Combining wet etching and real-time damage event imaging to reveal the most dangerous laser damage initiator in fused silica.

PubMed

Hu, Guohang; Zhao, Yuanan; Liu, Xiaofeng; Li, Dawei; Xiao, Qiling; Yi, Kui; Shao, Jianda

2013-08-01

A reliable method, combining a wet etch process and real-time damage event imaging during a raster scan laser damage test, has been developed to directly determine the most dangerous precursor inducing low-density laser damage at 355 nm in fused silica. It is revealed that ~16% of laser damage sites were initiated at the place of the scratches, ~49% initiated at the digs, and ~35% initiated at invisible defects. The morphologies of dangerous scratches and digs were compared with those of moderate ones. It is found that local sharp variation at the edge, twist, or inside of a subsurface defect is the most dangerous laser damage precursor.

Stoichiometry for binding and transport by the twin arginine translocation system.

PubMed

Celedon, Jose M; Cline, Kenneth

2012-05-14

Twin arginine translocation (Tat) systems transport large folded proteins across sealed membranes. Tat systems accomplish this feat with three membrane components organized in two complexes. In thylakoid membranes, cpTatC and Hcf106 comprise a large receptor complex containing an estimated eight cpTatC-Hcf106 pairs. Protein transport occurs when Tha4 joins the receptor complex as an oligomer of uncertain size that is thought to form the protein-conducting structure. Here, binding analyses with intact membranes or purified complexes indicate that each receptor complex could bind eight precursor proteins. Kinetic analysis of translocation showed that each precursor-bound site was independently functional for transport, and, with sufficient Tha4, all sites were concurrently active for transport. Tha4 titration determined that ∼26 Tha4 protomers were required for transport of each OE17 (oxygen-evolving complex subunit of 17 kD) precursor protein. Our results suggest that, when fully saturated with precursor proteins and Tha4, the Tat translocase is an ∼2.2-megadalton complex that can individually transport eight precursor proteins or cooperatively transport multimeric precursors.

Nanoscale liposomal formulation of a SYK P-site inhibitor against B-precursor leukemia

PubMed Central

Qazi, Sanjive; Cely, Ingrid; Sahin, Kazim; Shahidzadeh, Anoush; Ozercan, Ibrahim; Yin, Qian; Gaynon, Paul; Termuhlen, Amanda; Cheng, Jianjun

2013-01-01

We report preclinical proof of principle for effective treatment of B-precursor acute lymphoblastic leukemia (ALL) by targeting the spleen tyrosine kinase (SYK)–dependent antiapoptotic blast cell survival machinery with a unique nanoscale pharmaceutical composition. This nanoscale liposomal formulation (NLF) contains the pentapeptide mimic 1,4-Bis (9-O dihydroquinidinyl) phthalazine/hydroquinidine 1,4-phathalazinediyl diether (C61) as the first and only selective inhibitor of the substrate binding P-site of SYK. The C61 NLF exhibited a very favorable pharmacokinetic and safety profile in mice, induced apoptosis in primary B-precursor ALL blast cells taken directly from patients as well as in vivo clonogenic ALL xenograft cells, destroyed the in vivo clonogenic fraction of ALL blast cells, and, at nontoxic dose levels, exhibited potent in vivo antileukemic activity against patient-derived ALL cells in xenograft models of aggressive B-precursor ALL. Our findings establish SYK as an attractive molecular target for therapy of B-precursor ALL. Further development of the C61 NLF may provide the foundation for therapeutic innovation against therapy-refractory B-precursor ALL. PMID:23568490

EM Earthquake Precursor Detection Associated with Fluid Injection for Hydraulic Fracturing and Tectonic Sources

NASA Astrophysics Data System (ADS)

Jones, Kenneth B., II

2015-04-01

Many attempts have been made to determine an earthquake forecasting method and warn the public in turn. Presently, the animal kingdom leads the precursor list alluding to a transmission related source. By applying the animal-based model to an electromagnetic wave model, various hypotheses were formed, but only two seemed to take shape with the most interesting one requiring a magnetometer of a unique design. To date, numerous, high-end magnetometers have been in use in close proximity to fault zones for potential earthquake forecasting; however, results have had wide variability and problems still reside with what exactly is forecastable and the investigative direction of a true precursor. After a number of custom rock experiments, the two hypotheses were thoroughly tested to correlate the EM wave model. The first hypothesis involved sufficient and continuous electron movement either by surface or penetrative flow, and the second regarded a novel approach to radio wave generation. The second hypothesis resulted best with highly reproducible data, radio wave generation and detection, and worked numerous times with each laboratory test administered. In addition, internally introduced force on a small scale stressed a number of select rock types to emit radio waves well before catastrophic failure, and failure always went to completion. Comparatively, at a larger scale, highly detailed studies were procured to establish legitimate wave guides from potential hypocenters to epicenters and map the results, accordingly. Field testing in Southern California from 2006 to 2011 and outside the NE Texas town of Timpson in February, 2013 was conducted for detecting similar, laboratory generated, radio wave sources. At the Southern California field sites, signals were detected in numerous directions with varying amplitudes; therefore, a reactive approach was investigated in hopes of detecting possible aftershocks from large, tectonically related M5.0+ earthquakes. At the Timpson, Texas field sites, a proactive detection approach was taken, due to the heavy presence of hydraulic fracturing activity for regional hydrocarbon extraction, which appeared to be causing several rare M4.0+ earthquakes. As a result, detailed Southern California and Timpson, Texas field studies led to the improved design of two newer, prototype antennae and the first ever earthquake epicenter map. With more antennae and continuous monitoring, more fracture cycles can be established well ahead of the next earthquake. In addition, field data could be ascertained longer by the proper authorities and lead to significantly improved earthquake forecasting. The EM precursor determined by this method appears to surpass all prior precursor claims, and the general public may finally receive long overdue forecasting.

Two ways of legumin-precursor processing in conifers. Characterization and evolutionary relationships of Metasequoia cDNAs representing two divergent legumin gene subfamilies.

PubMed

Häger, K P; Wind, C

1997-06-15

Subunit monomers and oligomers of crystalloid-type legumins are major components of SDS-soluble fractions from Metasequoia glyptostroboides (Dawn redwood, Taxodiaceae) seed proteins. The subunits are made up of disulfide linked alpha-polypeptides and beta-polypeptides with molecular masses of 33 kDa and 23-25 kDa, respectively. Unusually for legumins, those from Metasequoia are glycosylated and the carbohydrate moieties are residing in the C-terminal region of the respective beta-polypeptides. A Metasequoia endosperm cDNA library has been constructed and legumin-encoding transcripts representing two divergent gene subfamilies have been characterized. Intersubfamily comparisons reveal 75% identity at the amino acid level and the values range from 53-35% when the legumin precursors deduced were compared with those from angiosperms. The predicted sequences together with data from amino acid sequencing prove that post-translational processing of Metasequoia prolegumins is directed to two different processing sites, each of them specific for one of the legumin subfamilies. The sites involved differ in their relative position and in the junction to be cleaved: Metasequoia legumin precursors MgLeg18 and MgLeg26 contain the conventional post-translational Asn-Gly processing site, which is generally regarded as highly conserved. In contrast, the MgLeg4 precursor is lacking this site and post-translational cleavage is directed to an unusual Asn-Thr processing site located in its hypervariable region, causing N-terminal extension of the beta-polypeptide relative to those hitherto known. Evidence is given that the unusual variant of processing also occurs in other conifers. Phylogenetic analysis reveals the precursors concerned as representatives of a distinct legumin subfamily, originating from duplication of an ancestral gene prior to or at the beginning of Taxodiaceae diversification.

Radon anomaly in soil gas as an earthquake precursor.

PubMed

Miklavcić, I; Radolić, V; Vuković, B; Poje, M; Varga, M; Stanić, D; Planinić, J

2008-10-01

The mechanical processes of earthquake preparation are always accompanied by deformations; afterwards, the complex short- or long-term precursory phenomena can appear. Anomalies of radon concentrations in soil gas are registered a few weeks or months before many earthquakes. Radon concentrations in soil gas were continuously measured by the LR-115 nuclear track detectors at site A (Osijek) during a 4-year period, as well as by the Barasol semiconductor detector at site B (Kasina) during 2 years. We investigated the influence of the meteorological parameters on the temporal radon variations, and we determined the equation of the multiple regression that enabled the reduction (deconvolution) of the radon variation caused by the barometric pressure, rainfall and temperature. The pre-earthquake radon anomalies at site A indicated 46% of the seismic events, on criterion M>or=3, R<200 km, and 21% at site B. Empirical equations between earthquake magnitude, epicenter distance and precursor time enabled estimation or prediction of an earthquake that will rise at the epicenter distance R from the monitoring site in expecting precursor time T.

Four residues of propeptide are essential for precursor folding of nattokinase.

PubMed

Jia, Yan; Cao, Xinhua; Deng, Yu; Bao, Wei; Tang, Changyan; Ding, Hanjing; Zheng, Zhongliang; Zou, Guolin

2014-11-01

Subtilisin propeptide functions as an intramolecular chaperone that guides precursor folding. Nattokinase, a member of subtilisin family, is synthesized as a precursor consisting of a signal peptide, a propeptide, and a subtilisin domain, and the mechanism of its folding remains to be understood. In this study, the essential residues of nattokinase propeptide which contribute to precursor folding were determined. Deletion analysis showed that the conserved regions in propeptide were important for precursor folding. Single-site and multi-site mutagenesis studies confirmed the role of Tyr10, Gly13, Gly34, and Gly35. During stage (i) and (ii) of precursor folding, Tyr10 and Gly13 would form the part of interface with subtilisin domain. While Gly34 and Gly35 connected with an α-helix that would stabilize the structure of propeptide. The quadruple Ala mutation, Y10A/G13A/G34A/G35A, resulted in a loss of the chaperone function for the propeptide. This work showed the essential residues of propeptide for precursor folding via secondary structure and kinetic parameter analyses. © The Author 2014. Published by ABBS Editorial Office in association with Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences.

In silico modeling and experimental evidence of coagulant protein interaction with precursors for nanoparticle functionalization.

PubMed

Okoli, Chuka; Sengottaiyan, Selvaraj; Arul Murugan, N; Pavankumar, Asalapuram R; Agren, Hans; Kuttuva Rajarao, Gunaratna

2013-10-01

The design of novel protein-nanoparticle hybrid systems has applications in many fields of science ranging from biomedicine, catalysis, water treatment, etc. The main barrier in devising such tool is lack of adequate information or poor understanding of protein-ligand chemistry. Here, we establish a new strategy based on computational modeling for protein and precursor linkers that can decorate the nanoparticles. Moringa oleifera (MO2.1) seed protein that has coagulation and antimicrobial properties was used. Superparamagnetic nanoparticles (SPION) with precursor ligands were used for the protein-ligand interaction studies. The molecular docking studies reveal that there are two binding sites, one is located at the core binding site; tetraethoxysilane (TEOS) or 3-aminopropyl trimethoxysilane (APTES) binds to this site while the other one is located at the side chain residues where trisodium citrate (TSC) or Si60 binds to this site. The protein-ligand distance profile analysis explains the differences in functional activity of the decorated SPION. Experimentally, TSC-coated nanoparticles showed higher coagulation activity as compared to TEOS- and APTES-coated SPION. To our knowledge, this is the first report on in vitro experimental data, which endorses the computational modeling studies as a powerful tool to design novel precursors for functionalization of nanomaterials; and develop interface hybrid systems for various applications.

Controlled fabrication of semiconductor-metal hybrid nano-heterostructures via site-selective metal photodeposition

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

Vela Becerra, Javier; Ruberu, T. Purnima A.

A method of synthesizing colloidal semiconductor-metal hybrid heterostructures is disclosed. The method includes dissolving semiconductor nanorods in a solvent to form a nanorod solution, and adding a precursor solution to the nanorod solution. The precursor solution contains a metal. The method further includes illuminating the combined precursor and nanorod solutions with light of a specific wavelength. The illumination causes the deposition of the metal in the precursor solution onto the surface of the semiconductor nanorods.

Simple, Rapid, and Highly Sensitive Detection of Diphosgene and Triphosgene by Spectrophotometric Methods

PubMed Central

Joy, Abraham; Anim-Danso, Emmanuel; Kohn, Joachim

2009-01-01

Methods for the detection and estimation of diphosgene and triphosgene are described. These compounds are widely used phosgene precursors which produce an intensely colored purple pentamethine oxonol dye when reacted with 1,3-dimethylbarbituric acid (DBA) and pyridine (or a pyridine derivative). Two quantitative methods are described, based on either UV absorbance or fluorescence of the oxonol dye. Detection limits are ~ 4 µmol/L by UV and <0.4 µmol/L by fluorescence. The third method is a test strip for the simple and rapid detection and semi-quantitative estimation of diphosgene and triphosgene, using a filter paper embedded with dimethylbarbituric acid and poly(4-vinylpyridine). Addition of a test solution to the paper causes a color change from white to light blue at low concentrations and to pink at higher concentrations of triphosgene. The test strip is useful for quick on-site detection of triphosgene and diphosgene in reaction mixtures. The test strip is easy to perform and provides clear signal readouts indicative of the presence of phosgene precursors. The utility of this method was demonstrated by the qualitative determination of residual triphosgene during the production of poly(Bisphenol A carbonate). PMID:19782219

SOA precursors at the T0 site during the 2010 CARES campaign

NASA Astrophysics Data System (ADS)

Wallace, H. W.; Jobson, B. T.; Erickson, M. H.

2010-12-01

Continuous measurements of C5 to C12 Volatile Organic Compounds (VOC) have been made using the Washington State University Mobile Atmospheric Chemistry Laboratory (MACL), at the T0 site during the month of June 2010 Carbonaceous Aerosol Carbonaceous Aerosols and Radiative Effects Study (CARES). These measurements were made to better understand aerosol formation and growth in Sacramento, CA and the surrounding areas. Using a sorbent based preconcentration sampling technique for our quadrupole ion trap gas chromatography mass spectrometer (GCMS), we have measured anthropogenic and biogenic secondary organic aerosol (SOA) precursors. Major biogenic VOCs identified include: α-pinene, limonene, isoprene, phellanderene and β-pinene. Diurnal profiles of the concentrations will be presented. Monoterpenes were highest in the mornings while isoprene was highest in the afternoon. In addition to understanding the diurnal profiles the SOA precursors at the T0 site, the relative contributions of biogenic and anthropogenic compounds to SOA formation will be presented.

Statistical study of spatio-temporal distribution of precursor solar flares associated with major flares

NASA Astrophysics Data System (ADS)

Gyenge, N.; Ballai, I.; Baranyi, T.

2016-07-01

The aim of the present investigation is to study the spatio-temporal distribution of precursor flares during the 24 h interval preceding M- and X-class major flares and the evolution of follower flares. Information on associated (precursor and follower) flares is provided by Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI). Flare list, while the major flares are observed by the Geostationary Operational Environmental Satellite (GOES) system satellites between 2002 and 2014. There are distinct evolutionary differences between the spatio-temporal distributions of associated flares in about one-day period depending on the type of the main flare. The spatial distribution was characterized by the normalized frequency distribution of the quantity δ (the distance between the major flare and its precursor flare normalized by the sunspot group diameter) in four 6 h time intervals before the major event. The precursors of X-class flares have a double-peaked spatial distribution for more than half a day prior to the major flare, but it changes to a lognormal-like distribution roughly 6 h prior to the event. The precursors of M-class flares show lognormal-like distribution in each 6 h subinterval. The most frequent sites of the precursors in the active region are within a distance of about 0.1 diameter of sunspot group from the site of the major flare in each case. Our investigation shows that the build-up of energy is more effective than the release of energy because of precursors.

Method and system for continuous atomic layer deposition

DOEpatents

Elam, Jeffrey W.; Yanguas-Gil, Angel; Libera, Joseph A.

2017-03-21

A system and method for continuous atomic layer deposition. The system and method includes a housing, a moving bed which passes through the housing, a plurality of precursor gases and associated input ports and the amount of precursor gases, position of the input ports, and relative velocity of the moving bed and carrier gases enabling exhaustion of the precursor gases at available reaction sites.

RIVERBANK FILTRATION: FATE OF DBP PRECURSORS AND SELECTED MICROORGANISMS

EPA Science Inventory

The fate of disinfection by-product (DBP) precursors and selected microorganisms during riverbank filtration (RBF) was monitored at three different mid-Western drinking water utilities. At all three sites, filtration (RBF) was monitored at three different mid-Western drinking wa...

Enabling Surgical Placement of Hydrogels through Achieving Paste-Like Rheological Behavior in Hydrogel Precursor Solutions

PubMed Central

Beck, Emily C.; Lohman, Brooke L.; Tabakh, Daniel B.; Kieweg, Sarah L.; Gehrke, Stevin H.; Berkland, Cory J.; Detamore, Michael S.

2015-01-01

Hydrogels are a promising class of materials for tissue regeneration, but they lack the ability to be molded into a defect site by a surgeon because hydrogel precursors are liquid solutions that are prone to leaking during placement. Therefore, although the main focus of hydrogel technology and developments are on hydrogels in their crosslinked form, our primary focus is on improving the fluid behavior of hydrogel precursor solutions. In this work, we introduce a method to achieve paste-like hydrogel precursor solutions by combining hyaluronic acid nanoparticles with traditional crosslinked hyaluronic acid hydrogels. Prior to crosslinking, the samples underwent rheological testing to assess yield stress and recovery using linear hyaluronic acid as a control. The experimental groups containing nanoparticles were the only solutions that exhibited a yield stress, demonstrating that the nanoparticulate rather than the linear form of hyaluronic acid was necessary to achieve paste-like behavior. The gels were also photocrosslinked and further characterized as solids, where it was demonstrated that the inclusion of nanoparticles did not adversely affect the compressive modulus and that encapsulated bone marrow-derived mesenchymal stem cells remained viable. Overall, this nanoparticle-based approach provides a platform hydrogel system that exhibits a yield stress prior to crosslinking, and can then be crosslinked into a hydrogel that is capable of encapsulating cells that remain viable. This behavior may hold significant impact for hydrogel applications where a paste-like behavior is desired in the hydrogel precursor solution. PMID:25691398

Engineering a monolignol 4- O-methyltransferase with high selectivity for the condensed lignin precursor coniferyl alchohol

DOE PAGES

Cai, Yuanheng; Shanklin, John; Mohammad -Wadud Bhuiya; ...

2015-09-16

Lignin, a rigid biopolymer in plant cell walls, is derived from the oxidative polymerization of three monolignols. The composition of monolignol monomers dictates the degree of lignin condensation, reactivity, and thus the degradability of plant cell walls. Guaiacyl lignin is regarded as the condensed structural unit. Polymerization of lignin is initiated through the deprotonation of the para-hydroxyl group of monolignols. Therefore, preferentially modifying the para-hydroxyl of a specific monolignol to deprive its dehydrogenation propensity would disturb the formation of particular lignin subunits. Here, we test the hypothesis that specific remodeling the active site of a monolignol 4-O-methyltransferase would create anmore » enzyme that specifically methylates the condensed guaiacyl lignin precursor coniferyl alcohol. Combining crystal structural information with combinatorial active site saturation mutagenesis and starting with the engineered promiscuous enzyme, MOMT5 (T133L/E165I/F175I/F166W/H169F), we incrementally remodeled its substrate binding pocket by the addition of four substitutions, i.e. M26H, S30R, V33S, and T319M, yielding a mutant enzyme capable of discriminately etherifying the para-hydroxyl of coniferyl alcohol even in the presence of excess sinapyl alcohol. The engineered enzyme variant has a substantially reduced substrate binding pocket that imposes a clear steric hindrance thereby excluding bulkier lignin precursors. Lastly, the resulting enzyme variant represents an excellent candidate for modulating lignin composition and/or structure in planta.« less

Engineering a Monolignol 4-O-Methyltransferase with High Selectivity for the Condensed Lignin Precursor Coniferyl Alcohol*

PubMed Central

Cai, Yuanheng; Bhuiya, Mohammad-Wadud; Shanklin, John; Liu, Chang-Jun

2015-01-01

Lignin, a rigid biopolymer in plant cell walls, is derived from the oxidative polymerization of three monolignols. The composition of monolignol monomers dictates the degree of lignin condensation, reactivity, and thus the degradability of plant cell walls. Guaiacyl lignin is regarded as the condensed structural unit. Polymerization of lignin is initiated through the deprotonation of the para-hydroxyl group of monolignols. Therefore, preferentially modifying the para-hydroxyl of a specific monolignol to deprive its dehydrogenation propensity would disturb the formation of particular lignin subunits. Here, we test the hypothesis that specific remodeling the active site of a monolignol 4-O-methyltransferase would create an enzyme that specifically methylates the condensed guaiacyl lignin precursor coniferyl alcohol. Combining crystal structural information with combinatorial active site saturation mutagenesis and starting with the engineered promiscuous enzyme, MOMT5 (T133L/E165I/F175I/F166W/H169F), we incrementally remodeled its substrate binding pocket by the addition of four substitutions, i.e. M26H, S30R, V33S, and T319M, yielding a mutant enzyme capable of discriminately etherifying the para-hydroxyl of coniferyl alcohol even in the presence of excess sinapyl alcohol. The engineered enzyme variant has a substantially reduced substrate binding pocket that imposes a clear steric hindrance thereby excluding bulkier lignin precursors. The resulting enzyme variant represents an excellent candidate for modulating lignin composition and/or structure in planta. PMID:26378240

Occurrence of select perfluoroalkyl substances at U.S. Air Force aqueous film-forming foam release sites other than fire-training areas: Field-validation of critical fate and transport properties.

PubMed

Anderson, R Hunter; Long, G Cornell; Porter, Ronald C; Anderson, Janet K

2016-05-01

The use of aqueous film-forming foam (AFFF) to extinguish hydrocarbon-based fires is recognized as a significant source of environmental poly- and perfluoroalkyl substances (PFASs). Although the occurrence of select PFASs in soil and groundwater at former fire-training areas (FTAs) at military installations operable since 1970 has been consistently confirmed, studies reporting the occurrence of PFASs at other AFFF-impacted sites (e.g. emergency response locations, AFFF lagoons, hangar-related AFFF storage tanks and pipelines, and fire station testing and maintenance areas) are largely missing from the literature. Further, studies have mostly focused on a single site (i.e., FTAs at military installations) and, thus, lack a comparison of sites with diverse AFFF release history. Therefore, the purpose of this investigation was to evaluate select PFAS occurrence at non-FTA sites on active U.S. Air Force installations with historic AFFF use of varying magnitude. Concentrations of fifteen perfluoroalkyl acids (PFAAs) and perfluorooctane sulfonamide (PFOSA), an important PFOS precursor, were measured from several hundred samples among multiple media (i.e., surface soil, subsurface soil, sediment, surface water, and groundwater) collected from forty AFFF-impacted sites across ten installations between March and September 2014, representing one of the most comprehensive datasets on environmental PFAS occurrence to date. Differences in detection frequencies and observed concentrations due to AFFF release volume are presented along with rigorous data analyses that quantitatively demonstrate phase-dependent (i.e., solid-phase vs aqueous-phase) differences in the chemical signature as a function of carbon chain-length and in situ PFOS (and to a slightly lesser extent PFHxS) formation, presumably due to precursor biotransformation. Published by Elsevier Ltd.

Monitoring of soil radon by SSNTD in Eastern India in search of possible earthquake precursor.

PubMed

Deb, Argha; Gazi, Mahasin; Ghosh, Jayita; Chowdhury, Saheli; Barman, Chiranjib

2018-04-01

The present paper deals with monitoring soil radon-222 concentration at two different locations, designated Site A and Site B, 200 m apart at Jadavpur University campus, Kolkata, India, with a view to find possible precursors for the earthquakes that occurred within a few hundred kilometers from the monitoring site. The solid state nuclear track detector CR-39 has been used for detection of radon gas coming out from soil. Radon-222 time series at both locations during the period August 2012-December 2013 have been analysed. Distinct anomalies in the soil radon time series have been observed for seven earthquakes of magnitude greater than 4.0 M that occurred during this time. Of these, radon anomalies for two earthquakes have been observed at both locations A and B. Absence of anomalies for some other earthquakes has been discussed, and the observations have been compared with some earthquake precursor models. Copyright © 2018. Published by Elsevier Ltd.

Introduction of the new concept: Potential Aerosol Mass (PAM) for Inorganic and Organic Secondary Aerosol

NASA Astrophysics Data System (ADS)

Kang, E.; Root, M. J.; Brune, W. H.

2006-12-01

A new concept, the Potential Aerosol Mass (PAM), is being developed and tested in the laboratory with the goal of deploying instruments to measure PAM in the atmosphere. PAM can be defined as the maximum aerosol mass that precursor gases can be oxidized to form. In the PAM concept, all precursor gases are oxidized to low volatile compounds with excessive amount of oxidants in a small continuous-flow Teflon cylinder, resulting in aerosol formation. Excessive amounts of OH and O3 are produced by a UV light that shines into the Teflon chamber. For our studies, the aerosol mass is then detected with a real-time aerosol mass measurement instrument, the Rupprecht and Patashnick Tapered Element Oscillating Microbalance (TEOM) and Filter Dynamic Measurement System (FDMS). As a test of the system, SO2 was oxidized to sulfate; the measured and calculated conversion ratios of sulfate aerosol mass to SO2 mass agree to within 10%. We will discuss the results of a series of laboratory tests that have been conducted with α-pinene to determine the variables that most affect its Secondary Organic Aerosol (SOA) yield. We will also discuss the results of some atmospheric measurement tests made at a site on the Penn State University campus.

Use of polysialic acid in repair of the central nervous system

PubMed Central

El Maarouf, Abderrahman; Petridis, Athanasios K.; Rutishauser, Urs

2006-01-01

Polysialic acid (PSA), a large cell-surface carbohydrate that regulates cell interactions, is used during vertebrate development to promote precursor cell migration and axon path-finding. The induction of PSA expression in damaged adult CNS tissues could help them to rebuild by creating conditions permissive for architectural remodeling. This possibility has been explored in two contexts, the regeneration of axons and the recruitment of endogenous neural precursors to a lesion. Glial scars that form at CNS injury sites block axon regeneration. It has been found that transfection of scar astrocytes by a viral vector encoding polysialyltransferase leads to sustained expression of high levels of PSA. With this treatment, a substantial portion of severed corticospinal tract axon processes were able to grow through a spinal injury site. In the studies of precursor cell migration to a cortical lesion, it was found that induced PSA expression in a path extending from the subventricular zone to a lesion near the cortical surface increased recruitment of BrdU/nestin-positive cells along the path and into the injury site. These displaced precursors were able to differentiate in a regionally appropriate manner. These findings suggest that induced PSA expression can be used as a strategy for promoting tissue repair involving both replacement of cells and rebuilding of neural connections. PMID:17075041

SVM-Based Prediction of Propeptide Cleavage Sites in Spider Toxins Identifies Toxin Innovation in an Australian Tarantula

PubMed Central

Wong, Emily S. W.; Hardy, Margaret C.; Wood, David; Bailey, Timothy; King, Glenn F.

2013-01-01

Spider neurotoxins are commonly used as pharmacological tools and are a popular source of novel compounds with therapeutic and agrochemical potential. Since venom peptides are inherently toxic, the host spider must employ strategies to avoid adverse effects prior to venom use. It is partly for this reason that most spider toxins encode a protective proregion that upon enzymatic cleavage is excised from the mature peptide. In order to identify the mature toxin sequence directly from toxin transcripts, without resorting to protein sequencing, the propeptide cleavage site in the toxin precursor must be predicted bioinformatically. We evaluated different machine learning strategies (support vector machines, hidden Markov model and decision tree) and developed an algorithm (SpiderP) for prediction of propeptide cleavage sites in spider toxins. Our strategy uses a support vector machine (SVM) framework that combines both local and global sequence information. Our method is superior or comparable to current tools for prediction of propeptide sequences in spider toxins. Evaluation of the SVM method on an independent test set of known toxin sequences yielded 96% sensitivity and 100% specificity. Furthermore, we sequenced five novel peptides (not used to train the final predictor) from the venom of the Australian tarantula Selenotypus plumipes to test the accuracy of the predictor and found 80% sensitivity and 99.6% 8-mer specificity. Finally, we used the predictor together with homology information to predict and characterize seven groups of novel toxins from the deeply sequenced venom gland transcriptome of S. plumipes, which revealed structural complexity and innovations in the evolution of the toxins. The precursor prediction tool (SpiderP) is freely available on ArachnoServer (http://www.arachnoserver.org/spiderP.html), a web portal to a comprehensive relational database of spider toxins. All training data, test data, and scripts used are available from the SpiderP website. PMID:23894279

The solubility and stabilization of ikaite (CaCO3.6H2O) from 0° to 25°C: environmental and paleoclimatic implications for thinolite tufa

USGS Publications Warehouse

Bischoff, James L.; Fitzpatrick, John A.; Rosenbauer, Robert J.

1993-01-01

We determined the solubility of ikaite from 0?? to 25??C to model its saturation state in natural waters and test the hypothesis that it is the precursor of the calcite pseudomorphs in thinolite tufa of Quaternary Lake Lahonta. Its precipitation in near-freezing marine sediments requires large additions of HCO3 to pore fluids from the diagenetic decomposition of organic matter. Its crystallization in tufas of alkaline lakes, however, requires only small additions of Ca from springs. Ikaite is stabilized in natural environments by orthophosphate. The presence of ikaite or its pseudomorphs is an indicator of near-freezing comditions in environments with high concentrations of orthophosphate. If ikaite is the precursor of thinolite tufa, then the thinolite likely grew below the sediment-water interface at the site of sublacustrine springs during prolonged cold periods. -from Authors

Regulation of endogenous neural stem/progenitor cells for neural repair—factors that promote neurogenesis and gliogenesis in the normal and damaged brain

PubMed Central

Christie, Kimberly J.; Turnley, Ann M.

2012-01-01

Neural stem/precursor cells in the adult brain reside in the subventricular zone (SVZ) of the lateral ventricles and the subgranular zone (SGZ) of the dentate gyrus in the hippocampus. These cells primarily generate neuroblasts that normally migrate to the olfactory bulb (OB) and the dentate granule cell layer respectively. Following brain damage, such as traumatic brain injury, ischemic stroke or in degenerative disease models, neural precursor cells from the SVZ in particular, can migrate from their normal route along the rostral migratory stream (RMS) to the site of neural damage. This neural precursor cell response to neural damage is mediated by release of endogenous factors, including cytokines and chemokines produced by the inflammatory response at the injury site, and by the production of growth and neurotrophic factors. Endogenous hippocampal neurogenesis is frequently also directly or indirectly affected by neural damage. Administration of a variety of factors that regulate different aspects of neural stem/precursor biology often leads to improved functional motor and/or behavioral outcomes. Such factors can target neural stem/precursor proliferation, survival, migration and differentiation into appropriate neuronal or glial lineages. Newborn cells also need to subsequently survive and functionally integrate into extant neural circuitry, which may be the major bottleneck to the current therapeutic potential of neural stem/precursor cells. This review will cover the effects of a range of intrinsic and extrinsic factors that regulate neural stem/precursor cell functions. In particular it focuses on factors that may be harnessed to enhance the endogenous neural stem/precursor cell response to neural damage, highlighting those that have already shown evidence of preclinical effectiveness and discussing others that warrant further preclinical investigation. PMID:23346046

AxBAxB… pulsed atomic layer deposition: Numerical growth model and experiments

NASA Astrophysics Data System (ADS)

Muneshwar, Triratna; Cadien, Ken

2016-02-01

Atomic layer deposition (ALD) is widely used for the fabrication of advanced semiconductor devices and related nanoscale structures. During ALD, large precursor doses (>1000 L per pulse) are often required to achieve surface saturation, of which only a small fraction is utilized in film growth while the rest is pumped from the system. Since the metal precursor constitutes a significant cost of ALD, strategies to enhance precursor utilization are essential for the scaling of ALD processes. In the precursor reaction step, precursor physisorption is restricted by steric hindrance (mA1) from ligands on the precursor molecules. On reaction, some of these ligands are removed as by-products resulting in chemisorbed species with reduced steric hindrance (mA1 → mA2, where mA2 < mA1) and some of the initially hindered surface reaction sites becoming accessible for further precursor physisorption. To utilize these additional reaction sites, we propose a generalized AxBAxB… pulsed deposition where the total precursor dose (ΦA) is introduced as multiple x (x > 1, x ∈ I) short-pulses rather than a single pulse. A numerical first-order surface reaction kinetics growth model is presented and applied to study the effect of AxBAxB… pulsed ALD on the growth per cycle (GPC). The model calculations predict higher GPC for AxBAxB… pulsing than with ABAB… deposition. In agreement with the model predictions, with AxBAxB… pulsed deposition, the GPC was found to increase by ˜46% for ZrN plasma enhanced ALD (PEALD), ˜49% for HfO2 PEALD, and ˜8% for thermal Al2O3 ALD with respect to conventional ABAB… pulsed growth.

Preparation of mesoporous alumina particles by spray pyrolysis and application to double bond migration of 2-butene.

PubMed

Song, Ki Chang; Kim, Joo Hyun; Kim, Jin Han; Jung, Kyeong Youl; Park, Young-Kwon; Jeon, Jong-Ki

2011-07-01

The objective of the present study is to investigate the catalytic performance of mesoporous alumina that were prepared via spray pyrolysis for double bond migration from 2-butene to 1-butene. The mesoporous alumina particles were prepared via spray pyrolysis by changing the types of organic surfactants and Al precursors. The texture and acidic properties of mesoporous alumina were analyzed through N2 adsorption, SEM, ammonia-temperature programmed desorption, and FT-IR of adsorbed pyridine. The morphologies and texture properties of the mesoporous alumina were found to have been strongly influenced by the combination of the Al precursor and the structure-directing agents. The mesoporous alumina samples had two kinds of acidic sites: a Lewis acid site and a H-bonded weak acid site. 1-Butene was produced selectively through double bond migration of 2-butene over all of the mesoporous alumina catalysts. The catalyst prepared by using a chloride compound as an aluminium precursor and CTAC as a structure-directing agent showed the highest activity in the double bond migration of 2-butene, which was attributed to its large surface area and an overall high amount of acid sites.

Develop and test fuel cell powered on-site integrated total energy system

NASA Technical Reports Server (NTRS)

Kaufman, A.; Johnson, G. K.

1982-01-01

Satisfactory performance is reported for the first 12-cell sub-stack of the 5 kW rebuild using improved ABA reactant distribution plates. Construction and test results are described for the first full-sized single-cell test (0.33 m x 0.56 m). Test duration was 450 hours. Plans are outlined for construction and testing of two methanol reformer units based on commercially-available shell-and-tube heat exchangers. A 5 kW-equivalent precursor and a 50 kW-equivalent prototype will be built. Supporting design and single-tube experimental data are presented. Stack support efforts are summarized on corrosion currents of graphite materials and acid-management of single-cell test facilities. Comparative properties are summarized for the two methanol/steam reforming catalysts evauated under Task V (now completed); T2107RS and C70-2RS.

Stepwise assembly of multiple Lin28 proteins on the terminal loop of let-7 miRNA precursors

PubMed Central

Desjardins, Alexandre; Bouvette, Jonathan; Legault, Pascale

2014-01-01

Lin28 inhibits the biogenesis of let-7 miRNAs through direct interactions with let-7 precursors. Previous studies have described seemingly inconsistent Lin28 binding sites on pre-let-7 RNAs. Here, we reconcile these data by examining the binding mechanism of Lin28 to the terminal loop of pre-let-7g (TL-let-7g) using biochemical and biophysical methods. First, we investigate Lin28 binding to TL-let-7g variants and short RNA fragments and identify three independent binding sites for Lin28 on TL-let-7g. We then determine that Lin28 assembles in a stepwise manner on TL-let-7g to form a stable 1:3 complex. We show that the cold-shock domain (CSD) of Lin28 is responsible for remodelling the terminal loop of TL-let-7g, whereas the NCp7-like domain facilitates the initial binding of Lin28 to TL-let-7g. This stable binding of multiple Lin28 molecules to the terminal loop of pre-let-7g extends to other precursors of the let-7 family, but not to other pre-miRNAs tested. We propose a model for stepwise assembly of the 1:1, 1:2 and 1:3 pre-let-7g/Lin28 complexes. Stepwise multimerization of Lin28 on pre-let-7 is required for maximum inhibition of Dicer cleavage for a least one member of the let-7 family and may be important for orchestrating the activity of the several factors that regulate let-7 biogenesis. PMID:24452802

Engineering a monolignol 4-O-methyltransferase with high selectivity for the condensed lignin precursor coniferyl alcohol.

PubMed

Cai, Yuanheng; Bhuiya, Mohammad-Wadud; Shanklin, John; Liu, Chang-Jun

2015-10-30

Lignin, a rigid biopolymer in plant cell walls, is derived from the oxidative polymerization of three monolignols. The composition of monolignol monomers dictates the degree of lignin condensation, reactivity, and thus the degradability of plant cell walls. Guaiacyl lignin is regarded as the condensed structural unit. Polymerization of lignin is initiated through the deprotonation of the para-hydroxyl group of monolignols. Therefore, preferentially modifying the para-hydroxyl of a specific monolignol to deprive its dehydrogenation propensity would disturb the formation of particular lignin subunits. Here, we test the hypothesis that specific remodeling the active site of a monolignol 4-O-methyltransferase would create an enzyme that specifically methylates the condensed guaiacyl lignin precursor coniferyl alcohol. Combining crystal structural information with combinatorial active site saturation mutagenesis and starting with the engineered promiscuous enzyme, MOMT5 (T133L/E165I/F175I/F166W/H169F), we incrementally remodeled its substrate binding pocket by the addition of four substitutions, i.e. M26H, S30R, V33S, and T319M, yielding a mutant enzyme capable of discriminately etherifying the para-hydroxyl of coniferyl alcohol even in the presence of excess sinapyl alcohol. The engineered enzyme variant has a substantially reduced substrate binding pocket that imposes a clear steric hindrance thereby excluding bulkier lignin precursors. The resulting enzyme variant represents an excellent candidate for modulating lignin composition and/or structure in planta. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Auditory enhancement of increments in spectral amplitude stems from more than one source.

PubMed

Carcagno, Samuele; Semal, Catherine; Demany, Laurent

2012-10-01

A component of a test sound consisting of simultaneous pure tones perceptually "pops out" if the test sound is preceded by a copy of itself with that component attenuated. Although this "enhancement" effect was initially thought to be purely monaural, it is also observable when the test sound and the precursor sound are presented contralaterally (i.e., to opposite ears). In experiment 1, we assessed the magnitude of ipsilateral and contralateral enhancement as a function of the time interval between the precursor and test sounds (10, 100, or 600 ms). The test sound, randomly transposed in frequency from trial to trial, was followed by a probe tone, either matched or mismatched in frequency to the test sound component which was the target of enhancement. Listeners' ability to discriminate matched probes from mismatched probes was taken as an index of enhancement magnitude. The results showed that enhancement decays more rapidly for ipsilateral than for contralateral precursors, suggesting that ipsilateral enhancement and contralateral enhancement stem from at least partly different sources. It could be hypothesized that, in experiment 1, contralateral precursors were effective only because they provided attentional cues about the target tone frequency. In experiment 2, this hypothesis was tested by presenting the probe tone before the precursor sound rather than after the test sound. Although the probe tone was then serving as a frequency cue, contralateral precursors were again found to produce enhancement. This indicates that contralateral enhancement cannot be explained by cuing alone and is a genuine sensory phenomenon.

40 CFR 766.38 - Reporting on precursor chemical substances.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 31 2011-07-01 2011-07-01 false Reporting on precursor chemical... SUBSTANCES CONTROL ACT DIBENZO-PARA-DIOXINS/DIBENZOFURANS Specific Chemical Testing/Reporting Requirements § 766.38 Reporting on precursor chemical substances. (a) Identification of precursor chemical substances...

40 CFR 766.38 - Reporting on precursor chemical substances.

Code of Federal Regulations, 2010 CFR

2010-07-01

... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Reporting on precursor chemical... SUBSTANCES CONTROL ACT DIBENZO-PARA-DIOXINS/DIBENZOFURANS Specific Chemical Testing/Reporting Requirements § 766.38 Reporting on precursor chemical substances. (a) Identification of precursor chemical substances...

40 CFR 766.38 - Reporting on precursor chemical substances.

Code of Federal Regulations, 2012 CFR

2012-07-01

... 40 Protection of Environment 32 2012-07-01 2012-07-01 false Reporting on precursor chemical... SUBSTANCES CONTROL ACT DIBENZO-PARA-DIOXINS/DIBENZOFURANS Specific Chemical Testing/Reporting Requirements § 766.38 Reporting on precursor chemical substances. (a) Identification of precursor chemical substances...

40 CFR 766.38 - Reporting on precursor chemical substances.

Code of Federal Regulations, 2014 CFR

2014-07-01

... 40 Protection of Environment 31 2014-07-01 2014-07-01 false Reporting on precursor chemical... SUBSTANCES CONTROL ACT DIBENZO-PARA-DIOXINS/DIBENZOFURANS Specific Chemical Testing/Reporting Requirements § 766.38 Reporting on precursor chemical substances. (a) Identification of precursor chemical substances...

40 CFR 766.38 - Reporting on precursor chemical substances.

Code of Federal Regulations, 2013 CFR

2013-07-01

... 40 Protection of Environment 32 2013-07-01 2013-07-01 false Reporting on precursor chemical... SUBSTANCES CONTROL ACT DIBENZO-PARA-DIOXINS/DIBENZOFURANS Specific Chemical Testing/Reporting Requirements § 766.38 Reporting on precursor chemical substances. (a) Identification of precursor chemical substances...

Testing the Predictors of Boredom at School: Development and Validation of the Precursors to Boredom Scales

ERIC Educational Resources Information Center

Daschmann, Elena C.; Goetz, Thomas; Stupnisky, Robert H.

2011-01-01

Background: Boredom has been found to be an important emotion for students' learning processes and achievement outcomes; however, the precursors of this emotion remain largely unexplored. Aim: In the current study, scales assessing the precursors to boredom in academic achievement settings were developed and tested. Sample: Participants were 1,380…

Enhancement of increments in spectral amplitude: further evidence for a mechanism based on central adaptation.

PubMed

Carcagno, Samuele; Semal, Catherine; Demany, Laurent

2013-01-01

The threshold for detecting a tone in a multitone masker is lower when the masker-plus-signal stimulus is preceded by a copy of the masker. One potential explanation of this "enhancement" phenomenon is that the -precursor stimulus acts as a "template" of the subsequent masker, thus helping listeners to segregate the signal from the masker. To assess this idea, we measured enhancement for precursors that were perceptually similar to the masker and for precursors that were made dissimilar to the masker by gating their components asynchronously. We found that the two types of precursor produced similar amounts of enhancement. This was true not only when the precursor and the subsequent test stimulus were presented to the same ear but also when they were presented to opposite ears. In a second experiment, we checked that the precursors with asynchronously gated components were perceptually poor templates of the subsequent maskers. Listeners now had to discriminate between test stimuli -containing the same components as the precursor and test stimuli containing all but one of the precursor components. We found that in this experimental situation, where enhancement could play no role, gating the precursor components asynchronously disrupted performance. Overall, our results are inconsistent with the hypothesis that precursors producing enhancement are beneficial because they are used as perceptual templates of the masker. Our results are instead consistent with an -explanation of enhancement based on selective neural adaptation taking place at a central locus of the auditory system.

Dual action of memantine in Alzheimer disease: a hypothesis.

PubMed

Wu, Tzong-Yuan; Chen, Chih-Ping

2009-09-01

In this study, we proposed a hypothesis to explain the mechanisms of memantine action in treating Alzheimer disease (AD). Memantine may reduce the expression of amyloid precursor protein and tau protein, as well as acting as an antagonist of N-methyl-D-aspartate receptors in the brain. Two neuropathologic characteristics of AD are neuritic plaques and neurofibrillary tangles. The major molecular components of the plaques and tangles are amyloid-beta peptide and tau, respectively. Drugs able to reduce the expression of amyloid-beta and tau protein provide potential pharmaceutical treatments for AD. We found that memantine inhibited internal ribosome entry site-mediated translation initiation in COS-1 cells. This suggests that the memantine may not only inhibit neuronal excitotoxicity, but also act as an inhibitor of the internal ribosome entry site, to block the expression of amyloid precursor protein and tau in neurons. Memantine may function not only as an antagonist of N-methyl-D-aspartate receptors, but also as an inhibitor of the internal ribosome entry site to block the expression of amyloid precursor protein and tau, and so ameliorate the symptoms of AD.

Photochemically consumed hydrocarbons and their relationship with ozone formation in two megacities of China

NASA Astrophysics Data System (ADS)

Chang, C.; Wang, J.; Liu, S.; Shao, M.; Zhang, Y.; Zhu, T.; Shiu, C.; Lai, C.

2010-12-01

Two on-site continuous measurements of ozone and its precursors in two megacities of China were carried out in an urban site of Beijing and a suburban site near Guangzhou in the Pearl River Delta (PRD) to estimate precursor consumption and to assess its relationship with oxidant (O3+NO2) formation level. An observation-based method (OBM) with the precursor consumption concept was adopted to assess the relationship between oxidant production and amounts of photochemically consumed non-methane hydrocarbons (NMHCs). In this approach, the ratio of ethylbenzene to m,p-xylenes was used to estimate the degree of photochemical processing, as well as the amounts of photochemically consumed NMHCs by reacting with OH. By trying to correlate the observed oxidant with the observed NMHC concentration, the two areas both revealed nearly no to low correlation between them. However, it existed fair to good correlations (R2=0.68 for Beijing, 0.53 for PRD) between the observed oxidant level and the degree of photochemical processing (ethylbenzene/m,p-xylenes). Furthermore, after taking the approach of consumption to estimate the consumed amounts of NMHCs, an interesting finding reveals that the definite correlation existed between the observed oxidant level and the total consumed NMHCs. The good correlations (R2=0.83 for Beijing, 0.81 for PRD) implies that the ambient oxidant level correlated to the amount of consumed NMHCs. The results of the two megacities in China by using the OBM with the precursor consumption concept can provide another pathway to explore the relationship between photochemically produced oxidant and consumed precursors, and will be helpful to validate model results and to reduce uncertainty of model predictions. However, the method has some room for uncertainty, as injection of fresh precursor emissions and additional boundary ozone involved, etc. could affect the estimation of consumed NMHCs and observed oxidant levels. Assistance of approaches in assessing the influence of the interfering factors would be helpful to acquire more reliable inferences of relationship between oxidant formation and precursor consumption.

The removal of disinfection by-product precursors from water with ceramic membranes.

PubMed

Harman, B I; Koseoglu, H; Yigit, N O; Sayilgan, E; Beyhan, M; Kitis, M

2010-01-01

The main objective of this work was to investigate the effectiveness of ceramic ultrafiltration (UF) membranes with different pore sizes in removing natural organic matter (NOM) from model solutions and drinking water sources. A lab-scale, cross-flow ceramic membrane test unit was used in all experiments. Two different single-channel tubular ceramic membrane modules were tested with average pore sizes of 4 and 10 nm. The impacts of membrane pore size and pressure on permeate flux and the removals of UV(280 nm) absorbance, specific UV absorbance (SUVA(280 nm)), and dissolved organic carbon (DOC) were determined. Prior to experiments with model solutions and raw waters, clean water flux tests were conducted. UV(280) absorbance reductions ranged between 63 and 83% for all pressures and membranes tested in the raw water. More than 90% of UV(280) absorbance reduction was consistently achieved with both membranes in the model NOM solutions. Such high UV absorbance reductions are advantageous due to the fact that UV absorbing sites of NOM are known to be one of the major precursors to disinfection by-products (DBP) such as trihalomethanes and haloacetic acids. For both UF membranes, the ranges of DOC removals in the raw water and model NOM solutions were 55-73% and 79-91%, respectively. SUVA(280) value of the raw water decreased from 2 to about 1.5 L/mg-m by both membranes. For the model solutions, SUVA(280) values were consistently reduced to < or =1 L/mg-m levels after membrane treatment. As the SUVA(280) value of the NOM source increased, the extent of SUVA(280) reduction and DOC removal by the tested ceramic UF membranes also increased. The results overall indicated that ceramic UF membranes, especially the one with 4 nm average pore size, appear to be effective in removing organic matter and DBP precursors from drinking water sources with relatively high and sustainable permeate flux values.

[Analysis of perfluoroalkyl substances precursors in human milk from 12 provinces of China].

PubMed

Yang, Lin; Yu, Xinping; Wang, Meng; Li, Jingguang; Wang, Yuxin; Zhao, Yunfeng; Wu, Yongning

2015-06-01

To explore the level of perfluoroalkyl substances (PFASs) precursors in Chinese human milk samples. The human milk samples were collected during the performance of Stockholm convention on survey of human milk in China in 2007. Based on the geographical location and dietary habits, China was divided into the south area and north area which 6 provinces were chosen from each area and there were 12 provinces in all. In each province, one urban site and two rural sites were selected to collect 80-110 samples. Mothers were randomly selected in each site to collect their breast milk. There were 1 237 individual human milk samples in all. For each province, the individual samples from the urban areas and the rural areas were pooled separately resulting in 24 pooled human milk samples. 11 PFAS precursors were measured in pooled samples by ultra-high performance liquid chromatography-tandem quadruple mass spectrometry (UPLC-MS/MS). The dietary exposure assessment of newborns was made. Three PFAS precursors were found above the detection limits, namely, 6:2 FTS, FHUEA, and 6:2 diPAP. Their concentration ranges were < Limit of determination (LOD) -47.46 pg/ml, < LOD -70.68 pg/ml and < LOD -35.08 pg/ml, respectively. The highest total PFAS precursor concentration 77.70 pg/ml was found in urban area samples from Shannxi Province. Rural area samples from Hubei had the lowest total PFAS precursor concentration, which was below the LOD. There were significant differences between rural and urban areas in many provinces, such as Shannxi (rural: 1.51 pg/ml; urban: 77.70 pg/ml), Shanghai (rural: 1.13 pg/ml; urban: 71.88 pg/ml), Jiangxi (rural: 65.39 pg/ml; urban: 0.55 pg/ml) and so on. The ranges estimated daily intake of 6:2 FTS, FHUEA and 6:2 diPAP of the samples from 12 provinces were 0.05-4.51, 1.13-6.72 and 1.15-3.34 ng · kg⁻¹ · d⁻¹. The results suggested the human exposure of PFAS precursors in China and the potential health impact of postnatal exposure through breastfeeding to infants. The level of PFAS precursors showed differences in regions, rural and urban places.

Investigation of copper(II) binding to the protein precursor of Non-Amyloid-Beta Component of Alzheimer Disease Amyloid Plaque

NASA Astrophysics Data System (ADS)

Rose, Francis; Hodak, Miroslav; Bernholc, Jerry

2007-03-01

The Non-Amyloid-Beta Component Precursor (NACP) is a natively unfolded synaptic protein that is implicated in Alzheimers and Parkinsons diseases. Its aggregation into fibrillar structures is accelerated by the binding of copper(II). Experimental studies suggest that the dominant copper binding site is located at the histidine residue in NACP. Based on this evidence we assembled a model fragment of the binding site and used DFT to analyze the conformational details of the most probable binding motifs. We investigated the overall conformational effects with classical MD by constraining the copper binding site to the most energetically favorable geometry obtained from the DFT calculations. These results are compared and contrasted with those of the unbound NACP.

Quantification of airborne fossil and biomass carbonylic carbon by combined radiocarbon and liquid chromatography mass spectrometry

NASA Astrophysics Data System (ADS)

Larsen, B. R.; Tudos, A.; Slanina, J.; Van der Borg, K.; Kotzias, D.

Airborne carbonyl compounds have been sampled at three European semi-remote to semi-urban test sites for radiocarbon ( 14C) analysis. The used methodology included collection on 2,4-dinitrophenylhydrazine coated silica gel cartridges, chromatographic isolation of the formed hydrazones, combustion into CO 2, reduction into graphite followed by accelerator mass spectrometry. In combination with this, liquid chromatography coupled to atmospheric pressure chemical ionisation mass spectrometry was used for chemical speciation of the collected carbonyls. At all sites the carbonyls were found to be of a mixed biogenic/anthropogenic origin. The determining factor for the proportion of fossil (anthropogenic) carbon in the samples was the vicinity of urban sources for carbonyls and their photochemical precursors. At meteorological conditions, which gave the test sites semi-rural/semi-remote characteristics the samples contained an average of 24% (range: 10-34%) of fossil carbonylic carbon. When air masses were transported from urban areas to the test-sites significantly higher proportions of fossil carbonylic carbon were determined with a maximum of 61%. Principal component analysis on this limited data set indicated that a low fossil proportion of carbonylic carbon is associated with high proportions of acetaldehyde, acetone, pentanone and acrolein. Until further radicarbon studies are carried out the conclusion remains that for the carbonyl compounds measured European background levels are of a predominant biogenic origin.

Acetone in the atmosphere of Hong Kong: Abundance, sources and photochemical precursors

NASA Astrophysics Data System (ADS)

Guo, H.; Ling, Z. H.; Cheung, K.; Wang, D. W.; Simpson, I. J.; Blake, D. R.

2013-02-01

Intensive field measurements were carried out at a mountain site and an urban site at the foot of the mountain from September to November 2010 in Hong Kong. Acetone was monitored using both canister air samples and 2,4-dinitrophenylhydrazine cartridges. The spatiotemporal patterns of acetone showed no difference between the two sites (p > 0.05), and the mean acetone mixing ratios on O3 episode days were higher than those on non-O3 episode days at both sites (p < 0.05). The source contributions to ambient acetone at both sites were estimated using a receptor model i.e. Positive Matrix Factorization (PMF). The PMF results showed that vehicular emission and secondary formation made the most important contribution to ambient acetone, followed by the solvent use at both sites. However, the contribution of biogenic emission at the mountain site was significantly higher than that at the urban site, whereas biomass burning made more remarkable contribution at the urban site than that at the mountain site. The mechanism of oxidation formation of acetone was investigated using a photochemical box model. The results indicated that i-butene was the main precursor of secondary acetone at the mountain site, while the oxidation of i-butane was the major source of secondary acetone at the urban site.

THE CRYSTALLIZATION AND SEROLOGICAL DIFFERENTIATION OF A STREPTOCOCCAL PROTEINASE AND ITS PRECURSOR

PubMed Central

Elliott, S. D.

1950-01-01

Grown in dialysate broth at a pH between 5.5 and 6.5, some strains of group A streptococci elaborate the precursor of a proteolytic enzyme. Within this range of hydrogen concentration the precursor is also produced when the streptococci are suspended in a peptone dialysate containing glucose and incubated at 37°C. The precursor does not appear to be produced at a neutral or alkaline reaction. Methods are described whereby the precursor and proteinase have been isolated in crystalline form. The precursor crystallizes from half-saturated ammonium sulfate at pH 8.0 and a temperature of 22°C. or higher; the proteinase crystallizes from 0.15 saturated ammonium sulfate at pH 8.0 but does so most readily at refrigerator temperature. The degree of purification achieved by these procedures is discussed. The activity of purified preparations of the precursor and of proteinase has been tested against α-benzoyl-l-arginineamide and, with this as a substrate, the conversion of precursor to proteinase by autocatalysis or by trypsin has been confirmed. Immunological experiments are described, the results of which provide evidence of the distinct antigenic specificity of the precursor and proteinase; the conversion of precursor to proteinase has been followed by means of serological tests. PMID:15436931

The construction and partial characterization of plasmids containing complementary DNA sequences to human calcitonin precursor polyprotein.

PubMed Central

Allison, J; Hall, L; MacIntyre, I; Craig, R K

1981-01-01

(1) Total poly(A)-containing RNA isolated from human thyroid medullary carcinoma tissue was shown to direct the synthesis in the wheat germ cell-free system of a major (Mr 21000) and several minor forms of human calcitonin precursor polyproteins. Evidence for processing of these precursor(s) by the wheat germ cell-free system is also presented. (2) A small complementary DNA (cDNA) plasmid library has been constructed in the PstI site of the plasmid pAT153, using total human thyroid medullary carcinoma poly(A)-containing RNA as the starting material. (3) Plasmids containing abundant cDNA sequences were selected by hybridization in situ, and two of these (ph T-B3 and phT-B6) were characterized by hybridization--translation and restriction analysis. Each was shown to contain human calcitonin precursor polyprotein cDNA sequences. (4) RNA blotting techniques demonstrate that the human calcitonin precursor polyprotein is encoded within a mRNA containing 1000 bases. (5) The results demonstrate that human calcitonin is synthesized as a precursor polyprotein. Images Fig. 1. Fig. 2. Fig. 3. PMID:6896146

Discharges of produced waters from oil and gas extraction via wastewater treatment plants are sources of disinfection by-products to receiving streams

USGS Publications Warehouse

Hladik, Michelle; Focazio, Michael J.; Engle, Mark

2014-01-01

Fluids co-produced with oil and gas production (produced waters) are often brines that contain elevated concentrations of bromide. Bromide is an important precursor of several toxic disinfection by-products (DBPs) and the treatment of produced water may lead to more brominated DBPs. To determine if wastewater treatment plants that accept produced waters discharge greater amounts of brominated DBPs, water samples were collected in Pennsylvania from four sites along a large river including an upstream site, a site below a publicly owned wastewater treatment plant (POTW) outfall (does not accept produced water), a site below an oil and gas commercial wastewater treatment plant (CWT) outfall, and downstream of the POTW and CWT. Of 29 DBPs analyzed, the site at the POTW outfall had the highest number detected (six) ranging in concentration from 0.01 to 0.09 μg L− 1 with a similar mixture of DBPs that have been detected at POTW outfalls elsewhere in the United States. The DBP profile at the CWT outfall was much different, although only two DBPs, dibromochloronitromethane (DBCNM) and chloroform, were detected, DBCNM was found at relatively high concentrations (up to 8.5 μg L− 1). The water at the CWT outfall also had a mixture of inorganic and organic precursors including elevated concentrations of bromide (75 mg L− 1) and other organic DBP precursors (phenol at 15 μg L− 1). To corroborate these DBP results, samples were collected in Pennsylvania from additional POTW and CWT outfalls that accept produced waters. The additional CWT also had high concentrations of DBCNM (3.1 μg L− 1) while the POTWs that accept produced waters had elevated numbers (up to 15) and concentrations of DBPs, especially brominated and iodinated THMs (up to 12 μg L− 1 total THM concentration). Therefore, produced water brines that have been disinfected are potential sources of DBPs along with DBP precursors to streams wherever these wastewaters are discharged.

The Dimer Interfaces of Protease and Extra-Protease Domains Influence the Activation of Protease and the Specificity of GagPol Cleavage

PubMed Central

Pettit, Steven C.; Gulnik, Sergei; Everitt, Lori; Kaplan, Andrew H.

2003-01-01

Activation of the human immunodeficiency virus type 1 (HIV-1) protease is an essential step in viral replication. As is the case for all retroviral proteases, enzyme activation requires the formation of protease homodimers. However, little is known about the mechanisms by which retroviral proteases become active within their precursors. Using an in vitro expression system, we have examined the determinants of activation efficiency and the order of cleavage site processing for the protease of HIV-1 within the full-length GagPol precursor. Following activation, initial cleavage occurs between the viral p2 and nucleocapsid proteins. This is followed by cleavage of a novel site located in the transframe domain. Mutational analysis of the dimer interface of the protease produced differential effects on activation and specificity. A subset of mutations produced enhanced cleavage at the amino terminus of the protease, suggesting that, in the wild-type precursor, cleavages that liberate the protease are a relatively late event. Replacement of the proline residue at position 1 of the protease dimer interface resulted in altered cleavage of distal sites and suggests that this residue functions as a cis-directed specificity determinant. In summary, our studies indicate that interactions within the protease dimer interface help determine the order of precursor cleavage and contribute to the formation of extended-protease intermediates. Assembly domains within GagPol outside the protease domain also influence enzyme activation. PMID:12477841

The dimer interfaces of protease and extra-protease domains influence the activation of protease and the specificity of GagPol cleavage.

PubMed

Pettit, Steven C; Gulnik, Sergei; Everitt, Lori; Kaplan, Andrew H

2003-01-01

Activation of the human immunodeficiency virus type 1 (HIV-1) protease is an essential step in viral replication. As is the case for all retroviral proteases, enzyme activation requires the formation of protease homodimers. However, little is known about the mechanisms by which retroviral proteases become active within their precursors. Using an in vitro expression system, we have examined the determinants of activation efficiency and the order of cleavage site processing for the protease of HIV-1 within the full-length GagPol precursor. Following activation, initial cleavage occurs between the viral p2 and nucleocapsid proteins. This is followed by cleavage of a novel site located in the transframe domain. Mutational analysis of the dimer interface of the protease produced differential effects on activation and specificity. A subset of mutations produced enhanced cleavage at the amino terminus of the protease, suggesting that, in the wild-type precursor, cleavages that liberate the protease are a relatively late event. Replacement of the proline residue at position 1 of the protease dimer interface resulted in altered cleavage of distal sites and suggests that this residue functions as a cis-directed specificity determinant. In summary, our studies indicate that interactions within the protease dimer interface help determine the order of precursor cleavage and contribute to the formation of extended-protease intermediates. Assembly domains within GagPol outside the protease domain also influence enzyme activation.

Modeling precursor diffusion and reaction of atomic layer deposition in porous structures

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

Keuter, Thomas, E-mail: t.keuter@fz-juelich.de; Menzler, Norbert Heribert; Mauer, Georg

2015-01-01

Atomic layer deposition (ALD) is a technique for depositing thin films of materials with a precise thickness control and uniformity using the self-limitation of the underlying reactions. Usually, it is difficult to predict the result of the ALD process for given external parameters, e.g., the precursor exposure time or the size of the precursor molecules. Therefore, a deeper insight into ALD by modeling the process is needed to improve process control and to achieve more economical coatings. In this paper, a detailed, microscopic approach based on the model developed by Yanguas-Gil and Elam is presented and additionally compared with themore » experiment. Precursor diffusion and second-order reaction kinetics are combined to identify the influence of the porous substrate's microstructural parameters and the influence of precursor properties on the coating. The thickness of the deposited film is calculated for different depths inside the porous structure in relation to the precursor exposure time, the precursor vapor pressure, and other parameters. Good agreement with experimental results was obtained for ALD zirconiumdioxide (ZrO{sub 2}) films using the precursors tetrakis(ethylmethylamido)zirconium and O{sub 2}. The derivation can be adjusted to describe other features of ALD processes, e.g., precursor and reactive site losses, different growth modes, pore size reduction, and surface diffusion.« less

System concepts for a large UV/optical/IR telescope on the moon

NASA Technical Reports Server (NTRS)

Nein, Max E.; Davis, Billy

1991-01-01

To assess the systems and technological requirements for constructing lunar telescopes in conjunction with the buildup of a lunar base for scientific exploration and as a waypoint for travel to Mars, the NASA Marshall Space Flight Center conducted concept studies of a 16-m-aperture large lunar telescope (LLT) and a 4-m-aperture precursor telescope, both operating in the UV/visible/IR spectral region. The feasibility of constructing a large telescope on the lunar surface is assessed, and its systems and subsystems are analyzed. Telescope site selection, environmental effects, and launch and assembly scenarios are also evaluated. It is argued that key technical drivers for the LLT must be tested in situ by precursor telescopes to evaluate such areas as the operations and long-term reliability of active optics, radiation protection of instruments, lunar dust mitigation, and thermal shielding of the telescope systems. For a manned lunar outpost or an LLT to become a reality, a low-cost dependable transportation system must be developed.

U.S. draws blueprints for first lunar base

NASA Astrophysics Data System (ADS)

Asker, James R.

1992-08-01

NASA's space exploration office has charted a detailed program to return astronauts to the moon to establish a permanent base that would allow humans and machines to perform a wide range of science activities. The base would serve as a test site for the hardware and techniques that would be used by the first explorers on Mars. The primary mission, named the First Lunar Outpost, starts with unmanned precursor missions of small, lunar orbiting spacecraft, followed by robotic and teleoperating missions on the lunar surface, with astronauts then returning to the moon before the end of the decade.

Human adenovirus serotype 12 virion precursors pMu and pVI are cleaved at amino-terminal and carboxy-terminal sites that conform to the adenovirus 2 endoproteinase cleavage consensus sequence.

PubMed

Freimuth, P; Anderson, C W

1993-03-01

The sequence of a 1158-base pair fragment of the human adenovirus serotype 12 (Ad12) genome was determined. This segment encodes the precursors for virion components Mu and VI. Both Ad12 precursors contain two sequences that conform to a consensus sequence motif for cleavage by the endoproteinase of adenovirus 2 (Ad2). Analysis of the amino terminus of VI and of the peptide fragments found in Ad12 virions demonstrated that these sites are cleaved during Ad12 maturation. This observation suggests that the recognition motif for adenovirus endoproteinases is highly conserved among human serotypes. The adenovirus 2 endoproteinase polypeptide requires additional co-factors for activity (C. W. Anderson, Protein Expression Purif., 1993, 4, 8-15). Synthetic Ad12 or Ad2 pVI carboxy-terminal peptides each permitted efficient cleavage of an artificial endoproteinase substrate by recombinant Ad2 endoproteinase polypeptide.

Molecular cloning and expression of a gene for a factor which stabilizes formation of inhibitor-mitochondrial ATPase complex from Saccharomyces cerevisiae.

PubMed

Akashi, A; Yoshida, Y; Nakagoshi, H; Kuroki, K; Hashimoto, T; Tagawa, K; Imamoto, F

1988-10-01

Stabilizing factor, a 9 kDa protein, stabilizes and facilitates formation of the complex between mitochondrial ATP synthase and its intrinsic inhibitor protein. A clone containing the gene encoding the 9 kDa protein was selected from a yeast genomic library to determine the structure of its precursor protein. As deduced from the nucleotide sequence, the precursor of the yeast 9 kDa stabilizing factor contains 86 amino acid residues and has a molecular weight of 10,062. From the predicted sequence we infer that the stabilizing factor precursor contains a presequence of 23 amino acid residues at its amino terminus. We also used S1 mapping to determine the initiation site of transcription under glucose-repressed or derepressed conditions. These experiments suggest that transcription of this gene starts at three different sites and that only one of them is not affected by the presence of glucose.

Design and implementation of an identification system in construction site safety for proactive accident prevention.

PubMed

Yang, Huanjia; Chew, David A S; Wu, Weiwei; Zhou, Zhipeng; Li, Qiming

2012-09-01

Identifying accident precursors using real-time identity information has great potential to improve safety performance in construction industry, which is still suffering from day to day records of accident fatality and injury. Based on the requirements analysis for identifying precursor and the discussion of enabling technology solutions for acquiring and sharing real-time automatic identification information on construction site, this paper proposes an identification system design for proactive accident prevention to improve construction site safety. Firstly, a case study is conducted to analyze the automatic identification requirements for identifying accident precursors in construction site. Results show that it mainly consists of three aspects, namely access control, training and inspection information and operation authority. The system is then designed to fulfill these requirements based on ZigBee enabled wireless sensor network (WSN), radio frequency identification (RFID) technology and an integrated ZigBee RFID sensor network structure. At the same time, an information database is also designed and implemented, which includes 15 tables, 54 queries and several reports and forms. In the end, a demonstration system based on the proposed system design is developed as a proof of concept prototype. The contributions of this study include the requirement analysis and technical design of a real-time identity information tracking solution for proactive accident prevention on construction sites. The technical solution proposed in this paper has a significant importance in improving safety performance on construction sites. Moreover, this study can serve as a reference design for future system integrations where more functions, such as environment monitoring and location tracking, can be added. Copyright © 2011 Elsevier Ltd. All rights reserved.

Determining sources of dissolved organic carbon and disinfection byproduct precursors to the McKenzie River, Oregon

USGS Publications Warehouse

Kraus, Tamara E.C.; Anderson, Chauncey W.; Morgenstern, Karl; Downing, Bryan D.; Pellerin, Brian A.; Bergamaschi, Brian A.

2010-01-01

This study was conducted to determine the main sources of dissolved organic carbon (DOC) and disinfection byproduct (DBP) precursors to the McKenzie River, Oregon (USA). Water samples collected from the mainstem, tributaries, and reservoir outflows were analyzed for DOC concentration and DBP formation potentials (trihalomethanes [THMFPs] and haloacetic acids [HAAFPs]). In addition, optical properties (absorbance and fluorescence) of dissolved organic matter (DOM) were measured to provide insight into DOM composition and assess whether optical properties are useful proxies for DOC and DBP precursor concentrations. Optical properties indicative of composition suggest that DOM in the McKenzie River mainstem was primarily allochthonous - derived from soils and plant material in the upstream watershed. Downstream tributaries had higher DOC concentrations than mainstem sites (1.6 ?? 0.4 vs. 0.7 ?? 0.3 mg L-1) but comprised <5% of mainstem flows and had minimal effect on overall DBP precursor loads. Water exiting two large upstream reservoirs also had higher DOC concentrations than the mainstem site upstream of the reservoirs, but optical data did not support in situ algal production as a source of the added DOC during the study. Results suggest that the first major rain event in the fall contributes DOM with high DBP precursor content. Although there was interference in the absorbance spectra in downstream tributary samples, fluorescence data were strongly correlated to DOC concentration (R 2 = 0.98), THMFP (R2 = 0.98), and HAAFP (R2 = 0.96). These results highlight the value of using optical measurements for identifying the concentration and sources of DBP precursors in watersheds, which will help drinking water utilities improve source water monitoring and management programs. Copyright ?? 2010 by the American Society of Agronomy.

