresponsive microrobot for targeted drug delivery using calcium alginate.

PubMed

Chengzhi Hu; Riederer, Katharina; Klemmer, Michael; Pane, Salvador; Nelson, Bradley J

2016-08-01

Targeted drug delivery systems deliver drugs precisely to a specific targeted site inside the body, and can also release the drugs with controlled kinetics to prolong the efficacy of single dose administration. The advantageous properties of hydrogels make them attractive for use in the area of drug delivery. Calcium alginate is a pH sensitive hydrogel stable in acidic media and soluble in basic media. This enables the hydrogel to absorb and release aqueous solutions at certain ranges of pH values. By absorbing an aqueous solution containing a drug, an active drug release can be triggered at a specified range of pH value. In this paper, we combined calcium alginate with cobalt nickel (CoNi) in a cylindrical hybrid micro robot by electrodeposition. The designed microrobot can be wirelessly actuated with an external magnetic manipulation system and, hence, targeted to a specific location in the human body. At this specific location, characterized by its pH range, the absorbed drug will be released. Here, the fabrication steps of the specified microrobot are characterized, namely the production of a template on a silicon chip and the subsequent template-assisted electrodeposition of CoNi and alginate. Additionally, the dynamics of drug release of calcium alginate is studied.

Rebound spiking in layer II medial entorhinal cortex stellate cells: Possible mechanism of grid cell function

PubMed Central

Shay, Christopher F.; Ferrante, Michele; Chapman, G. William; Hasselmo, Michael E.

2015-01-01

Rebound spiking properties of medial entorhinal cortex (mEC) stellate cells induced by inhibition may underlie their functional properties in awake behaving rats, including the temporal phase separation of distinct grid cells and differences in grid cell firing properties. We investigated rebound spiking properties using whole cell patch recording in entorhinal slices, holding cells near spiking threshold and delivering sinusoidal inputs, superimposed with realistic inhibitory synaptic inputs to test the capacity of cells to selectively respond to specific phases of inhibitory input. Stellate cells showed a specific phase range of hyperpolarizing inputs that elicited spiking, but non-stellate cells did not show phase specificity. In both cell types, the phase range of spiking output occurred between the peak and subsequent descending zero crossing of the sinusoid. The phases of inhibitory inputs that induced spikes shifted earlier as the baseline sinusoid frequency increased, while spiking output shifted to later phases. Increases in magnitude of the inhibitory inputs shifted the spiking output to earlier phases. Pharmacological blockade of h-current abolished the phase selectivity of hyperpolarizing inputs eliciting spikes. A network computational model using cells possessing similar rebound properties as found in vitro produces spatially periodic firing properties resembling grid cell firing when a simulated animal moves along a linear track. These results suggest that the ability of mEC stellate cells to fire rebound spikes in response to a specific range of phases of inhibition could support complex attractor dynamics that provide completion and separation to maintain spiking activity of specific grid cell populations. PMID:26385258

Development of responder criteria for multicomponent non-pharmacological treatment in fibromyalgia.

PubMed

Vervoort, Vera M; Vriezekolk, Johanna E; van den Ende, Cornelia H

2017-01-01

There is a need to identify individual treatment success in patients with fibromyalgia (FM) who received non-pharmacological treatment. The present study described responder criteria for multicomponent non-pharmacological treatment in FM, and estimated and compared their sensitivity and specificity. Candidate responder sets were 1) identified in literature; and 2) formulated by expert group consensus. All candidate responder sets were tested in a cohort of 129 patients with FM receiving multicomponent non-pharmacological treatment. We used two gold standards (both therapist's and patient's perspective), assessed at six months after the start of treatment. Seven responder sets were defined (three identified in literature and four formulated by expert group consensus), and comprised combinations of domains of 1) pain; 2) fatigue; 3) patient global assessment (PGA); 4) illness perceptions; 5) limitations in activities of daily living (ADL); and 6) sleep. The sensitivity and specificity of literature-based responder sets (n=3) ranged between 17%-99% and 15%-95% respectively, whereas the expert-based responder sets (n=4) performed slightly better with regard to sensitivity (range 41%-81%) and specificity (range 50%-96%). Of the literature-based responder sets the OMERACT-OARSI responder set with patient's gold standard performed best (sensitivity 63%, specificity 75% and ROC area = 0.69). Overall, the expert-based responder set comprising the domains illness perceptions and limitations in ADL with patient's gold standard performed best (sensitivity 47%, specificity 96% and ROC area = 0.71). We defined sets of responder criteria for multicomponent non-pharmacological treatment in fibromyalgia. Further research should focus on the validation of those sets with acceptable performance.

Electro-optical system for gunshot detection: analysis, concept, and performance

NASA Astrophysics Data System (ADS)

Kastek, M.; Dulski, R.; Madura, H.; Trzaskawka, P.; Bieszczad, G.; Sosnowski, T.

2011-08-01

The paper discusses technical possibilities to build an effective electro-optical sensor unit for sniper detection using infrared cameras. This unit, comprising of thermal and daylight cameras, can operate as a standalone device but its primary application is a multi-sensor sniper and shot detection system. At first, the analysis was presented of three distinguished phases of sniper activity: before, during and after the shot. On the basis of experimental data the parameters defining the relevant sniper signatures were determined which are essential in assessing the capability of infrared camera to detect sniper activity. A sniper body and muzzle flash were analyzed as targets and the descriptions of phenomena which make it possible to detect sniper activities in infrared spectra as well as analysis of physical limitations were performed. The analyzed infrared systems were simulated using NVTherm software. The calculations for several cameras, equipped with different lenses and detector types were performed. The simulation of detection ranges was performed for the selected scenarios of sniper detection tasks. After the analysis of simulation results, the technical specifications of infrared sniper detection system were discussed, required to provide assumed detection range. Finally the infrared camera setup was proposed which can detected sniper from 1000 meters range.

A Controlled Study of Mercury Levels in Hair Samples of Children with Autism as Compared to Their Typically Developing Siblings

ERIC Educational Resources Information Center

Williams, P. Gail; Hersh, Joseph H.; Allard, AnnaMary; Sears, Lonnie L.

2008-01-01

Autism is a developmental disability characterized by severe, pervasive deficits in social interaction, communication and range of interests and activities. The neurobiologic basis of autism is well accepted, although the specific etiology is unknown. It has been theorized that autism may result from a combination of predisposing genes and…

Uncertainty and probability in wildfire management decision support: An example from the United States [Chapter 4

Treesearch

Matthew Thompson; David Calkin; Joe H. Scott; Michael Hand

2017-01-01

Wildfire risk assessment is increasingly being adopted to support federal wildfire management decisions in the United States. Existing decision support systems, specifically the Wildland Fire Decision Support System (WFDSS), provide a rich set of probabilistic and risk‐based information to support the management of active wildfire incidents. WFDSS offers a wide range...

Starting with ABC and Finishing with XYZ: What Financial Reporting Model Best Fits a Faculty and Why?

ERIC Educational Resources Information Center

Berry, Prudence Jane

2014-01-01

This article looks at the range of financial reporting models available for use in the Australian higher education sector, the possible application of activity-based costing (ABC) in faculties and the eventual rejection of ABC in favour of a more qualitative model designed specifically for use in one institution, in a particular Faculty. The…

Using a Thematic Analysis of Literature to Survey Subfields within Communication Studies

ERIC Educational Resources Information Center

Garner, Johny T.; Ragland, J. Parker

2015-01-01

The activity described by the authors here is a thematic analysis of published articles in a broad area of study. Students search for articles relating to the topic of study in different academic journals that fall in a specific date range. Students record details about the topics covered and theories/methods used. The class then assembles to…

Passive Biobarrier for Treating Co-mingled Perchlorate and RDX in Groundwater at an Active Range

DTIC Science & Technology

2016-05-12

and Groundwater Temperature ............................. 102 6.1.2 Dissolved Oxygen (DO) and Oxidation Reduction Potential (ORP...22 or equivalent). Parameters, including temperature , conductivity, dissolved oxygen , oxidation-reduction potential (ORP), turbidity, and pH were...3% for temperature and specific conductivity, and ᝺% for dissolved oxygen , ORP, and turbidity. When parameters were stable according to the above

Layered Learning Design: Towards an Integration of Learning Design and Learning Object Perspectives

ERIC Educational Resources Information Center

Boyle, Tom

2010-01-01

The use of ICT to enhance teaching and learning depends on effective design, which operates at many levels of granularity from the small to the very large. This reflects the range of educational problems from course design down to the design of activities focused on specific learning objectives. For maximum impact these layers of design need to be…

77 FR 58570 - Notice of Intent To Prepare an Environmental Impact Statement for the Proposed Pacific Connector...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-21

... Survey and Manage species within the range of the northern spotted owl. This is a site-specific amendment... Owl Activity Centers on the BLM Roseburg District: The RMP for the Roseburg District would be amended to exempt the Pacific Connector pipeline project from the requirement to retain habitat in Known Owl...

Veterinary student attitudes toward curriculum integration at James Cook University.

PubMed

Cavalieri, John

2009-01-01

The aim of this study was to investigate the attitudes of veterinary science students to activities designed to promote curriculum integration. Students (N = 33) in their second year of a five-year veterinary degree were surveyed in regard to their attitudes to activities that aimed to promote integration. Imaging, veterinary practice practicals, and a field trip to a cattle property were classified as the three most valuable learning activities that were designed to promote integration. Veterinary practice practicals, case studies, and palpable anatomy were regarded by students as helping them to learn information presented in other teaching sessions. They also appeared to enhance student motivation, and students indicated that the activities assisted them with their preparation for and performance at examinations. Attitudes to whether the learning exercises helped improve a range of skills and specific knowledge varied, with 39-88% of students agreeing that specific skills and knowledge were enhanced to a large or very large extent by the learning activities. The results indicate that learning activities designed to promote curriculum integration helped improve motivation, reinforced learning, created links between foundational knowledge and its application, and assisted with the development of skills that are related to what students will do in their future careers.

Expression and characterization of fifteen Rhizopus oryzae 99-880 polygalacturonase enzymes in Pichia pastoris.

PubMed

Mertens, Jeffrey A; Bowman, Michael J

2011-04-01

Polygalacturonase (PG) enzymes hydrolyze the long polygalacturonic acid chains found in the smooth regions of pectin. Interest in this enzyme class continues due to their ability to macerate tissues of economically important crops and their use in a number of industrial processes. Rhizopus oryzae has a large PG gene family with 15 of 18 genes encoding unique active enzymes. The PG enzymes, 12 endo-PG and 3 exo-galacturonases, were expressed in Pichia pastoris and purified enabling biochemical characterization to gain insight into the maintenance of this large gene family within the Rhizopus genome. The 15 PG enzymes have a pH optima ranging from 4.0 to 5.0. Temperature optima of the 15 PG enzymes vary from 30 to 40 °C. While the pH and temperature optima do little to separate the enzymes, the specific activity of the enzymes is highly variable ranging from over 200 to less than 1 μmol/min/mg. A general pattern related to the groupings found in the phylogentic tree was visible with the group containing the exo-PG enzymes demonstrating the lowest specific activity. Finally, the progress curves of the PG enzymes, contained within the phylogenetic group that includes the exo-PG enzymes, acting on trigalacturonic acid lend additional support to the idea that the ancestral form of PG in Rhizopus is endolytic and exolytic function evolved later.

Lightweight fiber optic microphones and accelerometers

NASA Astrophysics Data System (ADS)

Bucaro, J. A.; Lagakos, N.

2001-06-01

We have designed, fabricated, and tested two lightweight fiber optic sensors for the dynamic measurement of acoustic pressure and acceleration. These sensors, one a microphone and the other an accelerometer, are required for active blanket sound control technology under development in our laboratory. The sensors were designed to perform to certain specifications dictated by our active sound control application and to do so without exhibiting sensitivity to the high electrical voltages expected to be present. Furthermore, the devices had to be small (volumes less than 1.5 cm3) and light (less than 2 g). To achieve these design criteria, we modified and extended fiber optic reflection microphone and fiber microbend displacement device designs reported in the literature. After fabrication, the performances of each sensor type were determined from measurements made in a dynamic pressure calibrator and on a shaker table. The fiber optic microbend accelerometer, which weighs less than 1.8 g, was found to meet all performance goals including 1% linearity, 90 dB dynamic range, and a minimum detectable acceleration of 0.2 mg/√Hz . The fiber optic microphone, which weighs less than 1.3 g, also met all goals including 1% linearity, 85 dB dynamic range, and a minimum detectable acoustic pressure level of 0.016 Pa/√Hz . In addition to our specific use in active sound control, these sensors appear to have application in a variety of other areas.

Dynamic range in the C. elegans brain network

NASA Astrophysics Data System (ADS)

Antonopoulos, Chris G.

2016-01-01

We study external electrical perturbations and their responses in the brain dynamic network of the Caenorhabditis elegans soil worm, given by the connectome of its large somatic nervous system. Our analysis is inspired by a realistic experiment where one stimulates externally specific parts of the brain and studies the persistent neural activity triggered in other cortical regions. In this work, we perturb groups of neurons that form communities, identified by the walktrap community detection method, by trains of stereotypical electrical Poissonian impulses and study the propagation of neural activity to other communities by measuring the corresponding dynamic ranges and Steven law exponents. We show that when one perturbs specific communities, keeping the rest unperturbed, the external stimulations are able to propagate to some of them but not to all. There are also perturbations that do not trigger any response. We found that this depends on the initially perturbed community. Finally, we relate our findings for the former cases with low neural synchronization, self-criticality, and large information flow capacity, and interpret them as the ability of the brain network to respond to external perturbations when it works at criticality and its information flow capacity becomes maximal.

Participation as an outcome measure in psychosocial oncology: content of cancer-specific health-related quality of life instruments.

PubMed

van der Mei, Sijrike F; Dijkers, Marcel P J M; Heerkens, Yvonne F

2011-12-01

To examine to what extent the concept and the domains of participation as defined in the International Classification of Functioning, Disability and Health (ICF) are represented in general cancer-specific health-related quality of life (HRQOL) instruments. Using the ICF linking rules, two coders independently extracted the meaningful concepts of ten instruments and linked these to ICF codes. The proportion of concepts that could be linked to ICF codes ranged from 68 to 95%. Although all instruments contained concepts linked to Participation (Chapters d7-d9 of the classification of 'Activities and Participation'), the instruments covered only a small part of all available ICF codes. The proportion of ICF codes in the instruments that were participation related ranged from 3 to 35%. 'Major life areas' (d8) was the most frequently used Participation Chapter, with d850 'remunerative employment' as the most used ICF code. The number of participation-related ICF codes covered in the instruments is limited. General cancer-specific HRQOL instruments only assess social life of cancer patients to a limited degree. This study's information on the content of these instruments may guide researchers in selecting the appropriate instrument for a specific research purpose.

[Extracellular proteolytic enzymes of Azospirillum brasilensis strain Sp7 and regulation of their activity by a homologous lectin].

PubMed

Chernyshova, M P; Alen'kina, S A; Nikitina, V E; Ignatov, V V

2005-01-01

It was found that Azospirillum brasilensis strain Sp7 is able to produce extracellular proteolytic enzymes. The enzymes were active within a broad range of pH values, with two peaks of activity being located in the acid and alkaline pH areas; required calcium ions; and exhibited substrate specificity with respect to azogelatin. Zymography allowed at least four proteolytic enzymes with molecular weights of 32, 45, 52, and 174 kDa to be detected in A. brasilense Sp7 culture liquid. It was shown that the lectin from A. brasilense Sp7 can inhibit proteolytic enzymes.

Production of β-Lactamase by Non-Streptomyces Actinomycetales

PubMed Central

Schwartz, Jeffrey L.; Schwartz, Surya P.

1979-01-01

Supernatants and whole cells from fermentation broths of Micromonospora, Nocardia, Oerskovia, and other genera of the Actinomycetales were examined for the presence of β-lactamase activity by using the chromogenic cephalosporin 87/312. Nearly 60% of the 250 isolates examined produced detectable levels of β-lactamase. All enzyme preparations were active over a range of pH values from 6.5 to 8.2, with maximum activity occurring between 7.0 and 7.8. The preparations varied in their stability at 60°C. An examination of selected enzyme preparations revealed a similarity between substrate specificities of the non-Streptomyces Actinomycetales and gram-negative-bacterial β-lactamases. PMID:311614

Investigation of Seasonal and Latitudinal Effects on the Expression of Clock Genes in Drosophila

NASA Astrophysics Data System (ADS)

Hosseini, Seyede Sanaz; Nazarimehr, Fahimeh; Jafari, Sajad

The primary goal in this work is to develop a dynamical model capturing the influence of seasonal and latitudinal variations on the expression of Drosophila clock genes. To this end, we study a specific dynamical system with strange attractors that exhibit changes of Drosophila activity in a range of latitudes and across different seasons. Bifurcations of this system are analyzed to peruse the effect of season and latitude on the behavior of clock genes. Existing experimental data collected from the activity of Drosophila melanogaster corroborate the dynamical model.

A Card-Sorting Activity to Engage Students in the Academic Language of Biology

PubMed Central

WALLON, ROBERT C.; JASTI, CHANDANA; HUG, BARBARA

2017-01-01

The activity described in this article is designed to provide biology students with opportunities to engage in a range of academic language as they learn the discipline-specific meanings of the terms “drug,” “poison,” “toxicant,” and “toxin.” Although intended as part of an introductory lesson in a comprehensive unit for the high school level, this approach to teaching academic language can be adapted for use with older or younger students and can be modified to teach other terms. PMID:29307894

Compressional ULF waves in the outer magnetosphere. 2: A case study of Pc 5 type wave activity

NASA Technical Reports Server (NTRS)

Zhu, Xiaoming; Kivelson, Margaret G.

1994-01-01

In previously published work (Zhu and Kivelson, 1991) the spatial distribution of compressional magnetic pulsations of period 2 - 20 min in the outer magnetosphere was described. In this companion paper, we study some specific compressional events within our data set, seeking to determine the structure of the waves and identifying the wave generation mechanism. We use both the magnetic field and three-dimensional plasma data observed by the International Sun-Earth Explorer (ISEE) 1 and/or 2 spacecraft to characterize eight compressional ultra low frequency (ULF) wave events with frequencies below 8 mHz in the outer magnetosphere. High time resolution plasma data for the event of July 24, 1978, made possible a detailed analysis of the waves. Wave properties specific to the event of July 24, 1978, can be summarized as follows: (1) Partial plasma pressures in the different energy ranges responded to the magnetic field pressure differently. In the low-energy range they oscillated in phase with the magnetic pressure, while oscillations in higher-energy ranges were out-of-phase; (2) Perpendicular wavelengths for the event were determined to be 60,000 and 30,000 km in the radial and azimuthal directions, respectively. Wave properties common to all events can be summarized as follows: (1) Compressional Pc 5 wave activity is correlated with Beta, the ratio of the plasma pressure to the magnetic pressure; the absolute magnitude of the plasma pressure plays a minor role for the wave activity; (2) The magnetic equator is a node of the compressional perturbation of the magnetic field; (3) The criterion for the mirror mode instability is often satisfied near the equator in the outer magnetosphere when the compressional waves are present. We believe these waves are generated by internal magnetohydrodynamic (MHD) instabilities.

Performance of a lateral flow immunochromatography test for the rapid diagnosis of active tuberculosis in a large multicentre study in areas with different clinical settings and tuberculosis exposure levels.

PubMed

Manga, Selene; Perales, Rocio; Reaño, Maria; D'Ambrosio, Lia; Migliori, Giovanni Battista; Amicosante, Massimo

2016-11-01

Tuberculosis (TB) continues to cause an outsized burden of morbidity and mortality worldwide, still missing efficient and largely accessible diagnostic tools determining an appropriate control of the disease. Serological tests have the potentially to impact TB diagnosis, in particular in extreme clinical settings. The diagnostic performances of the TB-XT HEMA EXPRESS (HEMA-EXPRESS) immunochromatographic rapid test for active TB diagnosis, based on use of multiple Mycobacterium tuberculosis (MTB) specific antigens, have been evaluated in a large study multicentre TB case-finding study, in populations with different exposure level to TB. A total of 1,386 subjects were enrolled in the six participating centres in Peru: 290 active-TB and 1,096 unaffected subjects. The TB prevalence (overall 20.5%) varied between 4.0% and 41.1% in the different study groups. Overall, the HEMA-EXPRESS test had 30.6% sensitivity (range 3.9-77.9%) and 84.6% specificity (range 51.6-97.3%). A significant inverse correlation between test accuracy (overall 73.5%, range 40.4-96.4%) and TB prevalence in the various study populations was observed (Pearson's r=-0.7985; P=0.05). HEMA-EXPRESS, is rapid and relatively inexpensive test suitable for routine use in TB diagnosis. In low TB prevalence conditions, test performance appears in line with WHO Target Product Profile for TB diagnostics. Performances appear suboptimal in high TB prevalence settings. Appropriate set-up in operative clinical settings has to be considered for novel serological tests for TB diagnosis, particularly for formats suitable for point-of-care use.

Synaptic Effects of Electric Fields

NASA Astrophysics Data System (ADS)

Rahman, Asif

Learning and sensory processing in the brain relies on the effective transmission of information across synapses. The strength and efficacy of synaptic transmission is modifiable through training and can be modulated with noninvasive electrical brain stimulation. Transcranial electrical stimulation (TES), specifically, induces weak intensity and spatially diffuse electric fields in the brain. Despite being weak, electric fields modulate spiking probability and the efficacy of synaptic transmission. These effects critically depend on the direction of the electric field relative to the orientation of the neuron and on the level of endogenous synaptic activity. TES has been used to modulate a wide range of neuropsychiatric indications, for various rehabilitation applications, and cognitive performance in diverse tasks. How can a weak and diffuse electric field, which simultaneously polarizes neurons across the brain, have precise changes in brain function? Designing therapies to maximize desired outcomes and minimize undesired effects presents a challenging problem. A series of experiments and computational models are used to define the anatomical and functional factors leading to specificity of TES. Anatomical specificity derives from guiding current to targeted brain structures and taking advantage of the direction-sensitivity of neurons with respect to the electric field. Functional specificity originates from preferential modulation of neuronal networks that are already active. Diffuse electric fields may recruit connected brain networks involved in a training task and promote plasticity along active synaptic pathways. In vitro, electric fields boost endogenous synaptic plasticity and raise the ceiling for synaptic learning with repeated stimulation sessions. Synapses undergoing strong plasticity are preferentially modulated over weak synapses. Therefore, active circuits that are involved in a task could be more susceptible to stimulation than inactive circuits. Moreover, stimulation polarity has asymmetric effects on synaptic strength making it easier to enhance ongoing plasticity. These results suggest that the susceptibility of brain networks to an electric field depends on the state of synaptic activity. Combining a training task, which activates specific circuits, with TES may lead to functionally-specific effects. Given the simplicity of TES and the complexity of brain function, understanding the mechanisms leading to specificity is fundamental to the rational advancement of TES.

X-ray crystal structure of plasmin with tranexamic acid-derived active site inhibitors.

PubMed

Law, Ruby H P; Wu, Guojie; Leung, Eleanor W W; Hidaka, Koushi; Quek, Adam J; Caradoc-Davies, Tom T; Jeevarajah, Devadharshini; Conroy, Paul J; Kirby, Nigel M; Norton, Raymond S; Tsuda, Yuko; Whisstock, James C

2017-05-09

The zymogen protease plasminogen and its active form plasmin perform key roles in blood clot dissolution, tissue remodeling, cell migration, and bacterial pathogenesis. Dysregulation of the plasminogen/plasmin system results in life-threatening hemorrhagic disorders or thrombotic vascular occlusion. Accordingly, inhibitors of this system are clinically important. Currently, tranexamic acid (TXA), a molecule that prevents plasminogen activation through blocking recruitment to target substrates, is the most widely used inhibitor for the plasminogen/plasmin system in therapeutics. However, TXA lacks efficacy on the active form of plasmin. Thus, there is a need to develop specific inhibitors that target the protease active site. Here we report the crystal structures of plasmin in complex with the novel YO ( trans -4-aminomethylcyclohexanecarbonyl-l-tyrosine- n -octylamide) class of small molecule inhibitors. We found that these inhibitors form key interactions with the S1 and S3' subsites of the catalytic cleft. Here, the TXA moiety of the YO compounds inserts into the primary (S1) specificity pocket, suggesting that TXA itself may function as a weak plasmin inhibitor, a hypothesis supported by subsequent biochemical and biophysical analyses. Mutational studies reveal that F587 of the S' subsite plays a key role in mediating the inhibitor interaction. Taken together, these data provide a foundation for the future development of small molecule inhibitors to specifically regulate plasmin function in a range of diseases and disorders.

X-ray crystal structure of plasmin with tranexamic acid–derived active site inhibitors

PubMed Central

Wu, Guojie; Leung, Eleanor W. W.; Hidaka, Koushi; Quek, Adam J.; Caradoc-Davies, Tom T.; Jeevarajah, Devadharshini; Kirby, Nigel M.; Norton, Raymond S.; Tsuda, Yuko; Whisstock, James C.

2017-01-01

The zymogen protease plasminogen and its active form plasmin perform key roles in blood clot dissolution, tissue remodeling, cell migration, and bacterial pathogenesis. Dysregulation of the plasminogen/plasmin system results in life-threatening hemorrhagic disorders or thrombotic vascular occlusion. Accordingly, inhibitors of this system are clinically important. Currently, tranexamic acid (TXA), a molecule that prevents plasminogen activation through blocking recruitment to target substrates, is the most widely used inhibitor for the plasminogen/plasmin system in therapeutics. However, TXA lacks efficacy on the active form of plasmin. Thus, there is a need to develop specific inhibitors that target the protease active site. Here we report the crystal structures of plasmin in complex with the novel YO (trans-4-aminomethylcyclohexanecarbonyl-l-tyrosine-n-octylamide) class of small molecule inhibitors. We found that these inhibitors form key interactions with the S1 and S3′ subsites of the catalytic cleft. Here, the TXA moiety of the YO compounds inserts into the primary (S1) specificity pocket, suggesting that TXA itself may function as a weak plasmin inhibitor, a hypothesis supported by subsequent biochemical and biophysical analyses. Mutational studies reveal that F587 of the S′ subsite plays a key role in mediating the inhibitor interaction. Taken together, these data provide a foundation for the future development of small molecule inhibitors to specifically regulate plasmin function in a range of diseases and disorders. PMID:29296720

On the conversion of tritium units to mass fractions for hydrologic applications

USGS Publications Warehouse

Stonestrom, David A.; Andraski, Brian J.; Cooper, Clay A.; Mayers, Charles J.; Michel, Robert L.

2013-01-01

We develop a general equation for converting laboratory-reported tritium levels, expressed either as concentrations (tritium isotope number fractions) or mass-based specific activities, to mass fractions in aqueous systems. Assuming that all tritium is in the form of monotritiated water simplifies the derivation and is shown to be reasonable for most environmental settings encountered in practice. The general equation is nonlinear. For tritium concentrations c less than 4.5×1012 tritium units (TU) - i.e. specific tritium activities11 Bq kg-1 - the mass fraction w of tritiated water is approximated to within 1 part per million by w ≈ c×2.22293×10-18, i.e. the conversion is linear for all practical purposes. Terrestrial abundances serve as a proxy for non-tritium isotopes in the absence of sample-specific data. Variation in the relative abundances of non-tritium isotopes in the terrestrial hydrosphere produces a minimum range for the mantissa of the conversion factor of [2.22287; 2.22300].

Specific DNA binding activity of T antigen subclasses varies among different SV40-transformed cell lines.

PubMed

Burger, C; Fanning, E

1983-04-15

Large tumor antigen (T antigen) occurs in at least three different oligomeric subclasses in cells infected or transformed by simian virus 40 (SV40): 5-7 S, 14-16 S, and 23-25 S. The 23-25 S form is complexed with a host phosphoprotein (p53). The DNA binding properties of these three subclasses of T antigen from nine different cell lines and free p53 protein were compared using an immunoprecipitation assay. All three subclasses of T antigen bound specifically to SV40 DNA sequences near the origin of replication. However, the DNA binding activity varied between different cell lines over a 40- to 50-fold range. The 23-25 S and 14-16 S forms from most of the cell lines tested bound much less SV40 origin DNA than 5-7 S T antigen. The free p53 phosphoprotein did not bind specifically to any SV40 DNA sequences.

A Systematic Review of the Effects of Exercise and Physical Activity on Non-Specific Chronic Low Back Pain

PubMed Central

Gordon, Rebecca; Bloxham, Saul

2016-01-01

Back pain is a major health issue in Western countries and 60%–80% of adults are likely to experience low back pain. This paper explores the impact of back pain on society and the role of physical activity for treatment of non-specific low back pain. A review of the literature was carried out using the databases SPORTDiscuss, Medline and Google Scholar. A general exercise programme that combines muscular strength, flexibility and aerobic fitness is beneficial for rehabilitation of non-specific chronic low back pain. Increasing core muscular strength can assist in supporting the lumbar spine. Improving the flexibility of the muscle-tendons and ligaments in the back increases the range of motion and assists with the patient’s functional movement. Aerobic exercise increases the blood flow and nutrients to the soft tissues in the back, improving the healing process and reducing stiffness that can result in back pain. PMID:27417610

Melting temperature and enthalpy variations of phase change materials (PCMs): a differential scanning calorimetry (DSC) analysis

NASA Astrophysics Data System (ADS)

Sun, Xiaoqin; Lee, Kyoung Ok; Medina, Mario A.; Chu, Youhong; Li, Chuanchang

2018-06-01

Differential scanning calorimetry (DSC) analysis is a standard thermal analysis technique used to determine the phase transition temperature, enthalpy, heat of fusion, specific heat and activation energy of phase change materials (PCMs). To determine the appropriate heating rate and sample mass, various DSC measurements were carried out using two kinds of PCMs, namely N-octadecane paraffin and calcium chloride hexahydrate. The variations in phase transition temperature, enthalpy, heat of fusion, specific heat and activation energy were observed within applicable heating rates and sample masses. It was found that the phase transition temperature range increased with increasing heating rate and sample mass; while the heat of fusion varied without any established pattern. The specific heat decreased with the increase of heating rate and sample mass. For accuracy purpose, it is recommended that for PCMs with high thermal conductivity (e.g. hydrated salt) the focus will be on heating rate rather than sample mass.

Effects of CO2 Concentration on Rubisco Activity, Amount, and Photosynthesis in Soybean Leaves 1

PubMed Central

Campbell, William J.; Allen, L. H.; Bowes, George

1988-01-01

Growth at an elevated CO2 concentration resulted in an enhanced capacity for soybean (Glycine max L. Merr. cv Bragg) leaflet photosynthesis. Plants were grown from seed in outdoor controlled-environment chambers under natural solar irradiance. Photosynthetic rates, measured during the seed filling stage, were up to 150% greater with leaflets grown at 660 compared to 330 microliters of CO2 per liter when measured across a range of intercellular CO2 concentrations and irradiance. Soybean plants grown at elevated CO2 concentrations had heavier pod weights per plant, 44% heavier with 660 compared to 330 microliters of CO2 per liter grown plants, and also greater specific leaf weights. Ribulose 1,5-bisphosphate carboxylase/oxygenase (rubisco) activity showed no response (mean activity of 96 micromoles of CO2 per square meter per second expressed on a leaflet area basis) to short-term (∼1 hour) exposures to a range of CO2 concentrations (110-880 microliters per liter), nor was a response of activity (mean activity of 1.01 micromoles of CO2 per minute per milligram of protein) to growth CO2 concentration (160-990 microliters per liter) observed. The amount of rubisco protein was constant, as growth CO2 concentration was varied, and averaged 55% of the total leaflet soluble protein. Although CO2 is required for activation of rubisco, results indicated that within the range of CO2 concentrations used (110-990 microliters per liter), rubisco activity in soybean leaflets, in the light, was not regulated by CO2. PMID:16666460

Transcriptome Analysis of Mycobacteria-Specific CD4+ T Cells Identified by Activation-Induced Expression of CD154.