Kinetic and Surface Study of Single-Walled Aluminosilicate Nanotubes and Their Precursors

PubMed Central

Arancibia-Miranda, Nicolás; Escudey, Mauricio; Molina, Mauricio; García-González, María Teresa

2013-01-01

The structural and surface changes undergone by the different precursors that are produced during the synthesis of imogolite are reported. The surface changes that occur during the synthesis of imogolite were determined by electrophoretic migration (EM) measurements, which enabled the identification of the time at which the critical precursor of the nanoparticles was generated. A critical parameter for understanding the evolution of these precursors is the isoelectric point (IEP), of which variation revealed that the precursors modify the number of active ≡Al-OH and ≡Si-OH sites during the formation of imogolite. We also found that the IEP is displaced to a higher pH level as a consequence of the surface differentiation that occurs during the synthesis. At the same time, we established that the pH of the reaction (pHrx) decreases with the evolution and condensation of the precursors during aging. Integration of all of the obtained results related to the structural and surface properties allows an overall understanding of the different processes that occur and the products that are formed during the synthesis of imogolite. PMID:28348326

Kinetic and Surface Study of Single-Walled Aluminosilicate Nanotubes and Their Precursors.

PubMed

Arancibia-Miranda, Nicolás; Escudey, Mauricio; Molina, Mauricio; García-González, María Teresa

2013-03-01

The structural and surface changes undergone by the different precursors that are produced during the synthesis of imogolite are reported. The surface changes that occur during the synthesis of imogolite were determined by electrophoretic migration (EM) measurements, which enabled the identification of the time at which the critical precursor of the nanoparticles was generated. A critical parameter for understanding the evolution of these precursors is the isoelectric point (IEP), of which variation revealed that the precursors modify the number of active ≡Al-OH and ≡Si-OH sites during the formation of imogolite. We also found that the IEP is displaced to a higher pH level as a consequence of the surface differentiation that occurs during the synthesis. At the same time, we established that the pH of the reaction (pH rx ) decreases with the evolution and condensation of the precursors during aging. Integration of all of the obtained results related to the structural and surface properties allows an overall understanding of the different processes that occur and the products that are formed during the synthesis of imogolite.

DNA precursor pool: a significant target for N-methyl-N-nitrosourea in C3H/10T1/2 clone 8 cells.

PubMed Central

Topal, M D; Baker, M S

1982-01-01

Synchronized C3H/10T1/2 clone 8 cells were treated in vitro with a nontoxic dose of N-methyl-N-nitrosourea during their S phase. Chromatographic isolation of the deoxyribonucleotide DNA precursor pool and measurement of the precursor content per cell showed that a nucleic acid residue in the precursor pool is 190-13,000 times more susceptible to methylation than a residue in the DNA duplex, depending on the site of methylation. This conclusion comes from measurements indicating that, for example, the N-1 position of adenine in dATP is 6.3 times more methylated than the same position in the DNA, even though the adenine content of the pool is only a fraction (0.0005) of the adenine content of the DNA helix. The comparative susceptibility between pool and DNA was found to vary with the site of methylation in the order the N-1 position of adenine greater than phosphate greater than the N-3 position of adenine greater than the O6 position of guanine greater than the N-7 position of guanine. The significance of these results for chemical mutagenesis and carcinogenesis is discussed. PMID:6954535

Simultaneous removal of ammonia and N-nitrosamine precursors from high ammonia water by zeolite and powdered activated carbon.

PubMed

Xue, Runmiao; Donovan, Ariel; Zhang, Haiting; Ma, Yinfa; Adams, Craig; Yang, John; Hua, Bin; Inniss, Enos; Eichholz, Todd; Shi, Honglan

2018-02-01

When adding sufficient chlorine to achieve breakpoint chlorination to source water containing high concentration of ammonia during drinking water treatment, high concentrations of disinfection by-products (DBPs) may form. If N-nitrosamine precursors are present, highly toxic N-nitrosamines, primarily N-nitrosodimethylamine (NDMA), may also form. Removing their precursors before disinfection should be a more effective way to minimize these DBPs formation. In this study, zeolites and activated carbon were examined for ammonia and N-nitrosamine precursor removal when incorporated into drinking water treatment processes. The test results indicate that Mordenite zeolite can remove ammonia and five of seven N-nitrosamine precursors efficiently by single step adsorption test. The practical applicability was evaluated by simulation of typical drinking water treatment processes using six-gang stirring system. The Mordenite zeolite was applied at the steps of lime softening, alum coagulation, and alum coagulation with powdered activated carbon (PAC) sorption. While the lime softening process resulted in poor zeolite performance, alum coagulation did not impact ammonia and N-nitrosamine precursor removal. During alum coagulation, more than 67% ammonia and 70%-100% N-nitrosamine precursors were removed by Mordenite zeolite (except 3-(dimethylaminomethyl)indole (DMAI) and 4-dimethylaminoantipyrine (DMAP)). PAC effectively removed DMAI and DMAP when added during alum coagulation. A combination of the zeolite and PAC selected efficiently removed ammonia and all tested seven N-nitrosamine precursors (dimethylamine (DMA), ethylmethylamine (EMA), diethylamine (DEA), dipropylamine (DPA), trimethylamine (TMA), DMAP, and DMAI) during the alum coagulation process. Copyright © 2017. Published by Elsevier B.V.

Analysis of RNA Processing Reactions Using Cell Free Systems: 3' End Cleavage of Pre-mRNA Substrates in vitro

PubMed Central

Jablonski, Joseph; Clementz, Mark; Ryan, Kevin; Valente, Susana T.

2014-01-01

The 3’ end of mammalian mRNAs is not formed by abrupt termination of transcription by RNA polymerase II (RNPII). Instead, RNPII synthesizes precursor mRNA beyond the end of mature RNAs, and an active process of endonuclease activity is required at a specific site. Cleavage of the precursor RNA normally occurs 10-30 nt downstream from the consensus polyA site (AAUAAA) after the CA dinucleotides. Proteins from the cleavage complex, a multifactorial protein complex of approximately 800 kDa, accomplish this specific nuclease activity. Specific RNA sequences upstream and downstream of the polyA site control the recruitment of the cleavage complex. Immediately after cleavage, pre-mRNAs are polyadenylated by the polyA polymerase (PAP) to produce mature stable RNA messages. Processing of the 3’ end of an RNA transcript may be studied using cellular nuclear extracts with specific radiolabeled RNA substrates. In sum, a long 32P-labeled uncleaved precursor RNA is incubated with nuclear extracts in vitro, and cleavage is assessed by gel electrophoresis and autoradiography. When proper cleavage occurs, a shorter 5’ cleaved product is detected and quantified. Here, we describe the cleavage assay in detail using, as an example, the 3’ end processing of HIV-1 mRNAs. PMID:24835792

Capability of cation exchange technology to remove proven N-nitrosodimethylamine precursors.

PubMed

Li, Shixiang; Zhang, Xulan; Bei, Er; Yue, Huihui; Lin, Pengfei; Wang, Jun; Zhang, Xiaojian; Chen, Chao

2017-08-01

N-nitrosodimethylamine (NDMA) precursors consist of a positively charged dimethylamine group and a non-polar moiety, which inspired us to develop a targeted cation exchange technology to remove NDMA precursors. In this study, we tested the removal of two representative NDMA precursors, dimethylamine (DMA) and ranitidine (RNTD), by strong acidic cation exchange resin. The results showed that pH greatly affected the exchange efficiency, with high removal (DMA>78% and RNTD>94%) observed at pHMg 2+ >RNTD + >K + >DMA + >NH 4 + >Na + . The partition coefficient of DMA + to Na + was 1.41±0.26, while that of RNTD + to Na + was 12.1±1.9. The pseudo second-order equation fitted the cation exchange kinetics well. Bivalent inorganic cations such as Ca 2+ were found to have a notable effect on NA precursor removal in softening column test. Besides DMA and RNTD, cation exchange process also worked well for removing other 7 model NDMA precursors. Overall, NDMA precursor removal can be an added benefit of making use of cation exchange water softening processes. Copyright © 2017. Published by Elsevier B.V.

Anti-CD22–chimeric antigen receptors targeting B-cell precursor acute lymphoblastic leukemia

PubMed Central

Haso, Waleed; Lee, Daniel W.; Shah, Nirali N.; Stetler-Stevenson, Maryalice; Yuan, Constance M.; Pastan, Ira H.; Dimitrov, Dimiter S.; Morgan, Richard A.; FitzGerald, David J.; Barrett, David M.; Wayne, Alan S.; Mackall, Crystal L.

2013-01-01

Immune targeting of B-cell malignancies using chimeric antigen receptors (CARs) is a promising new approach, but critical factors impacting CAR efficacy remain unclear. To test the suitability of targeting CD22 on precursor B-cell acute lymphoblastic leukemia (BCP-ALL), lymphoblasts from 111 patients with BCP-ALL were assayed for CD22 expression and all were found to be CD22-positive, with median CD22 expression levels of 3500 sites/cell. Three distinct binding domains targeting CD22 were fused to various TCR signaling domains ± an IgG heavy chain constant domain (CH2CH3) to create a series of vector constructs suitable to delineate optimal CAR configuration. CARs derived from the m971 anti-CD22 mAb, which targets a proximal CD22 epitope demonstrated superior antileukemic activity compared with those incorporating other binding domains, and addition of a 4-1BB signaling domain to CD28.CD3ζ constructs diminished potency, whereas increasing affinity of the anti-CD22 binding motif, and extending the CD22 binding domain away from the membrane via CH2CH3 had no effect. We conclude that second-generation m971 mAb-derived anti-CD22 CARs are promising novel therapeutics that should be tested in BCP-ALL. PMID:23243285

Anti-CD22-chimeric antigen receptors targeting B-cell precursor acute lymphoblastic leukemia.

PubMed

Haso, Waleed; Lee, Daniel W; Shah, Nirali N; Stetler-Stevenson, Maryalice; Yuan, Constance M; Pastan, Ira H; Dimitrov, Dimiter S; Morgan, Richard A; FitzGerald, David J; Barrett, David M; Wayne, Alan S; Mackall, Crystal L; Orentas, Rimas J

2013-02-14

Immune targeting of B-cell malignancies using chimeric antigen receptors (CARs) is a promising new approach, but critical factors impacting CAR efficacy remain unclear. To test the suitability of targeting CD22 on precursor B-cell acute lymphoblastic leukemia (BCP-ALL), lymphoblasts from 111 patients with BCP-ALL were assayed for CD22 expression and all were found to be CD22-positive, with median CD22 expression levels of 3500 sites/cell. Three distinct binding domains targeting CD22 were fused to various TCR signaling domains ± an IgG heavy chain constant domain (CH2CH3) to create a series of vector constructs suitable to delineate optimal CAR configuration. CARs derived from the m971 anti-CD22 mAb, which targets a proximal CD22 epitope demonstrated superior antileukemic activity compared with those incorporating other binding domains, and addition of a 4-1BB signaling domain to CD28.CD3 constructs diminished potency, whereas increasing affinity of the anti-CD22 binding motif, and extending the CD22 binding domain away from the membrane via CH2CH3 had no effect. We conclude that second-generation m971 mAb-derived anti-CD22 CARs are promising novel therapeutics that should be tested in BCP-ALL.

Precursors for the synthesis of citrulline in mice fed arginine free diets

USDA-ARS?s Scientific Manuscript database

Dietary arginine (Arg) is the main dietary precursor for citrulline (Cit) synthesis. To test the hypothesis that the contribution of dietary proline (Pro) and glutamine (Gln) increases during the feeding of an Arg free diet, rates of appearance (Ra) and precursor-intermediate-product relationships w...

Discharges of produced waters from oil and gas extraction via wastewater treatment plants are sources of disinfection by-products to receiving streams.

PubMed

Hladik, Michelle L; Focazio, Michael J; Engle, Mark

2014-01-01

Fluids co-produced with oil and gas production (produced waters) are often brines that contain elevated concentrations of bromide. Bromide is an important precursor of several toxic disinfection by-products (DBPs) and the treatment of produced water may lead to more brominated DBPs. To determine if wastewater treatment plants that accept produced waters discharge greater amounts of brominated DBPs, water samples were collected in Pennsylvania from four sites along a large river including an upstream site, a site below a publicly owned wastewater treatment plant (POTW) outfall (does not accept produced water), a site below an oil and gas commercial wastewater treatment plant (CWT) outfall, and downstream of the POTW and CWT. Of 29 DBPs analyzed, the site at the POTW outfall had the highest number detected (six) ranging in concentration from 0.01 to 0.09 μg L(-1) with a similar mixture of DBPs that have been detected at POTW outfalls elsewhere in the United States. The DBP profile at the CWT outfall was much different, although only two DBPs, dibromochloronitromethane (DBCNM) and chloroform, were detected, DBCNM was found at relatively high concentrations (up to 8.5 μg L(-1)). The water at the CWT outfall also had a mixture of inorganic and organic precursors including elevated concentrations of bromide (75 mg L(-1)) and other organic DBP precursors (phenol at 15 μg L(-1)). To corroborate these DBP results, samples were collected in Pennsylvania from additional POTW and CWT outfalls that accept produced waters. The additional CWT also had high concentrations of DBCNM (3.1 μg L(-1)) while the POTWs that accept produced waters had elevated numbers (up to 15) and concentrations of DBPs, especially brominated and iodinated THMs (up to 12 μg L(-1) total THM concentration). Therefore, produced water brines that have been disinfected are potential sources of DBPs along with DBP precursors to streams wherever these wastewaters are discharged. © 2013.

Nanostructured nonprecious metal catalysts for oxygen reduction reaction.

PubMed

Wu, Gang; Zelenay, Piotr

2013-08-20

Platinum-based catalysts represent a state of the art in the electrocatalysis of oxygen reduction reaction (ORR) from the point of view of their activity and durability in harnessing the chemical energy via direct electrochemical conversion. However, because platinum is both expensive and scarce, its widespread implementation in such clean energy applications is limited. Recent breakthroughs in the synthesis of high-performance nonprecious metal catalysts (NPMCs) make replacement of Pt in ORR electrocatalysts with earth-abundant elements, such as Fe, Co, N, and C, a realistic possibility. In this Account, we discuss how we can obtain highly promising M-N-C (M: Fe and/or Co) catalysts by simultaneously heat-treating precursors of nitrogen, carbon, and transition metals at 800-1000 °C. The activity and durability of resulting catalysts depend greatly on the selection of precursors and synthesis chemistry. In addition, they correlate quite well with the catalyst nanostructure. While chemists have presented no conclusive description of the active catalytic site for this class of NPMCs, they have developed a designed approach to making active and durable materials, focusing on the catalyst nanostructure. The approach consists of nitrogen doping, in situ carbon graphitization, and the usage of graphitic structures (possibly graphene and graphene oxides) as carbon precursors. Various forms of nitrogen, particularly pyridinic and quaternary, can act as n-type carbon dopants in the M-N-C catalysts, assisting in the formation of disordered carbon nanostructures and donating electrons to the carbon. The CNx structures are likely a crucial part of the ORR active site(s). Noteworthy, the ORR activity is not necessarily governed by the amount of nitrogen, but by how the nitrogen is incorporated into the nanostructures. Apart from the possibility of a direct participation in the active site, the transition metal often plays an important role in the in situ formation of various carbon nanostructures by catalyzing the decomposition of the nitrogen/carbon precursor. We can control the formation of different nanostructures during the synthesis of M-N-C catalysts. For example, in situ formed nitrogen-doped graphene-sheets can only be derived from polyaniline (PANI), probably due to structural similarities between the aromatic structures of PANI and graphene. Highly-graphitized carbon nanostructures may serve as a matrix for the formation of ORR-active groups with improved catalytic activity and durability, containing nitrogen and most probably also metal atoms. In the future, we will likely focus NPMC synthesis approaches on precise control of interactions between precursors of the metal and carbon/nitrogen during the heat treatment. The main purposes will be to maximize the number of active sites, optimize nitrogen doping levels, and generate morphologies capable of hosting active and stable ORR sites.

Analyzing the distribution of hydrogeomorphic characteristics across Pennsylvania as a precursor to Phosphorus Index modifications

USDA-ARS?s Scientific Manuscript database

Phosphorus site assessment is used nationally and internationally to assess the vulnerability of agricultural fields to phosphorus (P) loss and identify “critical source areas” controlling watershed P export. Current efforts to update P site assessment tools must ensure that the tools are representa...

Atomic layer deposition of hafnium oxide: A detailed reaction mechanism from first principles

NASA Astrophysics Data System (ADS)

Widjaja, Yuniarto; Musgrave, Charles B.

2002-08-01

Atomic layer deposition (ALD) of hafnium oxide (HfO2) using HfCl4 and H2O as precursors is studied using density functional theory. The mechanism consists of two deposition half-reactions: (1) HfCl4 with Hf-OH sites, and (2) H2O with Hf-Cl sites. Both half-reactions exhibit stable intermediates with energies lower than those of the final products. We show that increasing the temperature reduces the stability of the complex. However, increasing temperature also increases the dissociation free-energy barrier, which in turn results in increased desorption of adsorbed precursors. Both half-reactions are qualitatively similar to the corresponding reactions of ZrO2 ALD using ZrCl4 and H2O.

Chemical repair of base lesions, AP-sites, and strand breaks on plasmid DNA in dilute aqueous solution by ascorbic acid

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

Hata, Kuniki; Advanced Science Research Center, Japan Atomic Energy Agency, 2-4 Shirakatashirane, Tokai-mura, Naka-gun, Ibaraki 319-1195; Urushibara, Ayumi

Highlights: •We report a novel mechanism of radiation protection of DNA by chemical activity of ascorbic acid. •The “chemical repair” of DNA damage was revealed using biochemical assay and chemical kinetics analysis. •We found that ascorbic acid significantly repairs precursors of nucleobase lesions and abasic sites. •However, ascorbic acid seldom repairs precursors of DNA-strand breaks. -- Abstract: We quantified the damage yields produced in plasmid DNA by γ-irradiation in the presence of low concentrations (10–100 μM) of ascorbic acid, which is a major antioxidant in living systems, to clarify whether it chemically repairs radiation damage in DNA. The yield ofmore » DNA single strand breaks induced by irradiation was analyzed with agarose gel electrophoresis as conformational changes in closed circular plasmids. Base lesions and abasic sites were also observed as additional conformational changes by treating irradiated samples with glycosylase proteins. By comparing the suppression efficiencies to the induction of each DNA lesion, in addition to scavenging of the OH radicals derived from water radiolysis, it was found that ascorbic acid promotes the chemical repair of precursors of AP-sites and base lesions more effectively than those of single strand breaks. We estimated the efficiency of the chemical repair of each lesion using a kinetic model. Approximately 50–60% of base lesions and AP-sites were repaired by 10 μM ascorbic acid, although strand breaks were largely unrepaired by ascorbic acid at low concentrations. The methods in this study will provide a route to understanding the mechanistic aspects of antioxidant activity in living systems.« less

[BACE1 inhibitors for the treatment of Alzheimer disease].

PubMed

Tomita, Taisuke

2016-03-01

β-Site amyloid precursor protein cleaving enzyme 1 (BACEl) is the enzyme required for the production of the amyloid-β peptide(Aβ), which is associated with Alzheimer disease (AD). BACEl has emerged as a prime molecular target for reducing the brain Aβ levels. Recently, several BACEl inhibitors have been developed in clinical trials to test the efficacy in AD patients and individuals with prodromal AD. However, identification of BACE1 substrates and phenotypes of Bace1 knockout mice have raised concerns regarding potential mechanism-based adverse effects. This review summarizes the current status of the development of BACE1 inhibitors and the evaluation of their therapeutic potential against AD.

The cleavage specificity of the aspartic protease of cocoa beans involved in the generation of the cocoa-specific aroma precursors.

PubMed

Janek, Katharina; Niewienda, Agathe; Wöstemeyer, Johannes; Voigt, Jürgen

2016-11-15

Particular peptides generated from the vicilin-class(7S) globulin of the cocoa beans by acid-induced proteolysis during cocoa fermentation are essential precursors of the cocoa-specific aroma notes. As revealed by in vitro studies, the formation of the cocoa-specific aroma precursors depends on the particular cleavage specificity of the cocoa aspartic protease, which cannot be substituted by pepsin. Therefore, we have investigated the effects of aspartic protease inhibitors on both enzymes and comparatively studied their cleavage specificities using different protein substrates and MALDI-TOF mass spectrometric analyses of the generated oligopeptides. Three classes of cleavage sites have been identified and characterized: (I) sequences exclusively cleaved by the cocoa enzyme, (II) sequences cleaved by both pepsin and the cocoa enzyme, and (III) those cleaved exclusively by pepsin. In contrast to most aspartic proteases from other origins, basic amino acid residues, particularly lysine, were found to be abundant in the specific cleavage sites of the cocoa enzyme. Copyright © 2016 Elsevier Ltd. All rights reserved.

Nicotinamide Riboside Is a Major NAD+ Precursor Vitamin in Cow Milk.

PubMed

Trammell, Samuel Aj; Yu, Liping; Redpath, Philip; Migaud, Marie E; Brenner, Charles

2016-05-01

Nicotinamide riboside (NR) is a recently discovered NAD(+) precursor vitamin with a unique biosynthetic pathway. Although the presence of NR in cow milk has been known for more than a decade, the concentration of NR with respect to the other NAD(+) precursors was unknown. We aimed to determine NAD(+) precursor vitamin concentration in raw samples of milk from individual cows and from commercially available cow milk. LC tandem mass spectrometry and isotope dilution technologies were used to quantify NAD(+) precursor vitamin concentration and to measure NR stability in raw and commercial milk. Nuclear magnetic resonance (NMR) spectroscopy was used to test for NR binding to substances in milk. Cow milk typically contained ∼12 μmol NAD(+) precursor vitamins/L, of which 60% was present as nicotinamide and 40% was present as NR. Nicotinic acid and other NAD(+) metabolites were below the limits of detection. Milk from samples testing positive for Staphylococcus aureus contained lower concentrations of NR (Spearman ρ = -0.58, P = 0.014), and NR was degraded by S. aureus Conventional milk contained more NR than milk sold as organic. Nonetheless, NR was stable in organic milk and exhibited an NMR spectrum consistent with association with a protein fraction in skim milk. NR is a major NAD(+) precursor vitamin in cow milk. Control of S. aureus may be important to preserve the NAD(+) precursor vitamin concentration of milk. © 2016 American Society for Nutrition.

Activity-based assay for ricin-like toxins

DOEpatents

Keener, William K.; Ward, Thomas E.

2007-02-06

A method of detecting N-glycosylase activity in a sample involves incubating an oligodeoxyribonucleotide substrate containing a deoxyadenosine or deoxyuridine residue with the sample to be tested such that the N-glycosylase, if present, hydrolyzes the deoxyadenosine or deoxyuridine residue to result in an N-glycosylase product having an abasic site. A primer is annealed to the N-glycosylase product, and the primer is extended with a DNA polymerase, such as Taq DNA polymerase, that pauses at abasic sites. The resulting extension products are melted from the N-glycosylase product, allowed to form hairpins due to self-complementarity, and further extended in the presence of labeled precursors to result in labeled products. Extension products synthesized from undigested substrate as template do not result in labeled products. Thus, detection of labeled products results in detection of N-glycosylase activity. Oligodeoxyribonucleotide substrates, primer, and positive controls and a kit for N-glycosylase assay are also disclosed.

Nucleolus Precursor Bodies and Ribosome Biogenesis in Early Mammalian Embryos: Old Theories and New Discoveries.

PubMed

Fulka, Helena; Aoki, Fugaku

2016-06-01

In mammals, mature oocytes and early preimplantation embryos contain transcriptionally inactive structures termed nucleolus precursor bodies instead of the typical fibrillo-granular nucleoli. These nuclear organelles are essential and strictly of maternal origin. If they are removed from oocytes, the resulting embryos are unable to replace them and consequently fail to develop. Historically, nucleolus precursor bodies have been perceived as a passive repository site of nucleolar proteins that are required for embryos to form fully functional nucleoli. Recent results, however, contradict this long-standing dogma and show that these organelles are dispensable for nucleologenesis and ribosome biogenesis. In this article, we discuss the possible roles of nucleolus precursor bodies and propose how they might be involved in embryogenesis. Furthermore, we argue that these organelles are essential only shortly after fertilization and suggest that they might actively participate in centromeric chromatin establishment. © 2016 by the Society for the Study of Reproduction, Inc.

The Common Inhalational Anesthetic Sevoflurane Induces Apoptosis and Increases β-Amyloid Protein Levels

PubMed Central

Dong, Yuanlin; Zhang, Guohua; Zhang, Bin; Moir, Robert D.; Xia, Weiming; Marcantonio, Edward R.; Culley, Deborah J.; Crosby, Gregory; Tanzi, Rudolph E.; Xie, Zhongcong

2009-01-01

Objective: To assess the effects of sevoflurane, the most commonly used inhalation anesthetic, on apoptosis and β-amyloid protein (Aβ) levels in vitro and in vivo. Subjects: Naive mice, H4 human neuroglioma cells, and H4 human neuroglioma cells stably transfected to express full-length amyloid precursor protein. Interventions: Human H4 neuroglioma cells stably transfected to express full-length amyloid precursor protein were exposed to 4.1% sevoflurane for 6 hours. Mice received 2.5% sevoflurane for 2 hours. Caspase-3 activation, apoptosis, and Aβ levels were assessed. Results: Sevoflurane induced apoptosis and elevated levels of β-site amyloid precursor protein-cleaving enzyme and Aβ in vitro and in vivo. The caspase inhibitor Z-VAD decreased the effects of sevoflurane on apoptosis and Aβ. Sevoflurane-induced caspase-3 activation was attenuated by the γ-secretase inhibitor L-685,458 and was potentiated by Aβ. These results suggest that sevoflurane induces caspase activation which, in turn, enhances β-site amyloid precursor protein–cleaving enzyme and Aβ levels. Increased Aβ levels then induce further rounds of apoptosis. Conclusions: These results suggest that inhalational anesthetic sevoflurane may promote Alzheimer disease neuropathogenesis. If confirmed in human subjects, it may be prudent to caution against the use of sevoflurane as an anesthetic, especially in those suspected of possessing excessive levels of cerebral Aβ. PMID:19433662

Neurotensin and neuromedin N are differentially processed from a common precursor by prohormone convertases in tissues and cell lines.

PubMed

Kitabgi, Patrick

2010-01-01

Neurotensin (NT) is synthesized as part of a larger precursor that also contains neuromedin N (NN), a six amino acid NT-like peptide. NT and NN are located in the C-terminal region of the precursor (pro-NT/NN) where they are flanked and separated by three Lys-Arg sequences. A fourth dibasic sequence is present in the middle of the precursor. Dibasics are the consensus sites recognized and cleaved by specialized endoproteases that belong to the family of proprotein convertases (PCs). In tissues that express pro-NT/NN, the three C-terminal Lys-Arg sites are differentially processed, whereas the middle dibasic is poorly cleaved. Processing gives rise mainly to NT and NN in the brain, NT and a large peptide with a C-terminal NN moiety (large NN) in the gut, and NT, large NN, and a large peptide with a C-terminal NT moiety (large NT) in the adrenals. Recent evidence indicates that PC1, PC2, and PC5-A are the prohormone convertases responsible for the processing patterns observed in the gut, brain, and adrenals, respectively. As NT, NN, large NT, and large NN are all endowed with biological activity, the evidence reviewed here supports the idea that posttranslational processing of pro-NT/NN in tissues may generate biological diversity of pathophysiological relevance.

Prediction of proprotein convertase cleavage sites.

PubMed

Duckert, Peter; Brunak, Søren; Blom, Nikolaj

2004-01-01

Many secretory proteins and peptides are synthesized as inactive precursors that in addition to signal peptide cleavage undergo post-translational processing to become biologically active polypeptides. Precursors are usually cleaved at sites composed of single or paired basic amino acid residues by members of the subtilisin/kexin-like proprotein convertase (PC) family. In mammals, seven members have been identified, with furin being the one first discovered and best characterized. Recently, the involvement of furin in diseases ranging from Alzheimer's disease and cancer to anthrax and Ebola fever has created additional focus on proprotein processing. We have developed a method for prediction of cleavage sites for PCs based on artificial neural networks. Two different types of neural networks have been constructed: a furin-specific network based on experimental results derived from the literature, and a general PC-specific network trained on data from the Swiss-Prot protein database. The method predicts cleavage sites in independent sequences with a sensitivity of 95% for the furin neural network and 62% for the general PC network. The ProP method is made publicly available at http://www.cbs.dtu.dk/services/ProP.

Attribution of Trends and Variability in Surface Ozone over the United States

NASA Technical Reports Server (NTRS)

Strode, Sarah; Cooper, Owen; Damo, Megan; Logan, Jennifer; Rodriquez, Jose; Strahan, Susan; Witte, Jacquie

2013-01-01

Concentrations of tropospheric ozone, a greenhouse gas and air pollutant, are impacted by changes in precursor emissions as well meteorology and influx from the stratosphere. Observations show a decreasing trend in summertime surface ozone at rural stations in the eastern United States, while some western stations show increasing trends, particularly in springtime. We use the Global Modeling Initiative (GMI) global chemical transport model to investigate the roles of precursor emission changes, meteorological variability, and stratosphere-troposphere exchange (STE) in explaining observed trends in surface ozone from rural sites in the United States from 1991-2010. The model's interannual variability shows significant correlations with observations from many of the surface sites. We also compare the simulated ozone to ozonesonde data for several locations with sufficiently long records. We compare a simulation with time-dependent precursor emissions, including emission reductions over the United States and Europe and increases over Asia, to a simulation with fixed emissions to quantify the impact of changing emissions on the surface trends. The simulation with varying emissions reproduces much of the east-west difference in summertime ozone over the U.S., although it generally underestimates the negative trend in the East. In contrast, the fixed-emission simulation shows increasing ozone at both eastern and western sites. We will discuss possible causes of this behavior, including long-range transport and STE.

Undesired Small RNAs Originate from an Artificial microRNA Precursor in Transgenic Petunia (Petunia hybrida)

PubMed Central

Guo, Yulong; Han, Yao; Ma, Jing; Wang, Huiping; Sang, Xianchun; Li, Mingyang

2014-01-01

Although artificial microRNA (amiRNA) technology has been used frequently in gene silencing in plants, little research has been devoted to investigating the accuracy of amiRNA precursor processing. In this work, amiRNAchs1 (amiRchs1), based on the Arabidopsis miR319a precursor, was expressed in order to suppress the expression of CHS genes in petunia. The transgenic plants showed the CHS gene-silencing phenotype. A modified 5′ RACE technique was used to map small-RNA-directed cleavage sites and to detect processing intermediates of the amiRchs1 precursor. The results showed that the target CHS mRNAs were cut at the expected sites and that the amiRchs1 precursor was processed from loop to base. The accumulation of small RNAs in amiRchs1 transgenic petunia petals was analyzed using the deep-sequencing technique. The results showed that, alongside the accumulation of the desired artificial microRNAs, additional small RNAs that originated from other regions of the amiRNA precursor were also accumulated at high frequency. Some of these had previously been found to be accumulated at low frequency in the products of ath-miR319a precursor processing and some of them were accompanied by 3′-tailing variant. Potential targets of the undesired small RNAs were discovered in petunia and other Solanaceae plants. The findings draw attention to the potential occurrence of undesired target silencing induced by such additional small RNAs when amiRNA technology is used. No appreciable production of secondary small RNAs occurred, despite the fact that amiRchs1 was designed to have perfect complementarity to its CHS-J target. This confirmed that perfect pairing between an amiRNA and its targets is not the trigger for secondary small RNA production. In conjunction with the observation that amiRNAs with perfect complementarity to their target genes show high efficiency and specificity in gene silencing, this finding has an important bearing on future applications of amiRNAs in gene silencing in plants. PMID:24897430

Undesired small RNAs originate from an artificial microRNA precursor in transgenic petunia (Petunia hybrida).

PubMed

Guo, Yulong; Han, Yao; Ma, Jing; Wang, Huiping; Sang, Xianchun; Li, Mingyang

2014-01-01

Although artificial microRNA (amiRNA) technology has been used frequently in gene silencing in plants, little research has been devoted to investigating the accuracy of amiRNA precursor processing. In this work, amiRNAchs1 (amiRchs1), based on the Arabidopsis miR319a precursor, was expressed in order to suppress the expression of CHS genes in petunia. The transgenic plants showed the CHS gene-silencing phenotype. A modified 5' RACE technique was used to map small-RNA-directed cleavage sites and to detect processing intermediates of the amiRchs1 precursor. The results showed that the target CHS mRNAs were cut at the expected sites and that the amiRchs1 precursor was processed from loop to base. The accumulation of small RNAs in amiRchs1 transgenic petunia petals was analyzed using the deep-sequencing technique. The results showed that, alongside the accumulation of the desired artificial microRNAs, additional small RNAs that originated from other regions of the amiRNA precursor were also accumulated at high frequency. Some of these had previously been found to be accumulated at low frequency in the products of ath-miR319a precursor processing and some of them were accompanied by 3'-tailing variant. Potential targets of the undesired small RNAs were discovered in petunia and other Solanaceae plants. The findings draw attention to the potential occurrence of undesired target silencing induced by such additional small RNAs when amiRNA technology is used. No appreciable production of secondary small RNAs occurred, despite the fact that amiRchs1 was designed to have perfect complementarity to its CHS-J target. This confirmed that perfect pairing between an amiRNA and its targets is not the trigger for secondary small RNA production. In conjunction with the observation that amiRNAs with perfect complementarity to their target genes show high efficiency and specificity in gene silencing, this finding has an important bearing on future applications of amiRNAs in gene silencing in plants.

Effects of N-glycan precursor length diversity on quality control of protein folding and on protein glycosylation

PubMed Central

Samuelson, John; Robbins, Phillips W.

2014-01-01

Asparagine-linked glycans (N-glycans) of medically important protists have much to tell us about the evolution of N-glycosylation and of N-glycan-dependent quality control (N-glycan QC) of protein folding in the endoplasmic reticulum. While host N-glycans are built upon a dolichol-pyrophosphate-linked precursor with 14 sugars (Glc3Man9GlcNAc2), protist N-glycan precursors vary from Glc3Man9GlcNAc2 (Acanthamoeba) to Man9GlcNAc2 (Trypanosoma) to Glc3Man5GlcNAc2 (Toxoplasma) to Man5GlcNAc2 (Entamoeba, Trichomonas, and Eimeria) to GlcNAc2 (Plasmodium and Giardia) to zero (Theileria). As related organisms have differing N-glycan lengths (e.g. Toxoplasma, Eimeria, Plasmodium, and Theileria), the present N-glycan variation is based upon secondary loss of Alg genes, which encode enzymes that add sugars to the N-glycan precursor. An N-glycan precursor with Man5GlcNAc2 is necessary but not sufficient for N-glycan QC, which is predicted by the presence of the UDP-glucose:glucosyltransferase (UGGT) plus calreticulin and/or calnexin. As many parasites lack glucose in their N-glycan precursor, UGGT product may be identified by inhibition of glucosidase II. The presence of an armless calnexin in Toxoplasma suggests secondary loss of N-glycan QC from coccidia. Positive selection for N-glycan sites occurs in secreted proteins of organisms with NG-QC and is based upon an increased likelihood of threonine but not serine in the second position versus asparagine. In contrast, there appears to be selection against N-glycan length in Plasmodium and N-glycan site density in Toxoplasma. Finally, there is suggestive evidence for N-glycan-dependent ERAD in Trichomonas, which glycosylates and degrades the exogenous reporter mutant carboxypeptidase Y (CPY*). PMID:25475176

Analysis of Recent European Surface Ozone Trends Considering Site Representativeness and Mete-orology

NASA Astrophysics Data System (ADS)

Henne, S.; Fleming, Z.; Brunner, D.; Klausen, J.; Buchmann, B.

2009-04-01

Recent trends of surface ozone (O3) within Europe vary substantially depending on the location and surroundings of a measurement site. The influence of long-range transport from North America and Asia, changes in stratosphere-troposphere exchange, increase in lower stratospheric O3 and changes in advection patterns are possible drivers for the observed O3 trends. O3 concentrations greatly depend on meteorology (temperature and radiation) and local to regional emissions of precursor gases and therefore on the representativeness of a site (e.g. background vs. urban site) and regional emission trends. We investigated the representativeness of 1264 "rural" and "suburban" background sites (as available through the European Environment Agency (EEA )Airbase database) by analysing population density, land cover and topography in the surrounding of the sites. A hierarchical clustering method was applied to derive an independent site categorization. The two area types as specified by EEA are split into 7 categories: elevated, lowered, remote, rural, rural/coastal, rural/polluted, suburban. Furthermore, we analysed the trend of surface O3 and Ox (O3+NO2) for the mentioned sites based on the above site categorization, local meteorology and precursor emission trends. Of the 1264 sites 161 possess sufficiently long and complete O3 data series suitable for robust trend estimation, while for 100 sites both O3 and NO2 data are available. We present a strategy for further data exclusion based on available data quality information and a break detection algorithm. First results of the trend analysis applying different statistical approaches are discussed.

Book lung development in juveniles and adults of the cobweb spider, Parasteatoda tepidariorum C. L. Koch, 1841 (Araneomorphae, Theridiidae).

PubMed

Farley, Roger D

2018-03-01

Light and transmission electron microscopy were used to study the development of new book lung lamellae in juvenile and adult spiders (Parasteatoda tepidariorum). As hypothesized earlier in a study of embryos, mesenchyme cells dispersed throughout the opisthosoma (EMT) are a likely source of precursor epithelial cells (MET) for the new lamellae. The precursor cells in juveniles and adults continue many of the complex activities observed in embryos, e.g., migration, alignment, lumen formation, thinning, elongation, and secretion of the cuticle of air channel walls and trabeculae. The apicobasal polarity of precursor cells for new channels is apparently induced by the polarity pattern of precursor cells of channels produced earlier. Thus, new air and hemolymph channels extend and continue the alternating pattern of older channels. At sites more distant from the spiracle and atrium, new channels are usually produced by the mode II process (intracellular alignment and merging of vesicles). These air channels have bridging trabeculae and are quite stable in size throughout their length. At sites closer to the spiracle and atrium, new channels may be produced by mode I (coalescence of merocrine vesicle secretion). This raises the hypothesis that structural and functional differences in mode I and II channels and differing oxygen and fluid conditions with distance from the spiracle and atrium determine the mode of formation of new channels. Observations herein support an earlier hypothesis that there is some intercellular apical/apical and basal/basal affinity among the opposed surfaces of aligned precursor cells. This results in the alternating pattern of air channels at the apical and hemolymph channels at the basal cell surfaces. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

The parent body controls on cosmic spherule texture: Evidence from the oxygen isotopic compositions of large micrometeorites

NASA Astrophysics Data System (ADS)

van Ginneken, M.; Gattacceca, J.; Rochette, P.; Sonzogni, C.; Alexandre, A.; Vidal, V.; Genge, M. J.

2017-09-01

High-precision oxygen isotopic compositions of eighteen large cosmic spherules (>500 μm diameter) from the Atacama Desert, Chile, were determined using IR-laser fluorination - Isotope Ratio Mass spectrometry. The four discrete isotopic groups defined in a previous study on cosmic spherules from the Transantarctic Mountains (Suavet et al., 2010) were identified, confirming their global distribution. Approximately 50% of the studied cosmic spherules are related to carbonaceous chondrites, 38% to ordinary chondrites and 12% to unknown parent bodies. Approximately 90% of barred olivine (BO) cosmic spherules show oxygen isotopic compositions suggesting they are related to carbonaceous chondrites. Similarly, ∼90% porphyritic olivine (Po) cosmic spherules are related to ordinary chondrites and none can be unambiguously related to carbonaceous chondrites. Other textures are related to all potential parent bodies. The data suggests that the textures of cosmic spherules are mainly controlled by the nature of the precursor rather than by the atmospheric entry parameters. We propose that the Po texture may essentially be formed from a coarse-grained precursor having an ordinary chondritic mineralogy and chemistry. Coarse-grained precursors related to carbonaceous chondrites (i.e. chondrules) are likely to either survive atmospheric entry heating or form V-type cosmic spherules. Due to the limited number of submicron nucleation sites after total melting, ordinary chondrite-related coarse-grained precursors that suffer higher peak temperatures will preferentially form cryptocrystalline (Cc) textures instead of BO textures. Conversely, the BO textures would be mostly related to the fine-grained matrices of carbonaceous chondrites due to the wide range of melting temperatures of their constituent mineral phases, allowing the preservation of submicron nucleation sites. Independently of the nature of the precursors, increasing peak temperatures form glassy textures.

Evaluation of the chemical reactivity in lignin precursors using the Fukui function.

PubMed

Martinez, Carmen; Rivera, José L; Herrera, Rafael; Rico, José L; Flores, Nelly; Rutiaga, José G; López, Pablo

2008-02-01

The hydroxycinnamyl alcohols: p-coumarol, coniferol and sinapol are considered the basic units and precursors of lignins models. In this work, the specific reactivity of these molecules was studied. We investigate their intrinsic chemical reactivity in terms of the Fukui function, applying the principle of hard and soft acids and bases (HSAB) in the framework of the density functional theory (DFT). Comparisons of their nucleophilic, electrophilic and free radical reactivity show their most probably sites to form linkages among them. It is found that the most reactive sites, for reactions involving free radicals, are the carbons at the beta-position in the p-coumarol and sinapol molecules, whilst the regions around the carbon-oxygen bond of the phenoxyl group are the most reactive in coniferol.

Robots and Humans in Planetary Exploration: Working Together?

NASA Technical Reports Server (NTRS)

Landis, Geoffrey A.; Lyons, Valerie (Technical Monitor)

2002-01-01

Today's approach to human-robotic cooperation in planetary exploration focuses on using robotic probes as precursors to human exploration. A large portion of current NASA planetary surface exploration is focussed on Mars, and robotic probes are seen as precursors to human exploration in: Learning about operation and mobility on Mars; Learning about the environment of Mars; Mapping the planet and selecting landing sites for human mission; Demonstration of critical technology; Manufacture fuel before human presence, and emplace elements of human-support infrastructure

Adult subependymal neural precursors, but not differentiated cells, undergo rapid cathodal migration in the presence of direct current electric fields.

PubMed

Babona-Pilipos, Robart; Droujinine, Ilia A; Popovic, Milos R; Morshead, Cindi M

2011-01-01

The existence of neural stem and progenitor cells (together termed neural precursor cells) in the adult mammalian brain has sparked great interest in utilizing these cells for regenerative medicine strategies. Endogenous neural precursors within the adult forebrain subependyma can be activated following injury, resulting in their proliferation and migration toward lesion sites where they differentiate into neural cells. The administration of growth factors and immunomodulatory agents following injury augments this activation and has been shown to result in behavioural functional recovery following stroke. With the goal of enhancing neural precursor migration to facilitate the repair process we report that externally applied direct current electric fields induce rapid and directed cathodal migration of pure populations of undifferentiated adult subependyma-derived neural precursors. Using time-lapse imaging microscopy in vitro we performed an extensive single-cell kinematic analysis demonstrating that this galvanotactic phenomenon is a feature of undifferentiated precursors, and not differentiated phenotypes. Moreover, we have shown that the migratory response of the neural precursors is a direct effect of the electric field and not due to chemotactic gradients. We also identified that epidermal growth factor receptor (EGFR) signaling plays a role in the galvanotactic response as blocking EGFR significantly attenuates the migratory behaviour. These findings suggest direct current electric fields may be implemented in endogenous repair paradigms to promote migration and tissue repair following neurotrauma.

Preparing to return to the Moon: Lessons from science-driven analogue missions to the Mistastin Lake impact structure, Canada, a unique lunar analogue site

NASA Astrophysics Data System (ADS)

Osinski, G. R.; Barfoot, T.; Chanou, A.; Daly, M. G.; Francis, R.; Hodges, K. V.; Jolliff, B. L.; Mader, M. M.; McCullough, E. M.; Moores, J. E.; Pickersgill, A.; Pontefract, A.; Preston, L.; Shankar, B.; Singleton, A.; Sylvester, P.; Tornabene, L. L.; Young, K. E.

2013-12-01

Impact cratering is the dominant geological process on the Moon, Near Earth Asteroids (NEAs) and the moons of Mars - the objectives for the new Solar System Exploration Research Virtual Institute (SSERVI). Led by members of the Canadian Lunar Research Network (CLRN), funded by the Canadian Space Agency, and with participants from the U.S., we carried out a series of analogue missions on Earth in order to prepare and train for future potential robotic and human sample return missions. Critically, these analogue missions were driven by the paradigm that operational and technical objectives are conducted while conducting new science and addressing real overarching scientific objectives. An overarching operational goal was to assess the utility of a robotic field reconnaissance mission as a precursor to a human sortie sample return mission. Here, we focus on the results and lessons learned from a robotic precursor mission and follow on human-robotic mission to the Mistastin Lake impact structure in Labrador, northern Canada (55°53'N; 63°18'W). The Mistastin structure was chosen because it represents an exceptional analogue for lunar craters. This site includes both an anorthositic target, a central uplift, well-preserved impact melt rocks - mostly derived from melting anorthosite - and is (or was) relatively unexplored. This crater formed ~36 million years ago and has a diameter of ~28 km. The scientific goals for these analogue missions were to further our understanding of impact chronology, shock processes, impact ejecta and potential resources within impact craters. By combining these goals in an analogue mission campaign key scientific requirements for a robotic precursor were determined. From the outset, these analogue missions were formulated and executed like an actual space mission. Sites of interest were chosen using remote sensing imagery without a priori knowledge of the site through a rigorous site selection process. The first deployment occurred in August and September 2010 and involved simulated robotic surveying of selected 'landing sites' at the Mistastin structure. The second deployment took place at the same location in 2011, which included simulated astronaut surface operations with, and without, the aid of a robotic assistant. A mission control team, based at the University of Western Ontario, London, Ontario, 1,900 km from the field site, oversaw operations. Our study showed the value of precursor reconnaissance missions in providing surface geology visualization at resolutions and from viewpoints not achievable from orbit, including high-resolution surface imagery on the scale of 10s of metres to kilometres. Indeed, data collected during the robotic precursor mission led to the formulation of a hypothesis that a large impact melt outcrop - named Discovery Hill - represents an impact melt pond in the terraced region of the crater, analogous to similar ponds of melt documented around the rim of well-preserved lunar craters such as Tycho. Further discoveries, that will be highlight here, include documentation of ejecta deposits for the first time at Mistastin, quantification of shock in anorthosites, and refined age estimates for the Mistastin impact event.

Deposition and Characterization of Thin Films on Metallic Substrates

NASA Technical Reports Server (NTRS)

Gatica, Jorge E.

2005-01-01

A CVD method was successfully developed to produce conversion coatings on aluminum alloys surfaces with reproducible results with a variety of precursors. A well defined protocol to prepare the precursor solutions formulated in a previous research was extended to other additives. It was demonstrated that solutions prepared following such a protocol could be used to systematically generate protective coatings onto aluminum surfaces. Experiments with a variety of formulations revealed that a refined deposition protocol yields reproducible conversion coatings of controlled composition. A preliminary correlation between solution formulations and successful precursors was derived. Coatings were tested for adhesion properties enhancement for commercial paints. A standard testing method was followed and clear trends were identified. Only one precursors was tested systematically. Anticipated work on other precursors should allow a better characterization of the effect of intermetallics on the production of conversion/protective coatings on metals and ceramics. The significance of this work was the practical demonstration that chemical vapor deposition (CVD) techniques can be used to systematically generate protective/conversion coating on non-ferrous surfaces. In order to become an effective approach to replace chromate-based pre- treatment processes, namely in the aerospace or automobile industry, the process parameters must be defined more precisely. Moreover, the feasibility of scale-up designs necessitates a more comprehensive characterization of the fluid flow, transport phenomena, and chemical kinetics interacting in the process. Kinetic characterization showed a significantly different effect of magnesium-based precursors when compared to iron-based precursors. Future work will concentrate on refining the process through computer simulations and further experimental studies on the effect of other transition metals to induce deposition of conversion/protective films on aluminum and other metallic substrates.

Effects of P/Ni ratio and Ni content on performance of γ-Al2O3-supported nickel phosphides for deoxygenation of methyl laurate to hydrocarbons

NASA Astrophysics Data System (ADS)

Zhang, Zhena; Tang, Mingxiao; Chen, Jixiang

2016-01-01

γ-Al2O3-supported nickel phosphides (mNi-Pn) were prepared by the TPR method and tested for the deoxygenation of methyl laurate to hydrocarbons. The effects of the P/Ni ratio (n = 1.0-2.5) and Ni content (m = 5-15 wt.%) in the precursors on their structure and performance were investigated. Ni/γ-Al2O3 was also studied for comparison. It was found that the formation of AlPO4 in the precursor inhibited the reduction of phosphate and so the formation of nickel phosphides. With increasing the P/Ni ratio and Ni content, the Ni, Ni3P, Ni12P5 and Ni2P phases orderly formed, accompanying with the increases of their particle size and the amount of weak acid sites (mainly due to P-OH group), while the CO uptake and the amount of medium strong acid sites (mainly related to Ni sites) reached maximum on 10%Ni-P1.5. In the deoxygenation reaction, compared with Ni/γ-Al2O3, the mNi-Pn catalysts showed much lower activities for decarbonylation, Csbnd C hydrogenolysis and methanation due to the ligand and ensemble effects of P. The conversion and the selectivity to n-C11 and n-C12 hydrocarbons achieved maximum on 10%Ni-P 2.0 for the 10%Ni-Pn catalysts and on 8%Ni-P2.0 for the mNi-P2.0 catalysts, while the turnover frequency (TOF) of methyl laurate mainly increased with the P/Ni ratio and Ni content. We propose that TOF was influenced by the nickel phosphide phases, the catalyst acidity and the particle size as well as the synergetic effect between the Ni site and acid site. Again, the hydrodeoxygenation pathway of methyl laurate was promoted with increasing P/Ni ratio and Ni content, ascribed to the phase change in the order of Ni, Ni3P, Ni12P5 and Ni2P in the prepared catalysts.

Development of advanced test methods for the improvement of production standards for ceramic powders used in solid oxide fuel cells

NASA Astrophysics Data System (ADS)

Ward, Brian

Solid oxide fuel cells (SOFCs) are energy conversion devices that use ceramic powders as a precursor material for their electrodes. Presently, powder manufacturers are encountering complications producing consistent precursor powders. Through various thermal, chemical and physical tests, such as DSC and XRD, a preliminary production standard will be developed.

Surface reaction of silicon chlorides during atomic layer deposition of silicon nitride

NASA Astrophysics Data System (ADS)

Yusup, Luchana L.; Park, Jae-Min; Mayangsari, Tirta R.; Kwon, Young-Kyun; Lee, Won-Jun

2018-02-01

The reaction of precursor with surface active site is the critical step in atomic layer deposition (ALD) process. We performed the density functional theory calculation with DFT-D correction to study the surface reaction of different silicon chloride precursors during the first half cycle of ALD process. SiCl4, SiH2Cl2, Si2Cl6 and Si3Cl8 were considered as the silicon precursors, and an NH/SiNH2*-terminated silicon nitride surface was constructed to model the thermal ALD processes using NH3 as well as the PEALD processes using NH3 plasma. The total energies of the system were calculated for the geometry-optimized structures of physisorption, chemisorption, and transition state. The order of silicon precursors in energy barrier, from lowest to highest, is Si3Cl8 (0.92 eV), Si2Cl6 (3.22 eV), SiH2Cl2 (3.93 eV) and SiCl4 (4.49 eV). Silicon precursor with lower energy barrier in DFT calculation showed lower saturation dose in literature for both thermal and plasma-enhanced ALD of silicon nitride. Therefore, DFT calculation is a promising tool in predicting the reactivity of precursor during ALD process.

Processing of the precursor of protamine P2 in mouse. Peptide mapping and N-terminal sequence analysis of intermediates.

PubMed Central

Carré-Eusèbe, D; Lederer, F; Lê, K H; Elsevier, S M

1991-01-01

Protamine P2, the major basic chromosomal protein of mouse spermatozoa, is synthesized as a precursor almost twice as long as the mature protein, its extra length arising from an N-terminal extension of 44 amino acid residues. This precursor is integrated into chromatin of spermatids, and the extension is processed during chromatin condensation in the haploid cells. We have studied processing in the mouse and have identified two intermediates generated by proteolytic cleavage of the precursor. H.p.l.c. separated protamine P2 from four other spermatid proteins, including the precursor and three proteins known to possess physiological characteristics expected of processing intermediates. Peptide mapping indicated that all of these proteins were structurally similar. Two major proteins were further purified by PAGE, transferred to poly(vinylidene difluoride) membranes and submitted to automated N-terminal sequence analysis. Both sequences were found within the deduced sequence of the precursor extension. The N-terminus of the larger intermediate, PP2C, was Gly-12, whereas the N-terminus of the smaller, PP2D, was His-21. Both processing sites involved a peptide bond in which the carbonyl function was contributed by an acidic amino acid. Images Fig. 1. Fig. 3. Fig. 4. PMID:1854346

CXCR6 Expression Is Important for Retention and Circulation of ILC Precursors.

PubMed

Chea, Sylvestre; Possot, Cécilie; Perchet, Thibaut; Petit, Maxime; Cumano, Ana; Golub, Rachel

2015-01-01

Innate lymphoid cells are present at mucosal sites and represent the first immune barrier against infections, but what contributes to their circulation and homing is still unclear. Using Rag2(-/-) Cxcr6(Gfp/+) reporter mice, we assessed the expression and role of CXCR6 in the circulation of ILC precursors and their progeny. We identify CXCR6 expressing ILC precursors in the bone marrow and characterize their significant increase in CXCR6-deficient mice at steady state, indicating their partial retention in the bone marrow after CXCR6 ablation. Circulation was also impaired during embryonic life as fetal liver from CXCR6-deficient embryos displayed decreased numbers of ILC3 precursors. When injected, fetal CXCR6-deficient ILC3 precursors also fail to home and reconstitute ILC compartments in vivo. We show that adult intestinal ILC subsets have heterogeneous expression pattern of CXCR6, integrin α 4 β 7, CD62L, CD69, and CD44, with ILC1 and ILC3 being more likely tissue resident lymphocytes. Intestinal ILC subsets were unchanged in percentages and numbers in both mice. We demonstrate that the ILC frequency is maintained due to a significant increase of ILC peripheral proliferation, as well as an increased proliferation of the in situ ILC precursors to compensate their retention in the bone marrow.

Generation of amyloid-β is reduced by the interaction of calreticulin with amyloid precursor protein, presenilin and nicastrin.

PubMed

Stemmer, Nina; Strekalova, Elena; Djogo, Nevena; Plöger, Frank; Loers, Gabriele; Lutz, David; Buck, Friedrich; Michalak, Marek; Schachner, Melitta; Kleene, Ralf

2013-01-01

Dysregulation of the proteolytic processing of amyloid precursor protein by γ-secretase and the ensuing generation of amyloid-β is associated with the pathogenesis of Alzheimer's disease. Thus, the identification of amyloid precursor protein binding proteins involved in regulating processing of amyloid precursor protein by the γ-secretase complex is essential for understanding the mechanisms underlying the molecular pathology of the disease. We identified calreticulin as novel amyloid precursor protein interaction partner that binds to the γ-secretase cleavage site within amyloid precursor protein and showed that this Ca(2+)- and N-glycan-independent interaction is mediated by amino acids 330-344 in the C-terminal C-domain of calreticulin. Co-immunoprecipitation confirmed that calreticulin is not only associated with amyloid precursor protein but also with the γ-secretase complex members presenilin and nicastrin. Calreticulin was detected at the cell surface by surface biotinylation of cells overexpressing amyloid precursor protein and was co-localized by immunostaining with amyloid precursor protein and presenilin at the cell surface of hippocampal neurons. The P-domain of calreticulin located between the N-terminal N-domain and the C-domain interacts with presenilin, the catalytic subunit of the γ-secretase complex. The P- and C-domains also interact with nicastrin, another functionally important subunit of this complex. Transfection of amyloid precursor protein overexpressing cells with full-length calreticulin leads to a decrease in amyloid-β42 levels in culture supernatants, while transfection with the P-domain increases amyloid-β40 levels. Similarly, application of the recombinant P- or C-domains and of a synthetic calreticulin peptide comprising amino acid 330-344 to amyloid precursor protein overexpressing cells result in elevated amyloid-β40 and amyloid-β42 levels, respectively. These findings indicate that the interaction of calreticulin with amyloid precursor protein and the γ-secretase complex regulates the proteolytic processing of amyloid precursor protein by the γ-secretase complex, pointing to calreticulin as a potential target for therapy in Alzheimer's disease.

Atomistic kinetic Monte Carlo study of atomic layer deposition derived from density functional theory.

PubMed

Shirazi, Mahdi; Elliott, Simon D

2014-01-30

To describe the atomic layer deposition (ALD) reactions of HfO2 from Hf(N(CH3)2)4 and H2O, a three-dimensional on-lattice kinetic Monte-Carlo model is developed. In this model, all atomistic reaction pathways in density functional theory (DFT) are implemented as reaction events on the lattice. This contains all steps, from the early stage of adsorption of each ALD precursor, kinetics of the surface protons, interaction between the remaining precursors (steric effect), influence of remaining fragments on adsorption sites (blocking), densification of each ALD precursor, migration of each ALD precursors, and cooperation between the remaining precursors to adsorb H2O (cooperative effect). The essential chemistry of the ALD reactions depends on the local environment at the surface. The coordination number and a neighbor list are used to implement the dependencies. The validity and necessity of the proposed reaction pathways are statistically established at the mesoscale. The formation of one monolayer of precursor fragments is shown at the end of the metal pulse. Adsorption and dissociation of the H2O precursor onto that layer is described, leading to the delivery of oxygen and protons to the surface during the H2O pulse. Through these processes, the remaining precursor fragments desorb from the surface, leaving the surface with bulk-like and OH-terminated HfO2, ready for the next cycle. The migration of the low coordinated remaining precursor fragments is also proposed. This process introduces a slow reordering motion (crawling) at the mesoscale, leading to the smooth and conformal thin film that is characteristic of ALD. Copyright © 2013 Wiley Periodicals, Inc.

Mars Exploration 2003 to 2013 - An Integrated Perspective: Time Sequencing the Missions

NASA Technical Reports Server (NTRS)

Briggs, G.; McKay, C.

2000-01-01

The science goals for the Mars exploration program, together with the HEDS precursor environmental and technology needs, serve as a solid starting point for re-planning the program in an orderly way. Most recently, the community has recognized the significance of subsurface sampling as a key component in "following the water". Accessing samples from hundreds and even thousands of meters beneath the surface is a challenge that will call for technology development and for one or more demonstration missions. Recent mission failures and concerns about the complexity of the previously planned MSR missions indicate that, before we are ready to undertake sample return and deep sampling, the Mars exploration program needs to include: 1) technology development missions; and 2) basic landing site assessment missions. These precursor missions should demonstrate the capability for reliable & accurate soft landing and in situ propellant production. The precursor missions will need to carry out close-up site observations, ground-penetrating radar mapping from orbit and conduct seismic surveys. Clearly the programs should be planned as a single, continuous exploration effort. A prudent minimum list of missions, including surface rovers with ranges of more than 10 km, can be derived from the numerous goals and requirements; they can be sequenced in an orderly way to ensure that time is available to feed forward the results of the precursor missions. One such sequence of missions is proposed for the decade beginning in 2003.

One-dimensional α-MoO3 nanorods for high energy density pseudocapacitor

NASA Astrophysics Data System (ADS)

Dutta, Shibsankar; Pal, Shreyasi; De, Sukanta

2018-04-01

Ultralong α-MoO3 nanorods having length of 500 nm to 1 µm and uniform width of around ˜50 nm have been synthesized by a simple one step hydrothermal route using a molybdenum organic salt precursor. An evaluation of the electrochemical properties of the nanorods was done by cyclic voltammetry (CV), and galvanometric charging- discharging (GCD) test. Because of the high active sites and rapid ion diffusion and electron transport of the electrodes using as prepared nanorods reveals energy density of 65 Wh/kg at a power density of 940 W/ kg and a maximum specific capacitance of 474 F/g. It also shows excellent cycling stability.

Scanning electrochemical microscopy of precursor sites for pitting corrosion on titanium

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

Casillas, N.; Charlebois, S.J.; Smyrl, W.H.

1993-09-01

Scanning electrochemical microscopy, SECM, of oxide-covered titanium foils ([approximately]50 [angstrom] oxide thickness) immersed in potassium bromide solutions is reported. Electrogeneration of bromine (2 Br[sup [minus

The Efficiency of Dentin Sialoprotein-Phosphophoryn Processing Is Affected by Mutations Both Flanking and Distant from the Cleavage Site*

PubMed Central

Yang, Robert T.; Lim, Glendale L.; Dong, Zhihong; Lee, Arthur M.; Yee, Colin T.; Fuller, Robert S.; Ritchie, Helena H.

2013-01-01

Normal dentin mineralization requires two highly acidic proteins, dentin sialoprotein (DSP) and phosphophoryn (PP). DSP and PP are synthesized as part of a single secreted precursor, DSP-PP, which is conserved in marsupial and placental mammals. Using a baculovirus expression system, we previously found that DSP-PP is accurately cleaved into DSP and PP after secretion into medium by an endogenous, secreted, zinc-dependent Sf9 cell activity. Here we report that mutation of conserved residues near and distant from the G447↓D448 cleavage site in DSP-PP240 had dramatic effects on cleavage efficiency by the endogenous Sf9 cell processing enzyme. We found that: 1) mutation of residues flanking the cleavage site from P4 to P4′ blocked, impaired, or enhanced DSP-PP240 cleavage; 2) certain conserved amino acids distant from the cleavage site were important for precursor cleavage; 3) modification of the C terminus by appending a C-terminal tag altered the pattern of processing; and 4) mutations in DSP-PP240 had similar effects on cleavage by recombinant human BMP1, a candidate physiological processing enzyme, as was seen with the endogenous Sf9 cell activity. An analysis of a partial TLR1 cDNA from Sf9 cells indicates that residues that line the substrate-binding cleft of Sf9 TLR1 and human BMP1 are nearly perfectly conserved, offering an explanation of why Sf9 cells so accurately process mammalian DSP-PP. The fact that several mutations in DSP-PP240 significantly modified the amount of PP240 product generated from DSP-PP240 precursor protein cleavage suggests that such mutation may affect the mineralization process. PMID:23297400

The efficiency of dentin sialoprotein-phosphophoryn processing is affected by mutations both flanking and distant from the cleavage site.

PubMed

Yang, Robert T; Lim, Glendale L; Dong, Zhihong; Lee, Arthur M; Yee, Colin T; Fuller, Robert S; Ritchie, Helena H

2013-02-22

Normal dentin mineralization requires two highly acidic proteins, dentin sialoprotein (DSP) and phosphophoryn (PP). DSP and PP are synthesized as part of a single secreted precursor, DSP-PP, which is conserved in marsupial and placental mammals. Using a baculovirus expression system, we previously found that DSP-PP is accurately cleaved into DSP and PP after secretion into medium by an endogenous, secreted, zinc-dependent Sf9 cell activity. Here we report that mutation of conserved residues near and distant from the G(447)↓D(448) cleavage site in DSP-PP(240) had dramatic effects on cleavage efficiency by the endogenous Sf9 cell processing enzyme. We found that: 1) mutation of residues flanking the cleavage site from P(4) to P(4)' blocked, impaired, or enhanced DSP-PP(240) cleavage; 2) certain conserved amino acids distant from the cleavage site were important for precursor cleavage; 3) modification of the C terminus by appending a C-terminal tag altered the pattern of processing; and 4) mutations in DSP-PP(240) had similar effects on cleavage by recombinant human BMP1, a candidate physiological processing enzyme, as was seen with the endogenous Sf9 cell activity. An analysis of a partial TLR1 cDNA from Sf9 cells indicates that residues that line the substrate-binding cleft of Sf9 TLR1 and human BMP1 are nearly perfectly conserved, offering an explanation of why Sf9 cells so accurately process mammalian DSP-PP. The fact that several mutations in DSP-PP(240) significantly modified the amount of PP(240) product generated from DSP-PP(240) precursor protein cleavage suggests that such mutation may affect the mineralization process.

Sulfonium Ion Derivatization, Isobaric Stable Isotope Labeling and Data Dependent CID- and ETD-MS/MS for Enhanced Phosphopeptide Quantitation, Identification and Phosphorylation Site Characterization

PubMed Central

Lu, Yali; Zhou, Xiao; Stemmer, Paul M.; Reid, Gavin E.

2014-01-01

An amine specific peptide derivatization strategy involving the use of novel isobaric stable isotope encoded ‘fixed charge’ sulfonium ion reagents, coupled with an analysis strategy employing capillary HPLC, ESI-MS, and automated data dependent ion trap CID-MS/MS, -MS3, and/or ETD-MS/MS, has been developed for the improved quantitative analysis of protein phosphorylation, and for identification and characterization of their site(s) of modification. Derivatization of 50 synthetic phosphopeptides with S,S′-dimethylthiobutanoylhydroxysuccinimide ester iodide (DMBNHS), followed by analysis using capillary HPLC-ESI-MS, yielded an average 2.5-fold increase in ionization efficiencies and a significant increase in the presence and/or abundance of higher charge state precursor ions compared to the non-derivatized phosphopeptides. Notably, 44% of the phosphopeptides (22 of 50) in their underivatized states yielded precursor ions whose maximum charge states corresponded to +2, while only 8% (4 of 50) remained at this maximum charge state following DMBNHS derivatization. Quantitative analysis was achieved by measuring the abundances of the diagnostic product ions corresponding to the neutral losses of ‘light’ (S(CH3)2) and ‘heavy’ (S(CD3)2) dimethylsulfide exclusively formed upon CID-MS/MS of isobaric stable isotope labeled forms of the DMBNHS derivatized phosphopeptides. Under these conditions, the phosphate group stayed intact. Access for a greater number of peptides to provide enhanced phosphopeptide sequence identification and phosphorylation site characterization was achieved via automated data-dependent CID-MS3 or ETD-MS/MS analysis due to the formation of the higher charge state precursor ions. Importantly, improved sequence coverage was observed using ETD-MS/MS following introduction of the sulfonium ion fixed charge, but with no detrimental effects on ETD fragmentation efficiency. PMID:21952753

Production of NOx and other precursors of ozone formation in the Uinta Basin

NASA Astrophysics Data System (ADS)

Smith, E.; Lyman, S. N.; Martin, R. S.; Anderson, R.

2012-12-01

The Uinta Basin, located in northeastern Utah, sometimes experiences ozone mixing ratios greater than the EPA NAAQS during specific meteorological conditions that include a combination of snow cover and inversion. We monitored ozone and some of its precursors, including NO, NO2, NOx (NO + NO2), and NOy (sum of reactive nitrogen species), at two sites (Roosevelt and Horse Pool). The Roosevelt site is in a city of about 6,000 people, and the Horse Pool site is in an area of intensive oil and gas production. In February and March 2012, NO, NO2, and NOy mixing ratios were 0.5 ± 0.8, 5.2 ± 2.6, and 6.5 ± 3.9 ppb at Roosevelt and 0 ± 1.3, 2.8 ± 2.7, and 4.1 ± 4.4 ppb at Horse Pool, respectively (mean ± standard deviation). NO, NO2, and NOx were measured at 7 other sites around the Basin by other entities. The spatial and temporal patterns in NOx and NOy indicate the dominance of local source influences on observed mixing ratios. NOx at urban sites and in oil and gas production areas appeared strongly influenced by traffic patterns. At some sites, wind direction analysis and air trajectory analysis indicated that areas of oil and gas production are significant sources of NOx, though pinpointing individual NOx sources proved difficult.

Direct identification of the site of binding on the chaperone SecB for the amino terminus of the translocon motor SecA.

PubMed

Randall, Linda L; Henzl, Michael T

2010-06-01

Protein export mediated by the general secretory Sec system in Escherichia coli proceeds by a dynamic transfer of a precursor polypeptide from the chaperone SecB to the SecA ATPase motor of the translocon and subsequently into and through the channel of the membrane-embedded SecYEG heterotrimer. The complex between SecA and SecB is stabilized by several separate sites of contact. Here we have demonstrated directly an interaction between the N-terminal residues 2 through 11 of SecA and the C-terminal 13 residues of SecB by isothermal titration calorimetry and analytical sedimentation velocity centrifugation. We discuss the unusual binding properties of SecA and SecB in context of a model for transfer of the precursor along the pathway of export.

Evaluating Oil and Gas Speciation Profiles with Factor Analysis of Ambient Volatile Organic Compound Concentrations in the Colorado Front Range

NASA Astrophysics Data System (ADS)

Capps, S.; Paranjothi, G.; Pierce, G. E.; Milford, J. B.

2016-12-01

Increased oil and gas (O&G) development, particularly through the use of hydraulic fracturing, in the Denver-Julesburg Basin (DJB) in Colorado over the last decade has been identified as a source of emissions of air pollutants, which are now included in chemical transport modeling. As one effort to evaluate its impact, ambient concentrations of volatile organic compounds (VOCs) that serve as precursors to ozone formation were measured in an Ozone Precursor Study conducted by the Colorado Department of Public Health and Environment during 2013 and 2014. The study included 6 - 9 a.m. measurements of an extensive suite of ozone-precursor VOCs from a site in an area of intensive O&G development in Platteville, CO, and another site in downtown Denver, CO. To evaluate the influences of urban activity or O&G development on these ambient concentrations, we used the U.S. EPA's Positive Matrix Factorization (PMF) tool. A five-factor PMF solution was selected as providing the best fit to the dataset comprised of VOC measurements for both years and both sites. One PMF factor matches the VOC emissions speciation profile for the flashing gas composition for condensate tanks in the DJB that was developed by the Western Regional Air Partnership for use in chemical transport modeling in the region. The contribution of this factor to individual and total VOC concentrations and ozone production reactivity is evaluated for Platteville and Denver.