PubMed

Kunnath-Velayudhan, Shajo; Goldberg, Michael F; Saini, Neeraj K; Johndrow, Christopher T; Ng, Tony W; Johnson, Alison J; Xu, Jiayong; Chan, John; Jacobs, William R; Porcelli, Steven A

2017-10-01

Analysis of Ag-specific CD4 + T cells in mycobacterial infections at the transcriptome level is informative but technically challenging. Although several methods exist for identifying Ag-specific T cells, including intracellular cytokine staining, cell surface cytokine-capture assays, and staining with peptide:MHC class II multimers, all of these have significant technical constraints that limit their usefulness. Measurement of activation-induced expression of CD154 has been reported to detect live Ag-specific CD4 + T cells, but this approach remains underexplored and, to our knowledge, has not previously been applied in mycobacteria-infected animals. In this article, we show that CD154 expression identifies adoptively transferred or endogenous Ag-specific CD4 + T cells induced by Mycobacterium bovis bacillus Calmette-Guérin vaccination. We confirmed that Ag-specific cytokine production was positively correlated with CD154 expression by CD4 + T cells from bacillus Calmette-Guérin-vaccinated mice and show that high-quality microarrays can be performed from RNA isolated from CD154 + cells purified by cell sorting. Analysis of microarray data demonstrated that the transcriptome of CD4 + CD154 + cells was distinct from that of CD154 - cells and showed major enrichment of transcripts encoding multiple cytokines and pathways of cellular activation. One notable finding was the identification of a previously unrecognized subset of mycobacteria-specific CD4 + T cells that is characterized by the production of IL-3. Our results support the use of CD154 expression as a practical and reliable method to isolate live Ag-specific CD4 + T cells for transcriptomic analysis and potentially for a range of other studies in infected or previously immunized hosts. Copyright © 2017 by The American Association of Immunologists, Inc.

Mapping the functional landscape of frequent phenylalanine hydroxylase (PAH) genotypes promotes personalised medicine in phenylketonuria.

PubMed

Danecka, Marta K; Woidy, Mathias; Zschocke, Johannes; Feillet, François; Muntau, Ania C; Gersting, Søren W

2015-03-01

In phenylketonuria, genetic heterogeneity, frequent compound heterozygosity, and the lack of functional data for phenylalanine hydroxylase genotypes hamper reliable phenotype prediction and individualised treatment. A literature search revealed 690 different phenylalanine hydroxylase genotypes in 3066 phenylketonuria patients from Europe and the Middle East. We determined phenylalanine hydroxylase function of 30 frequent homozygous and compound heterozygous genotypes covering 55% of the study population, generated activity landscapes, and assessed the phenylalanine hydroxylase working range in the metabolic (phenylalanine) and therapeutic (tetrahydrobiopterin) space. Shared patterns in genotype-specific functional landscapes were linked to biochemical and pharmacological phenotypes, where (1) residual activity below 3.5% was associated with classical phenylketonuria unresponsive to pharmacological treatment; (2) lack of defined peak activity induced loss of response to tetrahydrobiopterin; (3) a higher cofactor need was linked to inconsistent clinical phenotypes and low rates of tetrahydrobiopterin response; and (4) residual activity above 5%, a defined peak of activity, and a normal cofactor need were associated with pharmacologically treatable mild phenotypes. In addition, we provide a web application for retrieving country-specific information on genotypes and genotype-specific phenylalanine hydroxylase function that warrants continuous extension, updates, and research on demand. The combination of genotype-specific functional analyses with biochemical, clinical, and therapeutic data of individual patients may serve as a powerful tool to enable phenotype prediction and to establish personalised medicine strategies for dietary regimens and pharmacological treatment in phenylketonuria. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Characterization and organic electric-double-layer-capacitor application of KOH activated coal-tar-pitch-based carbons: Effect of carbonization temperature

NASA Astrophysics Data System (ADS)

Choi, Poo Reum; Lee, Eunji; Kwon, Soon Hyung; Jung, Ji Chul; Kim, Myung-Soo

2015-12-01

The present study reports the influence of pre-carbonization on the properties of KOH-activated coal tar pitch (CTP). The change of crystallinity and pore structure of pre-carbonized CTPs as well as their activated carbons (ACs) as function of pre-carbonization temperature are investigated. The crystallinity of pre-carbonized CTPs increases with increasing the carbonization temperature up to 600 °C, but a disorder occurs during the carbonization around 700 °C and an order happens gradually with increasing the carbonization temperatures in range of 800-1000 °C. The CTPs pre-carbonized at high temperatures are more difficult to be activated with KOH than those pre-carbonized at low temperatures due to the increase of micro-crystalline size and the decrease of surface functional groups. The micro-pores and meso-pores are well developed at around 1.0 nm and 2.4 nm, respectively, as the ACs are pre-carbonized at temperatures of 500-600 °C, exhibiting high specific capacitances as electrode materials for electric double layer capacitor (EDLC). Although the specific surface area (SSA) and pore volume of ACs pre-carbonized at temperatures of 900-1000 °C are extraordinary low (non-porous) as compared to those of AC pre-carbonized at 600 °C, their specific capacitances are comparable to each other. The large specific capacitances with low SSA ACs can be attributed to the structural change resulting from the electrochemical activation during the 1st charge above 2.0 V.

Specific Synergist for Neonicotinoid Insecticides: IPPA08, a cis-Neonicotinoid Compound with a Unique Oxabridged Substructure.

PubMed

Bao, Haibo; Shao, Xusheng; Zhang, Yixi; Deng, Yayun; Xu, Xiaoyong; Liu, Zewen; Li, Zhong

2016-06-29

Insecticide synergists are key components to increase the control efficacy and reduce active ingredient use. Here, we describe a novel insecticide synergist with activity specific for insecticidal neonicotinoids. The synergist IPPA08, a cis configuration neonicotinoid compound with a unique oxabridged substructure, could increase the toxicity of most neonicotinoid insecticides belonging to the Insecticide Resistance Action Committee (IRAC) 4A subgroup against a range of insect species, although IPPA08 itself was almost inactive to insects at synergistic concentrations. Unfortunately, similar effects were observed on the honey bee (Apis mellifera) and the brown planthopper (Nilaparvata lugens), resistant to imidacloprid. IPPA08 did not show any effects on toxicity of insecticides with different targets, which made us define it as a neonicotinoid-specific synergist. Unlike most insecticide synergists, by inhibition of activities of detoxification enzymes, IPPA08 showed no effects on enzyme activities. The results revealed that IPPA08 worked as a synergist through a distinct way. Although the modulating insect nicotinic acetylcholine receptors (nAChRs, targets of neonicotinoid insecticides) were supposed as a possible mode of action for IPPA08 as a neonicotinoid-specific synergist, direct evidence is needed in further studies. In insect pest control, IPPA08 acts as a target synergist to increase neonicotinoid toxicity and reduce the amount of neonicotinoid used. Combinations of IPPA08 and insecticidal neonicotinoids may be developed into new insecticide formulations. In summary, combining an active ingredient with a "custom" synergist appears to be a very promising approach for the development of effective new insecticide products.

A peptide-based approach to evaluate the adaptability of influenza A virus to humans based on its hemagglutinin proteolytic cleavage site

PubMed Central

Straus, Marco R.; Whittaker, Gary R.

2017-01-01

Cleavage activation of the hemagglutinin (HA) protein by host proteases is a crucial step in the infection process of influenza A viruses (IAV). However, IAV exists in eighteen different HA subtypes in nature and their cleavage sites vary considerably. There is uncertainty regarding which specific proteases activate a given HA in the human respiratory tract. Understanding the relationship between different HA subtypes and human-specific proteases will be valuable in assessing the pandemic potential of circulating viruses. Here we utilized fluorogenic peptides mimicking the HA cleavage motif of representative IAV strains causing disease in humans or of zoonotic/pandemic potential and tested them with a range of proteases known to be present in the human respiratory tract. Our results show that peptides from the H1, H2 and H3 subtypes are cleaved efficiently by a wide range of proteases including trypsin, matriptase, human airway tryptase (HAT), kallikrein-related peptidases 5 (KLK5) and 12 (KLK12) and plasmin. Regarding IAVs currently of concern for human adaptation, cleavage site peptides from H10 viruses showed very limited cleavage by respiratory tract proteases. Peptide mimics from H6 viruses showed broader cleavage by respiratory tract proteases, while H5, H7 and H9 subtypes showed variable cleavage; particularly matriptase appeared to be a key protease capable of activating IAVs. We also tested HA substrate specificity of Factor Xa, a protease required for HA cleavage in chicken embryos and relevant for influenza virus production in eggs. Overall our data provide novel tool allowing the assessment of human adaptation of IAV HA subtypes. PMID:28358853

Comparison of the milk-clotting properties of three plant extracts.

PubMed

Mazorra-Manzano, Miguel A; Perea-Gutiérrez, Teresa C; Lugo-Sánchez, María E; Ramirez-Suarez, Juan C; Torres-Llanez, María J; González-Córdova, Aarón F; Vallejo-Cordoba, Belinda

2013-12-01

Several proteases from plant sources have been proposed as milk coagulants, however, limited research has been done on their milk-clotting properties. The effect of temperature on the milk-clotting activity of kiwi fruit, melon and ginger extracts was evaluated, as well as the effects of the different extracts on curd properties. Melon extracts showed high milk-clotting activity over a broad temperature range (45-75 °C) while kiwi fruit and ginger extracts showed high activity over a narrower temperature range, with a maximum at 40 and 63 °C, respectively. Curds produced using kiwi extracts had textural properties comparable with those obtained using commercial rennet, while melon extracts produced a fragile gel and low curd yield. The milk-clotting behavior of the three plant extracts was related to the protease specificity present in these extracts. The kiwi proteases displayed chymosin-like properties and thus hold the best potential for use as a milk coagulant in cheese production. Copyright © 2013 Elsevier Ltd. All rights reserved.

Optimization of auxiliary optics in active-optics telescopes

NASA Astrophysics Data System (ADS)

Ragazzoni, Roberto

1993-04-01

The a-priori knowledge of the availability of active optics in a telescope can be advantageous in the design, optimization, and specification of tolerances for auxiliary devices of such a telescope. A modification of the merit function to be used into the optimization process is given, together with some considerations about the design procedure. The different effects of aberrations typically depending upon the position of the field of view (like coma or astigmatism), with those typically constant over the whole field of view (like spherical aberration) are explicitly taken into account in the mathematical treatment. A possible range of applications (prime focus corrector, off-axis field corrector, field flattener, reducing camera, and so on) is discussed. A case study for a field flattener is shown. The general result that can be derived from this paper is that tolerances are generally strongly relaxed, while a significant improvement of the nominal performances can be obtained only in particular cases or assuming a high dynamic range of the active optics correction.

Synaptic dynamics contribute to long-term single neuron response fluctuations.

PubMed

Reinartz, Sebastian; Biro, Istvan; Gal, Asaf; Giugliano, Michele; Marom, Shimon

2014-01-01

Firing rate variability at the single neuron level is characterized by long-memory processes and complex statistics over a wide range of time scales (from milliseconds up to several hours). Here, we focus on the contribution of non-stationary efficacy of the ensemble of synapses-activated in response to a given stimulus-on single neuron response variability. We present and validate a method tailored for controlled and specific long-term activation of a single cortical neuron in vitro via synaptic or antidromic stimulation, enabling a clear separation between two determinants of neuronal response variability: membrane excitability dynamics vs. synaptic dynamics. Applying this method we show that, within the range of physiological activation frequencies, the synaptic ensemble of a given neuron is a key contributor to the neuronal response variability, long-memory processes and complex statistics observed over extended time scales. Synaptic transmission dynamics impact on response variability in stimulation rates that are substantially lower compared to stimulation rates that drive excitability resources to fluctuate. Implications to network embedded neurons are discussed.

Synthesis, alkaline phosphatase inhibition studies and molecular docking of novel derivatives of 4-quinolones.

PubMed

Miliutina, Mariia; Ejaz, Syeda Abida; Khan, Shafi Ullah; Iaroshenko, Viktor O; Villinger, Alexander; Iqbal, Jamshed; Langer, Peter

2017-01-27

New and convenient methods for the functionalization of the 4-quinolone scaffold at positions C-1, C-3 and C-6 were developed. The 4-quinolone derivatives were evaluated for their inhibitory potential on alkaline phosphatase isozymes. Most of the compounds exhibit excellent inhibitory activity and moderate selectivity. The IC 50 values on tissue non-specific alkaline phosphatase (TNAP) were in the range of 1.34 ± 0.11 to 44.80 ± 2.34 μM, while the values on intestinal alkaline phosphatase (IAP) were in the range of 1.06 ± 0.32 to 192.10 ± 3.78 μM. The most active derivative exhibits a potent inhibition on IAP with a ≈14 fold higher selectivity as compared to TNAP. Furthermore, molecular docking calculations were performed for the most potent inhibitors to show their binding interactions within the active site of the respective enzymes. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Quantitative X-ray - UV Line and Continuum Spectroscopy with Application to AGN: State-Specific Hydrogenic Recombination Cooling Coefficients for a Wide Range of Conditions

NASA Technical Reports Server (NTRS)

LaMothe, J.; Ferland, Gary J.

2002-01-01

Recombination cooling, in which a free electron emits light while being captured to an ion, is an important cooling process in photoionized clouds that are optically thick or have low metallicity. State specific rather than total recombination cooling rates are needed since the hydrogen atom tends to become optically thick in high-density regimes such as Active Galactic Nuclei. This paper builds upon previous work to derive the cooling rate over the full temperature range where the process can be a significant contributor in a photoionized plasma. We exploit the fact that the recombination and cooling rates are given by intrinsically similar formulae to express the cooling rate in terms of the closely related radiative recombination rate. We give an especially simple but accurate approximation that works for any high hydrogenic level and can be conveniently employed in large-scale numerical simulations.

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

Kvon, Evgeny Z.; Kamneva, Olga K.; Melo, Uirá S.

The evolution of body shape is thought to be tightly coupled to changes in regulatory sequences, but specific molecular events associated with major morphological transitions in vertebrates have remained elusive. In this paper, we identified snake-specific sequence changes within an otherwise highly conserved long-range limb enhancer of Sonic hedgehog (Shh). Transgenic mouse reporter assays revealed that the in vivo activity pattern of the enhancer is conserved across a wide range of vertebrates, including fish, but not in snakes. Genomic substitution of the mouse enhancer with its human or fish ortholog results in normal limb development. In contrast, replacement with snake orthologsmore » caused severe limb reduction. Synthetic restoration of a single transcription factor binding site lost in the snake lineage reinstated full in vivo function to the snake enhancer. Our results demonstrate changes in a regulatory sequence associated with a major body plan transition and highlight the role of enhancers in morphological evolution.« less

Feasibility and Effectiveness of Using Wearable Activity Trackers in Youth: A Systematic Review

PubMed Central

McNarry, Melitta A; Mackintosh, Kelly A

2016-01-01

Background The proliferation and popularity of wearable activity trackers (eg, Fitbit, Jawbone, Misfit) may present an opportunity to integrate such technology into physical activity interventions. While several systematic reviews have reported intervention effects of using wearable activity trackers on adults’ physical activity levels, none to date have focused specifically on children and adolescents. Objective The aim of this review was to examine the effectiveness of wearable activity trackers as a tool for increasing children’s and adolescents’ physical activity levels. We also examined the feasibility of using such technology in younger populations (age range 5-19 years). Methods We conducted a systematic search of 5 electronic databases, reference lists, and personal archives to identify articles published up until August 2016 that met the inclusion criteria. Articles were included if they (1) specifically examined the use of a wearable device within an intervention or a feasibility study; (2) included participants aged 5-19 years old; (3) had a measure of physical activity as an outcome variable for intervention studies; (4) reported process data concerning the feasibility of the device in feasibility studies; and (5) were published in English. Data were analyzed in August 2016. Results In total, we identified and analyzed 5 studies (3 intervention, 2 feasibility). Intervention delivery ranged from 19 days to 3 months, with only 1 study using a randomized controlled trial design. Wearable activity trackers were typically combined with other intervention approaches such as goal setting and researcher feedback. While intervention effects were generally positive, the reported differences were largely nonsignificant. The feasibility studies indicated that monitor comfort and design and feedback features were important factors to children and adolescents. Conclusions There is a paucity of research concerning the effectiveness and feasibility of wearable activity trackers as a tool for increasing children’s and adolescents’ physical activity levels. While there are some preliminary data to suggest these devices may have the potential to increase activity levels through self-monitoring and goal setting in the short term, more research is needed to establish longer-term effects on behavior. PMID:27881359

Direction-Specific Impairments in Cervical Range of Motion in Women with Chronic Neck Pain: Influence of Head Posture and Gravitationally Induced Torque.

PubMed

Rudolfsson, Thomas; Björklund, Martin; Svedmark, Åsa; Srinivasan, Divya; Djupsjöbacka, Mats

2017-01-01

Cervical range of motion (ROM) is commonly assessed in clinical practice and research. In a previous study we decomposed active cervical sagittal ROM into contributions from lower and upper levels of the cervical spine and found level- and direction-specific impairments in women with chronic non-specific neck pain. The present study aimed to validate these results and investigate if the specific impairments can be explained by the neutral posture (defining zero flexion/extension) or a movement strategy to avoid large gravitationally induced torques on the cervical spine. Kinematics of the head and thorax was assessed in sitting during maximal sagittal cervical flexion/extension (high torque condition) and maximal protraction (low torque condition) in 120 women with chronic non-specific neck pain and 40 controls. We derived the lower and upper cervical angles, and the head centre of mass (HCM), from a 3-segment kinematic model. Neutral head posture was assessed using a standardized procedure. Previous findings of level- and direction-specific impairments in neck pain were confirmed. Neutral head posture was equal between groups and did not explain the direction-specific impairments. The relative magnitude of group difference in HCM migration did not differ between high and low torques conditions, lending no support for our hypothesis that impairments in sagittal ROM are due to torque avoidance behaviour. The direction- and level-specific impairments in cervical sagittal ROM can be generalised to the population of women with non-specific neck pain. Further research is necessary to clarify if torque avoidance behaviour can explain the impairments.

Structural and kinetic studies of a novel nerol dehydrogenase from Persicaria minor, a nerol-specific enzyme for citral biosynthesis.

PubMed

Tan, Cheng Seng; Hassan, Maizom; Mohamed Hussein, Zeti Azura; Ismail, Ismanizan; Ho, Kok Lian; Ng, Chyan Leong; Zainal, Zamri

2018-02-01

Geraniol degradation pathway has long been elucidated in microorganisms through bioconversion studies, yet weakly characterised in plants; enzyme with specific nerol-oxidising activity has not been reported. A novel cDNA encodes nerol dehydrogenase (PmNeDH) was isolated from Persicaria minor. The recombinant PmNeDH (rPmNeDH) is a homodimeric enzyme that belongs to MDR (medium-chain dehydrogenases/reductases) superfamily that catalyses the first oxidative step of geraniol degradation pathway in citral biosynthesis. Kinetic analysis revealed that rPmNeDH has a high specificity for allylic primary alcohols with backbone ≤10 carbons. rPmNeDH has ∼3 fold higher affinity towards nerol (cis-3,7-dimethyl-2,6-octadien-1-ol) than its trans-isomer, geraniol. To our knowledge, this is the first alcohol dehydrogenase with higher preference towards nerol, suggesting that nerol can be effective substrate for citral biosynthesis in P. minor. The rPmNeDH crystal structure (1.54 Å) showed high similarity with enzyme structures from MDR superfamily. Structure guided mutation was conducted to describe the relationships between substrate specificity and residue substitutions in the active site. Kinetics analyses of wild-type rPmNeDH and several active site mutants demonstrated that the substrate specificity of rPmNeDH can be altered by changing any selected active site residues (Asp 280 , Leu 294 and Ala 303 ). Interestingly, the L294F, A303F and A303G mutants were able to revamp the substrate preference towards geraniol. Furthermore, mutant that exhibited a broader substrate range was also obtained. This study demonstrates that P. minor may have evolved to contain enzyme that optimally recognise cis-configured nerol as substrate. rPmNeDH structure provides new insights into the substrate specificity and active site plasticity in MDR superfamily. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Quality of Life Outcomes after Primary Treatment for Clinically Localised Prostate Cancer: A Systematic Review.

PubMed

Lardas, Michael; Liew, Matthew; van den Bergh, Roderick C; De Santis, Maria; Bellmunt, Joaquim; Van den Broeck, Thomas; Cornford, Philip; Cumberbatch, Marcus G; Fossati, Nicola; Gross, Tobias; Henry, Ann M; Bolla, Michel; Briers, Erik; Joniau, Steven; Lam, Thomas B; Mason, Malcolm D; Mottet, Nicolas; van der Poel, Henk G; Rouvière, Olivier; Schoots, Ivo G; Wiegel, Thomas; Willemse, Peter-Paul M; Yuan, Cathy Yuhong; Bourke, Liam

2017-12-01

Current evidence-based management for clinically localised prostate cancer includes active surveillance, surgery, external beam radiotherapy (EBRT) and brachytherapy. The impact of these treatment modalities on quality of life (QoL) is uncertain. To systematically review comparative studies investigating disease-specific QoL outcomes as assessed by validated cancer-specific patient-reported outcome measures with at least 1 yr of follow-up after primary treatment for clinically localised prostate cancer. MEDLINE, EMBASE, AMED, PsycINFO, and Cochrane Library were searched to identify relevant studies. Studies were critically appraised for the risk of bias. A narrative synthesis was undertaken. Of 11486 articles identified, 18 studies were eligible for inclusion, including three randomised controlled trials (RCTs; follow-up range: 60-72 mo) and 15 nonrandomised comparative studies (follow-up range: 12-180 mo) recruiting a total of 13604 patients. Two RCTs recruited small cohorts and only one was judged to have a low risk of bias. The quality of evidence from observational studies was low to moderate. For a follow-up of up to 6 yr, active surveillance was found to have the lowest impact on cancer-specific QoL, surgery had a negative impact on urinary and sexual function when compared with active surveillance and EBRT, and EBRT had a negative impact on bowel function when compared with active surveillance and surgery. Data from one small RCT reported that brachytherapy has a negative impact on urinary function 1 yr post-treatment, but no significant urinary toxicity was reported at 5 yr. This is the first systematic review comparing the impact of different primary treatments on cancer-specific QoL for men with clinically localised prostate cancer, using validated cancer-specific patient-reported outcome measures only. There is robust evidence that choice of primary treatment for localised prostate cancer has distinct impacts on patients' QoL. This should be discussed in detail with patients during pretreatment counselling. Our review of the current evidence suggests that for a period of up to 6 yr after treatment, men with localised prostate cancer who were managed with active surveillance reported high levels of quality of life (QoL). Men treated with surgery reported mainly urinary and sexual problems, while those treated with external beam radiotherapy reported mainly bowel problems. Men eligible for brachytherapy reported urinary problems up to a year after therapy, but then their QoL returned gradually to as it was before treatment. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

Activity-specific ecological niche models for planning reintroductions of California condors (Gymnogyps californianus)

USGS Publications Warehouse

D'Elia, Jesse; Haig, Susan M.; Johnson, Matthew J.; Marcot, Bruce G.; Young, Richard

2015-01-01

Ecological niche models can be a useful tool to identify candidate reintroduction sites for endangered species but have been infrequently used for this purpose. In this paper, we (1) develop activity-specific ecological niche models (nesting, roosting, and feeding) for the critically endangered California condor (Gymnogyps californianus) to aid in reintroduction planning in California, Oregon, and Washington, USA, (2) test the accuracy of these models using empirical data withheld from model development, and (3) integrate model results with information on condor movement ecology and biology to produce predictive maps of reintroduction site suitability. Our approach, which disentangles niche models into activity-specific components, has applications for other species where it is routinely assumed (often incorrectly) that individuals fulfill all requirements for life within a single environmental space. Ecological niche models conformed to our understanding of California condor ecology, had good predictive performance when tested with data withheld from model development, and aided in the identification of several candidate reintroduction areas outside of the current distribution of the species. Our results suggest there are large unoccupied regions of the California condor’s historical range that have retained ecological features similar to currently occupied habitats, and thus could be considered for future reintroduction efforts. Combining our activity-specific ENMs with ground reconnaissance and information on other threat factors that could not be directly incorporated into empirical ENMs will ultimately improve our ability to select successful reintroduction sites for the California condor.

Electrophoretic separation and analysis of living cells from solid tissues by several methods - Human embryonic kidney cell cultures as a model

NASA Technical Reports Server (NTRS)

Todd, Paul; Plank, Lindsay D.; Kunze, M. Elaine; Lewis, Marian L.; Morrison, Dennis R.

1986-01-01

The use of free-fluid electrophoresis methods to separate tissue cells having a specific function is discussed. It is shown that cells suspended by trypsinization from cultures of human embryonic kidney are electrophoretically heterogeneous and tolerate a wide range of electrophoresis buffers and conditions without significant attenuation of function. Moreover, these cells do not separate electrophoretically on the basis of size or cell position alone and can be separated according to their ability to give rise to progeny that produce specific plasminogen activators.

Parvovirus B19 Myocarditis of Fulminant Evolution.

PubMed

Spartalis, Michael; Tzatzaki, Eleni; Spartalis, Eleftherios; Damaskos, Christos; Mavrogeni, Sophie; Voudris, Vassilis

2017-08-01

Myocarditis is an inflammation of the myocardium. Clinical presentation ranges from non-specific systematic symptoms to fulminant collapse and sudden death. Sudden death occurs at rates of 8.6-12% and cardiomyopathy at 9%. In active myocarditis, there is inflammatory cellular infiltrate with myocardial necrosis. The disease is distinguished by clinical presentation in fulminant and non-fulminant myocarditis. We present a rare case of a parvovirus B19-induced fulminant viral myocarditis in a young female. The patient presented with acute onset heart failure mimicking a myocardial infarction, followed by non-specific symptoms that had been misdiagnosed as urinary tract infection.

Parvovirus B19 Myocarditis of Fulminant Evolution

PubMed Central

Spartalis, Michael; Tzatzaki, Eleni; Spartalis, Eleftherios; Damaskos, Christos; Mavrogeni, Sophie; Voudris, Vassilis

2017-01-01

Myocarditis is an inflammation of the myocardium. Clinical presentation ranges from non-specific systematic symptoms to fulminant collapse and sudden death. Sudden death occurs at rates of 8.6-12% and cardiomyopathy at 9%. In active myocarditis, there is inflammatory cellular infiltrate with myocardial necrosis. The disease is distinguished by clinical presentation in fulminant and non-fulminant myocarditis. We present a rare case of a parvovirus B19-induced fulminant viral myocarditis in a young female. The patient presented with acute onset heart failure mimicking a myocardial infarction, followed by non-specific symptoms that had been misdiagnosed as urinary tract infection. PMID:28868104

Managing military training-related environmental disturbance.

PubMed

Zentelis, Rick; Banks, Sam; Roberts, J Dale; Dovers, Stephen; Lindenmayer, David

2017-12-15

Military Training Areas (MTAs) cover at least 2 percent of the Earth's terrestrial surface and occur in all major biomes. These areas are potentially important for biodiversity conservation. The greatest challenge in managing MTAs is balancing the disturbance associated with military training and environmental values. These challenges are unique as no other land use is managed for these types of anthropogenic disturbances in a natural setting. We investigated how military training-related disturbance is best managed on MTAs. Specifically, we explored management options to maximise the amount of military training that can be undertaken on a MTA while minimising the amount of environmental disturbance. MTAs comprise of a number of ranges designed to facilitate different types of military training. We simulated military training-related environmental disturbance at different range usage rates under a typical range rotation use strategy, and compared the results to estimated ecosystem recovery rates from training activities. We found that even at relatively low simulated usage rates, random allocation and random spatial use of training ranges within an MTA resulted in environmental degradation under realistic ecological recovery rates. To avoid large scale environmental degradation, we developed a decision-making tool that details the best method for managing training-related disturbance by determining how training activities can be allocated to training ranges. Copyright © 2017 Elsevier Ltd. All rights reserved.

Formation of carbon nanosheets via simultaneous activation and catalytic carbonization of macroporous anion-exchange resin for supercapacitors application.

PubMed

Peng, Hui; Ma, Guofu; Sun, Kanjun; Mu, Jingjing; Zhang, Zhe; Lei, Ziqiang

2014-12-10

Two-dimensional mesoporous carbon nanosheets (CNSs) have been prepared via simultaneous activation and catalytic carbonization route using macroporous anion-exchange resin (AER) as carbon precursor and ZnCl2 and FeCl3 as activating agent and catalyst, respectively. The iron catalyst in the skeleton of the AER may lead to carburization to form a sheetlike structure during the carbonization process. The obtained CNSs have a large number of mesopores, a maximum specific surface area of 1764.9 m(2) g(-1), and large pore volume of 1.38 cm(3) g(-1). As an electrode material for supercapacitors application, the CNSs electrode possesses a large specific capacitance of 283 F g(-1) at 0.5 A g(-1) and excellent rate capability (64% retention ratio even at 50 A g(-1)) in 6 mol L(-1) KOH. Furthermore, CNSs symmetric supercapacitor exhibits specific energies of 17.2 W h kg(-1) at a power density of 224 W kg(-1) operated in the voltage range of 0-1.8 V in 0.5 mol L(-1) Na2SO4 aqueous electrolyte, and outstanding cyclability (retains about 96% initial capacitance after 5000 cycles).

Stated Uptake of Physical Activity Rewards Programmes Among Active and Insufficiently Active Full-Time Employees.

PubMed

Ozdemir, Semra; Bilger, Marcel; Finkelstein, Eric A

2017-10-01

Employers are increasingly relying on rewards programmes in an effort to promote greater levels of activity among employees; however, if enrolment in these programmes is dominated by active employees, then they are unlikely to be a good use of resources. This study uses a stated-preference survey to better understand who participates in rewards-based physical activity programmes, and to quantify stated uptake by active and insufficiently active employees. The survey was fielded to a national sample of 950 full-time employees in Singapore between 2012 and 2013. Participants were asked to choose between hypothetical rewards programmes that varied along key dimensions and whether or not they would join their preferred programme if given the opportunity. A mixed logit model was used to analyse the data and estimate predicted uptake for specific programmes. We then simulated employer payments based on predictions for the percentage of each type of employee likely to meet the activity goal. Stated uptake ranged from 31 to 67% of employees, depending on programme features. For each programme, approximately two-thirds of those likely to enrol were insufficiently active. Results showed that insufficiently active employees, who represent the majority, are attracted to rewards-based physical activity programmes, and at approximately the same rate as active employees, even when enrolment fees are required. This suggests that a programme with generous rewards and a modest enrolment fee may have strong employee support and be within the range of what employers may be willing to spend.

Active B12: a rapid, automated assay for holotranscobalamin on the Abbott AxSYM analyzer.

PubMed

Brady, Jeff; Wilson, Lesley; McGregor, Lynda; Valente, Edward; Orning, Lars

2008-03-01

Conventional tests for vitamin B(12) deficiency measure total serum vitamin B12, whereas only that portion of vitamin B12 carried by transcobalamin (holotranscobalamin) is metabolically active. Measurement of holotranscobalamin (holoTC) may be more diagnostically accurate for detecting B(12) deficiency that requires therapy. We developed an automated assay for holoTC that can be used on the Abbott AxSYM immunoassay analyzer. AxSYM Active B12 is a 2-step sandwich microparticle enzyme immunoassay. In step 1, a holoTC-specific antibody immobilized onto latex microparticles captures holoTC in samples of serum or plasma. In step 2, the captured holoTC is detected with a conjugate of alkaline phosphatase and antiTC antibody. Neither apoTC nor haptocorrin exhibited detectable cross-reactivity. The detection limit was < or = 0.1 pmol/L. Within-run and total imprecision (CV ranges) were 3.4%-5.1% and 6.3%-8.5%, respectively. Assay CVs were < 20% from at least 3 pmol/L to 107 pmol/L. With diluted serum samples, measured concentrations were 104%-114% of the expected values in the working range of the assay. No interference from bilirubin, hemoglobin, triglycerides, erythrocytes, rheumatoid factor, or total protein was detected at expected (abnormal) concentrations. A comparison of the AxSYM Active B12 assay with a commercial RIA for holoTC yielded the regression equation: AxSYM = 0.98RIA + 4.7 pmol/L (S(y x), 11.4 pmol/L; n = 204). Assay throughput was 45 tests/h. A 95% reference interval of 19-134 pmol/L holoTC was established with samples from 292 healthy individuals. The AxSYM Active B12 assay allows rapid, precise, sensitive, specific, and automated measurement of human holoTC in serum and plasma.

Delivering customized apps, multimedia and NASA data to libraries and their patrons

NASA Astrophysics Data System (ADS)

Harold, J. B.; Dusenbery, P.; Holland, A.; LaConte, K.; Johnson, A.; Randall, C.; Fitzhugh, G.

2017-12-01

With funding through NASA's Science Mission Directorate, the NASA @ My Library project has been working with the public library community to enhance the STEM literacy of library patrons throughout the nation. One element of the project is to disseminate a variety of materials to 75 partner libraries in order to support their implementation of hands-on, NASA related STEM activities for their patrons. These materials range from very low tech (UV beads) to high tech (a 4.5" Orion Dobsonian telescope), and include an 8" tablet. This tablet provides us with a wide range of possibilities for delivering NASA content. Besides NASA multimedia and real-time spacecraft data, the tablets can be used for interactive activities, including public apps as well as apps specifically designed for this program, such as a green screen app that incorporates NASA imagery as part of a larger storytelling activity. The tablets also include a full sensor suite (magnetometer, light sensor, accelerometer, etc.), allowing us to develop library activities that use the tablet as a measuring device - detecting magnetism in a "Meteorite or Wrong" activity, or using the light sensor as a transit device. The tablet is centrally managed and includes a "kiosk mode", allowing the libraries to use it in either a locked down or conventional mode. The management system also allows us to create a curated collection of apps and multimedia, push out updated software, and collect analytics data on how the tablet is being used. In this presentation we will discuss the library pre-survey that guided our tablet development process, as well as our lessons learned to date, including the practicality and effectiveness of deploying tablets at this scale, their ability to support NASA specific STEM efforts, and what we have learned about library usage.

[Distribution of 137Cs and relative influencing factors on typical karst sloping land].

PubMed

Zhang, Xiao-Nan; Wang, Ke-Lin; Zhang, Wei; Chen, Hong-Song; He, Xun-Yang; Zhang, Xin-Bao

2009-11-01

Based on the field survey and the analysis of a large number of soil samples, the distribution of 137 Cs and its influencing factors were studied using 137 Cs tracer technology on typical karst sloping land. The results indicate that the distribution of 137 Cs in soil profile in karst areas show the similar characteristics as that in non-karst areas, fitted an exponential pattern in forest soils and a uniform pattern in cultivated soils. In the sinkhole points in karst areas, 137 Cs exists in deep soil layers and its specific activity vary from 1.7 to 3.3 Bq/kg in soil layers above 45cm, suggesting the existing soil around karst sinkhole is mainly formed by the accumulation of erosion materials. The 137 Cs specific activity in the soil from two rock cracks are 16.8 Bq/kg and 37.6 Bq/kg respectively, which are much higher than that in the soil around the rock, this phenomenon indicates that bare rock is an important influencing factor for 137 Cs spatial movement. With the increment of altitude, the 137 Cs area activity exhibits an irregular fluctuation and evident spatial heterogeneity. On the forest land, the 137 Cs area activities which range from 299.4 to 1 592.6 Bq/m2 are highly positively correlated with the slope gradient and positively correlated with the altitude; while on the cultivated land, the 137 Cs area activities which range from 115.8 to 1478.6 Bq/m2 are negatively correlated with the slope gradient but negatively correlated with the altitude. Topography, geomorphology and human disturbance intensity are the key factors influencing 137 Cs spatial distribution.

Impact of study design on development and evaluation of an activity-type classifier.

PubMed

van Hees, Vincent T; Golubic, Rajna; Ekelund, Ulf; Brage, Søren

2013-04-01

Methods to classify activity types are often evaluated with an experimental protocol involving prescribed physical activities under confined (laboratory) conditions, which may not reflect real-life conditions. The present study aims to evaluate how study design may impact on classifier performance in real life. Twenty-eight healthy participants (21-53 yr) were asked to wear nine triaxial accelerometers while performing 58 activity types selected to simulate activities in real life. For each sensor location, logistic classifiers were trained in subsets of up to 8 activities to distinguish between walking and nonwalking activities and were then evaluated in all 58 activities. Different weighting factors were used to convert the resulting confusion matrices into an estimation of the confusion matrix as would apply in the real-life setting by creating four different real-life scenarios, as well as one traditional laboratory scenario. The sensitivity of a classifier estimated with a traditional laboratory protocol is within the range of estimates derived from real-life scenarios for any body location. The specificity, however, was systematically overestimated by the traditional laboratory scenario. Walking time was systematically overestimated, except for lower back sensor data (range: 7-757%). In conclusion, classifier performance under confined conditions may not accurately reflect classifier performance in real life. Future studies that aim to evaluate activity classification methods are warranted to pay special attention to the representativeness of experimental conditions for real-life conditions.

Identification of 6H1 as a P2Y purinoceptor: P2Y5.

PubMed

Webb, T E; Kaplan, M G; Barnard, E A

1996-02-06

We have determined the identity of the orphan G-protein coupled receptor cDNA, 6H1, present in activated chicken T cells, as a subtype of P2Y purinoceptor. This identification is based on first on the degree of sequence identity shared with recently cloned members of the P2Y receptor family and second on the pharmacological profile. Upon transient expression in COS-7 cells the 6H1 receptor bound the radiolabel [35S]dATP alpha S specifically and with high affinity (Kd, 10 nM). This specific binding could be competitively displaced by a range of ligands active at P2 purinoceptors, with ATP being the most active (K (i)), 116 nM). Such competition studies have established the following rank order of activity: ATP ADP 2-methylthioATP alpha, beta-methylene ATP, UTP, thus confirming 6H1 as a member of the growing family of P2Y purinoceptors. As the fifth receptor of this type to be identified we suggest that it be named P2Y5.

Cloning, Expression, and Biochemical Characterization of an Enantioselective Lipase, YLIP9, from Yarrowia lipolytica MSR80.

PubMed

Syal, Poonam; Gupta, Rani

2015-05-01

A novel lipase gene, ylip9, of Yarrowia lipolytica MSR80 was cloned and expressed in pEZZ18-HB101 system and was 99% identical to YLIP9 of Y. lipolytica CLIB122. It was purified using IgG-Sepharose as ZZ fused YLIP9 and had specific activity of 0.8 U/mg. ZZ-YLIP9 was most active at pH 8.0 and 70 °C. It was stable over a wide pH range of 3.0-11.0 and 100 % active at 70 °C up to 2 h and had t1/2 of 286.42 min at 80 °C. It showed high specificity toward p-nitrophenyldecanoate with kcat and catalytic efficiency of 30.17 s(-1) and 16.67 mM(-1) s(-1), respectively. It was non-regioselective, but an S-enantioselective lipase and the percentage conversion were enhanced in presence of hexane. ZZ-YLIP9 was stable in all of the organic solvents used, and its activity was enhanced by solvents having logP value less than 2.

Characterization of an aryl-alcohol oxidase from the plant saprophytic basidiomycete Coprinopsis cinerea with broad substrate specificity against aromatic alcohols.

PubMed

Tamaru, Yoshiaki; Umezawa, Kiwamu; Yoshida, Makoto

2018-07-01

The aim of the study was to obtain information about the enzymatic properties of aryl-alcohol oxidase from the plant saprophytic basidiomycete Coprinopsis cinerea (rCcAAO), which is classified into the auxiliary activities family 3 subfamily 2 (AA3_2). The gene encoding AAO from the plant saprophytic basidiomycete Coprinopsis cinerea (CcAAO) was cloned, and the recombinant CcAAO (rCcAAO) was heterologously expressed in the methylotrophic yeast Pichia pastoris. The purified rCcAAO showed significant activity not only against trans,trans-2,4-hexadien-1-ol but also against a broad range of aromatic alcohols including aromatic compounds that were reported to be poor substrates for known AAOs. Moreover, site-directed mutagenesis analysis demonstrated that mutants with substitutions from leucine to phenylalanine and tryptophan at position 416 exhibited decreases of activity for aromatic alcohols but still maintained the activity for trans,trans-2,4-hexadien-1-ol. Leucine 416 in CcAAO contributes to the broad substrate specificity against various aromatic alcohols, which is useful for the production of hydrogen peroxide using this enzyme.

Libraries of Synthetic TALE-Activated Promoters: Methods and Applications.

PubMed

Schreiber, T; Tissier, A

2016-01-01

The discovery of proteins with programmable DNA-binding specificities triggered a whole array of applications in synthetic biology, including genome editing, regulation of transcription, and epigenetic modifications. Among those, transcription activator-like effectors (TALEs) due to their natural function as transcription regulators, are especially well-suited for the development of orthogonal systems for the control of gene expression. We describe here the construction and testing of libraries of synthetic TALE-activated promoters which are under the control of a single TALE with a given DNA-binding specificity. These libraries consist of a fixed DNA-binding element for the TALE, a TATA box, and variable sequences of 19 bases upstream and 43 bases downstream of the DNA-binding element. These libraries were cloned using a Golden Gate cloning strategy making them usable as standard parts in a modular cloning system. The broad range of promoter activities detected and the versatility of these promoter libraries make them valuable tools for applications in the fine-tuning of expression in metabolic engineering projects or in the design and implementation of regulatory circuits. © 2016 Elsevier Inc. All rights reserved.

Actinobacteria possessing antimicrobial and antioxidant activities isolated from the pollen of scots pine (Pinus sylvestris) grown on the Baikal shore.

PubMed

Axenov-Gribanov, Denis V; Voytsekhovskaya, Irina V; Rebets, Yuriy V; Tokovenko, Bogdan T; Penzina, Tatyana A; Gornostay, Tatyana G; Adelshin, Renat V; Protasov, Eugenii S; Luzhetskyy, Andriy N; Timofeyev, Maxim A

2016-10-01

Isolated ecosystems existing under specific environmental conditions have been shown to be promising sources of new strains of actinobacteria. The taiga forest of Baikal Siberia has not been well studied, and its actinobacterial population remains uncharacterized. The proximity between the huge water mass of Lake Baikal and high mountain ranges influences the structure and diversity of the plant world in Siberia. Here, we report the isolation of eighteen actinobacterial strains from male cones of Scots pine trees (Pinus sylvestris) growing on the shore of the ancient Lake Baikal in Siberia. In addition to more common representative strains of Streptomyces, several species belonging to the genera Rhodococcus, Amycolatopsis, and Micromonospora were isolated. All isolated strains exhibited antibacterial and antifungal activities. We identified several strains that inhibited the growth of the pathogen Candida albicans but did not hinder the growth of Saccharomyces cerevisiae. Several isolates were active against Gram-positive and Gram-negative bacteria. The high proportion of biologically active strains producing antibacterial and specific antifungal compounds may reflect their role in protecting pollen against phytopathogens.

Rac1-PAK2 pathway is essential for zebrafish heart regeneration

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

Peng, Xiangwen; He, Quanze; Li, Guobao

P-21 activated kinases, or PAKs, are serine–threonine kinases that play important roles in diverse heart functions include heart development, cardiovascular development and function in a range of models; however, the mechanisms by which PAKs mediate heart regeneration are unknown. Here, we demonstrate that PAK2 and PAK4 expression is induced in cardiomyocytes and vessels, respectively, following zebrafish heart injury. Inhibition of PAK2 and PAK4 using a specific small molecule inhibitor impedes cardiomyocyte proliferation/dedifferentiation and cardiovascular regeneration, respectively. Cdc42 is specifically expressed in the ventricle and may function upstream of PAK2 but not PAK4 under normal conditions and that cardiomyocyte proliferentation duringmore » heart regeneration relies on Rac1-mediated activation of Pak2. Our results indicate that PAKs play a key role in heart regeneration.« less

The Mathematics of a Successful Deconvolution: A Quantitative Assessment of Mixture-Based Combinatorial Libraries Screened Against Two Formylpeptide Receptors

PubMed Central

Santos, Radleigh G.; Appel, Jon R.; Giulianotti, Marc A.; Edwards, Bruce S.; Sklar, Larry A.; Houghten, Richard A.; Pinilla, Clemencia

2014-01-01

In the past 20 years, synthetic combinatorial methods have fundamentally advanced the ability to synthesize and screen large numbers of compounds for drug discovery and basic research. Mixture-based libraries and positional scanning deconvolution combine two approaches for the rapid identification of specific scaffolds and active ligands. Here we present a quantitative assessment of the screening of 32 positional scanning libraries in the identification of highly specific and selective ligands for two formylpeptide receptors. We also compare and contrast two mixture-based library approaches using a mathematical model to facilitate the selection of active scaffolds and libraries to be pursued for further evaluation. The flexibility demonstrated in the differently formatted mixture-based libraries allows for their screening in a wide range of assays. PMID:23722730

CD86 expression as a surrogate cellular biomarker for pharmacological inhibition of the histone demethylase lysine-specific demethylase 1.

PubMed

Lynch, James T; Cockerill, Mark J; Hitchin, James R; Wiseman, Daniel H; Somervaille, Tim C P

2013-11-01

There is a lack of rapid cell-based assays that read out enzymatic inhibition of the histone demethylase LSD1 (lysine-specific demethylase 1). Through transcriptome analysis of human acute myeloid leukemia THP1 cells treated with a tranylcypromine-derivative inhibitor of LSD1 active in the low nanomolar range, we identified the cell surface marker CD86 as a sensitive surrogate biomarker of LSD1 inhibition. Within 24h of enzyme inhibition, there was substantial and dose-dependent up-regulation of CD86 expression, as detected by quantitative polymerase chain reaction, flow cytometry, and enzyme-linked immunosorbent assay. Thus, the use of CD86 expression may facilitate screening of compounds with putative LSD1 inhibitory activities in cellular assays. Copyright © 2013 Elsevier Inc. All rights reserved.

Functional microbiomics: Evaluation of gut microbiota-bile acid metabolism interactions in health and disease.

PubMed

Mullish, Benjamin H; Pechlivanis, Alexandros; Barker, Grace F; Thursz, Mark R; Marchesi, Julian R; McDonald, Julie A K

2018-04-26

There is an ever-increasing recognition that bile acids are not purely simple surfactant molecules that aid in lipid digestion, but are a family of molecules contributing to a diverse range of key systemic functions in the host. It is now also understood that the specific composition of the bile acid milieu within the host is related to the expression and activity of bacterially-derived enzymes within the gastrointestinal tract, as such creating a direct link between the physiology of the host and the gut microbiota. Coupled to the knowledge that perturbation of the structure and/or function of the gut microbiota may contribute to the pathogenesis of a range of diseases, there is a high level of interest in the potential for manipulation of the gut microbiota-host bile acid axis as a novel approach to therapeutics. Much of the growing understanding of the biology of this area reflects the recent development and refinement of a range of novel techniques; this study applies a number of those techniques to the analysis of human samples, aiming to illustrate their strengths, drawbacks and biological significance at all stages. Specifically, we used microbial profiling (using 16S rRNA gene sequencing), bile acid profiling (using liquid chromatography-mass spectrometry), bsh and baiCD qPCR, and a BSH enzyme activity assay to demonstrate differences in the gut microbiota and bile metabolism in stool samples from healthy and antibiotic-exposed individuals. Copyright © 2018 Elsevier Inc. All rights reserved.

Ambient concentrations of total suspended particulate matter and its elemental constituents at the wider area of the mining facilities of TVX Hellas in Chalkidiki, Greece.

PubMed

Gaidajis, George

2003-01-01

To assess ambient air quality at the wider area of TVX Hellas mining facilities, the Total Suspended Particulate matter (TSP) and its content in characteristic elements, i.e., As, Cd, Cu, Fe, Mn, Pb, Zn are being monitored for more than thirty months as part of the established Environmental Monitoring Program. High Volume air samplers equipped with Tissue Quartz filters were employed for the collection of TSP. Analyses were effected after digestion of the suspended particulate with an HNO3-HCl solution and determination of elemental concentrations with an Atomic Absorption Spectroscopy equipped with graphite furnace. The sampling stations were selected to record representatively the existing ambient air quality in the vicinity of the facilities and at remote sites not affected from industrial activities. Monitoring data indicated that the background TSP concentrations ranged from 5-60 microg/m3. Recorded TSP concentrations at the residential sites close to the facilities ranged between 20-100 microg/m3, indicating only a minimal influence from the mining and milling activities. Similar spatial variation was observed for the TSP constituents and specifically for Pb and Zn. To validate the monitoring procedures, a parallel sampling campaign took place with different High Volume samplers at days where low TSP concentrations were expected. The satisfactory agreement (+/- 11%) at low concentrations (50-100 microg/m3) clearly supported the reproducibility of the techniques employed specifically at the critical range of lower concentrations.

Commercially available interactive video games in burn rehabilitation: therapeutic potential.

PubMed

Parry, Ingrid S; Bagley, Anita; Kawada, Jason; Sen, Soman; Greenhalgh, David G; Palmieri, Tina L

2012-06-01

Commercially available interactive video games (IVG) like the Nintendo Wii™ (NW) and PlayStation™II Eye Toy (PE) are increasingly used in the rehabilitation of patients with burn. Such games have gained popularity in burn rehabilitation because they encourage range of motion (ROM) while distracting from pain. However, IVGs were not originally designed for rehabilitation purposes but rather for entertainment and may lack specificity for achieving rehabilitative goals. Objectively evaluating the specific demands of IVGs in relation to common burn therapy goals will determine their true therapeutic benefit and guide their use in burn rehabilitation. Upper extremity (UE) motion of 24 normal children was measured using 3D motion analysis during play with the two types of IVGs most commonly described for use after burn: NW and PE. Data was analyzed using t-tests and One-way Analysis of Variance. Active range of motion for shoulder flexion and abduction during play with both PE and NW was within functional range, thus supporting the idea that IVGs offer activities with therapeutic potential to improve ROM. PE resulted in higher demands and longer duration of UE motion than NW, and therefore may be the preferred tool when UE ROM or muscular endurance are the goals of rehabilitation. When choosing a suitable IVG for application in rehabilitation, the user's impairment together with the therapeutic attributes of the IVG should be considered to optimize outcome. Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.

Thermal Preference Ranges Correlate with Stable Signals of Universal Stress Markers in Lake Baikal Endemic and Holarctic Amphipods

PubMed Central

Axenov-Gribanov, Denis; Bedulina, Daria; Shatilina, Zhanna; Jakob, Lena; Vereshchagina, Kseniya; Lubyaga, Yulia; Gurkov, Anton; Shchapova, Ekaterina; Luckenbach, Till; Lucassen, Magnus; Sartoris, Franz Josef; Pörtner, Hans-Otto; Timofeyev, Maxim

2016-01-01

Temperature is the most pervasive abiotic environmental factor for aquatic organisms. Fluctuations in temperature range lead to changes in metabolic performance. Here, we aimed to identify whether surpassing the thermal preference zones is correlated with shifts in universal cellular stress markers of protein integrity, responses to oxidative stress and lactate content, as indicators of anaerobic metabolism. Exposure of the Lake Baikal endemic amphipod species Eulimnogammarus verrucosus (Gerstfeldt, 1858), Ommatogammarus flavus (Dybowski, 1874) and of the Holarctic amphipod Gammarus lacustris Sars 1863 (Amphipoda, Crustacea) to increasing temperatures resulted in elevated heat shock protein 70 (Hsp70) and lactate content, elevated antioxidant enzyme activities (i.e., catalase and peroxidase), and reduced lactate dehydrogenase and glutathione S-transferase activities. Thus, the zone of stability (absence of any significant changes) of the studied molecular and biochemical markers correlated with the behaviorally preferred temperatures. We conclude that the thermal behavioral responses of the studied amphipods are directly related to metabolic processes at the cellular level. Thus, the determined thermal ranges may possibly correspond to the thermal optima. This relationship between species-specific behavioral reactions and stress response metabolism may have significant ecological consequences that result in a thermal zone-specific distribution (i.e., depths, feed spectrum, etc.) of species. As a consequence, by separating species with different temperature preferences, interspecific competition is reduced, which, in turn, increases a species’ Darwinian fitness in its environment. PMID:27706227

Multiple, novel biologically active endophytic actinomycetes isolated from upper Amazonian rainforests.

PubMed

Bascom-Slack, Carol A; Ma, Cong; Moore, Emily; Babbs, Beatrice; Fenn, Kathleen; Greene, Joshua S; Hann, Bradley D; Keehner, Jocelyn; Kelley-Swift, Elizabeth G; Kembaiyan, Vivek; Lee, Sun Jin; Li, Puyao; Light, David Y; Lin, Emily H; Schorn, Michelle A; Vekhter, Daniel; Boulanger, Lori-Ann; Hess, W M; Vargas, Percy Núñez; Strobel, Gary A; Strobel, Scott A

2009-08-01

Microbial biodiversity provides an increasingly important source of medically and industrially useful compounds. We have isolated 14 actinomycete species from a collection of approximately 300 plant stem samples from the upper Amazonian rainforest in Peru. All of the cultured isolates produce substances with inhibitory activity directed at a range of potential fungal and bacterial pathogens. For some organisms, this activity is very broad in spectrum while other organisms show specific activity against a limited number of organisms. Two of these organisms preferentially inhibit bacterial test organisms over eukaryotic organisms. rDNA sequence analysis indicates that these organisms are not equivalent to any other cultured deposits in GenBank. Our results provide evidence of the untapped biodiversity in the form of biologically active microbes present within the tissues of higher plants.

Isolation and purification of Bacillus thuringiensis var. israelensis IМV В-7465 peptidase with specificity toward elastin and collagen.

PubMed

Nidialkova, N A; Varbanets, L D; Chernyshenko, V O

2016-01-01

Peptidase of Bacillus thuringiensis var. israelensis IМV В-7465 was isolated from culture supernatant using consecutive fractionations by an ammonium sulphate (60% saturation), ion-exchange chromatography and gel-filtration on the TSK-gels Toyoperl HW-55 and DEAE 650(M). Specific elastase (442 U∙mg of protein-1) and collagenase (212.7 U∙mg of protein-1) activities of the purified enzyme preparation were 8.0- and 6.1-fold, respectively higher than ones of the culture supernatant. Peptidase yields were 33.5% for elastase activity and 30.1% for collagenase activity. It was established that the enzyme is serine metal-dependent alkaline peptidase with Mr about 37 kDa. Maximal hydrolysis of elastin and collagen occurs at the optimum pH 8.0 and t° – 40 and 50 °С, respectively. The purified preparation has high stability at pH in the range of 7.0 to 10.0 and 40-50 °С.

Flute type micropores activated carbon from cotton stalk for high performance supercapacitors

NASA Astrophysics Data System (ADS)

Tian, Xun; Ma, Hongru; Li, Zhe; Yan, Shaocun; Ma, Lei; Yu, Feng; Wang, Gang; Guo, Xuhong; Ma, Yanqing; Wong, Chingping

2017-08-01

Flute type micropores activated carbon (FTMAC) has been successfully obtained from cotton stalk via KOH-chemical activation method. The synthesized carbon material exhibits an ordered pore structure with high specific surface area of 1964.46 m2 g-1 and pore volume of 1.03 m3 g-1. The assembled FTMAC-based electrode delivers a high specific capacitance of 254 F g-1 at a current density of 0.2 A g-1 in 1 M H2SO4 aqueous electrolyte. It still can maintain 221 F g-1at a current density of 10 A g-1, demonstrating a good rate capacity (87% retention), as well as long cyclic stability of 96% capacitance retention after 10000 charging and discharging cycles at current density of 1 A g-1. Moreover, the symmetric supercapacitor can deliver a high energy density of 18.14 W h kg-1 and a power density of 450.37 W kg-1 which is operated in the voltage range of 0-1.8 V.

Optically pure, water-stable metallo-helical ‘flexicate’ assemblies with antibiotic activity

NASA Astrophysics Data System (ADS)

Howson, Suzanne E.; Bolhuis, Albert; Brabec, Viktor; Clarkson, Guy J.; Malina, Jaroslav; Rodger, Alison; Scott, Peter

2012-01-01

The helicates—chiral assemblies of two or more metal atoms linked by short or relatively rigid multidentate organic ligands—may be regarded as non-peptide mimetics of α-helices because they are of comparable size and have shown some relevant biological activity. Unfortunately, these beautiful helical compounds have remained difficult to use in the medicinal arena because they contain mixtures of isomers, cannot be optimized for specific purposes, are insoluble, or are too difficult to synthesize. Instead, we have now prepared thermodynamically stable single enantiomers of monometallic units connected by organic linkers. Our highly adaptable self-assembly approach enables the rapid preparation of ranges of water-stable, helicate-like compounds with high stereochemical purity. One such iron(II) ‘flexicate’ system exhibits specific interactions with DNA, promising antimicrobial activity against a Gram-positive bacterium (methicillin-resistant Staphylococcus aureus, MRSA252), but also, unusually, a Gram-negative bacterium (Escherichia coli, MC4100), as well as low toxicity towards a non-mammalian model organism (Caenorhabditis elegans).

Citrus limon-derived nanovesicles inhibit cancer cell proliferation and suppress CML xenograft growth by inducing TRAIL-mediated cell death

PubMed Central

Raimondo, Stefania; Naselli, Flores; Fontana, Simona; Monteleone, Francesca; Lo Dico, Alessia; Saieva, Laura; Zito, Giovanni; Flugy, Anna; Manno, Mauro; Di Bella, Maria Antonietta; De Leo, Giacomo; Alessandro, Riccardo

2015-01-01

Nanosized vesicles are considered key players in cell to cell communication, thus influencing physiological and pathological processes, including cancer. Nanovesicles have also been found in edible-plants and have shown therapeutic activity in inflammatory bowel diseases; however information on their role in affecting cancer progression is missing. Our study identify for the first time a fraction of vesicles from lemon juice (Citrus limon L.), obtained as a result of different ultracentrifugation, with density ranging from 1,15 to 1,19 g/ml and specific proteomic profile. By using an in vitro approach, we show that isolated nanovesicles inhibit cancer cell proliferation in different tumor cell lines, by activating a TRAIL-mediated apoptotic cell death. Furthermore, we demonstrate that lemon nanovesicles suppress CML tumor growth in vivo by specifically reaching tumor site and by activating TRAIL-mediated apoptotic cell processes. Overall, this study suggests the possible use of plant-edible nanovesicles as a feasible approach in cancer treatment. PMID:26098775

Size-dependent electrocatalytic activity of gold nanoparticles on HOPG and highly boron-doped diamond surfaces.

PubMed

Brülle, Tine; Ju, Wenbo; Niedermayr, Philipp; Denisenko, Andrej; Paschos, Odysseas; Schneider, Oliver; Stimming, Ulrich

2011-12-06

Gold nanoparticles were prepared by electrochemical deposition on highly oriented pyrolytic graphite (HOPG) and boron-doped, epitaxial 100-oriented diamond layers. Using a potentiostatic double pulse technique, the average particle size was varied in the range from 5 nm to 30 nm in the case of HOPG as a support and between < 1 nm and 15 nm on diamond surfaces, while keeping the particle density constant. The distribution of particle sizes was very narrow, with standard deviations of around 20% on HOPG and around 30% on diamond. The electrocatalytic activity towards hydrogen evolution and oxygen reduction of these carbon supported gold nanoparticles in dependence of the particle sizes was investigated using cyclic voltammetry. For oxygen reduction the current density normalized to the gold surface (specific current density) increased for decreasing particle size. In contrast, the specific current density of hydrogen evolution showed no dependence on particle size. For both reactions, no effect of the different carbon supports on electrocatalytic activity was observed.

Gas1 extends the range of Hedgehog action by facilitating its signaling

PubMed Central

Martinelli, David C.; Fan, Chen-Ming

2007-01-01

Cellular signaling initiated by Hedgehog binding to Patched1 has profound importance in mammalian embryogenesis, genetic disease, and cancer. Hedgehog acts as a morphogen to specify distinctive cell fates using different concentration thresholds, but our knowledge of how the concentration gradient is interpreted into the activity gradient is incomplete. The membrane protein Growth Arrest-Specific Gene 1 (GAS1) was thought to be a negative regulator of the Hedgehog concentration gradient. Here, we report unexpected genetic evidence that Gas1 positively regulates Hedgehog signaling in multiple developmental contexts, an effect particularly noticeable at regions where Hedgehog acts at low concentration. Using a combination of in vitro cell culture and in ovo electroporation assays, we demonstrate that GAS1 acts cooperatively with Patched1 for Hedgehog binding and enhances signaling activity in a cell-autonomous manner. Our data support a model in which GAS1 helps transform the Hedgehog protein gradient into the observed activity gradient. We propose that Gas1 is an evolutionarily novel, vertebrate-specific Hedgehog pathway regulator. PMID:17504940

The interactions of normal and hyperactive children with their mothers in free play and structured tasks.

PubMed

Cunningham, C E; Barkley, R A

1979-03-01

Groups of 20 normal and 20 hyperactive boys ranging in age from 6 to 12 years were observed interacting with their mothers in 15-min free-play and 15-min structured-task situations. Using a 15-sec interval coding procedure, 1 observer recorded the mother's response to specific antecedent behaviors of the child while a second observer recorded the child's response to specific behaviors of the mother. Hyperactive boys proved more active, less compliant, and less likely to remain on task than nonhyperactive peers. Mothers of hyperactive boys were less likely to respond positively to the child's social interactions, solitary play activities, or compliant on-task behavior. In addition, mothers of hyperactive boys imposed more structure and control on the child's play, social interactions, and task-oriented activities. It is suggested that the controlling intrusive style observed among the mothers of hyperactive boys, while initially a response to the child's overactive, impulsive, inattentive style, may further contribute to the child's behavioral difficulties.

Global Representations of Goal-Directed Behavior in Distinct Cell Types of Mouse Neocortex

PubMed Central

Allen, William E.; Kauvar, Isaac V.; Chen, Michael Z.; Richman, Ethan B.; Yang, Samuel J.; Chan, Ken; Gradinaru, Viviana; Deverman, Benjamin E.; Luo, Liqun; Deisseroth, Karl

2017-01-01

SUMMARY The successful planning and execution of adaptive behaviors in mammals may require long-range coordination of neural networks throughout cerebral cortex. The neuronal implementation of signals that could orchestrate cortex-wide activity remains unclear. Here, we develop and apply methods for cortex-wide Ca2+ imaging in mice performing decision-making behavior and identify a global cortical representation of task engagement encoded in the activity dynamics of both single cells and superficial neuropil distributed across the majority of dorsal cortex. The activity of multiple molecularly defined cell types was found to reflect this representation with type-specific dynamics. Focal optogenetic inhibition tiled across cortex revealed a crucial role for frontal cortex in triggering this cortex-wide phenomenon; local inhibition of this region blocked both the cortex-wide response to task-initiating cues and the voluntary behavior. These findings reveal cell-type-specific processes in cortex for globally representing goal-directed behavior and identify a major cortical node that gates the global broadcast of task-related information. PMID:28521139

Enzyme specificity under dynamic control

NASA Astrophysics Data System (ADS)

Ota, Nobuyuki; Agard, David A.

2002-03-01

The contributions of conformational dynamics to substrate specificity have been examined by the application of principal component analysis to molecular dynamics trajectories of alpha-lytic protease. The wild-type alpha-lytic protease is highly specific for substrates with small hydrophobic side chains at the specificity pocket, while the Met190Ala binding pocket mutant has a much broader specificity, actively hydrolyzing substrates ranging from Ala to Phe. We performed a principal component analysis using 1-nanosecond molecular dynamics simulations using solvent boundary condition. We found that the walls of the wild-type substrate binding pocket move in tandem with one another, causing the pocket size to remain fixed so that only small substrates are recognized. In contrast, the M190A mutant shows uncoupled movement of the binding pocket walls, allowing the pocket to sample both smaller and larger sizes, which appears to be the cause of the observed broad specificity. The results suggest that the protein dynamics of alpha-lytic protease may play a significant role in defining the patterns of substrate specificity.