Precursor-Based Synthesis of Porous Colloidal Particles towards Highly Efficient Catalysts.

PubMed

Zheng, Yun; Geng, Hongbo; Zhang, Yufei; Chen, Libao; Li, Cheng Chao

2018-04-02

In recent years, porous colloidal particles have found promising applications in catalytic fields, such as photocatalysis, electrocatalysis, industrial and automotive byproducts removal, as well as biomass upgrading. These applications are critical for alleviating the energy crisis and environmental pollution. Porous colloidal particles have remarkable specific areas and abundant reactive sites, which can significantly improve the mass/charge transport and reaction rate in catalysis. Precursor-based synthesis is among the most facile and widely-adopted methods to achieve monodisperse and homogeneous porous colloidal particles. In the current review, we briefly introduce the general catalytic applications of porous colloidal particles. The conventional precursor-based methods are reviewed to design state-of-the-art porous colloidal particles as highly efficient catalysts. The recent development of porous colloidal particles derived from metal-organic frameworks (MOFs), glycerates, carbonate precursors, and ion exchange methods are reviewed. In the end, the current concerns and future development of porous colloidal particles are outlined. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Structural Basis For Antigenic Peptide Precursor Processing by the Endoplasmic Reticulum Aminopeptidase ERAP1

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

T Nguyen; S Chang; I Evnouchidou

2011-12-31

ERAP1 trims antigen precursors to fit into MHC class I proteins. To fulfill this function, ERAP1 has unique substrate preferences, trimming long peptides but sparing shorter ones. To identify the structural basis for ERAP1's unusual properties, we determined the X-ray crystal structure of human ERAP1 bound to bestatin. The structure reveals an open conformation with a large interior compartment. An extended groove originating from the enzyme's catalytic center can accommodate long peptides and has features that explain ERAP1's broad specificity for antigenic peptide precursors. Structural and biochemical analyses suggest a mechanism for ERAP1's length-dependent trimming activity, whereby binding of longmore » rather than short substrates induces a conformational change with reorientation of a key catalytic residue toward the active site. ERAP1's unique structural elements suggest how a generic aminopeptidase structure has been adapted for the specialized function of trimming antigenic precursors.« less

Photochemical Assessment Monitoring Stations (PAMS)

EPA Pesticide Factsheets

Photochemical Assessment Monitoring Stations (PAMS). This file provides information on the numbers and distribution (latitude/longitude) of air monitoring sites which measure ozone precursors (approximately 60 volatile hydrocarbons and carbonyl), as required by the 1990 Clean Air Act Amendments, in areas with persistently high ozone levels (mostly large metropolitan areas). In these areas, the States have established ambient air monitoring sites which collect and report detailed data for volatile organic compounds, nitrogen oxides, ozone and meteorological parameters. This file displays 199 monitoring sites reporting measurements for 2010. A wide range of related monitoring site attributes is also provided.

Design and crystal structure of a native-like HIV-1 envelope trimer that engages multiple broadly neutralizing antibody precursors in vivo

DOE PAGES

Medina-Ramírez, Max; Garces, Fernando; Escolano, Amelia; ...

2017-08-28

Induction of broadly neutralizing antibodies (bNAbs) by HIV-1 envelope glycoprotein immunogens would be a major advance toward an effective vaccine. A critical step in this process is the activation of naive B cells expressing germline (gl) antibody precursors that have the potential to evolve into bNAbs. Here, we reengineered the BG505 SOSIP.664 glycoprotein to engage gl precursors of bNAbs that target either the trimer apex or the CD4-binding site. The resulting BG505 SOSIP.v4.1-GT1 trimer binds multiple bNAb gl precursors in vitro. Immunization experiments in knock-in mice expressing gl-VRC01 or gl-PGT121 show that this trimer activates B cells in vivo, resultingmore » in the secretion of specific antibodies into the sera. A crystal structure of the gl-targeting trimer at 3.2-Å resolution in complex with neutralizing antibodies 35O22 and 9H+109L reveals a native-like conformation and the successful incorporation of design features associated with binding of multiple gl-bNAb precursors.« less

Design and crystal structure of a native-like HIV-1 envelope trimer that engages multiple broadly neutralizing antibody precursors in vivo

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

Medina-Ramírez, Max; Garces, Fernando; Escolano, Amelia

Induction of broadly neutralizing antibodies (bNAbs) by HIV-1 envelope glycoprotein immunogens would be a major advance toward an effective vaccine. A critical step in this process is the activation of naive B cells expressing germline (gl) antibody precursors that have the potential to evolve into bNAbs. Here, we reengineered the BG505 SOSIP.664 glycoprotein to engage gl precursors of bNAbs that target either the trimer apex or the CD4-binding site. The resulting BG505 SOSIP.v4.1-GT1 trimer binds multiple bNAb gl precursors in vitro. Immunization experiments in knock-in mice expressing gl-VRC01 or gl-PGT121 show that this trimer activates B cells in vivo, resultingmore » in the secretion of specific antibodies into the sera. A crystal structure of the gl-targeting trimer at 3.2-Å resolution in complex with neutralizing antibodies 35O22 and 9H+109L reveals a native-like conformation and the successful incorporation of design features associated with binding of multiple gl-bNAb precursors.« less

Precursor effect on the property and catalytic behavior of Fe-TS-1 in butadiene epoxidation

NASA Astrophysics Data System (ADS)

Wu, Mei; Zhao, Huahua; Yang, Jian; Zhao, Jun; Song, Huanling; Chou, Lingjun

2017-11-01

The effect of iron precursor on the property and catalytic behavior of iron modified titanium silicalite molecular sieve (Fe-TS-1) catalysts in butadiene selective epoxidation has been studied. Three Fe-TS-1 catalysts were prepared, using iron nitrate, iron chloride and iron sulfate as precursors, which played an important role in adjusting the textural properties and chemical states of TS-1. Of the prepared Fe-TS-1 catalysts, those modified by iron nitrate (FN-TS-1) exhibited a significant enhanced performance in butadiene selective epoxidation compared to those derived from iron sulfate (FS-TS-1) or iron chloride (FC-TS-1) precursors. To obtain a deep understanding of their structure-performance relationship, X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), Temperature programmed desorption of NH3 (NH3-TPD), Diffuse reflectance UV-Vis spectra (DR UV-Vis), Fourier transformed infrared spectra (FT-IR) and thermal gravimetric analysis (TGA) were conducted to characterize Fe-TS-1 catalysts. Experimental results indicated that textural structures and acid sites of modified catalysts as well as the type of Fe species influenced by the precursors were all responsible for the activity and product distribution.

Synthesis and characterization of mesoporous spinel NiCo2O4 using surfactant-assembled dispersion for asymmetric supercapacitors

NASA Astrophysics Data System (ADS)

Hsu, Chun-Tsung; Hu, Chi-Chang

2013-11-01

A simple and scalable process has been developed for synthesizing spinel NiCo2O4 nanocrystals through a thermal decomposition method. The introduction of hexadecyltrimethylammonium bromide (CTAB, (C16H33)N(CH3)3Br) into precursor solutions significantly enhances the homogeneity and porosity of spinel NiCo2O4. The porosity and high specific surface area of NiCo2O4 preserves the brilliant pseudo-capacitive performances due to providing smooth paths for electrolyte penetration and ion diffusion into inner active sites. Morphologies and microstructures of the active materials are examined by transmission electron microscopic (TEM) and X-ray diffraction (XRD) analyses. Thermogravimetric analysis (TGA) is used to evaluate the thermal properties of precursor solutions. The electrochemical performances of NiCo2O4 are systematically characterized by cyclic voltammetry and charge-discharge tests. Asymmetric supercapacitors are assembled with these brilliant binary oxides as the positive electrode and activated carbon as the negative electrode. The highly porous NiCo2O4 exhibits superior capacitive performances, i.e., high specific capacitance (764 F g-1 at 2 mV s-1) and long cycle life.

A multi-sensor approach to landslide monitoring of rainfall-induced failures in Scotland.

NASA Astrophysics Data System (ADS)

Gilles, Charlie; Hoey, Trevor; Williams, Richard

2017-04-01

Landslides are of significant interest in upland areas of the United Kingdom due to their: complex mechanics, potential to channelize into hazardous debris flows and their costly potential impacts on infrastructure. The British Geological Survey National Landslide Database contains an average of 367 landslides per year (from 1970). Slope failures in the UK are typically triggered by extended periods of intense rainfall, and can occur at any time of year. In any given rainfall event that triggers landslides, most potentially vulnerable slopes remain stable. Accurate warning systems would be facilitated by identifying landslide precursors prior to failure events. This project tests whether such precursors can be identified in the valley of Glen Ogle, Scotland (87 km north-west of Edinburgh), where in summer 2004 two debris flows blocked the main road (A85), trapping fifty-seven people. Two adjacent sites have been selected on a west facing slope in Glen Ogle, one of which (the control) has been stable since at least 2004 and the other failed in 2004 and remains unstable. Understanding the immediate causes and antecedent conditions responsible for landslides requires a multi-scale approach. This project uses multiple sensors to assess failure mechanisms of landslides in Glen Ogle: (1) 3-monthly, high (1.8 arcsec) resolution terrestrial laser scanning of topography to detect changes and identify patterns of movement prior to major failure, using the Riegl VZ-1000 (NERC Geophysical Equipment Fund); (2) rainfall and soil moisture data to monitor pore pressure of landslide failure prior to and after hydrologically triggered events; (3) monitoring ground motion using grain-scale sensors which are becoming lower cost, more efficient in terms of power, and can be wirelessly networked these will be used to detect small scale movement of the landslide. Comparative data from the control and test sites will be presented, from which patterns of surface deformation between failure events will be derived.

The p2 domain of human immunodeficiency virus type 1 Gag regulates sequential proteolytic processing and is required to produce fully infectious virions.

PubMed

Pettit, S C; Moody, M D; Wehbie, R S; Kaplan, A H; Nantermet, P V; Klein, C A; Swanstrom, R

1994-12-01

The proteolytic processing sites of the human immunodeficiency virus type 1 (HIV-1) Gag precursor are cleaved in a sequential manner by the viral protease. We investigated the factors that regulate sequential processing. When full-length Gag protein was digested with recombinant HIV-1 protease in vitro, four of the five major processing sites in Gag were cleaved at rates that differ by as much as 400-fold. Three of these four processing sites were cleaved independently of the others. The CA/p2 site, however, was cleaved approximately 20-fold faster when the adjacent downstream p2/NC site was blocked from cleavage or when the p2 domain of Gag was deleted. These results suggest that the presence of a C-terminal p2 tail on processing intermediates slows cleavage at the upstream CA/p2 site. We also found that lower pH selectively accelerated cleavage of the CA/p2 processing site in the full-length precursor and as a peptide primarily by a sequence-based mechanism rather than by a change in protein conformation. Deletion of the p2 domain of Gag results in released virions that are less infectious despite the presence of the processed final products of Gag. These findings suggest that the p2 domain of HIV-1 Gag regulates the rate of cleavage at the CA/p2 processing site during sequential processing in vitro and in infected cells and that p2 may function in the proper assembly of virions.

MULTIPOLLUTANT METHODS - METHODS FOR OZONE AND OZONE PRECURSORS

EPA Science Inventory

This task involves the development and testing of methods for monitoring ozone and compounds associated with the atmospheric chemistry of ozone production both as precursors and reaction products. Although atmospheric gases are the primary interest, separation of gas and particl...

Anatomical location of LPA1 activation and LPA phospholipid precursors in rodent and human brain.

PubMed

González de San Román, Estibaliz; Manuel, Iván; Giralt, María Teresa; Chun, Jerold; Estivill-Torrús, Guillermo; Rodríguez de Fonseca, Fernando; Santín, Luis Javier; Ferrer, Isidro; Rodríguez-Puertas, Rafael

2015-08-01

Lysophosphatidic acid (LPA) is a signaling molecule that binds to six known G protein-coupled receptors: LPA1 -LPA6 . LPA evokes several responses in the CNS, including cortical development and folding, growth of the axonal cone and its retraction process. Those cell processes involve survival, migration, adhesion proliferation, differentiation, and myelination. The anatomical localization of LPA1 is incompletely understood, particularly with regard to LPA binding. Therefore, we have used functional [(35) S]GTPγS autoradiography to verify the anatomical distribution of LPA1 binding sites in adult rodent and human brain. The greatest activity was observed in myelinated areas of the white matter such as corpus callosum, internal capsule and cerebellum. MaLPA1 -null mice (a variant of LPA1 -null) lack [(35) S]GTPγS basal binding in white matter areas, where the LPA1 receptor is expressed at high levels, suggesting a relevant role of the activity of this receptor in the most myelinated brain areas. In addition, phospholipid precursors of LPA were localized by MALDI-IMS in both rodent and human brain slices identifying numerous species of phosphatides and phosphatidylcholines. Both phosphatides and phosphatidylcholines species represent potential LPA precursors. The anatomical distribution of these precursors in rodent and human brain may indicate a metabolic relationship between LPA and LPA1 receptors. Lysophosphatidic acid (LPA) is a signaling molecule that binds to six known G protein-coupled receptors (GPCR), LPA1 to LPA6 . LPA evokes several responses in the central nervous system (CNS), including cortical development and folding, growth of the axonal cone and its retraction process. We used functional [(35) S]GTPγS autoradiography to verify the anatomical distribution of LPA1 -binding sites in adult rodent and human brain. The distribution of LPA1 receptors in rat, mouse and human brains show the highest activity in white matter myelinated areas. The basal and LPA-evoked activities are abolished in MaLPA1 -null mice. The phospholipid precursors of LPA are localized by MALDI-IMS. The anatomical distribution of LPA precursors in rodent and human brain suggests a relationship with functional LPA1 receptors. © 2015 International Society for Neurochemistry.

Sindbis virus glycoproteins are abnormally glycosylated in Chinese hamster ovary cells deprived of glucose.

PubMed

Davidson, S K; Hunt, L A

1985-07-01

We have previously demonstrated that Sindbis virus infection of Chinese hamster ovary (CHO) cells altered the protein glycosylation machinery of the cell, so that both normal, full-size (nine mannose-containing) oligosaccharides and abnormal, "truncated' (five mannose-containing) oligosaccharides are transferred from lipid-linked precursors to newly synthesized viral membrane glycoproteins. In the present studies, we have examined the precursor oligosaccharides on viral glycoproteins that were pulse-labelled with [3H]mannose in the presence or absence of glucose, since glucose starvation of uninfected CHO cells has been reported to induce synthesis of truncated precursor oligosaccharides. Pulse-labelling in the absence of glucose led to a greater than 10-fold increase in the relative amount of the truncated precursor oligosaccharides being transferred to the newly synthesized viral glycoproteins and to an apparent underglycosylation of some precursor viral polypeptides, with some asparaginyl sites not acquiring covalently linked oligosaccharides. The mature virion glycoproteins from CHO cells which were pulse-labelled in the absence of glucose and then 'chased' in the presence of glucose contained proportionately more unusual Man3GlcNAc2-size oligosaccharides. These small neutral-type oligosaccharides were apparently not as good a substrate for further processing into complex acidic-type oligosaccharides as the normal Man5GlcNAc2 intermediate that results from the full-size precursor oligosaccharides.

CXCR6 Expression Is Important for Retention and Circulation of ILC Precursors

PubMed Central

Chea, Sylvestre; Possot, Cécilie; Perchet, Thibaut; Petit, Maxime; Cumano, Ana; Golub, Rachel

2015-01-01

Innate lymphoid cells are present at mucosal sites and represent the first immune barrier against infections, but what contributes to their circulation and homing is still unclear. Using Rag2 −/− Cxcr6 Gfp/+ reporter mice, we assessed the expression and role of CXCR6 in the circulation of ILC precursors and their progeny. We identify CXCR6 expressing ILC precursors in the bone marrow and characterize their significant increase in CXCR6-deficient mice at steady state, indicating their partial retention in the bone marrow after CXCR6 ablation. Circulation was also impaired during embryonic life as fetal liver from CXCR6-deficient embryos displayed decreased numbers of ILC3 precursors. When injected, fetal CXCR6-deficient ILC3 precursors also fail to home and reconstitute ILC compartments in vivo. We show that adult intestinal ILC subsets have heterogeneous expression pattern of CXCR6, integrin α 4 β 7, CD62L, CD69, and CD44, with ILC1 and ILC3 being more likely tissue resident lymphocytes. Intestinal ILC subsets were unchanged in percentages and numbers in both mice. We demonstrate that the ILC frequency is maintained due to a significant increase of ILC peripheral proliferation, as well as an increased proliferation of the in situ ILC precursors to compensate their retention in the bone marrow. PMID:26494947

Global Operations and Biometrics: Next Generation Capabilities and Policy Implications

DTIC Science & Technology

2013-04-01

could help identify individuals likely to have handled certain chemical, biological or radiological precursor substances associated with weapons of...or biologic weapon production or storage site. See U.S. Department of the Army, Site Exploitation Operations, Army Field Manual FM 3-90.15...and nuclear) forces and shifting increasingly toward the non-nation state actors organized as networked violent extremists, often seeking weapons of

Optimizing the performance of catalytic traps for hydrocarbon abatement during the cold-start of a gasoline engine.

PubMed

Puértolas, B; Navlani-García, M; García, T; Navarro, M V; Lozano-Castelló, D; Cazorla-Amorós, D

2014-08-30

A key target to reduce current hydrocarbon emissions from vehicular exhaust is to improve their abatement under cold-start conditions. Herein, we demonstrate the potential of factorial analysis to design a highly efficient catalytic trap. The impact of the synthesis conditions on the preparation of copper-loaded ZSM-5 is clearly revealed by XRD, N2 sorption, FTIR, NH3-TPD, SEM and TEM. A high concentration of copper nitrate precursor in the synthesis improves the removal of hydrocarbons, providing both strong adsorption sites for hydrocarbon retention at low temperature and copper oxide nanoparticles for full hydrocarbon catalytic combustion at high temperature. The use of copper acetate precursor leads to a more homogeneous dispersion of copper oxide nanoparticles also providing enough catalytic sites for the total oxidation of hydrocarbons released from the adsorption sites, although lower copper loadings are achieved. Thus, synthesis conditions leading to high copper loadings jointly with highly dispersed copper oxide nanoparticles would result in an exceptional catalytic trap able to reach superior hydrocarbon abatement under highly demanding operational conditions. Copyright © 2014 Elsevier B.V. All rights reserved.

Design and synthesis of a tetradentate '3-amine-1-carboxylate' ligand to mimic the metal binding environment at the non-heme iron(II) oxidase active site.

PubMed

Dungan, Victoria J; Ortin, Yannick; Mueller-Bunz, Helge; Rutledge, Peter J

2010-04-07

Non-heme iron(II) oxidases (NHIOs) catalyse a diverse array of oxidative chemistry in Nature. As part of ongoing efforts to realize biomimetic, iron-mediated C-H activation, we report the synthesis of a new 'three-amine-one-carboxylate' ligand designed to complex with iron(II) and mimic the NHIO active site. The tetradentate ligand has been prepared as a single enantiomer in nine synthetic steps from N-Cbz-L-alanine, pyridine-2,6-dimethanol and diphenylamine, using Seebach oxazolidinone chemistry to control the stereochemistry. X-Ray crystal structures are reported for two important intermediates, along with variable temperature NMR experiments to probe the hindered interconversion of conformational isomers of several key intermediates, 2,6-disubstituted pyridine derivatives. The target ligand and an N-Cbz-protected precursor were each then complexed with iron(II) and tested for their ability to promote alkene dihydroxylation, using hydrogen peroxide as the oxidant.

Climatology of atmospheric PM10 concentration in the Po Valley

NASA Astrophysics Data System (ADS)

Bigi, A.; Ghermandi, G.

2014-01-01

The limits to atmospheric pollutant concentration set by the European Commission provide a challenging target for the municipalities in the Po Valley, because of the characteristic climatic conditions and high population density of this region. In order to assess climatology and trends in the concentration of atmospheric particles in the Po Valley, a dataset of PM10 data from 41 sites across the Po Valley have been analysed, including both traffic and background sites (either urban, suburban or rural). Of these 41 sites, 18 with 10 yr or longer record have been analysed for long term trend in de-seasonalized monthly means, in annual quantiles and in monthly frequency distribution. A widespread significant decreasing trend has been observed at most sites, up to few percent per year, by Generalised Least Square and Theil-Sen method. All 41 sites have been tested for significant weekly periodicity by Kruskal-Wallis test for mean anomalies and by Wilcoxon test for weekend effect magnitude. A significant weekly periodicity has been observed for most PM10 series, particularly in summer and ascribed mainly to anthropic particulate emissions. A cluster analysis has been applied in order to highlight stations sharing similar pollution conditions over the reference period. Five clusters have been found, two gathering the metropolitan areas of Torino and Milano and their respective nearby sites and the other three clusters gathering north-east, north-west and central Po Valley sites respectively. Finally the observed trends in atmospheric PM10 have been compared to trends in provincial emissions of particulates and PM precursors, and analysed along with data on vehicular fleet age, composition and fuel sales. Significant basin-wide drop in emissions occurred for gaseous pollutants, contrarily to emissions of PM10 and PM2.5, whose drop resulted low and restricted to few provinces. It is not clear whether the decrease for only gaseous emissions is sufficient to explain the observed drop in atmospheric PM10, or if the low drop in particulate emissions is indeed due to the uncertainty in the emission inventory data for this species.

Long-term trend and variability of atmospheric PM10 concentration in the Po Valley

NASA Astrophysics Data System (ADS)

Bigi, A.; Ghermandi, G.

2014-05-01

The limits to atmospheric pollutant concentration set by the European Commission provide a challenging target for the municipalities in the Po Valley, because of the characteristic climatic conditions and high population density of this region. In order to assess climatology and trends in the concentration of atmospheric particles in the Po Valley, a data set of PM10 data from 41 sites across the Po Valley have been analysed, including both traffic and background sites (either urban, suburban or rural). Of these 41 sites, 18 with 10 yr or longer record have been analysed for long-term trend in deseasonalized monthly means, in annual quantiles and in monthly frequency distribution. A widespread significant decreasing trend has been observed at most sites, up to a few percent per year, by a generalized least squares and Theil-Sen method. All 41 sites have been tested for significant weekly periodicity by Kruskal-Wallis test for mean anomalies and by Wilcoxon test for weekend effect magnitude. A significant weekly periodicity has been observed for most PM10 series, particularly in summer and ascribed mainly to anthropic particulate emissions. A cluster analysis has been applied in order to highlight stations sharing similar pollution conditions over the reference period. Five clusters have been found, two encompassing the metropolitan areas of Turin and Milan and their respective nearby sites and the other three clusters gathering northeast, northwest and central Po Valley sites respectively. Finally, the observed trends in atmospheric PM10 have been compared to trends in provincial emissions of particulates and PM precursors, and analysed along with data on vehicular fleet age, composition and fuel sales. A significant basin-wide drop in emissions occurred for gaseous pollutants, contrarily to emissions of PM10 and PM2.5, whose drop was low and restricted to a few provinces. It is not clear whether the decrease for only gaseous emissions is sufficient to explain the observed drop in atmospheric PM10, or if the low drop in particulate emissions is indeed due to the uncertainty in the emission inventory data for this species.

RNase MRP is required for entry of 35S precursor rRNA into the canonical processing pathway.

PubMed

Lindahl, Lasse; Bommankanti, Ananth; Li, Xing; Hayden, Lauren; Jones, Adrienne; Khan, Miriam; Oni, Tolulope; Zengel, Janice M

2009-07-01

RNase MRP is a nucleolar RNA-protein enzyme that participates in the processing of rRNA during ribosome biogenesis. Previous experiments suggested that RNase MRP makes a nonessential cleavage in the first internal transcribed spacer. Here we report experiments with new temperature-sensitive RNase MRP mutants in Saccharomyces cerevisiae that show that the abundance of all early intermediates in the processing pathway is severely reduced upon inactivation of RNase MRP. Transcription of rRNA continues unabated as determined by RNA polymerase run-on transcription, but the precursor rRNA transcript does not accumulate, and appears to be unstable. Taken together, these observations suggest that inactivation of RNase MRP blocks cleavage at sites A0, A1, A2, and A3, which in turn, prevents precursor rRNA from entering the canonical processing pathway (35S > 20S + 27S > 18S + 25S + 5.8S rRNA). Nevertheless, at least some cleavage at the processing site in the second internal transcribed spacer takes place to form an unusual 24S intermediate, suggesting that cleavage at C2 is not blocked. Furthermore, the long form of 5.8S rRNA is made in the absence of RNase MRP activity, but only in the presence of Xrn1p (exonuclease 1), an enzyme not required for the canonical pathway. We conclude that RNase MRP is a key enzyme for initiating the canonical processing of precursor rRNA transcripts, but alternative pathway(s) might provide a backup for production of small amounts of rRNA.

Sites of intermolecular crosslinking of fatty acyl chains in phospholipids carrying a photoactivable carbene precursor

PubMed Central

Gupta, Chhitar M.; Costello, Catherine E.; Khorana, H. Gobind

1979-01-01

Sonicated vesicles of 1-fatty acyl-2-ω-(2-diazo-3,3,3-trifluoropropionoxy) fatty acyl sn-glycero-3-phosphoryl-cholines were shown recently to form intermolecular crosslinks by insertion of the photogenerated carbene into a C—H bond of a neighboring hydrocarbon chain. We now report that photolysis of multilamellar dispersions gives a second series of products in which carbene insertion is accompanied by elimination of a molecule of hydrogen fluoride. The sites of crosslinking in the latter compounds have been studied by mass spectrometry using phospholipids with varying chain lengths of the fatty acyl groups carrying the carbene precursor. The patterns observed show that the point of maximum crosslinking is consistent with the recent conclusion that in phospholipids the sn-2 fatty acyl chain trails the sn-1 chain by 2-4 atoms. Images PMID:16592675

Preparation and Analysis of Oligonucleotides Containing the C4′-Oxidized Abasic Site and Related Mechanistic Probes

PubMed Central

Kim, Jaeseung; Kreller, Cortney R.; Greenberg, Marc M.

2005-01-01

The C4′-oxidized abasic site (C4-AP) is produced by a variety of DNA damaging agents. This alkali labile lesion can exist in up to four diastereomeric cyclic forms, in addition to the acyclic keto-aldehyde. Synthetic oligonucleotides containing the lesion were prepared from a stable photochemical precursor. Chemical integrity of the lesion containing oligonucleotides was probed using phosphodiesterase lability. Analysis of the 3′,5′-phosphate diester of the monomeric lesion released from single diastereomers of photolabile precursors by 1H NMR indicates that isomerization of the hemiacetal and/or hemiketal is rapid. The syntheses and characterization of oligonucleotides containing configurationally stable analogues of C4-AP, which serve as mechanistic probes for deciphering the structural basis of the biochemical and biological effects of the C4′-oxidized abasic lesion, are also described. PMID:16277338

Targeting SYK kinase-dependent anti-apoptotic resistance pathway in B-lineage acute lymphoblastic leukaemia (ALL) cells with a potent SYK inhibitory pentapeptide mimic.

PubMed

Uckun, Fatih M; Ek, Rauf O; Jan, Shyi-Tai; Chen, Chun-Lin; Qazi, Sanjive

2010-05-01

The present study found that the pentapeptide mimic C-61, targeting the substrate binding P-site of SYK tyrosine kinase acted as a potent inducer of apoptosis in chemotherapy-resistant SYK-expressing primary leukemic B-cell precursors taken directly from relapsed B-precursor leukaemia (BPL) patients (but not SYK-deficient infant pro-B leukaemia cells), exhibited favourable pharmacokinetics in mice and non-human primates, and eradicated in vivo clonogenic leukaemia cells in severe combined immunodeficient mouse xenograft models of chemotherapy-resistant human BPL at dose levels non-toxic to mice and non-human primates. These in vitro and in vivo findings provide proof of principle for effective treatment of chemotherapy-resistant BPL by targeting SYK-dependent anti-apoptotic blast cell survival machinery with a SYK P-Site inhibitor. Further development of C-61 may provide the foundation for therapeutic innovation against chemotherapy-resistant BPL.

CCl 4 chemistry on the magnetite selvedge of single-crystal hematite: competitive surface reactions

NASA Astrophysics Data System (ADS)

Adib, K.; Camillone, N., III; Fitts, J. P.; Rim, K. T.; Flynn, G. W.; Joyce, S. A.; Osgood, R. M., Jr.

2002-01-01

Temperature programmed reaction/desorption (TPR/D) studies were undertaken to characterize the surface chemistry which occurs between CCl 4 and the Fe 3O 4 (1 1 1) selvedge of single crystal α-Fe 2O 3 (0 0 0 1). Six separate desorption events are clearly observed and four desorbing species are identified: CCl 4, OCCl 2, C 2Cl 4 and FeCl 2. It is proposed that OCCl 2, CCl 4 and C 2Cl 4 are produced in reactions involving the same precursor, CCl 2. Three reaction paths compete for the CCl 2 precursor: oxygen atom abstraction (for OCCl 2), molecular recombinative desorption (for CCl 4) and associative desorption (for C 2Cl 4). During the TPR/D temperature ramp, the branching ratio is observed to depend upon temperature and the availability of reactive sites. The data are consistent with a rich site-dependent chemistry.

Overaccumulation of the chloroplast antisense RNA AS5 is correlated with decreased abundance of 5S rRNA in vivo and inefficient 5S rRNA maturation in vitro

PubMed Central

Sharwood, Robert E.; Hotto, Amber M.; Bollenbach, Thomas J.; Stern, David B.

2011-01-01

Post-transcriptional regulation in the chloroplast is exerted by nucleus-encoded ribonucleases and RNA-binding proteins. One of these ribonucleases is RNR1, a 3′-to-5′ exoribonuclease of the RNase II family. We have previously shown that Arabidopsis rnr1-null mutants exhibit specific abnormalities in the expression of the rRNA operon, including the accumulation of precursor 23S, 16S, and 4.5S species and a concomitant decrease in the mature species. 5S rRNA transcripts, however, accumulate to a very low level in both precursor and mature forms, suggesting that they are unstable in the rnr1 background. Here we demonstrate that rnr1 plants overaccumulate an antisense RNA, AS5, that is complementary to the 5S rRNA, its intergenic spacer, and the downstream trnR gene, which encodes tRNAArg, raising the possibility that AS5 destabilizes 5S rRNA or its precursor and/or blocks rRNA maturation. To investigate this, we used an in vitro system that supports 5S rRNA and trnR processing. We show that AS5 inhibits 5S rRNA maturation from a 5S-trnR precursor, and shorter versions of AS5 demonstrate that inhibition requires intergenic sequences. To test whether the sense and antisense RNAs form double-stranded regions in vitro, treatment with the single-strand-specific mung bean nuclease was used. These results suggest that 5S–AS5 duplexes interfere with a sense-strand secondary structure near the endonucleolytic cleavage site downstream from the 5S rRNA coding region. We hypothesize that these duplexes are degraded by a dsRNA-specific ribonuclease in vivo, contributing to the 5S rRNA deficiency observed in rnr1. PMID:21148395

Identified EM Earthquake Precursors

NASA Astrophysics Data System (ADS)

Jones, Kenneth, II; Saxton, Patrick

2014-05-01

Many attempts have been made to determine a sound forecasting method regarding earthquakes and warn the public in turn. Presently, the animal kingdom leads the precursor list alluding to a transmission related source. By applying the animal-based model to an electromagnetic (EM) wave model, various hypotheses were formed, but the most interesting one required the use of a magnetometer with a differing design and geometry. To date, numerous, high-end magnetometers have been in use in close proximity to fault zones for potential earthquake forecasting; however, something is still amiss. The problem still resides with what exactly is forecastable and the investigating direction of EM. After a number of custom rock experiments, two hypotheses were formed which could answer the EM wave model. The first hypothesis concerned a sufficient and continuous electron movement either by surface or penetrative flow, and the second regarded a novel approach to radio transmission. Electron flow along fracture surfaces was determined to be inadequate in creating strong EM fields, because rock has a very high electrical resistance making it a high quality insulator. Penetrative flow could not be corroborated as well, because it was discovered that rock was absorbing and confining electrons to a very thin skin depth. Radio wave transmission and detection worked with every single test administered. This hypothesis was reviewed for propagating, long-wave generation with sufficient amplitude, and the capability of penetrating solid rock. Additionally, fracture spaces, either air or ion-filled, can facilitate this concept from great depths and allow for surficial detection. A few propagating precursor signals have been detected in the field occurring with associated phases using custom-built loop antennae. Field testing was conducted in Southern California from 2006-2011, and outside the NE Texas town of Timpson in February, 2013. The antennae have mobility and observations were noted for recurrence, duration, and frequency response. At the Southern California field sites, one loop antenna was positioned for omni-directional reception and also detected a strong First Schumann Resonance; however, additional Schumann Resonances were absent. At the Timpson, TX field sites, loop antennae were positioned for directional reception, due to earthquake-induced, hydraulic fracturing activity currently conducted by the oil and gas industry. Two strong signals, one moderately strong signal, and approximately 6-8 weaker signals were detected in the immediate vicinity. The three stronger signals were mapped by a biangulation technique, followed by a triangulation technique for confirmation. This was the first antenna mapping technique ever performed for determining possible earthquake epicenters. Six and a half months later, Timpson experienced two M4 (M4.1 and M4.3) earthquakes on September 2, 2013 followed by a M2.4 earthquake three days later, all occurring at a depth of five kilometers. The Timpson earthquake activity now has a cyclical rate and a forecast was given to the proper authorities. As a result, the Southern California and Timpson, TX field results led to an improved design and construction of a third prototype antenna. With a loop antenna array, a viable communication system, and continuous monitoring, a full fracture cycle can be established and observed in real-time. In addition, field data could be reviewed quickly for assessment and lead to a much more improved earthquake forecasting capability. The EM precursors determined by this method appear to surpass all prior precursor claims, and the general public will finally receive long overdue forecasting.

HIV-specific cytotoxic T lymphocyte precursors exist in a CD28-CD8+ T cell subset and increase with loss of CD4 T cells.

PubMed

Lewis, D E; Yang, L; Luo, W; Wang, X; Rodgers, J R

1999-06-18

To determine whether the CD28-CD8+ T cells that develop during HIV infection contain HIV-specific cytotoxic precursor cells. CD8 subpopulations from six asymptomatic HIV-positive adults, with varying degrees of CD4 T cell loss, were sorted by flow cytometry and HIV-specific precursor cytotoxic T lymphocyte frequencies were measured. Three populations of CD8 T cells were tested: CD28+CD5-- T cells, CD28-CD57+ T cells (thought to be memory cells) and CD28-CD57- T cells (function unknown). Sorted CD8 subsets were stimulated with antigen presenting cells expressing HIV-1 Gag/Pol molecules. Cytotoxic T cell assays on Gag/Pol expressing 51Cr-labeled Epstein-Barr virus transformed autologous B cells lines or control targets were performed after 2 weeks. Specific lysis and precursor frequencies were calculated. Both CD28 positive and CD28-CD57+ populations contained appreciable numbers of precursors (9-1720 per 10(6) CD8+ T cells). However, the CD28-CD57- population had fewer precursors in five out of six people studied. More CD28 positive HIV-specific cytotoxic T lymphocyte precursors were found in patients with CD4:CD8 ratios > 1, whereas more CD28-CD57+ precursors were found in patients whose CD4:CD8 ratios were < 1 (r2, 0.68). Memory HIV-specific precursor cytotoxic T lymphocytes are found in both CD28 positive and CD28-CD8+ cells, however, a CD28-CD57- subpopulation had fewer. Because CD28-CD57+ cells are antigen-driven with limited diversity, the loss of CD28 on CD8 T cells during disease progression may reduce the response to new HIV mutations; this requires further testing.

Quantitative analysis of indigo and indigo precursors in leaves of Isatis spp. and Polygonum tinctorium.

PubMed

Gilbert, Kerry G; Maule, Hamish G; Rudolph, Bernd; Lewis, Mervyn; Vandenburg, Harold; Sales, Ester; Tozzi, Sabrina; Cooke, David T

2004-01-01

Analysis of extracts from two woad species (Isatis tinctoria and Isatis indigotica) and Polygonum tinctorium revealed that only one indigo precursor (indican) was present in Polygonum, but two precursors were found in Isatis spp. This was done using high performance liquid chromatography (HPLC), coupled to an evaporative light scattering detector (ELSD). In Isatis spp., the indigo precursors indican and a fraction representing isatan B were identified. The proportion of indican and isatan B was different between the two Isatis spp. tested. For the first time, it was possible to quantify the precursors in woad plant species, and the results were found to be in good agreement with those made from total indigo quantification using two different spectrophotometric methods or a derivatization technique.

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

Milbrandt, Anelia; Booth, Samuel

Carbon fiber (CF), known also as graphite fiber, is a lightweight, strong, and flexible material used in both structural (load-bearing) and non-structural applications (e.g., thermal insulation). The high cost of precursors (the starting material used to make CF, which comes predominately from fossil sources) and manufacturing have kept CF a niche market with applications limited mostly to high-performance structural materials (e.g., aerospace). Alternative precursors to reduce CF cost and dependence on fossil sources have been investigated over the years, including biomass-derived precursors such as rayon, lignin, glycerol, and lignocellulosic sugars. The purpose of this study is to provide a comprehensivemore » overview of CF precursors from biomass and their market potential. We examine the potential CF production from these precursors, the state of technology and applications, and the production cost (when data are available). We discuss their advantages and limitations. We also discuss the physical properties of biomass-based CF, and we compare them to those of polyacrylonitrile (PAN)-based CF. We also discuss manufacturing and end-product considerations for bio-based CF, as well as considerations for plant siting and biomass feedstock logistics, feedstock competition, and risk mitigation strategies. The main contribution of this study is that it provides detailed technical and market information about each bio-based CF precursor in one document while other studies focus on one precursor at a time or a particular topic (e.g., processing). Thus, this publication allows for a comprehensive view of the CF potential from all biomass sources and serves as a reference for both novice and experienced professionals interested in CF production from alternative sources.« less

Critical Surface Parameters for the Oxidative Coupling of Methane over the Mn-Na-W/SiO2 Catalyst.

PubMed

Hayek, Naseem S; Lucas, Nishita S; Warwar Damouny, Christine; Gazit, Oz M

2017-11-22

The work here presents a thorough evaluation of the effect of Mn-Na-W/SiO 2 catalyst surface parameters on its performance in the oxidative coupling of methane (OCM). To do so, we used microporous dealuminated β-zeolite (Zeo), or mesoporous SBA-15 (SBA), or macroporous fumed silica (Fum) as precursors for catalyst preparation, together with Mn nitrate, Mn acetate and Na 2 WO 4 . Characterizing the catalysts by inductively coupled plasma-optical emission spectroscopy, N 2 physisorption, X-ray diffraction, high-resolution scanning electron microscopy-energy-dispersive spectroscopy, X-ray photoelectron spectroscopy, and catalytic testing enabled us to identify critical surface parameters that govern the activity and C 2 selectivity of the Mn-Na-W/SiO 2 catalyst. Although the current paradigm views the phase transition of silica to α-cristobalite as the critical step in obtaining dispersed and stable metal sites, we show that the choice of precursors is equally or even more important with respect to tailoring the right surface properties. Specifically, the SBA-based catalyst, characterized by relatively closed surface porosity, demonstrated low activity and low C 2 selectivity. By contrast, for the same composition, the Zeo-based catalyst showed an open surface pore structure, which translated up to fourfold higher activity and enhanced selectivity. By varying the overall composition of the Zeo catalysts, we show that reducing the overall W concentration reduces the size of the Na 2 WO 4 species and increases the catalytic activity linearly as much as fivefold higher than the SBA catalyst. This linear dependence correlates well to the number of interfaces between the Na 2 WO 4 and Mn 2 O 3 species. Our results combined with prior studies lead us to single out the interface between Na 2 WO 4 and Mn 2 O 3 as the most probable active site for OCM using this catalyst. Synergistic interactions between the various precursors used and the phase transition are discussed in detail, and the conclusions are correlated to surface properties and catalysis.

Substrate Shuttling Between Active Sites of Uroporphyrinogen Decarboxylase in Not Required to Generate Coproporphyrinogen

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

Phillips, J.; Warby, C; Whitby, F

2009-01-01

Uroporphyrinogen decarboxylase (URO-D; EC 4.1.1.37), the fifth enzyme of the heme biosynthetic pathway, is required for the production of heme, vitamin B12, siroheme, and chlorophyll precursors. URO-D catalyzes the sequential decarboxylation of four acetate side chains in the pyrrole groups of uroporphyrinogen to produce coproporphyrinogen. URO-D is a stable homodimer, with the active-site clefts of the two subunits adjacent to each other. It has been hypothesized that the two catalytic centers interact functionally, perhaps by shuttling of reaction intermediates between subunits. We tested this hypothesis by construction of a single-chain protein (single-chain URO-D) in which the two subunits were connectedmore » by a flexible linker. The crystal structure of this protein was shown to be superimposable with wild-type activity and to have comparable catalytic activity. Mutations that impaired one or the other of the two active sites of single-chain URO-D resulted in approximately half of wild-type activity. The distributions of reaction intermediates were the same for mutant and wild-type sequences and were unaltered in a competition experiment using I and III isomer substrates. These observations indicate that communication between active sites is not required for enzyme function and suggest that the dimeric structure of URO-D is required to achieve conformational stability and to create a large active-site cleft.« less

The Lunar Mapping and Modeling Project

NASA Technical Reports Server (NTRS)

Nall, M.; French, R.; Noble, S.; Muery, K.

2010-01-01

The Lunar Mapping and Modeling Project (LMMP) is managing a suite of lunar mapping and modeling tools and data products that support lunar exploration activities, including the planning, de-sign, development, test, and operations associated with crewed and/or robotic operations on the lunar surface. Although the project was initiated primarily to serve the needs of the Constellation program, it is equally suited for supporting landing site selection and planning for a variety of robotic missions, including NASA science and/or human precursor missions and commercial missions such as those planned by the Google Lunar X-Prize participants. In addition, LMMP should prove to be a convenient and useful tool for scientific analysis and for education and public out-reach (E/PO) activities.

Precursors of Halobenzoquinones and Their Removal During Drinking Water Treatment Processes.

PubMed

Wang, Wei; Qian, Yichao; Jmaiff, Lindsay K; Krasner, Stuart W; Hrudey, Steve E; Li, Xing-Fang

2015-08-18

Halobenzoquinones (HBQs) widely occur in drinking water treatment plant (DWTP) effluents; however, HBQ precursors and their removal by treatments remain unclear. Thus, we have investigated HBQ precursors in plant influents and their removal by each treatment before chlorination in nine DWTPs. The levels of HBQ precursors were determined using formation potential (FP) tests for 2,6-dichloro-1,4-benzoquinone (DCBQ), 2,3,6-trichloro-1,4-benzoquinone (TCBQ), 2,6-dichloro-3-methyl-1,4-benzoquinone (DCMBQ), and 2,6-dibromo-1,4-benzoquinone (DBBQ). HBQ precursors were present in all plant influents. DCBQ precursors were the most abundant (DCBQ FP up to 205 ng/L). Coagulation removed dissolved organic carbon (DOC) (up to 56%) and HBQ precursors (up to 39% for DCBQ). The level of removal of DOC was significantly greater than the level of removal of HBQ FP, suggesting that organic matter removed by coagulation had a high proportion of non-HBQ-precursor material. Granular activated carbon (GAC) decreased the level of HBQ FPs by 10-20%, where DOC removal was only 0.2-4.7%, suggesting that the GAC was not in the adsorption mode and biodegradation of HBQ precursors may have been occurring. Ozonation destroyed/transformed HBQ FPs by 10-30%, whereas anthracite/sand filtration and UV irradiation appeared to have no impact. The results demonstrated that the combined treatments did not substantially reduce HBQ precursor levels in water.

The rRNA methyltransferase Bud23 shows functional interaction with components of the SSU processome and RNase MRP.

PubMed

Sardana, Richa; White, Joshua P; Johnson, Arlen W

2013-06-01

Bud23 is responsible for the conserved methylation of G1575 of 18S rRNA, in the P-site of the small subunit of the ribosome. bud23Δ mutants have severely reduced small subunit levels and show a general failure in cleavage at site A2 during rRNA processing. Site A2 is the primary cleavage site for separating the precursors of 18S and 25S rRNAs. Here, we have taken a genetic approach to identify the functional environment of BUD23. We found mutations in UTP2 and UTP14, encoding components of the SSU processome, as spontaneous suppressors of a bud23Δ mutant. The suppressors improved growth and subunit balance and restored cleavage at site A2. In a directed screen of 50 ribosomal trans-acting factors, we identified strong positive and negative genetic interactions with components of the SSU processome and strong negative interactions with components of RNase MRP. RNase MRP is responsible for cleavage at site A3 in pre-rRNA, an alternative cleavage site for separating the precursor rRNAs. The strong negative genetic interaction between RNase MRP mutants and bud23Δ is likely due to the combined defects in cleavage at A2 and A3. Our results suggest that Bud23 plays a role at the time of A2 cleavage, earlier than previously thought. The genetic interaction with the SSU processome suggests that Bud23 could be involved in triggering disassembly of the SSU processome, or of particular subcomplexes of the processome.

No Need for Templates in the Auditory Enhancement Effect

PubMed Central

Carcagno, Samuele; Semal, Catherine; Demany, Laurent

2013-01-01

The audibility of a target tone in a multitone background masker is enhanced by the presentation of a precursor sound consisting of the masker alone. There is evidence that precursor-induced neural adaptation plays a role in this perceptual enhancement. However, the precursor may also be strategically used by listeners as a spectral template of the following masker to better segregate it from the target. In the present study, we tested this hypothesis by measuring the audibility of a target tone in a multitone masker after the presentation of precursors which, in some conditions, were made dissimilar to the masker by gating their components asynchronously. The precursor and the following sound were presented either to the same ear or to opposite ears. In either case, we found no significant difference in the amount of enhancement produced by synchronous and asynchronous precursors. In a second experiment, listeners had to judge whether a synchronous multitone complex contained exactly the same tones as a preceding precursor complex or had one tone less. In this experiment, listeners performed significantly better with synchronous than with asynchronous precursors, showing that asynchronous precursors were poorer perceptual templates of the synchronous multitone complexes. Overall, our findings indicate that precursor-induced auditory enhancement cannot be fully explained by the strategic use of the precursor as a template of the following masker. Our results are consistent with an explanation of enhancement based on selective neural adaptation taking place at a central locus of the auditory system. PMID:23826348

No Need for Templates in the Auditory Enhancement Effect.

PubMed

Carcagno, Samuele; Semal, Catherine; Demany, Laurent

2013-01-01

The audibility of a target tone in a multitone background masker is enhanced by the presentation of a precursor sound consisting of the masker alone. There is evidence that precursor-induced neural adaptation plays a role in this perceptual enhancement. However, the precursor may also be strategically used by listeners as a spectral template of the following masker to better segregate it from the target. In the present study, we tested this hypothesis by measuring the audibility of a target tone in a multitone masker after the presentation of precursors which, in some conditions, were made dissimilar to the masker by gating their components asynchronously. The precursor and the following sound were presented either to the same ear or to opposite ears. In either case, we found no significant difference in the amount of enhancement produced by synchronous and asynchronous precursors. In a second experiment, listeners had to judge whether a synchronous multitone complex contained exactly the same tones as a preceding precursor complex or had one tone less. In this experiment, listeners performed significantly better with synchronous than with asynchronous precursors, showing that asynchronous precursors were poorer perceptual templates of the synchronous multitone complexes. Overall, our findings indicate that precursor-induced auditory enhancement cannot be fully explained by the strategic use of the precursor as a template of the following masker. Our results are consistent with an explanation of enhancement based on selective neural adaptation taking place at a central locus of the auditory system.

The chemokine CXCL16 induces migration and invasion of glial precursor cells via its receptor CXCR6.

PubMed

Hattermann, Kirsten; Ludwig, Andreas; Gieselmann, Volkmar; Held-Feindt, Janka; Mentlein, Rolf

2008-09-01

Chemokines are implicated in developmental and inflammatory processes in the brain. The transmembrane chemokine CXCL16 is produced in brain endothelial and reactive astroglial cells and released by shedding. Its receptor CXCR6 is detected during brain development highest at postnatal day 6, found in glial precursor cells differentiated from neural stem cells and in an A2B5-positive glial precursor cell line. Their stimulation by soluble CXCL16 induces the PI3-kinase/Akt and Erk pathways resulting in the activation of the transcription factor AP-1. As biological responses, soluble CXCL16 upregulates its own receptor, increases cell proliferation, stimulates cell migration in wound-healing and in spheroid confrontation assays. Invasion of CXCR6-positive glial cells into CXCL16-expressing spheroids can be blocked by sheddase inhibitors and CXCL16-antibody. Since CXCL16 is induced by cytokines at sites of inflammation, neurodegeneration, ischemia and malignant transformation, it should attract CXCR6-positive glial precursor cells, enhance their invasion and proliferation and thus favor astrogliosis.

Hydrothermal synthesis and characterization of Si and Sr co-substituted hydroxyapatite nanowires using strontium containing calcium silicate as precursors.

PubMed

Zhang, Na; Zhai, Dong; Chen, Lei; Zou, Zhaoyong; Lin, Kaili; Chang, Jiang

2014-04-01

In the absence of any organic surfactants and solvents, the silicon (Si) and strontium (Sr) co-substituted hydroxyapatite [Ca10(PO4)6(OH)2, Si/Sr-HAp] nanowires were synthesized via hydrothermal treatment of the Sr-containing calcium silicate (Sr-CS) powders as the precursors in trisodium phosphate (Na3PO4) aqueous solution. The morphology, phase, chemical compositions, lattice constants and the degradability of the products were characterized. The Si/Sr-HAp nanowires with diameter of about 60nm and up to 2μm in length were obtained after hydrothermal treatment of the Sr-CS precursors. The Sr and Si substitution amount of the HAp nanowires could be well regulated by facile tailoring the Sr substitution level of the precursors and the reaction ratio of the precursor/solution, respectively. The SiO4 tetrahedra and Sr(2+) ions occupied the crystal sites of the HAp, and the lattice constants increased apparently with the increase of the substitution amount. EDS mapping also suggested the uniform distribution of Si and Sr in the synthetic nanowires. Moreover, the Si/Sr-substitution apparently improved the degradability of the HAp materials. Our study suggested that the precursor transformation method provided a facile approach to synthesize the Si/Sr co-substituted HAp nanowires with controllable substitution amount, and the synthetic Si/Sr-HAp nanowires might be used as bioactive materials for hard tissue regeneration applications. Copyright © 2014 Elsevier B.V. All rights reserved.

Environmental-Fate Patterns for Perfluoroalkylates and their Precursors

EPA Science Inventory

Two sites with elevated concentrations of perfluoroalkylates (PFAs) and fluorotelomer alcohols (FTOHs) were studied: 1) agricultural fields near Decatur, AL on which sewage sludge had been applied; and 2) the Conasauga River system near Dalton, GA where treated sewage effluent is...

Immunological and biochemical characterization of processing products from the neurotensin/neuromedin N precursor in the rat medullary thyroid carcinoma 6-23 cell line.

PubMed Central

Bidard, J N; de Nadai, F; Rovere, C; Moinier, D; Laur, J; Martinez, J; Cuber, J C; Kitabgi, P

1993-01-01

Neurotensin (NT) and neuromedin N (NN) are two related biologically active peptides that are encoded in the same precursor molecule. In the rat, the precursor consists of a 169-residue polypeptide starting with an N-terminal signal peptide and containing in its C-terminal region one copy each of NT and NN. NN precedes NT and is separated from it by a Lys-Arg sequence. Two other Lys-Arg sequences flank the N-terminus of NN and the C-terminus of NT. A fourth Lys-Arg sequence occurs near the middle of the precursor and is followed by an NN-like sequence. Finally, an Arg-Arg pair is present within the NT moiety. The four Lys-Arg doublets represent putative processing sites in the precursor molecule. The present study was designed to investigate the post-translational processing of the NT/NN precursor in the rat medullary thyroid carcinoma (rMTC) 6-23 cell line, which synthesizes large amounts of NT upon dexamethasone treatment. Five region-specific antisera recognizing the free N- or C-termini of sequences adjacent to the basic doublets were produced, characterized and used for immunoblotting and radioimmunoassay studies in combination with gel filtration, reverse-phase h.p.l.c. and trypsin digestion of rMTC 6-23 cell extracts. Because two of the antigenic sequences, i.e. NN and the NN-like sequence, start with a lysine residue that is essential for recognition by their respective antisera, a micromethod by which trypsin specifically cleaves at arginine residues was developed. The results show that dexamethasone-treated rMTC 6-23 cells produced comparable amounts of NT, NN and a peptide corresponding to a large N-terminal precursor fragment lacking the NN and NT moieties. This large fragment was purified. N-Terminal sequencing revealed that it started at residue Ser23 of the prepro-NT/NN sequence, and thus established the Cys22-Ser23 bond as the cleavage site of the signal peptide. Two other large N-terminal fragments bearing respectively the NN and NT sequences at their C-termini were present in lower amounts. The NN-like sequence was internal to all the large fragments. There was no evidence for the presence of peptides with the NN-like sequence at their N-termini. This shows that, in rMTC 6-23 cells, the precursor is readily processed at the three Lys-Arg doublets that flank and separate the NT and NN sequences. In contrast, the Lys-Arg doublet that precedes the NN-like sequence is not processed in this system.(ABSTRACT TRUNCATED AT 400 WORDS) Images Figure 3 PMID:8471039

Pathways to Mathematics: Longitudinal Predictors of Performance

ERIC Educational Resources Information Center

LeFevre, Jo-Anne; Fast, Lisa; Skwarchuk, Sheri-Lynn; Smith-Chant, Brenda L.; Bisanz, Jeffrey; Kamawar, Deepthi; Penner-Wilger, Marcie

2010-01-01

A model of the relations among cognitive precursors, early numeracy skill, and mathematical outcomes was tested for 182 children from 4.5 to 7.5 years of age. The model integrates research from neuroimaging, clinical populations, and normal development in children and adults. It includes 3 precursor pathways: quantitative, linguistic, and spatial…

Mars MetNet Mission - Martian Atmospheric Observational Post Network

NASA Astrophysics Data System (ADS)

Haukka, Harri; Harri, Ari-Matti; Aleksashkin, Sergey; Arruego, Ignacio; Schmidt, Walter; Genzer, Maria; Vazquez, Luis; Siikonen, Timo; Palin, Matti

2016-10-01

A new kind of planetary exploration mission for Mars is under development in collaboration between the Finnish Meteorological Institute (FMI), Lavochkin Association (LA), Space Research Institute (IKI) and Institutio Nacional de Tecnica Aerospacial (INTA). The Mars MetNet mission is based on a new semi-hard landing vehicle called MetNet Lander (MNL).The scientific payload of the Mars MetNet Precursor mission is divided into three categories: Atmospheric instruments, Optical devices and Composition and structure devices. Each of the payload instruments will provide significant insights in to the Martian atmospheric behavior.The key technologies of the MetNet Lander have been qualified and the electrical qualification model (EQM) of the payload bay has been built and successfully tested.Full Qualification Model (QM) of the MetNet landing unit with the Precursor Mission payload is currently under functional tests. In the near future the QM unit will be exposed to environmental tests with qualification levels including vibrations, thermal balance, thermal cycling and mechanical impact shock. One complete flight unit of the entry, descent and landing systems (EDLS) has been manufactured and tested with acceptance levels. Another flight-like EDLS has been exposed to most of the qualification tests, and hence it may be used for flight after refurbishments. Accordingly two flight-capable EDLS systems exist. The eventual goal is to create a network of atmospheric observational posts around the Martian surface. The next step in the MetNet Precursor Mission is the demonstration of the technical robustness and scientific capabilities of the MetNet type of landing vehicle. Definition of the Precursor Mission and discussions on launch opportunities are currently under way. The baseline program development funding exists for the next five years. Flight unit manufacture of the payload bay takes about 18 months, and it will be commenced after the Precursor Mission has been defined.

Cellular compartmentalization of secondary metabolism

PubMed Central

Kistler, H. Corby; Broz, Karen

2015-01-01

Fungal secondary metabolism is often considered apart from the essential housekeeping functions of the cell. However, there are clear links between fundamental cellular metabolism and the biochemical pathways leading to secondary metabolite synthesis. Besides utilizing key biochemical precursors shared with the most essential processes of the cell (e.g., amino acids, acetyl CoA, NADPH), enzymes for secondary metabolite synthesis are compartmentalized at conserved subcellular sites that position pathway enzymes to use these common biochemical precursors. Co-compartmentalization of secondary metabolism pathway enzymes also may function to channel precursors, promote pathway efficiency and sequester pathway intermediates and products from the rest of the cell. In this review we discuss the compartmentalization of three well-studied fungal secondary metabolite biosynthetic pathways for penicillin G, aflatoxin and deoxynivalenol, and summarize evidence used to infer subcellular localization. We also discuss how these metabolites potentially are trafficked within the cell and may be exported. PMID:25709603

Biosynthesis of ependymins from goldfish brain.

PubMed

Königstorfer, A; Sterrer, S; Hoffmann, W

1989-08-15

Ependymins beta and gamma constitute a novel family of secretory proteins in the extracellular fluid of goldfish brain. Here we demonstrate that at least two different transcripts exist in goldfish brain differing mainly in the length of their 3' noncoding regions but encoding very similar precursors for ependymins. Both precursors consist of 216 amino acid residues including two potential N-glycosylation sites. Prepro-ependymin-I is the main but not the only precursor of ependymin beta, whereas prepro-ependymin-II is preferentially processed to ependymin gamma. This is in line with our results showing that both ependymins beta and gamma represent different glycoforms with very similar protein backbones. Additionally, we show that both ependymins share the same C-terminal ends indicating that ependymin gamma is not a proteolysis product of ependymin beta. We also demonstrate that processing at three internal pairs of basic residues does not occur in either ependymin.

S-Doped Sb2O3 Nanocrystal: an Efficient Visible-Light Catalyst for Organic Degradation

NASA Astrophysics Data System (ADS)

Xue, Hun; Lin, Xinyi; Chen, Qinghua; Qian, Qingrong; Lin, Suying; Zhang, Xiaoyan; Yang, Da-Peng; Xiao, Liren

2018-04-01

The S-doped Sb2O3 nanocrystals were successfully synthesized using SbCl3 and thioacetamide (TAA) as precursors via a facile one-step hydrothermal method. The effects of pH of the precursor reaction solution on the product composition and property were determined. The results indicated that the doping amount of S could be tuned by adjusting the pH of the precursor solution. Furthermore, the S entered into the interstitial site of Sb2O3 crystals as S2-, which broadened the absorption wavelength range of the Sb2O3 nanocrystal. The S-doped Sb2O3 exhibited an excellent visible-light-driven photocatalytic activity in the decomposition of methyl orange and 4-phenylazophenol. Last, a possible photocatalytic mechanism of the S-doped Sb2O3 under visible light irradiation was proposed.

Regional and local meteorology influences high-resolution tropospheric ozone concentration in the Los Angeles Basin

NASA Astrophysics Data System (ADS)

Koutzoukis, S.; Jenerette, D.; Chandler, M.; Wang, J.; Ge, C.; Ripplinger, J.

2017-12-01

Urban air quality and climate directly affect resident health. The Los Angeles (LA) Basin is a highly populated metropolitan area, with widespread point sources of ozone (O3) precursors (NOx , Volatile Organic Compounds, CO) from fossil fuel combustion. The LA basin exists on a coast-to-mountain gradient, with increasing temperatures towards the Transverse Ranges, which rise to 1700m. Frequently not compliant with 8-hour O3 standards, the LA and South Coast Air Basins are designated as severe and extreme non-attainment areas. Summer weather in the LA basin is characterized by a persistent high pressure system, creating an inversion that traps air pollutants, including O3 precursors, coupled with physical geography that blocks prevailing upper atmosphere air flow. These interactions make neighborhood-level O3 levels more variable than common regional models. Over the summer of 2017, we investigated the importance of local meteorology, wind patterns and air temperature, in transporting and mixing ozone precursors from point sources along the coast-to-mountain gradient. We deployed a network of six EPA federal equivalent method ozone and meteorological sensors in three campaigns in the LA basin along the coast-to-mountain transect. Each campaign, we collaborated with citizen scientists to deploy three sensor stations in two, 4 km2 quadrats, for a total of six high-resolution 4 km2 pixels. O3 concentrations vary greatly along the transect. At the coastal sites, daily O3 ranges from 0ppm to 60ppm and the range increases at the inland sites, to 100ppm. At all sites, there was a positive relationship between wind speed, air temperature, and O3 concentration, with increasing correlation inland. The Pearson correlation coefficient between wind speed and O3 concentration doubles from the coast to inland, and triples between air temperature and O3. The site-specific relationships between O3 and wind direction and temperature vary, suggesting neighborhood-effects from local point sources.

One precursor, three apolipoproteins: the relationship between two crustacean lipoproteins, the large discoidal lipoprotein and the high density lipoprotein/β-glucan binding protein.

PubMed

Stieb, Stefanie; Roth, Ziv; Dal Magro, Christina; Fischer, Sabine; Butz, Eric; Sagi, Amir; Khalaila, Isam; Lieb, Bernhard; Schenk, Sven; Hoeger, Ulrich

2014-12-01

The novel discoidal lipoprotein (dLp) recently detected in the crayfish, differs from other crustacean lipoproteins in its large size, apoprotein composition and high lipid binding capacity, We identified the dLp sequence by transcriptome analyses of the hepatopancreas and mass spectrometry. Further de novo assembly of the NGS data followed by BLAST searches using the sequence of the high density lipoprotein/1-glucan binding protein (HDL-BGBP) of Astacus leptodactylus as query revealed a putative precursor molecule with an open reading frame of 14.7 kb and a deduced primary structure of 4889 amino acids. The presence of an N-terminal lipid bind- ing domain and a DUF 1943 domain suggests the relationship with the large lipid transfer proteins. Two-putative dibasic furin cleavage sites were identified bordering the sequence of the HDL-BGBP. When subjected to mass spectroscopic analyses, tryptic peptides of the large apoprotein of dLp matched the N-terminal part of the precursor, while the peptides obtained for its small apoprotein matched the C-terminal part. Repeating the analysis in the prawn Macrobrachium rosenbergii revealed a similar protein with identical domain architecture suggesting that our findings do not represent an isolated instance. Our results indicate that the above three apolipoproteins (i.e HDL-BGBP and both the large and the small subunit of dLp) are translated as a large precursor. Cleavage at the furin type sites releases two subunits forming a heterodimeric dLP particle, while the remaining part forms an HDL-BGBP whose relationship with other lipoproteins as well as specific functions are yet to be elucidated.

Silica-supported, single-site titanium catalysts for olefin epoxidation. A molecular precursor strategy for control of catalyst structure.

PubMed

Jarupatrakorn, Jonggol; Don Tilley, T

2002-07-17

A molecular precursor approach involving simple grafting procedures was used to produce site-isolated titanium-supported epoxidation catalysts of high activity and selectivity. The tris(tert-butoxy)siloxy titanium complexes Ti[OSi(O(t)Bu)(3)](4) (TiSi4), ((i)PrO)Ti[OSi(O(t)Bu)(3)](3) (TiSi3), and ((t)BuO)(3)TiOSi(O(t)Bu)(3) (TiSi) react with the hydroxyl groups of amorphous Aerosil, mesoporous MCM-41, and SBA-15 via loss of HO(t)Bu and/or HOSi(O(t)Bu)(3) and introduction of titanium species onto the silica surface. Powder X-ray diffraction, nitrogen adsorption/desorption, infrared, and diffuse reflectance ultraviolet spectroscopies were used to investigate the structures and chemical natures of the surface-bound titanium species. The titanium species exist mainly in isolated, tetrahedral coordination environments. Increasing the number of siloxide ligands in the molecular precursor decreases the amount of titanium that can be introduced this way, but also enhances the catalytic activity and selectivity for the epoxidation of cyclohexene with cumene hydroperoxide as oxidant. In addition, the high surface area mesoporous silicas (MCM-41 and SBA-15) are more effective than amorphous silica as supports for these catalysts. Supporting TiSi3 on the SBA-15 affords highly active cyclohexene epoxidation catalysts (0.25-1.77 wt % Ti loading) that provide turnover frequencies (TOFs) of 500-1500 h(-1) after 1 h (TOFs are reduced by about half after calcination). These results demonstrate that oxygen-rich siloxide complexes of titanium are useful as precursors to supported epoxidation catalysts.

Spectroscopic insights into the nature of active sites in iron–nitrogen–carbon electrocatalysts for oxygen reduction in acid

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

Jia, Qingying; Ramaswamy, Nagappan; Tylus, Urszula

Developing efficient and inexpensive catalysts for the sluggish oxygen reduction reaction (ORR) constitutes one of the grand challenges in the fabrication of commercially viable fuel cell devices and metal–air batteries for future energy applications. Despite recent achievements in designing advanced Pt-based and Pt-free catalysts, current progress primarily involves an empirical approach of trial-and-error combination of precursors and synthesis conditions, which limits further progress. Rational design of catalyst materials requires proper understanding of the mechanistic origin of the ORR and the underlying surface properties under operating conditions that govern catalytic activity. Herein, several different groups of iron-based catalysts synthesized via differentmore » methods and/or precursors were systematically studied by combining multiple spectroscopic techniques under ex situ and in situ conditions in an effort to obtain a comprehensive understanding of the synthesis-products correlations, nature of active sites, and the reaction mechanisms. These catalysts include original macrocycles, macrocycle-pyrolyzed catalysts, and Fe-N–C catalysts synthesized from individual Fe, N, and C precursors including polymer-based catalysts, metal organic framework (MOF)-based catalysts, and sacrificial support method (SSM)-based catalysts. The latter group of catalysts is most promising as not only they exhibit exceptional ORR activity and/or durability, but also the final products are controllable. We show that the high activity observed for most pyrolyzed Fe-based catalysts can mainly be attributed to a single active site: non-planar Fe–N 4 moiety embedded in distorted carbon matrix characterized by a high potential for the Fe 2+/3+ redox transition in acidic electrolyte/environment. The high intrinsic ORR activity, or turnover frequency (TOF), of this site is shown to be accounted for by redox catalysis mechanism that highlights the dominant role of the site-blocking effect. Moreover, a highly active MOF-based catalyst without Fe–N moieties was developed, and the active sites were identified as nitrogen-doped carbon fibers with embedded iron particles that are not directly involved in the oxygen reduction pathway. The high ORR activity and durability of catalysts involving this second site, as demonstrated in fuel cell, are attributed to the high density of active sites and the elimination or reduction of Fenton-type processes. The latter are initiated by hydrogen peroxide but are known to be accelerated by iron ions exposed to the surface, resulting in the formation of damaging free-radicals.« less

Understanding the Thermal Properties of Precursor-Ionomers to Optimize Fabrication Processes for Ionic Polymer-Metal Composites (IPMCs)

PubMed Central

Choi, Kisuk; Olsen, Zakai; Hwang, Taeseon; Nam, Jae-Do

2018-01-01

Ionic polymer-metal composites (IPMCs) are one of many smart materials and have ionomer bases with a noble metal plated on the surface. The ionomer is usually Nafion, but recently Aquivion has been shown to be a promising alternative. Ionomers are available in the form of precursor pellets. This is an un-activated form that is able to melt, unlike the activated form. However, there is little study on the thermal characteristics of these precursor ionomers. This lack of knowledge causes issues when trying to fabricate ionomer shapes using methods such as extrusion, hot-pressing, and more recently, injection molding and 3D printing. To understand the two precursor-ionomers, a set of tests were conducted to measure the thermal degradation temperature, viscosity, melting temperature, and glass transition. The results have shown that the precursor Aquivion has a higher melting temperature (240 °C) than precursor Nafion (200 °C) and a larger glass transition range (32–65 °C compared with 21–45 °C). The two have the same thermal degradation temperature (~400 °C). Precursor Aquivion is more viscous than precursor Nafion as temperature increases. Based on the results gathered, it seems that the precursor Aquivion is more stable as temperature increases, facilitating the manufacturing processes. This paper presents the data collected to assist researchers in thermal-based fabrication processes. PMID:29693584

Preparation of metal/zeolite catalysts: Formation of palladium aquocomplexes in the precursor of palladium-mordenite catalysts

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

Not Available

1993-09-01

Previous research has revealed that the catalytic performance of metal/zeolite catalysts can be significantly modified by exposing the catalyst precursor to H[sub 2]O vapor during the period after calcination, but before reduction. For bimetallic PdCo/NaY catalysts used for CO hydrogenation, the selectivity was changed from predominant production of oxygenates to predominant production of higher hydrocarbons. For Pt/H-mordenite catalysts, this water treatment has been reported to improve the alkane isomerization activity. Although it is certain that Lewis sites are transformed to Bronsted sites by reaction with H[sub 2]O, the activity of the catalyst is affected most when the water is addedmore » after calcination, when the noble metal is present as ligand-free ions. This observation led to the hypothesis that complexation of transition metal ions with water might be instrumental for the observed effects. In zeolites containing cages, such as Y, the formation of metal-ligand complex ions appears to incite their migration from small to large cages. In cageless zeolites such as mordenite, however, it is not clear, a priori, whether hydration of transition metal ions will increase or decrease their reducibility and whether it will ultimately result in higher or lower metal dispersion. The authors have therefore undertaken research to clarify these issues. Palladium supported in H-mordenite (Pd/HMor) or Na-mordenite (Pd/Na-Mor) has been tested using methylcyclopentane as a probe reaction; temperature-programmed reduction (TPR), desorption (TPD), and extended X-ray absorption fine structure (EXAFS) spectroscopy have been used to characterize the effects of water treatment on the samples.« less

Product Distribution from Precursor Bite Angle Variation in Multitopic Alkyne Metathesis: Evidence for a Putative Kinetic Bottleneck.

PubMed

Moneypenny, Timothy P; Yang, Anna; Walter, Nathan P; Woods, Toby J; Gray, Danielle L; Zhang, Yang; Moore, Jeffrey S

2018-05-02

In the dynamic synthesis of covalent organic frameworks and molecular cages, the typical synthetic approach involves heuristic methods of discovery. While this approach has yielded many remarkable products, the ability to predict the structural outcome of subjecting a multitopic precursor to dynamic covalent chemistry (DCC) remains a challenge in the field. The synthesis of covalent organic cages is a prime example of this phenomenon, where precursors designed with the intention of affording a specific product may deviate dramatically when the DCC synthesis is attempted. As such, rational design principles are needed to accelerate discovery in cage synthesis using DCC. Herein, we test the hypothesis that precursor bite angle contributes significantly to the energy landscape and product distribution in multitopic alkyne metathesis (AM). By subjecting a series of precursors with varying bite angles to AM, we experimentally demonstrate that the product distribution, and convergence toward product formation, is strongly dependent on this geometric attribute. Surprisingly, we discovered that precursors with the ideal bite angle (60°) do not afford the most efficient pathway to the product. The systematic study reported here illustrates how seemingly minor adjustments in precursor geometry greatly affect the outcome of DCC systems. This research illustrates the importance of fine-tuning precursor geometric parameters in order to successfully realize desirable targets.

Mature clustered, regularly interspaced, short palindromic repeats RNA (crRNA) length is measured by a ruler mechanism anchored at the precursor processing site.

PubMed

Hatoum-Aslan, Asma; Maniv, Inbal; Marraffini, Luciano A

2011-12-27

Precise RNA processing is fundamental to all small RNA-mediated interference pathways. In prokaryotes, clustered, regularly interspaced, short palindromic repeats (CRISPR) loci encode small CRISPR RNAs (crRNAs) that protect against invasive genetic elements by antisense targeting. CRISPR loci are transcribed as a long precursor that is cleaved within repeat sequences by CRISPR-associated (Cas) proteins. In many organisms, this primary processing generates crRNA intermediates that are subject to additional nucleolytic trimming to render mature crRNAs of specific lengths. The molecular mechanisms underlying this maturation event remain poorly understood. Here, we defined the genetic requirements for crRNA primary processing and maturation in Staphylococcus epidermidis. We show that changes in the position of the primary processing site result in extended or diminished maturation to generate mature crRNAs of constant length. These results indicate that crRNA maturation occurs by a ruler mechanism anchored at the primary processing site. We also show that maturation is mediated by specific cas genes distinct from those genes involved in primary processing, showing that this event is directed by CRISPR/Cas loci.

Precursor-product discrimination by La protein during tRNA metabolism

PubMed Central

Bayfield, Mark A.; Maraia, Richard J.

2009-01-01

SUMMARY La proteins bind pre-tRNAs at their UUU-3'OH ends, facilitating their maturation. While the mechanism by which La binds pre-tRNA 3' trailers is known, the function of the RNA-binding β-sheet surface of RRM1 is unknown. How La dissociates from UUU-3'OH-containing trailers after 3' processing is also unknown. La preferentially binds pre-tRNAs over processed tRNAs or 3' trailer products through coupled use of two sites: one on the La motif and another on the RRM1 β surface that binds elsewhere on tRNA. Two sites provide stable pre-tRNA binding while processed tRNA and 3' trailer are released from their single sites relatively fast. RRM1 loop-3 mutations decrease affinity for pre-tRNA and tRNA but not UUU-3'OH trailer, and impair tRNA maturation in vivo. We propose that RRM1 functions in activities that are more complex than UUU-3'OH binding. Accordingly, the RRM1 mutations also impair a RNA chaperone activity of La. The results suggest how La distinguishes precursor from product RNAs, allowing it to recycle onto a new pre-tRNA. PMID:19287396

Mid-IR DIAL for high-resolution mapping of explosive precursors

NASA Astrophysics Data System (ADS)

Mitev, V.; Babichenko, S.; Bennes, J.; Borelli, R.; Dolfi-Bouteyre, A.; Fiorani, L.; Hespel, L.; Huet, T.; Palucci, A.; Pistilli, M.; Puiu, A.; Rebane, O.; Sobolev, I.

2013-10-01

A DIAL instrument on a moving platform is seen as a valuable remote sensing component in a sensor network for area monitoring, targeting sites involved in unauthorised explosive manufacturing. Such instrument will perform the area mapping of the vapour concentration of key substances, known to be used as precursors in explosive fabrication, such as acetone and nitromethane. The IR spectra of acetone and nitromethane vapours have been defined from available spectroscopy databases and from laboratory measurements as showing optimal spectral band for the DIAL operation in the spectral range of 3.0 μm - 3.5 μm. The DIAL operation has been numerically simulated, with inputs based on the HITRAN database, the U.S. Standard Atmosphere and aerosol simulation software package OPAC. A combination of OPO and OPA has been chosen as a transmitter, where the idler wavelength is used for probing, with wavelength tuning in sequence. A scanner mounted on top of the coaxially aligned laser and receiver, is capable of covering almost 360 degrees horizontally and +/-30 degrees vertically. The detection is performed by a photovoltaic photodiode with 4-stage cooling, with a signal digitalisation having 14 bit amplitude resolution and 125 Ms/s sampling rate. Here we present the development and the first test of the DIAL instrument.

The role of neural precursor cells and self assembling peptides in nerve regeneration

PubMed Central

2013-01-01

Objective Cranial nerve injury involves loss of central neural cells in the brain stem and surrounding support matrix, leading to severe functional impairment. Therapeutically targeting cellular replacement and enhancing structural support may promote neural regeneration. We examined the combinatorial effect of neural precursor cells (NPC) and self assembling peptide (SAP) administration on nerve regeneration. Methods Nerve injury was induced by clip compression of the rodent spinal cord. SAPs were injected immediately into the injured cord and NPCs at 2 weeks post-injury. Behavioral analysis was done weekly and rats were sacrificed at 11 weeks post injury. LFB-H&E staining was done on cord tissue to assess cavitation volume. Motor evoked potentials (MEP) were measured at week 11 to assess nerve conduction and Kaplan meier curves were created to compare survival estimates. Results NPCs and SAPs were distributed both caudal and rostral to the injury site. Behavioral analysis showed that SAP + NPC transplantation significantly improved locomotor score p <0.03) and enhanced survival (log rank test, p = 0.008) compared to control. SAP + NPC treatment also improved nerve conduction velocity (p = 0.008) but did not affect cavitation volume (p = 0.73). Conclusion Combinatorial NPC and SAP injection into injured nerve tissue may enhance neural repair and regeneration. PMID:24351041

The role of neural precursor cells and self assembling peptides in nerve regeneration.

PubMed

Zhao, Xiao; Yao, Gordon S; Liu, Yang; Wang, Jian; Satkunendrarajah, Kajana; Fehlings, Michael

2013-12-19

Cranial nerve injury involves loss of central neural cells in the brain stem and surrounding support matrix, leading to severe functional impairment. Therapeutically targeting cellular replacement and enhancing structural support may promote neural regeneration. We examined the combinatorial effect of neural precursor cells (NPC) and self assembling peptide (SAP) administration on nerve regeneration. Nerve injury was induced by clip compression of the rodent spinal cord. SAPs were injected immediately into the injured cord and NPCs at 2 weeks post-injury. Behavioral analysis was done weekly and rats were sacrificed at 11 weeks post injury. LFB-H&E staining was done on cord tissue to assess cavitation volume. Motor evoked potentials (MEP) were measured at week 11 to assess nerve conduction and Kaplan Meier curves were created to compare survival estimates. NPCs and SAPs were distributed both caudal and rostral to the injury site. Behavioral analysis showed that SAP + NPC transplantation significantly improved locomotor score p <0.03) and enhanced survival (log rank test, p = 0.008) compared to control. SAP + NPC treatment also improved nerve conduction velocity (p = 0.008) but did not affect cavitation volume (p = 0.73). Combinatorial NPC and SAP injection into injured nerve tissue may enhance neural repair and regeneration.

Islet amyloid polypeptide (IAPP):cDNA cloning and identification of an amyloidogenic region associated with the species-specific occurrence of age-related diabetes mellitus.

PubMed

Betsholtz, C; Svensson, V; Rorsman, F; Engström, U; Westermark, G T; Wilander, E; Johnson, K; Westermark, P

1989-08-01

We have cloned and sequenced a human islet amyloid polypeptide (IAPP) cDNA. A secretory 89 amino acid IAPP protein precursor is predicted from which the 37 amino acid IAPP molecule is formed by amino- and carboxyterminal proteolytic processing. The IAPP peptide is 43-46% identical in amino acid sequence to the two members of the calcitonin gene-related peptide (CGRP) family. Evolutionary conserved proteolytic processing sites indicate that similar proteases are involved in the maturation of IAPP and CGRP and that the IAPP amyloid polypeptide is identical to the normal proteolytic product of the IAPP precursor. A synthetic peptide corresponding to a carboxyteminal fragment of human IAPP is shown to spontaneously form amyloid-like fibrils in vitro. Antibodies against this peptide cross-react with IAPP from species that develop amyloid in pancreatic islets in conjunction with age-related diabetes mellitus (human, cat, racoon), but do not cross-react with IAPP from other tested species (mouse, rat, guinea pig, dog). Thus, a species-specific structural motif in the putative amyloidogenic region of IAPP is associated with both amyloid formation and the development of age-related diabetes mellitus. This provides a new molecular clue to the pathogenesis of this disease.

Fetzima (levomilnacipran), a drug for major depressive disorder as a dual inhibitor for human serotonin transporters and beta-site amyloid precursor protein cleaving enzyme-1.

PubMed

Rizvi, Syed Mohd Danish; Shaikh, Sibhghatulla; Khan, Mahiuddin; Biswas, Deboshree; Hameed, Nida; Shakil, Shazi

2014-01-01

Pharmacological management of Major Depressive Disorder includes the use of serotonin reuptake inhibitors which targets serotonin transporters (SERT) to increase the synaptic concentrations of serotonin. Beta-site amyloid precursor protein cleaving enzyme-1 (BACE-1) is responsible for amyloid β plaque formation. Hence it is an interesting target for Alzheimer's disease (AD) therapy. This study describes molecular interactions of a new Food and Drug Administration approved antidepressant drug named 'Fetzima' with BACE-1 and SERT. Fetzima is chemically known as levomilnacipran. The study has explored a possible link between the treatment of Depression and AD. 'Autodock 4.2' was used for docking study. The free energy of binding (ΔG) values for 'levomilnacipran-SERT' interaction and 'levomilnacipran-BACE1' interaction were found to be -7.47 and -8.25 kcal/mol, respectively. Levomilnacipran was found to interact with S438, known to be the most important amino acid residue of serotonin binding site of SERT during 'levomilnacipran-SERT' interaction. In the case of 'levomilnacipran-BACE1' interaction, levomilnacipran interacted with two very crucial aspartic acid residues of BACE-1, namely, D32 and D228. These residues are accountable for the cleavage of amyloid precursor protein and the subsequent formation of amyloid β plaques in AD brain. Hence, Fetzima (levomilnacipran) might act as a potent dual inhibitor of SERT and BACE-1 and expected to form the basis of a future dual therapy against depression and AD. It is an established fact that development of AD is associated with Major Depressive Disorder. Therefore, the design of new BACE-1 inhibitors based on antidepressant drug scaffolds would be particularly beneficial.

Analysis of Novel Prostate Cancer Biomarkers and their Predictive Utility in an Active Surveillance Protocol

DTIC Science & Technology

2014-05-01

Shock Protein, Annexin A3, Sorbitol Dehydrogenase, Fibrinogen Beta Chain Precursor, Creatine Kinase B-Type, Annexin A1, Cystatin B, and AZI. We have...Shock Protein, Annexin A3, Sorbitol Dehydrogenase, Fibrinogen Beta Chain Precursor, and Creatine Kinase B-Type. After testing these candidates with

Natural Organochlorines as Precursors of 3-Monochloropropanediol Esters in Vegetable Oils.

PubMed

Tiong, Soon Huat; Saparin, Norliza; Teh, Huey Fang; Ng, Theresa Lee Mei; Md Zain, Mohd Zairey Bin; Neoh, Bee Keat; Md Noor, Ahmadilfitri; Tan, Chin Ping; Lai, Oi Ming; Appleton, David Ross

2018-01-31

During high-temperature refining of vegetable oils, 3-monochloropropanediol (3-MCPD) esters, possible carcinogens, are formed from acylglycerol in the presence of a chlorine source. To investigate organochlorine compounds in vegetable oils as possible precursors for 3-MCPD esters, we tested crude palm, soybean, rapeseed, sunflower, corn, coconut, and olive oils for the presence of organochlorine compounds. Having found them in all vegetable oils tested, we focused subsequent study on oil palm products. Analysis of the chlorine isotope mass pattern exhibited in high-resolution mass spectrometry enabled organochlorine compound identification in crude palm oils as constituents of wax esters, fatty acid, diacylglycerols, and sphingolipids, which are produced endogenously in oil palm mesocarp throughout ripening. Analysis of thermal decomposition and changes during refining suggested that these naturally present organochlorine compounds in palm oils and perhaps in other vegetable oils are precursors of 3-MCPD esters. Enrichment and dose-response showed a linear relationship to 3-MCPD ester formation and indicated that the sphingolipid-based organochlorine compounds are the most active precursors of 3-MCPD esters.

Gamma-aminobutyric acid-modulated benzodiazepine binding sites in bacteria

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

Lummis, S.C.R.; Johnston, G.A.R.; Nicoletti, G.

1991-01-01

Benzodiazepine binding sites, which were once considered to exist only in higher vertebrates, are here demonstrated in the bacteria E. coli. The bacterial ({sup 3}H)diazepam binding sites are modulated by GABA; the modulation is dose dependent and is reduced at high concentrations. The most potent competitors of E.Coli ({sup 3}H)diazepam binding are those that are active in displacing ({sup 3}H)benzodiazepines from vertebrate peripheral benzodiazepine binding sites. These vertebrate sites are not modulated by GABA, in contrast to vertebrate neuronal benzodiazepine binding sites. The E.coli benzodiazepine binding sites therefore differ from both classes of vertebrate benzodiazepine binding sites; however the ligandmore » spectrum and GABA-modulatory properties of the E.coli sites are similar to those found in insects. This intermediate type of receptor in lower species suggests a precursor for at least one class of vertebrate benzodiazepine binding sites may have existed.« less

Comparison of preparation methods for ceria catalyst and the effect of surface and bulk sulfates on its activity toward NH3-SCR.

PubMed

Chang, Huazhen; Ma, Lei; Yang, Shijian; Li, Junhua; Chen, Liang; Wang, Wei; Hao, Jiming

2013-11-15

A series of CeO2 catalysts prepared with sulfate (S) and nitrate (N) precursors by hydrothermal (H) and precipitation (P) methods were investigated in selective catalytic reduction of NOx by NH3 (NH3-SCR). The catalytic activity of CeO2 was significantly affected by the preparation methods and the precursor type. CeO2-SH, which was prepared by hydrothermal method with cerium (IV) sulfate as a precursor, showed excellent SCR activity and high N2 selectivity in the temperature range of 230-450 °C. Based on the results obtained by temperature-programmed reduction (H2-TPR), transmission infrared spectra (IR) and thermal gravimetric analysis (TGA), the excellent performance of CeO2-SH was correlated with the surface sulfate species formed in the hydrothermal reaction. These results indicated that sulfate species bind with Ce(4+) on the CeO2-SH catalyst, and the specific sulfate species, such as Ce(SO4)2 or CeOSO4, were formed. The adsorption of NH3 was promoted by these sulfate species, and the probability of immediate oxidation of NH3 to N2O on Ce(4+) was reduced. Accordingly, the selective oxidation of NH3 was enhanced, which contributed to the high N2 selectivity in the SCR reaction. However, the location of sulfate on the CeO2-SP catalyst was different. Plenty of sulfate species were likely deposited on CeO2-SP surface, covering the active sites for NO oxidation, which resulted in poor SCR activity in the test temperature range. Moreover, the resistance to alkali metals, such as Na and K, was improved over the CeO2-SH catalyst. Copyright © 2013 Elsevier B.V. All rights reserved.

Synergy of iron and copper oxides in the catalytic formation of PCDD/Fs from 2-monochlorophenol.

PubMed

Potter, Phillip M; Guan, Xia; Lomnicki, Slawomir M

2018-07-01

Transition metal oxides present in waste incineration systems have the ability to catalyze the formation of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs) through surface reactions involving organic dioxin precursors. However, studies have concentrated on the catalytic effects of individual transition metal oxides, while the complex elemental composition of fly ash introduces the possibility of synergistic or inhibiting effects between multiple, catalytically active components. In this study, we have tested fly ash surrogates containing different ratios (by weight) of iron (III) oxide and copper (II) oxide. Such Fe 2 O 3 /CuO mixed-oxide surrogates (in the Fe:Cu ratio of 3.5, 0.9 and 0.2 ) were used to study the cooperative effects between two transition metals that are present in high concentrations in most combustion systems and are known to individually catalyze the formation of PCDD/Fs. The presence of both iron and copper oxides increased the oxidative power of the fly ash surrogates in oxygen rich conditions and led to extremely high PCDD/F yields under pyrolytic conditions (up to >5% yield) from 2-monochlorophenol precursor. PCDD/F congener profiles from the mixed oxide samples are similar to results obtained from only CuO, however the total PCDD/F yield increases with increasing Fe 2 O 3 content. Careful analysis of the reaction products and changes to the oxidation states of active metals indicate the CuO surface sites are centers for reaction while the Fe 2 O 3 is affecting the bonds in CuO and increasing the ability of copper centers to form surface-bound radicals that are precursors to PCDD/Fs. Copyright © 2018 Elsevier Ltd. All rights reserved.

Micrometric BN powders used as catalyst support: influence of the precursor on the properties of the BN ceramic

NASA Astrophysics Data System (ADS)

Perdigon-Melon, José Antonio; Auroux, Aline; Guimon, Claude; Bonnetot, Bernard

2004-02-01

Thin powders and foams of boron nitride have been prepared from molecular precursors for use as noble metal supports in the catalytic conversion of methane. Different precursors originating from borazines have been tested. The best results were obtained using a precursor derived from trichloroborazine (TCB) which, after reacting with ammonia at room temperature and then thermolyzing up to 1800°C, led to BN powders with a specific area of more than 300 m 2 g -1 and a micrometric spherical texture. Comparable results were obtained using polyborazylene under similar conditions. Aminoborazine-derived precursors did not yield such high specific area ceramics but the BN microstructure resembled a foam with a crystallized skin and amorphous internal part. These differences were related to the chemical mechanism of the conversion of the precursor into BN. Polyhaloborazines and polyborazines yielded BN through gas-solid reactions whereas aminoborazine polymers could be kept waxy up to high temperatures, which favored the glassy foam. Catalysts composed of BN support and platinum have been prepared using two routes: from a mixture of precursor or by impregnation of a BN powder leading to very different catalysts.

Analysis of secondary structural elements in human microRNA hairpin precursors.

PubMed

Liu, Biao; Childs-Disney, Jessica L; Znosko, Brent M; Wang, Dan; Fallahi, Mohammad; Gallo, Steven M; Disney, Matthew D

2016-03-01

MicroRNAs (miRNAs) regulate gene expression by targeting complementary mRNAs for destruction or translational repression. Aberrant expression of miRNAs has been associated with various diseases including cancer, thus making them interesting therapeutic targets. The composite of secondary structural elements that comprise miRNAs could aid the design of small molecules that modulate their function. We analyzed the secondary structural elements, or motifs, present in all human miRNA hairpin precursors and compared them to highly expressed human RNAs with known structures and other RNAs from various organisms. Amongst human miRNAs, there are 3808 are unique motifs, many residing in processing sites. Further, we identified motifs in miRNAs that are not present in other highly expressed human RNAs, desirable targets for small molecules. MiRNA motifs were incorporated into a searchable database that is freely available. We also analyzed the most frequently occurring bulges and internal loops for each RNA class and found that the smallest loops possible prevail. However, the distribution of loops and the preferred closing base pairs were unique to each class. Collectively, we have completed a broad survey of motifs found in human miRNA precursors, highly expressed human RNAs, and RNAs from other organisms. Interestingly, unique motifs were identified in human miRNA processing sites, binding to which could inhibit miRNA maturation and hence function.

Prohormone convertases differentially process pro-neurotensin/neuromedin N in tissues and cell lines.

PubMed

Kitabgi, Patrick

2006-08-01

Neurotensin (NT) is synthesized as part of a larger precursor that also contains neuromedin N (NN), a six-amino acid neurotensin-like peptide. NT and NN are located in the C-terminal region of the precursor (pro-NT/NN) where they are flanked and separated by three Lys-Arg sequences. A fourth dibasic sequence is present in the middle of the precursor. Dibasics are the consensus sites recognized and cleaved by specialized endoproteases that belong to the family of proprotein convertases (PCs). In tissues that express pro-NT/NN, the three C-terminal Lys-Arg sites are differentially processed, whereas the middle dibasic is poorly cleaved. Processing gives rise mainly to NT and NN in the brain, to NT and a large peptide with a C-terminal NN moiety (large NN) in the gut, and to NT, large NN, and a large peptide with a C-terminal NT moiety (large NT) in the adrenals. Recent evidence indicates that PC1, PC2, and PC5-A are the prohormone convertases responsible for the processing patterns observed in the gut, brain, and adrenals, respectively. As NT, NN, large NT, and large NN are all endowed with biological activity, the evidence reviewed in this paper supports the idea that posttranslational processing of pro-NT/NN in tissues may generate biological diversity of pathophysiological relevance.

Differential processing of pro-neurotensin/neuromedin N and relationship to pro-hormone convertases.

PubMed

Kitabgi, Patrick

2006-10-01

Neurotensin (NT) is synthesized as part of a larger precursor that also contains neuromedin N (NN), a six amino acid neurotensin-like peptide. NT and NN are located in the C-terminal region of the precursor (pro-NT/NN) where they are flanked and separated by three Lys-Arg sequences. A fourth dibasic sequence is present in the middle of the precursor. Dibasics are the consensus sites recognized and cleaved by endoproteases that belong to the recently identified family of pro-protein convertases (PCs). In tissues that express pro-NT/NN, the three C-terminal Lys-Arg sites are differentially processed, whereas the middle dibasic is poorly cleaved. Pro-NT/NN processing gives rise mainly to NT and NN in the brain, to NT and a large peptide ending with the NN sequence at its C-terminus (large NN) in the gut and to NT, large NN and a large peptide ending with the NT sequence (large NT) in the adrenals. Recent evidence indicates that PC1, PC2 and PC5-A are the pro-hormone convertases responsible for the processing patterns observed in the gut, brain and adrenals, respectively. As NT, NN, large NT and large NN are all endowed with biological activity, the evidence reviewed here supports the idea that post-translational processing of pro-NT/NN in tissues may generate biological diversity.

Gold-Copper Nanoparticles: Nanostructural Evolution and Bifunctional Catalytic Sites

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

Yin, Jun; Shan, Shiyao; Yang, Lefu

2012-12-12

Understanding of the atomic-scale structure is essential for exploiting the unique catalytic properties of any nanoalloy catalyst. This report describes novel findings of an investigation of the nanoscale alloying of gold-copper (AuCu) nanoparticles and its impact on the surface catalytic functions. Two pathways have been explored for the formation of AuCu nanoparticles of different compositons, including wet chemical synthesis from mixed Au- and Cu-precursor molecules, and nanoscale alloying via an evolution of mixed Au- and Cu-precursor nanoparticles near the nanoscale melting temperatures. For the evolution of mixed precursor nanoparticles, synchrotron x-ray based in-situ real time XRD was used to monitormore » the structural changes, revealing nanoscale alloying and reshaping towards an fcc-type nanoalloy (particle or cube) via a partial melting–resolidification mechanism. The nanoalloys supported on carbon or silica were characterized by in-situ high-energy XRD/PDFs, revealing an intriguing lattice "expanding-shrinking" phenomenon depending on whether the catalyst is thermochemically processed under oxidative or reductive atmosphere. This type of controllable structural changes is found to play an important role in determining the catalytic activity of the catalysts for carbon monoxide oxidation reaction. The tunable catalytic activities of the nanoalloys under thermochemically oxidative and reductive atmospheres are also discussed in terms of the bifunctional sites and the surface oxygenated metal species for carbon monoxide and oxygen activation.« less

A [4Fe-4S]-Fe(CO)(CN)-l-cysteine intermediate is the first organometallic precursor in [FeFe] hydrogenase H-cluster bioassembly

NASA Astrophysics Data System (ADS)

Rao, Guodong; Tao, Lizhi; Suess, Daniel L. M.; Britt, R. David

2018-05-01

Biosynthesis of the [FeFe] hydrogenase active site (the 'H-cluster') requires the interplay of multiple proteins and small molecules. Among them, the radical S-adenosylmethionine enzyme HydG, a tyrosine lyase, has been proposed to generate a complex that contains an Fe(CO)2(CN) moiety that is eventually incorporated into the H-cluster. Here we describe the characterization of an intermediate in the HydG reaction: a [4Fe-4S][(Cys)Fe(CO)(CN)] species, 'Complex A', in which a CO, a CN- and a cysteine (Cys) molecule bind to the unique 'dangler' Fe site of the auxiliary [5Fe-4S] cluster of HydG. The identification of this intermediate—the first organometallic precursor to the H-cluster—validates the previously hypothesized HydG reaction cycle and provides a basis for elucidating the biosynthetic origin of other moieties of the H-cluster.

Discovery of the 3-Imino-1,2,4-thiadiazinane 1,1-Dioxide Derivative Verubecestat (MK-8931)–A β-Site Amyloid Precursor Protein Cleaving Enzyme 1 Inhibitor for the Treatment of Alzheimer’s Disease

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

Scott, Jack D.; Li, Sarah W.; Brunskill, Andrew P. J.

Verubecestat 3 (MK-8931), a diaryl amide-substituted 3-imino-1,2,4-thiadiazinane 1,1-dioxide derivative, is a high-affinity β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitor currently undergoing Phase 3 clinical evaluation for the treatment of mild to moderate and prodromal Alzheimer’s disease. Although not selective over the closely related aspartyl protease BACE2, verubecestat has high selectivity for BACE1 over other key aspartyl proteases, notably cathepsin D, and profoundly lowers CSF and brain Aβ levels in rats and nonhuman primates and CSF Aβ levels in humans. In this annotation, we describe the discovery of 3, including design, validation, and selected SAR around the novel iminothiadiazinanemore » dioxide core as well as aspects of its preclinical and Phase 1 clinical characterization.« less

Visualizing the Reaction Cycle in an Iron(II)- and 2-(Oxo)-glutarate-Dependent Hydroxylase.

PubMed

Mitchell, Andrew J; Dunham, Noah P; Martinie, Ryan J; Bergman, Jonathan A; Pollock, Christopher J; Hu, Kai; Allen, Benjamin D; Chang, Wei-Chen; Silakov, Alexey; Bollinger, J Martin; Krebs, Carsten; Boal, Amie K

2017-10-04

Iron(II)- and 2-(oxo)-glutarate-dependent oxygenases catalyze diverse oxidative transformations that are often initiated by abstraction of hydrogen from carbon by iron(IV)-oxo (ferryl) complexes. Control of the relative orientation of the substrate C-H and ferryl Fe-O bonds, primarily by direction of the oxo group into one of two cis-related coordination sites (termed inline and offline), may be generally important for control of the reaction outcome. Neither the ferryl complexes nor their fleeting precursors have been crystallographically characterized, hindering direct experimental validation of the offline hypothesis and elucidation of the means by which the protein might dictate an alternative oxo position. Comparison of high-resolution X-ray crystal structures of the substrate complex, an Fe(II)-peroxysuccinate ferryl precursor, and a vanadium(IV)-oxo mimic of the ferryl intermediate in the l-arginine 3-hydroxylase, VioC, reveals coordinated motions of active site residues that appear to control the intermediate geometries to determine reaction outcome.

Structure and activation of pro-activin A

PubMed Central

Wang, Xuelu; Fischer, Gerhard; Hyvönen, Marko

2016-01-01

Activins are growth factors with multiple roles in the development and homeostasis. Like all TGF-β family of growth factors, activins are synthesized as large precursors from which mature dimeric growth factors are released proteolytically. Here we have studied the activation of activin A and determined crystal structures of the unprocessed precursor and of the cleaved pro-mature complex. Replacing the natural furin cleavage site with a HRV 3C protease site, we show how the protein gains its bioactivity after proteolysis and is as active as the isolated mature domain. The complex remains associated in conditions used for biochemical analysis with a dissociation constant of 5 nM, but the pro-domain can be actively displaced from the complex by follistatin. Our high-resolution structures of pro-activin A share features seen in the pro-TGF-β1 and pro-BMP-9 structures, but reveal a new oligomeric arrangement, with a domain-swapped, cross-armed conformation for the protomers in the dimeric protein. PMID:27373274

LiCoPO4 cathode from a CoHPO4·xH2O nanoplate precursor for high voltage Li-ion batteries

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

Choi, Daiwon; Li, Xiaolin; Henderson, Wesley A.

2016-02-01

Highly crystalline LiCoPO4/C cathode has been synthesized without any impurities via single step solid-state reaction using CoHPO4xH2O nanoplates as a precursor obtained by simple precipitation route. The electrochemical test shows specific capacity as high as 125mAh/g at charge/discharge rate of C/10. Synthesis approach for obtaining CoHPO4xH2O nanoplate precursor and final LiCoPO4/C cathode using single step solid-state reaction have been characterized using X-ray diffraction, thermos gravimetric analyses (TGA) – differential scanning calorimetry (DSC), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). The electrochemical test and cycling stability using different electrolytes, additive and separator have been investigated.

Nitrogen Incorporation Effects On Site-Controlled Quantum Dots

NASA Astrophysics Data System (ADS)

Juska, G.; Dimastrodonato, V.; Mereni, L. O.; Pelucchi, E.

2011-12-01

We report here on the optical properties of site-controlled diluted nitride In0.25Ga0.75As1-xNx quantum dots grown by metalorganic vapour phase epitaxy (MOVPE). We show photoluminescence energy shift as a function of nitrogen precursor U-dimethylhydrazine, with a maximum value of 35 meV achieved. Optical features, substantially different from the counterpart nitrogen-free dots, are presented: an antibinding biexciton, a large distribution of lifetimes, significantly reduced fine structure splitting.

Evolutionarily conserved morphogenetic movements at the vertebrate head-trunk interface coordinate the transport and assembly of hypopharyngeal structures.

PubMed

Lours-Calet, Corinne; Alvares, Lucia E; El-Hanfy, Amira S; Gandesha, Saniel; Walters, Esther H; Sobreira, Débora Rodrigues; Wotton, Karl R; Jorge, Erika C; Lawson, Jennifer A; Kelsey Lewis, A; Tada, Masazumi; Sharpe, Colin; Kardon, Gabrielle; Dietrich, Susanne

2014-06-15

The vertebrate head-trunk interface (occipital region) has been heavily remodelled during evolution, and its development is still poorly understood. In extant jawed vertebrates, this region provides muscle precursors for the throat and tongue (hypopharyngeal/hypobranchial/hypoglossal muscle precursors, HMP) that take a stereotype path rostrally along the pharynx and are thought to reach their target sites via active migration. Yet, this projection pattern emerged in jawless vertebrates before the evolution of migratory muscle precursors. This suggests that a so far elusive, more basic transport mechanism must have existed and may still be traceable today. Here we show for the first time that all occipital tissues participate in well-conserved cell movements. These cell movements are spearheaded by the occipital lateral mesoderm and ectoderm that split into two streams. The rostrally directed stream projects along the floor of the pharynx and reaches as far rostrally as the floor of the mandibular arch and outflow tract of the heart. Notably, this stream leads and engulfs the later emerging HMP, neural crest cells and hypoglossal nerve. When we (i) attempted to redirect hypobranchial/hypoglossal muscle precursors towards various attractants, (ii) placed non-migratory muscle precursors into the occipital environment or (iii) molecularly or (iv) genetically rendered muscle precursors non-migratory, they still followed the trajectory set by the occipital lateral mesoderm and ectoderm. Thus, we have discovered evolutionarily conserved morphogenetic movements, driven by the occipital lateral mesoderm and ectoderm, that ensure cell transport and organ assembly at the head-trunk interface. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Evolutionarily conserved morphogenetic movements at the vertebrate head–trunk interface coordinate the transport and assembly of hypopharyngeal structures

PubMed Central

Lours-Calet, Corinne; Alvares, Lucia E.; El-Hanfy, Amira S.; Gandesha, Saniel; Walters, Esther H.; Sobreira, Débora Rodrigues; Wotton, Karl R.; Jorge, Erika C.; Lawson, Jennifer A.; Kelsey Lewis, A.; Tada, Masazumi; Sharpe, Colin; Kardon, Gabrielle; Dietrich, Susanne

2014-01-01

The vertebrate head–trunk interface (occipital region) has been heavily remodelled during evolution, and its development is still poorly understood. In extant jawed vertebrates, this region provides muscle precursors for the throat and tongue (hypopharyngeal/hypobranchial/hypoglossal muscle precursors, HMP) that take a stereotype path rostrally along the pharynx and are thought to reach their target sites via active migration. Yet, this projection pattern emerged in jawless vertebrates before the evolution of migratory muscle precursors. This suggests that a so far elusive, more basic transport mechanism must have existed and may still be traceable today. Here we show for the first time that all occipital tissues participate in well-conserved cell movements. These cell movements are spearheaded by the occipital lateral mesoderm and ectoderm that split into two streams. The rostrally directed stream projects along the floor of the pharynx and reaches as far rostrally as the floor of the mandibular arch and outflow tract of the heart. Notably, this stream leads and engulfs the later emerging HMP, neural crest cells and hypoglossal nerve. When we (i) attempted to redirect hypobranchial/hypoglossal muscle precursors towards various attractants, (ii) placed non-migratory muscle precursors into the occipital environment or (iii) molecularly or (iv) genetically rendered muscle precursors non-migratory, they still followed the trajectory set by the occipital lateral mesoderm and ectoderm. Thus, we have discovered evolutionarily conserved morphogenetic movements, driven by the occipital lateral mesoderm and ectoderm, that ensure cell transport and organ assembly at the head–trunk interface. PMID:24662046

Potential anti-cholinesterase and β-site amyloid precursor protein cleaving enzyme 1 inhibitory activities of cornuside and gallotannins from Cornus officinalis fruits.

PubMed

Bhakta, Himanshu Kumar; Park, Chan Hum; Yokozawa, Takako; Tanaka, Takashi; Jung, Hyun Ah; Choi, Jae Sue

2017-07-01

Cholinesterase (ChE) and β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitors are promising agents for the treatment of Alzheimer's disease (AD). In the present study, we examined the inhibitory activity of seven compounds isolated from the fruits of Cornus officinalis, cornuside, polymeric proanthocyanidins, 1,2,3-tri-O-galloyl-β-D-glucose, 1,2,3,6-tetra-O-galloyl-β-D-glucose, tellimagrandin I, tellimagrandin II, and isoterchebin, against acetylcholinesterase (AChE), butyrylcholinesterase (BChE), and BACE1. All of the compounds displayed concentration-dependent in vitro inhibitory activity toward the ChEs and BACE1. Among them, tellimagrandin II exhibited the best inhibitory activity toward ChEs, whereas the best BACE1 inhibitor was 1,2,3,6-tetra-O-galloyl-β-D-glucose. Isoterchebin and polymeric proanthocyanidins were also significant ChE inhibitors. The kinetic and docking studies demonstrated that all compounds interacted with both the catalytic active sites and the peripheral anionic sites of the ChEs and BACE1. Tellimagrandin II, isoterchebin, and the polymeric proanthocyanidins exhibited concentration-dependent inhibition of peroxynitrite-mediated protein tyrosine nitration. In conclusion, we identified significant ChE and BACE1 inhibitors from Corni Fructus that could have value as new multi-targeted compounds for anti-AD agents.

Possible mechanism of structural incorporation of Al into diatomite during the deposition process I. Via a condensation reaction of hydroxyl groups.

PubMed

Liu, Dong; Yu, Wenbin; Deng, Liangliang; Yuan, Weiwei; Ma, Lingya; Yuan, Peng; Du, Peixin; He, Hongping

2016-01-01

The structural incorporation of aluminium (Al) into diatomite is investigated by preparing several Al-diatomite composites by loading an Al precursor, hydroxyl aluminum polymer (Al13), onto the surface of diatomite and heating at various temperatures. The results indicate that Al was incorporated and implanted into the structure of diatomite by the condensation reaction of the hydroxyl groups of Al13 and diatomite, and the Si-O-Al(OH) groups were formed during the condensation reaction. Al incorporation by the condensation reaction of hydroxyl groups of Al13 with single silanols of diatomite occurred more readily than that with geminal silanols. The Al incorporation increased solid acidity of diatomite after Al incorporation. The acidity improvement was various for different types of acid sites, depending on the preparation temperature of the Al-incorporated diatomite. Both Brønsted and Lewis acid sites increased greatly after heating at 250 and 350 °C, but only L acid sites significantly improved after heating at 500 °C. These results demonstrate that the structural incorporation of Al(3+) ions into diatomite can occur by the condensation reaction of the hydroxyl groups of the Al precursors and diatomite. Moreover, the rich solid acid sites of Al-incorporated diatomite show its promising application as a solid acid catalyst. Copyright © 2015 Elsevier Inc. All rights reserved.

Split2 Protein-Ligation Generates Active IL-6-Type Hyper-Cytokines from Inactive Precursors.

PubMed

Moll, Jens M; Wehmöller, Melanie; Frank, Nils C; Homey, Lisa; Baran, Paul; Garbers, Christoph; Lamertz, Larissa; Axelrod, Jonathan H; Galun, Eithan; Mootz, Henning D; Scheller, Jürgen

2017-12-15

Trans-signaling of the major pro- and anti-inflammatory cytokines Interleukin (IL)-6 and IL-11 has the unique feature to virtually activate all cells of the body and is critically involved in chronic inflammation and regeneration. Hyper-IL-6 and Hyper-IL-11 are single chain designer trans-signaling cytokines, in which the cytokine and soluble receptor units are trapped in one complex via a flexible peptide linker. Albeit, Hyper-cytokines are essential tools to study trans-signaling in vitro and in vivo, the superior potency of these designer cytokines are accompanied by undesirable stress responses. To enable tailor-made generation of Hyper-cytokines, we developed inactive split-cytokine-precursors adapted for posttranslational reassembly by split-intein mediated protein trans-splicing (PTS). We identified cutting sites within IL-6 (E 134 /S 135 ) and IL-11 (G 116 /S 117 ) and obtained inactive split-Hyper-IL-6 and split-Hyper-IL-11 cytokine precursors. After fusion with split-inteins, PTS resulted in reconstitution of active Hyper-cytokines, which were efficiently secreted from transfected cells. Our strategy comprises the development of a background-free cytokine signaling system from reversibly inactivated precursor cytokines.

Laboratory management of cervical intraepithelial neoplasia: proposing a new paradigm.

PubMed

Herfs, Michael; Crum, Christopher P

2013-03-01

Since the discovery of human papillomavirus (HPV) type 16 in early 80s, the link between HPV and cervical cancer has been established with certainty, a function of the discovery and cloning of a range of HPV types associated with both cancer precursors (cervical intraepithelial neoplasia or CIN) and carcinomas and extensive epidemiologic, clinical, pathologic, and experimental data. These accumulated results have culminated in new paradigms of cancer prevention through screening and triage. Despite this, the management of women with CIN is still suboptimal and the overtreatment of these conditions still occurs, largely due to the lack of clarity regarding which precancerous lesions are most likely to progress in grade. Recently, a discrete population of cuboidal cells was discovered at the cervical squamocolumnar junction, the anatomic site where the large majority of HPV-related (pre)neoplastic lesions develop. These cells seem to be embryonic in nature and participate both in benign metaplasias and the initial phase of precancer development. This review summarizes the historical evolution of precursor management, assesses the potential role of this and other discoveries in segregating lower from higher-risk precursors, and examines their potential impact on the management of women with real or potential cervical cancer precursors.

Preparation of activated carbon monolith by application of phenolic resins as carbon precursors

NASA Astrophysics Data System (ADS)

Sajad, Mehran; Kazemzad, Mahmood; Hosseinnia, Azarmidokht

2014-04-01

In the current work, activated carbon monoliths have been prepared by application of different phenolic hydrocarbons namely catechol and resorcinol as carbon precursors. For synthesis of carbon monolith, the precursors have been mixed with Genapol PF-10 as template and then polymerized in the presence of lysine as catalyst. Then the polymerized monolith carbonized in inert atmosphere at 700°C and activated by water steam at 550°C. It was found that resorcinol polymerization is easier than catechol and occurred at 90°C while for polymerization of catechol elevated temperature of 120°C at hydrothermal condition is necessary. The prepared activated carbon samples have been characterized by various analysis methods including scanning electron microscopy (SEM), surface area measurement, and transmission electron microscopy (TEM). The adsorptions of three different aromatic hydrocarbons by the prepared activated carbon samples have also been investigated by high performance liquid chromatography (HPLC) and UV-Vis spectroscopy. It was found that carbon monolith prepared by catechol as carbon precursor has higher adsorpability and strength in comparison with the other sample. The higher performance of carbon monolith prepared by catechol can be associated with its higher active sites in comparison with resorcinol.

Multifractal detrended cross-correlation analysis on NO, NO2 and O3 concentrations at traffic sites

NASA Astrophysics Data System (ADS)

Xu, Weijia; Liu, Chunqiong; Shi, Kai; Liu, Yonghong

2018-07-01

NOX plays the important role for O3 production in atmospheric photochemical processes. In this paper, the cross-correlations between NO (NO2) and O3 at three traffic sites in Hong Kong are investigated, using the multifractal detrended cross-correlation analysis (MFDCCA). The results show that the cross-correlations between NO (NO2) and O3 have multifractal nature and long term persistent power-law decaying behavior. The sources of multifractality are discussed based on the shuffling and phase randomization procedure. The chi square test is applied to identify the contributions degree of NO and NO2 to multifractality due to its own long term correlations respectively. And the temporal evolutions of the local contributions degree of NO and NO2 to multifractality are investigated by the sliding windows method. The differences between them are explained by the self-organized criticality mechanism of air pollution, combined with global solar radiation. MFDCCA provides a helpful approach for understanding the quantitative relationship between the O3 and its precursors.

Impact of Genetic Testing and Family Health History Based Risk Counseling on Behavior Change and Cognitive Precursors for Type 2 Diabetes.

PubMed

Wu, R Ryanne; Myers, Rachel A; Hauser, Elizabeth R; Vorderstrasse, Allison; Cho, Alex; Ginsburg, Geoffrey S; Orlando, Lori A

2017-02-01

Family health history (FHH) in the context of risk assessment has been shown to positively impact risk perception and behavior change. The added value of genetic risk testing is less certain. The aim of this study was to determine the impact of Type 2 Diabetes (T2D) FHH and genetic risk counseling on behavior and its cognitive precursors. Subjects were non-diabetic patients randomized to counseling that included FHH +/- T2D genetic testing. Measurements included weight, BMI, fasting glucose at baseline and 12 months and behavioral and cognitive precursor (T2D risk perception and control over disease development) surveys at baseline, 3, and 12 months. 391 subjects enrolled of which 312 completed the study. Behavioral and clinical outcomes did not differ across FHH or genetic risk but cognitive precursors did. Higher FHH risk was associated with a stronger perceived T2D risk (p Kendall  < 0.001) and with a perception of "serious" risk (p Kendall  < 0.001). Genetic risk did not influence risk perception, but was correlated with an increase in perception of "serious" risk for moderate (p Kendall  = 0.04) and average FHH risk subjects (p Kendall  = 0.01), though not for the high FHH risk group. Perceived control over T2D risk was high and not affected by FHH or genetic risk. FHH appears to have a strong impact on cognitive precursors of behavior change, suggesting it could be leveraged to enhance risk counseling, particularly when lifestyle change is desirable. Genetic risk was able to alter perceptions about the seriousness of T2D risk in those with moderate and average FHH risk, suggesting that FHH could be used to selectively identify individuals who may benefit from genetic risk testing.

Intercalation of Lithium in Pitch-Based Graphitized Carbon Fibers Chemically Modified by Fluorine: Soft Carbon With or Without an Oxide Surface

NASA Technical Reports Server (NTRS)

Hung, Ching-Chen; Prisko, Aniko

1999-01-01

The effects of carbon structure and surface oxygen on the carbon's performance as the anode in lithium-ion battery were studied. Two carbon materials were used for the electrochemical tests: soft carbon made from defluorination of graphite fluoride, and the carbon precursor from which the graphite fluoride was made. In this research the precursor was graphitized carbon fiber P-100. It was first fluorinated to form CF(0.68), then defluorinated slowly at 350 to 450 C in bromoform, and finally heated in 1000 C nitrogen before exposed to room temperature air, producing disordered soft carbon having basic surface oxides. This process caused very little carbon loss. The electrochemical test involved cycles of lithium intercalation and deintercalation using C/saturated LiI-50/50 (vol %) EC and DMC/Li half cell. The cycling test had four major results. (1) The presence of a basic oxide surface may prevent solvent from entering the carbon structure and therefore prolong the carbon's cycle life for lithium intercalation-deintercalation. (2) The disordered soft carbon can store lithium through two different mechanisms. One of them is lithium intercalation. which gives the disordered carbon an electrochemical behavior similar to its more ordered graphitic precursor. The other is unknown in its chemistry, but is responsible for the high-N,oltage portion (less than 0.3V) of the charge-discharge curve. (3) Under certain conditions, the disordered carbon can store more lithium than its precursor. (4) These sample and its precursor can intercalate at 200 mA/g. and deintercalate at a rate of 2000 mA/g without significant capacity loss.

Early embryonic sensitivity to cyclophosphamide in cardiac differentiation from human embryonic stem cells.

PubMed

Zhu, Ming-Xia; Zhao, Jin-Yuan; Chen, Gui-An; Guan, Li

2011-09-01

hESCs (human embryonic stem cells) can differentiate into tissue derivatives of all three germ layers in vitro and mimic the development of the embryo in vivo. In this study, we have investigated the potential of an hESC-based assay for the detection of toxicity to cardiac differentiation in embryonic development. First of all, we developed the protocol of cardiac induction from hESCs according to our previous work and distinguished cardiac precursor cells and late mature cardiomyocytes from differentiated cells, demonstrated by the Q-PCR (quantitative real-time PCR), immunocytochemistry and flow cytometry analysis. In order to test whether CPA (cyclophosphamide) induces developmental and cellular toxicity in the human embryo, we exposed the differentiating cells from hESCs to CPA (a well-known proteratogen) at different stages. We have found that a high concentration of CPA could inhibit cardiac differentiation of hESCs. Two separate exposure intervals were used to determine the effects of CPA on cardiac precursor cells and late mature cardiomyocytes respectively. The cardiac precursor cells were sensitive to CPA in non-cytotoxic concentrations for the expression of the cardiac-specific mRNA markers Nkx2.5 (NK2 transcription factor related, locus 5), GATA-4 (GATA binding protein 4 transcription factor) and TNNT2 (troponin T type 2). Non-cytotoxic CPA concentrations did not affect the mRNA markers' expression in late mature cardiomyocytes, indicating that cardiac precursors were more sensitive to CPA than late cardiomyocytes in cardiogenesis. We set up the in vitro developmental toxicity test model so as to reduce the number of test animals and expenses without compromising the safety of consumers and patients. Furthermore, such in vitro methods may be possibly suited to test a large number of chemicals than the classical employed in vivo tests.

Rapid identification of fluorochrome modification sites in proteins by LC ESI-Q-TOF mass spectrometry.

PubMed

Manikwar, Prakash; Zimmerman, Tahl; Blanco, Francisco J; Williams, Todd D; Siahaan, Teruna J

2011-07-20

Conjugation of either a fluorescent dye or a drug molecule to the ε-amino groups of lysine residues of proteins has many applications in biology and medicine. However, this type of conjugation produces a heterogeneous population of protein conjugates. Because conjugation of fluorochrome or drug molecule to a protein may have deleterious effects on protein function, the identification of conjugation sites is necessary. Unfortunately, the identification process can be time-consuming and laborious; therefore, there is a need to develop a rapid and reliable way to determine the conjugation sites of the fluorescent label or drug molecule. In this study, the sites of conjugation of fluorescein-5'-isothiocyanate and rhodamine-B-isothiocyanate to free amino groups on the insert-domain (I-domain) protein derived from the α-subunit of lymphocyte function-associated antigen-1 (LFA-1) were determined by electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-Q-TOF MS) along with peptide mapping using trypsin digestion. A reporter fragment of the fluorochrome moiety that is generated in the collision cell of the Q-TOF without explicit MS/MS precursor selection was used to identify the conjugation site. Selected ion plots of the reporter ion readily mark modified peptides in chromatograms of the complex digest. Interrogation of theses spectra reveals a neutral loss/precursor pair that identifies the modified peptide. The results show that one to seven fluorescein molecules or one to four rhodamine molecules were attached to the lysine residue(s) of the I-domain protein. No modifications were found in the metal ion-dependent adhesion site (MIDAS), which is an important binding region of the I-domain.

Development of a method for estimating emissions from oil and gas production sites utilizing remote observations

EPA Science Inventory

There is a lack of information on emissions of ozone precursors, hazardous air pollutants, and greenhouse gases from oil and gas production operations, and measurement of these emissions presents many challenges. Assessment is complicated by the fugitive nature ofthe emissions, v...

Production of jet fuel precursor monoterpenoids from engineered Escherichia coli: Production of Jet Fuel Precursor Monoterpenoids

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

Mendez-Perez, Daniel; Alonso-Gutierrez, Jorge; Hu, Qijun

Monoterpenes (C 10 isoprenoids) are the main components of essential oils and are possible precursors for many commodity chemicals and high energy density fuels. Monoterpenes are synthesized from geranyl diphosphate (GPP), which is also the precursor for the biosynthesis of farnesyl diphosphate (FPP). FPP biosynthesis diverts the carbon flux from monoterpene production to C 15 products and quinone biosynthesis. In this study, we tested a chromosomal mutation of Escherichia coli's native FPP synthase (IspA) to improve GPP availability for the production of monoterpenes using a heterologous mevalonate pathway. Monoterpene production at high levels required not only optimization of GPP productionmore » but also a basal level of FPP to maintain growth. The optimized strains produced two jet fuel precursor monoterpenoids 1,8-cineole and linalool at the titer of 653 mg/L and 505 mg/L, respectively, in batch cultures with 1% glucose. The engineered strains developed in this work provide useful resources for the production of high-value monoterpenes.« less

Production of jet fuel precursor monoterpenoids from engineered Escherichia coli: Production of Jet Fuel Precursor Monoterpenoids

DOE PAGES

Mendez-Perez, Daniel; Alonso-Gutierrez, Jorge; Hu, Qijun; ...

2017-05-18

Monoterpenes (C 10 isoprenoids) are the main components of essential oils and are possible precursors for many commodity chemicals and high energy density fuels. Monoterpenes are synthesized from geranyl diphosphate (GPP), which is also the precursor for the biosynthesis of farnesyl diphosphate (FPP). FPP biosynthesis diverts the carbon flux from monoterpene production to C 15 products and quinone biosynthesis. In this study, we tested a chromosomal mutation of Escherichia coli's native FPP synthase (IspA) to improve GPP availability for the production of monoterpenes using a heterologous mevalonate pathway. Monoterpene production at high levels required not only optimization of GPP productionmore » but also a basal level of FPP to maintain growth. The optimized strains produced two jet fuel precursor monoterpenoids 1,8-cineole and linalool at the titer of 653 mg/L and 505 mg/L, respectively, in batch cultures with 1% glucose. The engineered strains developed in this work provide useful resources for the production of high-value monoterpenes.« less

Sequence-based design of bioactive small molecules that target precursor microRNAs.

PubMed

Velagapudi, Sai Pradeep; Gallo, Steven M; Disney, Matthew D

2014-04-01

Oligonucleotides are designed to target RNA using base pairing rules, but they can be hampered by poor cellular delivery and nonspecific stimulation of the immune system. Small molecules are preferred as lead drugs or probes but cannot be designed from sequence. Herein, we describe an approach termed Inforna that designs lead small molecules for RNA from solely sequence. Inforna was applied to all human microRNA hairpin precursors, and it identified bioactive small molecules that inhibit biogenesis by binding nuclease-processing sites (44% hit rate). Among 27 lead interactions, the most avid interaction is between a benzimidazole (1) and precursor microRNA-96. Compound 1 selectively inhibits biogenesis of microRNA-96, upregulating a protein target (FOXO1) and inducing apoptosis in cancer cells. Apoptosis is ablated when FOXO1 mRNA expression is knocked down by an siRNA, validating compound selectivity. Markedly, microRNA profiling shows that 1 only affects microRNA-96 biogenesis and is at least as selective as an oligonucleotide.

Sequence-based design of bioactive small molecules that target precursor microRNAs

PubMed Central

Velagapudi, Sai Pradeep; Gallo, Steven M.; Disney, Matthew D.

2014-01-01

Oligonucleotides are designed to target RNA using base pairing rules, however, they are hampered by poor cellular delivery and non-specific stimulation of the immune system. Small molecules are preferred as lead drugs or probes, but cannot be designed from sequence. Herein, we describe an approach termed Inforna that designs lead small molecules for RNA from solely sequence. Inforna was applied to all human microRNA precursors and identified bioactive small molecules that inhibit biogenesis by binding to nuclease processing sites (41% hit rate). Amongst 29 lead interactions, the most avid interaction is between a benzimidazole (1) and precursor microRNA-96. Compound 1 selectively inhibits biogenesis of microRNA-96, upregulating a protein target (FOXO1) and inducing apoptosis in cancer cells. Apoptosis is ablated when FOXO1 mRNA expression is knocked down by an siRNA, validating compound selectivity. Importantly, microRNA profiling shows that 1 only significantly effects microRNA-96 biogenesis and is more selective than an oligonucleotide. PMID:24509821

Dehalogenation and coupling of a polycyclic hydrocarbon on an atomically thin insulator.

PubMed

Dienel, Thomas; Gómez-Díaz, Jaime; Seitsonen, Ari P; Widmer, Roland; Iannuzzi, Marcella; Radican, Kevin; Sachdev, Hermann; Müllen, Klaus; Hutter, Jürg; Gröning, Oliver

2014-07-22

Catalytic activity is of pivotal relevance in enabling efficient and selective synthesis processes. Recently, covalent coupling reactions catalyzed by solid metal surfaces opened the rapidly evolving field of on-surface chemical synthesis. Tailored molecular precursors in conjunction with the catalytic activity of the metal substrate allow the synthesis of novel, technologically highly relevant materials such as atomically precise graphene nanoribbons. However, the reaction path on the metal substrate remains unclear in most cases, and the intriguing question is how a specific atomic configuration between reactant and catalyst controls the reaction processes. In this study, we cover the metal substrate with a monolayer of hexagonal boron nitride (h-BN), reducing the reactivity of the metal, and gain unique access to atomistic details during the activation of a polyphenylene precursor by sequential dehalogenation and the subsequent coupling to extended oligomers. We use scanning tunneling microscopy and density functional theory to reveal a reaction site anisotropy, induced by the registry mismatch between the precursor and the nanostructured h-BN monolayer.

Tropospheric Ozone Over North America

NASA Astrophysics Data System (ADS)

Oltmans, S. J.; Thompson, A. M.; Cooper, O. R.; Merrill, J. T.; Tarasick, D. W.; Newchurch, M. J.

2007-05-01

Ozone in the troposphere plays a significant role as an absorber of infrared radiation (greenhouse gas), in the cleansing capacity of the atmosphere as a precursor of hydroxol radical formation, and a regulated air pollutant capable of deleterious health and ecosystem effects. Knowledge of the ozone budget in the troposphere over North America (NA) is required to properly understand the various mechanisms that contribute to the measured distribution and to develop and test models capable of simulating and predicting this key player in atmospheric chemical and physical processes. Recent field campaigns including the 2004 and 2006 INTEX Ozone Network Studies (IONS) http:croc.gsfc.nasa.gov/intexb/ions06.html that have included intensive ozone profile measurements from ozonesondes provide a unique data set for describing tropospheric ozone over a significant portion of the North American continent. These campaigns have focused on the spring and summer seasons when tropospheric ozone over NA is particularly influenced by long-range transport processes, significant photochemical ozone production resulting from both anthropogenic and natural (lightning) precursor emissions, and exchange with the stratosphere. This study uses ozone profiles measured over NA in the latitude band from approximately 12-60N, extending from the tropics to the high mid latitudes, to describe the seasonal behavior of tropospheric ozone over NA with an emphasis on the spring and summer. This includes the variability within seasons at a particular site as well as the contrasts between the seasons. Emphasis is placed on the variations among the sites including latitudinal and longitudinal gradients and how these differ through the seasons and with altitude in the troposphere. Regional differences are most pronounced during the summer season likely reflecting the influence of a wider variation in processes influencing the tropospheric ozone distribution including lightning NOX production in the upper troposphere and active photochemistry from human emitted precursors in the lower troposphere. In all seasons, including the summer, transfer from the stratosphere significantly influences the upper tropospheric distribution at mid latitude (35-55N) locations. Although the seasonal maximum is found in spring in most locations and throughout much of the troposphere, this season tends to show less geographic variability compared to the summer. The FLEXPART Lagrangian tracer model is used to help identify processes associated with distinctive profile characteristics in the ozonesonde measurements.

Are Oppositional-Defiant and Hyperactive-Inattentive Symptoms Developmental Precursors to Conduct Problems in Late Childhood?: Genetic and Environmental Links

ERIC Educational Resources Information Center

Lahey, Benjamin B.; Van Hulle, Carol A.; Rathouz, Paul J.; Rodgers, Joseph Lee; D'Onofrio, Brian M.; Waldman, Irwin D.

2009-01-01

Inattentive-hyperactive and oppositional behavior have been hypothesized to be developmental precursors to conduct problems. We tested these hypotheses using a longitudinal sample of 6,466 offspring of women selected from nationally representative US households. Conduct problems across 8-13 years were robustly predicted by conduct problems at 4-7…

Effects of Varium and a pre-cursor formula on cytokine production in broiler chickens challenged with Eimeria maxima and Clostridium perfringens

USDA-ARS?s Scientific Manuscript database

Two studies were conducted to evaluate the ability of new products with toxin binding properties on cytokine production during a necrotic enteritis challenge. A precursor (PV) formula to the product Varium (V) was tested in experiment one, and PV and V formulas were included in the second experimen...

Whole-cell fungal transformation of precursors into dyes

PubMed Central

2010-01-01

Background Chemical methods of producing dyes involve extreme temperatures and unsafe toxic compounds. Application of oxidizing enzymes obtained from fungal species, for example laccase, is an alternative to chemical synthesis of dyes. Laccase can be replaced by fungal biomass acting as a whole-cell biocatalyst with properties comparable to the isolated form of the enzyme. The application of the whole-cell system simplifies the transformation process and reduces the time required for its completion. In the present work, four fungal strains with a well-known ability to produce laccase were tested for oxidation of 17 phenolic and non-phenolic precursors into stable and non-toxic dyes. Results An agar-plate screening test of the organic precursors was carried out using four fungal strains: Trametes versicolor, Fomes fomentarius, Abortiporus biennis, and Cerrena unicolor. Out of 17 precursors, nine were transformed into coloured substances in the presence of actively growing fungal mycelium. The immobilized fungal biomass catalyzed the transformation of 1 mM benzene and naphthalene derivatives in liquid cultures yielding stable and non-toxic products with good dyeing properties. The type of fungal strain had a large influence on the absorbance of the coloured products obtained after 48-hour transformation of the selected precursors, and the most effective was Fomes fomentarius (FF25). Whole-cell transformation of AHBS (3-amino-4-hydroxybenzenesulfonic acid) into a phenoxazinone dye was carried out in four different systems: in aqueous media comprising low amounts of carbon and nitrogen source, in buffer, and in distilled water. Conclusions This study demonstrated the ability of four fungal strains belonging to the ecological type of white rot fungi to transform precursors into dyes. This paper highlights the potential of fungal biomass for replacing isolated enzymes as a cheaper industrial-grade biocatalyst for the synthesis of dyes and other commercially important products. The use of immobilized fungal biomass limits free migration of cells and facilitates their reuse in a continuous system for precursor transformation. PMID:20598166

Selenium containing imidazolium salt in designing single source precursors for silver bromide and selenide nano-particles.

PubMed

Joshi, Hemant; Sharma, Kamal Nayan; Singh, Ved Vati; Singh, Pradhumn; Singh, Ajai Kumar

2013-02-21

The AgBr and Ag(2)Se nanoparticles (NPs) have been synthesized for the first time from two single source precursors ([Ag(2)(L)(2)Br(2)] (1) and [Ag(L-HBr)(2)]BF(4) (2) respectively) designed using the same ligand 3-benzyl-1-(2-phenylselanyl-ethyl)-3H-imidazolium bromide (L). The ODE-ODA-OA (1 : 1 : 2) and TOP-OA (1 : 2) are most suitable solvents for thermolysis of 1 and 2 respectively, resulting in the NPs. The composition of the solvent used in thermolysis affects the purity of NPs. The bonding of L in 1 is unique, as it has a pre-carbene site intact.

hUTP24 is essential for processing of the human rRNA precursor at site A1, but not at site A0

PubMed Central

Tomecki, Rafal; Labno, Anna; Drazkowska, Karolina; Cysewski, Dominik; Dziembowski, Andrzej

2015-01-01

Production of ribosomes relies on more than 200 accessory factors to ensure the proper sequence of steps and faultless assembly of ribonucleoprotein machinery. Among trans-acting factors are numerous enzymes, including ribonucleases responsible for processing the large rRNA precursor synthesized by RNA polymerase I that encompasses sequences corresponding to mature 18S, 5.8S, and 25/28S rRNA. In humans, the identity of most enzymes responsible for individual processing steps, including endoribonucleases that cleave pre-rRNA at specific sites within regions flanking and separating mature rRNA, remains largely unknown. Here, we investigated the role of hUTP24 in rRNA maturation in human cells. hUTP24 is a human homolog of the Saccharomyces cerevisiae putative PIN domain-containing endoribonuclease Utp24 (yUtp24), which was suggested to participate in the U3 snoRNA-dependent processing of yeast pre-rRNA at sites A0, A1, and A2. We demonstrate that hUTP24 interacts to some extent with proteins homologous to the components of the yeast small subunit (SSU) processome. Moreover, mutation in the putative catalytic site of hUTP24 results in slowed growth of cells and reduced metabolic activity. These effects are associated with a defect in biogenesis of the 40S ribosomal subunit, which results from decreased amounts of 18S rRNA as a consequence of inaccurate pre-rRNA processing at the 5′-end of the 18S rRNA segment (site A1). Interestingly, and in contrast to yeast, site A0 located upstream of A1 is efficiently processed upon UTP24 dysfunction. Finally, hUTP24 inactivation leads to aberrant processing of 18S rRNA 2 nucleotides downstream of the normal A1 cleavage site. PMID:26237581

N-nitrosamine formation by monochloramine, free chlorine, and peracetic acid disinfection with presence of amine precursors in drinking water system.

PubMed

West, Danielle M; Wu, Qihua; Donovan, Ariel; Shi, Honglan; Ma, Yinfa; Jiang, Hua; Wang, Jianmin

2016-06-01

In this study, the formation of eight N-nitrosamines, N-nitrosodimethylamine (NDMA), N-nitrosodiethylamine, N-nitrosomethylamine, N-nitrosodi-n-propylamine, N-nitrosodi-n-butylamine, N-Nitrosopiperidine, N-Nitrosopyrrolidine, N-Nitrosomorpholine, were systematically evaluated with respect to seven N-nitrosamine precursors (dimethylamine, trimethylamine, 3-(dimethylaminomethyl)indole, 4-dimethylaminoantipyrine, ethylmethylamine, diethylamine, dipropylamine) and three disinfectants (monochloramine, free chlorine, peracetic acid) under variable dosages, exposure times, and pH in a drinking water system. Without the presence of the seven selected N-nitrosamine precursors N-nitrosamine formation was not observed under any tested condition except very low levels of N-Nitrosopyrrolidine under some conditions. With selected N-nitrosamine precursors present N-nitrosamines formed at different levels under different conditions. The highest N-nitrosamine formation was NDMA with a maximum concentration of 1180 ng/L by monochloramine disinfection with precursors present; much lower levels of N-nitrosamines were formed by free chlorine disinfection; and no detectable level of N-nitrosamines were observed by peracetic acid disinfection except low level of N-Nitrosodi-n-propylamine under some conditions. NDMA formation was not affected by pH while four other N-nitrosamine formations were slightly affected by sample pH tested between 7 and 9, with formation decreasing with increasing pH. Monochloramine exposure time study displayed fast formation of N-nitrosamines, largely formed in four hours of exposure and maximized after seven days. This was a systematic study on the N-nitrosamine formation with the seven major N-nitrosamine precursors presence and absence under different conditions, including peracetic acid disinfection which has not been studied elsewhere. Copyright © 2016 Elsevier Ltd. All rights reserved.

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

Lewis, M.E.; Khachaturian, H.; Watson, S.J.

Using adjacent section autoradiography-immunocytochemistry, the distribution of (TH)naloxone binding sites was studied in relation to neuronal systems containing (Leu)enkephalin, dynorphin A, or beta-endorphin immunoreactivity in rat brain. Brain sections from formaldehyde-perfused rats show robust specific binding of (TH)naloxone, the pharmacological (mu-like) properties of which appear unaltered. In contrast, specific binding of the delta ligand (TH)D-Ala2,D-Leu5-enkephalin was virtually totally eliminated as a result of formaldehyde perfusion. Using adjacent section analysis, the authors have noted associations between (TH)naloxone binding sites and one, two, or all three opioid systems in different brain regions; however, in some areas, no apparent relationship could be observed.more » Within regions, the relationship was complex. The complexity of the association between (TH)naloxone binding sites and the multiple opioid systems, and previous reports of co-localization of mu and kappa receptors in rat brain, are inconsistent with a simple-one-to-one relationship between a given opioid precursor and opioid receptor subtype. Instead, since differential processing of the three precursors gives rise to peptides of varying receptor subtype potencies and selectivities, the multiple peptide-receptor relationships may point to a key role of post-translational processing in determining the physiological consequences of opioid neurotransmission.« less

Structural Characterization of the E2 Domain of APL-1, a C. Elegans Homolog of Human Amyloid Precursor Protein, and its Heparin Binding Site

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

Hoopes, J.; Liu, X; Xu, X

2010-01-01

The amyloid {beta}-peptide deposit found in the brain tissue of patients with Alzheimer disease is derived from a large heparin-binding protein precursor APP. The biological function of APP and its homologs is not precisely known. Here we report the x-ray structure of the E2 domain of APL-1, an APP homolog in Caenorhabditis elegans, and compare it to the human APP structure. We also describe the structure of APL-1 E2 in complex with sucrose octasulfate, a highly negatively charged disaccharide, which reveals an unexpected binding pocket between the two halves of E2. Based on the crystal structure, we are able tomore » map, using site-directed mutagenesis, a surface groove on E2 to which heparin may bind. Our biochemical data also indicate that the affinity of E2 for heparin is influenced by pH: at pH 5, the binding appears to be much stronger than that at neutral pH. This property is likely caused by histidine residues in the vicinity of the mapped heparin binding site and could be important for the proposed adhesive function of APL-1.« less

Precursor-product discrimination by La protein during tRNA metabolism.

PubMed

Bayfield, Mark A; Maraia, Richard J

2009-04-01

La proteins bind pre-tRNAs at their UUU-3'OH ends, facilitating their maturation. Although the mechanism by which La binds pre-tRNA 3' trailers is known, the function of the RNA binding beta-sheet surface of the RNA-recognition motif (RRM1) is unknown. How La dissociates from UUU-3'OH-containing trailers after 3' processing is also unknown. Here we show that La preferentially binds pre-tRNAs over processed tRNAs or 3' trailer products through coupled use of two sites: one on the La motif and another on the RRM1 beta-surface that binds elsewhere on tRNA. Two sites provide stable pre-tRNA binding, whereas the processed tRNA and 3' trailer are released from their single sites relatively fast. RRM1 loop-3 mutations decrease affinity for pre-tRNA and tRNA, but not for the UUU-3'OH trailer, and impair tRNA maturation in vivo. We propose that RRM1 functions in activities that are more complex than UUU-3'OH binding. Accordingly, the RRM1 mutations also impair an RNA chaperone activity of La. The results suggest how La distinguishes precursor from product RNAs, allowing it to recycle onto a new pre-tRNA.

Micro-structural evolution and biomineralization behavior of carbon nanofiber/bioactive glass composites induced by precursor aging time.