Return to Sports and Physical Activities After Primary Partial Arthrodesis for Lisfranc Injuries in Young Patients.

PubMed

MacMahon, Aoife; Kim, Paul; Levine, David S; Burket, Jayme; Roberts, Matthew M; Drakos, Mark C; Deland, Jonathan T; Elliott, Andrew J; Ellis, Scott J

2016-04-01

Research regarding outcomes in sports and physical activities after primary partial arthrodesis for Lisfranc injuries has been sparse. The purposes of this study were to assess various sports and physical activities in young patients following primary partial arthrodesis for Lisfranc injuries and to compare these with clinical outcomes. Patients who underwent primary partial arthrodesis for a Lisfranc injury were identified by a retrospective registry review. Thirty-eight of 46 eligible patients (83%) responded for follow-up at a mean of 5.2 (range, 1.0 to 9.3) years with a mean age at surgery of 31.8 (range, 16.8 to 50.3) years. Physical activity participation was assessed with a new sports-specific, patient-administered questionnaire. Clinical outcomes were assessed with the Foot and Ankle Outcome Score (FAOS). Patients participated in 29 different and 155 total physical activities preoperatively, and 27 different and 145 total physical activities postoperatively. Preoperatively, 47.1% were high impact, and postoperatively, 44.8% were high impact. The most common activities were walking, bicycling, running, and weightlifting. Compared to preoperatively, difficulty was the same in 66% and increased in 34% of physical activities. Participation levels were improved in 11%, the same in 64%, and impaired in 25% of physical activities. Patients spent on average 4.2 (range, 0.0 to 19.8) hours per week exercising postoperatively. In regard to return to physical activity, 97% of respondents were satisfied with their operative outcome. Mean postoperative FAOS subscores were significantly worse for patients who had increased physical activity difficulty. Most patients were able to return to their previous physical activities following primary partial arthrodesis for a Lisfranc injury, many of which were high-impact. However, the decreased participation or increase in difficulty of some activities suggests that some patients experienced postoperative limitations in exercise. Future studies could compare sports outcomes between primary partial arthrodesis and open reduction internal fixation for Lisfranc injuries. Level IV, retrospective case series. © The Author(s) 2015.

Does arthroscopic rotator cuff repair improve patients' activity levels?

PubMed

Baumgarten, Keith M; Chang, Peter S; Dannenbring, Tasha M; Foley, Elaine K

2018-06-04

Rotator cuff repair decreases pain, improves range of motion, and increases strength. Whether these improvements translate to an improvement in a patient's activity level postoperatively remains unknown. The Shoulder Activity Level is a valid and reliable outcomes survey that can be used to measure a patient's shoulder-specific activity level. Currently, there are no studies that examine the effect of rotator cuff repair on shoulder activity level. Preoperative patient-determined outcomes scores collected prospectively on patients undergoing rotator cuff repair were compared with postoperative scores at a minimum of 2 years. These scores included the Shoulder Activity Level, Western Ontario Rotator Cuff Index, American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form, Single Assessment Numeric Evaluation, and simple shoulder test. Inclusion criteria were patients undergoing arthroscopic rotator cuff repair. Included were 281 shoulders from 273 patients with a mean follow-up of 3.7 years. The postoperative median Western Ontario Rotator Cuff Index (42 vs. 94), American Shoulder and Elbow Surgeons (41 vs. 95), Single Assessment Numeric Evaluation (30 vs. 95), and simple shoulder test (4 vs. 11) scores were statistically significantly improved compared with preoperative scores (P < .0001). The postoperative median Shoulder Activity Level score decreased compared with the preoperative score (12 vs. 11; P < .0001). Patients reported a statistically significant deterioration of their Shoulder Activity Level score after rotator cuff repair compared with their preoperative scores, although disease-specific and joint-specific quality of life scores all had statistically significantly improvement. This study suggests that patients generally have (1) significant improvements in their quality of life and (2) small deteriorations in activity level after arthroscopic rotator cuff repair. Copyright © 2018 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Patterns of muscle activity underlying object-specific grasp by the macaque monkey.

PubMed

Brochier, T; Spinks, R L; Umilta, M A; Lemon, R N

2004-09-01

During object grasp, a coordinated activation of distal muscles is required to shape the hand in relation to the physical properties of the object. Despite the fundamental importance of the grasping action, little is known of the muscular activation patterns that allow objects of different sizes and shapes to be grasped. In a study of two adult macaque monkeys, we investigated whether we could distinguish between EMG activation patterns associated with grasp of 12 differently shaped objects, chosen to evoke a wide range of grasping postures. Each object was mounted on a horizontal shuttle held by a weak spring (load force 1-2 N). Objects were located in separate sectors of a "carousel," and inter-trial rotation of the carousel allowed sequential presentation of the objects in pseudorandom order. EMG activity from 10 to 12 digit, hand, and arm muscles was recorded using chronically implanted electrodes. We show that the grasp of different objects was characterized by complex but distinctive patterns of EMG activation. Cluster analysis shows that these object-related EMG patterns were specific and consistent enough to identify the object unequivocally from the EMG recordings alone. EMG-based object identification required a minimum of six EMGs from simultaneously recorded muscles. EMG patterns were consistent across recording sessions in a given monkey but showed some differences between animals. These results identify the specific patterns of activity required to achieve distinct hand postures for grasping, and they open the way to our understanding of how these patterns are generated by the central motor network.

Multiscale predictions of aviation-attributable PM2.5 for U.S. airports modeled using CMAQ with plume-in-grid and an aircraft-specific 1-D emission model

EPA Science Inventory

Aviation activities represent an important and unique mode of transportation, but also impact air quality. In this study, we aim to quantify the impact of aircraft on air quality, focusing on aviation-attributable PM2.5 at scales ranging from local (a few kilometers) to continent...

The Environment of the Long-Range Theater Nuclear Force Program, Its Opponents and the Effects of Specifics of the Program on Opposition.

DTIC Science & Technology

1983-06-07

107 DANGER OF RADICAL RIGHT IN WEST GERMANY QUESTION: "RECENTLY WE HAVE MORE OFTEN HEARD ABOUT ACTIVITIES OF RADICAL RIGHT GROUPS IN THE FEDERAL...OKTO- BERFEST, IN WHICH 13 PEOPLE WERE KILLED AND 219 WOUNDED. OFFICIALS SUSPECTED THE RADICAL RIGHT WAS RESPONSIBLE FOR THE EXPLOSION. POLL TAKEN 11/12

Health state utilities among contemporary prostate cancer patients on active surveillance.

PubMed

Loeb, Stacy; Curnyn, Caitlin; Walter, Dawn; Fagerlin, Angela; Siebert, Uwe; Mühlberger, Nick; Braithwaite, R Scott; Schwartz, Mark D; Lepor, Herbert; Sedlander, Erica

2018-04-01

Active surveillance (AS) is the most rapidly expanding management option for favorable-risk prostate cancer (PCa). Early studies suggested substantial decrements in utility (quality of life weights) from disease-related anxiety. Our objective was to determine utilities for contemporary AS patients using different instruments. We performed a systematic review of PubMed, PMC and OVID for utility measurements in modern AS patients. We then examined utilities among 37 men on AS participating in focus groups between 2015-2016 using the generic EurQol five dimensions questionnaire (EQ-5D-3L) and Patient Oriented Prostate Utility Scale (PORPUS), a PCa-specific instrument. The systematic review found previous studies with utilities for PCa treatment and historical watchful waiting populations, but none specifically in contemporary AS. In our AS population, the mean EQ-5D-3L score was 0.90±0.16 (median, 1.00; range, 0.21-1.00) and PORPUS was 0.98±0.03 (median, 0.99; range, 0.84-1.00). The Spearman correlation between the EQ-5D-3L and PORPUS was 0.87 (P<0.0001), and 38% of patients had a difference >0.1 between instruments. Most contemporary AS patients had high utility scores suggesting that they perceive themselves in good health without a major decrement in quality of life from the disease. However, some patients had substantial differences in utility measured with generic versus disease-specific instruments. Further study is warranted into the optimal instrument for utility assessment in contemporary AS patients.

Virulence Factor Targeting of the Bacterial Pathogen Staphylococcus aureus for Vaccine and Therapeutics

PubMed Central

Kane, Trevor L.; Carothers, Katelyn E.; Lee, Shaun W.

2018-01-01

Background Staphylococcus aureus is a major bacterial pathogen capable of causing a range of infections in humans from gastrointestinal disease, skin and soft tissue infections, to severe outcomes such as sepsis. Staphylococcal infections in humans can be frequent and recurring, with treatments becoming less effective due to the growing persistence of antibiotic resistant S. aureus strains. Due to the prevalence of antibiotic resistance, and the current limitations on antibiotic development, an active and highly promising avenue of research has been to develop strategies to specifically inhibit the activity of virulence factors produced S. aureus as an alternative means to treat disease. Objective In this review we specifically highlight several major virulence factors produced by S. aureus for which recent advances in antivirulence approaches may hold promise as an alternative means to treating diseases caused by this pathogen. Strategies to inhibit virulence factors can range from small molecule inhibitors, to antibodies, to mutant and toxoid forms of the virulence proteins. Conclusion The major prevalence of antibiotic resistant strains of S. aureus combined with the lack of new antibiotic discoveries highlight the need for vigorous research into alternative strategies to combat diseases caused by this highly successful pathogen. Current efforts to develop specific antivirulence strategies, vaccine approaches, and alternative therapies for treating severe disease caused by S. aureus have the potential to stem the tide against the limitations that we face in the post-antibiotic era. PMID:27894236

Ngram time series model to predict activity type and energy cost from wrist, hip and ankle accelerometers: implications of age

PubMed Central

Strath, Scott J; Kate, Rohit J; Keenan, Kevin G; Welch, Whitney A; Swartz, Ann M

2016-01-01

To develop and test time series single site and multi-site placement models, we used wrist, hip and ankle processed accelerometer data to estimate energy cost and type of physical activity in adults. Ninety-nine subjects in three age groups (18–39, 40–64, 65 + years) performed 11 activities while wearing three triaxial accelereometers: one each on the non-dominant wrist, hip, and ankle. During each activity net oxygen cost (METs) was assessed. The time series of accelerometer signals were represented in terms of uniformly discretized values called bins. Support Vector Machine was used for activity classification with bins and every pair of bins used as features. Bagged decision tree regression was used for net metabolic cost prediction. To evaluate model performance we employed the jackknife leave-one-out cross validation method. Single accelerometer and multi-accelerometer site model estimates across and within age group revealed similar accuracy, with a bias range of −0.03 to 0.01 METs, bias percent of −0.8 to 0.3%, and a rMSE range of 0.81–1.04 METs. Multi-site accelerometer location models improved activity type classification over single site location models from a low of 69.3% to a maximum of 92.8% accuracy. For each accelerometer site location model, or combined site location model, percent accuracy classification decreased as a function of age group, or when young age groups models were generalized to older age groups. Specific age group models on average performed better than when all age groups were combined. A time series computation show promising results for predicting energy cost and activity type. Differences in prediction across age group, a lack of generalizability across age groups, and that age group specific models perform better than when all ages are combined needs to be considered as analytic calibration procedures to detect energy cost and type are further developed. PMID:26449155

Dysfunctional long-range coordination of neural activity during Gestalt perception in schizophrenia.

PubMed

Uhlhaas, Peter J; Linden, David E J; Singer, Wolf; Haenschel, Corinna; Lindner, Michael; Maurer, Konrad; Rodriguez, Eugenio

2006-08-02

Recent theoretical and empirical research on schizophrenia converges on the notion that core aspects of the pathophysiology of the disorder may arise from a dysfunction in the coordination of distributed neural activity. Synchronization of neural responses in the beta-band (15-30 Hz) and gamma-band range (30-80 Hz) has been implicated as a possible neural substrate for dysfunctional coordination in schizophrenia. To test this hypothesis, we examined the electroencephalography (EEG) activity in 19 patients with a Diagnostic and Statistical Manual of Mental Disorder, edition IV criteria, diagnosis of schizophrenia and 19 healthy control subjects during a Gestalt perception task. EEG data were analyzed for phase synchrony and induced spectral power as an index of neural synchronization. Schizophrenia patients were impaired significantly in the detection of images that required the grouping of stimulus elements into coherent object representations. This deficit was accompanied by longer reaction times in schizophrenia patients. Deficits in Gestalt perception in schizophrenia patients were associated with reduced phase synchrony in the beta-band (20-30 Hz), whereas induced spectral power in the gamma-band (40-70 Hz) was mainly intact. Our findings suggest that schizophrenia patients are impaired in the long-range synchronization of neural responses, which may reflect a core deficit in the coordination of neural activity and underlie the specific cognitive dysfunctions associated with the disorder.

Which domains of childhood physical activity predict physical activity in adulthood? A 20-year prospective tracking study.

PubMed

Cleland, Verity; Dwyer, Terence; Venn, Alison

2012-06-01

It is important to examine how childhood physical activity is related to adult physical activity in order to best tailor physical activity-promotion strategies. The time- and resource-intensive nature of studies spanning childhood into adulthood means the understanding of physical activity trajectories over this time span is limited. This study aimed to determine whether childhood domain-specific physical activities predict domain-specific physical activity 20 years later in adulthood, and whether age and sex play a role in these trajectories. In 1985, 6412 children of age 9-15 years self-reported frequency and duration of discretionary sport and exercise (leisure activity), transport activity, school sport and physical education (PE) in the past week and number of sports played in the past year. In 2004-2006, 2201 of these participants (aged 26-36 years) completed the long International Physical Activity Questionnaire and/or wore a Yamax pedometer. Analyses included partial correlation coefficients and log-binomial regression. Childhood and adult activity were weakly correlated (r=-0.08-0.14). Total weekly physical activity in childhood did not predict adult activity. School PE predicted adult total weekly physical activity and daily steps (older females), while school sport demonstrated inconsistent associations. Leisure and transport activity in childhood predicted adult leisure activity among younger males and older females, respectively. Childhood past year sport participation positively predicted adult physical activity (younger males and older females). Despite modest associations between childhood and adult physical activity that varied by domain, age and sex, promoting a range of physical activities to children of all ages is warranted.

Vitamin effects on the immune system: vitamins A and D take centre stage.

PubMed

Mora, J Rodrigo; Iwata, Makoto; von Andrian, Ulrich H

2008-09-01

Vitamins are essential constituents of our diet that have long been known to influence the immune system. Vitamins A and D have received particular attention in recent years as these vitamins have been shown to have an unexpected and crucial effect on the immune response. We present and discuss our current understanding of the essential roles of vitamins in modulating a broad range of immune processes, such as lymphocyte activation and proliferation, T-helper-cell differentiation, tissue-specific lymphocyte homing, the production of specific antibody isotypes and regulation of the immune response. Finally, we discuss the clinical potential of vitamin A and D metabolites for modulating tissue-specific immune responses and for preventing and/or treating inflammation and autoimmunity.

Vitamin effects on the immune system: vitamins A and D take centre stage

PubMed Central

Mora, J. Rodrigo; Iwata, Makoto; von Andrian, Ulrich H.

2010-01-01

Vitamins are essential constituents of our diet that have long been known to influence the immune system. Vitamins A and D have received particular attention in recent years as these vitamins have been shown to have an unexpected and crucial effect on the immune response. We present and discuss our current understanding of the essential roles of vitamins in modulating a broad range of immune processes, such as lymphocyte activation and proliferation, T-helper-cell differentiation, tissue-specific lymphocyte homing, the production of specific antibody isotypes and regulation of the immune response. Finally, we discuss the clinical potential of vitamin A and D metabolites for modulating tissue-specific immune responses and for preventing and/or treating inflammation and autoimmunity. PMID:19172691

Tauroursodeoxycholic acid binds to the G-protein site on light activated rhodopsin.

PubMed

Lobysheva, E; Taylor, C M; Marshall, G R; Kisselev, O G

2018-05-01

The heterotrimeric G-protein binding site on G-protein coupled receptors remains relatively unexplored regarding its potential as a new target of therapeutic intervention or as a secondary site of action by the existing drugs. Tauroursodeoxycholic acid bears structural resemblance to several compounds that were previously identified to specifically bind to the light-activated form of the visual receptor rhodopsin and to inhibit its activation of transducin. We show that TUDCA stabilizes the active form of rhodopsin, metarhodopsin II, and does not display the detergent-like effects of common amphiphilic compounds that share the cholesterol scaffold structure, such as deoxycholic acid. Computer docking of TUDCA to the model of light-activated rhodopsin revealed that it interacts using similar mode of binding to the C-terminal domain of transducin alpha subunit. The ring regions of TUDCA made hydrophobic contacts with loop 3 region of rhodopsin, while the tail of TUDCA is exposed to solvent. The results show that TUDCA interacts specifically with rhodopsin, which may contribute to its wide-ranging effects on retina physiology and as a potential therapeutic compound for retina degenerative diseases. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

A Generalizable Platform for Interrogating Target- and Signal-Specific Consequences of Electrophilic Modifications in Redox-Dependent Cell Signaling

PubMed Central

Lin, Hong-Yu; Haegele, Joseph A.; Disare, Michael T.; Lin, Qishan; Aye, Yimon

2015-01-01

Despite the known propensity of small-molecule electrophiles to react with numerous cysteine-active proteins, biological actions of individual signal inducers have emerged to be chemotype-specific. To pinpoint and quantify the impacts of modifying one target out of the whole proteome, we develop a target-protein-personalized “electrophile toolbox” with which specific intracellular targets can be selectively modified at a precise time by specific reactive signals. This general methodology—T-REX (targetable reactive electrophiles & oxidants)—is established by: (1) constructing a platform that can deliver a range of electronic and sterically different bioactive lipid-derived signaling electrophiles to specific proteins in cells; (2) probing the kinetics of targeted delivery concept which revealed that targeting efficiency in cells is largely driven by initial on-rate of alkylation; and (3) evaluating the consequences of protein-target- and small-molecule-signal-specific modifications on the strength of downstream signaling. These data show that T-REX allows quantitative interrogations into the extent to which the Nrf2 transcription factor-dependent antioxidant response element (ARE) signaling is activated by selective electrophilic modifications on Keap1 protein—one of several redox-sensitive regulators of the Nrf2–ARE axis. The results document Keap1 as a promiscuous electrophile-responsive sensor able to respond with similar efficiencies to discrete electrophilic signals, promoting comparable strength of Nrf2–ARE induction. T-REX is also able to elicit cell activation in cases in which whole-cell electrophile flooding fails to stimulate ARE induction prior to causing cytotoxicity. The platform presents a previously unavailable opportunity to elucidate the functional consequences of small-molecule-signal- and protein-target-specific electrophilic modifications in an otherwise unaffected cellular background. PMID:25909755

A generalizable platform for interrogating target- and signal-specific consequences of electrophilic modifications in redox-dependent cell signaling.

PubMed

Lin, Hong-Yu; Haegele, Joseph A; Disare, Michael T; Lin, Qishan; Aye, Yimon

2015-05-20

Despite the known propensity of small-molecule electrophiles to react with numerous cysteine-active proteins, biological actions of individual signal inducers have emerged to be chemotype-specific. To pinpoint and quantify the impacts of modifying one target out of the whole proteome, we develop a target-protein-personalized "electrophile toolbox" with which specific intracellular targets can be selectively modified at a precise time by specific reactive signals. This general methodology, T-REX (targetable reactive electrophiles and oxidants), is established by (1) constructing a platform that can deliver a range of electronic and sterically different bioactive lipid-derived signaling electrophiles to specific proteins in cells; (2) probing the kinetics of targeted delivery concept, which revealed that targeting efficiency in cells is largely driven by initial on-rate of alkylation; and (3) evaluating the consequences of protein-target- and small-molecule-signal-specific modifications on the strength of downstream signaling. These data show that T-REX allows quantitative interrogations into the extent to which the Nrf2 transcription factor-dependent antioxidant response element (ARE) signaling is activated by selective electrophilic modifications on Keap1 protein, one of several redox-sensitive regulators of the Nrf2-ARE axis. The results document Keap1 as a promiscuous electrophile-responsive sensor able to respond with similar efficiencies to discrete electrophilic signals, promoting comparable strength of Nrf2-ARE induction. T-REX is also able to elicit cell activation in cases in which whole-cell electrophile flooding fails to stimulate ARE induction prior to causing cytotoxicity. The platform presents a previously unavailable opportunity to elucidate the functional consequences of small-molecule-signal- and protein-target-specific electrophilic modifications in an otherwise unaffected cellular background.

The food colorant erythrosine is a promiscuous protein-protein interaction inhibitor.

PubMed

Ganesan, Lakshmi; Margolles-Clark, Emilio; Song, Yun; Buchwald, Peter

2011-03-15

Following our observation that erythrosine B (FD&C Red No. 3) is a relatively potent inhibitor of the TNF-R-TNFα and CD40-CD154 protein-protein interactions, we investigated whether this inhibitory activity extends to any other protein-protein interactions (PPI) as well as whether any other approved food colors possess such inhibitory activity. We found erythrosine, a poly-iodinated xanthene dye, to be a non-specific promiscuous inhibitor of a number of PPIs within the tumor necrosis factor superfamily (TNF-R-TNFα, CD40-CD154, BAFF-R-BAFF, RANK-RANKL, OX40-OX40L, 4-1BB-4-1BBL) as well as outside of it (EGF-R-EGF) with a remarkably consistent median inhibitory concentration (IC(50)) in the 2-20 μM (approximately 2-20mg/L) range. In agreement with this, erythrosine also showed cellular effects including clear cytotoxic effects around this concentration range (IC₅₀≈50 μM). Among the seven FDA-approved food colorants, only erythrosine showed consistent PPI inhibitory activity in the sub-100 μM range, which might also explain (at least partially) why it also has the lowest approved acceptable daily intake (ADI) (0.1 mg/kg body weight/day). Among a number of xanthene structural analogs of erythrosine tested for activity, rose Bengal, a food colorant approved in Japan, showed similar, maybe even more pronounced, promiscuous inhibitory activity, whereas fluorescein was inactive and gallein, phloxine, and eosin were somewhat active in some of the assays. Copyright © 2011 Elsevier Inc. All rights reserved.

The antibacterial activity of compounds isolated from oakmoss against Legionella pneumophila and other Legionella spp.

PubMed

Nomura, Harue; Isshiki, Yasunori; Sakuda, Keisuke; Sakuma, Katsuya; Kondo, Seiichi

2012-01-01

Oakmoss is a natural fragrance ingredient exhibiting highly specific, potent antibacterial activity against Legionella pneumophila, a causative agent of severe water-bone pneumonia. In the present study, the antibacterial activity of individual compounds isolated from oakmoss was investigated against L. pneumophila and other Legionella spp. A total of 18 known compounds and two minor novel compounds (i.e., 3-methoxy-5-methylphenyl-2,4-dihydroxy-6-methylbenzoate (compound 9) and 8-(2,4-dihydroxy-6-(2-oxoheptyl)-phenoxy)-6-hydroxy-3-pentyl-1H-isochromen-1-one (compound 20)) were purified from oakmoss. The minimum inhibitory concentrations (MICs) against clinical and environmental isolates of L. pneumophila, L. bozemanii, L. micdadei, L. longbeachae, and L. dumoffii for 11 of the 20 compounds were less than 100 µg/mL (range 0.8-64.0 µg/mL). Novel compounds 9 and 20 exhibited potent antibacterial activity against L. pneumophila strains (MIC ranges of 1.3-8.0 µg/mL and 3.3-13.3 µg/mL, respectively) and also against four other Legionella species (MIC ranges of 0.8-8.0 µg/mL and 3.3-21.3 µg/mL, respectively). Time-kill assays indicated that compounds 9 and 20 kill bacteria at a concentration equivalent to 2×MIC after 1 h and 6 h co-incubations, respectively. While oakmoss and the purified components exhibited antibacterial activity against Legionella spp., they were not active against other Gram-negative and -positive bacteria such as Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis and Staphylococcus aureus.

Canadian and U.S. Cooperation for the development of standards and specifications for emerging mapping technologies

USGS Publications Warehouse

Habib, A.; Jarvis, A.; Al-Durgham, M. M.; Lay, J.; Quackenbush, P.; Stensaas, G.; Moe, D.

2007-01-01

The mapping community is witnessing significant advances in available sensors, such as medium format digital cameras (MFDC) and Light Detection and Ranging (LiDAR) systems. In this regard, the Digital Photogrammetry Research Group (DPRG) of the Department of Geomatics Engineering at the University of Calgary has been actively involved in the development of standards and specifications for regulating the use of these sensors in mapping activities. More specifically, the DPRG has been working on developing new techniques for the calibration and stability analysis of medium format digital cameras. This research is essential since these sensors have not been developed with mapping applications in mind. Therefore, prior to their use in Geomatics activies, new standards should be developed to ensure the quality of the developed products. In another front, the persistent improvement in direct geo-referencing technology has led to an expansion in the use of LiDAR systems for the acquisition of dense and accurate surface information. However, the processing of the raw LiDAR data (e.g., ranges, mirror angles, and navigation data) remains a non-transparent process that is proprietary to the manufacturers of LiDAR systems. Therefore, the DPRG has been focusing on the development of quality control procedures to quantify the accuracy of LiDAR output in the absence of initial system measurements. This paper presents a summary of the research conducted by the DPRG together with the British Columbia Base Mapping and Geomatic Services (BMGS) and the United States Geological Survey (USGS) for the development of quality assurance and quality control procedures for emerging mapping technologies. The outcome of this research will allow for the possiblity of introducing North American Standards and Specifications to regulate the use of MFDC and LiDAR systems in the mapping industry.

Binding affinities of vascular endothelial growth factor (VEGF) for heparin-derived oligosaccharides

PubMed Central

Zhao, Wenjing; McCallum, Scott A.; Xiao, Zhongping; Zhang, Fuming; Linhardt, Robert J.

2011-01-01

Heparin and heparan sulphate (HS) exert their wide range of biological activities by interacting with extracellular protein ligands. Among these important protein ligands are various angiogenic growth factors and cytokines. HS-binding to vascular endothelial growth factor (VEGF) regulates multiple aspects of vascular development and function through its specific interaction with HS. Many studies have focused on HS-derived or HS-mimicking structures for the characterization of VEGF165 interaction with HS. Using a heparinase 1-prepared small library of heparin-derived oligosaccharides ranging from hexasaccharide to octadecasaccharide, we systematically investigated the heparin-specific structural features required for VEGF binding. We report the apparent affinities for the association between the heparin-derived oligosaccharides with both VEGF165 and VEGF55, a peptide construct encompassing exclusively the heparin-binding domain of VEGF165. An octasaccharide was the minimum size of oligosaccharide within the library to efficiently bind to both forms of VEGF and that a tetradecasaccharide displayed an effective binding affinity to VEGF165 comparable to unfractionated heparin. The range of relative apparent binding affinities among VEGF and the panel of heparin-derived oligosaccharides demonstrate that VEGF binding affinity likely depends on the specific structural features of these oligosaccharides including their degree of sulphation and sugar ring stereochemistry and conformation. Notably, the unique 3-O-sulpho group found within the specific antithrombin binding site of heparin is not required for VEGF165 binding. These findings afford new insight into the inherent kinetics and affinities for VEGF association with heparin and heparin-derived oligosaccharides with key residue specific modifications and may potentially benefit the future design of oligosaccharide-based anti-angiogenesis drugs. PMID:21658003

Topographical Organization of Attentional, Social, and Memory Processes in the Human Temporoparietal Cortex123

PubMed Central

Webb, Taylor W.; Kelly, Yin T.; Graziano, Michael S. A.

2016-01-01

Abstract The temporoparietal junction (TPJ) is activated in association with a large range of functions, including social cognition, episodic memory retrieval, and attentional reorienting. An ongoing debate is whether the TPJ performs an overarching, domain-general computation, or whether functions reside in domain-specific subdivisions. We scanned subjects with fMRI during five tasks known to activate the TPJ, probing social, attentional, and memory functions, and used data-driven parcellation (independent component analysis) to isolate task-related functional processes in the bilateral TPJ. We found that one dorsal component in the right TPJ, which was connected with the frontoparietal control network, was activated in all of the tasks. Other TPJ subregions were specific for attentional reorienting, oddball target detection, or social attribution of belief. The TPJ components that participated in attentional reorienting and oddball target detection appeared spatially separated, but both were connected with the ventral attention network. The TPJ component that participated in the theory-of-mind task was part of the default-mode network. Further, we found that the BOLD response in the domain-general dorsal component had a longer latency than responses in the domain-specific components, suggesting an involvement in distinct, perhaps postperceptual, computations. These findings suggest that the TPJ performs both domain-general and domain-specific computations that reside within spatially distinct functional components. PMID:27280153

Inferior colliculus contributions to phase encoding of stop consonants in an animal model

PubMed Central

Warrier, Catherine M; Abrams, Daniel A; Nicol, Trent G; Kraus, Nina

2011-01-01

The human auditory brainstem is known to be exquisitely sensitive to fine-grained spectro-temporal differences between speech sound contrasts, and the ability of the brainstem to discriminate between these contrasts is important for speech perception. Recent work has described a novel method for translating brainstem timing differences in response to speech contrasts into frequency-specific phase differentials. Results from this method have shown that the human brainstem response is surprisingly sensitive to phase-differences inherent to the stimuli across a wide extent of the spectrum. Here we use an animal model of the auditory brainstem to examine whether the stimulus-specific phase signatures measured in human brainstem responses represent an epiphenomenon associated with far field (i.e., scalp-recorded) measurement of neural activity, or alternatively whether these specific activity patterns are also evident in auditory nuclei that contribute to the scalp-recorded response, thereby representing a more fundamental temporal processing phenomenon. Responses in anaesthetized guinea pigs to three minimally-contrasting consonant-vowel stimuli were collected simultaneously from the cortical surface vertex and directly from central nucleus of the inferior colliculus (ICc), measuring volume conducted neural activity and multiunit, near-field activity, respectively. Guinea pig surface responses were similar to human scalp-recorded responses to identical stimuli in gross morphology as well as phase characteristics. Moreover, surface recorded potentials shared many phase characteristics with near-field ICc activity. Response phase differences were prominent during formant transition periods, reflecting spectro-temporal differences between syllables, and showed more subtle differences during the identical steady-state periods. ICc encoded stimulus distinctions over a broader frequency range, with differences apparent in the highest frequency ranges analyzed, up to 3000 Hz. Based on the similarity of phase encoding across sites, and the consistency and sensitivity of response phase measured within ICc, results suggest that a general property of the auditory system is a high degree of sensitivity to fine-grained phase information inherent to complex acoustical stimuli. Furthermore, results suggest that temporal encoding in ICc contributes to temporal features measured in speech-evoked scalp-recorded responses. PMID:21945200

The GLAMA (Girls! Lead! Achieve! Mentor! Activate!) physical activity and peer leadership intervention pilot project: A process evaluation using the RE-AIM framework

PubMed Central

2012-01-01

Background Implementing new initiatives and physical activity interventions in schools represents a myriad of challenges that if overcome can potentially facilitate a range of behavioural changes. The aim of this paper is to describe the process evaluation of specific design constructs used in the GLAMA (Girls! Lead! Achieve! Mentor! Activate!) peer leadership and physical activity pilot project. Conducted in a state secondary school in Australia, the intervention was designed to provide students with opportunities to develop leadership skills, school and social connectedness in addition to a range of physical activity experiences. Methods This process evaluation used the RE-AIM (Reach, Efficacy, Adoption, Implementation and Maintenance) health promotion evaluation framework to assess three design constructs of the intervention: the effectiveness of leadership training and leader preparedness, activity suitability and participation, and the barriers to implementation of the intervention and potential solutions to overcome these barriers. As it was not the specific aim of this pilot, no behavioural change data were collected from students. Data were collected using a mixed methods approach including student questionnaires, teachers and researchers reporting on their own observations and feedback from students. Results There were three main considerations evident across more than one RE-AIM dimension that need to be addressed to assist with future GLAMA dissemination. Firstly, the development of teacher, school and student participation. This needs to be through a variety of professional development opportunities for teachers, integration of the program within timetabled classes within the school and promoting the program to students as an opportunity to develop a range of skills to apply to future learning and workplace environments. Secondly, the successful translation of leadership training to practice is necessary to ensure that leaders are effectively able to motivate, facilitate and activate their teams. Finally, the need for consistent activity implementation requires sequential, competitive elements, purposeful team selection and clearly defined scoring and time periods for team 'challenges'. Conclusions Factors that have the greatest impact on intervention success are those that come from within the school setting including: the structure of the curriculum, pressure to meet curriculum and assessment content, lack of support for new initiatives, multiple programs already running within the school, time allowances for teachers, appropriate training for teachers, and support for students to participate. These barriers need to be considered when developing all secondary school interventions. PMID:22260195

TALE-mediated modulation of transcriptional enhancers in vivo.