PubMed

Jia, Xiaolong; Tang, Tianhong; Cheng, Dan; Zhang, Cuihua; Zhang, Ran; Cai, Qing; Yang, Xiaoping

2015-12-01

Bioactive glass (BG)-containing carbon nanofibers (CNFs) are promising orthopaedic biomaterials. Herein, CNF composites were produced from electrospinning of polyacrylonitrile (PAN)/BG sol-gel precursor solution, followed by carbonization. Choosing 58S-type BG (mol%: 58.0% SiO2-26.3% CaO-15.7% P2O5) as the model, micro-structural evolution of CNF/BG composites was systematically evaluated in relating to aging times of BG precursor solution. With aging time prolonging, BG precursors underwent morphological changes from small sol clusters with loosely and randomly branched structure to highly crosslinked Si-network structure, showing continuous increase in solution viscosity. BG precursor solution with low viscosity could mix well with PAN solution, resulting in CNF composite with homogeneously distributed BG component. Whereas, BG precursor gel with densely crosslinked Si-network structure led to uneven distribution of BG component along final CNFs due to its significant phase separation from PAN component. Meanwhile, BG nanoparticles in CNFs demonstrated micro-structural evolution that they transited from weak to strong crystal state along with longer aging time. Biomineralization in simulated body fluid and in vitro osteoblasts proliferation were then applied to determine the bioactivity of CNF/BG composites. CNF/BG composites prepared from shorter aging time could induce both faster apatite deposition and cell proliferation rate. It was suggested weakly crystallized BG nanoparticles along CNFs dissolved fast and was able to provide numerous nucleation sites for apatite deposition, which also favored the proliferation of osteoblasts cells. Aging time could thus be a useful tool to regulate the biological features of CNF/BG composites. Copyright © 2015 Elsevier B.V. All rights reserved.

Biogenesis of lysosomal enzymes in the alpha-glucosidase II-deficient modA mutant of Dictyostelium discoideum: retention of alpha-1,3-linked glucose on N-linked oligosaccharides delays intracellular transport but does not alter sorting of alpha-mannosidase or beta-glucosidase.

PubMed

Ebert, D L; Bush, J M; Dimond, R L; Cardelli, J A

1989-09-01

The endoplasmic reticulum-localized enzyme alpha-glucosidase II is responsible for removing the two alpha-1,3-linked glucose residues from N-linked oligosaccharides of glycoproteins. This activity is missing in the modA mutant strain, M31, of Dictyostelium discoideum. Results from both radiolabeled pulse-chase and subcellular fractionation experiments indicate that this deficiency did not prevent intracellular transport and proteolytic processing of the lysosomal enzymes, alpha-mannosidase and beta-glucosidase. However, the rate at which the glucosylated precursors left the rough endoplasmic reticulum was several-fold slower than the rate at which the wild-type precursors left this compartment. Retention of glucose residues did not disrupt the binding of the precursor forms of the enzymes with intracellular membranes, indicating that the delay in movement of proteins from the ER did not result from lack of association with membranes. However, the mutant alpha-mannosidase precursor contained more trypsin-sensitive sites than did the wild-type precursor, suggesting that improper folding of precursor molecules might account for the slow rate of transport to the Golgi complex. Percoll density gradient fractionation of extracts prepared from M31 cells indicated that the proteolytically processed mature forms of alpha-mannosidase and beta-glucosidase were localized to lysosomes. Finally, the mutation in M31 may have other, more dramatic, effects on the lysosomal system since two enzymes, N-acetylglucosaminidase and acid phosphatase, were secreted much less efficiently from lysosomal compartments by the mutant strain.

Assessing the contribution of wetlands and subsided islands to dissolved organic matter and disinfection byproduct precursors in the Sacramento-San Joaquin River Delta: A geochemical approach

USGS Publications Warehouse

Kraus, T.E.C.; Bergamaschi, B.A.; Hernes, P.J.; Spencer, R.G.M.; Stepanauskas, R.; Kendall, C.; Losee, R.F.; Fujii, R.

2008-01-01

This study assesses how rivers, wetlands, island drains and open water habitats within the Sacramento-San Joaquin River Delta affect dissolved organic matter (DOM) content and composition, and disinfection byproduct (DBP) formation. Eleven sites representative of these habitats were sampled on six dates to encompass seasonal variability. Using a suite of qualitative analyses, including specific DBP formation potential, absorbance, fluorescence, lignin content and composition, C and N stable isotopic compositions, and structural groupings determined using CPMAS (cross polarization, magic angle spinning) 13C NMR, we applied a geochemical fingerprinting approach to characterize the DOM from different Delta habitats, and infer DOM and DBP precursor sources and estimate the relative contribution from different sources. Although river input was the predominant source of dissolved organic carbon (DOC), we observed that 13-49% of the DOC exported from the Delta originated from sources within the Delta, depending on season. Interaction with shallow wetlands and subsided islands significantly increased DOC and DBP precursor concentrations and affected DOM composition, while deep open water habitats had little discernable effect. Shallow wetlands contributed the greatest amounts of DOM and DBP precursors in the spring and summer, in contrast to island drains which appeared to be an important source during winter months. The DOM derived from wetlands and island drains had greater haloacetic acid precursor content relative to incoming river water, while two wetlands contributed DOM with greater propensity to form trihalomethanes. These results are pertinent to restoration of the Delta. Large scale introduction of shallow wetlands, a proposed restoration strategy, could alter existing DOC and DBP precursor concentrations, depending on their hydrologic connection to Delta channels. ?? 2008 Elsevier Ltd.

Proteolytic events in the post-translational processing of somatostatin precursors from rat brain cortex and anglerfish pancreatic islets.

PubMed

Cohen, P; Morel, A; Gluschankof, P; Gomez, S; Nicolas, P

1985-01-01

An Arg-Lys esteropeptidase which converts somatostatin-28 (S-28) into somatostatin-14 (S-14) was detected in rat brain cortical extracts using a synthetic undecapeptide substrate mimicking the octacosapeptide sequence at the restriction site. This enzyme system was unable to release either the octacosapeptide or S-14 from the 15,000 mol wt (15K) rat hypothalamic precursor. This argues in favor of sequential degradation of the precursor into S-14 via S-28 as an obligatory intermediate. Another in vivo processing system was analyzed in the anglerfish pancreatic Brockmann organs. Here, cloning of two cDNA corresponding to two mRNA species predicts two distinct somatostatins precursors, called prosomatostatins I and II (Hobart et al., Nature 288:137, 1980). While a single S-14 can be detected in extracts made from this pancreatic tissue, indistinguishable from the mammalian species, two S-28 species could be separated by HPLC. Immunochemical and biochemical evidence indicates that the second species should correspond to anglerfish S-28 (AF S-28), the product of prosomatostatin-II processing in vivo. Amino acid analysis, together with the determined complete amino acid sequence of this peptide, demonstrates that this is indeed the case and that AF S-28 contains in its C-terminal half the [Tyr7, Gly10] derivative of S-14. These observations give an example of a AF S-28 being a terminal active product of prosomatostatin processing. They suggest that this octacosapeptide, which is potent on the inhibition of growth hormone release by anterior pituitary cells, may play such a role in the gastrointestinal tract of the anglerfish. These results, while not excluding alternative routes, give support to a sequential processing of the 15 K precursor----S-28----S-14.

Space Shuttle main engine product improvement

NASA Technical Reports Server (NTRS)

Lucci, A. D.; Klatt, F. P.

1985-01-01

The current design of the Space Shuttle Main Engine has passed 11 certification cycles, amassed approximately a quarter million seconds of engine test time in 1200 tests and successfully launched the Space Shuttle 17 times of 51 engine launches through May 1985. Building on this extensive background, two development programs are underway at Rocketdyne to improve the flow of hot gas through the powerhead and evaluate the changes to increase the performance margins in the engine. These two programs, called Phase II+ and Technology Test Bed Precursor program are described. Phase II+ develops a two-tube hot-gas manifold that improves the component environment. The Precursor program will evaluate a larger throat main combustion chamber, conduct combustion stability testing of a baffleless main injector, fabricate an experimental weld-free heat exchanger tube, fabricate and test a high pressure oxidizer turbopump with an improved inlet, and develop and test methods for reducing temperature transients at start and shutdown.

ATP-binding cassette-like transporters are involved in the transport of lignin precursors across plasma and vacuolar membranes

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

Miao, Y.C.; Liu, C.

2010-12-28

Lignin is a complex biopolymer derived primarily from the condensation of three monomeric precursors, the monolignols. The synthesis of monolignols occurs in the cytoplasm. To reach the cell wall where they are oxidized and polymerized, they must be transported across the cell membrane. However, the molecular mechanisms underlying the transport process are unclear. There are conflicting views about whether the transport of these precursors occurs by passive diffusion or is an energized active process; further, we know little about what chemical forms are required. Using isolated plasma and vacuolar membrane vesicles prepared from Arabidopsis, together with applying different transporter inhibitorsmore » in the assays, we examined the uptake of monolignols and their derivatives by these native membrane vesicles. We demonstrate that the transport of lignin precursors across plasmalemma and their sequestration into vacuoles are ATP-dependent primary-transport processes, involving ATP-binding cassette-like transporters. Moreover, we show that both plasma and vacuolar membrane vesicles selectively transport different forms of lignin precursors. In the presence of ATP, the inverted plasma membrane vesicles preferentially take up monolignol aglycones, whereas the vacuolar vesicles are more specific for glucoconjugates, suggesting that the different ATP-binding cassette-like transporters recognize different chemical forms in conveying them to distinct sites, and that glucosylation of monolignols is necessary for their vacuolar storage but not required for direct transport into the cell wall in Arabidopsis.« less

Synthesis and Characterization of Chalcopyrite (CuInS2 and CuhInSe2) Colloidal Nanoparticles for Optoelectronic Applications via Low-Temperature Pyrolysis of Single-Source Precursors

NASA Technical Reports Server (NTRS)

Castro, S. L.; Bailey, S. G.; Raffaelle, R. P.; Banger, K. K.; Fahey, Stephen; Hepp, A. F.

2003-01-01

Nanocrystalline (or quantum dot) materials hold potential as components of next-generation photovoltaic (PV) devices. The inclusion of quantum dots in PV devices has been proposed as a means to improve the efficiency of photon conversion (quantum dot solar cell), enable low-cost deposition of thin-films, provide sites for exciton dissociation, and pathways for electron transport. Quantum dots are also expected to be more resistant to degradation from electron, proton, and alpha particle radiation than the corresponding bulk material, a requirement for use in space solar sells. Chalcopyrite nanocrystals can be produced by low-temperature thermal decomposition of single-source precursors such as (PR3)2CuIn(ER')4 (R = Ph, R' = Et, E = S; R = R' = Ph, E = Se). Single-source precursors are molecules which contain all the necessary elements for synthesis of a desired material. Thermal decomposition of the precursor results in the formation of material with the correct stoichiometry as a nanocrystalline powder or a thin film, often at significantly lower temperatures than those typically employed for thin-film deposition by multi-source evaporation techniques, typically less than 500 C. We show that CuInSz and CuInSe2 nanocrystals can be synthesized from the precursors at temperatures as low as 250 C. The nanocrystals are characterized by optical spectroscopy, X-ray diffraction, and electron microscopy.

Detection and Site Localization of Phosphorylcholine-Modified Peptides by NanoLC-ESI-MS/MS Using Precursor Ion Scanning and Multiple Reaction Monitoring Experiments

NASA Astrophysics Data System (ADS)

Timm, Thomas; Lenz, Christof; Merkel, Dietrich; Sadiffo, Christian; Grabitzki, Julia; Klein, Jochen; Lochnit, Guenter

2015-03-01

Phosphorylcholine (PC)-modified biomolecules like lipopolysaccharides, glycosphingolipids, and (glyco)proteins are widespread, highly relevant antigens of parasites, since this small hapten shows potent immunomodulatory capacity, which allows the establishment of long-lasting infections of the host. Especially for PC-modified proteins, structural data is rare because of the zwitterionic nature of the PC substituent, resulting in low sensitivities and unusual but characteristic fragmentation patterns. We have developed a targeted mass spectrometric approach using hybrid triple quadrupole/linear ion trap (QTRAP) mass spectrometry coupled to nanoflow chromatography for the sensitive detection of PC-modified peptides from complex proteolytic digests, and the localization of the PC-modification within the peptide backbone. In a first step, proteolytic digests are screened using precursor ion scanning for the marker ions of choline ( m/z 104.1) and phosphorylcholine ( m/z 184.1) to establish the presence of PC-modified peptides. Potential PC-modified precursors are then subjected to a second analysis using multiple reaction monitoring (MRM)-triggered product ion spectra for the identification and site localization of the modified peptides. The approach was first established using synthetic PC-modified synthetic peptides and PC-modified model digests. Following the optimization of key parameters, we then successfully applied the method to the detection of PC-peptides in the background of a proteolytic digest of a whole proteome. This methodological invention will greatly facilitate the detection of PC-substituted biomolecules and their structural analysis.

Mutations near the cleavage site of enterocin NKR-5-3B prepeptide reveal new insights into its biosynthesis.

PubMed

Perez, Rodney H; Sugino, Haruki; Ishibashi, Naoki; Zendo, Takeshi; Wilaipun, Pongtep; Leelawatcharamas, Vichien; Nakayama, Jiro; Sonomoto, Kenji

2017-04-01

Enterocin NKR-5-3B (Ent53B) is a 64-residue novel circular bacteriocin synthesized from an 87-residue prepeptide. Albeit through a still unknown mechanism, the EnkB1234 biosynthetic enzyme complex processes the prepeptide to yield its mature active, circular form. To gain insights into the key region/residue that plays a role in Ent53 maturation, several mutations near the cleavage site on the precursor peptide were generated. The interaction of the precursor peptide and EnkB1234 appeared to be hydrophobic in nature. At the Leu1 position, only mutations with helix structure-promoting hydrophobic residues (Ala, Ile, Val or Phe) were able to yield the mature Ent53B derivative. In this study, we also highlight the possible conformation-stabilizing role of the Ent53B leader peptide on the precursor peptide for its interaction with its biosynthetic enzyme complex. Any truncations of the leader peptide moiety interfered in the processing of the prepeptide. However, when propeptides of other circular bacteriocins (circularin A, leucocyclicin Q or lactocyclicin Q) were cloned at the C-terminus of the leader peptide, EnkB1234 could not process them to yield a mature bacteriocin. Taken together, these findings offer new perspectives in our understanding of the possible molecular mechanism of the biosynthesis of this circular bacteriocin. These new perspectives will help advance our current understanding to eventually elucidate circular bacteriocin biosynthesis. Understanding the biosynthetic mechanism of circular bacteriocins will materialize their application potential.

Synthesis, characterization and inhibitory activities of (4-N3[3,5-3H]Phe10)PKI(6-22)amide and its precursors: photoaffinity labeling peptides for the active site of cyclic AMP-dependent protein kinase.

PubMed

Katz, B M; Lundquist, L J; Walsh, D A; Glass, D B

1989-06-01

PKI(6-22)amide is a 17 residue peptide corresponding to the active portion of the heat-stable inhibitor of cAMP-dependent protein kinase. The peptide is a potent (Ki = 1.6 nM), competitive inhibitor of the enzyme. The photoreactive peptide analog (4-azidophenylalanine10)PKI(6-22)amide was synthesized in both its non-radiolabeled and tritiated forms by chemical modification of precursor peptides that were prepared by stepwise solid-phase synthesis. (4-Amino[3,5-3H]phenylalanine10)PKI(6-22)amide, the precursor for the radiolabeled arylazide peptide, was obtained by catalytic reduction of the corresponding peptide containing the 3,5-diiodo-4-aminophenylalanine residue at position 10. The purified PKI peptides were analyzed by HPLC, amino acid analysis, and u.v. spectra. In the dark, (4-azidophenylalanine10)PKI(6-22)amide inhibited the catalytic subunit of cAMP-dependent protein kinase with a Ki value of 2.8 nM. The photoreactivity of the arylazide peptide was demonstrated by time-dependent u.v. spectral changes on exposure to light. Photolysis of the catalytic subunit (4-azido[3,5-3H]phenylalanine10)PKI(6-22)amide complex resulted in specific covalent labeling of the enzyme. The data indicate that this peptide is a useful photoaffinity labeling reagent for the active site of the protein kinase.

The nucleotide sequence of the putative transcription initiation site of a cloned ribosomal RNA gene of the mouse.

PubMed Central

Urano, Y; Kominami, R; Mishima, Y; Muramatsu, M

1980-01-01

Approximately one kilobase pairs surrounding and upstream the transcription initiation site of a cloned ribosomal DNA (rDNA) of the mouse were sequenced. The putative transcription initiation site was determined by two independent methods: one nuclease S1 protection and the other reverse transcriptase elongation mapping using isolated 45S ribosomal RNA precursor (45S RNA) and appropriate restriction fragments of rDNA. Both methods gave an identical result; 45S RNA had a structure starting from ACTCTTAG---. Characteristically, mouse rDNA had many T clusters (greater than or equal to 5) upstream the initiation site, the longest being 21 consecutive T's. A pentadecanucleotide, TGCCTCCCGAGTGCA, appeared twice within 260 nucleotides upstream the putative initiation site. No such characteristic sequences were found downstream this site. Little similarity was found in the upstream of the transcription initiation site between the mouse, Xenopus laevis and Saccharomyces cerevisiae rDNA. Images PMID:6162156

Microparticle Shedding from Neural Progenitor Cells and Vascular Compartment Cells Is Increased in Ischemic Stroke.

PubMed

Chiva-Blanch, Gemma; Suades, Rosa; Crespo, Javier; Peña, Esther; Padró, Teresa; Jiménez-Xarrié, Elena; Martí-Fàbregas, Joan; Badimon, Lina

2016-01-01

Ischemic stroke has shown to induce platelet and endothelial microparticle shedding, but whether stroke induces microparticle shedding from additional blood and vascular compartment cells is unclear. Neural precursor cells have been shown to replace dying neurons at sites of brain injury; however, if neural precursor cell activation is associated to microparticle shedding, and whether this activation is maintained at long term and associates to stroke type and severity remains unknown. We analyzed neural precursor cells and blood and vascular compartment cells microparticle shedding after an acute ischemic stroke. Forty-four patients were included in the study within the first 48h after the onset of stroke. The cerebral lesion size was evaluated at 3-7 days of the stroke. Circulating microparticles from neural precursor cells and blood and vascular compartment cells (platelets, endothelial cells, erythrocytes, leukocytes, lymphocytes, monocytes and smooth muscle cells) were analyzed by flow cytometry at the onset of stroke and at 7 and 90 days. Forty-four age-matched high cardiovascular risk subjects without documented vascular disease were used as controls. Compared to high cardiovascular risk controls, patients showed higher number of neural precursor cell- and all blood and vascular compartment cell-derived microparticles at the onset of stroke, and after 7 and 90 days. At 90 days, neural precursor cell-derived microparticles decreased and smooth muscle cell-derived microparticles increased compared to levels at the onset of stroke, but only in those patients with the highest stroke-induced cerebral lesions. Stroke increases blood and vascular compartment cell and neural precursor cell microparticle shedding, an effect that is chronically maintained up to 90 days after the ischemic event. These results show that stroke induces a generalized blood and vascular cell activation and the initiation of neuronal cell repair process after stroke. Larger cerebral lesions associate with deeper vessel injury affecting vascular smooth muscle cells.

Preliminary assessment of DOC and THM precursor loads from a freshwater restored wetland, an agricultural field, and a tidal wetland in the Sacramento-San Joaquin River Delta

USGS Publications Warehouse

Fujii, R.; Bergamaschi, B.A.; Ganju, N.K.; Fleck, J.A.; Burow-Fogg, K.R.; Schoellhamer, D.; Deverel, S.J.

2003-01-01

Water exported from the Sacramento-San Joaquin River Delta supplies drinking water to more than 22 million people in California. At certain times of the year, Delta waters contain relatively high concentrations of dissolved organic carbon (DOC) and bromide. During these times, chlorination of Delta water for drinking water disinfection will form disinfection byproducts, such as trihalomethanes (THMs), that can exceed the U.S. Environmental Protection Agency's maximum contaminant level for THMs of 80 mg/L. Important sources of DOC and THM precursors (types of DOC that form THMs when chlorinated) to the Delta include rivers, drainage water from peat islands, water from wetlands and areas with extensive riparian vegetation, and in-channel growth of algae and macrophytes. Due to proposed ecosystem restoration and creation of wetlands in the Delta, there is an urgent need for information on the relative loads of DOC and THM precursors produced from three different land uses: restored wetlands constructed for subsidence mitigation, tidal wetlands, and agricultural operations. We have been conducting research in the Delta to provide this information. A restored wetland and agricultural field located on Twitchell Island, and a tidal wetland on Browns Island have been monitored for flow, DOC, and THM precursors. Initial results indicate that the loads of DOC and THM precursors are similar for the restored wetland (surface water only) and the agricultural field. These land uses produce DOC loads of about 14 and 11 g C/m2/yr, respectively, and THM precursor loads of about 1.7 and 1.0 g THM/m2/yr, respectively. Estimates of DOC and THM precursor loads for the tidal wetland site on Browns Island and seepage associated with the restored wetland are being developed.

Microparticle Shedding from Neural Progenitor Cells and Vascular Compartment Cells Is Increased in Ischemic Stroke

PubMed Central

Chiva-Blanch, Gemma; Suades, Rosa; Crespo, Javier; Peña, Esther; Padró, Teresa; Jiménez-Xarrié, Elena; Martí-Fàbregas, Joan; Badimon, Lina

2016-01-01

Purpose Ischemic stroke has shown to induce platelet and endothelial microparticle shedding, but whether stroke induces microparticle shedding from additional blood and vascular compartment cells is unclear. Neural precursor cells have been shown to replace dying neurons at sites of brain injury; however, if neural precursor cell activation is associated to microparticle shedding, and whether this activation is maintained at long term and associates to stroke type and severity remains unknown. We analyzed neural precursor cells and blood and vascular compartment cells microparticle shedding after an acute ischemic stroke. Methods Forty-four patients were included in the study within the first 48h after the onset of stroke. The cerebral lesion size was evaluated at 3–7 days of the stroke. Circulating microparticles from neural precursor cells and blood and vascular compartment cells (platelets, endothelial cells, erythrocytes, leukocytes, lymphocytes, monocytes and smooth muscle cells) were analyzed by flow cytometry at the onset of stroke and at 7 and 90 days. Forty-four age-matched high cardiovascular risk subjects without documented vascular disease were used as controls. Results Compared to high cardiovascular risk controls, patients showed higher number of neural precursor cell- and all blood and vascular compartment cell-derived microparticles at the onset of stroke, and after 7 and 90 days. At 90 days, neural precursor cell-derived microparticles decreased and smooth muscle cell-derived microparticles increased compared to levels at the onset of stroke, but only in those patients with the highest stroke-induced cerebral lesions. Conclusions Stroke increases blood and vascular compartment cell and neural precursor cell microparticle shedding, an effect that is chronically maintained up to 90 days after the ischemic event. These results show that stroke induces a generalized blood and vascular cell activation and the initiation of neuronal cell repair process after stroke. Larger cerebral lesions associate with deeper vessel injury affecting vascular smooth muscle cells. PMID:26815842

Single cell cultures of Drosophila neuroectodermal and mesectodermal central nervous system progenitors reveal different degrees of developmental autonomy.

PubMed

Lüer, Karin; Technau, Gerhard M

2009-08-03

The Drosophila embryonic central nervous system (CNS) develops from two sets of progenitor cells, neuroblasts and ventral midline progenitors, which behave differently in many respects. Neuroblasts derive from the neurogenic region of the ectoderm and form the lateral parts of the CNS. Ventral midline precursors are formed by two rows of mesectodermal cells and build the CNS midline. There is plenty of evidence that individual identities are conferred to precursor cells by positional information in the ectoderm. It is unclear, however, how far the precursors can maintain their identities and developmental properties in the absence of normal external signals. To separate the respective contributions of autonomous properties versus extrinsic signals during their further development, we isolated individual midline precursors and neuroectodermal precursors at the pre-mitotic gastrula stage, traced their development in vitro, and analyzed the characteristics of their lineages in comparison with those described for the embryo. Although individually cultured mesectodermal cells exhibit basic characteristics of CNS midline progenitors, the clones produced by these progenitors differ from their in situ counterparts with regard to cell numbers, expression of molecular markers, and the separation of neuronal and glial fate. In contrast, clones derived from individually cultured precursors taken from specific dorsoventral zones of the neuroectoderm develop striking similarities to the lineages of neuroblasts that normally delaminate from these zones and develop in situ. This in vitro analysis allows for the first time a comparison of the developmental capacities in situ and in vitro of individual neural precursors of defined spatial and temporal origin. The data reveal that cells isolated at the pre-mitotic and pre-delamination stage express characteristics of the progenitor type appropriate to their site of origin in the embryo. However, presumptive neuroblasts, once specified in the neuroectoderm, exhibit a higher degree of autonomy regarding generation of their lineages compared to mesectodermal midline progenitors.

The effects of shock wave precursors ahead of hypersonic entry vehicles

NASA Technical Reports Server (NTRS)

Stanley, Scott A.; Carlson, Leland A.

1991-01-01

A model has been developed to predict the magnitude and characteristics of the shock wave precursor ahead of a hypervelocity vehicle. This model includes both chemical and thermal nonequilibrium, utilizes detailed mass production rates for the photodissociation and photoionization reactions, and accounts for the effects of radiative absorption and emission on the individual internal energy modes of both atomic and diatomic species. Comparison of the present results with shock tube data indicates that the model is reasonably accurate. A series of test cases representing earth aerocapture return from Mars indicate that there is significant production of atoms, ions and electrons ahead of the shock front due to radiative absorption and that the precursor is characterized by an enhanced electron/electronic temperature and molecular ionization. However, the precursor has a negligible effect on the shock layer flow field.

Carbene complexes of rhodium and iridium from tripodal N-heterocyclic carbene ligands: synthesis and catalytic properties.

PubMed

Mas-Marzá, Elena; Poyatos, Macarena; Sanaú, Mercedes; Peris, Eduardo

2004-03-22

Two tripodal trisimidazolium ligand precursors have been tested in the synthesis of new N-heterocyclic carbene rhodium and iridium complexes. [Tris(3-methylbenzimidazolium-1-yl)]methane sulfate gave products with coordination of the decomposed precursor. [1,1,1-Tris(3-butylimidazolium-1-yl)methyl]ethane trichloride (TIMEH(3)(Bu)) coordinated to the metal in a chelate and bridged-chelate form, depending on the reaction conditions. The crystal structures of two of the products are described. The compounds resulting from the coordination with TIME(Bu) were tested in the catalytic hydrosilylation of terminal alkynes.

Studies on the site of biosynthesis of acidic glycoproteins of guinea-pig serum

PubMed Central

Simkin, J. L.; Jamieson, J. C.

1967-01-01

1. Studies were carried out to determine the cellular and subcellular site of biosynthesis of components of fraction I, an α-globulin fraction containing acidic glycoproteins isolated from guinea-pig serum. l-[U-14C]Leucine or -valine and d-[1-14C]glucosamine were used as precursors. 2. A lag of about 10min. occurred before appreciable label appeared in fraction I of serum after injection of leucine or glucosamine. Label in fraction I after 60min. labelling with glucosamine was present almost entirely in hexosamine and sialic acid. 3. Site of synthesis was investigated by studies in vivo up to 17min. after injection of precursor. Particulate subcellular fractions isolated from liver, spleen and kidney or homogenates of the latter two tissues were extracted with Lubrol. Extracts were allowed to react by double diffusion with antisera to fraction I or to subfractions isolated from it, and gels were subsequently subjected to radioautography. With either amino acid or glucosamine as precursor, only extracts of the microsome fraction of liver formed precipitin lines that were appreciably radioactive. 4. The role of the microsome fraction of liver in the synthesis of these glycoproteins was confirmed by immunological studies after incubation of liver slices with leucine or glucosamine. Incorporation of leucine was also investigated in a cell-free microsome system. 5. Material was also precipitated from certain Lubrol extracts of liver microsomes by direct addition of antiserum and its radioactivity measured. Degradation of material thus precipitated and use of heterologous immune systems showed that labelling of precipitin lines represented biosynthesis. 6. A study of extraction procedures suggested that the substances present in the microsome fraction of liver that react with specific antisera are associated with membranous structures. 7. Most or all precipitin lines formed by Lubrol extracts of liver microsomes interacted with precipitin lines given by guinea-pig serum or fraction I, immunological identity being apparent with some lines. The microsome-bound substances thus represent serum glycoproteins or precursors of them. 8. The distribution of label in various tissues and in the protein of subcellular fractions of liver after administration of [14C]glucosamine to the guinea pig was also studied. Some variation in results obtained with liver was found depending on the fractionation medium used. Images(a)(b)(a)(b) PMID:4962164

Thin Film CuInS2 Prepared by Spray Pyrolysis with Single-Source Precursors

NASA Technical Reports Server (NTRS)

Jin, Michael H.; Banger, Kulinder K.; Harris, Jerry D.; Cowen, Jonathan E.; Hepp, Aloysius F.; Lyons, Valerie (Technical Monitor)

2002-01-01

Both horizontal hot-wall and vertical cold-wall atmospheric chemical spray pyrolysis processes deposited near single-phase stoichiometric CuInS2 thin films. Single-source precursors developed for ternary chalcopyrite materials were used for this study, and a new liquid phase single-source precursor was tested with a vertical cold-wall reactor. The depositions were carried out under an argon atmosphere, and the substrate temperature was kept at 400 C. Columnar grain structure was obtained with vapor deposition, and the granular structure was obtained with (liquid) droplet deposition. Conductive films were deposited with planar electrical resistivities ranging from 1 to 30 Omega x cm.

Fidelity of metal insertion into hydrogenases.

PubMed

Magalon, A; Blokesch, M; Zehelein, E; Böck, A

2001-06-15

The fidelity of metal incorporation into the active center of hydrogenase 3 from Escherichia coli was studied by analyzing the inhibition of the maturation pathway by zinc and other transition metals. Hydrogenase maturation of wild-type cells was significantly affected only by concentrations of zinc or cadmium higher than 200 microM, whereas a mutant with a lesion in the nickel uptake system displayed a total blockade of the proteolytic processing of the precursor form into the mature form of the large subunit after growth in the presence of 10 microM Zn(2+). The precursor could not be processed in vitro by the maturation endopeptidase even in the presence of an excess of nickel ions. Evidence is presented that zinc does not interfere with the incorporation of iron into the metal center. Precursor of the large subunit accumulated in nickel proficient cells formed a transient substrate complex with the cognate endoprotease HycI whereas that of zinc-supplemented cells did not. The results show that zinc can intrude the nickel-dependent maturation pathway only when nickel uptake is blocked. Under this condition zinc appears to be incorporated at the nickel site of the large subunit and delivers a precursor not amenable to proteolytic processing since the interaction with the endoprotease is blocked.

Effect of copper concentration in the electrolyte on the surface morphology and the microstructure of CuInSe2 films

NASA Astrophysics Data System (ADS)

Hung, Pin-Kun; Kuo, Ting-Wei; Huang, Kuo-Chan; Wang, Na-Fu; Hsieh, Po-Tsung; Houng, Mau-Phon

2012-07-01

The surface morphology and the microstructure of CuInSe2 precursor films have been investigated by co-electrodeposition with different [Cu2+] concentrations from 2 mM to 4 mM. The characteristic of the precursor films was examined using field-emission scanning electron microscopy (FE-SEM), energy dispersive X-ray spectroscopy (EDS), glancing incidence angle X-ray diffraction (GIXRD) and micro-Raman spectrometer, respectively. The surface morphology of the precursor films become more smoother and compact with choice of appropriate [Cu2+] concentration (3-3.5 mM) in the electrolyte. The relation between surface morphology and [Cu2+] concentration is also considered in terms of electrodeposition nucleation mechanisms using the mathematical models of Scharifker and Hills. It is suggested that the higher [Cu2+] concentrations can provide more numbers of nucleation sites on the surface of the electrode. Results simulated from the Rietveld refinement method suggest that decreasing dCusbnd Se is related to charge transfer from interstitial copper atoms and can affect the film microstructure. Micro-Raman spectrum also shows that the excess Cu atoms in the precursor films does not contribute significantly to large amounts of secondary phases but rather exists in the crystallite structure as other defect types.

Structure prediction and functional analysis of a non-permutated lectin from Dioclea grandiflora.

PubMed

de Sousa, Bruno Lopes; Nagano, Celso Shiniti; Simões, Rafael da Conceição; Silva-Filho, José Caetano; Cunha, Rodrigo Maranguape da Silva; Cajazeiras, João Batista; do Nascimento, Kyria Santiago; Cavada, Benildo Sousa

2016-12-01

Legume lectins have been widely studied and applied for many purposes in the last few decades, but many of their physiological aspects remain elusive. The Diocleinae legume subtribe, which includes intensively explored lectins, such as ConA, presents an unusual and extensive post-translational process which results in minor alterations in protein structure, in turn making its function elusive. Despite previous reports about Diocleinae precursor activity, no structural or functional analyses have ever been carried out to understand the impacts of post-translational processing relative to lectin structure and binding specificity. Here we analyzed the functionality of a non glycosylated, recombinantly expressed lectin precursor from Dioclea grandiflora through inhibition assays, corroborating the experimental data with structural information generated by molecular modeling, docking calculations and molecular dynamics simulations. We demonstrate that Diocleinae precursors are active and share the same carbohydrate specificity as mature lectins. At the same time, however, subtle structural alterations were detected and mostly result in an "incomplete" functionality of the precursor, as consequence of an immature binding site and an unstructured tetramer interface, affecting carbohydrate binding and oligomer formation, respectively. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Real time validation of GPS TEC precursor mask for Greece

NASA Astrophysics Data System (ADS)

Pulinets, Sergey; Davidenko, Dmitry

2013-04-01

It was established by earlier studies of pre-earthquake ionospheric variations that for every specific site these variations manifest definite stability in their temporal behavior within the time interval few days before the seismic shock. This self-similarity (characteristic to phenomena registered for processes observed close to critical point of the system) permits us to consider these variations as a good candidate to short-term precursor. Physical mechanism of GPS TEC variations before earthquakes is developed within the framework of Lithosphere-Atmosphere-Ionosphere Coupling (LAIC) model. Taking into account the different tectonic structure and different source mechanisms of earthquakes in different regions of the globe, every site has its individual behavior in pre-earthquake activity what creates individual "imprint" on the ionosphere behavior at every given point. Just this so called "mask" of the ionosphere variability before earthquake in the given point creates opportunity to detect anomalous behavior of electron concentration in ionosphere basing not only on statistical processing procedure but applying the pattern recognition technique what facilitates the automatic recognition of short-term ionospheric precursors of earthquakes. Such kind of precursor mask was created using the GPS TEC variation around the time of 9 earthquakes with magnitude from M6.0 till M6.9 which took place in Greece within the time interval 2006-2011. The major anomaly revealed in the relative deviation of the vertical TEC was the positive anomaly appearing at ~04PM UT one day before the seismic shock and lasting nearly 12 hours till ~04AM UT. To validate this approach it was decided to check the mask in real-time monitoring of earthquakes in Greece starting from the 1 of December 2012 for the earthquakes with magnitude more than 4.5. During this period (till 9 of January 2013) 4 cases of seismic shocks were registered, including the largest one M5.7 on 8 of January. For all of them the mask confirmed its validity and 6 of December event was predicted in advance.

Perceived discrimination and sexual precursor behaviors in Mexican American preadolescent girls: The role of psychological distress, sexual attitudes, and marianismo beliefs.

PubMed

Sanchez, Delida; Whittaker, Tiffany A; Hamilton, Emma; Zayas, Luis H

2016-07-01

This study explored the relation between perceived discrimination and sexual precursor behaviors among 205 Mexican American preadolescent middle school girls. In addition, this study examined whether psychological distress and sexual attitudes mediated and whether marianismo beliefs moderated this relation. A categorical confirmatory factor analysis (CCFA) of the Marianismo Beliefs Scale (MBS) was conducted to test the factor structure with a preadolescent Mexican American population (ages 11-14). A path analysis of analytic models was then performed to examine the hypothesized relations between perceived discrimination, psychological distress, sexual attitudes, marianismo beliefs, and sexual precursor behaviors. Results of the CCFA did not support the original 5-factor structure of the MBS for preadolescent Latina girls. However, a revised version of the MBS indicated an acceptable model fit, and findings from the path analysis indicated that perceived discrimination was both directly and indirectly linked to sexual precursor behaviors via psychological distress. Marianismo was not found to moderate the relation between perceived discrimination and sexual risk behaviors, however certain marianismo pillars were significantly negatively linked with sexual attitudes and precursor behaviors. This study underscores the importance of psychological distress in the perceived discrimination and sexual precursor link as well as the compensatory aspects of marianismo against sexual precursor behaviors in Mexican American preadolescent girls. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Transcription termination and RNA processing in the 3'-end spacer of mouse ribosomal RNA genes.

PubMed Central

Miwa, T; Kominami, R; Yoshikura, H; Sudo, K; Muramatsu, M

1987-01-01

The 3' termini of ribosomal RNA precursors from mouse FM3A cultured cells are mapped to eight sites within 625 bp downstream from the 3' terminus of 28 S rRNA. Three additional sites are mapped in liver RNA from C3H/He strain mice. Two of them, the sites at 570 bp and 625 bp are assumed to be termination sites in vivo, because they correspond to in vitro termination sites of RNA polymerase I, and 45 S RNAs having these 3' termini decay with kinetics distinct from others. The amount of 45 S RNA having the 3' terminus at other sites is variable among several mouse strains, despite their having the same DNA sequence in these regions. The ability to produce 3' termini in these sites seems to follow Mendel's law of inheritance. Therefore, we postulate that these nine sites are RNA processing sites which are controlled genetically. Images PMID:3031586

Structural basis of glycan specificity in neonate-specific bovine-human reassortant rotavirus

DOE PAGES

Hu, Liya; Ramani, Sasirekha; Czako, Rita; ...

2015-09-30

We report that strain-dependent variation of glycan recognition during initial cell attachment of viruses is a critical determinant of host specificity, tissue-tropism and zoonosis. Rotaviruses (RVs), which cause life-threatening gastroenteritis in infants and children, display significant genotype-dependent variations in glycan recognition resulting from sequence alterations in the VP8* domain of the spike protein VP4. The structural basis of this genotype-dependent glycan specificity, particularly in human RVs, remains poorly understood. Here, from crystallographic studies, we show how genotypic variations configure a novel binding site in the VP8* of a neonate-specific bovine-human reassortant to uniquely recognize either type I or type IImore » precursor glycans, and to restrict type II glycan binding in the bovine counterpart. In conclusion, such a distinct glycan-binding site that allows differential recognition of the precursor glycans, which are developmentally regulated in the neonate gut and abundant in bovine and human milk provides a basis for age-restricted tropism and zoonotic transmission of G10P[11] rotaviruses.« less

Structural basis of glycan specificity in neonate-specific bovine-human reassortant rotavirus

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

Hu, Liya; Ramani, Sasirekha; Czako, Rita

We report that strain-dependent variation of glycan recognition during initial cell attachment of viruses is a critical determinant of host specificity, tissue-tropism and zoonosis. Rotaviruses (RVs), which cause life-threatening gastroenteritis in infants and children, display significant genotype-dependent variations in glycan recognition resulting from sequence alterations in the VP8* domain of the spike protein VP4. The structural basis of this genotype-dependent glycan specificity, particularly in human RVs, remains poorly understood. Here, from crystallographic studies, we show how genotypic variations configure a novel binding site in the VP8* of a neonate-specific bovine-human reassortant to uniquely recognize either type I or type IImore » precursor glycans, and to restrict type II glycan binding in the bovine counterpart. In conclusion, such a distinct glycan-binding site that allows differential recognition of the precursor glycans, which are developmentally regulated in the neonate gut and abundant in bovine and human milk provides a basis for age-restricted tropism and zoonotic transmission of G10P[11] rotaviruses.« less

Despacito: the slow evolutionary changes in plant microRNAs.

PubMed

Baldrich, Patricia; Beric, Aleksandra; Meyers, Blake C

2018-02-12

MicroRNAs (miRNAs) are key regulators of gene expression. A handful of miRNAs are broadly conserved in land plants, while the majority are lineage specific; this review describes the processes by which new miRNAs are hypothesized to have emerged. Two major models describe miRNA origins, firstly, de novo emergence via inverted duplication of target gene fragments, and secondly, the expansion and neofunctionalization of existing miRNA families. The occasional acquisition of target sites by previously un-targeted genes adds further dynamism to the process by which miRNAs may shift roles during evolution. Additional factors guiding miRNA evolution include functional constraints on their length and the importance of precursor conservation that is observed in regions above or below the mature miRNA duplex; these regions represent recognition sites for components of biogenesis machinery and direct precursor processing. Insights into the mechanisms of miRNA emergence and divergence are important for understanding plant genome evolution and the impact of miRNA regulatory networks. Copyright © 2018 Elsevier Ltd. All rights reserved.

Solution-processed flexible fluorine-doped indium zinc oxide thin-film transistors fabricated on plastic film at low temperature.

PubMed

Seo, Jin-Suk; Jeon, Jun-Hyuck; Hwang, Young Hwan; Park, Hyungjin; Ryu, Minki; Park, Sang-Hee Ko; Bae, Byeong-Soo

2013-01-01

Transparent flexible fluorine-doped indium zinc oxide (IZO:F) thin-film transistors (TFTs) were demonstrated using the spin-coating method of the metal fluoride precursor aqueous solution with annealing at 200°C for 2 hrs on polyethylene naphthalate films. The proposed thermal evolution mechanism of metal fluoride aqueous precursor solution examined by thermogravimetric analysis and Raman spectroscopy can easily explain oxide formation. The chemical composition analysed by XPS confirms that the fluorine was doped in the thin films annealed below 250°C. In the IZO:F thin films, a doped fluorine atom substitutes for an oxygen atom generating a free electron or occupies an oxygen vacancy site eliminating an electron trap site. These dual roles of the doped fluorine can enhance the mobility and improve the gate bias stability of the TFTs. Therefore, the transparent flexible IZO:F TFT shows a high mobility of up to 4.1 cm(2)/V·s and stable characteristics under the various gate bias and temperature stresses.

Solution-Processed Flexible Fluorine-doped Indium Zinc Oxide Thin-Film Transistors Fabricated on Plastic Film at Low Temperature

PubMed Central

Seo, Jin-Suk; Jeon, Jun-Hyuck; Hwang, Young Hwan; Park, Hyungjin; Ryu, Minki; Park, Sang-Hee Ko; Bae, Byeong-Soo

2013-01-01

Transparent flexible fluorine-doped indium zinc oxide (IZO:F) thin-film transistors (TFTs) were demonstrated using the spin-coating method of the metal fluoride precursor aqueous solution with annealing at 200°C for 2 hrs on polyethylene naphthalate films. The proposed thermal evolution mechanism of metal fluoride aqueous precursor solution examined by thermogravimetric analysis and Raman spectroscopy can easily explain oxide formation. The chemical composition analysed by XPS confirms that the fluorine was doped in the thin films annealed below 250°C. In the IZO:F thin films, a doped fluorine atom substitutes for an oxygen atom generating a free electron or occupies an oxygen vacancy site eliminating an electron trap site. These dual roles of the doped fluorine can enhance the mobility and improve the gate bias stability of the TFTs. Therefore, the transparent flexible IZO:F TFT shows a high mobility of up to 4.1 cm2/V·s and stable characteristics under the various gate bias and temperature stresses. PMID:23803977

Truncated presequences of mitochondrial F1-ATPase beta subunit from Nicotiana plumbaginifolia transport CAT and GUS proteins into mitochondria of transgenic tobacco.

PubMed

Chaumont, F; Silva Filho, M de C; Thomas, D; Leterme, S; Boutry, M

1994-02-01

The mitochondrial F1-ATPase beta subunit (ATPase-beta) of Nicotiana plumbaginifolia is nucleus-encoded as a precursor containing an NH2-terminal extension. By sequencing the mature N. tabacum ATPase-beta, we determined the length of the presequence, viz. 54 residues. To define the essential regions of this presequence, we produced a series of 3' deletions in the sequence coding for the 90 NH2-terminal residues of ATPase-beta. The truncated sequences were fused with the chloramphenicol acetyl transferase (cat) and beta-glucuronidase (gus) genes and introduced into tobacco plants. From the observed distribution of CAT and GUS activity in the plant cells, we conclude that the first 23 amino-acid residues of ATPase-beta remain capable of specifically targeting reporter proteins into mitochondria. Immunodetection in transgenic plants and in vitro import experiments with various CAT fusion proteins show that the precursors are processed at the expected cleavage site but also at a cryptic site located in the linker region between the presequence and the first methionine of native CAT.

Mucosal colonization by metastatic carcinoma in the gastrointestinal tract: a potential mimic of primary neoplasia.

PubMed

Estrella, Jeannelyn S; Wu, Tsung-Teh; Rashid, Asif; Abraham, Susan C

2011-04-01

The gastrointestinal (GI) tract is a common site for both primary and metastatic carcinomas. Distinguishing the two can occasionally be difficult, particularly when metastatic tumor reaches the mucosal surface. Features that are typically used to make this distinction include the presence of an adenomatous precursor lesion, regional lymph node involvement, and gross configuration of the tumor. However, we recently encountered 2 index cases of metastatic carcinoma in the small intestine (1 from the colorectum and 1 of endocervical origin) that were initially misinterpreted as primary small bowel carcinomas because of apparent in situ growth in the mucosal surface resembling polypoid, adenomatous precursor lesions. We, therefore, studied 100 GI resections from 1987 to 2009 that were reported to show mucosal involvement by metastatic carcinoma, and compared the histologic features with a control group of 29 primary small bowel adenocarcinomas. Gross descriptions and histologic sections were evaluated for the following: (1) tumor spread along an intact basement membrane of villi/crypts (mucosal colonization), (2) resemblance to an adenoma/precursor lesion, (3) gross configuration of the tumor, (4) lymphovascular invasion, and (5) regional lymph node involvement in the metastatic site. Metastatic sites included the small intestine (n=74), colorectum (n=16), or both (n=10). Primary tumors were GI (n=55, with 47 from colorectum), gynecologic (n=28), pulmonary (n=8), genitourinary (n=6), head and neck (n=2), and breast (n=1). Overall, 42 (42%) of the metastases that reached the mucosal surface of the bowel showed at least focal mucosal colonization, 26% resembled a precursor adenoma, 62% had regional lymph node positivity, and only 24% cases showed a classic serosal-based configuration. In 4 cases (2 of GI origin and 2 of gynecologic origin), metastatic tumors were initially interpreted as new primaries by the pathologist (n=2) or clinicians (n=2). Metastatic carcinomas originating from the GI tract were significantly more likely to show mucosal colonization (60% vs. 20%, P<0.0001) and resemblance to a precursor lesion (45% vs. 2%, P<0.0001) than other primary tumors. In a comparison between 29 primary small bowel carcinomas and 41 metastatic colorectal carcinomas in the small bowel, metastatic tumors were distinguished by a higher prevalence of multiple lesions (0% vs. 39%, P<0.0001), whereas small bowel primaries were more likely to show high tumor grade (41% vs. 17%, P=0.03). There were no significant differences in the mean age (61.4 y vs. 60.9 y), number of male participants (69% vs. 56%), growth along basement membranes (62% vs. 63%), apparent precursor lesion (55% vs. 46%), lymphovascular invasion (69% vs. 73%), or lymph node positivity (68% vs. 37.5%, P=0.065). These results confirm that metastatic carcinomas involving the mucosal surface of the intestines frequently exhibit gross and histologic features, which mimic second primaries, especially when they originate from the GI tract. In situ growth and presence of an apparent adenoma cannot be taken as prima facie evidence of a primary neoplasm.

Applying polarity rapid assessment method and ultrafiltration to characterize NDMA precursors in wastewater effluents.

PubMed

Chen, Chao; Leavey, Shannon; Krasner, Stuart W; Mel Suffet, I H

2014-06-15

Certain nitrosamines in water are disinfection byproducts that are probable human carcinogens. Nitrosamines have diverse and complex precursors that include effluent organic matter, some anthropogenic chemicals, and natural (likely non-humic) substances. An easy and selective tool was first developed to characterize nitrosamine precursors in treated wastewaters, including different process effluents. This tool takes advantages of the polarity rapid assessment method (PRAM) and ultrafiltration (UF) (molecular weight distribution) to locate the fractions with the strongest contributions to the nitrosamine precursor pool in the effluent organic matter. Strong cation exchange (SCX) and C18 solid-phase extraction cartridges were used for their high selectivity for nitrosamine precursors. The details of PRAM operation, such as cartridge clean-up, capacity, pH influence, and quality control were included in this paper, as well as the main parameters of UF operation. Preliminary testing of the PRAM/UF method with effluents from one wastewater treatment plant gave very informative results. SCX retained 45-90% of the N-nitrosodimethylamine (NDMA) formation potential (FP)-a measure of the precursors-in secondary and tertiary wastewater effluents. These results are consistent with NDMA precursors likely having a positively charged amine group. C18 adsorbed 30-45% of the NDMAFP, which indicates that a substantial portion of these precursors were non-polar. The small molecular weight (MW) (<1 kDa) and large MW (>10 kDa) fractions obtained from UF were the primary contributors to NDMAFP. The combination of PRAM and UF brings important information on the characteristics of nitrosamine precursors in water with easy operation. Copyright © 2014 Elsevier Ltd. All rights reserved.

"Captive Column" Crash Tests : Crash Testing of a Light Standard Luminaire Pole

DOT National Transportation Integrated Search

1981-03-01

Under contract No. DOT-FH-11-9606 the Nevada Department of Transportation (NDOT) conducted crash testing to study the capability of "Captive Column" light standard appurtenances under controlled conditions. The studies were precursors of actual on si...

Induction of colonic aberrant crypts in mice by feeding apparent N-nitroso compounds derived from hot dogs

PubMed Central

Davis, Michael E; Lisowyj, Michal P; Zhou, Lin; Wisecarver, James L; Gulizia, James M; Shostrom, Valerie K; Naud, Nathalie; Corpet, Denis E; Mirvish, Sidney S

2012-01-01

Nitrite-preserved meats (e.g., hot dogs) may help cause colon cancer because they contain N-nitroso compounds. We tested whether purified hot-dog-derived total apparent N-nitroso compounds (ANC) could induce colonic aberrant crypts, which are putative precursors of colon cancer. We purified ANC precursors in hot dogs and nitrosated them to produce ANC. In preliminary tests, CF1 mice received 1 or 3 i.p. injections of 5mg azoxymethane (AOM)/kg. In Experiments 1 and 2, female A/J mice received ANC in diet. In Experiment 1, ANC dose initially dropped sharply because the ANC precursors had mostly decomposed but, later in Experiment 1 and throughout Experiment 2, ANC remained at 85 nmol/g diet. Mice were killed after 8 (AOM tests) or 17–34 (ANC tests) wk. Median numbers of aberrant crypts in the distal 2 cm of the colon for 1 and 3 AOM injections, CF1 controls, ANC (Experiment 1), ANC (Experiment 2),and untreated A/J mice were 31, 74, 12, 20, 12, and 5–6, with P < 0.01 for both ANC tests. Experiment 2 showed somewhat increased numbers of colonic mucin-depleted foci in the ANC-treated group. We conclude that hot-dog-derived ANC induced significant numbers of aberrant crypts in the mouse colon. PMID:22293095

Determinants of the VP1/2A junction cleavage by the 3C protease in foot-and-mouth disease virus-infected cells.

PubMed

Kristensen, Thea; Normann, Preben; Gullberg, Maria; Fahnøe, Ulrik; Polacek, Charlotta; Rasmussen, Thomas Bruun; Belsham, Graham J

2017-03-01

The foot-and-mouth disease virus (FMDV) capsid precursor, P1-2A, is cleaved by FMDV 3C protease to yield VP0, VP3, VP1 and 2A. Cleavage of the VP1/2A junction is the slowest. Serotype O FMDVs with uncleaved VP1-2A (having a K210E substitution in VP1; at position P2 in cleavage site) have been described previously and acquired a second site substitution (VP1 E83K) during virus rescue. Furthermore, introduction of the VP1 E83K substitution alone generated a second site change at the VP1/2A junction (2A L2P, position P2' in cleavage site). These virus adaptations have now been analysed using next-generation sequencing to determine sub-consensus level changes in the virus; this revealed other variants within the E83K mutant virus population that changed residue VP1 K210. The construction of serotype A viruses with a blocked VP1/2A cleavage site (containing K210E) has now been achieved. A collection of alternative amino acid substitutions was made at this site, and the properties of the mutant viruses were determined. Only the presence of a positively charged residue at position P2 in the cleavage site permitted efficient cleavage of the VP1/2A junction, consistent with analyses of diverse FMDV genome sequences. Interestingly, in contrast to the serotype O virus results, no second site mutations occurred within the VP1 coding region of serotype A viruses with the blocked VP1/2A cleavage site. However, some of these viruses acquired changes in the 2C protein that is involved in enterovirus morphogenesis. These results have implications for the testing of potential antiviral agents targeting the FMDV 3C protease.

Crypteins derived from the mouse neuropeptide FF (NPFF)A precursor display NPFF-like effects in nociceptive tests in mice.

PubMed

Kotlinska, Jolanta H; Gibula-Bruzda, Ewa; Suder, Piotr; Wasielak, Magdalena; Bray, Lauriane; Raoof, Hana; Bodzon-Kulakowska, Anna; Silberring, Jerzy

2012-07-01

NPFF precursor, pro-NPFF(A) contains three known bioactive sequences: NPFF (FLFQPQRF-NH(2)), neuropeptide AF (NPAF; AGEGLSSPFWSLAAPQRF-NH(2)) and neuropeptide SF (NPSF; SLAAPQRF-NH(2)). The key-feature of these fragments is their common PQRF-amidated sequence at their C termini. Here, we evaluated the biological activity of two other sequences derived from the mouse NPFF(A) precursor, that does not have PQRF-amidated C-terminus. One peptide was residing between positions 85 and 99 in the mice pro-NPFF(A). This peptide was referred to as neuropeptide SA (NPSA; SAWGSWSKEQLNPQA), assigned due to its flanking amino acids. Another sequence used in the experiments was N-terminal fragment of NPSA, here referred to as neuropeptide SS (NPSS; SAWGSWS). These two peptides, classified as crypteins, were synthesized and tested in the hot-plate and tail immersion tests in mice for their pharmacological activity in morphine-induced antinociception. The effects of both crypteins were compared to NPFF. Our experiments indicated that both crypteins inhibited morphine antinociception and their effects were reversed by RF9, an antagonist of NPFF receptors. These data show that NPSA and NPSS possess NPFF-like anti-opioid activity in these behavioral tests. Copyright © 2012 Elsevier Inc. All rights reserved.

Transitions in Al Coordination during Gibbsite Crystallization Using High-Field 27 Al and 23 Na MAS NMR Spectroscopy

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

Hu, Jian Zhi; Zhang, Xin; Jaegers, Nicholas R.

Mechanisms of nucleation and growth of Al hydroxides such as gibbsite from aqueous solution, particularly in highly alkaline conditions, remain poorly understood. In this work, quantitative 27Al and 22Na MAS NMR experiments were conducted on solid samples extracted from the crystallization of gibbsite from an amorphous aluminum hydroxide gel precursor. The use of high magnetic field and fast sample spinning allowed transitional tetrahedral (AlT) and pentahedral (AlP) aluminum species to be observed along with the octahedral aluminum (AlO) that dominates the gibbsite product. Low-coordinated Al species could be detected at concentrations as low as 0.1% of the total Al sites.more » It is established that (a) AlT and AlP coexist on the surface of growing gibbsites even with a combined percentage over the total Al sites of less than 1%; (b) Different synthesis methods generate gibbsite with varying amounts of low-coordinated Al; (c) the amorphous gel precursor contains a significant amount of low-coordinated Al sites with AO: AlP: AlT ratios of approximately 4:2:1; (d) upon hydration, the external, low-coordinated Al sites become six-fold coordinated by interacting with the oxygen in H2O and the 27Al MAS NMR peak position shifts to that for the AlO sites; (e) gibbsite with increased long range order is synthesized over longer times by gradually incorporating residual AlP and AlT sites into octahedrally-coordinated AlO sites; (f) trace Na is predominantly a surface species on gibbsite particles. These findings provide a basis for understanding the gibbsite crystallization mechanism, along with a general means of characterizing gibbsite surface properties that are of equal importance for understanding related processes such as dissolution behavior.« less

Enzymatic characteristics of I213T mutant presenilin-1/gamma-secretase in cell models and knock-in mouse brains: familial Alzheimer disease-linked mutation impairs gamma-site cleavage of amyloid precursor protein C-terminal fragment beta.

PubMed

Shimojo, Masafumi; Sahara, Naruhiko; Mizoroki, Tatsuya; Funamoto, Satoru; Morishima-Kawashima, Maho; Kudo, Takashi; Takeda, Masatoshi; Ihara, Yasuo; Ichinose, Hiroshi; Takashima, Akihiko

2008-06-13

Presenilin (PS)/gamma-secretase-mediated intramembranous proteolysis of amyloid precursor protein produces amyloid beta (Abeta) peptides in which Abeta species of different lengths are generated through multiple cleavages at the gamma-, zeta-, and epsilon-sites. An increased Abeta42/Abeta40 ratio is a common characteristic of most cases of familial Alzheimer disease (FAD)-linked PS mutations. However, the molecular mechanisms underlying amyloid precursor protein proteolysis leading to increased Abeta42/Abeta40 ratios still remain unclear. Here, we report our findings on the enzymatic analysis of gamma-secretase derived from I213T mutant PS1-expressing PS1/PS2-deficient (PS(-/-)) cells and from the brains of I213T mutant PS1 knock-in mice. Kinetics analyses revealed that the FAD mutation reduced de novo Abeta generation, suggesting that mutation impairs the total catalytic rate of gamma-secretase. Analysis of each Abeta species revealed that the FAD mutation specifically reduced Abeta40 levels more drastically than Abeta42 levels, leading to an increased Abeta42/Abeta40 ratio. By contrast, the FAD mutation increased the generation of longer Abeta species such as Abeta43, Abeta45, and >Abeta46. These results were confirmed by analyses of gamma-secretase derived from I213T knock-in mouse brains, in which the reduction of de novo Abeta generation was mutant allele dose-dependent. Our findings clearly indicate that the mechanism underlying the increased Abeta42/Abeta40 ratio observed in cases of FAD mutations is related to the differential inhibition of gamma-site cleavage reactions, in which the reaction producing Abeta40 is subject to more inhibition than that producing Abeta42. Our results also provide novel insight into how enhancing the generation of longer Abetas may contribute to Alzheimer disease onset.

The impacts of precursor reduction and meteorology on ground-level ozone in the Greater Toronto Area

NASA Astrophysics Data System (ADS)

Pugliese, S. C.; Murphy, J. G.; Geddes, J. A.; Wang, J. M.

2014-08-01

Tropospheric ozone (O3) is a major component of photochemical smog and is a known human health hazard, as well as a damaging factor for vegetation. Its precursor compounds, nitrogen oxides (NOx) and volatile organic compounds (VOCs), have a variety of anthropogenic and biogenic sources and exhibit non-linear effects on ozone production. As an update to previous studies on ground-level ozone in the Greater Toronto Area (GTA), we present an analysis of NO2, VOC and O3 data from federal and provincial governmental monitoring sites in the GTA from 2000 to 2012. We show that, over the study period, summertime 24 h VOC reactivity and NO2 midday (11:00-15:00) concentrations at all sites decreased significantly; since 2000, all sites experienced a decrease in NO2 of 28-62% and in measured VOC reactivity of at least 53-71%. Comparing 2002-2003 to 2011-2012, the summed reactivity of OH towards NO2 and a suite of measured VOCs decreased from 8.6 to 4.6 s-1. Ratios of reactive VOC pairs indicate that the effective OH concentration experienced by primary pollutants in the GTA has increased significantly over the study period. Despite the continuous decrease in precursor levels, ozone concentrations are not following the same pattern at all stations; it was found that the Canada-wide Standard for ozone continues to be exceeded at all monitoring stations. Additionally, while the years 2008-2011 had consistently lower ozone levels than previous years, 2012 experienced one of the highest recorded summertime ozone concentrations and a large number of smog episodes. We demonstrate that these high ozone observations in 2012 may be a result of the number of days with high solar radiation, the number of stagnant periods and the transport of high ozone levels from upwind regions.

The impacts of precursor reduction and meteorology on ground-level ozone in the Greater Toronto Area

NASA Astrophysics Data System (ADS)

Pugliese, S. C.; Murphy, J. G.; Geddes, J. A.; Wang, J. M.

2014-04-01

Tropospheric ozone (O3) is a major component of photochemical smog and is a known human health hazard as well as a damaging factor for vegetation. Its precursor compounds, nitrogen oxides (NOx) and volatile organic compounds (VOCs), have a variety of anthropogenic and biogenic sources and exhibit non-linear effects on ozone production. As an update to previous studies on ground-level ozone in the GTA, we present an analysis of NO2, VOC and O3 data from federal and provincial governmental monitoring sites in the GTA from 2000-2012. We show that over the study period, summertime 24 h VOC reactivity and NO2 midday (11:00-15:00) concentrations at all sites decreased significantly; since 2000, all sites experienced a decrease in NO2 of 28-62% and in measured VOC reactivity of at least 53-71%. Comparing 2002/2003 to 2011/2012, the summed reactivity of OH towards NO2 and a suite of measured VOCs decreased from 8.6 to 4.6 s-1. Ratios of reactive VOC pairs indicate that the effective OH concentration experienced by primary pollutants in the GTA has increased significantly over the study period. Despite the continuous decrease in precursor levels, ozone concentrations are not following the same pattern at all stations; it was found that the Canada-Wide Standard for ozone continues to be exceeded at all monitoring stations. Additionally, while the years 2008-2011 had consistently lower ozone levels than previous years, 2012 experienced one of the highest recorded summertime ozone concentrations and a large number of smog episodes. We demonstrate that these high ozone observations in 2012 may be a result of the number of days with high solar radiation, the number of stagnant periods and the transport of high ozone levels from upwind regions.

Molecular characterization of an ependymin precursor from goldfish brain.

PubMed

Königstorfer, A; Sterrer, S; Eckerskorn, C; Lottspeich, F; Schmidt, R; Hoffmann, W

1989-01-01

Ependymins are thought to be implicated in fundamental processes involved in plasticity of the goldfish CNS. Gas-phase sequencing of purified ependymins beta and gamma revealed that they share the same N-terminal sequence. Each sequence displays microheterogeneities at several positions. Based on the protein sequences obtained, we constructed synthetic oligonucleotides and used them as hybridization probes for screening cDNA libraries of goldfish brain. In this article we describe the full-length sequence of a mRNA encoding a precursor of ependymins. A cleavable signal sequence characteristic of secretory proteins is located at the N-terminal end, followed directly by the ependymin sequence. Also, two potential N-glycosylation sites were detected. A computer search revealed that ependymins form a novel family of unique proteins.

Synthesis of novel reactive N-halamine precursors and application in antimicrobial cellulose

NASA Astrophysics Data System (ADS)

Jiang, Zhiming; Ma, Kaikai; Du, Jinmei; Li, Rong; Ren, Xuehong; Huang, T. S.

2014-01-01

2,4,6-Trichloro-s-triazine has been used as one of the important linkers of reactive dyes for textiles such as cellulosic fibers. N-Halamine precursors could be bonded to a triazine-based linker by the chloride displacement reaction, and the synthesized compounds could attach to cotton fabrics by covalent bonds through a reactive dyeing process. In this study, two novel antimicrobial N-halamine precursors, 2,2,6,6-tetramethyl-4-piperidinol-s-trizine (TMPT) and 4-(4-(2,2,6,6-tetramethyl-4-piperidinol)-6-chloro-1,3,5-triazinylamino)-benzenesulfonate (BTMPT), were synthesized and used to coat cotton fabrics. The synthesized s-triazine-based N-halamine precursors react with cellulose to produce biocidal cellulosic fibers upon exposure to diluted household bleach. The coated fabrics were characterized by FT-IR and SEM. The chlorinated treated cotton swatches demonstrated excellent antimicrobial properties against S. aureus (Gram-positive) and E. coli O157:H7 (Gram-negative) with short contact times. Washing test and UVA light test showed that chlorinated BTMPT-coated cotton fabrics were more stable than TMPT-coated cotton fabrics. Compared to the traditional pad-dry-cure technique to produce antimicrobial textiles, the novel process in this study has advantages of saving energy and maintaining tensile strength of fabrics.

FABRIC FILTER MODEL SENSITIVITY ANALYSIS

EPA Science Inventory

The report gives results of a series of sensitivity tests of a GCA fabric filter model, as a precursor to further laboratory and/or field tests. Preliminary tests had shown good agreement with field data. However, the apparent agreement between predicted and actual values was bas...

Dissolved Organic Carbon and Disinfection By-Product Precursor Release from Managed Peat Soils

USGS Publications Warehouse

Fleck, J.A.; Bossio, D.A.; Fujii, R.

2004-01-01

A wetland restoration demonstration project examined the effects of a permanently flooded wetland on subsidence of peat soils. The project, started in 1997, was done on Twitchell Island, in the Sacramento-San Joaquin Delta of California. Conversion of agricultural land to a wetland has changed many of the biogeochemical processes controlling dissolved organic carbon (DOC) release from the peat soils, relative to the previous land use. Dissolved organic C in delta waters is a concern because it reacts with chlorine, added as a disinfectant in municipal drinking waters, to form carcinogenic disinfection byproducts (DBPs), including trihalomethanes (THMs) and haloacetic acids (HAAs). This study explores the effects of peat soil biogeochemistry on DOC and DBP release under agricultural and wetland management. Results indicate that organic matter source, extent of soil organic matter decomposition, and decomposition pathways all are factors in THM formation. The results show that historical management practices dominate the release of DOC and THM precursors. However, within-site differences indicate that recent management decisions can contribute to changes in DOC quality and THM precursor formation. Not all aromatic forms of carbon are highly reactive and certain environmental conditions produce the specific carbon structures that form THMs. Both HAA and THM precursors are elevated in the DOC released under wetland conditions. The findings of this study emphasize the need to further investigate the roles of organic matter sources, microbial decomposition pathways, and decomposition status of soil organic matter in the release of DOC and DBP precursors from delta soils under varying land-use practices.

Role of defects in laser-induced modifications of silica coatings and fused silica using picosecond pulses at 1053 nm: II Scaling laws and the density of precursors

DOE PAGES

Laurence, T. A.; Negres, R. A.; Ly, S.; ...

2017-06-22

Here, we investigate the role of defects in laser-induced damage of fused silica and of silica coatings produced by e-beam and PIAD processes which are used in damage resistant, multi-layer dielectric, reflective optics. We perform experiments using 1053 nm, 1–60 ps laser pulses with varying beam size, number of shots, and pulse widths in order to understand the characteristics of defects leading to laser-induced damage. This pulse width range spans a transition in mechanisms from intrinsic material ablation for short pulses to defect-dominated damage for longer pulses. We show that for pulse widths as short as 10 ps, laser-induced damagemore » properties of fused silica and silica films are dominated by isolated absorbers. The density of these precursors and their fluence dependence of damage initiation suggest a single photon process for initial energy absorption in these precursors. Higher density precursors that initiate close to the ablation threshold at shorter pulse widths are also observed in fused silica, whose fluence and pulse width scaling suggest a multiphoton initiation process. We also show that these initiated damage sites grow with subsequent laser pulses. We show that scaling laws obtained in more conventional ways depend on the beam size and on the definition of damage for ps pulses. For this reason, coupling scaling laws with the density of precursors are critical to understanding the damage limitations of optics in the ps regime.« less

Role of defects in laser-induced modifications of silica coatings and fused silica using picosecond pulses at 1053 nm: II Scaling laws and the density of precursors

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

Laurence, T. A.; Negres, R. A.; Ly, S.

Here, we investigate the role of defects in laser-induced damage of fused silica and of silica coatings produced by e-beam and PIAD processes which are used in damage resistant, multi-layer dielectric, reflective optics. We perform experiments using 1053 nm, 1–60 ps laser pulses with varying beam size, number of shots, and pulse widths in order to understand the characteristics of defects leading to laser-induced damage. This pulse width range spans a transition in mechanisms from intrinsic material ablation for short pulses to defect-dominated damage for longer pulses. We show that for pulse widths as short as 10 ps, laser-induced damagemore » properties of fused silica and silica films are dominated by isolated absorbers. The density of these precursors and their fluence dependence of damage initiation suggest a single photon process for initial energy absorption in these precursors. Higher density precursors that initiate close to the ablation threshold at shorter pulse widths are also observed in fused silica, whose fluence and pulse width scaling suggest a multiphoton initiation process. We also show that these initiated damage sites grow with subsequent laser pulses. We show that scaling laws obtained in more conventional ways depend on the beam size and on the definition of damage for ps pulses. For this reason, coupling scaling laws with the density of precursors are critical to understanding the damage limitations of optics in the ps regime.« less

A critical tryptophan and Ca2+ in activation and catalysis of TPPI, the enzyme deficient in classic late-infantile neuronal ceroid lipofuscinosis.

PubMed

Kuizon, Salomon; DiMaiuta, Kathleen; Walus, Marius; Jenkins, Edmund C; Kuizon, Marisol; Kida, Elizabeth; Golabek, Adam A; Espinoza, Daniel O; Pullarkat, Raju K; Junaid, Mohammed A

2010-08-03

Tripeptidyl aminopeptidase I (TPPI) is a crucial lysosomal enzyme that is deficient in the fatal neurodegenerative disorder called classic late-infantile neuronal ceroid lipofuscinosis (LINCL). It is involved in the catabolism of proteins in the lysosomes. Recent X-ray crystallographic studies have provided insights into the structural/functional aspects of TPPI catalysis, and indicated presence of an octahedrally coordinated Ca(2+). Purified precursor and mature TPPI were used to study inhibition by NBS and EDTA using biochemical and immunological approaches. Site-directed mutagenesis with confocal imaging technique identified a critical W residue in TPPI activity, and the processing of precursor into mature enzyme. NBS is a potent inhibitor of the purified TPPI. In mammalian TPPI, W542 is critical for tripeptidyl peptidase activity as well as autocatalysis. Transfection studies have indicated that mutants of the TPPI that harbor residues other than W at position 542 have delayed processing, and are retained in the ER rather than transported to lysosomes. EDTA inhibits the autocatalytic processing of the precursor TPPI. We propose that W542 and Ca(2+) are critical for maintaining the proper tertiary structure of the precursor proprotein as well as the mature TPPI. Additionally, Ca(2+) is necessary for the autocatalytic processing of the precursor protein into the mature TPPI. We have identified NBS as a potent TPPI inhibitor, which led in delineating a critical role for W542 residue. Studies with such compounds will prove valuable in identifying the critical residues in the TPPI catalysis and its structure-function analysis.

Qualification of a sublimation tool applied to the case of metalorganic chemical vapor deposition of In{sub 2}O{sub 3} from In(tmhd){sub 3} as a solid precursor

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

Szkutnik, P. D., E-mail: pierre.szkutnik@cea.fr; Jiménez, C.; Angélidès, L.

2016-02-15

A solid delivery system consisting of a source canister, a gas management, and temperature controlled enclosure designed and manufactured by Air Liquide Electronics Systems was tested in the context of gas-phase delivery of the In(tmhd){sub 3} solid precursor. The precursor stream was delivered to a thermal metalorganic chemical vapor deposition reactor to quantify deposition yield under various conditions of carrier gas flow and sublimation temperature. The data collected allowed the determination of characteristic parameters such as the maximum precursor flow rate (18.2 mg min{sup −1} in specified conditions) and the critical mass (defined as the minimum amount of precursor ablemore » to attain the maximum flow rate) found to be about 2.4 g, as well as an understanding of the influence of powder distribution inside the canister. Furthermore, this qualification enabled the determination of optimal delivery conditions which allowed for stable and reproducible precursor flow rates over long deposition times (equivalent to more than 47 h of experiment). The resulting In{sub 2}O{sub 3} layers was compared with those elaborated via pulsed liquid injection obtained in the same chemical vapor deposition chamber and under the same deposition conditions.« less

Nondestructive Examination (NDE) Detection and Characterization of Degradation Precursors, Technical Progress Report for FY 2012

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

Ramuhalli, P.; Meyer, R.M.; Fricke, J.M.

2012-09-01

The overall objective of this project was to investigate the effectiveness of nondestructive examination (NDE) technology in detecting material degradation precursors by initiating and growing cracks in selected materials and using NDE methods to measure crack precursors prior to the onset of cracking. Nuclear reactor components are subject to stresses over time that are not precisely known and that make the life expectancy of components difficult to determine. To prevent future issues with the operation of these plants because of unforeseen failure of components, NDE technology is needed that can be used to identify and quantify precursors to macroscopic degradationmore » of materials. Some of the NDE methods being researched as possible solutions to the precursor detection problem are magnetic Barkhausen noise, nonlinear ultrasonics, acoustic emission, eddy current measurements, and guided wave technology. In FY12, the objective was to complete preliminary assessment of advanced NDE techniques for sensitivity to degradation precursors, using prototypical degradation mechanisms in laboratory-scale measurements. This present document reports on the deliverable that meets the following milestone: M3LW-12OR0402143 – Report detailing an initial demonstration on samples from the crack-initiation tests will be provided (demonstrating acceleration of the work).« less

Cryopreservation of GABAergic Neuronal Precursors for Cell-Based Therapy

PubMed Central

2017-01-01

Cryopreservation protocols are essential for stem cells storage in order to apply them in the clinic. Here we describe a new standardized cryopreservation protocol for GABAergic neural precursors derived from the medial glanglionic eminence (MGE), a promising source of GABAergic neuronal progenitors for cell therapy against interneuron-related pathologies. We used 10% Me2SO as cryoprotectant and assessed the effects of cell culture amplification and cellular organization, as in toto explants, neurospheres, or individualized cells, on post-thaw cell viability and retrieval. We confirmed that in toto cryopreservation of MGE explants is an optimal preservation system to keep intact the interneuron precursor properties for cell transplantation, together with a high cell viability (>80%) and yield (>70%). Post-thaw proliferation and self-renewal of the cryopreserved precursors were tested in vitro. In addition, their migration capacity, acquisition of mature neuronal morphology, and potency to differentiate into multiple interneuron subtypes were also confirmed in vivo after transplantation. The results show that the cryopreserved precursor features remained intact and were similar to those immediately transplanted after their dissection from the MGE. We hope this protocol will facilitate the generation of biobanks to obtain a permanent and reliable source of GABAergic precursors for clinical application in cell-based therapies against interneuronopathies. PMID:28122047

On-fiber furan formation from volatile precursors: a critical example of artefact formation during Solid-Phase Microextraction.

PubMed

Adams, An; Van Lancker, Fien; De Meulenaer, Bruno; Owczarek-Fendor, Agnieszka; De Kimpe, Norbert

2012-05-15

For the analysis of furan, a possible carcinogen formed during thermal treatment of food, Solid-Phase Microextraction (SPME) is a preferred and validated sampling method. However, when volatile furan precursors are adsorbed on the carboxen/PDMS fiber, additional amounts of furan can be formed on the fiber during thermal desorption, as shown here for 2-butenal and furfural. No significant increase in furan amounts was found upon heating the furan precursor 2-butenal, indicating that the furan amounts formed during precursor heating experiments are negligible as compared to the additional amounts of furan formed during fiber desorption. This artefactual furan formation increased with increasing desorption time, but especially with increasing desorption temperature. Although this effect was most pronounced on the Carboxen/PDMS SPME-fiber, it was also noted on two other SPME-fibers tested (PDMS and DVB/Carboxen/PDMS). The general impact on furan data from food and model systems in literature will depend on the amounts of volatile precursors present, but will probably remain limited. However, considering the importance of this worldwide food contaminant, special care has to be taken during SPME-analysis of furan. Especially when performing precursor studies, static headspace sampling should preferably be applied for furan analysis. Copyright © 2012 Elsevier B.V. All rights reserved.

Probing platinum degradation in polymer electrolyte membrane fuel cells by synchrotron X-ray microscopy.

PubMed

Berejnov, Viatcheslav; Martin, Zulima; West, Marcia; Kundu, Sumit; Bessarabov, Dmitri; Stumper, Jürgen; Susac, Darija; Hitchcock, Adam P

2012-04-14

Synchrotron-based scanning transmission X-ray spectromicroscopy (STXM) was used to characterize the local chemical environment at and around the platinum particles in the membrane (PTIM) which form in operationally tested (end-of-life, EOL) catalyst coated membranes (CCMs) of polymer electrolyte membrane fuel cells (PEM-FC). The band of metallic Pt particles in operationally tested CCM membranes was imaged using transmission electron microscopy (TEM). The cathode catalyst layer in the beginning-of-life (BOL) CCMs was fabricated using commercially available catalysts created from Pt precursors with and without nitrogen containing ligands. The surface composition of these catalyst powders was measured by X-ray Photoelectron Spectroscopy (XPS). The local chemical environment of the PTIM in EOL CCMs was found to be directly related to the Pt precursor used in CCM fabrication. STXM chemical mapping at the N 1s edge revealed a characteristic spectrum at and around the dendritic Pt particles in CCMs fabricated with nitrogen containing Pt-precursors. This N 1s spectrum was identical to that of the cathode and different from the membrane. For CCM samples fabricated without nitrogen containing Pt-precursors the N 1s spectrum at the Pt particles was indistinguishable from that of the adjacent membrane. We interpret these observations to indicate that nitrogenous ligands in the nitrogen containing precursors, or decomposition product(s) from that source, are transported together with the dissolved Pt from the cathode into the membrane as a result of the catalyst degradation process. This places constraints on possible mechanisms for the PTIM band formation process.

CLONING AND CHARACTERIZATION OF OSTEOCLAST PRECURSORS FROM THE RAW264.7 CELL LINE

PubMed Central

Cuetara, Bethany L. V.; Crotti, Tania N.; O'Donoghue, Anthony J.

2006-01-01

SUMMARY Osteoclasts are bone-resorbing cells that differentiate from macrophage precursors in response to receptor activator of NF-κB (RANKL). In vitro models of osteoclast differentiation are principally based on primary cell culture, which are poorly suited to molecular and transgene studies due to the limitations associated with the use of primary macrophage. RAW264.7 is a transfectable macrophage cell line with the capacity to form osteoclast-like cells. In the present study we have identified osteoclast precursors among clones of RAW264.7 cells. RAW264.7 cell were cloned by limiting dilution and induced to osteoclast differentiation by treatment with recombinant RANKL. Individual RAW264.7 cell clones formed tartrate resistant acid phosphatase (TRAP) positive multinuclear cells to various degrees with RANKL treatment. All clones tested expressed the RANKL receptor RANK. Each of the clones expressed the osteoclast marker genes TRAP and cathepsin-K mRNA with RANKL treatment. However, we noted that only select clones were able to form large, well-spread, TRAP positive multinuclear cells. Clones capable of forming large TRAP positive multinuclear cells also expressed β3 integrin and calcitonin receptor mRNAs and were capable of resorbing a mineralized matrix. All clones tested activated NF-κB with RANKL treatment. cDNA expression profiling of osteoclast precursor RAW264.7 cell clones demonstrates appropriate expression of a large number of genes before and after osteoclastic differentiation. These osteoclast precursor RAW264.7 cell clones provide a valuable model for dissecting the cellular and molecular regulation of osteoclast differentiation and activation. PMID:16948499

Regulation of Pyrimidine Biosynthesis in Intact Cells of Cucurbita pepo.

PubMed

Lovatt, C J; Albert, L S

1979-10-01

The occurrence of the complete orotic acid pathway for the biosynthesis de novo of pyrimidine nucleotides was demonstrated in the intact cells of roots excised from summer squash (Cucurbita pepo L. cv. Early Prolific Straightneck). Evidence that the biosynthesis of pyrimidine nucleotides proceeds via the orotate pathway in C. pepo included: (a) demonstration of the incorporation of [(14)C]NaHCO(3), [(14)C]carbamylaspartate, and [(14)C]orotic acid into uridine nucleotides; (b) the isolation of [(14)C]orotic acid when [(14)C]NaHCO(3) and [(14)C]carbamylaspartate were used as precursors; (c) the observation that 6-azauridine, a known inhibitor of the pathway, blocked the incorporation of early precursors into uridine nucleotides while causing a concomitant accumulation of orotic acid; and (d) demonstration of the activities of the component enzymes of the orotate pathway in assays employing cell-free extracts.Regulation of the activity of the orotate pathway by end product inhibition was demonstrated in the intact cells of excised roots by measuring the influence of added pyrimidine nucleosides on the incorporation of [(14)C]NaHCO(3) into uridine nucleotides. The addition of either uridine or cytidine inhibited the incorporation of [(14)C]NaHCO(3) into uridine nucleotides by about 80%. The observed inhibition was demonstrated to be readily reversible upon transfer of the roots to a nucleoside-free medium. Experiments employing various radiolabeled precursors indicated that one or both of the first two enzymes in the orotate pathway are the only site(s) of regulation of physiological importance.

Synthesis of Supported Pd 0 Nanoparticles from a Single-Site Pd 2+ Surface Complex by Alkene Reduction

DOE PAGES

Mouat, Aidan R.; Whitford, Cassandra L.; Chen, Bor-Rong; ...

2018-02-02

Here, a surface metal–organic complex, (-AlO x)Pd(acac) (acac = acetylacetonate), is prepared by chemically grafting the precursor Pd(acac) 2 onto γ-Al 2O 3 in toluene at 25 °C. The resulting surface complex is characterized by inductively coupled plasma atomic emission spectroscopy (ICP-AES), X-ray photoelectron spectroscopy (XPS), X-ray absorption spectroscopy (XAS), and dynamic nuclear polarization surface-enhanced solid-state nuclear magnetic resonance spectroscopy (DNP SENS). This surface complex is a precursor in the direct synthesis of size-controlled Pd nanoparticles under mild reductive conditions and in the absence of additional stabilizers or pretreatments. Indeed, upon exposure to gaseous ethylene or liquid 1-octene at 25more » °C, the Pd 2+ species is reduced to form Pd 0 nanoparticles with a mean diameter of 4.3 ± 0.6 nm, as determined by scanning transmission electron microscopy (STEM). These nanoparticles are catalytically relevant using the aerobic 1-phenylethanol oxidation as a probe reaction, with rates comparable to a conventional Pd/Al 2O 3 catalyst but without an induction period. Diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and temperature-programmed reaction mass spectrometry (TPR-MS) reveal that the surface complex reduction with ethylene coproduces H 2, acetylene, and 1,3-butadiene. This process reasonably proceeds via an olefin activation/coordination/insertion pathway, followed by β-hydride elimination to generate free Pd 0. Lastly, the well-defined nature of the single-site supported Pd 2+ precursor provides direct mechanistic insights into this unusual and likely general reductive process.« less

SOT1, a pentatricopeptide repeat protein with a small MutS-related domain, is required for correct processing of plastid 23S-4.5S rRNA precursors in Arabidopsis thaliana.

PubMed

Wu, Wenjuan; Liu, Sheng; Ruwe, Hannes; Zhang, Delin; Melonek, Joanna; Zhu, Yajuan; Hu, Xupeng; Gusewski, Sandra; Yin, Ping; Small, Ian D; Howell, Katharine A; Huang, Jirong

2016-03-01

Ribosomal RNA processing is essential for plastid ribosome biogenesis, but is still poorly understood in higher plants. Here, we show that SUPPRESSOR OF THYLAKOID FORMATION1 (SOT1), a plastid-localized pentatricopeptide repeat (PPR) protein with a small MutS-related domain, is required for maturation of the 23S-4.5S rRNA dicistron. Loss of SOT1 function leads to slower chloroplast development, suppression of leaf variegation, and abnormal 23S and 4.5S processing. Predictions based on the PPR motif sequences identified the 5' end of the 23S-4.5S rRNA dicistronic precursor as a putative SOT1 binding site. This was confirmed by electrophoretic mobility shift assay, and by loss of the abundant small RNA 'footprint' associated with this site in sot1 mutants. We found that more than half of the 23S-4.5S rRNA dicistrons in sot1 mutants contain eroded and/or unprocessed 5' and 3' ends, and that the endonucleolytic cleavage product normally released from the 5' end of the precursor is absent in a sot1 null mutant. We postulate that SOT1 binding protects the 5' extremity of the 23S-4.5S rRNA dicistron from exonucleolytic attack, and favours formation of the RNA structure that allows endonucleolytic processing of its 5' and 3' ends. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

Synthesis of Supported Pd 0 Nanoparticles from a Single-Site Pd 2+ Surface Complex by Alkene Reduction

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

Mouat, Aidan R.; Whitford, Cassandra L.; Chen, Bor-Rong

Here, a surface metal–organic complex, (-AlO x)Pd(acac) (acac = acetylacetonate), is prepared by chemically grafting the precursor Pd(acac) 2 onto γ-Al 2O 3 in toluene at 25 °C. The resulting surface complex is characterized by inductively coupled plasma atomic emission spectroscopy (ICP-AES), X-ray photoelectron spectroscopy (XPS), X-ray absorption spectroscopy (XAS), and dynamic nuclear polarization surface-enhanced solid-state nuclear magnetic resonance spectroscopy (DNP SENS). This surface complex is a precursor in the direct synthesis of size-controlled Pd nanoparticles under mild reductive conditions and in the absence of additional stabilizers or pretreatments. Indeed, upon exposure to gaseous ethylene or liquid 1-octene at 25more » °C, the Pd 2+ species is reduced to form Pd 0 nanoparticles with a mean diameter of 4.3 ± 0.6 nm, as determined by scanning transmission electron microscopy (STEM). These nanoparticles are catalytically relevant using the aerobic 1-phenylethanol oxidation as a probe reaction, with rates comparable to a conventional Pd/Al 2O 3 catalyst but without an induction period. Diffuse reflectance infrared Fourier transform spectroscopy (DRIFTS) and temperature-programmed reaction mass spectrometry (TPR-MS) reveal that the surface complex reduction with ethylene coproduces H 2, acetylene, and 1,3-butadiene. This process reasonably proceeds via an olefin activation/coordination/insertion pathway, followed by β-hydride elimination to generate free Pd 0. Lastly, the well-defined nature of the single-site supported Pd 2+ precursor provides direct mechanistic insights into this unusual and likely general reductive process.« less

Distinct regulators of Shh transcription in the floor plate and notochord indicate separate origins for these tissues in the mouse node.

PubMed

Jeong, Yongsu; Epstein, Douglas J

2003-08-01

The establishment of the floor plate at the ventral midline of the CNS is dependent on an inductive signaling process mediated by the secreted protein Sonic hedgehog (Shh). To understand molecularly how floor plate induction proceeds we identified a Shh-responsive regulatory element that directs transgene reporter expression to the ventral midline of the CNS and notochord in a Shh-like manner and characterized critical cis-acting sequences regulating this element. Cross-species comparisons narrowed the activity of the Shh floor plate enhancer to an 88-bp sequence within intron 2 of Shh that included highly conserved binding sites matching the consensus for homeodomain, Tbx and Foxa transcription factors. Mutational analysis revealed that the homeodomain and Foxa binding sites are each required for activation of the Shh floor plate enhancer, whereas the Tbx site was required for repression in regions of the CNS where Shh is not normally expressed. We further show that Shh enhancer activity was detected in the mouse node from where the floor plate and notochord precursors derive. Shh reporter expression was restricted to the ventral (mesodermal) layer of the node in a pattern similar to endogenous Shh. X-gal-positive cells emerging from the node were only detected in the notochord lineage, suggesting that the floor plate and notochord arise from distinct precursors in the mouse node.

Role of Exposed Surfaces on Zinc Oxide Nanostructures in the Catalytic Ethanol Transformation.

PubMed

Morales, María V; Asedegbega-Nieto, Esther; Iglesias-Juez, Ana; Rodríguez-Ramos, Inmaculada; Guerrero-Ruiz, Antonio

2015-07-08

For a series of nanometric ZnO materials, the relationship between their morphological and surface functionalities and their catalytic properties in the selective decomposition of ethanol to yield acetaldehyde was explored. Six ZnO solids were prepared by a microemulsion-precipitation method and the thermal decomposition of different precursors and compared with a commercial sample. All these materials were characterized intensively by XRD and SEM to obtain their morphological specificities. Additionally, surface area determinations and IR spectroscopy were used to detect differences in the surface properties. The density of acid surface sites was determined quantitatively using an isopropanol dehydration test. Based on these characterization studies and on the results of the catalytic tests, it has been established that ZnO basal surfaces seem to be responsible for the production of ethylene as a minor product as well as for secondary reactions that yield acetyl acetate. Furthermore, one specific type of exposed hydroxyl groups appears to govern the surface catalytic properties. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Discovery of a Prefusion Respiratory Syncytial Virus F-Specific Monoclonal Antibody That Provides Greater In Vivo Protection than the Murine Precursor of Palivizumab.

PubMed

Zhao, Min; Zheng, Zi-Zheng; Chen, Man; Modjarrad, Kayvon; Zhang, Wei; Zhan, Lu-Ting; Cao, Jian-Li; Sun, Yong-Peng; McLellan, Jason S; Graham, Barney S; Xia, Ning-Shao

2017-08-01

Palivizumab, a humanized murine monoclonal antibody that recognizes antigenic site II on both the prefusion (pre-F) and postfusion (post-F) conformations of the respiratory syncytial virus (RSV) F glycoprotein, is the only prophylactic agent approved for use for the treatment of RSV infection. However, its relatively low neutralizing potency and high cost have limited its use to a restricted population of infants at high risk of severe disease. Previously, we isolated a high-potency neutralizing antibody, 5C4, that specifically recognizes antigenic site Ø at the apex of the pre-F protein trimer. We compared in vitro and in vivo the potency and protective efficacy of 5C4 and the murine precursor of palivizumab, antibody 1129. Both antibodies were synthesized on identical murine backbones as either an IgG1 or IgG2a subclass and evaluated for binding to multiple F protein conformations, in vitro inhibition of RSV infection and propagation, and protective efficacy in mice. Although 1129 and 5C4 had similar pre-F protein binding affinities, the 5C4 neutralizing activity was nearly 50-fold greater than that of 1129 in vitro In BALB/c mice, 5C4 reduced the peak titers of RSV 1,000-fold more than 1129 did in both the upper and lower respiratory tracts. These data indicate that antibodies specific for antigenic site Ø are more efficacious at preventing RSV infection than antibodies specific for antigenic site II. Our data also suggest that site Ø-specific antibodies may be useful for the prevention or treatment of RSV infection and support the use of the pre-F protein as a vaccine antigen. IMPORTANCE There is no vaccine yet available to prevent RSV infection. The use of the licensed antibody palivizumab, which recognizes site II on both the pre-F and post-F proteins, is restricted to prophylaxis in neonates at high risk of severe RSV disease. Recommendations for using passive immunization in the general population or for therapy in immunocompromised persons with persistent infection is limited because of cost, determined from the high doses needed to compensate for its relatively low neutralizing potency. Prior efforts to improve the in vitro potency of site II-specific antibodies did not translate to significant in vivo dose sparing. We isolated a pre-F protein-specific, high-potency neutralizing antibody (5C4) that recognizes antigenic site Ø and compared its efficacy to that of the murine precursor of palivizumab (antibody 1129) matched for isotype and pre-F protein binding affinities. Our findings demonstrate that epitope specificity is an important determinant of antibody neutralizing potency, and defining the mechanisms of neutralization has the potential to identify improved products for the prevention and treatment of RSV infection. Copyright © 2017 American Society for Microbiology.

Intercalation of paracetamol into the hydrotalcite-like host

NASA Astrophysics Data System (ADS)

Kovanda, František; Maryšková, Zuzana; Kovář, Petr

2011-12-01

Hydrotalcite-like compounds are often used as host structures for intercalation of various anionic species. The product intercalated with the nonionic, water-soluble pharmaceuticals paracetamol, N-(4-hydroxyphenyl)acetamide, was prepared by rehydration of the Mg-Al mixed oxide obtained by calcination of hydrotalcite-like precursor at 500 °C. The successful intercalation of paracetamol molecules into the interlayer space was confirmed by powder X-ray diffraction and infrared spectroscopy measurements. Molecular simulations showed that the phenolic hydroxyl groups of paracetamol interact with hydroxide sheets of the host via the hydroxyl groups of the positively charged sites of Al-containing octahedra; the interlayer water molecules are located mostly near the hydroxide sheets. The arrangement of paracetamol molecules in the interlayer is rather disordered and interactions between neighboring molecules cause their tilting towards the hydroxide sheets. Dissolution tests in various media showed slower release of paracetamol intercalated in the hydrotalcite-like host in comparison with tablets containing the powdered pharmaceuticals.

Effect of TiO2 calcination temperature on the photocatalytic oxidation of gaseous NH3.

PubMed

Wu, Hongmin; Ma, Jinzhu; Zhang, Changbin; He, Hong

2014-03-01

Carbon-modified titanium dioxide (TiO2) was prepared by a sol-gel method using tetrabutyl titanate as precursor, with calcination at various temperatures, and tested for the photocatalytic oxidation (PCO) of gaseous NH3 under visible and UV light. The test results showed that no samples had visible light activity, while the TiO2 calcined at 400°C had the best UV light activity among the series of catalysts, and was even much better than the commercial catalyst P25. The catalysts were then characterized by X-ray diffractometry, Brunauer-Emmett-Teller adsorption analysis, Raman spectroscopy, thermogravimetry/differential scanning calorimetry coupled with mass spectrometry, ultraviolet-visible diffuse reflectance spectra, photoluminescence spectroscopy and in situ diffuse reflectance infrared Fourier transform spectroscopy. It was shown that the carbon species residuals on the catalyst surfaces induced the visible light adsorption of the samples calcined in the low temperature range (< 300°C). However, the surface acid sites played a determining role in the PCO of NH3 under visible and UV light over the series of catalysts. Although the samples calcined at low temperatures had very high SSA, good crystallinity, strong visible light absorption and also low PL emission intensity, they showed very low PCO activity due to their very low number of acid sites for NH3 adsorption and activation. The TiO2 sample calcined at 400°C contained the highest number of acid sites among the series of catalysts, therefore showing the highest performance for the PCO of NH3 under UV light. Copyright © 2014 The Research Centre for Eco-Environmental Sciences, Chinese Academy of Sciences. Published by Elsevier B.V. All rights reserved.

Autocatalytic maturation, physical/chemical properties, and crystal structure of group N HIV-1 protease: relevance to drug resistance.

PubMed

Sayer, Jane M; Agniswamy, Johnson; Weber, Irene T; Louis, John M

2010-11-01

The mature protease from Group N human immunodeficiency virus Type 1 (HIV-1) (PR1(N)) differs in 20 amino acids from the extensively studied Group M protease (PR1(M)) at positions corresponding to minor drug-resistance mutations (DRMs). The first crystal structure (1.09 Å resolution) of PR1(N) with the clinical inhibitor darunavir (DRV) reveals the same overall structure as PR1(M), but with a slightly larger inhibitor-binding cavity. Changes in the 10s loop and the flap hinge propagate to shift one flap away from the inhibitor, whereas L89F and substitutions in the 60s loop perturb inhibitor-binding residues 29-32. However, kinetic parameters of PR1(N) closely resemble those of PR1(M), and calorimetric results are consistent with similar binding affinities for DRV and two other clinical PIs, suggesting that minor DRMs coevolve to compensate for the detrimental effects of drug-specific major DRMs. A miniprecursor (TFR 1-61-PR1(N)) comprising the transframe region (TFR) fused to the N-terminus of PR1(N) undergoes autocatalytic cleavage at the TFR/PR1(N) site concomitant with the appearance of catalytic activity characteristic of the dimeric, mature enzyme. This cleavage is inhibited at an equimolar ratio of precursor to DRV (∼6 μM), which partially stabilizes the precursor dimer from a monomer. However, cleavage at L34/W35 within the TFR, which precedes the TFR 1-61/PR1(N) cleavage at pH ≤ 5, is only partially inhibited. Favorable properties of PR1(N) relative to PR1(M) include its suitability for column fractionation by size under native conditions and >10-fold higher dimer dissociation constant (150 nM). Exploiting these properties may facilitate testing of potential dimerization inhibitors that perturb early precursor processing steps.

Recovery of Recombinant Crimean Congo Hemorrhagic Fever Virus Reveals a Function for Non-structural Glycoproteins Cleavage by Furin.

PubMed

Bergeron, Éric; Zivcec, Marko; Chakrabarti, Ayan K; Nichol, Stuart T; Albariño, César G; Spiropoulou, Christina F

2015-05-01

Crimean Congo hemorrhagic fever virus (CCHFV) is a negative-strand RNA virus of the family Bunyaviridae (genus: Nairovirus). In humans, CCHFV causes fever, hemorrhage, severe thrombocytopenia, and high fatality. A major impediment in precisely determining the basis of CCHFV's high pathogenicity has been the lack of methodology to produce recombinant CCHFV. We developed a reverse genetics system based on transfecting plasmids into BSR-T7/5 and Huh7 cells. In our system, bacteriophage T7 RNA polymerase produced complementary RNA copies of the viral S, M, and L segments that were encapsidated with the support, in trans, of CCHFV nucleoprotein and L polymerase. The system was optimized to systematically recover high yields of infectious CCHFV. Additionally, we tested the ability of the system to produce specifically designed CCHFV mutants. The M segment encodes a polyprotein that is processed by host proprotein convertases (PCs), including the site-1 protease (S1P) and furin-like PCs. S1P and furin cleavages are necessary for producing the non-structural glycoprotein GP38, while S1P cleavage yields structural Gn. We studied the role of furin cleavage by rescuing a recombinant CCHFV encoding a virus glycoprotein precursor lacking a functional furin cleavage motif (RSKR mutated to ASKA). The ASKA mutation blocked glycoprotein precursor's maturation to GP38, and Gn precursor's maturation to Gn was slightly diminished. Furin cleavage was not essential for replication, as blocking furin cleavage resulted only in transient reduction of CCHFV titers, suggesting that either GP38 and/or decreased Gn maturation accounted for the reduced virion production. Our data demonstrate that nairoviruses can be produced by reverse genetics, and the utility of our system uncovered a function for furin cleavage. This viral rescue system could be further used to study the CCHFV replication cycle and facilitate the development of efficacious vaccines to counter this biological and public health threat.

Chemical State of Surface Oxygen on Carbon and Its Effects on the Capacity of the Carbon Anode in a Lithium-Ion Battery Investigated

NASA Technical Reports Server (NTRS)

Hung, Ching-Cheh

2001-01-01

In a lithium-ion battery, the lithium-storage capacity of the carbon anode is greatly affected by a surface layer formed during the first half cycle of lithium insertion and release into and out of the carbon anode. The formation of this solid-electrolyte interface, in turn, is affected by the chemistry of the carbon surface. A study at the NASA Glenn Research Center examined the cause-and-effect relations. Information obtained from this research could contribute in designing a high-capacity lithium-ion battery and, therefore, small, powerful spacecraft. In one test, three types of surfaces were examined: (1) a surface with low oxygen content (1.5 at.%) and a high concentration of active sites, (2) a surface with 4.5 at.% -OH or -OC type oxygen, and (3) a surface with 6.5 at.% O=C type oxygen. The samples were made from the same precursor and had similar bulk properties. They were tested under a constant current of 10 mA/g in half cells that used lithium metal as the counter electrode and 0.5 M lithium iodide in 50/50 (vol%) ethylene carbonate and dimethyl carbonate as the electrolyte. For the first cycle of the electrochemical test, the graph describes the voltage of the carbon anode versus the lithium metal as a function of the capacity (amount of lithium insertion or release). From these data, it can be observed that the surface with low oxygen and a high concentration of active sites could result in a high irreversible capacity. Such a high irreversible capacity could be prevented if the active sites were allowed to react with oxygen in air, producing -OH or -OC type oxygen. The O=C type oxygen, on the other hand, could greatly reduce the capacity of lithium intercalation and, therefore, needs to be avoided during battery fabrication.

Probing the Active Surface Sites for CO Reduction on Oxide-Derived Copper Electrocatalysts

DOE PAGES

Verdaguer-Casadevall, Arnau; Li, Christina W.; Johansson, Tobias P.; ...

2015-07-30

CO electroreduction activity on oxide-derived Cu (OD-Cu) was found to correlate with metastable surface features that bind CO strongly. OD-Cu electrodes prepared by H 2 reduction of Cu 2O precursors reduce CO to acetate and ethanol with nearly 50% Faradaic efficiency at moderate overpotential. Temperature-programmed desorption of CO on OD-Cu revealed the presence of surface sites with strong CO binding that are distinct from the terraces and stepped sites found on polycrystalline Cu foil. After annealing at 350 °C, the surface-area corrected current density for CO reduction is 44-fold lower and the Faradaic efficiency is less than 5%. These changesmore » are accompanied by a reduction in the proportion of strong CO binding sites. Here, we propose that the active sites for CO reduction on OD-Cu surfaces are strong CO binding sites that are supported by grain boundaries. Uncovering these sites is a first step toward understanding the surface chemistry necessary for efficient CO electroreduction.« less

Numerical simulation of Composition B high explosive charge desensitization in gap test assembly after loading by precursor wave

NASA Astrophysics Data System (ADS)

Balagansky, I. A.; Stepanov, A. A.

2016-03-01

Results of numerical research into the desensitization of high explosive charges in water gap test-based experimental assemblies are presented. The experimental data are discussed, and the analysis using ANSYS AUTODYN 14.5 is provided. The desensitization phenomenon is well reproduced in numerical simulation using the JWL EOS and the Lee-Tarver kinetic equation for modeling of the initiation of heterogeneous high explosives with as well as without shock front waves. The analysis of the wave processes occurring during the initiation of the acceptor HE charge has been carried out. Peculiarities of the wave processes in the water gap test assemblies, which can influence the results of sensitivity measurement, have been studied. In particular, it has been established that precursor waves in the walls of the gap test assemblies can influence the detonation transmission distance.

Surface chemistry of copper metal and copper oxide atomic layer deposition from copper(ii) acetylacetonate: a combined first-principles and reactive molecular dynamics study.

PubMed

Hu, Xiao; Schuster, Jörg; Schulz, Stefan E; Gessner, Thomas

2015-10-28

Atomistic mechanisms for the atomic layer deposition using the Cu(acac)2 (acac = acetylacetonate) precursor are studied using first-principles calculations and reactive molecular dynamics simulations. The results show that Cu(acac)2 chemisorbs on the hollow site of the Cu(110) surface and decomposes easily into a Cu atom and the acac-ligands. A sequential dissociation and reduction of the Cu precursor [Cu(acac)2 → Cu(acac) → Cu] are observed. Further decomposition of the acac-ligand is unfavorable on the Cu surface. Thus additional adsorption of the precursors may be blocked by adsorbed ligands. Molecular hydrogen is found to be nonreactive towards Cu(acac)2 on Cu(110), whereas individual H atoms easily lead to bond breaking in the Cu precursor upon impact, and thus release the surface ligands into the gas-phase. On the other hand, water reacts with Cu(acac)2 on a Cu2O substrate through a ligand-exchange reaction, which produces gaseous H(acac) and surface OH species. Combustion reactions with the main by-products CO2 and H2O are observed during the reaction between Cu(acac)2 and ozone on the CuO surface. The reactivity of different co-reactants toward Cu(acac)2 follows the order H > O3 > H2O.

Anatomical Location of LPA1 Activation and LPA Phospholipid Precursors in Rodent and Human Brain

PubMed Central

González de San Román, E; Manuel, I; Giralt, MT; Chun, J; Estivill-Torrús, G; Rodriguez de Fonseca, F; Santín, LJ; Ferrer, I; Rodriguez-Puertas, R

2016-01-01

Lysophosphatidic acid (LPA) is a signaling molecule that binds to six known G protein-coupled receptors (GPCRs): LPA1–LPA6. LPA evokes several responses in the CNS including cortical development and folding, growth of the axonal cone and its retraction process. Those cell processes involve survival, migration, adhesion proliferation, differentiation and myelination. The anatomical localization of LPA1 is incompletely understood, particularly with regard to LPA binding. Therefore, we have used functional [35S]GTPγS autoradiography to verify the anatomical distribution of LPA1 binding sites in adult rodent and human brain. The greatest activity was observed in myelinated areas of the white matter such as corpus callosum, internal capsule and cerebellum. MaLPA1-null mice (a variant of LPA1-null) lack [35S]GTPγS basal binding in white matter areas, where the LPA1 receptor is expressed at high levels, suggesting a relevant role of the activity of this receptor in the most myelinated brain areas. In addition, phospholipid precursors of LPA were localized by MALDI-IMS in both rodent and human brain slices identifying numerous species of phosphatides (PA) and phosphatidylcholines (PC). Both PA and PC species represent potential LPA precursors. The anatomical distribution of these precursors in rodent and human brain may indicate a metabolic relationship between LPA and LPA1 receptors. PMID:25857358

HAL-2 Promotes Homologous Pairing during Caenorhabditis elegans Meiosis by Antagonizing Inhibitory Effects of Synaptonemal Complex Precursors

PubMed Central

Zhang, Weibin; Miley, Natasha; Zastrow, Michael S.; MacQueen, Amy J.; Sato, Aya; Nabeshima, Kentaro; Martinez-Perez, Enrique; Mlynarczyk-Evans, Susanna; Carlton, Peter M.; Villeneuve, Anne M.

2012-01-01

During meiosis, chromosomes align with their homologous pairing partners and stabilize this alignment through assembly of the synaptonemal complex (SC). Since the SC assembles cooperatively yet is indifferent to homology, pairing and SC assembly must be tightly coordinated. We identify HAL-2 as a key mediator in this coordination, showing that HAL-2 promotes pairing largely by preventing detrimental effects of SC precursors (SYP proteins). hal-2 mutants fail to establish pairing and lack multiple markers of chromosome movement mediated by pairing centers (PCs), chromosome sites that link chromosomes to cytoplasmic microtubules through nuclear envelope-spanning complexes. Moreover, SYP proteins load inappropriately along individual unpaired chromosomes in hal-2 mutants, and markers of PC-dependent movement and function are restored in hal-2; syp double mutants. These and other data indicate that SYP proteins can impede pairing and that HAL-2 promotes pairing predominantly but not exclusively by counteracting this inhibition, thereby enabling activation and regulation of PC function. HAL-2 concentrates in the germ cell nucleoplasm and colocalizes with SYP proteins in nuclear aggregates when SC assembly is prevented. We propose that HAL-2 functions to shepherd SYP proteins prior to licensing of SC assembly, preventing untimely interactions between SC precursors and chromosomes and allowing sufficient accumulation of precursors for rapid cooperative assembly upon homology verification. PMID:22912597

HAL-2 promotes homologous pairing during Caenorhabditis elegans meiosis by antagonizing inhibitory effects of synaptonemal complex precursors.

PubMed

Zhang, Weibin; Miley, Natasha; Zastrow, Michael S; MacQueen, Amy J; Sato, Aya; Nabeshima, Kentaro; Martinez-Perez, Enrique; Mlynarczyk-Evans, Susanna; Carlton, Peter M; Villeneuve, Anne M

2012-01-01

During meiosis, chromosomes align with their homologous pairing partners and stabilize this alignment through assembly of the synaptonemal complex (SC). Since the SC assembles cooperatively yet is indifferent to homology, pairing and SC assembly must be tightly coordinated. We identify HAL-2 as a key mediator in this coordination, showing that HAL-2 promotes pairing largely by preventing detrimental effects of SC precursors (SYP proteins). hal-2 mutants fail to establish pairing and lack multiple markers of chromosome movement mediated by pairing centers (PCs), chromosome sites that link chromosomes to cytoplasmic microtubules through nuclear envelope-spanning complexes. Moreover, SYP proteins load inappropriately along individual unpaired chromosomes in hal-2 mutants, and markers of PC-dependent movement and function are restored in hal-2; syp double mutants. These and other data indicate that SYP proteins can impede pairing and that HAL-2 promotes pairing predominantly but not exclusively by counteracting this inhibition, thereby enabling activation and regulation of PC function. HAL-2 concentrates in the germ cell nucleoplasm and colocalizes with SYP proteins in nuclear aggregates when SC assembly is prevented. We propose that HAL-2 functions to shepherd SYP proteins prior to licensing of SC assembly, preventing untimely interactions between SC precursors and chromosomes and allowing sufficient accumulation of precursors for rapid cooperative assembly upon homology verification.

Plasmodium vivax: a monoclonal antibody recognizes a circumsporozoite protein precursor on the sporozoite surface.

PubMed

Gonzalez-Ceron, L; Rodriguez, M H; Wirtz, R A; Sina, B J; Palomeque, O L; Nettel, J A; Tsutsumi, V

1998-11-01

The major surface circumsporozoite (CS) proteins are known to play a role in malaria sporozoite development and invasion of invertebrate and vertebrate host cells. Plasmodium vivax CS protein processing during mosquito midgut oocyst and salivary gland sporozoite development was studied using monoclonal antibodies which recognize different CS protein epitopes. Monoclonal antibodies which react with the CS amino acid repeat sequences by ELISA recognized a 50-kDa precursor protein in immature oocyst and additional 47- and 42-kDa proteins in older oocysts. A 42-kDa CS protein was detected after initial sporozoite invasion of mosquito salivary glands and an additional 50-kDa precursor CS protein observed later in infected salivary glands. These data confirm previous results with other Plasmodium species, in which more CS protein precursors were detected in oocysts than in salivary gland sporozoites. A monoclonal antibody (PvPCS) was characterized which reacts with an epitope found only in the 50-kDa precursor CS protein. PvPCS reacted with all P. vivax sporozoite strains tested by indirect immunofluorescent assay, homogeneously staining the sporozoite periphery with much lower intensity than that produced by anti-CS repeat antibodies. Immunoelectron microscopy using PvPCS showed that the CS protein precursor was associated with peripheral cytoplasmic vacuoles and membranes of sporoblast and budding sporozoites in development oocysts. In salivary gland sporozoites, the CS protein precursor was primarily associated with micronemes and sporozoite membranes. Our results suggest that the 50-kDa CS protein precursor is synthesized intracellularly and secreted on the membrane surface, where it is proteolytically processed to form the 42-kDa mature CS protein. These data indicate that differences in CS protein processing in oocyst and salivary gland sporozoites development may occur. Copyright 1998 Academic Press.

The protocol for the isolation and cryopreservation of osteoclast precursors from mouse bone marrow and spleen.

PubMed

Boraschi-Diaz, Iris; Komarova, Svetlana V

2016-01-01

Osteoclasts are responsible for physiological bone remodeling as well as pathological bone destruction in osteoporosis, periodontitis and rheumatoid arthritis, and thus represent a pharmacological target for drug development. We aimed to characterize and compare the cytokine-induced osteoclastogenesis of bone marrow and spleen precursors. Established protocols used to generate osteoclasts from bone marrow were modified to examine osteoclastogenesis of the spleen cells of healthy mice. Osteoclast formation was successfully induced from spleen precursors using receptor activator of nuclear factor κB ligand (50 ng/ml) and macrophage colony stimulating factor (50 ng/ml). Compared to bone marrow cultures, differentiation from spleen required a longer cultivation time (9 days for spleen, as compared to 5 days for marrow cultures) and a higher plating density of non-adherent cells (75,000/cm(2) for spleen, as compared to 50,000/cm(2) for bone marrow). Osteoclasts generated from spleen precursors expressed osteoclast marker genes calcitonin receptor, cathepsin K and matrix metalloproteinase 9 and were capable of resorbing hydroxyapatite. The differentiation capacity of spleen and bone marrow precursors was comparable for BALB/c, C57BL/6 and FVB mice. We also developed and tested a cryopreservation protocol for the osteoclast precursors. While 70-80 % of cells were lost during the first week of freezing, during the subsequent 5 weeks the losses were within 2-5 % per week. Osteoclastogenesis from the recovered bone marrow precursors was successful up to 5 weeks after freezing. Spleen precursors retained their osteoclastogenic capacity for 1 week after freezing, but not thereafter. The described protocol is useful for the studies of genetically modified animals as well as for screening new osteoclast-targeting therapeutics.

Assessing the effects of oil sands related ozone precursor emissions on ambient ozone levels in the Alberta oil sands region, Canada

NASA Astrophysics Data System (ADS)

Cho, Sunny; Vijayaraghavan, Krish; Spink, David; Cosic, Biljana; Davies, Mervyn; Jung, Jaegun

2017-11-01

A study was undertaken to determine whether, and the extent to which, increased ground-level ozone (O3) precursor emissions from oil sands development have impacted ambient air quality in the north-eastern Alberta, Canada, over the period 1998 to 2012. Temporal trends in emissions of O3 precursors (NOx and VOC) and ambient air concentrations of O3 precursors, and O3 were examined using the Theil-Sen statistical analysis method. Statistically significant correlations between NOx emissions and ambient NOx concentrations were found mainly near surface (open-pit) mining areas where mine fleets are a large source of NOx emissions. No statistically significant trends in the 4th highest daily maximum 8-hr average O3 at any of the continuous and passive ambient air monitoring stations were found. A significant long-term decrease in monthly averaged O3 is observed at some ambient monitoring sites in summer. A visual examination of long-term variations in annual NOx and VOC emissions and annual 4th highest daily maximum 8-hr O3 concentrations does not reveal any indication of a correlation between O3 concentrations and O3 precursor emissions or ambient levels in the study area. Despite a significant increase in oil sands NOx emissions (8%/yr), there is no statistically significant increase in long-term O3 concentrations at any of monitoring stations considered. This suggests that there is surplus NOx available in the environment which results in a titration of ambient O3 in the areas that have ambient monitoring. The limited ambient O3 monitoring data distant from NOx emission sources makes it impossible to assess the impact of these increased O3 precursor levels on O3 levels on a regional scale. As a precautionary measure, the increasing oil sands development O3 precursor emissions would require that priority be given to the management of these emissions to prevent possible future O3 ambient air quality issues.

Cloning and determination of the transcription termination site of ribosomal RNA gene of the mouse.

PubMed Central

Kominami, R; Mishima, Y; Urano, Y; Sakai, M; Muramatsu, M

1982-01-01

A Eco RI 6.6 kb DNA fragment containing the 3'-end of 28S ribosomal RNA gene of the mouse was detected by Southern blot hybridization, and cloned in a lambda-phage vector. The site of transcription termination and the processed 3'-end of 28S RNA were determined on the cloned fragment and the surrounding nucleotide sequence determined. The 3'-terminal nucleotides of mouse 28S RNA are similar to those of yeast, Drosophila and Xenopus although the homology was lost drastically beyond the 3'-end of 28S RNA. 45S precursor RNA terminated at 30 nucleotides downstream from the 3'-end of 28S RNA gene. A structure of a dyad symmetry with a loop was found immediately prior to the termination site of 45S RNA. The rDNA termination site thus shares some common features with termination sites recognized by other RNA polymerases. Images PMID:6281727

Role of meteorological processes in two New England ozone episodes during summer 2001

NASA Astrophysics Data System (ADS)

Mao, Huiting; Talbot, Robert

2004-10-01

We examined the impact of dynamical processes on spatial variability in ozone (O3) mixing ratios at closely spaced air monitoring sites in southern New Hampshire (NH) during two O3 episodes, July 21-25 and August 2, 2001. The Meso-scale Meteorological Model (MM5) and the Community Multiscale Air Quality (CMAQ) photochemical model were applied together with ground-based atmospheric chemistry observations conducted by the Atmospheric Investigation, Regional Modeling, Analysis and Prediction (AIRMAP) program at the University of New Hampshire. Observations and model simulations suggested that during the July episode long-range transport via the nocturnal low-level jet (LLJ) played an important role in producing elevated daytime mixing ratios of O3. The marine site Isle of Shoals experienced the highest level of O3, possibly a result of having more diverse upwind sources and less ventilation compared to continental sites. Our model results suggest that during daytime the shallow sea breeze circulation contributes to high levels of O3 at coastal and marine sites while the channeling effect of the Appalachian Mountains influences inland locations. In contrast to the July event, the event on August 2 was characterized by weak and transient synoptic flows, indicating insufficient time for transport of O3 and its precursors from distant sources to inland sites in NH. Backward trajectories for both events showed that O3-rich air masses from the Boston metropolitan area can contribute to the high levels of O3 (>120 ppbv) at coastal and marine sites in southern NH. Our results suggest that the International Consortium of Atmospheric Research on Transport and Transformation (ICARTT), an international field campaign based in the northeastern United States in summer 2004, should coordinate mobile platforms to investigate the vertical structure and chemical composition of the LLJ, the sea breeze, and the terrain-forced flows, and estimate the influx of O3 and its precursors to central New England.

Spatiotemporal variation of ozone precursors and ozone formation in Hong Kong: Grid field measurement and modelling study.

PubMed

Lyu, X P; Liu, M; Guo, H; Ling, Z H; Wang, Y; Louie, P K K; Luk, C W Y

2016-11-01

Grid field measurements of volatile organic compounds (VOCs) covering the entire territory of Hong Kong were simultaneously carried out twice daily on 27 September 2013 and 24 September 2014, respectively, to advance our understanding on the spatiotemporal variations of VOCs and ozone (O3) formation, the factors controlling O3 formation and the efficacy of a control measure in Hong Kong. From before to after the control measure on liquefied petroleum gas (LPG) fueled vehicles, the VOCs originated from LPG vehicle exhaust deceased from 41.3±1.2μg/m(3) (49.7±1.5%) to 32.8±1.4μg/m(3) (38.8±1.7%) (p<0.05). In contrast, the contribution to VOCs made by gasoline and diesel vehicle exhaust and solvent usage increased (p<0.05). VOCs and nitric oxide (NO) in LPG source experienced the highest reductions at the roadside sites, while the variations were not significant at the urban and new town sites (p>0.05). For O3 production, LPG vehicle exhaust generally made a negative contribution (-0.17±0.06 ppbv) at the roadside sites, however it turned to a slightly positive contribution (0.004±0.038 ppbv) after the control measure. At the urban sites, although the reductions of VOCs and NO were minor (p>0.05), O3 produced by LPG vehicle significantly reduced from 4.19±1.92 ppbv to 0.95±0.38 ppbv (p<0.05). Meanwhile, O3 produced by LPG at the new town sites remained stable. The analysis of O3-precursor relationships revealed that alkenes and aromatics were the main species limiting roadside O3 formation, while aromatics were the most predominant controlling factor at urban and new town sites. In contrast, isoprene and sometimes NOx limited the O3 formation in rural environment. Copyright © 2016 Elsevier B.V. All rights reserved.

Modelling winter organic aerosol at the European scale with CAMx: evaluation and source apportionment with a VBS parameterization based on novel wood burning smog chamber experiments

NASA Astrophysics Data System (ADS)

Ciarelli, Giancarlo; Aksoyoglu, Sebnem; El Haddad, Imad; Bruns, Emily A.; Crippa, Monica; Poulain, Laurent; Äijälä, Mikko; Carbone, Samara; Freney, Evelyn; O'Dowd, Colin; Baltensperger, Urs; Prévôt, André S. H.

2017-06-01

We evaluated a modified VBS (volatility basis set) scheme to treat biomass-burning-like organic aerosol (BBOA) implemented in CAMx (Comprehensive Air Quality Model with extensions). The updated scheme was parameterized with novel wood combustion smog chamber experiments using a hybrid VBS framework which accounts for a mixture of wood burning organic aerosol precursors and their further functionalization and fragmentation in the atmosphere. The new scheme was evaluated for one of the winter EMEP intensive campaigns (February-March 2009) against aerosol mass spectrometer (AMS) measurements performed at 11 sites in Europe. We found a considerable improvement for the modelled organic aerosol (OA) mass compared to our previous model application with the mean fractional bias (MFB) reduced from -61 to -29 %. We performed model-based source apportionment studies and compared results against positive matrix factorization (PMF) analysis performed on OA AMS data. Both model and observations suggest that OA was mainly of secondary origin at almost all sites. Modelled secondary organic aerosol (SOA) contributions to total OA varied from 32 to 88 % (with an average contribution of 62 %) and absolute concentrations were generally under-predicted. Modelled primary hydrocarbon-like organic aerosol (HOA) and primary biomass-burning-like aerosol (BBPOA) fractions contributed to a lesser extent (HOA from 3 to 30 %, and BBPOA from 1 to 39 %) with average contributions of 13 and 25 %, respectively. Modelled BBPOA fractions were found to represent 12 to 64 % of the total residential-heating-related OA, with increasing contributions at stations located in the northern part of the domain. Source apportionment studies were performed to assess the contribution of residential and non-residential combustion precursors to the total SOA. Non-residential combustion and road transportation sector contributed about 30-40 % to SOA formation (with increasing contributions at urban and near industrialized sites), whereas residential combustion (mainly related to wood burning) contributed to a larger extent, around 60-70 %. Contributions to OA from residential combustion precursors in different volatility ranges were also assessed: our results indicate that residential combustion gas-phase precursors in the semivolatile range (SVOC) contributed from 6 to 30 %, with higher contributions predicted at stations located in the southern part of the domain. On the other hand, the oxidation products of higher-volatility precursors (the sum of intermediate-volatility compounds (IVOCs) and volatile organic compounds (VOCs)) contribute from 15 to 38 % with no specific gradient among the stations. Although the new parameterization leads to a better agreement between model results and observations, it still under-predicts the SOA fraction, suggesting that uncertainties in the new scheme and other sources and/or formation mechanisms remain to be elucidated. Moreover, a more detailed characterization of the semivolatile components of the emissions is needed.

Influence of methyl and propyl groups on the vibrational spectra of two imidazolium ionic liquids and their non-ionic precursors

NASA Astrophysics Data System (ADS)

Haddad, Boumediene; Mokhtar, Drai; Goussem, Mimanne; Belarbi, El-habib; Villemin, Didier; Bresson, Serge; Rahmouni, Mustapha; Dhumal, Nilesh R.; Kim, Hyung J.; Kiefer, Johannes

2017-04-01

Imidazolium-based ionic liquids (ILs) are usually synthesized using non-ionic imidazole compounds as precursors. While the ILs have been extensively studied in the past, the precursors was not paid much attention to. The structural analysis of the precursors, however, may offer an opportunity to better understand the behavior of the ionic compounds of interest. In this paper, a comparative study of two ionic liquids and their imidazole precursors is presented. The precursors 1-methylimidazole [1-MIM] and 1,2-dimethylimidazole [1,2-DMIM] are compared in order to explain the influences of the methyl group at the C(2) position (methylation). Since the imidazole compounds are non-ionic, the spectroscopic properties of [1-MIM] and [1,2-DMIM] are not affected by cation-anion interactions. In addition, the products obtained by alkylation using propyl iodide leading to the corresponding IL compounds 1-methyl-3-propylimidazolium iodide [1-MPrIM+][I-] and 1,2-dimethyl-3-propylimidazolium iodide [1,2-DMPrIM+][I-] were studied. For this purpose, vibrational spectroscopy in terms of FT-Raman and FTIR in the wavenumber range from [45 to 3500 cm-1] and from [600 to 4000 cm-1], respectively, was performed. Moreover, to aid the spectral assignment, density functional theory (DFT) calculations were carried out. The aim was to investigate the vibrational structure, to understand the effects of the propyl group at the N(3) and of the methyl group at the C(2) position, and to analyze the resulting cation-anion interactions. The data indicate that the iodide ion predominantly interacts with the C(2)sbnd H group via hydrogen bonding. Upon methylation, the C(4/5)sbnd H moiety becomes the main interaction site. However, an interaction takes place only with one of the two hydrogen atoms resulting in a split of the initially degenerate CH stretching modes.

Quantum dot multiplexing for the profiling of cellular receptors

NASA Astrophysics Data System (ADS)

Lee-Montiel, Felipe T.; Li, Peter; Imoukhuede, P. I.

2015-11-01

The profiling of cellular heterogeneity has wide-reaching importance for our understanding of how cells function and react to their environments in healthy and diseased states. Our ability to interpret and model cell behavior has been limited by the difficulties of measuring cell differences, for example, comparing tumor and non-tumor cells, particularly at the individual cell level. This demonstrates a clear need for a generalizable approach to profile fluorophore sites on cells or molecular assemblies on beads. Here, a multiplex immunoassay for simultaneous detection of five different angiogenic markers was developed. We targeted angiogenic receptors in the vascular endothelial growth factor family (VEGFR1, VEGFR2 and VEGFR3) and Neuropilin (NRP) family (NRP1 and NRP2), using multicolor quantum dots (Qdots). Copper-free click based chemistry was used to conjugate the monoclonal antibodies with 525, 565, 605, 655 and 705 nm CdSe/ZnS Qdots. We tested and performed colocalization analysis of our nanoprobes using the Pearson correlation coefficient statistical analysis. Human umbilical vein endothelial cells (HUVEC) were tested. The ability to easily monitor the molecular indicators of angiogenesis that are a precursor to cancer in a fast and cost effective system is an important step towards personalized nanomedicine.The profiling of cellular heterogeneity has wide-reaching importance for our understanding of how cells function and react to their environments in healthy and diseased states. Our ability to interpret and model cell behavior has been limited by the difficulties of measuring cell differences, for example, comparing tumor and non-tumor cells, particularly at the individual cell level. This demonstrates a clear need for a generalizable approach to profile fluorophore sites on cells or molecular assemblies on beads. Here, a multiplex immunoassay for simultaneous detection of five different angiogenic markers was developed. We targeted angiogenic receptors in the vascular endothelial growth factor family (VEGFR1, VEGFR2 and VEGFR3) and Neuropilin (NRP) family (NRP1 and NRP2), using multicolor quantum dots (Qdots). Copper-free click based chemistry was used to conjugate the monoclonal antibodies with 525, 565, 605, 655 and 705 nm CdSe/ZnS Qdots. We tested and performed colocalization analysis of our nanoprobes using the Pearson correlation coefficient statistical analysis. Human umbilical vein endothelial cells (HUVEC) were tested. The ability to easily monitor the molecular indicators of angiogenesis that are a precursor to cancer in a fast and cost effective system is an important step towards personalized nanomedicine. Electronic supplementary information (ESI) available: Additional information of Qdot size, spectra, images of HUVEC, HDFa cells, confocal microscopy setting and colocalization analysis results. See DOI: 10.1039/c5nr01455g

Highly efficient red-emitting BaMgBO3F:Eu3+,R+ (R: Li, Na, K, Rb) phosphor for near-UV excitation synthesized via glass precursor solid-state reaction

NASA Astrophysics Data System (ADS)

Shinozaki, Kenji; Akai, Tomoko

2017-09-01

Eu3+-doped fluoroborate crystals of BaMgBO3F were synthesized by a solid-state reaction using a glassy precursor material, and their photoluminescence (PL) was investigated. To compensate for the incorporation of Eu3+ into Ba2+ sites, samples codoped with alkali ions (Li+, Na+, K+, Rb+) were also prepared. The Eu3+-doped sample showed red PL with a quantum yield (QY) of 65% caused by near-UV excitation (λ = 393 nm), and PL intensity and QY increased with the codoping of Eu3+ and alkali ions. It was found that the Eu3+,Li+-codoped sample showed the highest PL intensity and a QY of 83%.

A sensitive assay using a native protein substrate for screening HIV-1 maturation inhibitors targeting the protease cleavage site between the matrix and capsid.

PubMed

Lee, Sook-Kyung; Cheng, Nancy; Hull-Ryde, Emily; Potempa, Marc; Schiffer, Celia A; Janzen, William; Swanstrom, Ronald

2013-07-23

The matrix/capsid processing site in the HIV-1 Gag precursor is likely the most sensitive target to inhibit HIV-1 replication. We have previously shown that modest incomplete processing at the site leads to a complete loss of virion infectivity. In the study presented here, a sensitive assay based on fluorescence polarization that can monitor cleavage at the MA/CA site in the context of the folded protein substrate is described. The substrate, an MA/CA fusion protein, was labeled with the fluorescein-based FlAsH (fluorescein arsenical hairpin) reagent that binds to a tetracysteine motif (CCGPCC) that was introduced within the N-terminal domain of CA. By limiting the size of CA and increasing the size of MA (with an N-terminal GST fusion), we were able to measure significant differences in polarization values as a function of HIV-1 protease cleavage. The sensitivity of the assay was tested in the presence of increasing amounts of an HIV-1 protease inhibitor, which resulted in a gradual decrease in the fluorescence polarization values demonstrating that the assay is sensitive in discerning changes in protease processing. The high-throughput screening assay validation in 384-well plates showed that the assay is reproducible and robust with an average Z' value of 0.79 and average coefficient of variation values of <3%. The robustness and reproducibility of the assay were further validated using the LOPAC(1280) compound library, demonstrating that the assay provides a sensitive high-throughput screening platform that can be used with large compound libraries for identifying novel maturation inhibitors targeting the MA/CA site of the HIV-1 Gag polyprotein.

Effect of precursor concentration and spray pyrolysis temperature upon hydroxyapatite particle size and density.

PubMed

Cho, Jung Sang; Lee, Jeong-Cheol; Rhee, Sang-Hoon

2016-02-01

In the synthesis of hydroxyapatite powders by spray pyrolysis, control of the particle size was investigated by varying the initial concentration of the precursor solution and the pyrolysis temperature. Calcium phosphate solutions (Ca/P ratio of 1.67) with a range of concentrations from 0.1 to 2.0 mol/L were prepared by dissolving calcium nitrate tetrahydrate and diammonium hydrogen phosphate in deionized water and subsequently adding nitric acid. Hydroxyapatite powders were then synthesized by spray pyrolysis at 900°C and at 1500°C, using these calcium phosphate precursor solutions, under the fixed carrier gas flow rate of 10 L/min. The particle size decreased as the precursor concentration decreased and the spray pyrolysis temperature increased. Sinterability tests conducted at 1100°C for 1 h showed that the smaller and denser the particles were, the higher the relative densities were of sintered hydroxyapatite disks formed from these particles. The practical implication of these results is that highly sinterable small and dense hydroxyapatite particles can be synthesized by means of spray pyrolysis using a low-concentration precursor solution and a high pyrolysis temperature under a fixed carrier gas flow rate. © 2015 Wiley Periodicals, Inc.

Effects of copper-precursors on the catalytic activity of Cu/graphene catalysts for the selective catalytic oxidation of ammonia

NASA Astrophysics Data System (ADS)

Li, Jingying; Tang, Xiaolong; Yi, Honghong; Yu, Qingjun; Gao, Fengyu; Zhang, Runcao; Li, Chenlu; Chu, Chao

2017-08-01

Different copper-precursors were used to prepare Cu/graphene catalysts by an impregnation method. XRD, Raman spectra, TEM, BET, XPS, H2-TPR, NH3-TPD, DRIFTS and catalytic activity test were used to characterize and study the effect of precursors on the catalytic activity of Cu/graphene catalysts for NH3-SCO reaction. The large specific surface area of Cu/graphene catalysts and high dispersion of the metal particles on the graphene caused the well catalytic activity of NH3-SCO reaction. Compared to Cu/GE(AC), Cu/GE(N) showed better catalytic performance, and the complete NH3 removal efficiency was obtained at 250 °C with N2 selectivity of 85%. The copper-precursors had influence on the distribution of surface Cu species and further affected the catalytic activity of Cu/GE catalysts. The more amount of surface Cu species and highly dispersed CuO particles on the graphene surface formed by using copper nitrate as precursor could significantly improve the reducibility of catalysts and enhance NH3 adsorption, thereby improving the catalytic activity of Cu/graphene catalyst.

Effect of elicitors and precursors on azadirachtin production in hairy root culture of Azadirachta indica.

PubMed

Srivastava, Smita; Srivastava, A K

2014-02-01

The present study involved strategies for enhancement in in vitro azadirachtin (commercially used biopesticide) production by hairy root cultivation of Azadirachta indica. Improvement in the azadirachtin production via triggering its biosynthetic pathway in plant cells was carried out by the exogenous addition of precursors and elicitors in the growth medium. Among the different abiotic stress inducers (Ag(+), Hg(+2), Co(+2), Cu(+2)) and signal molecules (methyl jasmonate and salicylic acid) tested, salicylic acid at 15 mg l(-1) of concentration was found to enhance the azadirachtin yield in the hairy roots to the maximum (up to 4.95 mg g(-1)). Similarly, among the different biotic elicitors tested (filter-sterilized fungal culture filtrates of Phoma herbarium, Alternaria alternata, Myrothecium sp., Fusarium solani, Curvularia lunata, and Sclerotium rolfsii; yeast extract; and yeast extract carbohydrate fraction), addition of filter-sterilized fungal culture filtrate of C. lunata (1 % v/v) resulted in maximum azadirachtin yield enhancement in hairy root biomass (up to 7.1 mg g(-1)) with respect to the control (3.3 mg g(-1)). Among all the biosynthetic precursors studied (sodium acetate, cholesterol, squalene, isopentynyl pyrophosphate, mavalonic acid lactone, and geranyl pyrophosphate), the overall azadirachtin production (70.42 mg l(-1) in 25 days) was found to be the highest with cholesterol (50 mg l(-1)) addition as an indirect precursor in the medium.

N-nitrosodimethylamine formation upon ozonation and identification of precursors source in a municipal wastewater treatment plant.

PubMed

Sgroi, Massimiliano; Roccaro, Paolo; Oelker, Gregg L; Snyder, Shane A

2014-09-02

Ozone doses normalized to the dissolved organic carbon concentration were applied to the primary influent, primary effluent, and secondary effluent of a wastewater treatment plant producing water destined for potable reuse. Results showed the most N-Nitrosodimethylamine (NDMA) production from primary effluent, and the recycle streams entering the primary clarifiers were identified as the main source of NDMA precursors. The degradation of aminomethylated polyacrylamide (Mannich) polymer used for sludge treatment was a significant cause of precursor occurrence. A strong correlation between NDMA formation and ammonia concentration was found suggesting an important role of ammonia oxidation on NDMA production. During ozonation tests in DI water using dimethylamine (DMA) as model precursor, the NDMA yield significantly increased in the presence of ammonia and bromide due to the formation of hydroxylamine and brominated nitrogenous oxidants. In addition, NDMA formation during ozonation of dimethylformamide (DMF), the other model precursor used in this study, occurred only in the presence of ammonia, and it was attributable to the oxidation of DMF by hydroxyl radicals. Filtered wastewater samples (0.7 μm) produced more NDMA than unfiltered samples, suggesting that ozone reacted with dissolved precursors and supporting the hypothesis of polymer degradation. Particularly, the total suspended solids content similarly affected NDMA formation and the UV absorbance decrease during ozonation due to the different ozone demand created in filtered and unfiltered samples.

Lack of association of ghrelin precursor gene variants and percentage body fat or serum lipid profiles.

PubMed

Martin, Glynn R; Loredo, J C; Sun, Guang

2008-04-01

Ghrelin has been recognized for its involvement in food intake, control of energy homeostasis, and lipid metabolism. However, the roles of genetic variations in the ghrelin precursor gene (GHRL) on body compositions and serum lipids are not clear in humans. Our study investigated five single-nucleotide polymorphisms (SNPs) within GHRL to determine their relationship with body fat percentage (BF), trunk fat percentage (TF), lower body (legs) fat percentage (LF), and serum lipids in 1,464 subjects, which were recruited from the genetically homogeneous population of Newfoundland and Labrador (NL), Canada. Serum glucose, insulin, total cholesterol, high-density lipoprotein-cholesterol, low-density lipoprotein-cholesterol, and triglycerides were determined. Five SNPs are rs35684 (A/G: a transition substitution in exon 1), rs4684677 (A/T: a missense mutation), rs2075356 (C/T: intron), rs26802 (G/T: intron), and rs26311 (A/G: near the 3' untranslated region) of GHRL were genotyped using TaqMan validated or functionally tested SNP genotyping assays. Our study found no significant evidence of an allele or genotype association between any of the variant sites and body compositions or serum lipids. Furthermore, haplotype frequencies were not found to be significantly different between lean and obese subjects. In summary, the results of our study do not support a significant role for genetic variations in GHRL in the differences of body fat and serum lipid profiles in the NL population.

L-arginine enhances cell proliferation and reduces apoptosis in human endometrial RL95-2 cells

USDA-ARS?s Scientific Manuscript database

L-arginine is considered to be one of the most versatile amino acids due to the fact that it serves as a precursor for many important molecules in cellular physiology. When supplemented in the diet, L-arginine can increase the number of implantation sites in mice and rats, suggesting an effect at th...

A summary of major NASA launches, 1 October 1958 - 31 December 1979

NASA Technical Reports Server (NTRS)

Jarrett, F.

1980-01-01

Major NASA launches conducted under the direction of the John F. Kennedy Space Center (or its precursors) are listed within broad categories. Individual launches are summarized in chronological order under each category. The mission name, launch date/time, launch vehicle, NASA code, and site/pad are identified as well as the degree of success of the mission.

Reduction of randomness in seismic noise as a short-term precursor to a volcanic eruption.

PubMed

Glynn, C C; Konstantinou, K I

2016-11-24

Ambient seismic noise is characterized by randomness incurred by the random position and strength of the noise sources as well as the heterogeneous properties of the medium through which it propagates. Here we use ambient noise data recorded prior to the 1996 Gjálp eruption in Iceland in order to show that a reduction of noise randomness can be a clear short-term precursor to volcanic activity. The eruption was preceded on 29 September 1996 by a Mw ~5.6 earthquake that occurred in the caldera rim of the Bárdarbunga volcano. A significant reduction of randomness started occurring 8 days before the earthquake and 10 days before the onset of the eruption. This reduction was observed even at stations more than 100 km away from the eruption site. Randomness increased to its previous levels 160 minutes after the Bárdarbunga earthquake, during which time aftershocks migrated from the Bárdarbunga caldera to a site near the Gjálp eruption fissure. We attribute this precursory reduction of randomness to the lack of higher frequencies (>1 Hz) in the noise wavefield caused by high absorption losses as hot magma ascended in the upper crust.

Circulating osteogentic precursor cells in non-hereditary heterotopic ossification.

PubMed

Egan, Kevin P; Duque, Gustavo; Keenan, Mary Ann; Pignolo, Robert J

2018-04-01

Non-hereditary heterotopic ossification (NHHO) may occur after musculoskeletal trauma, central nervous system (CNS) injury, or surgery. We previously described circulating osteogenic precursor (COP) cells as a bone marrow-derived type 1 collagen + CD45 + subpopulation of mononuclear adherent cells that are able of producing extraskeletal ossification in a murine in vivo implantation assay. In the current study, we performed a tissue analysis of COP cells in NHHO secondary to defined conditions, including traumatic brain injury, spinal cord injury, cerebrovascular accident, trauma without neurologic injury, and joint arthroplasty. All bone specimens revealed the presence of COP cells at 2-14 cells per high power field. COP cells were localized to early fibroproliferative and neovascular lesions of NHHO with evidence for their circulatory status supported by their presence near blood vessels in examined lesions. This study provides the first systematic evaluation of COP cells as a contributory histopathological finding associated with multiple forms of NHHO. These data support that circulating, hematopoietic-derived cells with osteogenic potential can seed inflammatory sites, such as those subject to soft tissue injury, and due to their migratory nature, may likely be involved in seeding sites distant to CNS injury. Copyright © 2018 Elsevier Inc. All rights reserved.

Reduction of randomness in seismic noise as a short-term precursor to a volcanic eruption

PubMed Central

Glynn, C. C.; Konstantinou, K. I.

2016-01-01

Ambient seismic noise is characterized by randomness incurred by the random position and strength of the noise sources as well as the heterogeneous properties of the medium through which it propagates. Here we use ambient noise data recorded prior to the 1996 Gjálp eruption in Iceland in order to show that a reduction of noise randomness can be a clear short-term precursor to volcanic activity. The eruption was preceded on 29 September 1996 by a Mw ~5.6 earthquake that occurred in the caldera rim of the Bárdarbunga volcano. A significant reduction of randomness started occurring 8 days before the earthquake and 10 days before the onset of the eruption. This reduction was observed even at stations more than 100 km away from the eruption site. Randomness increased to its previous levels 160 minutes after the Bárdarbunga earthquake, during which time aftershocks migrated from the Bárdarbunga caldera to a site near the Gjálp eruption fissure. We attribute this precursory reduction of randomness to the lack of higher frequencies (>1 Hz) in the noise wavefield caused by high absorption losses as hot magma ascended in the upper crust. PMID:27883050

Glutamate-dependent ectodomain shedding of neuregulin-1 type II precursors in rat forebrain neurons.