PubMed

Crocker, Justin; Stern, David L

2013-08-01

We tested whether transcription activator-like effectors (TALEs) could mediate repression and activation of endogenous enhancers in the Drosophila genome. TALE repressors (TALERs) targeting each of the five even-skipped (eve) stripe enhancers generated repression specifically of the focal stripes. TALE activators (TALEAs) targeting the eve promoter or enhancers caused increased expression primarily in cells normally activated by the promoter or targeted enhancer, respectively. This effect supports the view that repression acts in a dominant fashion on transcriptional activators and that the activity state of an enhancer influences TALE binding or the ability of the VP16 domain to enhance transcription. In these assays, the Hairy repression domain did not exhibit previously described long-range transcriptional repression activity. The phenotypic effects of TALER and TALEA expression in larvae and adults are consistent with the observed modulations of eve expression. TALEs thus provide a novel tool for detection and functional modulation of transcriptional enhancers in their native genomic context.

A model to assess lactic acid bacteria aminopeptidase activities in Parmigiano Reggiano cheese during ripening.

PubMed

Gatti, M; De Dea Lindner, J; Gardini, F; Mucchetti, G; Bevacqua, D; Fornasari, M E; Neviani, E

2008-11-01

The aim of this work was to investigate in which phases of ripening of Parmigiano Reggiano cheese lactic acid bacteria aminopeptidases present in cheese extract could be involved in release of free amino acids and to better understand the behavior of these enzymes in physical-chemical conditions that are far from their optimum. In particular, we evaluated 6 different substrates to reproduce broad-specificity aminopeptidase N, broad-specificity aminopeptidase C, glutamyl aminopeptidase A, peptidase with high specificity for leucine and alanine, proline iminopeptidase, and X-prolyl dipeptidyl aminopeptidase activities releasing different N-terminal amino acids. The effects of pH, NaCl concentration, and temperature on the enzyme activities of amino acid beta-naphthylamide (betaNA)-substrates were determined by modulating the variables in 19 different runs of an experimental design, which allowed the building of mathematical models able to assess the effect on aminopeptidases activities over a range of values, obtained with bibliographic data, covering different environmental conditions in different zones of the cheese wheel at different aging times. The aminopeptidases tested in this work were present in cell-free Parmigiano Reggiano cheese extract after a 17-mo ripening and were active when tested in model system. The modeling approach shows that to highlight the individual and interactive effects of chemical-physical variables on enzyme activities, it is helpful to determine the true potential of an amino-peptidase in cheese. Our results evidenced that the 6 different lactic acid bacteria peptidases participate in cheese proteolysis and are induced or inhibited by the cheese production parameters that, in turn, depend on the cheese dimension. Generally, temperature and pH exerted the more relevant effects on the enzymatic activities, and in many cases, a relevant interactive effect of these variables was observed. Increasing salt concentration slowed down broad-specificity amino-peptidase C, glutamyl aminopeptidase A, proline iminopeptidase, and peptidase with high specificity for leucine and alanine. Interestingly, this variable did not affect broad-specificity aminopeptidase N and positively affected X-prolyl dipeptidyl aminopeptidase. The models elaborated varying pH, temperatures, and salt concentration and were a useful, low cost, and fast tool to understand the role of the main peptidases in the different phases of cheese ripening in relation to the major environmental factors influencing enzyme activity.

Origami-inspired active graphene-based paper for programmable instant self-folding walking devices.

PubMed

Mu, Jiuke; Hou, Chengyi; Wang, Hongzhi; Li, Yaogang; Zhang, Qinghong; Zhu, Meifang

2015-11-01

Origami-inspired active graphene-based paper with programmed gradients in vertical and lateral directions is developed to address many of the limitations of polymer active materials including slow response and violent operation methods. Specifically, we used function-designed graphene oxide as nanoscale building blocks to fabricate an all-graphene self-folding paper that has a single-component gradient structure. A functional device composed of this graphene paper can (i) adopt predesigned shapes, (ii) walk, and (iii) turn a corner. These processes can be remote-controlled by gentle light or heating. We believe that this self-folding material holds potential for a wide range of applications such as sensing, artificial muscles, and robotics.

Does processing a shallow and a deep orthography produce different brain activity patterns? An ERP study conducted in Hebrew.

PubMed

Bar-Kochva, Irit

2011-01-01

Orthographies range from shallow orthographies with transparent grapheme-phoneme relations, to deep orthographies, in which these relations are opaque. Two forms of script transcribe the Hebrew language: the shallow pointed script (with diacritics) and the deep unpointed script (without diacritics). This study was set out to examine whether the reading of these scripts evokes distinct brain activity. Preliminary results indicate distinct Event-related-potentials (ERPs). As an equivalent finding was absent when ERPs of non-orthographic stimuli with and without meaningless diacritics were compared, the results imply that print-specific aspects of processing account for the distinct activity elicited by the pointed and unpointed scripts.

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

Duran, S.; Gueray, R. T.; Yalcin, C.

In this study, 137Cs specific activities were measured in surface soil samples collected from undisturbed areas over the eastern part of the Black Sea coast line of Turkey, between Trabzon and Hopa, in August 2004 and January 2005. A total number of 41 surface soil samples were counted using an HpGe spectrometer system. The results indicate that 137Cs levels show a large variation over the coast ranging between 10 Bq/kg and 1000 Bq/kg. The soil activities are generally higher in the eastern part of the coast. Exposure rates above the ground surface due to 137Cs activity in soil estimated tomore » vary between 0.1mR/s and 9 mR/s.« less

Depot-specific Regulation of the Conversion of Cortisone to Cortisol in Human Adipose Tissue

PubMed Central

Lee, Mi-Jeong; Fried, Susan K.; Mundt, Steven S.; Wang, Yanxin; Sullivan, Sean; Stefanni, Alice; Daugherty, Bruce L.; Hermanowski-Vosatka, Anne

2015-01-01

Objective Our main objective was to compare the regulation of cortisol production within omental (Om) and abdominal subcutaneous (Abd sc) human adipose tissue. Methods and Procedures Om and Abd sc adipose tissue were obtained at surgery from subjects with a wide range of BMI. Hydroxysteroid dehydrogenase (HSD) activity (3H-cortisone and 3H-cortisol interconversion) and expression were measured before and after organ culture with insulin and/or dexamethasone. Results Type 1 HSD (HSD1) mRNA and reductase activity were mainly expressed within adipocytes and tightly correlated with adipocyte size within both depots. There was no depot difference in HSD1 expression or reductase activity, while cortisol inactivation and HSD2 mRNA expression (expressed in stromal cells) were higher in Om suggesting higher cortisol turnover in this depot. Culture with insulin decreased HSD reductase activity in both depots. Culture with dexamethasone plus insulin compared to insulin alone increased HSD reductase activity only in the Om depot. This depot-specific increase in reductase activity could not be explained by an alteration in HSD1 mRNA or protein, which was paradoxically decreased. However, in Om only, hexose-6-phosphate dehydrogenase (H6PDH) mRNA levels were increased by culture with dexamethasone plus insulin compared to insulin alone, suggesting that higher nicotinamide adenine dinucleotide phosphate-oxidase (NADPH) production within the endoplasmic reticulum (ER) contributed to the higher HSD reductase activity. Discussion We conclude that in the presence of insulin, glucocorticoids cause a depot-specific increase in the activation of cortisone within Om adipose tissue, and that this mechanism may contribute to adipocyte hypertrophy and visceral obesity. PMID:18388900

Combined Functional and Immunochemical Analysis of Normal and Abnormal Human Factor X

PubMed Central

Fair, Daryl S.; Plow, Edward F.; Edgington, Thomas S.

1979-01-01

Human Factor X was isolated from Cohn fraction III and characterized by polyacrylamide gel electrophoresis, amino acid composition, and isoelectric focusing. Two molecular forms with biological activity were observed at isoelectric points of 4.8 and 5.0. Antisera generated to Factor X was monospecific and used to establish an equilibrium competitive inhibition radioimmunoassay. This assay was specific for human Factor X and did not cross-react with human prothrombin or bovine Factor X within the sensitivity range of 6-300 ng Factor X antigen/ml. The mean concentration of Factor X based on the antigen was 11.9 μg/ml, whereas concentration values based on coagulant activity was 7.8 μg/ml. This 30% difference in measurement appears to result from the presence of a subpopulation of Factor X molecules devoid of coagulant activity. The radioimmunoassay was used to qualitatively and quantitatively compare purified Factor X to plasmic Factor X obtained from normal, warfarintreated, acquired Factor X-deficient, and congenitaldeficient patients. In all but one case, the Factor X present in these plasmas was immunochemically identical to the purified Factor X and permitted precise quantitation of these abnormal Factor X molecules. Factor X procoagulant activity was analyzed relative to Factor X antigen and the specific activities were used to characterize normal and abnormal Factor X molecules. Reduced Factor X activity in plasmas from warfarin-treated and acquired Factor X-deficient patients was attributed to both decreases in Factor X antigen and decreased function of the Factor X molecules. Congenitally deficient patients, in general, showed a reduction in Factor X antigen in parallel with Factor X procoagulant activities resulting from comparable decreases in specific biological activity of the molecules. Images PMID:90058

Auditory cortex of newborn bats is prewired for echolocation.

PubMed

Kössl, Manfred; Voss, Cornelia; Mora, Emanuel C; Macias, Silvio; Foeller, Elisabeth; Vater, Marianne

2012-04-10

Neuronal computation of object distance from echo delay is an essential task that echolocating bats must master for spatial orientation and the capture of prey. In the dorsal auditory cortex of bats, neurons specifically respond to combinations of short frequency-modulated components of emitted call and delayed echo. These delay-tuned neurons are thought to serve in target range calculation. It is unknown whether neuronal correlates of active space perception are established by experience-dependent plasticity or by innate mechanisms. Here we demonstrate that in the first postnatal week, before onset of echolocation and flight, dorsal auditory cortex already contains functional circuits that calculate distance from the temporal separation of a simulated pulse and echo. This innate cortical implementation of a purely computational processing mechanism for sonar ranging should enhance survival of juvenile bats when they first engage in active echolocation behaviour and flight.

Effects of Stopping Ions and LET Fluctuations on Soft Error Rate Prediction.

DOE PAGES

Weeden-Wright, S. L.; King, Michael Patrick; Hooten, N. C.; ...

2015-02-01

Variability in energy deposition from stopping ions and LET fluctuations is quantified for specific radiation environments. When compared to predictions using average LET via CREME96, LET fluctuations lead to an order-of-magnitude difference in effective flux and a nearly 4x decrease in predicted soft error rate (SER) in an example calculation performed on a commercial 65 nm SRAM. The large LET fluctuations reported here will be even greater for the smaller sensitive volumes that are characteristic of highly scaled technologies. End-of-range effects of stopping ions do not lead to significant inaccuracies in radiation environments with low solar activity unless the sensitivevolumemore » thickness is 100 μm or greater. In contrast, end-of-range effects for stopping ions lead to significant inaccuracies for sensitive- volume thicknesses less than 10 μm in radiation environments with high solar activity.« less

Distinct lateral inhibitory circuits drive parallel processing of sensory information in the mammalian olfactory bulb

PubMed Central

Geramita, Matthew A; Burton, Shawn D; Urban, Nathan N

2016-01-01

Splitting sensory information into parallel pathways is a common strategy in sensory systems. Yet, how circuits in these parallel pathways are composed to maintain or even enhance the encoding of specific stimulus features is poorly understood. Here, we have investigated the parallel pathways formed by mitral and tufted cells of the olfactory system in mice and characterized the emergence of feature selectivity in these cell types via distinct lateral inhibitory circuits. We find differences in activity-dependent lateral inhibition between mitral and tufted cells that likely reflect newly described differences in the activation of deep and superficial granule cells. Simulations show that these circuit-level differences allow mitral and tufted cells to best discriminate odors in separate concentration ranges, indicating that segregating information about different ranges of stimulus intensity may be an important function of these parallel sensory pathways. DOI: http://dx.doi.org/10.7554/eLife.16039.001 PMID:27351103

One-step formation of TiO2 hollow spheres via a facile microwave-assisted process for photocatalytic activity

NASA Astrophysics Data System (ADS)

Mohamad Alosfur, Firas K.; Ridha, Noor J.; Hafizuddin Haji Jumali, Mohammad; Radiman, S.

2018-04-01

Mesoporous TiO2 hollow spherical nanostructures with high surface areas were successfully prepared using a microwave method. The prepared hollow spheres had a size range between 200 and 500 nm. The spheres consisted of numerous smaller TiO2 nanoparticles with an average diameter of 8 nm. The particles had an essentially mesoporous structure, with a pore size in the range of 2-50 nm. The results confirmed that the synthesised of anatase TiO2 nanoparticles with specific surface area approximately 172.3 m2 g-1. The effect of ultraviolet and visible light irradiation and catalyst dosage on the TiO2 photocatalytic activity was studied by measuring the degradation rate of methylene blue. The maximum dye degradation performances with low catalyst loading (30 mg) were 99% and 63.4% using the same duration of ultraviolet and visible light irradiation, respectively (120 min).

Earth orbital experiment program and requirements study, volume 1, sections 1 - 6

NASA Technical Reports Server (NTRS)

1971-01-01

A reference manual for planners of manned earth-orbital research activity is presented. The manual serves as a systems approach to experiment and mission planning based on an integrated consideration of candidate research programs and the appropriate vehicle, mission, and technology development requirements. Long range goals and objectives for NASA activities during the 1970 to 1980 time period are analyzed. The useful and proper roles of manned and automated spacecraft for implementing NASA experiments are described. An integrated consideration of NASA long range goals and objectives, the system and mission requirements, and the alternative implementation plans are developed. Specific areas of investigation are: (1) manned space flight requirements, (2) space biology, (3) spaceborne astronomy, (4) space communications and navigation, (5) earth observation, (6) supporting technology development requirements, (7) data management system matrices, (8) instrumentation matrices, and (9) biotechnology laboratory experiments.

Allergy and allergic mediators in tears.

PubMed

Leonardi, Andrea

2013-12-01

The identification of inflammatory mediators in the tear fluid have been extensively used in ocular allergy to find either a 'disease marker', to better understand the immune mechanisms involved in the ocular surface inflammation, or to identify potential targets for therapeutic interventions. While the clinical characteristics allow a relatively convincing diagnosis of ocular allergic diseases, in the initial, non active phases, or in the chronic stages, the diagnosis may not be clear. Although not highly specific, total tear IgE can be measured with local tests by inserting a paper strip in the lower meniscus. The measurement of tear specific inflammatory markers, such as histamine, tryptase, ECP, IL-4, IL-5 and eotaxin, may be useful for the diagnosis or monitoring ocular allergy. New technologies such as multiplex bead assays, membrane-bound antibody array and proteomic techniques can characterize the distribution of a wide range of bioactive trace proteins in tears. Dozens of mediators, cytokines, chemokines, growth factors, angiogenic modulators, enzymes and inhibitors were thus identified in small tear samples using these techniques, providing the possible identification of specific biomarker for either specific disease or disease activity. However, to date, there is no a single specific laboratory test suitable for the diagnosis and monitoring of allergic conjunctivitis. Copyright © 2013 Elsevier Ltd. All rights reserved.

The Dynamic Range of LZ

NASA Astrophysics Data System (ADS)

Yin, Jun; LZ Collaboration

2015-10-01

The electronics of the LZ experiment, the 7-ton dark matter detector to be installed at the Sanford Underground Research Facility (SURF), is designed to provide a 70% efficiency for events that produce three photoelectrons in the photomultiplier tubes (PMTs). This corresponds approximately to the lowest energy threshold achievable in such a detector, and drives the noise specifications for the front end. The upper limit of the LZ dynamic range is defined by the electroluminescence (S2) signals. The low-energy channels of the LZ amplifiers provide the dynamic range required for the tritium and krypton calibrations. The high-energy channels provide the dynamic range required to measure the activated Xe lines. S2 signals induced by alpha particles from radon decay will saturate one or more channels of the top PMT array but techniques are being developed to recover the information lost due to saturation. This work was supported by the Department of Energy, Grant DE-SC0006605.

Childhood mortality impact and costs of integrating vitamin A supplementation into immunization campaigns.

PubMed Central

Ching, P; Birmingham, M; Goodman, T; Sutter, R; Loevinsohn, B

2000-01-01

Country-specific activity and coverage data were used to estimate the childhood mortality impact (deaths averted) and costs of integrating vitamin A supplements into immunization campaigns conducted in 1998 and 1999. More than 94 million doses of vitamin A were administered in 41 countries in 1998, helping to avert nearly 169,000 deaths. During 1999, delivery of more than 97 million doses in 50 countries helped avert an estimated 242,000 deaths. The estimated incremental cost per death averted was US$72 (range: 36-142) in 1998 and US$64 (range: 32-126) in 1999. The estimated average total cost of providing supplementation per death averted was US$310 (range: 157-609) in 1998 and US$276 (range: 139-540) in 1999. Costs per death averted varied by campaign, depending on the number and proportion of the child population reached, number of doses received per child, and child mortality rates. PMID:11029982

Amperometric biosensors for the determination of heavy metals

NASA Astrophysics Data System (ADS)

Compagnone, Dario; Palleschi, Giuseppe; Varallo, Giuseppe; Imperiali, PierLuigi

1995-10-01

A bioelectrochemical method for the determination of heavy metal ions has been developed. This method is based on the inhibition effect of metal ions on the enzymatic activity of oxidase enzymes. The enzymatic activity was determined with an amperometric hydrogen peroxide probe. The inhibition effect on enzymes in solution and covalently immobilized on polymeric supports has been evaluated. Hg(II) was the metal ion that inhibited almost all the enzymes, particularly glycerol-3-P oxidase. Hg(II) was detected in the 0.05/0.5 ppm range with the enzyme in solution. Calibration curves for Hg(II) were also obtained with the other oxidase enzymes in the 0.5/10 ppm range. The other metal ions tested inhibited the enzymes more specifically. The metal ion/enzyme systems which gave the best inhibition were Se(IV)/glutathione oxidase, Ni(II)/sarcosine oxidase, V(V)/glutathione oxidase, Cu(II)/alcohol oxidase from Pichia Pastoris and Cd(II)/D-aminoacid oxidase. All these metal ions were detected in the 0.1/10 ppm range using the enzymes in solution or covalently immobilized.

Plasma for environment

NASA Astrophysics Data System (ADS)

Van Oost, G.

2017-11-01

Human activity is associated with the permanent emergence of a very wide range of waste streams. The most widely used treatment of waste is thermal processing such as incineration. An alternative environmentally friendly process is based on thermal plasma technology which is a very flexible tool because it allows to operate in a wide temperature range with almost any chemical composition of waste and chemicals needed for processing this waste, and to convert organic waste into energy or chemical substances as well as to destroy toxic organic compounds, and to vitrify radioactive waste in a scenario that for each specific type of waste can be considered optimal, both in terms of energy efficiency and environmental safety.

Plasma for environment

NASA Astrophysics Data System (ADS)

Van Oost, G.

2017-12-01

Human activity is associated with the permanent emergence of a very wide range of waste streams. The most widely used treatment of waste is thermal processing such as incineration. An alternative environmentally friendly process is based on thermal plasma technology which is a very flexible tool because it allows to operate in a wide temperature range with almost any chemical composition of waste and chemicals needed for processing this waste. It allows the conversion of organic waste into energy or chemical substances as well as the destruction of toxic organic compounds in a scenario that for each specific type of waste can be considered optimal, both in terms of energy efficiency and environmental safety.

Protein design to understand peptide ligand recognition by tetratricopeptide repeat proteins.

PubMed

Cortajarena, Aitziber L; Kajander, Tommi; Pan, Weilan; Cocco, Melanie J; Regan, Lynne

2004-04-01

Protein design aims to understand the fundamentals of protein structure by creating novel proteins with pre-specified folds. An equally important goal is to understand protein function by creating novel proteins with pre-specified activities. Here we describe the design and characterization of a tetratricopeptide (TPR) protein, which binds to the C-terminal peptide of the eukaryotic chaperone Hsp90. The design emphasizes the importance of both direct, short-range protein-peptide interactions and of long-range electrostatic optimization. We demonstrate that the designed protein binds specifically to the desired peptide and discriminates between it and the similar C-terminal peptide of Hsp70.

Derated ion thruster design issues

NASA Technical Reports Server (NTRS)

Patterson, Michael J.; Rawlin, Vincent K.

1991-01-01

Preliminary activities to develop and refine a lightweight 30 cm engineering model ion thruster are discussed. The approach is to develop a 'derated' ion thruster capable of performing both auxiliary and primary propulsion roles over an input power range of at least 0.5 to 5.0 kilo-W. Design modifications to a baseline thruster to reduce mass and volume are discussed. Performance data over an order of magnitude input power range are presented, with emphasis on the performance impact of engine throttling. Thruster design modifications to optimize performance over specific power envelopes are discussed. Additionally, lifetime estimates based on wear test measurements are made for the operation envelope of the engine.

Critical mingling and universal correlations in model binary active liquids

NASA Astrophysics Data System (ADS)

Bain, Nicolas; Bartolo, Denis

2017-06-01

Ensembles of driven or motile bodies moving along opposite directions are generically reported to self-organize into strongly anisotropic lanes. Here, building on a minimal model of self-propelled bodies targeting opposite directions, we first evidence a critical phase transition between a mingled state and a phase-separated lane state specific to active particles. We then demonstrate that the mingled state displays algebraic structural correlations also found in driven binary mixtures. Finally, constructing a hydrodynamic theory, we single out the physical mechanisms responsible for these universal long-range correlations typical of ensembles of oppositely moving bodies.

Applications of Optical Neuroimaging in Usability Research

PubMed Central

Hill, Audrey P.; Bohil, Corey J.

2016-01-01

FEATURE AT A GLANCE In this article we review recent and potential applications of optical neuroimaging to human factors and usability research. We focus specifically on functional near-infrared spectroscopy (fNIRS) because of its cost-effectiveness and ease of implementation. Researchers have used fNIRS to assess a range of psychological phenomena relevant to human factors, such as cognitive workload, attention, motor activity, and more. It offers the opportunity to measure hemodynamic correlates of mental activity during task completion in human factors and usability studies. We also consider some limitations and future research directions. PMID:28286404

Spectrum of the Reductive Dehalogenation Activity of Desulfitobacterium frappieri PCP-1

PubMed Central

Dennie, D.; Gladu, I.; Lépine, F.; Villemur, R.; Bisaillon, J.-G.; Beaudet, R.

1998-01-01

Desulfitobacterium frappieri PCP-1 was induced for ortho- and para-dechlorinating activities by different chlorophenols. Dehalogenation rates ranging from 25 to 1,158 nmol/min/mg of cell protein were observed according to the chlorophenol tested and the position of the chlorine removed. D. frappieri shows a broad substrate specificity; in addition to tetrachloroethylene and pentachloropyridine, strain PCP-1 can dehalogenate at ortho, meta, and para positions a large variety of aromatic molecules with substituted hydroxyl or amino groups. Reactions of O demethylation and reduction of nitro to amino substituents on aromatic molecules were also observed. PMID:9797330

Deciphering the molecular and functional basis of Dbl family proteins: a novel systematic approach toward classification of selective activation of the Rho family proteins.

PubMed

Jaiswal, Mamta; Dvorsky, Radovan; Ahmadian, Mohammad Reza

2013-02-08

The diffuse B-cell lymphoma (Dbl) family of the guanine nucleotide exchange factors is a direct activator of the Rho family proteins. The Rho family proteins are involved in almost every cellular process that ranges from fundamental (e.g. the establishment of cell polarity) to highly specialized processes (e.g. the contraction of vascular smooth muscle cells). Abnormal activation of the Rho proteins is known to play a crucial role in cancer, infectious and cognitive disorders, and cardiovascular diseases. However, the existence of 74 Dbl proteins and 25 Rho-related proteins in humans, which are largely uncharacterized, has led to increasing complexity in identifying specific upstream pathways. Thus, we comprehensively investigated sequence-structure-function-property relationships of 21 representatives of the Dbl protein family regarding their specificities and activities toward 12 Rho family proteins. The meta-analysis approach provides an unprecedented opportunity to broadly profile functional properties of Dbl family proteins, including catalytic efficiency, substrate selectivity, and signaling specificity. Our analysis has provided novel insights into the following: (i) understanding of the relative differences of various Rho protein members in nucleotide exchange; (ii) comparing and defining individual and overall guanine nucleotide exchange factor activities of a large representative set of the Dbl proteins toward 12 Rho proteins; (iii) grouping the Dbl family into functionally distinct categories based on both their catalytic efficiencies and their sequence-structural relationships; (iv) identifying conserved amino acids as fingerprints of the Dbl and Rho protein interaction; and (v) defining amino acid sequences conserved within, but not between, Dbl subfamilies. Therefore, the characteristics of such specificity-determining residues identified the regions or clusters conserved within the Dbl subfamilies.

In Vitro and In Vivo Plant Growth Promoting Activities and DNA Fingerprinting of Antagonistic Endophytic Actinomycetes Associates with Medicinal Plants.

PubMed

Passari, Ajit Kumar; Mishra, Vineet Kumar; Gupta, Vijai Kumar; Yadav, Mukesh Kumar; Saikia, Ratul; Singh, Bhim Pratap

2015-01-01

Endophytic actinomycetes have shown unique plant growth promoting as well as antagonistic activity against fungal phytopathogens. In the present study forty-two endophytic actinomycetes recovered from medicinal plants were evaluated for their antagonistic potential and plant growth-promoting abilities. Twenty-two isolates which showed the inhibitory activity against at least one pathogen were subsequently tested for their plant-growth promoting activities and were compared genotypically using DNA based fingerprinting, including enterobacterial repetitive intergenic consensus (ERIC) and BOX repetitive elements. Genetic relatedness based on both ERIC and BOX-PCR generates specific patterns corresponding to particular genotypes. Exponentially grown antagonistic isolates were used to evaluate phosphate solubilization, siderophores, HCN, ammonia, chitinase, indole-3-acetic acid production, as well as antifungal activities. Out of 22 isolates, the amount of indole-3-acetic acid (IAA) ranging between 10-32 μg/ml was produced by 20 isolates and all isolates were positive for ammonia production ranging between 5.2 to 54 mg/ml. Among 22 isolates tested, the amount of hydroxamate-type siderophores were produced by 16 isolates ranging between 5.2 to 36.4 μg/ml, while catechols-type siderophores produced by 5 isolates ranging from 3.2 to 5.4 μg/ml. Fourteen isolates showed the solubilisation of inorganic phosphorous ranging from 3.2 to 32.6 mg/100ml. Chitinase and HCN production was shown by 19 and 15 different isolates, respectively. In addition, genes of indole acetic acid (iaaM) and chitinase (chiC) were successively amplified from 20 and 19 isolates respectively. The two potential strains Streptomyces sp. (BPSAC34) and Leifsonia xyli (BPSAC24) were tested in vivo and improved a range of growth parameters in chilli (Capsicum annuum L.) under greenhouse conditions. This study is the first published report that actinomycetes can be isolated as endophytes from within these plants and were shown to have antagonistic and plant growth promoting abilities. These results clearly suggest the possibility of using endophytic actinomycetes as bioinoculant for plant growth promotion, nutrient mobilization or as biocontrol agent against fungal phytopathogens for sustainable agriculture.

Specific Caleosin/Peroxygenase and Lipoxygenase Activities Are Tissue-Differentially Expressed in Date Palm (Phoenix dactylifera L.) Seedlings and Are Further Induced Following Exposure to the Toxin 2,3,7,8-tetrachlorodibenzo-p-dioxin.

PubMed

Hanano, Abdulsamie; Almousally, Ibrahem; Shaban, Mouhnad; Rahman, Farzana; Hassan, Mehedi; Murphy, Denis J

2016-01-01

Two caleosin/peroxygenase isoforms from date palm, Phoenix dactylifera L., PdCLO2 and PdCLO4, were characterized with respect to their tissue expression, subcellular localization, and oxylipin pathway substrate specificities in developing seedlings. Both PdCLO2 and PdCLO4 had peroxygenase activities that peaked at the mid-stage (radicle length of 2.5 cm) of seedling growth and were associated with the lipid droplet (LD) and microsomal fractions. Recombinant PdCLO2 and PdCLO4 proteins heterologously expressed in yeast cells were localized in both LD and microsomal fractions. Each of the purified recombinant proteins exhibited peroxygenase activity but they were catalytically distinct with respect to their specificity and product formation from fatty acid epoxide and hydroxide substrates. We recently showed that date palm CLO genes were upregulated following exposure to the potent toxin, 2,3,7,8-tetrachlorodibenzo- p -dioxin (TCDD) (Hanano et al., 2016), and we show here that transcripts of 9- and 13-lipoxygenase (LOX) genes were also induced by TCDD exposure. At the enzyme level, 9-LOX and 13-LOX activities were present in a range of seedling tissues and responded differently to TCDD exposure, as did the 9- and 13-fatty acid hydroperoxide reductase activities. This demonstrates that at least two branches of the oxylipin pathway are involved in responses to the environmental organic toxin, TCDD in date palm.

Electrochemical biosensor for carbofuran pesticide based on esterases from Eupenicillium shearii FREI-39 endophytic fungus.

PubMed

Grawe, Gregory Ferreira; de Oliveira, Tássia Regina; de Andrade Narciso, Esther; Moccelini, Sally Katiuce; Terezo, Ailton José; Soares, Marcos Antonio; Castilho, Marilza

2015-01-15

In this work, a biosensor was constructed by physical adsorption of the isolated endophytic fungus Eupenicillium shearii FREI-39 esterase on halloysite, using graphite powder, multi-walled carbon nanotubes and mineral oil for the determination of carbofuran pesticide by inhibition of the esterase using square-wave voltammetry (SWV). Specific esterase activities were determined each 2 days over a period of 15 days of growth in four different inoculation media. The highest specific activity was found on 6th day, with 33.08 U on PDA broth. The best performance of the proposed biosensor was obtained using 0.5 U esterase activity. The carbofuran concentration response was linear in the range from 5.0 to 100.0 µg L(-1) (r=0.9986) with detection and quantification limits of 1.69 µg L(-1) and 5.13 µg L(-1), respectively. A recovery study of carbofuran in spiked water samples showed values ranging from 103.8±6.7% to 106.7±9.7%. The biosensor showed good repeatability and reproducibility and remained stable for a period of 20 weeks. The determination of carbofuran in spiked water samples using the proposed biosensor was satisfactory when compared to the chromatographic reference method. The results showed no significant difference at the 95% confidence level with t-test statistics. The application of enzymes from endophytic fungi in constructing biosensors broadens the biotechnological importance of these microorganisms. Copyright © 2014 Elsevier B.V. All rights reserved.

Yeast surface displaying glucose oxidase as whole-cell biocatalyst: construction, characterization, and its electrochemical glucose sensing application.