PubMed

Iwakura, Yuriko; Wang, Ran; Inamura, Naoko; Araki, Kazuaki; Higashiyama, Shigeki; Takei, Nobuyuki; Nawa, Hiroyuki

2017-01-01

The neurotrophic factor neuregulin 1 (NRG1) regulates neuronal development, glial differentiation, and excitatory synapse maturation. NRG1 is synthesized as a membrane-anchored precursor and is then liberated by proteolytic processing or exocytosis. Mature NRG1 then binds to its receptors expressed by neighboring neurons or glial cells. However, the molecular mechanisms that govern this process in the nervous system are not defined in detail. Here we prepared neuron-enriched and glia-enriched cultures from embryonic rat neocortex to investigate the role of neurotransmitters that regulate the liberation/release of NRG1 from the membrane of neurons or glial cells. Using a two-site enzyme immunoassay to detect soluble NRG1, we show that, of various neurotransmitters, glutamate was the most potent inducer of NRG1 release in neuron-enriched cultures. NRG1 release in glia-enriched cultures was relatively limited. Furthermore, among glutamate receptor agonists, N-Methyl-D-Aspartate (NMDA) and kainate (KA), but not AMPA or tACPD, mimicked the effects of glutamate. Similar findings were acquired from analysis of the hippocampus of rats with KA-induced seizures. To evaluate the contribution of members of a disintegrin and metalloproteinase (ADAM) families to NRG1 release, we transfected primary cultures of neurons with cDNA vectors encoding NRG1 types I, II, or III precursors, each tagged with the alkaline phosphatase reporter. Analysis of alkaline phosphatase activity revealed that the NRG1 type II precursor was subjected to tumor necrosis factor-α-converting enzyme (TACE) / a Disintegrin And Metalloproteinase 17 (ADAM17) -dependent ectodomain shedding in a protein kinase C-dependent manner. These results suggest that glutamatergic neurotransmission positively regulates the ectodomain shedding of NRG1 type II precursors and liberates the active NRG1 domain in an activity-dependent manner.

A Critical Tryptophan and Ca2+ in Activation and Catalysis of TPPI, the Enzyme Deficient in Classic Late-Infantile Neuronal Ceroid Lipofuscinosis

PubMed Central

Kuizon, Salomon; DiMaiuta, Kathleen; Walus, Marius; Jenkins, Edmund C.; Kuizon, Marisol; Kida, Elizabeth; Golabek, Adam A.; Espinoza, Daniel O.; Pullarkat, Raju K.; Junaid, Mohammed A.

2010-01-01

Background Tripeptidyl aminopeptidase I (TPPI) is a crucial lysosomal enzyme that is deficient in the fatal neurodegenerative disorder called classic late-infantile neuronal ceroid lipofuscinosis (LINCL). It is involved in the catabolism of proteins in the lysosomes. Recent X-ray crystallographic studies have provided insights into the structural/functional aspects of TPPI catalysis, and indicated presence of an octahedrally coordinated Ca2+. Methodology Purified precursor and mature TPPI were used to study inhibition by NBS and EDTA using biochemical and immunological approaches. Site-directed mutagenesis with confocal imaging technique identified a critical W residue in TPPI activity, and the processing of precursor into mature enzyme. Principal Findings NBS is a potent inhibitor of the purified TPPI. In mammalian TPPI, W542 is critical for tripeptidyl peptidase activity as well as autocatalysis. Transfection studies have indicated that mutants of the TPPI that harbor residues other than W at position 542 have delayed processing, and are retained in the ER rather than transported to lysosomes. EDTA inhibits the autocatalytic processing of the precursor TPPI. Conclusions/Significance We propose that W542 and Ca2+ are critical for maintaining the proper tertiary structure of the precursor proprotein as well as the mature TPPI. Additionally, Ca2+ is necessary for the autocatalytic processing of the precursor protein into the mature TPPI. We have identified NBS as a potent TPPI inhibitor, which led in delineating a critical role for W542 residue. Studies with such compounds will prove valuable in identifying the critical residues in the TPPI catalysis and its structure-function analysis. PMID:20689811

Spectroscopic determination of thermal impulse in sub-second heating events using lanthanide-doped oxide precursors and phenomenological modeling

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

Anderson, Benjamin R., E-mail: branderson@wsu.edu; Gunawidjaja, Ray; Price, Patrick

2016-08-28

Using a mixture of crystalline-Ho:ZrO{sub 2}, precursor-Dy:Y{sub 2}O{sub 3}, and precursor-Eu:ZrO{sub 2} nanoparticles we develop thermal impulse sensors capable of measuring equivalent isothermal temperatures and durations during a heating event, with response times of <100 ms, and a temperature range of at least 673 K to 1173 K. In order to determine the temperature and duration from the sensors after the heating event we measure the sensors' fluorescence spectrum, which is then compared with lab based calibration data. By using two precursor materials with different reaction kinetics we are able to extract both temperature and duration. Based on blind sample testing we findmore » that the sensors and calculation method are accurate for measuring temperature and duration, but currently suffer a lack of precision due to difficulties in producing homogeneously heated samples.« less

Single Atomic Iron Catalysts for Oxygen Reduction in Acidic Media: Particle Size Control and Thermal Activation

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

Zhang, Hanguang; Hwang, Sooyeon; Wang, Maoyu

It remains a grand challenge to replace platinum group metal (PGM) catalysts with earth-abundant materials for the oxygen reduction reaction (ORR) in acidic media, which is crucial for large-scale deployment of proton exchange membrane fuel cells (PEMFCs). Here, we report a high-performance atomic Fe catalyst derived from chemically Fe-doped zeolitic imidazolate frameworks (ZIFs) by directly bonding Fe ions to imidazolate ligands within 3D frameworks. Although the ZIF was identified as a promising precursor, the new synthetic chemistry enables the creation of well-dispersed atomic Fe sites embedded into porous carbon without the formation of aggregates. The size of catalyst particles ismore » tunable through synthesizing Fe-doped ZIF nanocrystal precursors in a wide range from 20 to 1000 nm followed by one-step thermal activation. Similar to Pt nanoparticles, the unique size control without altering chemical properties afforded by this approach is able to increase the number of PGM-free active sites. The best ORR activity is measured with the catalyst at a size of 50 nm. Further size reduction to 20 nm leads to significant particle agglomeration, thus decreasing the activity. Using the homogeneous atomic Fe model catalysts, we elucidated the active site formation process through correlating measured ORR activity with the change of chemical bonds in precursors during thermal activation up to 1100 °C. The critical temperature to form active sites is 800 °C, which is associated with a new Fe species with a reduced oxidation number (from Fe3+ to Fe2+) likely bonded with pyridinic N (FeN4) embedded into the carbon planes. Further increasing the temperature leads to continuously enhanced activity, linked to the rise of graphitic N and Fe–N species. The new atomic Fe catalyst has achieved respectable ORR activity in challenging acidic media (0.5 M H2SO4), showing a half-wave potential of 0.85 V vs RHE and leaving only a 30 mV gap with Pt/C (60 μgPt/cm2). Enhanced stability is attained with the same catalyst, which loses only 20 mV after 10 000 potential cycles (0.6–1.0 V) in O2 saturated acid. The high-performance atomic Fe PGM-free catalyst holds great promise as a replacement for Pt in future PEMFCs.« less

Single Atomic Iron Catalysts for Oxygen Reduction in Acidic Media: Particle Size Control and Thermal Activation

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

Zhang, Hanguang; Hwang, Sooyeon; Wang, Maoyu

It remains a grand challenge to replace platinum group metal (PGM) catalysts with earth-abundant materials for the oxygen reduction reaction (ORR) in acidic media, which is crucial for large-scale deployment of proton exchange membrane fuel cells (PEMFCs). We report a high-performance atomic Fe catalyst derived from chemically Fe-doped zeolitic imidazolate frameworks (ZIFs) by directly bonding Fe ions to imidazolate ligands within 3D frameworks. Although the ZIF was identified as a promising precursor, the new synthetic chemistry enables the creation of well-dispersed atomic Fe sites embedded into porous carbon without the formation of aggregates. The size of catalyst particles is tunablemore » through synthesizing Fe-doped ZIF nanocrystal precursors in a wide range from 20 to 1000 nm followed by one-step thermal activation. Similar to Pt nanoparticles, the unique size control without altering chemical properties afforded by this approach is able to increase the number of PGM-free active sites. The best ORR activity is measured with the catalyst at a size of 50 nm. Further size reduction to 20 nm leads to significant particle agglomeration, thus decreasing the activity. In using the homogeneous atomic Fe model catalysts, we elucidated the active site formation process through correlating measured ORR activity with the change of chemical bonds in precursors during thermal activation up to 1100 °C. The critical temperature to form active sites is 800 °C, which is associated with a new Fe species with a reduced oxidation number (from Fe 3+ to Fe 2+) likely bonded with pyridinic N (FeN 4) embedded into the carbon planes. Further increasing the temperature leads to continuously enhanced activity, linked to the rise of graphitic N and Fe–N species. The new atomic Fe catalyst has achieved respectable ORR activity in challenging acidic media (0.5 M H 2SO 4), showing a half-wave potential of 0.85 V vs RHE and leaving only a 30 mV gap with Pt/C (60 μg Pt/cm 2). Finally, enhanced stability is attained with the same catalyst, which loses only 20 mV after 10 000 potential cycles (0.6–1.0 V) in O 2 saturated acid. The high-performance atomic Fe PGM-free catalyst holds great promise as a replacement for Pt in future PEMFCs.« less

Single Atomic Iron Catalysts for Oxygen Reduction in Acidic Media: Particle Size Control and Thermal Activation

DOE PAGES

Zhang, Hanguang; Hwang, Sooyeon; Wang, Maoyu; ...

2017-09-13

It remains a grand challenge to replace platinum group metal (PGM) catalysts with earth-abundant materials for the oxygen reduction reaction (ORR) in acidic media, which is crucial for large-scale deployment of proton exchange membrane fuel cells (PEMFCs). We report a high-performance atomic Fe catalyst derived from chemically Fe-doped zeolitic imidazolate frameworks (ZIFs) by directly bonding Fe ions to imidazolate ligands within 3D frameworks. Although the ZIF was identified as a promising precursor, the new synthetic chemistry enables the creation of well-dispersed atomic Fe sites embedded into porous carbon without the formation of aggregates. The size of catalyst particles is tunablemore » through synthesizing Fe-doped ZIF nanocrystal precursors in a wide range from 20 to 1000 nm followed by one-step thermal activation. Similar to Pt nanoparticles, the unique size control without altering chemical properties afforded by this approach is able to increase the number of PGM-free active sites. The best ORR activity is measured with the catalyst at a size of 50 nm. Further size reduction to 20 nm leads to significant particle agglomeration, thus decreasing the activity. In using the homogeneous atomic Fe model catalysts, we elucidated the active site formation process through correlating measured ORR activity with the change of chemical bonds in precursors during thermal activation up to 1100 °C. The critical temperature to form active sites is 800 °C, which is associated with a new Fe species with a reduced oxidation number (from Fe 3+ to Fe 2+) likely bonded with pyridinic N (FeN 4) embedded into the carbon planes. Further increasing the temperature leads to continuously enhanced activity, linked to the rise of graphitic N and Fe–N species. The new atomic Fe catalyst has achieved respectable ORR activity in challenging acidic media (0.5 M H 2SO 4), showing a half-wave potential of 0.85 V vs RHE and leaving only a 30 mV gap with Pt/C (60 μg Pt/cm 2). Finally, enhanced stability is attained with the same catalyst, which loses only 20 mV after 10 000 potential cycles (0.6–1.0 V) in O 2 saturated acid. The high-performance atomic Fe PGM-free catalyst holds great promise as a replacement for Pt in future PEMFCs.« less

Organic-Inorganic Hybrids Using Novel Phenylethynyl Imide Silanes

NASA Technical Reports Server (NTRS)

Park, C.; Lowther, S. E.; Smith, J. G., Jr.

2001-01-01

In this presentation, polyimide-silica hybrids using novel phenylethynyl imide silanes are reported. The phenylethynyl group is present in the organic precursor as either a pendent or an end group to bond chemically with the polyimide adhesive containing phenylethynyl groups during processing, while the silane group of the organic precursor would chemically react with the inorganic precursor through oxane bond formation. The chemical compositions of these novel hybrids were examined using X-ray mapping modes of scanning electron microscopy (SEM), which revealed a silicon gradient interphase between the high surface energy substrate and the polyimide adhesive. Novel aromatic phenylethynyl imide silanes (APEISs) and pendent phenylethynyl imide oligomeric disilanes (PPEIDSs) have been synthesized, and sol-gel solutions containing the new silanes, a phenylethynyl terminated imide oligomer (PETI-5), and an inorganic precursor were formulated to develop a gradient hybrid interphase between a titanium alloy and the adhesive. Two different sol-gel systems were investigated to develop organic-inorganic hybrids. Hybrid I was composed of an organic precursor containing both phenylethynyl and silane groups (PPEIDS) and an inorganic precursor. Functional group concentrations were controlled by the variation of the molecular weight of the imide backbone of PPEIDS. Hybrid II was composed of organic and inorganic precursors and a coupling agent containing both phenylethynyl and silane groups. Morphology and chemical composition of the hybrid interphase between the inorganic substrate and the adhesive were investigated, and the bond strength and durability were evaluated using lap shear tests at various conditions. The assessment of how the bonding at an interface is affected by various sol-gel solution compositions and environments is reported.

Hypoxia is increasing in the coastal zone of the Baltic Sea.

PubMed

Conley, Daniel J; Carstensen, Jacob; Aigars, Juris; Axe, Philip; Bonsdorff, Erik; Eremina, Tatjana; Haahti, Britt-Marie; Humborg, Christoph; Jonsson, Per; Kotta, Jonne; Lännegren, Christer; Larsson, Ulf; Maximov, Alexey; Medina, Miguel Rodriguez; Lysiak-Pastuszak, Elzbieta; Remeikaité-Nikiené, Nijolé; Walve, Jakob; Wilhelms, Sunhild; Zillén, Lovisa

2011-08-15

Hypoxia is a well-described phenomenon in the offshore waters of the Baltic Sea with both the spatial extent and intensity of hypoxia known to have increased due to anthropogenic eutrophication, however, an unknown amount of hypoxia is present in the coastal zone. Here we report on the widespread unprecedented occurrence of hypoxia across the coastal zone of the Baltic Sea. We have identified 115 sites that have experienced hypoxia during the period 1955-2009 increasing the global total to ca. 500 sites, with the Baltic Sea coastal zone containing over 20% of all known sites worldwide. Most sites experienced episodic hypoxia, which is a precursor to development of seasonal hypoxia. The Baltic Sea coastal zone displays an alarming trend with hypoxia steadily increasing with time since the 1950s effecting nutrient biogeochemical processes, ecosystem services, and coastal habitat.

Linking structure to function: The search for active sites in non-platinum group metal oxygen reduction reaction catalysts

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

Holby, Edward F.; Zelenay, Piotr

Atomic-scale structures of oxygen reduction reaction (ORR) active sites in non-platinum group metal (non-PGM) catalysts, made from pyrolysis of carbon, nitrogen, and transition-metal (TM) precursors have been the subject of continuing discussion in the fuel cell electrocatalysis research community. We found that quantum chemical modeling is a path forward for understanding of these materials and how they catalyze the ORR. Here, we demonstrate through literature examples of how such modeling can be used to better understand non-PGM ORR active site relative stability and activity and how such efforts can also aid in the interpretation of experimental signatures produced by thesemore » materials.« less

Linking structure to function: The search for active sites in non-platinum group metal oxygen reduction reaction catalysts

DOE PAGES

Holby, Edward F.; Zelenay, Piotr

2016-05-17

Atomic-scale structures of oxygen reduction reaction (ORR) active sites in non-platinum group metal (non-PGM) catalysts, made from pyrolysis of carbon, nitrogen, and transition-metal (TM) precursors have been the subject of continuing discussion in the fuel cell electrocatalysis research community. We found that quantum chemical modeling is a path forward for understanding of these materials and how they catalyze the ORR. Here, we demonstrate through literature examples of how such modeling can be used to better understand non-PGM ORR active site relative stability and activity and how such efforts can also aid in the interpretation of experimental signatures produced by thesemore » materials.« less

Synthesis of α-MoC1-x Nanoparticles with a Surface-Modified SBA-15 Hard Template: Determination of Structure-Function Relationships in Acetic Acid Deoxygenation.

PubMed

Baddour, Frederick G; Nash, Connor P; Schaidle, Joshua A; Ruddy, Daniel A

2016-07-25

Surface modification of mesoporous SBA-15 silica generated a hydrophobic environment for a molybdenum diamine (Mo-diamine) precursor solution, enabling direct growth of isolated 1.9±0.4 nm α-MoC1-x nanoparticles (NPs) inside the pores of the support. The resulting NP catalysts are bifunctional, and compared to bulk α-MoC1-x and β-Mo2 C, the NPs exhibit a greater acid-site:H-site ratio and a fraction of stronger acid sites. The greater acid-site:H-site ratio results in higher decarbonylation (DCO) selectivity during acetic acid hydrodeoxygenation (HDO) reactions, and the stronger acid sites lead to higher activity and ketonization (KET) selectivity at high temperatures. The hard-templating synthetic method could be a versatile route toward carbide NPs of varying size, composition, and phase, on a range of mesoporous oxide supports. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Synthesis of α-MoC 1-x Nanoparticles with a Surface-Modified SBA-15 Hard Template: Determination of Structure-Function Relationships in Acetic Acid Deoxygenation

DOE PAGES

Baddour, Frederick G.; Nash, Connor P.; Schaidle, Joshua A.; ...

2016-06-07

Surface modification of mesoporous SBA-15 silica generated a hydrophobic environment for a molybdenum diamine (Mo-diamine) precursor solution, enabling direct growth of isolated 1.9 ± 0.4 nm α-MoC 1-x nanoparticles (NPs) inside the pores of the support. The resulting NP catalysts are bifunctional, and compared to bulk α-MoC 1-x and β-Mo 2C, the NPs exhibit a greater acid-site:H-site ratio and a fraction of stronger acid sites. The greater acid-site:H-site ratio results in higher decarbonylation (DCO) selectivity during acetic acid hydrodeoxygenation (HDO) reactions, and the stronger acid sites lead to higher activity and ketonization (KET) selectivity at high temperatures. Lastly, the hard-templatingmore » synthetic method could be a versatile route toward carbide NPs of varying size, composition, and phase, on a range of mesoporous oxide supports.« less

Long-term trends and weekday-to-weekend differences in ozone, its precursors, and other secondary pollutants in Atlanta, Georgia

NASA Astrophysics Data System (ADS)

Pollack, I. B.; Ryerson, T. B.; Baumann, K.; Edgerton, E. S.; De Gouw, J. A.; Gilman, J.; Graus, M.; Holloway, J.; Lerner, B. M.; Neuman, J. A.; Roberts, J. M.; Veres, P. R.; Warneke, C.; Trainer, M.; Parrish, D. D.

2013-12-01

In an environment rich in biogenic volatile organic compounds (VOCs), decreasing concentrations of ozone (-1.3 % yr-1) and other secondary pollutants (-8.2 % yr-1 for nitric acid, HNO3; and -7.9 % yr-1 for peroxyacetyl nitrate, PAN) in Atlanta, Georgia over the past fifteen years are primarily attributed to decreases in local emissions of nitrogen oxides (NOx=NO+NO2). Large reductions in abundances of NOx in the Southeast U.S. over the years (-8.0 % yr-1 for total reactive nitrogen, NOy) are the direct result of control strategies implemented to reduced emissions from electric-power generation plants and on-road motor vehicles. Here, we compile an extensive historical data set of trace gas measurements spanning fifteen years between 1998 and 2013 from a surface monitoring network site in downtown Atlanta (i.e. the SEARCH network Jefferson Street site) and research aircraft (e.g. the 2013 Southeast Atmosphere Study and 1999 Southern Oxidants Study aboard the NOAA P-3 aircraft). With this data set we confirm and extend long-term trends and weekday-to-weekend differences in ozone, its precursors, and other secondary pollutants during summertime in Atlanta. Long-term changes in abundances and enhancement ratios of secondary oxidation products indicate changes in pollutant formation chemistry in Atlanta resulting from the significant decrease in NOx precursor emissions over the past fifteen years. The most noteworthy changes include: 1) an increase in enhancement ratios of odd oxygen (Ox=O3+NO2) to (PAN+HNO3) of +5.5 % yr-1 indicating an increase in ozone production efficiency by a factor of 2 over the fifteen year period, 2) no significant change in the fraction of oxidized NOx out of NOy over time indicating little change in the extent of photochemical processing of the NOx emissions, and 3) a flip in observed ozone concentrations from higher average ozone on weekends to higher average ozone on weekdays after 2004. The observations for Atlanta will also be contrasted with results from a similar analysis of California's Los Angeles air basin, a region with considerably different precursor abundances and emissions, control strategies, transport, and meteorology.

Simplified aerosol modeling for variational data assimilation

NASA Astrophysics Data System (ADS)

Huneeus, N.; Boucher, O.; Chevallier, F.

2009-11-01

We have developed a simplified aerosol model together with its tangent linear and adjoint versions for the ultimate aim of optimizing global aerosol and aerosol precursor emission using variational data assimilation. The model was derived from the general circulation model LMDz; it groups together the 24 aerosol species simulated in LMDz into 4 species, namely gaseous precursors, fine mode aerosols, coarse mode desert dust and coarse mode sea salt. The emissions have been kept as in the original model. Modifications, however, were introduced in the computation of aerosol optical depth and in the processes of sedimentation, dry and wet deposition and sulphur chemistry to ensure consistency with the new set of species and their composition. The simplified model successfully manages to reproduce the main features of the aerosol distribution in LMDz. The largest differences in aerosol load are observed for fine mode aerosols and gaseous precursors. Differences between the original and simplified models are mainly associated to the new deposition and sedimentation velocities consistent with the definition of species in the simplified model and the simplification of the sulphur chemistry. Furthermore, simulated aerosol optical depth remains within the variability of monthly AERONET observations for all aerosol types and all sites throughout most of the year. Largest differences are observed over sites with strong desert dust influence. In terms of the daily aerosol variability, the model is less able to reproduce the observed variability from the AERONET data with larger discrepancies in stations affected by industrial aerosols. The simplified model however, closely follows the daily simulation from LMDz. Sensitivity analyses with the tangent linear version show that the simplified sulphur chemistry is the dominant process responsible for the strong non-linearity of the model.

IMPROVED CATALYSTS FOR HEAVY OIL UPGRADING BASED ON ZEOLITE Y NANOPARTICLES ENCAPSULATED IN STABLE NANOPOROUS HOST

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

Conrad Ingram; Mark Mitchell

2005-11-15

Composite materials of SBA-15/zeolite Y were synthesized from zeolite Y precursor and a synthesis mixture of mesoporous silicate SBA-15 via a hydrothermal process in the presence of a slightly acidic media of pH 4-6 with 2M H{sub 2}SO{sub 4}. The SBA-15/ZY composites showed Type IV adsorption isotherms, narrow BJH average pore size distribution of 4.9 nm, surface areas up to 800 m{sup 2}2/g and pore volumes 1.03 cm{sup 3}, all comparable to pure SBA-15 synthesized under similar conditions. Chemical analysis revealed Si/Al ratio down to 8.5 in the most aluminated sample, and {sup 27}AlSS MAS NMR confirmed aluminum was inmore » tetrahedral coordination. This method of introduction of Al in pure T{sub d} coordination is effective in comparison to other direct and post synthesis alumination methods. Bronsted acid sites were evident from a pyridinium peak at 1544 cm-1 in the FTIR spectrum after pyridine adsorption, and from NH{sub 3} -TPD experiments. SBA-15/ZY composites showed significant catalytic activities for the dealkylation of isopropylbenzene to benzene and propene, similar to those of commercial zeolite Y. It was observed that higher conversion for catalysts synthesized with high amount of ZY precursor mixture added to the SBA-15. Over all the composites has shown good catalytic activity. Further studies will be focused on gaining a better understand the nature of the precursor, and to characterize and to locate the acid sites in the composite material. The composite will also be evaluated for heavy oil conversion to naphtha and middle distillates.« less

Out-of-equilibrium Sm Fe based phases

NASA Astrophysics Data System (ADS)

Djéga-Mariadassou, C.; Bessais, L.

2008-02-01

Structure and magnetic properties of nanocrystalline P6/mmm out-of-equilibrium precursors of hard magnetic R-3m Sm2(Fe,M)17C (M=Ga,Si,) and I4/mmm Sm(Fe,Co,Ti)11 equilibrium phases, are presented. Their structure is explained with a model ground on the R1 - s T5 + 2 s formula (R=rare-earth, s=vacancy rate, T=transition metal) where s Sm atoms are statistically substituted by s transition metal pairs. The Rietveld analysis (RA) provides the stoichiometry of the precursors, 1:9 and 1:10, respectively precursor of 2:17 and 1:12 phases. The interpretation of the Mössbauer spectra of the 1:9 and 1:10 phases, is based on the correlation between δ and the Wigner Seitz Cell volumes, calculated from the structural parameters. The δ behaviour of each crystallographic site versus Co content, defines the Co location while it confirms that of Si and Ga obtained by RA. Substitution occurs in 3 g site, whatever Co or M. The Sm(Fe,Co,Ti)10 and Sm(Fe,M)9C Curie temperature (Tc) are compared to those of the equilibrium phases, the effects of Fe substitution and C addition are discussed. The maximum μ 0Hc is obtained for low M or Co content, for auto-coherent diffraction domain size ˜30 nm. SmFe8.75Ga0.25C and SmFe8.75Si0.25C with Tc of 680 and 690 K, show respectively Mr and μ 0Hc of 58 emu/g, 27 kOe and 95 emu/g, 15 kOe, values higher than those obtained for Sm2(Fe,M)17 carbides.

Chaotic Time Series Analysis Method Developed for Stall Precursor Identification in High-Speed Compressors

NASA Technical Reports Server (NTRS)

1997-01-01

A new technique for rotating stall precursor identification in high-speed compressors has been developed at the NASA Lewis Research Center. This pseudo correlation integral method uses a mathematical algorithm based on chaos theory to identify nonlinear dynamic changes in the compressor. Through a study of four various configurations of a high-speed compressor stage, a multistage compressor rig, and an axi-centrifugal engine test, this algorithm, using only a single pressure sensor, has consistently predicted the onset of rotating stall.

NEEMO 18-20: Analog Testing for Mitigation of Communication Latency During Human Space Exploration

NASA Technical Reports Server (NTRS)

Chappell, Steven P.; Beaton, Kara H.; Miller, Matthew J.; Graff, Trevor G.; Abercromby, Andrew F. J.; Gernhardt, Michael L.; Halcon, Christopher

2016-01-01

NASA Extreme Environment Mission Operations (NEEMO) is an underwater spaceflight analog that allows a true mission-like operational environment and uses buoyancy effects and added weight to simulate different gravity levels. Three missions were undertaken from 2014-2015, NEEMO's 18-20. All missions were performed at the Aquarius undersea research habitat. During each mission, the effects of communication latencies on operations concepts, timelines, and tasks were studied. METHODS: Twelve subjects (4 per mission) were weighed out to simulate near-zero or partial gravity extravehicular activity (EVA) and evaluated different operations concepts for integration and management of a simulated Earth-based science team (ST) to provide input and direction during exploration activities. Exploration traverses were preplanned based on precursor data. Subjects completed science-related tasks including pre-sampling surveys, geologic-based sampling, and marine-based sampling as a portion of their tasks on saturation dives up to 4 hours in duration that were designed to simulate extravehicular activity (EVA) on Mars or the moons of Mars. One-way communication latencies, 5 and 10 minutes between space and mission control, were simulated throughout the missions. Objective data included task completion times, total EVA times, crew idle time, translation time, ST assimilation time (defined as time available for ST to discuss data/imagery after data acquisition). Subjective data included acceptability, simulation quality, capability assessment ratings, and comments. RESULTS: Precursor data can be used effectively to plan and execute exploration traverse EVAs (plans included detailed location of science sites, high-fidelity imagery of the sites, and directions to landmarks of interest within a site). Operations concepts that allow for pre-sampling surveys enable efficient traverse execution and meaningful Mission Control Center (MCC) interaction across communication latencies and can be done with minimal crew idle time. Imagery and contextual information from the EVA crew that is transmitted real-time to the intravehicular (IV) crewmember(s) can be used to verify that exploration traverse plans are being executed correctly. That same data can be effectively used by MCC (across comm latency) to provide meaningful feedback and instruction to the crew regarding sampling priorities, additional tasks, and changes to the EVA timeline. Text / data capabilities are preferred over voice capabilities between MCC and IV when executing exploration traverse plans over communication latency.

Behavioural Precursors and HIV Testing Behaviour among African American Women

ERIC Educational Resources Information Center

Uhrig, Jennifer D.; Davis, Kevin C.; Rupert, Doug; Fraze, Jami

2012-01-01

Objective: To examine whether there is an association between knowledge, attitudes and beliefs, reported intentions to get an HIV test, and reported HIV testing behaviour at a later date among a sample of African American women. Design: Secondary analysis of data collected from October 2007 through March 2008 for a randomized controlled experiment…

The structure and properties of the carbon non-wovens modified with bioactive nanoceramics for medical applications.

PubMed

Fraczek-Szczypta, A; Rabiej, S; Szparaga, G; Pabjanczyk-Wlazlo, E; Krol, P; Brzezinska, M; Blazewicz, S; Bogun, M

2015-06-01

The paper presents the results of the manufacture of carbon fibers (CF) from polyacrylonitrile fiber precursor containing bioactive ceramic nanoparticles. In order to modify the precursor fibers two types of bio-glasses and wollastonite in the form of nanoparticles were used. The processing variables of the thermal conversion of polyacrylonitrile (PAN) precursor fibers into carbon fibers were determined using the FTIR method. The carbonization process of oxidized PAN fibers was carried out up to 1000°C. The carbon fibers were characterized by a low ordered crystalline structure. The bioactivity tests of carbon fibers modified with a ceramic nanocomponent carried out in the artificial serum (SBF) revealed the apatite precipitation on the fibers' surfaces. Copyright © 2015 Elsevier B.V. All rights reserved.

Disentangling early language development: modeling lexical and grammatical acquisition using an extension of case-study methodology.

PubMed

Robinson, B F; Mervis, C B

1998-03-01

The early lexical and grammatical development of 1 male child is examined with growth curves and dynamic-systems modeling procedures. Lexical-development described a pattern of logistic growth (R2 = .98). Lexical and plural development shared the following characteristics: Plural growth began only after a threshold was reached in vocabulary size; lexical growth slowed as plural growth increased. As plural use reached full mastery, lexical growth began again to increase. It was hypothesized that a precursor model (P. van Geert, 1991) would fit these data. Subsequent testing indicated that the precursor model, modified to incorporate brief yet intensive plural growth, provided a suitable fit. The value of the modified precursor model for the explication of processes implicated in language development is discussed.

Ceramic fibers from Si-B-C polymer precursors

NASA Technical Reports Server (NTRS)

Riccitiello, S. R.; Hsu, M. S.; Chen, T. S.

1993-01-01

Non-oxide ceramics such as silicon carbide (SiC), silicon nitride (Si3N4), and silicon borides (SiB4, SiB6) have thermal stability, oxidation resistance, hardness, and varied electrical properties. All these materials can be prepared in a fiber form from a suitable polymer precursor. The above mentioned fibers, when tested over a temperature range from 25 to 1400 C, experience degradation at elevated temperatures. Past work in ceramic materials has shown that the strength of ceramics containing both carbides and borides is sustained at elevated temperatures, with minimum oxidation. The work presented here describes the formation of ceramic fibers containing both elements, boron and silicon, prepared via the polymer precursor route previously reported by the authors, and discusses the fiber mechanical properties that are retained over the temperature range studied.

A single amino acid difference between the intracellular domains of amyloid precursor protein and amyloid-like precursor protein 2 enables induction of synaptic depression and block of long-term potentiation.

PubMed

Trillaud-Doppia, Emilie; Paradis-Isler, Nicolas; Boehm, Jannic

2016-07-01

Alzheimer disease (AD) is initially characterized as a disease of the synapse that affects synaptic transmission and synaptic plasticity. While amyloid-beta and tau have been traditionally implicated in causing AD, recent studies suggest that other factors, such as the intracellular domain of the amyloid-precursor protein (APP-ICD), can also play a role in the development of AD. Here, we show that the expression of APP-ICD induces synaptic depression, while the intracellular domain of its homolog amyloid-like precursor protein 2 (APLP2-ICD) does not. We are able to show that this effect by APP-ICD is due to a single alanine vs. proline difference between APP-ICD and APLP2-ICD. The alanine in APP-ICD and the proline in APLP2-ICD lie directly behind a conserved caspase cleavage site. Inhibition of caspase cleavage of APP-ICD prevents the induction of synaptic depression. Finally, we show that the expression of APP-ICD increases and facilitates long-term depression and blocks induction of long-term potentiation. The block in long-term potentiation can be overcome by mutating the aforementioned alanine in APP-ICD to the proline of APLP2. Based on our results, we propose the emergence of a new APP critical domain for the regulation of synaptic plasticity and in consequence for the development of AD. Copyright © 2016 Elsevier Inc. All rights reserved.

[Proteolytic events in the maturation of pro-neuropeptides. The somatostatin model].

PubMed

Morel, A; Gluschankof, P; Gomez, S; Cohen, P

1986-01-01

The post-translational processing (maturation) of the precursors was studied on the model of the prosomatostatin. We have shown the presence of a single and common precursor to both somatostatin -28 and -14 in mouse hypothalamus, in contrast with the situation in the Teleostean fish, Lophius piscatorius. The search for a maturation activity was carried out using a synthetic undecapeptide substrate including in its sequence the cleavage site for somatostatin-14 release. Using this peptide, we characterized in rat brain cortex extracts a specific enzyme activity of 90 kD. This "maturase", colocalized in the neurosecretory granules with the somatostatin products, generates both the N-terminal peptide S-28, and the tetradecapeptide hormone (S-14) from the somatostatin-28, acting as a "S-28 convertase" producing free Arg and Lys residues present at the pair of basic amino acids signal. We propose a model where three peptide bonds are cleaved by this enzymatic activity. In the teleostean fish: Lophius piscatorius, two precursors coding for two different somatostatin were predicted by the determination of cDNA sequence. In this system, we observed the presence of a unique form of the tetradecapeptide hormone. We show that the final maturation product of the second precursor is a new 28 amino acid hormone called Somatostatin-28 II. Moreover, the product of this second gene after the action of the Somatostatin-28 convertase from rat brain cortex is the (Tyr7, Gly 10)S-14 derivative predicted by the clone.(ABSTRACT TRUNCATED AT 250 WORDS)

Splicing-independent loading of TREX on nascent RNA is required for efficient expression of dual-strand piRNA clusters in Drosophila

PubMed Central

Hur, Junho K.; Luo, Yicheng; Moon, Sungjin; Ninova, Maria; Marinov, Georgi K.; Chung, Yun D.; Aravin, Alexei A.

2016-01-01

The conserved THO/TREX (transcription/export) complex is critical for pre-mRNA processing and mRNA nuclear export. In metazoa, TREX is loaded on nascent RNA transcribed by RNA polymerase II in a splicing-dependent fashion; however, how TREX functions is poorly understood. Here we show that Thoc5 and other TREX components are essential for the biogenesis of piRNA, a distinct class of small noncoding RNAs that control expression of transposable elements (TEs) in the Drosophila germline. Mutations in TREX lead to defects in piRNA biogenesis, resulting in derepression of multiple TE families, gametogenesis defects, and sterility. TREX components are enriched on piRNA precursors transcribed from dual-strand piRNA clusters and colocalize in distinct nuclear foci that overlap with sites of piRNA transcription. The localization of TREX in nuclear foci and its loading on piRNA precursor transcripts depend on Cutoff, a protein associated with chromatin of piRNA clusters. Finally, we show that TREX is required for accumulation of nascent piRNA precursors. Our study reveals a novel splicing-independent mechanism for TREX loading on nascent RNA and its importance in piRNA biogenesis. PMID:27036967

Lithium chloride increases the production of amyloid-beta peptide independently from its inhibition of glycogen synthase kinase 3.

PubMed

Feyt, Christine; Kienlen-Campard, Pascal; Leroy, Karelle; N'Kuli, Francisca; Courtoy, Pierre J; Brion, Jean-Pierre; Octave, Jean-Noël

2005-09-30

Glycogen synthase kinase 3 (GSK3) is able to phosphorylate tau at many sites that are found to be phosphorylated in paired helical filaments in Alzheimer disease. Lithium chloride (LiCl) efficiently inhibits GSK3 and was recently reported to also decrease the production of amyloid-beta peptide (Abeta) from its precursor, the amyloid precursor protein. Therefore, lithium has been proposed as a combined therapeutic agent, inhibiting both the hyperphosphorylation of tau and the production of Abeta. Here, we demonstrate that the inhibition of GSK3 by LiCl induced the nuclear translocation of beta-catenin in Chinese hamster ovary cells and rat cultured neurons, in which a decrease in tau phosphorylation was observed. In both cellular models, a nontoxic concentration of LiCl increased the production of Abeta by increasing the beta-cleavage of amyloid precursor protein, generating more substrate for an unmodified gamma-secretase activity. SB415286, another GSK3 inhibitor, induced the nuclear translocation of beta-catenin and slightly decreased Abeta production. It is concluded that the LiCl-mediated increase in Abeta production is not related to GSK3 inhibition.

Parameter Space of Atomic Layer Deposition of Ultrathin Oxides on Graphene

PubMed Central

2016-01-01

Atomic layer deposition (ALD) of ultrathin aluminum oxide (AlOx) films was systematically studied on supported chemical vapor deposition (CVD) graphene. We show that by extending the precursor residence time, using either a multiple-pulse sequence or a soaking period, ultrathin continuous AlOx films can be achieved directly on graphene using standard H2O and trimethylaluminum (TMA) precursors even at a high deposition temperature of 200 °C, without the use of surfactants or other additional graphene surface modifications. To obtain conformal nucleation, a precursor residence time of >2s is needed, which is not prohibitively long but sufficient to account for the slow adsorption kinetics of the graphene surface. In contrast, a shorter residence time results in heterogeneous nucleation that is preferential to defect/selective sites on the graphene. These findings demonstrate that careful control of the ALD parameter space is imperative in governing the nucleation behavior of AlOx on CVD graphene. We consider our results to have model system character for rational two-dimensional (2D)/non-2D material process integration, relevant also to the interfacing and device integration of the many other emerging 2D materials. PMID:27723305

Molecular cloning of mevalonate pathway genes from Taraxacum brevicorniculatum and functional characterisation of the key enzyme 3-hydroxy-3-methylglutaryl-coenzyme A reductase.

PubMed

van Deenen, Nicole; Bachmann, Anne-Lena; Schmidt, Thomas; Schaller, Hubert; Sand, Jennifer; Prüfer, Dirk; Schulze Gronover, Christian

2012-04-01

Taraxacum brevicorniculatum is known to produce high quality rubber. The biosynthesis of rubber is dependent on isopentenyl pyrophosphate (IPP) precursors derived from the mevalonate (MVA) pathway. The cDNA sequences of seven MVA pathway genes from latex of T. brevicorniculatum were isolated, including three cDNA sequences encoding for 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductases (TbHMGR1-3). Expression analyses indicate an important role of TbHMGR1 as well as for the HMG-CoA synthase (TbHMGS), the diphosphomevalonate decarboxylase and the mevalonate kinase in the provision of precursors for rubber biosynthesis. The amino acid sequences of the TbHMGRs show the typical motifs described for plant HMGRs such as two transmembrane domains and a catalytic domain containing two HMG-CoA and two NADP(H) binding sites. The functionality of the HMGRs was demonstrated by complementation assay using an IPP auxotroph mutant of Escherichia coli. Furthermore, the transient expression of the catalytic domains of TbHMGR1 and TbHMGR2 in Nicotiana benthamiana resulted in a strong accumulation of sterol precursors, one of the major groups of pathway end-products.

Time series analysis of infrared satellite data for detecting thermal anomalies: a hybrid approach

NASA Astrophysics Data System (ADS)

Koeppen, W. C.; Pilger, E.; Wright, R.

2011-07-01

We developed and tested an automated algorithm that analyzes thermal infrared satellite time series data to detect and quantify the excess energy radiated from thermal anomalies such as active volcanoes. Our algorithm enhances the previously developed MODVOLC approach, a simple point operation, by adding a more complex time series component based on the methods of the Robust Satellite Techniques (RST) algorithm. Using test sites at Anatahan and Kīlauea volcanoes, the hybrid time series approach detected ~15% more thermal anomalies than MODVOLC with very few, if any, known false detections. We also tested gas flares in the Cantarell oil field in the Gulf of Mexico as an end-member scenario representing very persistent thermal anomalies. At Cantarell, the hybrid algorithm showed only a slight improvement, but it did identify flares that were undetected by MODVOLC. We estimate that at least 80 MODIS images for each calendar month are required to create good reference images necessary for the time series analysis of the hybrid algorithm. The improved performance of the new algorithm over MODVOLC will result in the detection of low temperature thermal anomalies that will be useful in improving our ability to document Earth's volcanic eruptions, as well as detecting low temperature thermal precursors to larger eruptions.

Gene therapy for Parkinson's disease: Disease modification by GDNF family of ligands.

PubMed

Kirik, Deniz; Cederfjäll, Erik; Halliday, Glenda; Petersén, Åsa

2017-01-01

Gene transfer is a promising drug delivery method of advanced therapeutic entities for Parkinson's disease. One advantage over conventional therapies, such as peripheral delivery of the dopamine pre-cursor l-DOPA, is site-specific expression of proteins with regenerative, disease-modifying and potentially neuroprotective capacity. Several clinical trials have been performed to test the capacity of glial-cell line derived neurotrophic factor and neurturin to rescue degenerating dopaminergic neurons in the substantia nigra and their axon terminals in the striatum by delivery of these neurotrophic factors either as purified protein or by means of viral vector mediated gene delivery to the brain. Although gene therapy approaches tested so far have been shown to be safe, none met their primary endpoints in phase II clinical trials designed and powered to test the efficacy of the intervention. Within the scope of this review we aim to describe the state-of-the-art in the field, how different technical parameters were translated from pre-clinical studies in non-human primates to clinical trials, and what these trials taught us regarding important factors that may pave the way to the success of gene therapy for the treatment of Parkinson's disease. Copyright © 2016 Elsevier Inc. All rights reserved.

Web-ware bioinformatical analysis and structure modelling of N-terminus of human multisynthetase complex auxiliary component protein p43.

PubMed

Deineko, Viktor

2006-01-01

Human multisynthetase complex auxiliary component, protein p43 is an endothelial monocyte-activating polypeptide II precursor. In this study, comprehensive sequence analysis of N-terminus has been performed to identify structural domains, motifs, sites of post-translation modification and other functionally important parameters. The spatial structure model of full-chain protein p43 is obtained.

Proflavine sensitivity of RNA processing in isolated nuclei.

PubMed Central

Yannarell, A; Niemann, M; Schumm, D E; Webb, T E

1977-01-01

The intercalating agent proflavine inhibits the processing and subsequent release of preformed messenger RNA and ribosomal RNA from isolated liver nuclei to surrogate cytoplasm. The direct effect of proflavine on these processes, as monitored in a reconstituted cell-free system, supports the theory that base-paired segments (i.e. hairpin loops) in the precursor RNA's are involved as recognition sites in nuclear RNA processing. PMID:866181

Structural and Functional Dissection of the Heterocyclic Peptide Cytotoxin Streptolysin S*S⃞

PubMed Central

Mitchell, Douglas A.; Lee, Shaun W.; Pence, Morgan A.; Markley, Andrew L.; Limm, Joyce D.; Nizet, Victor; Dixon, Jack E.

2009-01-01

The human pathogen Streptococcus pyogenes secretes a highly cytolytic toxin known as streptolysin S (SLS). SLS is a key virulence determinant and responsible for the β-hemolytic phenotype of these bacteria. Despite over a century of research, the chemical structure of SLS remains unknown. Recent experiments have revealed that SLS is generated from an inactive precursor peptide that undergoes extensive post-translational modification to an active form. In this work, we address outstanding questions regarding the SLS biosynthetic process, elucidating the features of substrate recognition and sites of posttranslational modification to the SLS precursor peptide. Further, we exploit these findings to guide the design of artificial cytolytic toxins that are recognized by the SLS biosynthetic enzymes and others that are intrinsically cytolytic. This new structural information has ramifications for future antimicrobial therapies. PMID:19286651

Adsorption of N-nitrosodimethylamine precursors by powdered and granular activated carbon.

PubMed

Hanigan, David; Zhang, Jinwei; Herckes, Pierre; Krasner, Stuart W; Chen, Chao; Westerhoff, Paul

2012-11-20

Activated carbon (AC) has been shown to remove precursors of halogenated disinfection byproducts. Granular and powdered activated carbon (GAC, PAC) were investigated for their potential to adsorb N-nitrosodimethylamine (NDMA) precursors from blends of river water and effluent from a wastewater treatment plant (WWTP). At bench scale, waters were exposed to lignite or bituminous AC, either as PAC in bottle point experiments or as GAC in rapid small-scale column tests (RSSCTs). NDMA formation potential (FP) was used as a surrogate for precursor removal. NDMA FP was reduced by 37, 59, and 91% with 3, 8, and 75 mg/L of one PAC, respectively, with a 4-h contact time. In RSSCTs and in full-scale GAC contactors, NDMA FP removal always exceeded that of the bulk dissolved organic carbon (DOC) and UV absorbance at 254 nm. For example, whereas DOC breakthrough exceeded 90% of its influent concentration after 10,000 bed volumes of operation in an RSSCT, NDMA FP was less than 40% of influent concentration after the same bed life of the GAC. At full or pilot scale, high NDMA FP reduction ranging from >60 to >90% was achieved across GAC contactors, dependent upon the GAC bed life and/or use of a preoxidant (chlorine or ozone). In all experiments, NDMA formation was not reduced to zero, which suggests that although some precursors are strongly sorbed, others are not. This is among the first studies to show that AC is capable of adsorbing NDMA precursors, but further research is needed to better understand NDMA precursor chemical properties (e.g., hydrophobicity, molecular size) and evaluate how best to incorporate this finding into full-scale designs and practice.

A Ploidy-Sensitive Mechanism Regulates Aperture Formation on the Arabidopsis Pollen Surface and Guides Localization of the Aperture Factor INP1

PubMed Central

Reeder, Sarah H.; Lee, Byung Ha; Fox, Ronald; Dobritsa, Anna A.

2016-01-01

Pollen presents a powerful model for studying mechanisms of precise formation and deposition of extracellular structures. Deposition of the pollen wall exine leads to the generation of species-specific patterns on pollen surface. In most species, exine does not develop uniformly across the pollen surface, resulting in the formation of apertures–openings in the exine that are species-specific in number, morphology and location. A long time ago, it was proposed that number and positions of apertures might be determined by the geometry of tetrads of microspores–the precursors of pollen grains arising via meiotic cytokinesis, and by the number of last-contact points between sister microspores. We have tested this model by characterizing Arabidopsis mutants with ectopic apertures and/or abnormal geometry of meiotic products. Here we demonstrate that contact points per se do not act as aperture number determinants and that a correct geometric conformation of a tetrad is neither necessary nor sufficient to generate a correct number of apertures. A mechanism sensitive to pollen ploidy, however, is very important for aperture number and positions and for guiding the aperture factor INP1 to future aperture sites. In the mutants with ectopic apertures, the number and positions of INP1 localization sites change depending on ploidy or ploidy-related cell size and not on INP1 levels, suggesting that sites for aperture formation are specified before INP1 is brought to them. PMID:27177036

The contribution of general cognitive abilities and approximate number system to early mathematics.

PubMed

Passolunghi, Maria Chiara; Cargnelutti, Elisa; Pastore, Massimiliano

2014-12-01

Math learning is a complex process that entails a wide range of cognitive abilities to be fulfilled. There is sufficient evidence that both general and specific cognitive skills assume a fundamental role, despite the absence of shared consensus about the relative extent of their involvement. Moreover, regarding general abilities, there is no agreement about the recruitment of the different memory components or of intelligence. In relation to specific factors, great debate subsists regarding the role of the approximate number system (ANS). Starting from these considerations, we wanted to conduct a wide assessment of memory components and ANS, by controlling for the effects associated with intelligence and also exploring possible relationships between all precursors. To achieve this purpose, a sample of 157 children was tested at both beginning and end of their Grade 1. Both general (memory and intelligence) and specific (ANS) precursors were evaluated by a wide battery of tests and put in relation to concurrent and subsequent math skills. Memory was explored in passive and active aspects involving both verbal and visuo-spatial components. Path analysis results demonstrated that memory, and especially the more active processes, and intelligence were the strongest precursors in both assessment times. ANS had a milder role which lost significance by the end of the school year. Memory and ANS seemed to influence early mathematics almost independently. Both general and specific precursors seemed to have a crucial role in early math competences, despite the lower involvement of ANS. © 2014 The British Psychological Society.

Quantum cascade laser-based screening portal for the detection of explosive precursors

NASA Astrophysics Data System (ADS)

Lindley, Ruth; Normand, Erwan; Howieson, Iain; McCulloch, Michael; Black, Paul; Lewis, Colin; Foulger, Brian

2007-10-01

In recent years, quantum cascade lasers (QCL) have been proven in robust, high-performance gas analyzers designed for continuous emission monitoring (CEM) in harsh environments. In 2006, Cascade Technologies reported progress towards adapting its patented technology for homeland security applications by publishing initial results on explosive compound detection. This paper presents the performance and results from a QCL-based people screening portal developed during the past year and aimed at the detection of precursors used in the make up of improvised explosive devices (IED). System tests have been carried out on a large number of potential interferents, together with target precursor materials, reinforcing original assumptions that compound fingerprinting can be effectively demonstrated using this technique. Results have shown that an extremely high degree of specificity can be achieved with a sub-second response time. Furthermore, it has been shown that unambiguous precursor signature recognition can be extended to compound mixtures associated with the intermediate stages in the make up of IEDs, whilst maintaining interferent immunity. The portal sensitivity was configured for parts per billion (ppb) detection level thresholds, but is currently being reconfigured for sub-ppb detection. In summary, the results obtained from the QCL based portal indicate that development of a low cost detection system, with enhanced features such as low false positive and high throughput screening of individuals or items, is possible. Development and testing was carried out with the support of the UK government.

Magnetic Memory from Site Isolated Dy(III) on Silica Materials

PubMed Central

2017-01-01

Achieving magnetic remanence at single isolated metal sites dispersed at the surface of a solid matrix has been envisioned as a key step toward information storage and processing in the smallest unit of matter. Here, we show that isolated Dy(III) sites distributed at the surface of silica nanoparticles, prepared with a simple and scalable two-step process, show magnetic remanence and display a hysteresis loop open at liquid 4He temperature, in contrast to the molecular precursor which does not display any magnetic memory. This singular behavior is achieved through the controlled grafting of a tailored Dy(III) siloxide complex on partially dehydroxylated silica nanoparticles followed by thermal annealing. This approach allows control of the density and the structure of isolated, “bare” Dy(III) sites bound to the silica surface. During the process, all organic fragments are removed, leaving the surface as the sole ligand, promoting magnetic remanence. PMID:28386602

Magnetic memory from site isolated Dy(III) on silica materials

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

Allouche, Florian; Lapadula, Giuseppe; Siddiqi, Georges

Achieving magnetic remanence at single isolated metal sites dispersed at the surface of a solid matrix has been envisioned as a key step toward information storage and processing in the smallest unit of matter. Here, we show that isolated Dy(III) sites distributed at the surface of silica nanoparticles, prepared with a simple and scalable two-step process, show magnetic remanence and display a hysteresis loop open at liquid 4He temperature, in contrast to the molecular precursor which does not display any magnetic memory. This singular behavior is achieved through the controlled grafting of a tailored Dy(III) siloxide complex on partially dehydroxylatedmore » silica nanoparticles followed by thermal annealing. This approach allows control of the density and the structure of isolated, “bare” Dy(III) sites bound to the silica surface. Throughout the process, all organic fragments are removed, leaving the surface as the sole ligand, promoting magnetic remanence.« less

Magnetic memory from site isolated Dy(III) on silica materials

DOE PAGES

Allouche, Florian; Lapadula, Giuseppe; Siddiqi, Georges; ...

2017-02-22

Achieving magnetic remanence at single isolated metal sites dispersed at the surface of a solid matrix has been envisioned as a key step toward information storage and processing in the smallest unit of matter. Here, we show that isolated Dy(III) sites distributed at the surface of silica nanoparticles, prepared with a simple and scalable two-step process, show magnetic remanence and display a hysteresis loop open at liquid 4He temperature, in contrast to the molecular precursor which does not display any magnetic memory. This singular behavior is achieved through the controlled grafting of a tailored Dy(III) siloxide complex on partially dehydroxylatedmore » silica nanoparticles followed by thermal annealing. This approach allows control of the density and the structure of isolated, “bare” Dy(III) sites bound to the silica surface. Throughout the process, all organic fragments are removed, leaving the surface as the sole ligand, promoting magnetic remanence.« less

MicroRNA-339-5p down-regulates protein expression of β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) in human primary brain cultures and is reduced in brain tissue specimens of Alzheimer disease subjects.

PubMed

Long, Justin M; Ray, Balmiki; Lahiri, Debomoy K

2014-02-21

Alzheimer disease (AD) results, in part, from the excess accumulation of the amyloid-β (Aβ) peptide as neuritic plaques in the brain. The short Aβ peptide is derived from the large transmembrane Aβ precursor protein (APP). The rate-limiting step in the production of Aβ from APP is mediated by the β-site APP-cleaving enzyme 1 (BACE1). Dysregulation of BACE1 levels leading to excess Aβ deposition is implicated in sporadic AD. Thus, elucidating the full complement of regulatory pathways that control BACE1 expression is key to identifying novel drug targets central to the Aβ-generating process. MicroRNAs (miRNAs) are expected to participate in this molecular network. Here, we identified a known miRNA, miR-339-5p, as a key contributor to this regulatory network. Two distinct miR-339-5p target sites were predicted in the BACE1 3'-UTR by in silico analyses. Co-transfection of miR-339-5p with a BACE1 3'-UTR reporter construct resulted in significant reduction in reporter expression. Mutation of both target sites eliminated this effect. Delivery of the miR-339-5p mimic also significantly inhibited expression of BACE1 protein in human glioblastoma cells and human primary brain cultures. Delivery of target protectors designed against the miR-339-5p BACE1 3'-UTR target sites in primary human brain cultures significantly elevated BACE1 expression. Finally, miR-339-5p levels were found to be significantly reduced in brain specimens isolated from AD patients as compared with age-matched controls. Therefore, miR-339-5p regulates BACE1 expression in human brain cells and is most likely dysregulated in at least a subset of AD patients making this miRNA a novel drug target.

MicroRNA-339-5p Down-regulates Protein Expression of β-Site Amyloid Precursor Protein-Cleaving Enzyme 1 (BACE1) in Human Primary Brain Cultures and Is Reduced in Brain Tissue Specimens of Alzheimer Disease Subjects*

PubMed Central

Long, Justin M.; Ray, Balmiki; Lahiri, Debomoy K.

2014-01-01

Alzheimer disease (AD) results, in part, from the excess accumulation of the amyloid-β (Aβ) peptide as neuritic plaques in the brain. The short Aβ peptide is derived from the large transmembrane Aβ precursor protein (APP). The rate-limiting step in the production of Aβ from APP is mediated by the β-site APP-cleaving enzyme 1 (BACE1). Dysregulation of BACE1 levels leading to excess Aβ deposition is implicated in sporadic AD. Thus, elucidating the full complement of regulatory pathways that control BACE1 expression is key to identifying novel drug targets central to the Aβ-generating process. MicroRNAs (miRNAs) are expected to participate in this molecular network. Here, we identified a known miRNA, miR-339-5p, as a key contributor to this regulatory network. Two distinct miR-339-5p target sites were predicted in the BACE1 3′-UTR by in silico analyses. Co-transfection of miR-339-5p with a BACE1 3′-UTR reporter construct resulted in significant reduction in reporter expression. Mutation of both target sites eliminated this effect. Delivery of the miR-339-5p mimic also significantly inhibited expression of BACE1 protein in human glioblastoma cells and human primary brain cultures. Delivery of target protectors designed against the miR-339-5p BACE1 3′-UTR target sites in primary human brain cultures significantly elevated BACE1 expression. Finally, miR-339-5p levels were found to be significantly reduced in brain specimens isolated from AD patients as compared with age-matched controls. Therefore, miR-339-5p regulates BACE1 expression in human brain cells and is most likely dysregulated in at least a subset of AD patients making this miRNA a novel drug target. PMID:24352696

Atomic and molecular oxygen adsorbed on (111) transition metal surfaces: Cu and Ni

NASA Astrophysics Data System (ADS)

López-Moreno, S.; Romero, A. H.

2015-04-01

Density functional theory is used to investigate the reaction of oxygen with clean copper and nickel [111]-surfaces. We study several alternative adsorption sites for atomic and molecular oxygen on both surfaces. The minimal energy geometries and adsorption energies are in good agreement with previous theoretical studies and experimental data. From all considered adsorption sites, we found a new O2 molecular precursor with two possible dissociation paths on the Cu(111) surface. Cross barrier energies for the molecular oxygen dissociation have been calculated by using the climbing image nudge elastic band method, and direct comparison with experimental results is performed. Finally, the structural changes and adsorption energies of oxygen adsorbed on surface when there is a vacancy nearby the adsorption site are also considered.

Atomic and molecular oxygen adsorbed on (111) transition metal surfaces: Cu and Ni.

PubMed

López-Moreno, S; Romero, A H

2015-04-21

Density functional theory is used to investigate the reaction of oxygen with clean copper and nickel [111]-surfaces. We study several alternative adsorption sites for atomic and molecular oxygen on both surfaces. The minimal energy geometries and adsorption energies are in good agreement with previous theoretical studies and experimental data. From all considered adsorption sites, we found a new O2 molecular precursor with two possible dissociation paths on the Cu(111) surface. Cross barrier energies for the molecular oxygen dissociation have been calculated by using the climbing image nudge elastic band method, and direct comparison with experimental results is performed. Finally, the structural changes and adsorption energies of oxygen adsorbed on surface when there is a vacancy nearby the adsorption site are also considered.

The SIQ-III Test: Gender Issues in Literacy

ERIC Educational Resources Information Center

Cassidy, Jack; Garcia, Roberto; Boggs, Merry

2005-01-01

The authors address concern in the field today about the literacy needs of boys. In a 1977 precursor to this article, it was literacy issues related to girls that appeared to command attention. As in that article and another preceding one, information is presented here as a true-false test. After taking the test, readers are provided with answers…

Developing an Undergraduate Assessment Test: A Mechanism for Faculty Feedback about Retention

ERIC Educational Resources Information Center

Callahan, Thomas J.; Strandholm, Karen; Dziekan, Julie

2010-01-01

A regional business school chose to self develop an assessment test of the fundamental concepts of the undergraduate business core. Above and beyond the demands of AACSB accreditation, faculty identified feedback from such a test as an essential precursor to changing both overall curriculum and individual class content. The authors describe the…

Cloning, expression and decoding of the cold adaptation of a new widely represented thermolabile subtilisin-like protease.

PubMed

Acevedo, J P; Rodriguez, V; Saavedra, M; Muñoz, M; Salazar, O; Asenjo, J A; Andrews, B A

2013-02-01

Cloning, expression and characterization of a new cold-adapted protease with potential biotechnological application, isolated from Antarctic bacteria. A subtilisin-like gene was isolated from several Antarctic bacterial genus using CODPEHOP-designed primers and a genome walking method. This gene encodes a precursor protein, which undergoes an autocatalytic cleavage resulting in a 34.6 kDa active cold-adapted protease with a maximum activity at 25-35°C and optimum pH of 8.0-9.0. It showed a higher catalytic efficiency at lower temperatures compared to its mesophilic counterpart. Heat-induced inactivation resulted in a very low melting point. Local packing analysis using the homology model indicated Ala284 as an important cold-adaptation determinant, which was corroborated by the site-directed mutagenesis. A new thermolabile subtilisin-like protease has been successfully cloned and analysed, and an important hot spot in the evolution of the cold adaptation and substrate specificity of this enzyme was identified and tested. This work reports a new cold-adapted protease with a vast representation amongst Antarctic genus, suggesting therefore its evolutionary success in this cold environment. Likewise, important sites for genetic potentiation have been identified, which are extrapolated to other enzymes of the same kind. © 2012 The Society for Applied Microbiology.

Radioactive cesium isotope ratios as a tool for determining dispersal and re-dispersal mechanisms downwind from the Nevada Nuclear Security Site.

PubMed

Snyder, Darin C; Delmore, James E; Tranter, Troy; Mann, Nick R; Abbott, Michael L; Olson, John E

2012-08-01

Fractionation of the two longer-lived radioactive cesium isotopes ((135)Cs and (137)Cs) produced by above ground nuclear tests have been measured and used to clarify the dispersal mechanisms of cesium deposited in the area between the Nevada Nuclear Security Site and Lake Mead in the southwestern United States. Fractionation of these isotopes is due to the 135-decay chain requiring several days to completely decay to (135)Cs, and the 137-decay chain less than one hour decay to (137)Cs. Since the Cs precursors are gases, iodine and xenon, the (135)Cs plume was deposited farther downwind than the (137)Cs plume. Sediment core samples were obtained from the Las Vegas arm of Lake Mead, sub-sampled and analyzed for (135)Cs/(137)Cs ratios by thermal ionization mass spectrometry. The layers proved to have nearly identical highly fractionated isotope ratios. This information is consistent with a model where the cesium was initially deposited onto the land area draining into Lake Mead and the composite from all of the above ground shots subsequently washed onto Lake Mead by high intensity rain and wind storms producing a layering of Cs activity, where each layer is a portion of the composite. Copyright © 2012 Elsevier Ltd. All rights reserved.

Peroxyl radical reactions with carotenoids in microemulsions: Influence of microemulsion composition and the nature of peroxyl radical precursor.

PubMed

El-Agamey, Ali; McGarvey, David J

2016-01-01

The reactions of acetylperoxyl radicals with different carotenoids (7,7'-dihydro-β-carotene and ζ-carotene) in SDS and CTAC microemulsions of different compositions were investigated using laser flash photolysis (LFP) coupled with kinetic absorption spectroscopy. The primary objective of this study was to explore the influence of microemulsion composition and the type of surfactant used on the yields and kinetics of various transients formed from the reaction of acetylperoxyl radicals with carotenoids. Also, the influence of the site (hydrocarbon phases or aqueous phase) of generation of the peroxyl radical precursor was examined by using 4-acetyl-4-phenylpiperidine hydrochloride (APPHCl) and 1,1-diphenylacetone (11DPA) as water-soluble and lipid-soluble peroxyl radical precursors, respectively. LFP of peroxyl radical precursors with 7,7'-dihydro-β-carotene (77DH) in different microemulsions gives rise to the formation of three distinct transients namely addition radical (λmax=460 nm), near infrared transient1 (NIR, λmax=700 nm) and 7,7'-dihydro-β-carotene radical cation (77DH(•+), λmax=770 nm). In addition, for ζ-carotene (ZETA) two transients (near infrared transient1 (NIR1, λmax=660 nm) and ζ-carotene radical cation (ZETA(•+), λmax=730-740 nm)) are generated following LFP of peroxyl radical precursors in the presence of ζ-carotene (ZETA) in different microemulsions. The results show that the composition of the microemulsion strongly influences the observed yield and kinetics of the transients formed from the reactions of peroxyl radicals (acetylperoxyl radicals) with carotenoids (77DH and ZETA). Also, the type of surfactant used in the microemulsions influences the yield of the transients formed. The dependence of the transient yields and kinetics on microemulsion composition (or the type of surfactant used in the microemulsion) can be attributed to the change of the polarity of the microenvironment of the carotenoid. Furthermore, the nature of the peroxyl radical precursor used (water-soluble or lipid-soluble peroxyl radical precursors) has little influence on the yields and kinetics of the transients formed from the reaction of peroxyl radicals with carotenoids. In the context of the interest in carotenoids as radical scavenging antioxidants, the fates of the addition radicals (formed from the reaction of carotenoid with peroxyl radicals) and carotenoid radical cations are discussed. Copyright © 2015 Elsevier Inc. All rights reserved.

In vitro biosynthesis of 17 alpha,20 alpha,20 beta-dihydroxy-4-pegnen-3-one by the ovaries, testes, and head kidneys of the Atlantic salmon Salmo salar

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

Sangalang, G.B.; Freeman, H.C.

Ovaries, testes, and head kidneys of sexually mature Atlantic salmon, Salmo salar, biosynthesized 17 alpha,20 beta-dihydroxy-4-pregnen-3-one (17 alpha,20 beta-diOHP) from equimolar amounts of (/sup 3/H)pregnenolone plus (4-/sup 14/C)progesterone in vitro. The /sup 3/H:/sup 14/C isotope ratios of steroid metabolites indicated that the biosynthetic pathways to 17 alpha,20 beta-diOHP in the testes differed from those observed in the ovaries and head kidneys. (4-/sup 14/C)progesterone appeared to be the principal precursor of 17 alpha,20 beta-diOHP in the testes, whereas both precursors were efficiently biotransformed to 17 alpha,20 beta-diOPH in the ovaries and head kidneys. 17 alpha-Hydroxy-4-pregnen-3-one (17 alpha-OHP) was the immediate precursormore » to 17 alpha,20 beta-diOHP in all tissues. However, appreciable amounts of 17 alpha,20 beta-diOHP accumulated in vitro in the testes only in the presence of exogenous (/sup 14/C)progesterone. Incubation of the testes, ovaries, and head kidneys with (/sup 14/C)pregnenolone resulted in high yields of 17 alpha,20 beta-diOHP in the ovaries and head kidneys but no detectable amounts of the steroid in the testes. The results confirm that progesterone is the favored precursor to 17 alpha,20 beta-diOHP in the testes. The results also suggest that the head kidneys may be an excellent cellular source of 17 alpha,20 beta-diOHP in both male and female. Atlantic salmon and may play an important role in the sexual maturation process in this fish. It is suggested that biosynthetic control mechanism affecting 17 alpha,20 beta-diOHP synthesis and/or spermiation and ovulation may differ in male and female Atlantic salmon.« less

In vitro genotoxicity assessment of MTES, GPTES and TEOS, three precursors intended for use in food contact coatings.

PubMed

Lionti, Krystelle; Séverin, Isabelle; Dahbi, Laurence; Toury, Bérangère; Chagnon, Marie-Christine

2014-03-01

Organoalkoxysilanes are precursors that are used increasingly in the synthesis of food contact coatings. To comply with the EU regulation, their potential toxicity must be assessed, and very little information is known. The genotoxicity of three common precursors was studied, namely, tetraethylorthosilicate (TEOS), methyltriethoxysilane (MTES) and 3-glycidyloxypropyltriethoxysilane (GPTES). By the Ames test, MTES and TEOS were not mutagenic for bacteria. A significant positive response was observed with GPTES in the TA100 and TA1535 strains. The mutagenic effect was more pronounced in the presence of the exogenous metabolic activation system with an increase of the induction factor (ten-fold higher for the TA1535 strain). In the micronucleus assay performed with a human hepatoma cell line (HepG2 cells), GPTES gave negative results even in the presence of an exogenous activation system. To ascertain the possibility of using this precursor in food contact material, its migration must be monitored according to the coating formulation because migration might result in hazardous human exposure. Copyright © 2014. Published by Elsevier Ltd.

Amyloid-like aggregation of provasopressin in diabetes insipidus and secretory granule sorting.

PubMed

Beuret, Nicole; Hasler, Franziska; Prescianotto-Baschong, Cristina; Birk, Julia; Rutishauser, Jonas; Spiess, Martin

2017-01-26

Aggregation of peptide hormone precursors in the trans-Golgi network is an essential process in the biogenesis of secretory granules in endocrine cells. It has recently been proposed that this aggregation corresponds to the formation of functional amyloids. Our previous finding that dominant mutations in provasopressin, which cause cell degeneration and diabetes insipidus, prevent native folding and produce fibrillar aggregates in the endoplasmic reticulum (ER) might thus reflect mislocalized amyloid formation by sequences that evolved to mediate granule sorting. Here we identified two sequences responsible for fibrillar aggregation of mutant precursors in the ER: the N-terminal vasopressin nonapeptide and the C-terminal glycopeptide. To test their role in granule sorting, the glycopeptide was deleted and/or vasopressin mutated to inactivate ER aggregation while still permitting precursor folding and ER exit. These mutations strongly reduced sorting into granules and regulated secretion in endocrine AtT20 cells. The same sequences - vasopressin and the glycopeptide - mediate physiological aggregation of the wild-type hormone precursor into secretory granules and the pathological fibrillar aggregation of disease mutants in the ER. These findings support the amyloid hypothesis for secretory granule biogenesis.

Production of jet fuel precursor monoterpenoids from engineered Escherichia coli.