PubMed

Wang, Hongwei; Lang, Qiaolin; Li, Liang; Liang, Bo; Tang, Xiangjiang; Kong, Lingrang; Mascini, Marco; Liu, Aihua

2013-06-18

The display of glucose oxidase (GOx) on yeast cell surface using a-agglutinin as an anchor motif was successfully developed. Both the immunochemical analysis and enzymatic assay showed that active GOx was efficiently expressed and translocated on the cell surface. Compared with conventional GOx, the yeast cell surface that displayed GOx (GOx-yeast) demonstrated excellent enzyme properties, such as good stability within a wide pH range (pH 3.5-11.5), good thermostability (retaining over 94.8% enzyme activity at 52 °C and 84.2% enzyme activity at 56 °C), and high d-glucose specificity. In addition, direct electrochemistry was achieved at a GOx-yeast/multiwalled-carbon-nanotube modified electrode, suggesting that the host cell of yeast did not have any adverse effect on the electrocatalytic property of the recombinant GOx. Thus, a novel electrochemical glucose biosensor based on this GOx-yeast was developed. The as-prepared biosensor was linear with the concentration of d-glucose within the range of 0.1-14 mM and a low detection limit of 0.05 mM (signal-to-noise ratio of S/N = 3). Moreover, the as-prepared biosensor is stable, specific, reproducible, simple, and cost-effective, which can be applicable for real sample detection. The proposed strategy to construct robust GOx-yeast may be applied to explore other oxidase-displaying-system-based whole-cell biocatalysts, which can find broad potential application in biosensors, bioenergy, and industrial catalysis.

Human and mouse homo-oligomeric meprin A metalloendopeptidase: substrate and inhibitor specificities.

PubMed

Bylander, John E; Bertenshaw, Greg P; Matters, Gail L; Hubbard, Simon J; Bond, Judith S

2007-11-01

Meprin metalloproteinases have been implicated in the susceptibility to and progression of diabetic nephropathy and inflammatory bowel diseases. Our studies with experimental models of these diseases in mice are congruent with the conclusion that meprins modulate the inflammatory responses and tissue damage. To determine whether the mouse and human enzymes differ, recombinant forms of meprin A from the two species were compared with respect to structure, substrates and inhibitors. Human homo-oligomeric meprin A formed oligomers ranging from 950,000 to 1,500,000 Da vs. 900,000 Da for mouse meprin A. Human and mouse meprin A exhibited similar activity against azocasein, fibronectin, collagen IV, and peptides such as parathyroid hormone, ghrelin, and gastrin-releasing peptide. The human enzyme had lower activity against gelatin, bradykinin, alpha-melanocyte-stimulating hormone and neurotensin, and higher activity against secretin and orcokinin. Human meprin A showed a preference for acidic residues in the P1' position of the substrate, unlike mouse meprin A. Several metalloproteinase inhibitors had IC(50) values in the nanomolar range, but potency ranged from similar values to a difference of several orders of magnitude for meprins from the two species. This work provides valuable data to improve predictability for human systems based on meprin functions in mouse models.

Expression, purification and immobilization of tannase from Staphylococcus lugdunensis MTCC 3614.

PubMed

Chaitanyakumar, Amballa; Anbalagan, M

2016-12-01

Enzymes find their applications in various industries, due to their error free conversion of substrate into product. Tannase is an enzyme used by various industries for degradation of tannin. Biochemical characterization of a specific enzyme from one organism to other is one of the ways to search for enzymes with better traits for industrial applications. Here, tannase encoding gene from Staphylococcus lugdunensis was cloned and suitability of the enzyme in various conditions was analysed to find its application in various industry. The recombinant protein was expressed with 6× His tag and purified using nickel affinity beads. The enzyme was purified up to homogeneity, with approximate molecular weight of 66 kDa. Purified tannase exhibited specific activity of about 716 U/mg. Optimum enzyme activity was found to be 40 °C at pH 7.0. Biochemical characterization revealed; metal ions such as Zn 2+ , Fe 2+ , Fe 3+ and Mn 2+ inhibited tannase activity, and SDS at lower concentration, increased tannase activity. Non polar organic solvents increased the tannase activity and polar solvents inhibited the tannase activity. Tannase immobilization studies show protection of the enzyme under wide range of pH and temperature. Also in this study we report a method for recovery and repeated use of the tannase.

A spatiotemporal profile of visual system activation revealed by current source density analysis in the awake macaque.

PubMed

Schroeder, C E; Mehta, A D; Givre, S J

1998-01-01

We investigated the spatiotemporal activation pattern, produced by one visual stimulus, across cerebral cortical regions in awake monkeys. Laminar profiles of postsynaptic potentials and action potentials were indexed with current source density (CSD) and multiunit activity profiles respectively. Locally, we found contrasting activation profiles in dorsal and ventral stream areas. The former, like V1 and V2, exhibit a 'feedforward' profile, with excitation beginning at the depth of Lamina 4, followed by activation of the extragranular laminae. The latter often displayed a multilaminar/columnar profile, with initial responses distributed across the laminae and reflecting modulation rather than excitation; CSD components were accompanied by either no changes or by suppression of action potentials. System-wide, response latencies indicated a large dorsal/ventral stream latency advantage, which generalizes across a wide range of methods. This predicts a specific temporal ordering of dorsal and ventral stream components of visual analysis, as well as specific patterns of dorsal-ventral stream interaction. Our findings support a hierarchical model of cortical organization that combines serial and parallel elements. Critical in such a model is the recognition that processing within a location typically entails multiple temporal components or 'waves' of activity, driven by input conveyed over heterogeneous pathways from the retina.

Improvements in knee biomechanics during walking are associated with increased physical activity after total knee arthroplasty.

PubMed

Arnold, John B; Mackintosh, Shylie; Olds, Timothy S; Jones, Sara; Thewlis, Dominic

2015-12-01

Total knee arthroplasty (TKA) in people with knee osteoarthritis increases knee-specific and general physical function, but it has not been established if there is a relationship between changes in these elements of functional ability. This study investigated changes and relationships between knee biomechanics during walking, physical activity, and use of time after TKA. Fifteen people awaiting TKA underwent 3D gait analysis before and six months after surgery. Physical activity and use of time were determined in free-living conditions from a high resolution 24-h activity recall. After surgery, participants displayed significant improvements in sagittal plane knee biomechanics and improved their physical activity profiles, standing for 105 more minutes (p=0.001) and performing 64 min more inside chores on average per day (p=0.008). Changes in sagittal plane knee range of motion (ROM) and peak knee flexion positively correlated with changes in total daily energy expenditure, time spent undertaking moderate to vigorous physical activity, inside chores and passive transport (r=0.52-0.66, p=0.005-0.047). Restoration of knee function occurs in parallel and is associated with improvements in physical activity and use of time after TKA. Increased functional knee ROM is required to support improvements in total and context specific physical activity. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

In vitro antifungal activity and probable fungicidal mechanism of aqueous extract of Barleria grandiflora.

PubMed

Kumari, Suman; Jain, Preeti; Sharma, Bhawana; Kadyan, Preeti; Dabur, Rajesh

2015-04-01

Barleria grandiflora Dalz. (Acanthaceae) is being used in India to treat different types of disorders including skin infections. Therefore, there are good possibilities to find antifungal compounds in its extracts with novel mechanism of action. The main objectives of the present study were to evaluate the antifungal activity of plant extracts and to study its effects on metabolic pathways of A. fumigatus. The microbroth dilution assay was used to explore antifungal activity and MIC of various extracts. Metabolic profiles of control and treated cultures were collected from Q-TOF-MS interfaced with HPLC. Affected metabolic pathways of A. fumigatus after the treatment were analyzed by discrimination analysis of mass data. Antifungal activities were observed in hot and cold water extracts of the plant. Hot water extract of B. grandiflora showed significant activity against tested fungi in the range 0.625-1.25 mg/mL. Partial least discrimination analysis revealed that the hot water plant extract downregulated amino acid, glyoxylate pathway, and methylcitrate pathways at the same time due to the synergistic effects of secondary metabolites. Hot water extract also downregulated several other metabolic pathways unique to fungi indicating its specific activity toward fungi. B. grandiflora showed promising antifungal activity which can further be exploited by identification of active compounds, to inhibit the specific fungal pathways and development of novel therapeutic antifungal drugs.

A benefit-cost framework of motivation for a specific activity.

PubMed

Studer, B; Knecht, S

2016-01-01

How can an individual be motivated to perform a target exercise or activity? This question arises in training, therapeutic, and education settings alike, yet despite-or even because of-the large range of extant motivation theories, finding a clear answer to this question can be challenging. Here we propose an application-friendly framework of motivation for a specific activity or exercise that incorporates core concepts from several well-regarded psychological and economic theories of motivation. The key assumption of this framework is that motivation for performing a given activity is determined by the expected benefits and the expected costs of (performance of) the activity. Benefits comprise positive feelings, gains, and rewards experienced during performance of the activity (intrinsic benefits) or achieved through the activity (extrinsic benefits). Costs entail effort requirements, time demands, and other expenditure (intrinsic costs) as well as unwanted associated outcomes and missing out on alternative activities (extrinsic costs). The expected benefits and costs of a given exercise are subjective and state dependent. We discuss convergence of the proposed framework with a selection of extant motivation theories and briefly outline neurobiological correlates of its main components and assumptions. One particular strength of our framework is that it allows to specify five pathways to increasing motivation for a target exercise, which we illustrate and discuss with reference to previous empirical data. © 2016 Elsevier B.V. All rights reserved.

Reward-based hypertension control by a synthetic brain-dopamine interface.

PubMed

Rössger, Katrin; Charpin-El Hamri, Ghislaine; Fussenegger, Martin

2013-11-05

Synthetic biology has significantly advanced the design of synthetic trigger-controlled devices that can reprogram mammalian cells to interface with complex metabolic activities. In the brain, the neurotransmitter dopamine coordinates communication with target neurons via a set of dopamine receptors that control behavior associated with reward-driven learning. This dopamine transmission has recently been suggested to increase central sympathetic outflow, resulting in plasma dopamine levels that correlate with corresponding brain activities. By functionally rewiring the human dopamine receptor D1 (DRD1) via the second messenger cyclic adenosine monophosphate (cAMP) to synthetic promoters containing cAMP response element-binding protein 1(CREB1)-specific cAMP-responsive operator modules, we have designed a synthetic dopamine-sensitive transcription controller that reversibly fine-tunes specific target gene expression at physiologically relevant brain-derived plasma dopamine levels. Following implantation of circuit-transgenic human cell lines insulated by semipermeable immunoprotective microcontainers into mice, the designer device interfaced with dopamine-specific brain activities and produced a systemic expression response when the animal's reward system was stimulated by food, sexual arousal, or addictive drugs. Reward-triggered brain activities were able to remotely program peripheral therapeutic implants to produce sufficient amounts of the atrial natriuretic peptide, which reduced the blood pressure of hypertensive mice to the normal physiologic range. Seamless control of therapeutic transgenes by subconscious behavior may provide opportunities for treatment strategies of the future.

A microfluorometric assay for cholinesterases, suitable for multiple kinetic determinations of picomoles of released thiocholine.

PubMed

Parvari, R; Pecht, I; Soreq, H

1983-09-01

A highly sensitive microfluorometric assay for cholinesterases has been developed. Enzymatic activity is measured by monitoring the thiocholine produced by specific hydrolysis of acetylthiocholine. This is carried out by reacting the thiocholine formed with the fluorogenic compound N-(4(7 diethylamino-4-methylcoumarin-3-yl)phenyl)maleimide to yield an intensely fluorescent product. The assay is linear over a range extending from a few picomoles to nanomoles of thiocholine. The specificity and accuracy of this microfluorometric assay were examined using microgram quantities of rat brain tissue as a source for cholinesterases. The specific activities and the Km values determined by this new method for both cholinesterase activities present in the brain (acetylcholine hydrolase, EC 3.1.1.7, and "nonspecific" cholinesterase-acylcholine acylhydrolase, EC 3.1.1.8) were identical to those reported earlier using the less sensitive spectrophotometric and radiometric methods. The background emission caused by nonenzymatic hydrolysis of the substrate is relatively low, and does not exceed background values encountered in other methods. The assay may be used for monitoring the kinetics of enzymatic activities in microscale reaction mixtures, providing a linear determination of the thiocholine produced over a period of at least 30 h at room temperature. The method can also be adapted for use in other enzymatic assays where reagents containing thiol groups can be produced or consumed.

Development and validation of a new self-report instrument for measuring sedentary behaviors and light-intensity physical activity in adults.

PubMed

Barwais, Faisal Awad; Cuddihy, Thomas F; Washington, Tracy; Tomson, L Michaud; Brymer, Eric

2014-08-01

Low levels of physical activity and high levels of sedentary behavior (SB) are major public health concerns. This study was designed to develop and validate the 7-day Sedentary (S) and Light Intensity Physical Activity (LIPA) Log (7-day SLIPA Log), a self-report measure of specific daily behaviors. To develop the log, 62 specific SB and LIPA behaviors were chosen from the Compendium of Physical Activities. Face-to-face interviews were conducted with 32 sedentary volunteers to identify domains and behaviors of SB and LIPA. To validate the log, a further 22 sedentary adults were recruited to wear the GT3x for 7 consecutive days and nights. Pearson correlations (r) between the 7-day SLIPA Log and GT3x were significant for sedentary (r = .86, P < .001), for LIPA (r = .80, P < .001). Lying and sitting postures were positively correlated with GT3x output (r = .60 and r = .64, P < .001, respectively). No significant correlation was found for standing posture (r = .14, P = .53).The kappa values between the 7-day SLIPA Log and GT3x variables ranged from 0.09 to 0.61, indicating poor to good agreement. The 7-day SLIPA Log is a valid self-report measure of SB and LIPA in specific behavioral domains.

Identification of small molecule inhibitors of ERCC1-XPF that inhibit DNA repair and potentiate cisplatin efficacy in cancer cells

PubMed Central

Arora, Sanjeevani; Heyza, Joshua; Zhang, Hao; Kalman-Maltese, Vivian; Tillison, Kristin; Floyd, Ashley M.; Chalfin, Elaine M.; Bepler, Gerold; Patrick, Steve M.

2016-01-01

ERCC1-XPF heterodimer is a 5′-3′ structure-specific endonuclease which is essential in multiple DNA repair pathways in mammalian cells. ERCC1-XPF (ERCC1-ERCC4) repairs cisplatin-DNA intrastrand adducts and interstrand crosslinks and its specific inhibition has been shown to enhance cisplatin cytotoxicity in cancer cells. In this study, we describe a high throughput screen (HTS) used to identify small molecules that inhibit the endonuclease activity of ERCC1-XPF. Primary screens identified two compounds that inhibit ERCC1-XPF activity in the nanomolar range. These compounds were validated in secondary screens against two other non-related endonucleases to ensure specificity. Results from these screens were validated using an in vitro gel-based nuclease assay. Electrophoretic mobility shift assays (EMSAs) further show that these compounds do not inhibit the binding of purified ERCC1-XPF to DNA. Next, in lung cancer cells these compounds potentiated cisplatin cytotoxicity and inhibited DNA repair. Structure activity relationship (SAR) studies identified related compounds for one of the original Hits, which also potentiated cisplatin cytotoxicity in cancer cells. Excitingly, dosing with NSC16168 compound potentiated cisplatin antitumor activity in a lung cancer xenograft model. Further development of ERCC1-XPF DNA repair inhibitors is expected to sensitize cancer cells to DNA damage-based chemotherapy. PMID:27650543

Direction-Specific Impairments in Cervical Range of Motion in Women with Chronic Neck Pain: Influence of Head Posture and Gravitationally Induced Torque

PubMed Central

Björklund, Martin; Svedmark, Åsa; Srinivasan, Divya; Djupsjöbacka, Mats

2017-01-01

Background Cervical range of motion (ROM) is commonly assessed in clinical practice and research. In a previous study we decomposed active cervical sagittal ROM into contributions from lower and upper levels of the cervical spine and found level- and direction-specific impairments in women with chronic non-specific neck pain. The present study aimed to validate these results and investigate if the specific impairments can be explained by the neutral posture (defining zero flexion/extension) or a movement strategy to avoid large gravitationally induced torques on the cervical spine. Methods Kinematics of the head and thorax was assessed in sitting during maximal sagittal cervical flexion/extension (high torque condition) and maximal protraction (low torque condition) in 120 women with chronic non-specific neck pain and 40 controls. We derived the lower and upper cervical angles, and the head centre of mass (HCM), from a 3-segment kinematic model. Neutral head posture was assessed using a standardized procedure. Findings Previous findings of level- and direction-specific impairments in neck pain were confirmed. Neutral head posture was equal between groups and did not explain the direction-specific impairments. The relative magnitude of group difference in HCM migration did not differ between high and low torques conditions, lending no support for our hypothesis that impairments in sagittal ROM are due to torque avoidance behaviour. Interpretation The direction- and level-specific impairments in cervical sagittal ROM can be generalised to the population of women with non-specific neck pain. Further research is necessary to clarify if torque avoidance behaviour can explain the impairments. PMID:28099504

Carbon-14 Specific Activity Model Validation for Biota in Wetland Environments

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

Yankovich, T.L.; Sharp, K.J.; Benz, M.L.

2008-01-15

In many cases, contaminants, such as radionuclides, can show highly localized spatial distributions in natural systems. Therefore, a key question for environmental assessment and monitoring becomes, how can these localized distributions of contaminants in the environment lead to organism exposure, and ultimately, the potential for effects to receptor biota? To address this question, an important first step is to conduct field surveys at sites of interest to map out the spatial distribution and extent of contaminants in areas that are being occupied and utilized by resident receptor biota. Work can then be conducted to establish predictive relationships between contaminant concentrationsmore » in biota tissues and those in environmental media with which biota interact, to gain an understanding of how representative ambient contaminant concentrations are of biota exposure. The objectives of this study were: - To conduct a field survey in a wetland ecosystem to characterize the spatial distribution of carbon- 14 ({sup 14}C), a radionuclide with dynamics in natural systems that can be described using a specific activity model; and - To determine whether {sup 14}C concentrations in environmental media reflect those measured in tissues of resident flora and fauna. A detailed field campaign was carried out in summer 2001 to characterize the spatial distribution and areal coverage of {sup 14}C in Duke Swamp, a wetland ecosystem on Atomic Energy of Canada Limited (AECL)'s Chalk River Laboratories (CRL) site that receives {sup 14}C through releases from an up-gradient Waste Management Area (WMA), primarily through groundwater influx. Sampling of surface vegetation (dominantly comprised of Sphagnum moss) was conducted at a total of 69 locations, with complementary sampling of air, soil, fungi, aerial insects, ground-dwelling insects, amphibians, small mammals and snakes being carried out at a subset of five locations with varying {sup 14}C concentrations. Concentrations of {sup 14}C in resident Duke Swamp biota were compared to levels measured in environmental media (including moss, soil and air) to determine whether concentrations in such media reflect animal exposure, for application in routine environmental monitoring programs on the CRL site. In general, for most types of receptor animals, {sup 14}C specific activities were found to be similar to or less than those measured in air, soil and surface vegetation at all locations sampled, suggesting that in most cases, estimates of {sup 14}C levels in animals could either be realistically or conservatively predicted based on the values measured in environmental media. In the case of fungi, receptor-to-media {sup 14}C specific activity ratios fell between 0.04 and 0.23 relative to air, between 0.03 and 0.70 relative to soil, and between 0.078 and 0.31 relative to moss. Small mammal specific activities also generally fell well below those that would be predicted based on specific activities measured in environmental media, with ratios ranging from 0.11 to 0.36 relative to air, from 0.17 to 0.85 relative to soil and from 0.21 to 0.58 relative to moss. Similar ratios were also established for snakes; however, a notable exception occurred for amphibians, a type of animal that tends to spend relatively more time in aquatic environments than the other species tested. In the case of Duke Swamp amphibians, animal-to-air {sup 14}C specific activity ratios ranged from 0.40 to 2.3, animal-to-soil ratios ranged from 0.81 to 3.4 and animal-to-moss ratios ranged from 1.5 to 2.4. These higher {sup 14}C levels in amphibians relative to the environmental media may be due to increased {sup 14}C exposure of aquatic or amphibious animals that occupy systems receiving inputs via groundwater. In such systems, {sup 14}C is incorporated in aquatic plants and animals, and later transferred to higher predatory species, such as amphibians, that consume them. Therefore, with the exception of amphibians and other aquatic receptor species, it is reasonable to estimate concentrations of {sup 14}C in receptor biota in wetland environments like Duke Swamp at CRL, based on measurements of {sup 14}C in environmental media, including air, soil and surface vegetation. In the case of Duke Swamp amphibians, environmental media concentrations could still be roughly predicted if they are multiplied by a 4-fold correction factor. In addition, our study findings also confirm that in cases where elevated {sup 14}C levels are highly localized, elevated exposures to resident biota are also highly localized. Such information is critical to the development of cost-effective environmental monitoring programs that are protective of nonhuman biota, while reducing the need to capture and euthanize animals during routine monitoring.« less

A Comparison of Single-Wall Carbon Nanotube Electrochemical Capacitor Electrode Fabrication Methods

DTIC Science & Technology

2012-01-24

REPORT A comparison of single-wall carbon nanotube electrochemical capacitor electrode fabrication methods 14. ABSTRACT 16. SECURITY CLASSIFICATION OF... Carbon nanotubes (CNTs) are being widely investigated as a replacement for activated carbon in super- capacitors. A wide range of CNT specific...ORGANIZATION NAMES AND ADDRESSES U.S. Army Research Office P.O. Box 12211 Research Triangle Park, NC 27709-2211 15. SUBJECT TERMS Carbon nanotube

Range of control of cardiovascular variables by the hypothalamus

NASA Technical Reports Server (NTRS)

Smith, O. A.; Stephenson, R. B.; Randall, D. C.

1974-01-01

New methodologies were utilized to study the influence of the hypothalamus on the cardiovascular system. The regulation of myocardial activity was investigated in monkeys with hypothalamic lesions that eliminate cardiovascular responses. Observations showed that a specific part of the hypothalamus regulates changes in myocardial contractility that accompanies emotion. Studies of the hypothalamus control of renal blood flow showed the powerful potential control of this organ over renal circulation.

Toward an Evaluation Framework for Doctoral Education in Social Work: A 10-Year Retrospective of One PhD Program's Assessment Experiences

ERIC Educational Resources Information Center

Bentley, Kia J.

2013-01-01

This article presents a framework for evaluation in social work doctoral education and details 10 years of successes and challenges in one PhD program's use of the framework, including planning and implementing specific assessment activities around student learning outcomes and larger program goals. The article argues that a range of…

The impact of Internet-based specific activities on the perceptions of Internet addiction, quality of life, and excessive usage: A cross-sectional study.

PubMed

Pontes, Halley M; Szabo, Attila; Griffiths, Mark D

2015-06-01

Recent research has examined the context in which preference for specific online activities arises, leading researchers to suggest that excessive Internet users are engaged in specific activities rather than 'generalized' Internet use. The present study aimed to partially replicate and expand these findings by addressing four research questions regarding (i) participants' preferred online activities, (i) possible expected changes in online behavior in light of hypothetical scenarios, (iii) perceived quality of life when access to Internet was not possible, and (iv) how participants with self-diagnosed Internet addiction relate to intensity and frequency of Internet use. A cross-sectional design was adopted using convenience and snowball sampling to recruit participants. A total of 1057 Internet users with ages ranging from 16 to 70 years (M age  = 30 years, SD = 10.84) were recruited online via several English-speaking online forums. Most participants indicated that their preferred activities were (i) accessing general information and news, (ii) social networking, and (iii) using e-mail and/or online chatting. Participants also reported that there would be a significant decrease of their Internet use if access to their preferred activities was restricted. The study also found that 51% of the total sample perceived themselves as being addicted to the Internet, while 14.1% reported that without the Internet their life would be improved. The context in which the Internet is used appears to determine the intensity and the lengths that individuals will go to use this tool. The implications of these findings are further discussed.

Patient-reported physical activity questionnaires: A systematic review of content and format

PubMed Central

2012-01-01

Background Many patients with chronic illness are limited in their physical activities. This systematic review evaluates the content and format of patient-reported outcome (PRO) questionnaires that measure physical activity in elderly and chronically ill populations. Methods Questionnaires were identified by a systematic literature search of electronic databases (Medline, Embase, PsychINFO & CINAHL), hand searches (reference sections and PROQOLID database) and expert input. A qualitative analysis was conducted to assess the content and format of the questionnaires and a Venn diagram was produced to illustrate this. Each stage of the review process was conducted by at least two independent reviewers. Results 104 questionnaires fulfilled our criteria. From these, 182 physical activity domains and 1965 items were extracted. Initial qualitative analysis of the domains found 11 categories. Further synthesis of the domains found 4 broad categories: 'physical activity related to general activities and mobility', 'physical activity related to activities of daily living', 'physical activity related to work, social or leisure time activities', and '(disease-specific) symptoms related to physical activity'. The Venn diagram showed that no questionnaires covered all 4 categories and that the '(disease-specific) symptoms related to physical activity' category was often not combined with the other categories. Conclusions A large number of questionnaires with a broad range of physical activity content were identified. Although the content could be broadly organised, there was no consensus on the content and format of physical activity PRO questionnaires in elderly and chronically ill populations. Nevertheless, this systematic review will help investigators to select a physical activity PRO questionnaire that best serves their research question and context. PMID:22414164

[Evaluation of residual osteomuscular function using computerised movement analysis for building sector workers: specificity and technical problem].

PubMed

D'Orso, M I; Centemeri, R; Latocca, R; Riva, M; Cesana, G

2012-01-01

Occupational Health Doctors active in building sector firms frequently have to evaluate residual workers' osteomuscular function in patients coming back to work after an accident happened during work time or free time. Definition of their specific individual work suitability is usually carried out utilizing semeiotic tests in which subjective evaluation of every single Medical Doctor is real important in definition of final results and this fact can cause legal controversies. In our research we describe the application of computerised movement analysis on 10 workers of building sector. In every patient examined this technical method has been able to study objectively the tridimensional ranges of motion of most important osteomuscular districts. The possibility to have an objective evaluation of residual osteomuscular function has a relevant importance both in definition of workers' work suitability at the moment in which they start again their activities and in possible future legal conflicts.

Practical Approach To Building A Mid-Wave Remote Sensing System

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

Pyke, Benjamin J.

The purpose of this project, Laser Active Transmitter & Receiver (LATR), was to build a mobile ground based remote sensing system that can detect, identify and quantify a specific gaseous species using Differential Absorption LIDAR (DIAL). This thesis project is concerned with the development and field testing of a mid-wave infrared active remote sensing system, capable of identifying and quantifying emissions in the 3.2 – 3.5 micron range. The goal is to give a brief description of what remote sensing is about and the specific technique used to analyze the collected data. The thesis will discuss the transmitter and themore » associated subsystems used to create the required wavelength, and the receiver used to collect the returns. And finally, the thesis will discuss the process of collecting the data and some of the results from field and lab collections.« less

Porous carbon derived from aniline-modified fungus for symmetrical supercapacitor electrodes

DOE PAGES

Wang, Keliang; Xu, Ming; Wang, Xiaomin; ...

2017-01-23

N incorporated carbon materials are proven to be efficient EDLCs electrode materials. In this work, aniline modified fungus served as a raw material, and N-doped porous activated carbon is prepared via an efficient KOH activation method. A porous network with a high specific surface area of 2339 m 2g -1 is displayed by the prepared carbon material, resulting in a high accessible surface area and low ion diffusion resistance which is desirable for EDLC electrode materials. In assembled EDLCs, the N–AC based electrode exhibits a specific capacitance of 218 F g -1 at a current density of 0.1 A gmore » -1. Besides, excellent stability is displayed after 5000 continuous cycles at different current densities ranging from 0.1 to 10 A g -1. Thus, the present work reveals a promising candidate for electrode materials of EDLCs.« less

A three-dimensional actuated origami-inspired transformable metamaterial with multiple degrees of freedom

NASA Astrophysics Data System (ADS)

Overvelde, Johannes T. B.; de Jong, Twan A.; Shevchenko, Yanina; Becerra, Sergio A.; Whitesides, George M.; Weaver, James C.; Hoberman, Chuck; Bertoldi, Katia

2016-03-01

Reconfigurable devices, whose shape can be drastically altered, are central to expandable shelters, deployable space structures, reversible encapsulation systems and medical tools and robots. All these applications require structures whose shape can be actively controlled, both for deployment and to conform to the surrounding environment. While most current reconfigurable designs are application specific, here we present a mechanical metamaterial with tunable shape, volume and stiffness. Our approach exploits a simple modular origami-like design consisting of rigid faces and hinges, which are connected to form a periodic structure consisting of extruded cubes. We show both analytically and experimentally that the transformable metamaterial has three degrees of freedom, which can be actively deformed into numerous specific shapes through embedded actuation. The proposed metamaterial can be used to realize transformable structures with arbitrary architectures, highlighting a robust strategy for the design of reconfigurable devices over a wide range of length scales.

The endolysins of bacteriophages CMP1 and CN77 are specific for the lysis of Clavibacter michiganensis strains.

PubMed

Wittmann, Johannes; Eichenlaub, Rudolf; Dreiseikelmann, Brigitte

2010-08-01

Putative endolysin genes of bacteriophages CMP1 and CN77, which infect Clavibacter michiganensis subsp. michiganensis and C. michiganensis subsp. nebraskensis, respectively, were cloned and expressed in Escherichia coli. The His-tagged endolysin of CMP1 consists of 306 amino acids and has a calculated molecular mass of 34.8 kDa, while the His-tagged endolysin of CN77 has 290 amino acids with a molecular mass of 31.9 kDa. The proteins were purified and their bacteriolytic activity was demonstrated. The bacteriolytic activity of both enzymes showed a host range which was limited to the respective C. michiganensis subspecies and did not affect other bacteria, even those closely related to Clavibacter. Due to the high specificity of the CMP1 and CN77 endolysins they may be useful tools for biocontrol of plant-pathogenic C. michiganensis without affecting other bacteria in the soil.

Subtle Changes in Motif Positioning Cause Tissue-Specific Effects on Robustness of an Enhancer's Activity

PubMed Central

Erceg, Jelena; Saunders, Timothy E.; Girardot, Charles; Devos, Damien P.; Hufnagel, Lars; Furlong, Eileen E. M.

2014-01-01

Deciphering the specific contribution of individual motifs within cis-regulatory modules (CRMs) is crucial to understanding how gene expression is regulated and how this process is affected by sequence variation. But despite vast improvements in the ability to identify where transcription factors (TFs) bind throughout the genome, we are limited in our ability to relate information on motif occupancy to function from sequence alone. Here, we engineered 63 synthetic CRMs to systematically assess the relationship between variation in the content and spacing of motifs within CRMs to CRM activity during development using Drosophila transgenic embryos. In over half the cases, very simple elements containing only one or two types of TF binding motifs were capable of driving specific spatio-temporal patterns during development. Different motif organizations provide different degrees of robustness to enhancer activity, ranging from binary on-off responses to more subtle effects including embryo-to-embryo and within-embryo variation. By quantifying the effects of subtle changes in motif organization, we were able to model biophysical rules that explain CRM behavior and may contribute to the spatial positioning of CRM activity in vivo. For the same enhancer, the effects of small differences in motif positions varied in developmentally related tissues, suggesting that gene expression may be more susceptible to sequence variation in one tissue compared to another. This result has important implications for human eQTL studies in which many associated mutations are found in cis-regulatory regions, though the mechanism for how they affect tissue-specific gene expression is often not understood. PMID:24391522

Somatostatin displayed on filamentous phage as a receptor-specific agonist

PubMed Central

Rousch, Mat; Lutgerink, Jan T; Coote, James; de Bruïne, Adriaan; Arends, Jan-Willem; Hoogenboom, Hennie R

1998-01-01

In search of methods to identify bio-active ligands specific for G protein-coupled receptors with seven transmembrane spanning regions, we have developed a filamentous phage-based selection and functional screening method. First, methods for panning peptide phage on cells were established, using the hormone somatostatin as a model. Somatostatin was displayed on the surface of filamentous phage by cloning into phage(mid) vectors and fusion to either pIII or pVIII viral coat proteins. Peptide displaying phage bound to a polyclonal anti-somatostatin serum, and, more importantly, to several somatostatin receptor subtypes (Sst) expressed on transfected CHO-K1 cells, in a pattern which was dependent on the used display method. Binding was competed with somatostatin, with an IC50 in the nanomolar range. The phage were specifically enriched by panning on cells, establishing conditions for cell selections of phage libraries. Binding of somatostatin displaying phage to sst2 on a reporter cell line, in which binding of natural ligand reduces secretion of alkaline phosphatase (via a cyclic AMP responsive element sensitive promoter), proved that the phage particles act as receptor-specific agonists. Less than 100 phage particles per cell were required for this activity, which is approximately 1000 fold less than soluble somatostatin, suggesting that phage binding interferes with normal receptor desensitization and/or recycling. The combination of biopanning of phage libraries on cells with functional screening of phage particles for receptor triggering activity, may be used to select novel, bio-active ligands from phage libraries of random peptides, antibody fragments, or libraries based on the natural receptor ligand. PMID:9776337

Single molecule optical measurements of orientation and rotations of biological macromolecules.

PubMed

Shroder, Deborah Y; Lippert, Lisa G; Goldman, Yale E

2016-11-22

Subdomains of macromolecules often undergo large orientation changes during their catalytic cycles that are essential for their activity. Tracking these rearrangements in real time opens a powerful window into the link between protein structure and functional output. Site-specific labeling of individual molecules with polarized optical probes and measurement of their spatial orientation can give insight into the crucial conformational changes, dynamics, and fluctuations of macromolecules. Here we describe the range of single molecule optical technologies that can extract orientation information from these probes, review the relevant types of probes and labeling techniques, and highlight the advantages and disadvantages of these technologies for addressing specific inquiries.

A disposable tear glucose biosensor--part 3: assessment of enzymatic specificity.

PubMed

Lan, Kenneth; McAferty, Kenyon; Shah, Pankti; Lieberman, Erica; Patel, Dharmendra R; Cook, Curtiss B; La Belle, Jeffrey T

2011-09-01

A concept for a tear glucose sensor based on amperometric measurement of enzymatic oxidation of glucose was previously presented, using glucose dehydrogenase flavin adenine dinucleotide (GDH-FAD) as the enzyme. Glucose dehydrogenase flavin adenine dinucleotide is further characterized in this article and evaluated for suitability in glucose-sensing applications in purified tear-like saline, with specific attention to the effect of interfering substances only. These interferents are specifically saccharides that could interact with the enzymatic activity seen in the sensor's performance. Bench top amperometric glucose assays were performed using an assay solution of GDH-FAD and ferricyanide redox mediator with samples of glucose, mannose, lactose, maltose, galactose, fructose, sucrose, and xylose at varying concentrations to evaluate specificity, linear dynamic range, signal size, and signal-to-noise ratio. A comparison study was done by substituting an equivalent activity unit concentration of glucose oxidase (GOx) for GDH-FAD. Glucose dehydrogenase flavin adenine dinucleotide was found to be more sensitive than GOx, producing larger oxidation currents than GOx on an identical glucose concentration gradient, and GDH-FAD exhibited larger slope response (-5.65 × 10(-7) versus -3.11 × 10(-7) A/mM), signal-to-noise ratio (18.04 versus 2.62), and linear dynamic range (0-30 versus 0-10 mM), and lower background signal (-7.12 versus -261.63 nA) than GOx under the same assay conditions. GDH-FAD responds equally to glucose and xylose but is otherwise specific for glucose. Glucose dehydrogenase flavin adenine dinucleotide compares favorably with GOx in many sensor-relevant attributes and may enable measurement of glucose concentrations both higher and lower than those measurable by GOx. GDH-FAD is a viable enzyme to use in the proposed amperometric tear glucose sensor system and perhaps also in detecting extreme hypoglycemia or hyperglycemia in blood. © 2011 Diabetes Technology Society.

A Disposable Tear Glucose Biosensor—Part 3: Assessment of Enzymatic Specificity

PubMed Central

Lan, Kenneth; McAferty, Kenyon; Shah, Pankti; Lieberman, Erica; Patel, Dharmendra R; Cook, Curtiss B; La Belle, Jeffrey T

2011-01-01

Background A concept for a tear glucose sensor based on amperometric measurement of enzymatic oxidation of glucose was previously presented, using glucose dehydrogenase flavin adenine dinucleotide (GDH-FAD) as the enzyme. Glucose dehydrogenase flavin adenine dinucleotide is further characterized in this article and evaluated for suitability in glucose-sensing applications in purified tear-like saline, with specific attention to the effect of interfering substances only. These interferents are specifically saccharides that could interact with the enzymatic activity seen in the sensor's performance. Methods Bench top amperometric glucose assays were performed using an assay solution of GDH-FAD and ferricyanide redox mediator with samples of glucose, mannose, lactose, maltose, galactose, fructose, sucrose, and xylose at varying concentrations to evaluate specificity, linear dynamic range, signal size, and signal-to-noise ratio. A comparison study was done by substituting an equivalent activity unit concentration of glucose oxidase (GOx) for GDH-FAD. Results Glucose dehydrogenase flavin adenine dinucleotide was found to be more sensitive than GOx, producing larger oxidation currents than GOx on an identical glucose concentration gradient, and GDH-FAD exhibited larger slope response (-5.65 × 10-7 versus -3.11 × 10-7 A/mM), signal-to-noise ratio (18.04 versus 2.62), and linear dynamic range (0–30 versus 0–10 mM), and lower background signal (-7.12 versus -261.63 nA) than GOx under the same assay conditions. GDH-FAD responds equally to glucose and xylose but is otherwise specific for glucose. Conclusion Glucose dehydrogenase flavin adenine dinucleotide compares favorably with GOx in many sensor-relevant attributes and may enable measurement of glucose concentrations both higher and lower than those measurable by GOx. GDH-FAD is a viable enzyme to use in the proposed amperometric tear glucose sensor system and perhaps also in detecting extreme hypoglycemia or hyperglycemia in blood. PMID:22027303

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

Shamoo, D.A.; Johnson, T.R.; Trim, S.C.

We investigated summer activity patterns in a panel of volunteers drawn from a population segment with potentially high exposure to ambient oxidant pollution. The subjects were 15 men and 5 women aged 19-50, all of whom worked outdoors in the Los Angeles area at least 10 hr per week. The general approach was to (i) calibrate the relationship between ventilation rate (VR) and heart rate (HR) for each subject in controlled exercise; (ii) have subjects monitor their own normal activities with diaries and electronic HR recorders; (iii) estimate VR from HR recordings; and (iv) relate VR with diary descriptions ofmore » activities. Calibration data were fit to the equation log (VR) = (intercept) + (slope x HR), intercept and slope being determined separately for each individual to provide a specific equation to predict her/his VR from measured HR. Individuals' correlation coefficients relating log (VR) with HR ranged from 0.83 to 0.95. Subjects monitored themselves for three 24-hr periods during one week, including their most active work day and their most active non-work day. They wore Heart Watch(R) athletic training instruments which recorded HR once per minute; and recorded each change in their activity, location, or breathing rate in diaries. Breathing rates were classified as sleep, slow, medium, or fast. Diaries showed that sleep occupied about 33% of subject's time, slow activity 59%, medium 7%, and fast 1%. Fast activity was reported only at leisure, never at work. For the group, arithmetic means and standard deviations of predicted VR were 7 +/- 3 L/min for sleep, 12 +/- 7 for slow activity, 14 +/- 8 for medium, and 44 +/- 36 for fast. For the group and for most individuals, distributions of predicted VR within a given activity level (breathing rate) were approximately lognormal, with many values in a narrow range below the arithmetic mean and fewer values in a broader range above it.« less

Rapid Diagnosis of Smear-Negative Tuberculosis Using Immunology and Microbiology with Induced Sputum in HIV-Infected and Uninfected Individuals

PubMed Central

Breen, Ronan A. M.; Hardy, Gareth A. D.; Perrin, Felicity M. R.; Lear, Sara; Kinloch, Sabine; Smith, Colette J.; Cropley, Ian; Janossy, George; Lipman, Marc C. I.

2007-01-01

Rationale and Objectives Blood-based studies have demonstrated the potential of immunological assays to detect tuberculosis. However lung fluid sampling may prove superior as it enables simultaneous microbiological detection of mycobacteria to be performed. Until now this has only been possible using the expensive and invasive technique of broncho-alveolar lavage. We sought to evaluate an immunoassay using non-invasive induced-sputum to diagnose active tuberculosis. Methods and Results Prospective cohort study of forty-two spontaneous sputum smear-negative or sputum non-producing adults under investigation for tuberculosis. CD4 lymphocytes specific to purified-protein-derivative of Mycobacterium tuberculosis actively synthesising interferon-gamma were measured by flow cytometry and final diagnosis compared to immunoassay using a cut-off of 0.5%. Sixteen subjects (38%) were HIV-infected (median CD4 count [range] = 332 cells/µl [103–748]). Thirty-eight (90%) were BCG-vaccinated. In 27 subjects diagnosed with active tuberculosis, the median [range] percentage of interferon-gamma synthetic CD4+ lymphocytes was 2.77% [0–23.93%] versus 0% [0–2.10%] in 15 negative for active infection (p<0.0001). Sensitivity and specificity of the immunoassay versus final diagnosis of active tuberculosis were 89% (24 of 27) and 80% (12 of 15) respectively. The 3 positive assays in the latter group occurred in subjects diagnosed with quiescent/latent tuberculosis. Assay performance was unaffected by HIV-status, BCG-vaccination or disease site. Combining this approach with traditional microbiological methods increased the diagnostic yield to 93% (25 of 27) alongside acid-fast bacilli smear and 96% (26 of 27) alongside tuberculosis culture. Conclusions These data demonstrate for the first time that a rapid immunological assay to diagnose active tuberculosis can be performed successfully in combination with microbiological methods on a single induced-sputum sample. PMID:18092001

Characterization of the receptor-destroying enzyme activity from infectious salmon anaemia virus.

PubMed

Kristiansen, Marianne; Frøystad, Marianne K; Rishovd, Anne Lise; Gjøen, Tor

2002-11-01

Infectious salmon anaemia virus (ISAV) infects cells via the endocytic pathway and, like many other enveloped viruses, ISAV contains a receptor-destroying enzyme. We have analysed this acetylesterase activity with respect to substrate specificity, enzyme kinetics, inhibitors, temperature and pH stability. The ISAV acetylesterase was inhibited by di-isopropyl fluorophosphate (DFP) in a dose-dependent fashion but not by other known hydrolase inhibitors, suggesting that a serine residue is part of the active site. The pH optimum of the enzyme was in the range 7.5-8.0 and the enzymatic activity was lessened at temperatures above 40 degrees C. The effect of DFP on agglutination/elution of erythrocytes by ISAV demonstrated that the acetylesterase activity is the bona fide receptor-destroying enzyme. A haemadsorption assay was used to analyse whether the esterase was active on the surface of infected cells or not.

Personality, Emotional Qualities of Leisure, and Subjective Well-Being in the Elderly.

PubMed

Kahlbaugh, Patricia; Huffman, Loreen

2017-07-01

In this study, we examined personality traits of older adults and their emotional experiences associated with engaging in specific leisure activities. Older individuals (17 males, 32 females), ages ranging from 65 to 97 years (mean age 74), completed measures of Big Five personality traits, positive and negative affect, subjective well-being (SWB), independent functioning, and an emotion-activity inventory. As expected, Extraversion, Agreeableness, Conscientiousness, and Openness to experience were related to positive affect, while Neuroticism was related to negative affect. Openness and Agreeableness were related to positive emotions experienced in social and cognitive domains, and Agreeableness was related to greater SWB, greater positive affect, and more positively experienced activities. Neuroticism was related to lower SWB and fewer positively experienced activities. These findings suggest that assessing the fit between personality and emotions experienced during activities should be considered when creating programs tailored to elderly individuals, with the goal of encouraging more active and rewarding lives.

Engineering Translational Activators with CRISPR-Cas System.

PubMed

Du, Pei; Miao, Chensi; Lou, Qiuli; Wang, Zefeng; Lou, Chunbo

2016-01-15

RNA parts often serve as critical components in genetic engineering. Here we report a design of translational activators which is composed of an RNA endoribonuclease (Csy4) and two exchangeable RNA modules. Csy4, a member of Cas endoribonuclease, cleaves at a specific recognition site; this cleavage releases a cis-repressive RNA module (crRNA) from the masked ribosome binding site (RBS), which subsequently allows the downstream translation initiation. Unlike small RNA as a translational activator, the endoribonuclease-based activator is able to efficiently unfold the perfect RBS-crRNA pairing. As an exchangeable module, the crRNA-RBS duplex was forwardly and reversely engineered to modulate the dynamic range of translational activity. We further showed that Csy4 and its recognition site, together as a module, can also be replaced by orthogonal endoribonuclease-recognition site homologues. These modularly structured, high-performance translational activators would endow the programming of gene expression in the translation level with higher feasibility.

Effect of Low and Very Low Doses of Simple Phenolics on Plant Peroxidase Activity

PubMed Central

Malarczyk, Elżbieta; Kochmańska-Rdest, Janina; Paździoch-Czochra, Marzanna

2004-01-01

Changes in the activity of horseradish peroxidase resulting from an addition of ethanol water dilutions of 19 phenolic compounds were observed. For each compound, the enzyme activity was plotted against the degree of dilution expressed as n = –log100 (mol/L) in the range 0 ≤ n ≥ 20. All the curves showed sinusoidal activity, more or less regular, with two to four peaks on average. Each analyzed compound had a characteristic sinusoidal shape, which was constant for samples of peroxidase from various commercial firms. This was clearly visible after function fitting to experimental results based on the Marquadt–Levenberg algorithm using the least-squares method. Among the 19 phenolics, the highest amplitudes were observed for phenol and iso- and vanillate acids and aldehydes. The specific character of each of the analyzed curves offers a possibility of choosing proper dilutions of phenolic compound for activating or inhibiting of peroxidase activity. PMID:19330128

Secondary cell with orthorhombic alkali metal/manganese oxide phase active cathode material

DOEpatents

Doeff, Marca M.; Peng, Marcus Y.; Ma, Yanping; Visco, Steven J.; DeJonghe, Lutgard C.

1996-01-01

An alkali metal manganese oxide secondary cell is disclosed which can provide a high rate of discharge, good cycling capabilities, good stability of the cathode material, high specific energy (energy per unit of weight) and high energy density (energy per unit volume). The active material in the anode is an alkali metal and the active material in the cathode comprises an orthorhombic alkali metal manganese oxide which undergoes intercalation and deintercalation without a change in phase, resulting in a substantially linear change in voltage with change in the state of charge of the cell. The active material in the cathode is an orthorhombic structure having the formula M.sub.x Z.sub.y Mn.sub.(1-y) O.sub.2, where M is an alkali metal; Z is a metal capable of substituting for manganese in the orthorhombic structure such as iron, cobalt or titanium; x ranges from about 0.2 in the fully charged state to about 0.75 in the fully discharged state, and y ranges from 0 to 60 atomic %. Preferably, the cell is constructed with a solid electrolyte, but a liquid or gelatinous electrolyte may also be used in the cell.

A 5000-Fold Increase in the Specificity of a Bacterial Phosphotriesterase for Malathion through Combinatorial Active Site Mutagenesis

PubMed Central

Naqvi, Tatheer; Warden, Andrew C.; French, Nigel; Sugrue, Elena; Carr, Paul D.; Jackson, Colin J.; Scott, Colin

2014-01-01

Phosphotriesterases (PTEs) have been isolated from a range of bacterial species, including Agrobcaterium radiobacter (PTEAr), and are efficient enzymes with broad substrate ranges. The turnover rate of PTEAr for the common organophosphorous insecticide malathion is lower than expected based on its physical properties; principally the pka of its leaving group. In this study, we rationalise the turnover rate of PTEAr for malathion using computational docking of the substrate into a high resolution crystal structure of the enzyme, suggesting that malathion is too large for the PTEAr binding pocket. Protein engineering through combinatorial active site saturation testing (CASTing) was then used to increase the rate of malathion turnover. Variants from a CASTing library in which Ser308 and Tyr309 were mutated yielded variants with increased activity towards malathion. The most active PTEAr variant carried Ser308Leu and Tyr309Ala substitutions, which resulted in a ca. 5000-fold increase in k cat/K M for malathion. X-ray crystal structures for the PTEAr Ser308Leu\\Tyr309Ala variant demonstrate that the access to the binding pocket was enhanced by the replacement of the bulky Tyr309 residue with the smaller alanine residue. PMID:24721933

Secondary cell with orthorhombic alkali metal/manganese oxide phase active cathode material

DOEpatents

Doeff, M.M.; Peng, M.Y.; Ma, Y.; Visco, S.J.; DeJonghe, L.C.

1996-09-24

An alkali metal manganese oxide secondary cell is disclosed which can provide a high rate of discharge, good cycling capabilities, good stability of the cathode material, high specific energy (energy per unit of weight) and high energy density (energy per unit volume). The active material in the anode is an alkali metal and the active material in the cathode comprises an orthorhombic alkali metal manganese oxide which undergoes intercalation and deintercalation without a change in phase, resulting in a substantially linear change in voltage with change in the state of charge of the cell. The active material in the cathode is an orthorhombic structure having the formula M{sub x}Z{sub y}Mn{sub (1{minus}y)}O{sub 2}, where M is an alkali metal; Z is a metal capable of substituting for manganese in the orthorhombic structure such as iron, cobalt or titanium; x ranges from about 0.2 in the fully charged state to about 0.75 in the fully discharged state, and y ranges from 0 to 60 atomic %. Preferably, the cell is constructed with a solid electrolyte, but a liquid or gelatinous electrolyte may also be used in the cell. 11 figs.

Diterpenoids from Azorella compacta (Umbelliferae) active on Trypanosoma cruzi.

PubMed

Araya, Jorge E; Neira, Iván; da Silva, Solange; Mortara, Renato A; Manque, Patricio; Cordero, Esteban; Sagua, Hernán; Loyola, Alberto; Bórquez, Jorge; Morales, Glauco; González, Jorge

2003-04-01

The anti-Trypanosoma cruzi activity of natural products isolated from Azorella compacta was evaluated, with particular emphasis on their effect against intracellular amastigotes. Five diterpenoids from A. compacta derived from mulinane and azorellane were isolated and identified. Only two products, named azorellanol (Y-2) and mulin-11,3-dien-20-oic acid (Y-5), showed trypanocidal activity against all stages of T. cruzi including intracellular amastigotes. At 10 M, these compounds displayed a strong lytic activity. It ranged from 88.4 0.6 to 99.0 1 % for all strains and stages evaluate, with an IC50 /18 h values of 20-84 M and 41-87 M, respectively. The development of intracellular amastigotes was also inhibited by nearly 60% at 25 M. The trypanocidal molecules Y-2 and Y-5 did show different degrees of cytotoxicity depending on the cell line tested, with an IC50 /24 h ranging from 33.2 to 161.2 M. We evaluated the effect of diterpenoids against intracellular T. cruzi forms by immunofluorescent identification of a specific membrane molecular marker (Ssp-4 antigen) of the T. cruzi amastigote forms. The accuracy and reproducibility of the measurements were found to be outstanding when examined by confocal microscopy.

Cross-continental comparison of the association between the physical environment and active transportation in children: a systematic review.

PubMed

D'Haese, Sara; Vanwolleghem, Griet; Hinckson, Erica; De Bourdeaudhuij, Ilse; Deforche, Benedicte; Van Dyck, Delfien; Cardon, Greet

2015-11-26

The purpose of this systematic review was to determine the relationship between a wide range of physical environmental characteristics and different contexts of active transportation in 6- to 12-year-old children across different continents. A systematic search was conducted in six databases (Pubmed, Web of Science, Cinahl, SportDiscus, TRIS and Cochrane) resulting in 65 papers, eligible for inclusion. The investigated physical environmental variables were grouped into six categories: walkability, accessibility, walk/cycle facilities, aesthetics, safety, recreation facilities. The majority of the studies were conducted in North America (n = 35), Europe (n = 17) and Australia (n = 11). Active transportation to school (walking or cycling) was positively associated with walkability. Walking to school was positively associated with walkability, density and accessibility. Evidence for a possible association was found for traffic safety and all forms of active transportation to school. No convincing evidence was found for associations between the physical environment and active transportation during leisure. General safety and traffic safety were associated with active transportation to school in North America and Australia but not associated with active transportation to school in Europe. The physical environment was mainly associated with active transportation to school. Continent specific associations were found, indicating that safety measures were most important in relation to active commuting to school in North America and Australia. There is a need for longitudinal studies and studies conducted in Asia, Africa and South-America and studies focusing specifically on active transportation during leisure.

On the feasibility of automatic detection of range deviations from in-beam PET data

NASA Astrophysics Data System (ADS)

Helmbrecht, S.; Santiago, A.; Enghardt, W.; Kuess, P.; Fiedler, F.

2012-03-01

In-beam PET is a clinically proven method for monitoring ion beam cancer treatment. The objective is predominantly the verification of the range of the primary particles. Due to different processes leading to dose and activity, evaluation is done by comparing measured data to simulated. Up to now, the comparison is performed by well-trained observers (clinicians, physicists). This process is very time consuming and low in reproducibility. However, an automatic method is desirable. A one-dimensional algorithm for range comparison has been enhanced and extended to three dimensions. System-inherent uncertainties are handled by means of a statistical approach. To test the method, a set of data was prepared. Distributions of β+-activity calculated from treatment plans were compared to measurements performed in the framework of the German Heavy Ion Tumor Therapy Project at GSI Helmholtz Centre for Heavy Ion Research, Darmstadt, Germany. Artificial range deviations in the simulations served as test objects for the algorithm. Range modifications of different depth (4, 6 and 10 mm water equivalent path length) can be detected. Even though the sensitivity and specificity of a visual evaluation are higher, the method is feasible as the basis for the selection of patients from the data pool for retrospective evaluation of treatment and treatment plans and correlation with follow-up data. Furthermore, it can be used for the development of an assistance tool for a clinical application.

Structural mechanism underlying capsaicin binding and activation of TRPV1 ion channel

PubMed Central

Cheng, Wei; Yang, Wei; Yu, Peilin; Song, Zhenzhen; Yarov-Yarovoy, Vladimir; Zheng, Jie

2015-01-01

Capsaicin bestows spiciness by activating TRPV1 channel with exquisite potency and selectivity. Capsaicin-bound channel structure was previously resolved by cryo-EM at 4.2-to-4.5 Å resolution, however important details required for mechanistic understandings are unavailable: capsaicin was registered as a small electron density, reflecting neither its chemical structure nor specific ligand-channel interactions. We obtained the missing atomic-level details by iterative computation, which were confirmed by systematic site-specific functional tests. We observed that the bound capsaicin takes “tail-up, head-down” configurations. The vanillyl and amide groups form specific interactions to anchor its bound position, while the aliphatic tail may sample a range of conformations, making it invisible in cryo-EM images. Capsaicin stabilizes the open state by “pull-and-contact” interactions between the vanillyl group and the S4-S5 linker. Our study provided a structural mechanism for the agonistic function of capsaicin and its analogs, and demonstrated an effective approach to obtain atomic level information from cryo-EM structures. PMID:26053297

Antibodies elicited by the first non-viral prophylactic cancer vaccine show tumor-specificity and immunotherapeutic potential

PubMed Central

Lohmueller, Jason J.; Sato, Shuji; Popova, Lana; Chu, Isabel M.; Tucker, Meghan A.; Barberena, Roberto; Innocenti, Gregory M.; Cudic, Mare; Ham, James D.; Cheung, Wan Cheung; Polakiewicz, Roberto D.; Finn, Olivera J.

2016-01-01

MUC1 is a shared tumor antigen expressed on >80% of human cancers. We completed the first prophylactic cancer vaccine clinical trial based on a non-viral antigen, MUC1, in healthy individuals at-risk for colon cancer. This trial provided a unique source of potentially effective and safe immunotherapeutic drugs, fully-human antibodies affinity-matured in a healthy host to a tumor antigen. We purified, cloned, and characterized 13 IgGs specific for several tumor-associated MUC1 epitopes with a wide range of binding affinities. These antibodies bind hypoglycosylated MUC1 on human cancer cell lines and tumor tissues but show no reactivity against fully-glycosylated MUC1 on normal cells and tissues. We found that several antibodies activate complement-mediated cytotoxicity and that T cells carrying chimeric antigen receptors with the antibody variable regions kill MUC1+ target cells, express activation markers, and produce interferon gamma. Fully-human and tumor-specific, these antibodies are candidates for further testing and development as immunotherapeutic drugs. PMID:27545199

Aldehyde Dehydrogenases in Arabidopsis thaliana: Biochemical Requirements, Metabolic Pathways, and Functional Analysis.

PubMed

Stiti, Naim; Missihoun, Tagnon D; Kotchoni, Simeon O; Kirch, Hans-Hubert; Bartels, Dorothea

2011-01-01

Aldehyde dehydrogenases (ALDHs) are a family of enzymes which catalyze the oxidation of reactive aldehydes to their corresponding carboxylic acids. Here we summarize molecular genetic and biochemical analyses of selected ArabidopsisALDH genes. Aldehyde molecules are very reactive and are involved in many metabolic processes but when they accumulate in excess they become toxic. Thus activity of aldehyde dehydrogenases is important in regulating the homeostasis of aldehydes. Overexpression of some ALDH genes demonstrated an improved abiotic stress tolerance. Despite the fact that several reports are available describing a role for specific ALDHs, their precise physiological roles are often still unclear. Therefore a number of genetic and biochemical tools have been generated to address the function with an emphasis on stress-related ALDHs. ALDHs exert their functions in different cellular compartments and often in a developmental and tissue specific manner. To investigate substrate specificity, catalytic efficiencies have been determined using a range of substrates varying in carbon chain length and degree of carbon oxidation. Mutational approaches identified amino acid residues critical for coenzyme usage and enzyme activities.

Long-range population dynamics of anatomically defined neocortical networks

PubMed Central

Chen, Jerry L; Voigt, Fabian F; Javadzadeh, Mitra; Krueppel, Roland; Helmchen, Fritjof

2016-01-01

The coordination of activity across neocortical areas is essential for mammalian brain function. Understanding this process requires simultaneous functional measurements across the cortex. In order to dissociate direct cortico-cortical interactions from other sources of neuronal correlations, it is furthermore desirable to target cross-areal recordings to neuronal subpopulations that anatomically project between areas. Here, we combined anatomical tracers with a novel multi-area two-photon microscope to perform simultaneous calcium imaging across mouse primary (S1) and secondary (S2) somatosensory whisker cortex during texture discrimination behavior, specifically identifying feedforward and feedback neurons. We find that coordination of S1-S2 activity increases during motor behaviors such as goal-directed whisking and licking. This effect was not specific to identified feedforward and feedback neurons. However, these mutually projecting neurons especially participated in inter-areal coordination when motor behavior was paired with whisker-texture touches, suggesting that direct S1-S2 interactions are sensory-dependent. Our results demonstrate specific functional coordination of anatomically-identified projection neurons across sensory cortices. DOI: http://dx.doi.org/10.7554/eLife.14679.001 PMID:27218452

Aldehyde Dehydrogenases in Arabidopsis thaliana: Biochemical Requirements, Metabolic Pathways, and Functional Analysis

PubMed Central

Stiti, Naim; Missihoun, Tagnon D.; Kotchoni, Simeon O.; Kirch, Hans-Hubert; Bartels, Dorothea

2011-01-01

Aldehyde dehydrogenases (ALDHs) are a family of enzymes which catalyze the oxidation of reactive aldehydes to their corresponding carboxylic acids. Here we summarize molecular genetic and biochemical analyses of selected Arabidopsis ALDH genes. Aldehyde molecules are very reactive and are involved in many metabolic processes but when they accumulate in excess they become toxic. Thus activity of aldehyde dehydrogenases is important in regulating the homeostasis of aldehydes. Overexpression of some ALDH genes demonstrated an improved abiotic stress tolerance. Despite the fact that several reports are available describing a role for specific ALDHs, their precise physiological roles are often still unclear. Therefore a number of genetic and biochemical tools have been generated to address the function with an emphasis on stress-related ALDHs. ALDHs exert their functions in different cellular compartments and often in a developmental and tissue specific manner. To investigate substrate specificity, catalytic efficiencies have been determined using a range of substrates varying in carbon chain length and degree of carbon oxidation. Mutational approaches identified amino acid residues critical for coenzyme usage and enzyme activities. PMID:22639603

Normalization of Blood Pressure With Spinal Cord Epidural Stimulation After Severe Spinal Cord Injury

PubMed Central

Harkema, Susan J.; Wang, Siqi; Angeli, Claudia A.; Chen, Yangsheng; Boakye, Maxwell; Ugiliweneza, Beatrice; Hirsch, Glenn A.

2018-01-01

Chronic low blood pressure and orthostatic hypotension remain challenging clinical issues after severe spinal cord injury (SCI), affecting health, rehabilitation, and quality of life. We previously reported that targeted lumbosacral spinal cord epidural stimulation (scES) could promote stand and step functions and restore voluntary movement in patients with chronic motor complete SCI. This study addresses the effects of targeted scES for cardiovascular function (CV-scES) in individuals with severe SCI who suffer from chronic hypotension. We tested the hypothesis that CV-scES can increase resting blood pressure and attenuate chronic hypotension in individuals with chronic cervical SCI. Four research participants with chronic cervical SCI received an implant of a 16-electrode array on the dura (L1–S1 cord segments, T11–L1 vertebrae). Individual-specific CV-scES configurations (anode and cathode electrode selection, voltage, frequency, and pulse width) were identified to maintain systolic blood pressure within targeted normative ranges without skeletal muscle activity of the lower extremities as assessed by electromyography. These individuals completed five 2-h sessions using CV-scES in an upright, seated position during measurement of blood pressure and heart rate. Noninvasive continuous blood pressure was measured from a finger cuff by plethysmograph technique. For each research participant there were statistically significant increases in mean arterial pressure in response to CV-scES that was maintained within normative ranges. This result was reproducible over the five sessions with concomitant decreases or no changes in heart rate using individual-specific CV-scES that was modulated with modest amplitude changes throughout the session. Our study shows that stimulating dorsal lumbosacral spinal cord can effectively and safely activate mechanisms to elevate blood pressures to normal ranges from a chronic hypotensive state in humans with severe SCI with individual-specific CV-scES. PMID:29568266

Structural insights into GDP-mediated regulation of a bacterial acyl-CoA thioesterase.

PubMed

Khandokar, Yogesh B; Srivastava, Parul; Cowieson, Nathan; Sarker, Subir; Aragao, David; Das, Shubagata; Smith, Kate M; Raidal, Shane R; Forwood, Jade K

2017-12-15

Thioesterases catalyze the cleavage of thioester bonds within many activated fatty acids and acyl-CoA substrates. They are expressed ubiquitously in both prokaryotes and eukaryotes and are subdivided into 25 thioesterase families according to their catalytic active site, protein oligomerization, and substrate specificity. Although many of these enzyme families are well-characterized in terms of function and substrate specificity, regulation across most thioesterase families is poorly understood. Here, we characterized a TE6 thioesterase from the bacterium Neisseria meningitidis Structural analysis with X-ray crystallographic diffraction data to 2.0-Å revealed that each protein subunit harbors a hot dog-fold and that the TE6 enzyme forms a hexamer with D3 symmetry. An assessment of thioesterase activity against a range of acyl-CoA substrates revealed the greatest activity against acetyl-CoA, and structure-guided mutagenesis of putative active site residues identified Asn 24 and Asp 39 as being essential for activity. Our structural analysis revealed that six GDP nucleotides bound the enzyme in close proximity to an intersubunit disulfide bond interactions that covalently link thioesterase domains in a double hot dog dimer. Structure-guided mutagenesis of residues within the GDP-binding pocket identified Arg 93 as playing a key role in the nucleotide interaction and revealed that GDP is required for activity. All mutations were confirmed to be specific and not to have resulted from structural perturbations by X-ray crystallography. This is the first report of a bacterial GDP-regulated thioesterase and of covalent linkage of thioesterase domains through a disulfide bond, revealing structural similarities with ADP regulation in the human ACOT12 thioesterase. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Enhanced functional stability of plasminogen activator inhibitor-1 in patients with livedoid vasculopathy.

PubMed

Agirbasli, Mehmet; Eren, Mesut; Eren, Fatih; Murphy, Sheila B; Serdar, Zehra A; Seckin, Dilek; Zara, Tuba; Cem Mat, M; Demirkesen, Cuyan; Vaughan, Douglas E

2011-07-01

Livedoid vasculopathy (LV) is a chronic, recurrent, painful cutaneous disease with distinctive clinical features and an uncertain etiology. The skin lesions are recognizable by focal purpura, depigmentation and shallow ulcers. Thrombophilic conditions occur frequently in patients with LV. While no definitive treatment exists for LV, smoking cessation, antiplatelet therapy, immunosuppressive treatment, and anabolic steroids are often included in the therapeutic ladder. Recently, a possible link between LV and impaired fibrinolysis was established as cutaneous LV lesions responded to tissue plasminogen activator (t-PA) infusion suggesting that inhibition of the fibrinolysis through plasminogen activator inhibitor-1 (PAI-1) activity may determine the disease course in patients with LV. In this study, we investigated PAI-1 antigen (Ag) and activity levels in 20 patients with biopsy proven LV (mean age 26 ± 11, M/F = 7/13, median disease duration 3.5 years). All patients received antiplatelet treatment with aspirin and/or dipyrimadole and 14 patients received anabolic steroids or immunosuppressive treatment. Fasting PAI-1 Ag and activity levels were measured at 9 AM in all patients. Both Ag (34 (26) ng/ml) (median (interquartile range)) and specific activity (17 (23) IU/fmole) levels of PAI-1 were moderately elevated in LV patients compared to the controls, however, PAI-1 kinetic studies demonstrated markedly enhanced stability of PAI-1 activity in plasma from patients with LV. Specific activity at 16 h was significantly higher than expected specific activity levels (7 (11) vs. 0.07 (0.09) IU/fmole, P < 0.01). While the exact mechanism of increased stability of PAI-1 activity is not known, it may be due to post-translational modifications or increased binding affinity for a stabilizing cofactor. In conclusion, enhanced stability of PAI-1 may contribute to the pathophysiology of LV, and systemic or local treatment with PAI-1 inhibitors may offer a potential treatment alternative in patients with LV.

Phylogenetic and experimental characterization of an acyl-ACP thioesterase family reveals significant diversity in enzymatic specificity and activity.

PubMed

Jing, Fuyuan; Cantu, David C; Tvaruzkova, Jarmila; Chipman, Jay P; Nikolau, Basil J; Yandeau-Nelson, Marna D; Reilly, Peter J

2011-08-10

Acyl-acyl carrier protein thioesterases (acyl-ACP TEs) catalyze the hydrolysis of the thioester bond that links the acyl chain to the sulfhydryl group of the phosphopantetheine prosthetic group of ACP. This reaction terminates acyl chain elongation of fatty acid biosynthesis, and in plant seeds it is the biochemical determinant of the fatty acid compositions of storage lipids. To explore acyl-ACP TE diversity and to identify novel acyl ACP-TEs, 31 acyl-ACP TEs from wide-ranging phylogenetic sources were characterized to ascertain their in vivo activities and substrate specificities. These acyl-ACP TEs were chosen by two different approaches: 1) 24 TEs were selected from public databases on the basis of phylogenetic analysis and fatty acid profile knowledge of their source organisms; and 2) seven TEs were molecularly cloned from oil palm (Elaeis guineensis), coconut (Cocos nucifera) and Cuphea viscosissima, organisms that produce medium-chain and short-chain fatty acids in their seeds. The in vivo substrate specificities of the acyl-ACP TEs were determined in E. coli. Based on their specificities, these enzymes were clustered into three classes: 1) Class I acyl-ACP TEs act primarily on 14- and 16-carbon acyl-ACP substrates; 2) Class II acyl-ACP TEs have broad substrate specificities, with major activities toward 8- and 14-carbon acyl-ACP substrates; and 3) Class III acyl-ACP TEs act predominantly on 8-carbon acyl-ACPs. Several novel acyl-ACP TEs act on short-chain and unsaturated acyl-ACP or 3-ketoacyl-ACP substrates, indicating the diversity of enzymatic specificity in this enzyme family. These acyl-ACP TEs can potentially be used to diversify the fatty acid biosynthesis pathway to produce novel fatty acids.

Phylogenetic and experimental characterization of an acyl-ACP thioesterase family reveals significant diversity in enzymatic specificity and activity

PubMed Central

2011-01-01

Background Acyl-acyl carrier protein thioesterases (acyl-ACP TEs) catalyze the hydrolysis of the thioester bond that links the acyl chain to the sulfhydryl group of the phosphopantetheine prosthetic group of ACP. This reaction terminates acyl chain elongation of fatty acid biosynthesis, and in plant seeds it is the biochemical determinant of the fatty acid compositions of storage lipids. Results To explore acyl-ACP TE diversity and to identify novel acyl ACP-TEs, 31 acyl-ACP TEs from wide-ranging phylogenetic sources were characterized to ascertain their in vivo activities and substrate specificities. These acyl-ACP TEs were chosen by two different approaches: 1) 24 TEs were selected from public databases on the basis of phylogenetic analysis and fatty acid profile knowledge of their source organisms; and 2) seven TEs were molecularly cloned from oil palm (Elaeis guineensis), coconut (Cocos nucifera) and Cuphea viscosissima, organisms that produce medium-chain and short-chain fatty acids in their seeds. The in vivo substrate specificities of the acyl-ACP TEs were determined in E. coli. Based on their specificities, these enzymes were clustered into three classes: 1) Class I acyl-ACP TEs act primarily on 14- and 16-carbon acyl-ACP substrates; 2) Class II acyl-ACP TEs have broad substrate specificities, with major activities toward 8- and 14-carbon acyl-ACP substrates; and 3) Class III acyl-ACP TEs act predominantly on 8-carbon acyl-ACPs. Several novel acyl-ACP TEs act on short-chain and unsaturated acyl-ACP or 3-ketoacyl-ACP substrates, indicating the diversity of enzymatic specificity in this enzyme family. Conclusion These acyl-ACP TEs can potentially be used to diversify the fatty acid biosynthesis pathway to produce novel fatty acids. PMID:21831316

Human Monoclonal Antibodies Against a Plethora of Viral Pathogens From Single Combinatorial Libraries

NASA Astrophysics Data System (ADS)

Williamson, R. Anthony; Burioni, Roberto; Sanna, Pietro P.; Partridge, Lynda J.; Barbas, Carlos F., III; Burton, Dennis R.

1993-05-01

Conventional antibody generation usually requires active immunization with antigen immediately prior to the preparation procedure. Combinatorial antibody library technology offers the possibility of cloning a range of antibody specificities at a single point in time and then accessing these specificities at will. Here we show that human monoclonal antibody Fab fragments against a plethora of infectious agents can be readily derived from a single library. Further examination of a number of libraries shows that whenever antibody against a pathogen can be detected in the serum of the donor, then specific antibodies can be derived from the corresponding library. We describe the generation of human Fab fragments against herpes simplex virus types 1 and 2, human cytomegalovirus, varicella zoster virus, rubella, human immunodeficiency virus type 1, and respiratory syncytial virus. The antibodies are shown to be highly specific and a number are effective in neutralizing virus in vitro.

Variations in teenage birth rates, 1991-98: national and state trends.

PubMed

Ventura, S J; Curtin, S C; Mathews, T J

2000-04-24

This report presents national birth rates for teenagers for 1991-98 and the percent change, 1991-98. State-specific teenage birth rates by age, race, and Hispanic origin for 1991 and 1998 and the percent change, 1991 to 1998, are also presented. Tabular and graphical descriptions of the trends in teenage birth rates for the Nation and each State, by age group, race, and Hispanic origin of the mother, are discussed. Birth rates for teenagers 15-19 years declined nationally between 1991 and 1998 for all age and race and Hispanic origin populations, with the steepest declines recorded for black teenagers. State-specific rates fell significantly in all States for ages 15-19 years; declines ranged from 10 to 38 percent. In general, rates by State fell more for younger than for older teenagers, ranging by State from 10 to 46 percent for ages 15-17 years. Statistically significant reductions for older teenagers ranged from 3 to 39 percent. Reductions by State were largest for black teenagers 15-19 years, with rates falling 30 percent or more in 15 States. Among the factors accounting for these declines are decreased sexual activity, increases in condom use, and the adoption of the implant and injectable contraceptives.

Antimicrobial potential of Australian macrofungi extracts against foodborne and other pathogens.

PubMed

Bala, Neeraj; Aitken, Elizabeth A B; Cusack, Andrew; Steadman, Kathryn J

2012-03-01

Basidiomycetous macrofungi have therapeutic potential due to antimicrobial activity but little information is available for Australian macrofungi. Therefore, the present study investigated 12 Australian basidiomycetous macrofungi, previously shown to have promising activity against Staphylococcus aureus and Escherichia coli, for their antimicrobial potential against a range of other clinically relevant micro-organisms. Fruiting bodies were collected from across Queensland, Australia, freeze-dried and sequentially extracted with water and ethanol. The crude extracts were tested at 10 mg/mL and 1 mg/mL against six pathogens including two Gram-positive and two Gram-negative bacteria along with two fungi using a high throughput 96-well microplate bioassay. A degree of specificity in activity was exhibited by the water extract of Ramaria sp. (Gomphaceae) and the ethanol extracts of Psathyrella sp. (Psathyrellaceae) and Hohenbuehelia sp., which inhibited the growth of the two fungal pathogens used in the assay. Similarly, the ethanol extract of Fomitopsis lilacinogilva (Fomitopsidaceae) was active against the Gram-positive bacteria B. cereus only. Activity against a wider range of the microorganisms used in the assay was exhibited by the ethanol extract of Ramaria sp. and the water extract of Hohenbuehelia sp. (Pleurotaceae). These macrofungi can serve as new sources for the discovery and development of much needed new antimicrobials. Copyright © 2011 John Wiley & Sons, Ltd.

Voltage-independent inhibition of Ca(V)2.2 channels is delimited to a specific region of the membrane potential in rat SCG neurons.

PubMed

Vivas, Oscar; Arenas, Isabel; García, David E

2012-06-01

Neurotransmitters and hormones regulate Ca(V)2.2 channels through a voltage-independent pathway which is not well understood. It has been suggested that this voltage-independent inhibition is constant at all membrane voltages. However, changes in the percent of voltage-independent inhibition of Ca(V)2.2 have not been tested within a physiological voltage range. Here, we used a double-pulse protocol to isolate the voltage-independent inhibition of Ca(V)2.2 channels induced by noradrenaline in rat superior cervical ganglion neurons. To assess changes in the percent of the voltage-independent inhibition, the activation voltage of the channels was tested between -40 and +40 mV. We found that the percent of voltage-independent inhibition induced by noradrenaline changed with the activation voltage used. In addition, voltage-independent inhibition induced by oxo-M, a muscarinic agonist, exhibited the same dependence on activation voltage, which supports that this pattern is not exclusive for adrenergic activation. Our results suggested that voltage-independent inhibition of Ca(V)2.2 channels depends on the activation voltage of the channel in a physiological voltage range. This may have relevant implications in the understanding of the mechanism involved in voltage-independent inhibition.

Effects of Age, Task Performance, and Structural Brain Development on Face Processing

PubMed Central

Cohen Kadosh, Kathrin; Johnson, Mark H; Dick, Frederic; Cohen Kadosh, Roi; Blakemore, Sarah-Jayne

2013-01-01

In this combined structural and functional MRI developmental study, we tested 48 participants aged 7–37 years on 3 simple face-processing tasks (identity, expression, and gaze task), which were designed to yield very similar performance levels across the entire age range. The same participants then carried out 3 more difficult out-of-scanner tasks, which provided in-depth measures of changes in performance. For our analysis we adopted a novel, systematic approach that allowed us to differentiate age- from performance-related changes in the BOLD response in the 3 tasks, and compared these effects to concomitant changes in brain structure. The processing of all face aspects activated the core face-network across the age range, as well as additional and partially separable regions. Small task-specific activations in posterior regions were found to increase with age and were distinct from more widespread activations that varied as a function of individual task performance (but not of age). Our results demonstrate that activity during face-processing changes with age, and these effects are still observed when controlling for changes associated with differences in task performance. Moreover, we found that changes in white and gray matter volume were associated with changes in activation with age and performance in the out-of-scanner tasks. PMID:22661406

Site Safety Plan for Lawrence Livermore National Laboratory CERCLA investigations

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

Bainer, R.; Duarte, J.

1993-07-01

The safety policy of LLNL is to take every reasonable precaution in the performance of work to protect the environment and the health and safety of employees and the public, and to prevent property damage. With respect to hazardous agents, this protection is provided by limiting human exposures, releases to the environment, and contamination of property to levels that are as low as reasonably achievable (ALARA). It is the intent of this Plan to supply the broad outline for completing environmental investigations within ALARA guidelines. It may not be possible to determine actual working conditions in advance of the work;more » therefore, planning must allow the opportunity to provide a range of protection based upon actual working conditions. Requirements will be the least restrictive possible for a given set of circumstances, such that work can be completed in an efficient and timely fashion. Due to the relatively large size of the LLNL Site and the different types of activities underway, site-specific Operational Safety Procedures (OSPs) will be prepared to supplement activities not covered by this Plan. These site-specific OSPs provide the detailed information for each specific activity and act as an addendum to this Plan, which provides the general plan for LLNL Main Site operation.« less

Factors affecting oxygen consumption in wild-caught yellow-bellied marmots (Marmota flaviventris).

PubMed

Armitage, K B; Salsbury, C M

1992-12-01

1. All age groups gained mass during the active season, but mass-gain of adult females was delayed during lactation. 2. The relationship of body mass to metabolic rate varied widely; when the relationship was significant, R2 varied from 10.3 to 72.6%. Body mass affects VO2 more during lactation than at any other period. 3. Mean VO2 of adult males was higher in June than that of adult, non-lactating females. 4. VO2 of reproductive females was significantly higher during lactation than during gestation or postlactation because specific VO2 varied. Specific VO2 of non-reproductive females declined over the active season. 5. Specific VO2 of all age groups declined between the premolt and postmolt periods. The reduced maintenance costs can contribute 20-46% to daily growth. 6. Observed VO2 was lower than the value predicted from intraspecific or interspecific Bm:M regressions. 7. VO2 of wild-caught marmots was lower than that of marmots maintained in the laboratory, probably because of dietary differences. 8. Because basal metabolism is a stage on a food-deprivation curve, we suggest that basal metabolic rate is not an appropriate measure of the metabolic activity of free-ranging animals.

NADP-dependent enzymes are involved in response to salt and hypoosmotic stress in cucumber plants.

PubMed

Hýsková, Veronika; Plisková, Veronika; Červený, Václav; Ryšlavá, Helena

2017-07-01

Salt stress is one of the most damaging plant stressors, whereas hypoosmotic stress is not considered to be a dangerous type of stress in plants and has been less extensively studied. This study was performed to compare the metabolism of cucumber plants grown in soil with plants transferred to distilled water and to a 100 mM NaCl solution. Even though hypoosmotic stress caused by distilled water did not cause such significant changes in the relative water content, Na+/K+ ratio and Rubisco content as those caused by salt stress, it was accompanied by more pronounced changes in the specific activities of NADP-dependent enzymes. After 3 days, the specific activities of NADP-isocitrate dehydrogenase, glucose-6-phosphate dehydrogenase, NADP-malic enzyme and non-phosphorylating glyceraldehyde-3-phosphate dehydrogenase in leaves were highest under hypoosmotic stress, and lowest in plants grown in soil. In roots, salt stress caused a decrease in the specific activities of major NADP-enzymes. However, at the beginning of salt stress, NADP-galactose-1-dehydrogenase and ribose-1-dehydrogenase were involved in a plant defense response in both roots and leaves. Therefore, the enhanced demands of NADPH in stress can be replenished by a wide range of NADP-dependent enzymes.

Thresholds of physical activity associated with obesity by level of sedentary behaviour in children.

PubMed

Chaput, J-P; Barnes, J D; Tremblay, M S; Fogelholm, M; Hu, G; Lambert, E V; Maher, C; Maia, J; Olds, T; Onywera, V; Sarmiento, O L; Standage, M; Tudor-Locke, C; Katzmarzyk, P T

2018-03-24

It is unknown whether moderate-to-vigorous physical activity (MVPA) thresholds for obesity should be adapted depending on level of sedentary behaviour in children. The objective of the study is to determine the MVPA thresholds that best discriminate between obese and non-obese children, by level of screen time and total sedentary time in 12 countries. This multinational, cross-sectional study included 6522 children 9-11 years of age. MVPA and sedentary time were assessed using waist-worn accelerometry, while screen time was self-reported. Obesity was defined according to the World Health Organization reference data. Receiver operating characteristic curve analyses showed that the best thresholds of MVPA to predict obesity ranged from 53.8 to 73.9 min d -1 in boys and from 41.7 to 58.7 min d -1 in girls, depending on the level of screen time. The MVPA cut-offs to predict obesity ranged from 37.9 to 75.9 min d -1 in boys and from 32.5 to 62.7 min d -1 in girls, depending on the level of sedentary behaviour. The areas under the curve ranged from 0.57 to 0.73 ('fail' to 'fair' accuracy), and most sensitivity and specificity values were below 85%, similar to MVPA alone. Country-specific analyses provided similar findings. The addition of sedentary behaviour levels to MVPA did not result in a better predictive ability to classify children as obese/non-obese compared with MVPA alone. © 2018 World Obesity Federation.

Phosphoester hydrolysis: the incoming substrate turns the bridging hydroxido nucleophile into a terminal one.

PubMed

Gouré, Eric; Carboni, Michaël; Troussier, Angélique; Lebrun, Colette; Pécaut, Jacques; Jacquot, Jean-François; Dubourdeaux, Patrick; Clémancey, Martin; Blondin, Geneviève; Latour, Jean-Marc

2015-05-26

Identifying the active nucleophile in hydrolysis reactions catalyzed by binuclear hydrolases is a recurrent problem and a matter of intense debate. We report on the phosphate ester hydrolysis by a Fe(III)Fe(II) complex of a binucleating ligand. This complex presents activities in the range of those observed for similar biomimetic compounds in the literature. The specific electronic properties of the Fe(III)Fe(II) complex allowed us to use (1)H NMR and Mössbauer spectroscopies to investigate the nature of the various species present in the solution in the pH range of 5-10. Both techniques showed that the hydrolysis activity is associated to a μ-hydroxido Fe(III)Fe(II) species. Further (1)H NMR experiments show that binding of anions or the substrate changes this bonding mode suggesting that a terminal hydroxide is the likely nucleophile in these hydrolysis reactions. This view is further supported by the structure determination of the hydrolysis product. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Beyond conventional dose-response curves: Sensorgram comparison in SPR allows single concentration activity and similarity assessment.

PubMed

Gassner, C; Karlsson, R; Lipsmeier, F; Moelleken, J

2018-05-30

Previously we have introduced two SPR-based assay principles (dual-binding assay and bridging assay), which allow the determination of two out of three possible interaction parameters for bispecific molecules within one assay setup: two individual interactions to both targets, and/or one simultaneous/overall interaction, which potentially reflects the inter-dependency of both individual binding events. However, activity and similarity are determined by comparing report points over a concentration range, which also mirrors the way data is generated by conventional ELISA-based methods So far, binding kinetics have not been specifically considered in generic approaches for activity assessment. Here, we introduce an improved slope-ratio model which, together with a sensorgram comparison based similarity assessment, allows the development of a detailed, USP-conformal ligand binding assay using only a single sample concentration. We compare this novel analysis method to the usual concentration-range approach for both SPR-based assay principles and discuss its impact on data quality and increased sample throughput. Copyright © 2018 Elsevier B.V. All rights reserved.

How the Emitted Size Distribution and Mixing State of Feldspar Affect Ice Nucleating Particles in a Global Model

NASA Technical Reports Server (NTRS)

Perlwitz, Jan P.; Fridlind, Ann M.; Knopf, Daniel A.; Miller, Ron L.; García-Pando, Carlos Perez

2017-01-01

The effect of aerosol particles on ice nucleation and, in turn, the formation of ice and mixed phase clouds is recognized as one of the largest sources of uncertainty in climate prediction. We apply an improved dust mineral specific aerosol module in the NASA GISS Earth System ModelE, which takes into account soil aggregates and their fragmentation at emission as well as the emission of large particles. We calculate ice nucleating particle concentrations from K-feldspar abundance for an active site parameterization for a range of activation temperatures and external and internal mixing assumption. We find that the globally averaged INP concentration is reduced by a factor of two to three, compared to a simple assumption on the size distribution of emitted dust minerals. The decrease can amount to a factor of five in some geographical regions. The results vary little between external and internal mixing and different activation temperatures, except for the coldest temperatures. In the sectional size distribution, the size range 24 micrometer contributes the largest INP number.

An experimental test of the fluctuation relation in an active camphor boat system

NASA Astrophysics Data System (ADS)

Paroor, H. M.; Nambiar, N.; Bandi, M. M.

The Gallavotti-Cohen fluctuation relation (FR) posits a specific symmetry between positive and negative fluctuations in entropy production, or a related quantity (e.g power) for systems in non-equilibrium stationary state. Successful tests in a variety of systems suggest the FR may be more generally applicable than the conditions under which it was originally derived. Systems where the FR fails are therefore valuable for the insight they provide into the FR's general success. It has recently been suggested that ``active matter'' should not satisfy the fluctuation-dissipation theorem or FR. We experimentally test this possibility in a system of active camphor boats, self-propelled by surface tension gradients at air-water interfaces. The boats interact via short-range capillary attraction which competes with long-range surface tension mediated repulsion. Tuning interaction strength with number density, we test the FR through the statistics of power as one goes from a free non-interacting camphor boat, through a few weakly interacting boats to several, strongly interacting boats. We present preliminary results of our experiments and data analysis.

How the Emitted Size Distribution and Mixing State of Feldspar Affect Ice Nucleating Particles in a Global Model

NASA Astrophysics Data System (ADS)

Perlwitz, J. P.; Fridlind, A. M.; Knopf, D. A.; Miller, R. L.; Pérez García-Pando, C.

2017-12-01

The effect of aerosol particles on ice nucleation and, in turn, the formation of ice and mixed phase clouds is recognized as one of the largest sources of uncertainty in climate prediction. We apply an improved dust mineral specific aerosol module in the NASA GISS Earth System ModelE, which takes into account soil aggregates and their fragmentation at emission as well as the emission of large particles. We calculate ice nucleating particle concentrations from K-feldspar abundance for an active site parameterization for a range of activation temperatures and external and internal mixing assumption. We find that the globally averaged INP concentration is reduced by a factor of two to three, compared to a simple assumption on the size distribution of emitted dust minerals. The decrease can amount to a factor of five in some geographical regions. The results vary little between external and internal mixing and different activation temperatures, except for the coldest temperatures. In the sectional size distribution, the size range 2-4 μm contributes the largest INP number.

p21-Activated kinase inhibitors: a patent review.

PubMed

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

2012-03-01

The p21-activated kinase (PAK) family of serine/threonine protein kinases is activated by binding to the small (p21) GTP-binding proteins Cdc42 and Rac. The PAK family plays important roles in cytoskeletal organisation, cellular morphogenesis and survival, and members of this family have been implicated in a wide range of diseases including cancer, infectious diseases, neurological disorders and arthritis. The present review seeks to summarise recent (up to 2011) reports of small-molecule inhibitors of p21-activated kinases. Where patent applications describe activity against a broad range of kinases and no information was provided specifically on PAK inhibition, these are excluded from this review. In patents considered to be relevant, exemplary compounds were selected and highlighted based on their representation of the chemical matter claimed, potencies, structural features and subsequent disclosure of their properties. Selected information from non-patent literature was also included. A considerable amount of research has been devoted over the past 15 years to exploring the role of PAKs in a wide range of diseases, with a focus on oncology. Published PAK inhibitors are still comparatively rare and few exhibit satisfactory kinase selectivity and 'drug-like' properties. A key question is which profile, pan-PAK, group selective or isoform selective, holds the most promise from both therapeutic and safety standpoints. To investigate this question, isoform-selective, as well as kinome-selective, PAK inhibitor tool compounds will be needed. Pfizer was the first company to progress a PAK inhibitor (pan-PAK) to clinical development; it is expected that, despite the difficulties, other PAK inhibitors will soon follow.

NIK and IKKbeta interdependence in NF-kappaB signalling--flux analysis of regulation through metabolites.

PubMed

Kim, Hong-Bum; Evans, Iona; Smallwood, Rod; Holcombe, Mike; Qwarnstrom, Eva E

2010-02-01

Activation of the transcription factor NF-kappaB is central to control of immune and inflammatory responses. Cytokine induced activation through the classical or canonical pathway relies on degradation of the inhibitor, IkappaBalpha and regulation by the IKKbeta kinase. In addition, the NF-kappaB is activated through the NF-kappaB-inducing kinase, NIK. Analysis of the IKK/NIK inter-relationship and its impact on NF-kappaB control, were analysed by mathematical modelling, using matrix formalism and stoichiometrically balanced reactions. The analysis considered a range of bio-reactions and core metabolites and their role in relation to kinase activation and in control of specific steps of the NF-kappaB pathway. The model predicts a growth-rate and time-dependent transfer of the primary kinase activity from IKKbeta to NIK. In addition, it suggests that NIK/IKKbeta interdependence is controlled by intermediates of phosphoribosylpyrophosphate (PRPP) within the glycolysis pathway, and thus, identifies a link between specific metabolic events and kinase activation in inflammatory signal transduction. Subsequent in vitro experiments, carried out to validate the impact of IKK/NIK interdependence, confirmed signal amplification at the level of the NF-kappaB/IkappaBalpha complex control in the presence of both kinases. Further, they demonstrate that the induced potentiation is due to synergistic enhancement of relA-dependent activation. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

Improving the neutral phytase activity from Bacillus amyloliquefaciens DSM 1061 by site-directed mutagenesis.

PubMed

Xu, Wei; Shao, Rong; Wang, Zupeng; Yan, Xiuhua

2015-03-01

Neutral phytase is used as a feed additive for degradation of anti-nutritional phytate in aquatic feed industry. Site-directed mutagenesis of Bacillus amyloliquefaciens DSM 1061 phytase was performed with an aim to increase its activity. Mutation residues were chosen based on multiple sequence alignments and structure analysis of neutral phytsaes from different microorganisms. The mutation sites on surface (D148E, S197E and N156E) and around the active site (D52E) of phytase were selected. Analysis of the phytase variants showed that the specific activities of mutants D148E and S197E remarkably increased by about 35 and 13% over a temperature range of 40-75 °C at pH 7.0, respectively. The k cat of mutants D148E and S197E were 1.50 and 1.25 times than that of the wild-type phytase, respectively. Both D148E and S197E showed much higher thermostability than that of the wild-type phytase. However, mutants N156E and D52E led to significant loss of specific activity of the enzyme. Structural analysis revealed that these mutations may affect conformation of the active site of phytase. The present mutant phytases D148E and S197E with increased activities and thermostabilities have application potential as additives in aquaculture feed.

Visual impairment, visual functioning, and quality of life assessments in patients with glaucoma.

PubMed Central

Parrish, R K

1996-01-01

BACKGROUND/PURPOSE: To determine the relation between visual impairment, visual functioning, and the global quality of life in patients with glaucoma. METHODS: Visual impairment, defined with the American Medical Association Guides to the Evaluation of Permanent Impairment; visual functioning, measured with the VF-14 and the Field Test Version of the National Eye Institute-Visual Functioning Questionnaire (NEI-VFQ); and the global quality of life, assessed with the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), were determined in 147 consecutive patients with glaucoma. RESULTS: None of the SF-36 domains demonstrated more than a weak correlation with visual impairment. The VF-14 scores were moderately correlated with visual impairment. Of the twelve NEI-VFQ scales, distance activities and vision specific dependency were moderately correlated with visual impairment. Of the twelve NEI-VFQ scales, distance activities and vision specific dependency were moderately correlated with visual field impairment; vision specific social functioning, near activities, vision specific role difficulties, general vision, vision specific mental health, color vision, and driving were modestly correlated; visual pain was weakly correlated; and two were not significantly correlated. Correcting for visual actuity weakened the strength of the correlation coefficients. CONCLUSIONS: The SF-36 is unlikely to be useful in determining visual impairment in patients with glaucoma. Based on the moderate correlation between visual field impairment and the VF-14 score, this questionnaire may be generalizable to patients with glaucoma. Several of the NEI-VFQ scales correlate with visual field impairment scores in patients with a wide range of glaucomatous damage. PMID:8981717

Rapid screening for lipid storage disorders using biochemical markers. Expert center data and review of the literature.

PubMed

Voorink-Moret, M; Goorden, S M I; van Kuilenburg, A B P; Wijburg, F A; Ghauharali-van der Vlugt, J M M; Beers-Stet, F S; Zoetekouw, A; Kulik, W; Hollak, C E M; Vaz, F M

2018-02-01

In patients suspected of a lipid storage disorder (sphingolipidoses, lipidoses), confirmation of the diagnosis relies predominantly on the measurement of specific enzymatic activities and genetic studies. New UPLC-MS/MS methods have been developed to measure lysosphingolipids and oxysterols, which, combined with chitotriosidase activity may represent a rapid first tier screening for lipid storage disorders. A lysosphingolipid panel consisting of lysoglobotriaosylceramide (LysoGb3), lysohexosylceramide (LysoHexCer: both lysoglucosylceramide and lysogalactosylceramide), lysosphingomyelin (LysoSM) and its carboxylated analogue lysosphingomyelin-509 (LysoSM-509) was measured in control subjects and plasma samples of predominantly untreated patients affected with lipid storage disorders (n=74). In addition, the oxysterols cholestane-3β,5α,6β-triol and 7-ketocholesterol were measured in a subset of these patients (n=36) as well as chitotriosidase activity (n=43). A systematic review of the literature was performed to assess the usefulness of these biochemical markers. Specific elevations of metabolites, i.e. without overlap between controls and other lipid storage disorders, were found for several lysosomal storage diseases: increased LysoSM levels in acid sphingomyelinase deficiency (Niemann-Pick disease type A/B), LysoGb3 levels in males with classical phenotype Fabry disease and LysoHexCer (i.e. lysoglucosylceramide/lysogalactosylceramide) in Gaucher and Krabbe diseases. While elevated levels of LysoSM-509 and cholestane-3β,5α,6β-triol did not discriminate between Niemann Pick disease type C and acid sphingomyelinase deficiency, LysoSM-509/LysoSM ratio was specifically elevated in Niemann-Pick disease type C. In Gaucher disease type I, mild increases in several lysosphingolipids were found including LysoGb3 with levels in the range of non-classical Fabry males and females. Chitotriosidase showed specific elevations in symptomatic Gaucher disease, and was mildly elevated in all other lipid storage disorders. Review of the literature identified 44 publications. Most findings were in line with our cohort. Several moderate elevations of biochemical markers were found across a wide range of other, mainly inherited metabolic, diseases. Measurement in plasma of LysoSLs and oxysterols by UPLC-MS/MS in combination with activity of chitotriosidase provides a useful first tier screening of patients suspected of lipid storage disease. The LysoSM-509/LysoSM ratio is a promising parameter in Niemann-Pick disease type C. Further studies in larger groups of untreated patients and controls are needed to improve the specificity of the findings. Copyright © 2018 Elsevier Inc. All rights reserved.