PubMed

Mendez-Perez, Daniel; Alonso-Gutierrez, Jorge; Hu, Qijun; Molinas, Margaux; Baidoo, Edward E K; Wang, George; Chan, Leanne J G; Adams, Paul D; Petzold, Christopher J; Keasling, Jay D; Lee, Taek S

2017-08-01

Monoterpenes (C 10 isoprenoids) are the main components of essential oils and are possible precursors for many commodity chemicals and high energy density fuels. Monoterpenes are synthesized from geranyl diphosphate (GPP), which is also the precursor for the biosynthesis of farnesyl diphosphate (FPP). FPP biosynthesis diverts the carbon flux from monoterpene production to C 15 products and quinone biosynthesis. In this study, we tested a chromosomal mutation of Escherichia coli's native FPP synthase (IspA) to improve GPP availability for the production of monoterpenes using a heterologous mevalonate pathway. Monoterpene production at high levels required not only optimization of GPP production but also a basal level of FPP to maintain growth. The optimized strains produced two jet fuel precursor monoterpenoids 1,8-cineole and linalool at the titer of 653 mg/L and 505 mg/L, respectively, in batch cultures with 1% glucose. The engineered strains developed in this work provide useful resources for the production of high-value monoterpenes. Biotechnol. Bioeng. 2017;114: 1703-1712. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

cGMP production of patient-specific iPSCs and photoreceptor precursor cells to treat retinal degenerative blindness

PubMed Central

Wiley, Luke A.; Burnight, Erin R.; DeLuca, Adam P.; Anfinson, Kristin R.; Cranston, Cathryn M.; Kaalberg, Emily E.; Penticoff, Jessica A.; Affatigato, Louisa M.; Mullins, Robert F.; Stone, Edwin M.; Tucker, Budd A.

2016-01-01

Immunologically-matched, induced pluripotent stem cell (iPSC)-derived photoreceptor precursor cells have the potential to restore vision to patients with retinal degenerative diseases like retinitis pigmentosa. The purpose of this study was to develop clinically-compatible methods for manufacturing photoreceptor precursor cells from adult skin in a non-profit cGMP environment. Biopsies were obtained from 35 adult patients with inherited retinal degeneration and fibroblast lines were established under ISO class 5 cGMP conditions. Patient-specific iPSCs were then generated, clonally expanded and validated. Post-mitotic photoreceptor precursor cells were generated using a stepwise cGMP-compliant 3D differentiation protocol. The recapitulation of the enhanced S-cone phenotype in retinal organoids generated from a patient with NR2E3 mutations demonstrated the fidelity of these protocols. Transplantation into immune compromised animals revealed no evidence of abnormal proliferation or tumor formation. These studies will enable clinical trials to test the safety and efficiency of patient-specific photoreceptor cell replacement in humans. PMID:27471043

Vision Screening by Color Photography

NASA Technical Reports Server (NTRS)

Jayroe, R.; Richardson, J. R.; Kerr, J.; Hay, S.; Mcbride, R.

1985-01-01

Screening test developed for detecting a range of vision defects in eye, including common precursors to amblyopia. Test noninvasive, safe, and administered easily in field by operator with no medical training. Only minimal momentary cooperation of subject required: Thus, test shows promise for use with very young children. Test produces color-slide images of retinas of eyes under specially-controlled lighting conditions. Trained observer screens five children per minute.

A 3-dimensional human embryonic stem cell (hESC)-derived model to detect developmental neurotoxicity of nanoparticles.

PubMed

Hoelting, Lisa; Scheinhardt, Benjamin; Bondarenko, Olesja; Schildknecht, Stefan; Kapitza, Marion; Tanavde, Vivek; Tan, Betty; Lee, Qian Yi; Mecking, Stefan; Leist, Marcel; Kadereit, Suzanne

2013-04-01

Nanoparticles (NPs) have been shown to accumulate in organs, cross the blood-brain barrier and placenta, and have the potential to elicit developmental neurotoxicity (DNT). Here, we developed a human embryonic stem cell (hESC)-derived 3-dimensional (3-D) in vitro model that allows for testing of potential developmental neurotoxicants. Early central nervous system PAX6(+) precursor cells were generated from hESCs and differentiated further within 3-D structures. The 3-D model was characterized for neural marker expression revealing robust differentiation toward neuronal precursor cells, and gene expression profiling suggested a predominantly forebrain-like development. Altered neural gene expression due to exposure to non-cytotoxic concentrations of the known developmental neurotoxicant, methylmercury, indicated that the 3-D model could detect DNT. To test for specific toxicity of NPs, chemically inert polyethylene NPs (PE-NPs) were chosen. They penetrated deep into the 3-D structures and impacted gene expression at non-cytotoxic concentrations. NOTCH pathway genes such as HES5 and NOTCH1 were reduced in expression, as well as downstream neuronal precursor genes such as NEUROD1 and ASCL1. FOXG1, a patterning marker, was also reduced. As loss of function of these genes results in severe nervous system impairments in mice, our data suggest that the 3-D hESC-derived model could be used to test for Nano-DNT.

Pleiotropic analysis of cancer risk loci on esophageal adenocarcinoma risk

PubMed Central

Lee, Eunjung; Stram, Daniel O.; Ek, Weronica E.; Onstad, Lynn E; MacGregor, Stuart; Gharahkhani, Puya; Ye, Weimin; Lagergren, Jesper; Shaheen, Nicholas J.; Murray, Liam J.; Hardie, Laura J; Gammon, Marilie D.; Chow, Wong-Ho; Risch, Harvey A.; Corley, Douglas A.; Levine, David M; Whiteman, David C.; Bernstein, Leslie; Bird, Nigel C.; Vaughan, Thomas L.; Wu, Anna H.

2015-01-01

Background Several cancer-associated loci identified from genome-wide association studies (GWAS) have been associated with risks of multiple cancer sites, suggesting pleiotropic effects. We investigated whether GWAS-identified risk variants for other common cancers are associated with risk of esophageal adenocarcinoma (EA) or its precursor, Barrett's esophagus (BE). Methods We examined the associations between risks of EA and BE and 387 single nucleotide polymorphisms (SNPs) that have been associated with risks of other cancers, by using genotype imputation data on 2,163 control participants and 3,885 (1,501 EA and 2,384 BE) case patients from the Barrett's and Esophageal Adenocarcinoma Genetic Susceptibility Study, and investigated effect modification by smoking history, body mass index (BMI), and reflux/heartburn. Results After correcting for multiple testing, none of the tested 387 SNPs were statistically significantly associated with risk of EA or BE. No evidence of effect modification by smoking, BMI, or reflux/heartburn was observed. Conclusions Genetic risk variants for common cancers identified from GWAS appear not to be associated with risks of EA or BE. Impact To our knowledge, this is the first investigation of pleiotropic genetic associations with risks of EA and BE. PMID:26364162

Injectable visible light-cured glycol chitosan hydrogels with controlled release of anticancer drugs for local cancer therapy in vivo: a feasible study.

PubMed

Hyun, Hoon; Park, Min Ho; Lim, Wonbong; Kim, So Yeon; Jo, Danbi; Jung, Jin Seok; Jo, Gayoung; Um, Sewook; Lee, Deok-Won; Yang, Dae Hyeok

2018-05-11

Currently available chemotherapy is associated with serious side effects, and therefore novel drug delivery systems (DDSs) are required to specifically deliver anticancer drugs to targeted sites. In this study, we evaluated the feasibility of visible light-cured glycol chitosan (GC) hydrogels with controlled release of doxorubicin⋅hydrochloride (DOX⋅HCl) as local DDSs for effective cancer therapy in vivo. The storage modulus of the hydrogel precursor solutions was increased as a function of visible light irradiation time. In addition, the swelling ratio of the hydrogel irradiated for 10 s (GC 10 /DOX) was greater than in 60 s (GC 60 /DOX). In vitro release test showed that DOX was rapidly released in GC 10 /DOX compared with GC 60 /DOX due to the density of cross-linking. In vitro and in vivo tests including cell viability and measurement of tumor volume showed that the local treatment of GC 10 /DOX yielded substantially greater antitumor effect compared with that of GC 60 /DOX. Therefore, the visible light-cured GC hydrogel system may exhibit clinical potential as a local DDS of anticancer drugs with controlled release, by modulating cross-linking density.

Progress of the Mars Array Technology Experiment (MATE) on the 2001 Lander

NASA Technical Reports Server (NTRS)

Scheiman, David A.; Baraona, Cosmo; Wilt, Dave; Jenkins, Phil; Krasowski, Michael; Greer, Lawrence; Lekki, John; Spina, Daniel; Landis, Geoff

2005-01-01

NASA is planning missions to Mars every two years until 2010, these missions will rely on solar power. Sunlight on the surface of Mars is altered by airborne dust and fluctuates from day to day. The MATE flight experiment was designed to evaluate solar cell performance and will fly on the Mars 2001 surveyor Lander as part of the Mars In-Situ Propellant Production Precursor (MIP) package. MATE will measure several solar cell technologies and characterize the Martian environment's solar power. This will be done by measuring full IV curvers on solar cells, direct and global insolation, temperature, and spectral content. The lander is scheduled to launch in April 2001 and arrive on Mars in January of 2002. The site location has not been identified but will be near the equator, is a powered landing, and is baselined for 90 sols. The intent of this paper is to provide a brief overview of the MATE experiment and progress to date. The MATE Development Unit (DU) hardware has been built and has completed testing, work is beginning in the Qualification Unit which will start testing later this year, Flight Hardware is to be delivered next spring.

Climatic Zones, Soil Moisture Seasonality and Biomass Burning and Their Influence On Ozone Precursor Concentrations Over West Africa as Retrieved from Satellites

NASA Astrophysics Data System (ADS)

Onojeghuo, A. R.; Balzter, H.; Monks, P. S.

2015-12-01

West Africa is a region with six different climatic zones including a rich savannah affected by biomass burning annually, the Niger delta oil producing region with major gas flaring sites and a long coastline. Research on atmospheric pollution using remotely sensed data over West Africa has mostly been conducted at regional scale or for individual countries, with little emphasis on the dynamics of climatic zones and the diversity of land cover types. This study analyses annual seasonal dynamics of emissions of two ozone precursors stratified by climatic zone: nitrogen dioxide (NO2) from OMI and carbon monoxide (CO) from TES. The different sources of these pollutants and their seasonality are explicitly considered. Results indicate that the highest annual wet season NO2 column concentrations were in the semi-arid zone (1.33 x 1015 molecules cm-2) after prolonged periods of low soil moisture while the highest dry season were observed in the wet sub-humid zone (2.62 x 1015 molecules cm-2) where the savannah fires occur annually. The highest annual CO concentrations (> 3.1 x 1018 molecules cm-2) were from the Niger Delta, located in the humid zone. There were indications of atmospheric transport of CO from the southern hemisphere in the west season. Climate change induced soil moisture variability was most prominent in the dry sub-humid and semi-arid climatic zones (±0.015m3m-3) . The causal effects of soil moisture variability on NO2 emissions and their seasonal cycles were tested using the Granger causality test. Causal effects of inter-zonal exchanges/transport of NO2 and CO emissions respectively were inferred using Directed Acyclic Graphs. The results indicate that NO2, CO and their seasonal ratios are strongly affected by changes in soil moisture.

Monitoring of precursor landslide surface deformation using InSAR image in Kuchi-Sakamoto, Shizuoka Prefecture, Japan

NASA Astrophysics Data System (ADS)

Sato, H. P.; Nakajima, H.; Nakano, T.; Daimaru, H.

2014-12-01

Synthetic Aperture Radar (SAR) is the technique to obtain ground surface images using microwave that is emitted from and received on the antenna. The Kuchi-Sakamoto area, 2.2 km2 in precipitous mountains, central Japan, has suffered from frequent landslides, and slow landslide surface deformation has been monitored by on-site extensometer; however, such the monitoring method cannot detect the deformation in the whole area. Because satellite InSAR is effective tool to monitor slow landslide suface deformation, it is a promising tool for detecting precursor deformation and preparing effective measures against serious landslide disasters. In this study Advanced Land Observing Satellite (ALOS) / Phased Array type L-band SAR (PALSAR) data were used, and InSAR images were produced from the PALSAR data that were observed between 5 Sep 2008 and 21 Oct 2008 (from descending orbit) and between 20 Jul 2008 and 7 Sep 2009 (from ascending orbit). InSAR image from descending orbit was found to detect clear precursor landslide surface deformation on a slope; however, InSAR image on ascending orbit did not always detect clear precursor deformation. It is thought to be related with atmospheric moisture condition, length of observation baseline and so on. Furthermore, after phase unwrapping on InSAR images, 2.5-dimensional deformation was analized. This analysis needed both ascending and descending InSAR images and culculated quasi east-west deformation component (Figs. (a) and (b)) and quasi up-down deformation component (Figs. (c) and (d)). The resulting 2.5D calculation gave westward deformation and mixture of upward and downward deformations on the precursor landslide surface deformation slope (blue circles in Figs. (c) and (d)), where remarkable disrupted deep landslide occurred during Nov 2012 and 25 Jun 2013, judging from result of airborne LiDAR survey and field survey; the occurrence date is not precisely identified. The figure remains the issue that eliminating "real" precursor deformation from other candidate deformations. Preparation of this paper was supported by part of Individual Research Fund in College of Humanities and Sciences, Nihon University and part of Grants-in-Aid for Scientific Research, Challenging Exploratory (#25560185, Principal Investigator: Dr. Hiromu Daimaru).

Atomic Layer Deposition of GeSe Films Using HGeCl3 and [(CH3)3Si]2Se with the Discrete Feeding Method for the Ovonic Threshold Switch.

PubMed

Kim, Woohyun; Yoo, Sijung; Yoo, Chanyoung; Park, Eui-Sang; Jeon, Jeongwoo; Kwon, Young Jae; Woo, Kyung Seok; Kim, Han Joon; Lee, Yoon Kyeung; Hwang, Cheol Seong

2018-06-19

The ovonic threshold switch (OTS) based on the voltage snapback of amorphous chalcogenides possesses several desirable characteristics for passive memory array. Among the materials that can be used as OTS, GeSe has a strong glass-forming ability (~350°C crystallization temperature), with a simple binary composition. Described herein is a new method of depositing GeSe films through atomic layer deposition (ALD), in which HGeCl3 and [(CH3)3Si]2Se are used as Ge and Se precursors, respectively. The stoichiometric GeSe thin films were formed through a ligand exchange reaction between the two precursor molecules, without the adoption of an additional reaction gas, at low substrate temperatures ranging from 70 to 150°C. The pseudo-saturation behavior of ALD, however, which requires a long time to achieve the saturation growth rate, was observed. This was due to the adverse influence of the physisorbed precursor and byproduct molecules on the efficient chemical adsorption reaction between the precursors and reaction sites. To overcome the slow saturation and excessive use of the Ge precursor, the discrete feeding method (DFM), where HGeCl3 is supplied multiple times consecutively with subdivided pulse times, was adopted. DFM led to the saturation of the GeSe growth rate at a much shorter total injection time of the Ge precursor, and improved the film density and oxidation resistance properties. The GeSe film grown via DFM exhibited a short OTS time of ~40 ns, a ~107 ON/OFF current ratio, and ~104 selectivity. The OTS behavior was consistent with the modified Poole-Frenkel (PF) mechanism in the OFF state. In contrast, the similar GeSe film grown through the conventional ALD showed a low density and high vulnerability to oxidation, which prevented the OTS performance. The ALD method of GeSe films introduced here will contribute to the fabrication of a three-dimensionally integrated memory as a selector device for preventing sneak current. © 2018 IOP Publishing Ltd.

Surface passivation of Fe{sub 3}O{sub 4} nanoparticles with Al{sub 2}O{sub 3} via atomic layer deposition in a rotating fluidized bed reactor

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

Duan, Chen-Long; Deng, Zhang; Cao, Kun

2016-07-15

Iron(II,III) oxide (Fe{sub 3}O{sub 4}) nanoparticles have shown great promise in many magnetic-related applications such as magnetic resonance imaging, hyperthermia treatment, and targeted drug delivery. Nevertheless, these nanoparticles are vulnerable to oxidation and magnetization loss under ambient conditions, and passivation is usually required for practical applications. In this work, a home-built rotating fluidized bed (RFB) atomic layer deposition (ALD) reactor was employed to form dense and uniform nanoscale Al{sub 2}O{sub 3} passivation layers on Fe{sub 3}O{sub 4} nanoparticles. The RFB reactor facilitated the precursor diffusion in the particle bed and intensified the dynamic dismantling of soft agglomerates, exposing every surfacemore » reactive site to precursor gases. With the aid of in situ mass spectroscopy, it was found that a thicker fluidization bed formed by larger amount of particles increased the residence time of precursors. The prolonged residence time allowed more thorough interactions between the particle surfaces and the precursor gas, resulting in an improvement of the precursor utilization from 78% to nearly 100%, even under a high precursor feeding rate. Uniform passivation layers around the magnetic cores were demonstrated by both transmission electron microscopy and the statistical analysis of Al mass concentrations. Individual particles were coated instead of the soft agglomerates, as was validated by the specific surface area analysis and particle size distribution. The results of thermogravimetric analysis suggested that 5 nm-thick ultrathin Al{sub 2}O{sub 3} coatings could effectively protect the Fe{sub 3}O{sub 4} nanoparticles from oxidation. The x-ray diffraction patterns also showed that the magnetic core crystallinity of such passivated nanoparticles could be well preserved under accelerated oxidation conditions. The precise thickness control via ALD maintained the saturation magnetization at 66.7 emu/g with a 5 nm-thick Al{sub 2}O{sub 3} passivation layer. This good preservation of the magnetic properties with superior oxidation resistance will be beneficial for practical magnetic-based applications.« less

Estimating contribution of wildland fires to ambient ozone levels in National Parks in the Sierra Nevada, California

Treesearch

Haiganoush K. Preisler; Shiyuan (Sharon) Zhong; Annie Esperanza; Timothy J. Brown; Andrzej Bytnerowicz; Leland Tarnay

2010-01-01

Data from four continuous ozone and weather monitoring sites operated by the National Park Service in Sierra Nevada, California, are used to develop an ozone forecasting model and to estimate the contribution of wildland fires on ambient ozone levels. The analyses of weather and ozone data pointed to the transport of ozone precursors from the Central Valley as an...

Large Population-Based Study Reveals Disparities in Myeloma Precursor Disease | Center for Cancer Research

Cancer.gov

Multiple myeloma (MM) is a cancer of plasma cells, which are antibody-producing white blood cells. Patients with MM have a characteristic excess of monoclonal antibodies, so called M proteins, in their serum, urine, or both and plasma cell infiltration into their bone marrow at multiple sites. African Americans are more than twice as likely as whites to develop MM, but the

Ten-year helium anomaly prior to the 2014 Mt Ontake eruption

PubMed Central

Sano, Yuji; Kagoshima, Takanori; Takahata, Naoto; Nishio, Yoshiro; Roulleau, Emilie; Pinti, Daniele L.; Fischer, Tobias P.

2015-01-01

Mt Ontake in central Japan suddenly erupted on 27th September 2014, killing 57 people with 6 still missing. It was a hydro-volcanic eruption and new magmatic material was not detected. There were no precursor signals such as seismicity and edifice inflation. It is difficult to predict hydro-volcanic eruptions because they are local phenomena that only affect a limited area surrounding the explosive vent. Here we report a long-term helium anomaly measured in hot springs close to the central cone. Helium-3 is the most sensitive tracer of magmatic volatiles. We have conducted spatial surveys around the volcano at once per few years since November 1981. The 3He/4He ratios of the closest site to the cone stayed constant until June 2000 and increased significantly from June 2003 to November 2014, while those of distant sites showed no valuable change. These observations suggest a recent re-activation of Mt Ontake and that helium-3 enhancement may have been a precursor of the 2014 eruption. We show that the eruption was ultimately caused by the increased input of magmatic volatiles over a ten-year period which resulted in the slow pressurization of the volcanic conduit leading to the hydro-volcanic event in September 2014. PMID:26286468

Lipid synthesis under hydrothermal conditions by Fischer-Tropsch-type reactions

NASA Technical Reports Server (NTRS)

McCollom, T. M.; Ritter, G.; Simoneit, B. R.

1999-01-01

Ever since their discovery in the late 1970's, mid-ocean-ridge hydrothermal systems have received a great deal of attention as a possible site for the origin of life on Earth (and environments analogous to mid-ocean-ridge hydrothermal systems are postulated to have been sites where life could have originated or Mars and elsewhere as well). Because no modern-day terrestrial hydrothermal systems are free from the influence of organic compounds derived from biologic processes, laboratory experiments provide the best opportunity for confirmation of the potential for organic synthesis in hydrothermal systems. Here we report on the formation of lipid compounds during Fischer-Tropsch-type synthesis from aqueous solutions of formic acid or oxalic acid. Optimum synthesis occurs in stainless steel vessels by heating at 175 degrees C for 2-3 days and produces lipid compounds ranging from C2 to > C35 which consist of n-alkanols, n-alkanoic acids, n-alkenes, n-alkanes and alkanones. The precursor carbon sources used are either formic acid or oxalic acid, which disproportionate to H2, CO2 and probably CO. Both carbon sources yield the same lipid classes with essentially the same ranges of compounds. The synthesis reactions were confirmed by using 13C labeled precursor acids.

Phosphopeptidomics Reveals Differential Phosphorylation States and Novel SxE Phosphosite Motifs of Neuropeptides in Dense Core Secretory Vesicles

NASA Astrophysics Data System (ADS)

Lietz, Christopher B.; Toneff, Thomas; Mosier, Charles; Podvin, Sonia; O'Donoghue, Anthony J.; Hook, Vivian

2018-05-01

Neuropeptides are vital for cell-cell communication and function in the regulation of the nervous and endocrine systems. They are generated by post-translational modification (PTM) steps resulting in small active peptides generated from prohormone precursors. Phosphorylation is a significant PTM for the bioactivity of neuropeptides. From the known diversity of distinct neuropeptide functions, it is hypothesized that the extent of phosphorylation varies among different neuropeptides. To assess this hypothesis, neuropeptide-containing dense core secretory vesicles from bovine adrenal medullary chromaffin cells were subjected to global phosphopeptidomics analyses by liquid chromatography (LC)-mass spectrometry (MS/MS). Phosphopeptides were identified directly by LC-MS/MS and indirectly by phosphatase treatment followed by LC-MS/MS. The data identified numerous phosphorylated peptides derived from neuropeptide precursors such as chromogranins, secretogranins, proenkephalin and pro-NPY. Phosphosite occupancies were observed at high and low levels among identified peptides and many of the high occupancy phosphopeptides represent prohormone-derived peptides with currently unknown bioactivities. Peptide sequence analyses demonstrated SxE as the most prevalent phosphorylation site motif, corresponding to phosphorylation sites of the Fam20C protein kinase known to be present in the secretory pathway. The range of high to low phosphosite occupancies for neuropeptides demonstrates cellular regulation of neuropeptide phosphorylation. [Figure not available: see fulltext.

Phosphopeptidomics Reveals Differential Phosphorylation States and Novel SxE Phosphosite Motifs of Neuropeptides in Dense Core Secretory Vesicles

NASA Astrophysics Data System (ADS)

Lietz, Christopher B.; Toneff, Thomas; Mosier, Charles; Podvin, Sonia; O'Donoghue, Anthony J.; Hook, Vivian

2018-03-01

Neuropeptides are vital for cell-cell communication and function in the regulation of the nervous and endocrine systems. They are generated by post-translational modification (PTM) steps resulting in small active peptides generated from prohormone precursors. Phosphorylation is a significant PTM for the bioactivity of neuropeptides. From the known diversity of distinct neuropeptide functions, it is hypothesized that the extent of phosphorylation varies among different neuropeptides. To assess this hypothesis, neuropeptide-containing dense core secretory vesicles from bovine adrenal medullary chromaffin cells were subjected to global phosphopeptidomics analyses by liquid chromatography (LC)-mass spectrometry (MS/MS). Phosphopeptides were identified directly by LC-MS/MS and indirectly by phosphatase treatment followed by LC-MS/MS. The data identified numerous phosphorylated peptides derived from neuropeptide precursors such as chromogranins, secretogranins, proenkephalin and pro-NPY. Phosphosite occupancies were observed at high and low levels among identified peptides and many of the high occupancy phosphopeptides represent prohormone-derived peptides with currently unknown bioactivities. Peptide sequence analyses demonstrated SxE as the most prevalent phosphorylation site motif, corresponding to phosphorylation sites of the Fam20C protein kinase known to be present in the secretory pathway. The range of high to low phosphosite occupancies for neuropeptides demonstrates cellular regulation of neuropeptide phosphorylation. [Figure not available: see fulltext.

Ten-year helium anomaly prior to the 2014 Mt Ontake eruption

NASA Astrophysics Data System (ADS)

Sano, Yuji; Kagoshima, Takanori; Takahata, Naoto; Nishio, Yoshiro; Roulleau, Emilie; Pinti, Daniele L.; Fischer, Tobias P.

2015-08-01

Mt Ontake in central Japan suddenly erupted on 27th September 2014, killing 57 people with 6 still missing. It was a hydro-volcanic eruption and new magmatic material was not detected. There were no precursor signals such as seismicity and edifice inflation. It is difficult to predict hydro-volcanic eruptions because they are local phenomena that only affect a limited area surrounding the explosive vent. Here we report a long-term helium anomaly measured in hot springs close to the central cone. Helium-3 is the most sensitive tracer of magmatic volatiles. We have conducted spatial surveys around the volcano at once per few years since November 1981. The 3He/4He ratios of the closest site to the cone stayed constant until June 2000 and increased significantly from June 2003 to November 2014, while those of distant sites showed no valuable change. These observations suggest a recent re-activation of Mt Ontake and that helium-3 enhancement may have been a precursor of the 2014 eruption. We show that the eruption was ultimately caused by the increased input of magmatic volatiles over a ten-year period which resulted in the slow pressurization of the volcanic conduit leading to the hydro-volcanic event in September 2014.

Lipid Synthesis Under Hydrothermal Conditions by Fischer- Tropsch-Type Reactions

NASA Astrophysics Data System (ADS)

McCollom, Thomas M.; Ritter, Gilles; Simoneit, Bernd R. T.

1999-03-01

Ever since their discovery in the late 1970's, mid-ocean-ridge hydrothermal systems have received a great deal of attention as a possible site for the origin of life on Earth (and environments analogous to mid-ocean-ridge hydrothermal systems are postulated to have been sites where life could have originated on Mars and elsewhere as well). Because no modern-day terrestrial hydrothermal systems are free from the influence of organic compounds derived from biologic processes, laboratory experiments provide the best opportunity for confirmation of the potential for organic synthesis in hydrothermal systems. Here we report on the formation of lipid compounds during Fischer-Tropsch-type synthesis from aqueous solutions of formic acid or oxalic acid. Optimum synthesis occurs in stainless steel vessels by heating at 175 °C for 2-3 days and produces lipid compounds ranging from C2 to >C35 which consist of n-alkanols, n- alkanoic acids, n-alkenes, n-alkanes and alkanones. The precursor carbon sources used are either formic acid or oxalic acid, which disproportionate to H2, CO2 and probably CO. Both carbon sources yield the same lipid classes with essentially the same ranges of compounds. The synthesis reactions were confirmed by using 13C labeled precursor acids.

Lipid synthesis under hydrothermal conditions by Fischer-Tropsch-type reactions.

PubMed

McCollom, T M; Ritter, G; Simoneit, B R

1999-03-01

Ever since their discovery in the late 1970's, mid-ocean-ridge hydrothermal systems have received a great deal of attention as a possible site for the origin of life on Earth (and environments analogous to mid-ocean-ridge hydrothermal systems are postulated to have been sites where life could have originated or Mars and elsewhere as well). Because no modern-day terrestrial hydrothermal systems are free from the influence of organic compounds derived from biologic processes, laboratory experiments provide the best opportunity for confirmation of the potential for organic synthesis in hydrothermal systems. Here we report on the formation of lipid compounds during Fischer-Tropsch-type synthesis from aqueous solutions of formic acid or oxalic acid. Optimum synthesis occurs in stainless steel vessels by heating at 175 degrees C for 2-3 days and produces lipid compounds ranging from C2 to > C35 which consist of n-alkanols, n-alkanoic acids, n-alkenes, n-alkanes and alkanones. The precursor carbon sources used are either formic acid or oxalic acid, which disproportionate to H2, CO2 and probably CO. Both carbon sources yield the same lipid classes with essentially the same ranges of compounds. The synthesis reactions were confirmed by using 13C labeled precursor acids.

Ten-year helium anomaly prior to the 2014 Mt Ontake eruption.

PubMed

Sano, Yuji; Kagoshima, Takanori; Takahata, Naoto; Nishio, Yoshiro; Roulleau, Emilie; Pinti, Daniele L; Fischer, Tobias P

2015-08-19

Mt Ontake in central Japan suddenly erupted on 27(th) September 2014, killing 57 people with 6 still missing. It was a hydro-volcanic eruption and new magmatic material was not detected. There were no precursor signals such as seismicity and edifice inflation. It is difficult to predict hydro-volcanic eruptions because they are local phenomena that only affect a limited area surrounding the explosive vent. Here we report a long-term helium anomaly measured in hot springs close to the central cone. Helium-3 is the most sensitive tracer of magmatic volatiles. We have conducted spatial surveys around the volcano at once per few years since November 1981. The (3)He/(4)He ratios of the closest site to the cone stayed constant until June 2000 and increased significantly from June 2003 to November 2014, while those of distant sites showed no valuable change. These observations suggest a recent re-activation of Mt Ontake and that helium-3 enhancement may have been a precursor of the 2014 eruption. We show that the eruption was ultimately caused by the increased input of magmatic volatiles over a ten-year period which resulted in the slow pressurization of the volcanic conduit leading to the hydro-volcanic event in September 2014.

Microprocessor-dependent processing of Splice site Overlapping microRNA exons does not result in changes in alternative splicing.

PubMed

Pianigiani, Giulia; Licastro, Danilo; Fortugno, Paola; Castiglia, Daniele; Petrovic, Ivana; Pagani, Franco

2018-06-12

MicroRNAs are found throughout the genome and are processed by the microprocessor complex (MPC) from longer precursors. Some precursor miRNAs overlap intron:exon junctions. These Splice site Overlapping microRNAs (SO-miRNAs) are mostly located in coding genes. It has been intimated, in the rarer examples of SO-miRNAs in non-coding RNAs, that the competition between the spliceosome and the MPC modulates alternative splicing. However, the effect of this overlap on coding transcripts is unknown. Unexpectedly, we show that neither Drosha silencing nor SF3b1 silencing changed the inclusion ratio of SO-miRNA exons. Two SO-miRNAs, located in genes that code for basal membrane proteins, are known to inhibit proliferation in primary keratinocytes. These SO-miRNAs were upregulated during differentiation and the host mRNAs were downregulated, but again there was no change in inclusion ratio of the SO-miRNA exons. Interestingly, Drosha silencing increased nascent RNA density, on chromatin, downstream of SO-miRNA exons. Overall our data suggest a novel mechanism for regulating gene expression in which MPC-dependent cleavage of SO-miRNA exons could cause premature transcriptional termination of coding genes rather than affecting alternative splicing. Published by Cold Spring Harbor Laboratory Press for the RNA Society.

Increased precursor microRNA-21 following status epilepticus can compete with mature microRNA-21 to alter translation

PubMed Central

Chak, Kayam; Roy-Chaudhuri, Biswajoy; Kim, Hak Kyun; Kemp, Kayla C; Kay, Mark A

2016-01-01

MicroRNA-21 (miR-21) is consistently up-regulated in various neurological disorders, including epilepsy. Here, we show that the biogenesis of miR-21 is altered following pilocarpine status epilepticus (SE) with an increase in precursor miR-21 (pre-miR-21) in rats. We demonstrate that pre-miR-21 has an energetically favorable site overlapping with the miR-21 binding site and competes with mature miR-21 for binding in the 3′UTR of TGFBR2 mRNA, but not NT-3 mRNA in vitro. This binding competition influences miR-21-mediated repression in vitro and correlates with the increase in TGFBR2 and decrease in NT-3 following SE. Polysome profiling reveals co-localization of pre-miR-21 in the ribosome fraction with translating mRNAs in U-87 cells. The current work suggests that pre-miR-21 may post-transcriptionally counteract miR-21-mediated suppression following SE and could potentially lead to prolonged TGF-β receptor expression impacting epileptogenesis. The study further supports that the ratio of the pre to mature miRNA may be important in determining the regulatory effects of a miRNA gene. PMID:27725160

Controllable site occupation of Eu in intricate superstructure of perovskite Sr3Al2O6: Eu, Dy, Li to produce red luminescence

NASA Astrophysics Data System (ADS)

Zhu, Mei; Tian, Yunfei; Chen, Jie; Fei, Mi; He, Liangrui; Chen, Lei; Peng, Fang; Zhang, Qingli; Chan, Ting-Shan

An oxide red phosphor, with outstanding superiority in manufacturing cost, is particular desired for white light-emitting diodes (LEDs). In this work, a strategy to controllable site occupation of Eu in Sr3Al2O6 to give red light emission was employed with a three-step route: the combustion of sol-gel to prepare superfine precursor, the solid-sate reaction of precursor to incorporate Eu into small voids, and a second reduction in 25%H2+75%N2 atmosphere. Accordingly, a new red phosphor of Sr3Al2O6:Eu,Dy,Li was developed. The results shows the red luminescence of Sr3Al2O6:Eu could be improved by doping Dy3+ and be further improved by co-doping Li+. The red luminescence involves the 4f-5d transition of Eu2+ and the auto-ionization of electron from Eu2+ to conduction band. Dy3+ acts as a trap center of the thermally released electrons then with electrons returned to the 4f ground state of Eu2+, red light was emitted. The co-substitution of Sr2+-Sr2+ by Dy3+-Li+ is helpful to balance defects and improve crystallization.

Absolute Side-chain Structure at Position 13 Is Required for the Inhibitory Activity of Bromein*

PubMed Central

Sawano, Yoriko; Hatano, Ken-ichi; Miyakawa, Takuya; Tanokura, Masaru

2008-01-01

Bromelain isoinhibitor (bromein), a cysteine proteinase inhibitor from pineapple stem, has a unique double-chain structure. The bromein precursor protein includes three homologous inhibitor domains, each containing an interchain peptide between the light and heavy chains. The interchain peptide in the single-chain precursor is immediately processed by bromelain, a target proteinase. In the present study, to clarify the essential inhibitory site of bromein, we constructed 44 kinds of site-directed and deletion mutants and investigated the inhibitory activity of each toward bromelain. As a result, the complete chemical structure of Leu13 in the light chain was revealed to be essential for inhibition. Pro12 prior to the leucine residue was also involved in the inhibitory activity and would control the location of the leucine side chain by the fixed φ dihedral angle of proline. Furthermore, the five-residue length of the interchain peptide was strictly required for the inhibitory activity. On the other hand, no inhibitory activity against bromelain was observed by the substitution of proline for the N terminus residue Thr15 of the interchain peptide. In summary, these mutational analyses of bromein demonstrated that the appropriate position and conformation of Leu13 are absolutely crucial for bromelain inhibition. PMID:18948264

The roles of SSU processome components and surveillance factors in the initial processing of human ribosomal RNA

PubMed Central

Sloan, Katherine E.; Bohnsack, Markus T.; Schneider, Claudia; Watkins, Nicholas J.

2014-01-01

During eukaryotic ribosome biogenesis, three of the mature ribosomal (r)RNAs are released from a single precursor transcript (pre-rRNA) by an ordered series of endonucleolytic cleavages and exonucleolytic processing steps. Production of the 18S rRNA requires the removal of the 5′ external transcribed spacer (5′ETS) by endonucleolytic cleavages at sites A0 and A1/site 1. In metazoans, an additional cleavage in the 5′ETS, at site A′, upstream of A0, has also been reported. Here, we have investigated how A′ processing is coordinated with assembly of the early preribosomal complex. We find that only the tUTP (UTP-A) complex is critical for A′ cleavage, while components of the bUTP (UTP-B) and U3 snoRNP are important, but not essential, for efficient processing at this site. All other factors involved in the early stages of 18S rRNA processing that were tested here function downstream from this processing step. Interestingly, we show that the RNA surveillance factors XRN2 and MTR4 are also involved in A′ cleavage in humans. A′ cleavage is largely bypassed when XRN2 is depleted, and we also discover that A′ cleavage is not always the initial processing event in all cell types. Together, our data suggest that A′ cleavage is not a prerequisite for downstream pre-rRNA processing steps and may, in fact, represent a quality control step for initial pre-rRNA transcripts. Furthermore, we show that components of the RNA surveillance machinery, including the exosome and TRAMP complexes, also play key roles in the recycling of excised spacer fragments and degradation of aberrant pre-rRNAs in human cells. PMID:24550520

Structural and Functional Adaptation of Vancomycin Resistance VanT Serine Racemases.

PubMed

Meziane-Cherif, Djalal; Stogios, Peter J; Evdokimova, Elena; Egorova, Olga; Savchenko, Alexei; Courvalin, Patrice

2015-08-11

Vancomycin resistance in Gram-positive bacteria results from the replacement of the D-alanyl-D-alanine target of peptidoglycan precursors with D-alanyl-D-lactate or D-alanyl-D-serine (D-Ala-D-Ser), to which vancomycin has low binding affinity. VanT is one of the proteins required for the production of D-Ala-D-Ser-terminating precursors by converting L-Ser to D-Ser. VanT is composed of two domains, an N-terminal membrane-bound domain, likely involved in L-Ser uptake, and a C-terminal cytoplasmic catalytic domain which is related to bacterial alanine racemases. To gain insight into the molecular function of VanT, the crystal structure of the catalytic domain of VanTG from VanG-type resistant Enterococcus faecalis BM4518 was determined. The structure showed significant similarity to type III pyridoxal 5'-phosphate (PLP)-dependent alanine racemases, which are essential for peptidoglycan synthesis. Comparative structural analysis between VanTG and alanine racemases as well as site-directed mutagenesis identified three specific active site positions centered around Asn696 which are responsible for the L-amino acid specificity. This analysis also suggested that VanT racemases evolved from regular alanine racemases by acquiring additional selectivity toward serine while preserving that for alanine. The 4-fold-lower relative catalytic efficiency of VanTG against L-Ser versus L-Ala implied that this enzyme relies on its membrane-bound domain for L-Ser transport to increase the overall rate of d-Ser production. These findings illustrate how vancomycin pressure selected for molecular adaptation of a housekeeping enzyme to a bifunctional enzyme to allow for peptidoglycan remodeling, a strategy increasingly observed in antibiotic-resistant bacteria. Vancomycin is one of the drugs of last resort against Gram-positive antibiotic-resistant pathogens. However, bacteria have evolved a sophisticated mechanism which remodels the drug target, the D-alanine ending precursors in cell wall synthesis, into precursors terminating with D-lactate or D-serine, to which vancomycin has less affinity. D-Ser is synthesized by VanT serine racemase, which has two unusual characteristics: (i) it is one of the few serine racemases identified in bacteria and (ii) it contains a membrane-bound domain involved in L-Ser uptake. The structure of the catalytic domain of VanTG showed high similarity to alanine racemases, and we identified three specific active site substitutions responsible for L-Ser specificity. The data provide the molecular basis for VanT evolution to a bifunctional enzyme coordinating both transport and racemization. Our findings also illustrate the evolution of the essential alanine racemase into a vancomycin resistance enzyme in response to antibiotic pressure. Copyright © 2015 Meziane-Cherif et al.

Fast detection of narcotics by single photon ionization mass spectrometry and laser ion mobility spectrometry

NASA Astrophysics Data System (ADS)

Laudien, Robert; Schultze, Rainer; Wieser, Jochen

2010-10-01

In this contribution two analytical devices for the fast detection of security-relevant substances like narcotics and explosives are presented. One system is based on an ion trap mass spectrometer (ITMS) with single photon ionization (SPI). This soft ionization technique, unlike electron impact ionization (EI), reduces unwanted fragment ions in the mass spectra allowing the clear determination of characteristic (usually molecular) ions. Their enrichment in the ion trap and identification by tandem MS investigations (MS/MS) enables the detection of the target substances in complex matrices at low concentrations without time-consuming sample preparation. For SPI an electron beam pumped excimer light source of own fabrication (E-Lux) is used. The SPI-ITMS system was characterized by the analytical study of different drugs like cannabis, heroin, cocaine, amphetamines, and some precursors. Additionally, it was successfully tested on-site in a closed illegal drug laboratory, where low quantities of MDMA could be directly detected in samples from floors, walls and lab equipments. The second analytical system is based on an ion mobility (IM) spectrometer with resonant multiphoton ionization (REMPI). With the frequency quadrupled Nd:YAG laser (266 nm), used for ionization, a selective and sensitive detection of aromatic compounds is possible. By application of suited aromatic dopants, in addition, also non-aromatic polar compounds are accessible by ion molecule reactions like proton transfer or complex formation. Selected drug precursors could be successfully detected with this device as well, qualifying it to a lower-priced alternative or useful supplement of the SPI-ITMS system for security analysis.

Novel fragmentation pathways of anionic adducts of steroids formed by electrospray anion attachment involving regioselective attachment, regiospecific decompositions, charge-induced pathways, and ion-dipole complex intermediates.

PubMed

Rannulu, Nalaka S; Cole, Richard B

2012-09-01

The analysis of several bifunctional neutral steroids, 5-α-pregnane diol (5-α-pregnane-3α-20βdiol), estradiol (3,17α-dihydroxy-1,3,5(10)-estratriene), progesterone (4-pregnene-3,20-dione), lupeol (3β-hydroxy-20(29)-lupene), pregnenolone (5-pregnen-3β-ol-20-one), and pregnenolone acetate (5-pregnen-3β-ol-20-one acetate) was accomplished by negative ion electrospray mass spectrometry (ESI-MS) employing adduct formation with various anions: fluoride, bicarbonate, acetate, and chloride. Fluoride yielded higher abundances of anionic adducts and more substantial abundances of deprotonated molecules compared with other investigated anions. Collision-induced dissociation (CID) of precursor [M + anion](-) adducts of these steroids revealed that fluoride adduct [M + F](-) precursors first lose HF to produce [M - H](-) and then undergo consecutive decompositions to yield higher abundances of structurally-informative product ions than the other tested anions. In addition to charge-remote fragmentations, the majority of CID pathways of estradiol are deduced to occur via charge-induced fragmentation. Most interestingly, certain anions exhibit preferential attachment to a specific site on these bifunctional steroid molecules, which we are calling "regioselective anion attachment." Regioselective anion attachment is evidenced by subsequent regiospecific decomposition. Regioselective attachment of fluoride (and acetate) anions to low (and moderate) acidity functional groups of pregnenolone, respectively, is demonstrated using deuterated compounds. Moreover, the formation of unique intermediate ion-dipole complexes leading to novel fragmentation pathways of fluoride adducts of pregnenolone acetate, and bicarbonate adducts of d(4)-pregnenolone, are also discussed.

Novel Fragmentation Pathways of Anionic Adducts of Steroids Formed by Electrospray Anion Attachment Involving Regioselective Attachment, Regiospecific Decompositions, Charge-Induced Pathways, and Ion-Dipole Complex Intermediates

NASA Astrophysics Data System (ADS)

Rannulu, Nalaka S.; Cole, Richard B.

2012-09-01

The analysis of several bifunctional neutral steroids, 5-α-pregnane diol (5-α-pregnane-3α-20βdiol), estradiol (3,17α-dihydroxy-1,3,5(10)-estratriene), progesterone (4-pregnene-3,20-dione), lupeol (3β-hydroxy-20(29)-lupene), pregnenolone (5-pregnen-3β-ol-20-one), and pregnenolone acetate (5-pregnen-3β-ol-20-one acetate) was accomplished by negative ion electrospray mass spectrometry (ESI-MS) employing adduct formation with various anions: fluoride, bicarbonate, acetate, and chloride. Fluoride yielded higher abundances of anionic adducts and more substantial abundances of deprotonated molecules compared with other investigated anions. Collision-induced dissociation (CID) of precursor [M + anion]- adducts of these steroids revealed that fluoride adduct [M + F]- precursors first lose HF to produce [M - H]- and then undergo consecutive decompositions to yield higher abundances of structurally-informative product ions than the other tested anions. In addition to charge-remote fragmentations, the majority of CID pathways of estradiol are deduced to occur via charge-induced fragmentation. Most interestingly, certain anions exhibit preferential attachment to a specific site on these bifunctional steroid molecules, which we are calling "regioselective anion attachment." Regioselective anion attachment is evidenced by subsequent regiospecific decomposition. Regioselective attachment of fluoride (and acetate) anions to low (and moderate) acidity functional groups of pregnenolone, respectively, is demonstrated using deuterated compounds. Moreover, the formation of unique intermediate ion-dipole complexes leading to novel fragmentation pathways of fluoride adducts of pregnenolone acetate, and bicarbonate adducts of d4-pregnenolone, are also discussed.

Evaluation of Cu(i) binding to the E2 domain of the amyloid precursor protein - a lesson in quantification of metal binding to proteins via ligand competition.

PubMed

Young, Tessa R; Wedd, Anthony G; Xiao, Zhiguang

2018-01-24

The extracellular domain E2 of the amyloid precursor protein (APP) features a His-rich metal-binding site (denoted as the M1 site). In conjunction with surrounding basic residues, the site participates in interactions with components of the extracellular matrix including heparins, a class of negatively charged polysaccharide molecules of varying length. This work studied the chemistry of Cu(i) binding to APP E2 with the probe ligands Bcs, Bca, Fz and Fs. APP E2 forms a stable Cu(i)-mediated ternary complex with each of these anionic ligands. The complex with Bca was selected for isolation and characterization and was demonstrated, by native ESI-MS analysis, to have the stoichiometry E2 : Cu(i) : Bca = 1 : 1 : 1. Formation of these ternary complexes is specific for the APP E2 domain and requires Cu(i) coordination to the M1 site. Mutation of the M1 site was consistent with the His ligands being part of the E2 ligand set. It is likely that interactions between the negatively charged probe ligands and a positively charged patch on the surface of APP E2 are one aspect of the generation of the stable ternary complexes. Their formation prevented meaningful quantification of the affinity of Cu(i) binding to the M1 site with these probe ligands. However, the ternary complexes are disrupted by heparin, allowing reliable determination of a picomolar Cu(i) affinity for the E2/heparin complex with the Fz or Bca probe ligands. This is the first documented example of the formation of stable ternary complexes between a Cu(i) binding protein and a probe ligand. The ready disruption of the complexes by heparin identified clear 'tell-tale' signs for diagnosis of ternary complex formation and allowed a systematic review of conditions and criteria for reliable determination of affinities for metal binding via ligand competition. This study also provides new insights into a potential correlation of APP functions regulated by copper binding and heparin interaction.

High grade anal intraepithelial neoplasia among HIV-1-infected men screening for a multi-center clinical trial of a human papillomavirus vaccine

PubMed Central

Wilkin, Timothy; Lee, Jeannette Y.; Lensing, Shelly Y.; Stier, Elizabeth A.; Goldstone, Stephen E.; Berry, J. Michael; Jay, Naomi; Aboulafia, David M.; Einstein, Mark H.; Saah, Alfred; Mitsuyasu, Ronald T.; Palefsky, Joel M.

2013-01-01

Purpose High-grade anal intraepithelial neoplasia (HGAIN) is the precursor lesion to invasive anal cancer. HPV vaccination holds great promise for preventing anal cancer. Methods We examined 235 HIV-1-infected men screening for participation in a multi-site clinical trial of a quadrivalent HPV vaccine. All participants had anal swabs obtained for HPV testing and cytology, and high resolution anoscopy with biopsies of visible lesions to assess for HGAIN. Results HPV 16 and 18 were detected in 23% and 10%, respectively; abnormal anal cytology was found in 56% and HGAIN in 30%. HGAIN prevalence was significantly higher in those with HPV 16 detection compared to those without (38% vs. 17%, P=.01). Use of antiretroviral therapy, nadir and current CD4+ cell count were not associated with abnormal anal cytology or HGAIN. Conclusion HGAIN is highly prevalent in HIV-infected men. Further studies are needed on treatment and prevention of HGAIN. PMID:23611828

Homoepitaxial growth of non-polar AlN crystals using molecular dynamics simulations

NASA Astrophysics Data System (ADS)

Leathersich, Jeff; Suvarna, Puneet; Tungare, Mihir; Shahedipour-Sandvik, F. (Shadi)

2013-11-01

Homoepitaxial growth of AlN on (11-20) a-plane and (1-100) m-plane under varying deposition temperatures and aluminum to nitrogen flux ratios was carried out using molecular dynamics (MD) simulations with a Tersoff based interatomic potential. The results indicate that much thicker overgrown films are obtained on m-plane as compared to the a-plane, for the same temperature, N:Al flux, and number of precursor atoms. Crystallinity of the depositions improves as the temperature is increased above 1000 K, accompanied with a better stoichiometry due to increased adatom mobility. Improvement in crystal quality with a N:Al ratio greater than 1 is seen because N atoms desorb more easily than Al atoms. Increasing the N:Al ratio too high limits Al adatom mobility as well as causes site blocking for Al atoms and degrades the deposition quality. The optimum value for N:Al flux ratio was found to be between 1.2 and 1.8 for the deposition temperatures tested based on crystallinity and stoichiometry.

Enhanced Performance of non-PGM Catalysts in Air Operated PEM-Fuel Cells

DOE PAGES

Barkholtz, Heather M.; Chong, Lina; Kaiser, Zachary Brian; ...

2016-10-13

Here a non-platinum group metal (non-PGM) oxygen reduction catalyst was prepared from “support-free” zeolitic imidazolate framework (ZIF) precursor and tested in the proton exchange membrane fuel cell with air as the cathode feed. The iron nitrogen and carbon composite (FeeNeC) based catalyst has high specific surface area decorated uniformly with active sites, which redefines the triple phase boundary (TPB) and requires re-optimization of the cathodic membrane electrode fabrication to ensure efficient mass and charge transports to the catalyst surface. This study reports an effort in optimizing catalytic ink formulation for the membrane electrode preparation and its impact to the fuelmore » cell performance under air. Through optimization, the fuel cell areal current density as high as 115.2 mA/cm 2 at 0.8 V or 147.6 mA/cm 2 at 0.8 V iR-free has been achieved under one bar air. We also investigated impacts on fuel cell internal impedance and the water formation.« less

2D PdAg Alloy Nanodendrites for Enhanced Ethanol Electroxidation.

PubMed

Huang, Wenjing; Kang, Xiaolin; Xu, Cheng; Zhou, Junhua; Deng, Jun; Li, Yanguang; Cheng, Si

2018-03-01

The development of highly active and stable electrocatalysts for ethanol electroxidation is of decisive importance to the successful commercialization of direct ethanol fuel cells. Despite great efforts invested over the past decade, their progress has been notably slower than expected. In this work, the facile solution synthesis of 2D PdAg alloy nanodendrites as a high-performance electrocatalyst is reported for ethanol electroxidation. The reaction is carried out via the coreduction of Pd and Ag precursors in aqueous solution with the presence of octadecyltrimethylammonium chloride as the structural directing agent. Final products feature small thickness (5-7 nm) and random in-plane branching with enlarged surface areas and abundant undercoordinated sites. They exhibit enhanced electrocatalytic activity (large specific current ≈2600 mA mgPd-1) and excellent operation stability (as revealed from both the cycling and chronoamperometric tests) for ethanol electroxidation. Control experiments show that the improvement comes from the combined electronic and structural effects. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Circular RNA biogenesis can proceed through an exon-containing lariat precursor.

PubMed

Barrett, Steven P; Wang, Peter L; Salzman, Julia

2015-06-09

Pervasive expression of circular RNA is a recently discovered feature of eukaryotic gene expression programs, yet its function remains largely unknown. The presumed biogenesis of these RNAs involves a non-canonical 'backsplicing' event. Recent studies in mammalian cell culture posit that backsplicing is facilitated by inverted repeats flanking the circularized exon(s). Although such sequence elements are common in mammals, they are rare in lower eukaryotes, making current models insufficient to describe circularization. Through systematic splice site mutagenesis and the identification of splicing intermediates, we show that circular RNA in Schizosaccharomyces pombe is generated through an exon-containing lariat precursor. Furthermore, we have performed high-throughput and comprehensive mutagenesis of a circle-forming exon, which enabled us to discover a systematic effect of exon length on RNA circularization. Our results uncover a mechanism for circular RNA biogenesis that may account for circularization in genes that lack noticeable flanking intronic secondary structure.

Environmental effects on lunar astronomical observatories

NASA Technical Reports Server (NTRS)

Johnson, Stewart W.; Taylor, G. Jeffrey; Wetzel, John P.

1992-01-01

The Moon offers a stable platform with excellent seeing conditions for astronomical observations. Some troublesome aspects of the lunar environment will need to be overcome to realize the full potential of the Moon as an observatory site. Mitigation of negative effects of vacuum, thermal radiation, dust, and micrometeorite impact is feasible with careful engineering and operational planning. Shields against impact, dust, and solar radiation need to be developed. Means of restoring degraded surfaces are probably essential for optical and thermal control surfaces deployed in long-lifetime lunar facilities. Precursor missions should be planned to validate and enhance the understanding of the lunar environment (e.g., dust behavior without and with human presence) and to determine environmental effects on surfaces and components. Precursor missions should generate data useful in establishing keepout zones around observatory facilities where rocket launches and landings, mining, and vehicular traffic could be detrimental to observatory operation.

Environmental effects on an optical-UV-IR synthesis array

NASA Technical Reports Server (NTRS)

Johnson, Stewart W.; Taylor, G. Jeffrey; Wetzel, John P.

1992-01-01

The Moon offers a stable platform with excellent seeing conditions for the Lunar Optical-UV-IR Synthesis Array (LOUISA). Some troublesome aspects of the lunar environment will need to be overcome to realize the full potential of the Moon as an observatory site. Mitigation of negative effects of vacuum, thermal radiation, dust, and micrometeorite impact is feasible with careful engineering and operational planning. Shields against impact, dust, and solar radiation need to be developed. Means of restoring degraded surfaces are probably essential for optical and thermal control surfaces deployed in long-lifetime lunar facilities. Precursor missions should be planned to validate and enhance the understanding of the lunar environment (e.g., dust behavior without and with human presence and to determine environmental effects on surfaces and components. Precursor missions should generate data useful in establishing keepout zones around observatory facilities while rocket launches and landings, mining, and vehicular traffic could be detrimental to observatory operation.

Poliovirus RNA synthesis in vitro: structural elements and antibody inhibition

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

Semler, B.L.; Hanecak, R.; Dorner, L.F.

1983-01-01

The poliovirus RNA polymerase complex has been analyzed by immunoautoradiography using antibody probes derived from purified replicase (P3) region viral polypeptides. Antibody preparations made against the polio RNA polymerase, P3-4b, detected a previously unreported cellular protein that copurifies with the RNA polymerase. An IgG fraction purified from rabbit antiserum to polypeptide P3-2, a precursor fo the RNA polymerase, specifically inhibits poliovirus RNA synthesis in vitro. The authors have also immunoprecipitated a 60,000-dalton protein (P3-4a) with antiserum to protein P3-4b and have determined the precise genomic map position of this protein by automated Edman degradation. Protein P3-4a originates by cleavage ofmore » the RNA polymerase precursor at a glutamine-glucine amino acid pair not previously reported to be a viral cleavage site.« less

Modular architecture of eukaryotic RNase P and RNase MRP revealed by electron microscopy.

PubMed

Hipp, Katharina; Galani, Kyriaki; Batisse, Claire; Prinz, Simone; Böttcher, Bettina

2012-04-01

Ribonuclease P (RNase P) and RNase MRP are closely related ribonucleoprotein enzymes, which process RNA substrates including tRNA precursors for RNase P and 5.8 S rRNA precursors, as well as some mRNAs, for RNase MRP. The structures of RNase P and RNase MRP have not yet been solved, so it is unclear how the proteins contribute to the structure of the complexes and how substrate specificity is determined. Using electron microscopy and image processing we show that eukaryotic RNase P and RNase MRP have a modular architecture, where proteins stabilize the RNA fold and contribute to cavities, channels and chambers between the modules. Such features are located at strategic positions for substrate recognition by shape and coordination of the cleaved-off sequence. These are also the sites of greatest difference between RNase P and RNase MRP, highlighting the importance of the adaptation of this region to the different substrates.

Recent studies implicate the nucleolus as the major site of nuclear translation.

PubMed

McLeod, Tina; Abdullahi, Akilu; Li, Min; Brogna, Saverio

2014-08-01

The nucleolus is the most prominent morphological feature within the nucleus of eukaryotic cells and is best known for its role in ribosome biogenesis. It forms around highly transcribed ribosomal RNA gene repeats which yield precursor rRNAs that are co-transcriptionally processed, folded and, while still within the nucleolus, associate with most of the ribosomal proteins. The nucleolus is therefore often thought of as a factory for making ribosomal subunits, which are exported as inactive precursors to the cytoplasm where late maturation makes them capable of mRNA binding and translation initiation. However, recent studies have shown substantial evidence for the presence of functional, translation competent ribosomal subunits within the nucleus, particularly in the nucleolus. These observations raise the intriguing possibility that the nucleolus, as well as being a ribosome factory, is also an important nuclear protein-synthesis plant.

A-site- and/or B-site-modified PbZrTiO3 materials and (Pb, Sr, Ca, Ba, Mg) (Zr, Ti, Nb, Ta)O3 films having utility in ferroelectric random access memories and high performance thin film microactuators

NASA Technical Reports Server (NTRS)

Bilodeau, Steven (Inventor); Baum, Thomas H. (Inventor); Roeder, Jeffrey F. (Inventor); Chen, Ing-Shin (Inventor)

2001-01-01

A modified PbZrTiO.sub.3 perovskite crystal material thin film, wherein the PbZrTiO.sub.3 perovskite crystal material includes crystal lattice A-sites and B-sites at least one of which is modified by the presence of a substituent selected from the group consisting of (i) A-site substituents consisting of Sr, Ca, Ba and Mg, and (ii) B-site substituents selected from the group consisting of Nb and Ta. The perovskite crystal thin film material may be formed by liquid delivery MOCVD from metalorganic precursors of the metal components of the thin film, to form PZT and PSZT, and other piezoelectric and ferroelectric thin film materials. The thin films of the invention have utility in non-volatile ferroelectric memory devices (NV-FeRAMs), and in microelectromechanical systems (MEMS) as sensor and/or actuator elements, e.g., high speed digital system actuators requiring low input power levels.

A-SITE-AND/OR B-SITE-MODIFIED PBZRTIO3 MATERIALS AND (PB, SR, CA, BA, MG) (ZR, TI,NB, TA)O3 FILMS HAVING UTILITY IN FERROELECTRIC RANDOM ACCESS MEMORIES AND HIGH PERFORMANCE THIN FILM MICROACTUATORS

NASA Technical Reports Server (NTRS)

Bilodeau, Steven (Inventor); Baum, Thomas H. (Inventor); Roeder, Jeffrey F. (Inventor); Chen, Ing-Shin (Inventor)

2004-01-01

A modified PbZrTiO.sub.3 perovskite crystal material thin film, wherein the PbZrTiO.sub.3 perovskite crystal material includes crystal lattice A-sites and B-sites at least one of which is modified by the presence of a substituent selected from the group consisting of (i) A-site substituents consisting of Sr, Ca, Ba and Mg, and (ii) B-site substituents selected from the group consisting of Nb and Ta. The perovskite crystal thin film material may be formed by liquid delivery MOCVD from metalorganic precursors of the metal components of the thin film, to form PZT and PSZT, and other piezoelectric and ferroelectric thin film materials. The thin films of the invention have utility in non-volatile ferroelectric memory devices (NV-FeRAMs), and in microelectromechanical systems (MEMS) as sensor and/or actuator elements, e.g., high speed digital system actuators requiring low input power levels.

Naturally-Occurring DMSP Analogs as Potential Precursors of Dimethyl Sulfide (DMS) and Methanethiol (MeSH) in Coastal Seawater

NASA Astrophysics Data System (ADS)

Cordero, D.; Kiene, R. P.

2016-02-01

Dimethylsulfoniopropionate (DMSP) is an osmolyte produced by various macroalgae and phytoplankton in the marine environment. DMSP is known to be the main precursor for dimethyl sulfide (DMS), the major natural sulfur gas emitted from the oceans to the atmosphere. DMS contributes to formation and growth of sulfur-containing aerosols in our stratosphere. These aerosols influence Earth's solar radiation balance and potentially affect the formation of clouds, which could function as a counter-effect to global warming. Bacterioplankton are capable of converting DMSP into DMS via the enzyme DMSP lyase. But not all DMSP in the ocean is converted into DMS. A significant fraction of the DMSP available in the ocean is converted to methanethiol (MeSH) via the bacterial demethylation/demethiolation pathway, with a portion of the MeSH being assimilated as both a carbon and sulfur source. Here we test whether several other naturally-occurring dimethyl sulfonium compounds could be precursors of DMS and MeSH. To test this, we carried out experiments with estuarine water samples from Mobile Bay in the Northern Gulf of Mexico. After collection, unfiltered seawater and seawater filtrate samples, the later containing bacteria only, were treated with 50 nM additions of either 2-dimethylsulfononioacetate (DMSA) or S-Methylmethionine (SMM). After addition of the dimethyl sulfonium compounds, samples were analyzed for sulfur gases with Gas Chromatography-Flame Photometric Detection, using cryogenic-trapping techniques. Addition of DMSA resulted in an immediate increase in MeSH production in both seawater and seawater filtrate containing bacteria only, producing even more MeSH than DMSP. This suggests that DMSA is potentially a significant precursor for MeSH. DMS was not produced in significant amounts from DMSA. Addition of SMM resulted in low rates of both DMS and MeSH accumulation in both seawater samples, indicating that SMM may be a minor precursor for both gases compared to DMSP.

γ-Secretase Modulators and APH1 Isoforms Modulate γ-Secretase Cleavage but Not Position of ε-Cleavage of the Amyloid Precursor Protein (APP).

PubMed

Lessard, Christian B; Cottrell, Barbara A; Maruyama, Hiroko; Suresh, Suraj; Golde, Todd E; Koo, Edward H

2015-01-01

The relative increase in Aβ42 peptides from familial Alzheimer disease (FAD) linked APP and PSEN mutations can be related to changes in both ε-cleavage site utilization and subsequent step-wise cleavage. Cleavage at the ε-site releases the amyloid precursor protein (APP) intracellular domain (AICD), and perturbations in the position of ε-cleavage are closely associated with changes in the profile of amyloid β-protein (Aβ) species that are produced and secreted. The mechanisms by which γ-secretase modulators (GSMs) or FAD mutations affect the various γ-secretase cleavages to alter the generation of Aβ peptides have not been fully elucidated. Recent studies suggested that GSMs do not modulate ε-cleavage of APP, but the data were derived principally from recombinant truncated epitope tagged APP substrate. Here, using full length APP from transfected cells, we investigated whether GSMs modify the ε-cleavage of APP under more native conditions. Our results confirmed the previous findings that ε-cleavage is insensitive to GSMs. In addition, fenofibrate, an inverse GSM (iGSM), did not alter the position or kinetics of ε-cleavage position in vitro. APH1A and APH1B, a subunit of the γ-secretase complex, also modulated Aβ42/Aβ40 ratio without any alterations in ε-cleavage, a result in contrast to what has been observed with PS1 and APP FAD mutations. Consequently, GSMs and APH1 appear to modulate γ-secretase activity and Aβ42 generation by altering processivity but not ε-cleavage site utilization.

Structures of the peptide-modifying radical SAM enzyme SuiB elucidate the basis of substrate recognition.

PubMed

Davis, Katherine M; Schramma, Kelsey R; Hansen, William A; Bacik, John P; Khare, Sagar D; Seyedsayamdost, Mohammad R; Ando, Nozomi

2017-09-26

Posttranslational modification of ribosomally synthesized peptides provides an elegant means for the production of biologically active molecules known as RiPPs (ribosomally synthesized and posttranslationally modified peptides). Although the leader sequence of the precursor peptide is often required for turnover, the exact mode of recognition by the modifying enzymes remains unclear for many members of this class of natural products. Here, we have used X-ray crystallography and computational modeling to examine the role of the leader peptide in the biosynthesis of a homolog of streptide, a recently identified peptide natural product with an intramolecular lysine-tryptophan cross-link, which is installed by the radical S -adenosylmethionine (SAM) enzyme, StrB. We present crystal structures of SuiB, a close ortholog of StrB, in various forms, including apo SuiB, SAM-bound SuiB, and a complex of SuiB with SAM and its peptide substrate, SuiA. Although the N-terminal domain of SuiB adopts a typical RRE (RiPP recognition element) motif, which has been implicated in precursor peptide recognition, we observe binding of the leader peptide in the catalytic barrel rather than the N-terminal domain. Computational simulations support a mechanism in which the leader peptide guides posttranslational modification by positioning the cross-linking residues of the precursor peptide within the active site. Together the results shed light onto binding of the precursor peptide and the associated conformational changes needed for the formation of the unique carbon-carbon cross-link in the streptide family of natural products.

Effects of N precursor on the agglomeration and visible light photocatalytic activity of N-doped TiO2 nanocrystalline powder.

PubMed

Hu, Yulong; Liu, Hongfang; Rao, Qiuhua; Kong, Xiaodong; Sun, Wei; Guo, Xingpeng

2011-04-01

N-doped TiO2 nanocrystalline powders were prepared by the sol-gel method using various N precursors, including triethylamine, hydrazine hydrate, ethylenediamine, ammonium hydroxide, and urea. The samples were characterized by X-ray diffraction, N2 adsorption isotherms, transmission electron microscopy, ultraviolet-visible diffuse reflectance spectroscopy, Fourier transform infrared spectroscopy, and X-ray photoelectron spectroscopy. The photocatalytic activities of as-prepared samples under irradiation of visible light (lambda > 405 nm) were evaluated by photodecomposition of methyl orange. The alkalinity of N precursor was found to play a key role in the gel process. The N precursor with moderate alkalinity causes TiO2 nanoparticles to be sol-transformed into a loosely agglomerated gel. This transformation facilitates the preparation of an N-doped TiO2 powder with small nanocrystal size, large specific surface area, and high N doping level and results in high visible light photocatalytic activity. The N in TiO2 with N is binding energy at 399-400 eV may be assigned to the N-H species located in interstitial sites of TiO2 lattice which is the active N species responsible for the visible light photocatalytic activity. The N species of N 1s peak at 402 and 405 eV are ineffective to the visible light photocatalytic activity and may inhibit the photocatalytic activity. Moreover, a TiO2 nanoparticle powder with large specific area can be achieved by using urea as a template and then by using ammonium hydroxide to transform the sol into gel.

RNAi Mediated curcin precursor gene silencing in Jatropha (Jatropha curcas L.).

PubMed

Patade, Vikas Yadav; Khatri, Deepti; Kumar, Kamal; Grover, Atul; Kumari, Maya; Gupta, Sanjay Mohan; Kumar, Devender; Nasim, Mohammed

2014-07-01

Curcin, a type I ribosomal inhibiting protein-RIP, encoded by curcin precursor gene, is a phytotoxin present in Jatropha (Jatropha curcas L.). Here, we report designing of RNAi construct for the curcin precursor gene and further its genetic transformation of Jatropha to reduce its transcript expression. Curcin precursor gene was first cloned from Jatropha strain DARL-2 and part of the gene sequence was cloned in sense and antisense orientation separated by an intron sequence in plant expression binary vector pRI101 AN. The construction of the RNAi vector was confirmed by double digestion and nucleotide sequencing. The vector was then mobilized into Agrobacterium tumefaciens strain GV 3101 and used for tissue culture independent in planta transformation protocol optimized for Jatropha. Germinating seeds were injured with a needle before infection with Agrobacterium and then transferred to sterilized sand medium. The seedlings were grown for 90 days and genomic DNA was isolated from leaves for transgenic confirmation based on real time PCR with NPT II specific dual labeled probe. Result of the transgenic confirmation analysis revealed presence of the gene silencing construct in ten out of 30 tested seedlings. Further, quantitative transcript expression analysis of the curcin precursor gene revealed reduction in the transcript abundance by more than 98% to undetectable level. The transgenic plants are being grown in containment for further studies on reduction in curcin protein content in Jatropha seeds.

Enrichment of skin-derived neural precursor cells from dermal cell populations by altering culture conditions.

PubMed

Bayati, Vahid; Gazor, Rohoullah; Nejatbakhsh, Reza; Negad Dehbashi, Fereshteh

2016-01-01

As stem cells play a critical role in tissue repair, their manipulation for being applied in regenerative medicine is of great importance. Skin-derived precursors (SKPs) may be good candidates for use in cell-based therapy as the only neural stem cells which can be isolated from an accessible tissue, skin. Herein, we presented a simple protocol to enrich neural SKPs by monolayer adherent cultivation to prove the efficacy of this method. To enrich neural SKPs from dermal cell populations, we have found that a monolayer adherent cultivation helps to increase the numbers of neural precursor cells. Indeed, we have cultured dermal cells as monolayer under serum-supplemented (control) and serum-supplemented culture, followed by serum free cultivation (test) and compared. Finally, protein markers of SKPs were assessed and compared in both experimental groups and differentiation potential was evaluated in enriched culture. The cells of enriched culture concurrently expressed fibronectin, vimentin and nestin, an intermediate filament protein expressed in neural and skeletal muscle precursors as compared to control culture. In addition, they possessed a multipotential capacity to differentiate into neurogenic, glial, adipogenic, osteogenic and skeletal myogenic cell lineages. It was concluded that serum-free adherent culture reinforced by growth factors have been shown to be effective on proliferation of skin-derived neural precursor cells (skin-NPCs) and drive their selective and rapid expansion.

Synthesis of silver nanoparticles in the presence of diethylaminoethyl-dextran hydrochloride polymer and their SERS activity

NASA Astrophysics Data System (ADS)

Mikac, L.; Jurkin, T.; Štefanić, G.; Ivanda, Mile; Gotić, Marijan

2017-09-01

The silver nanoparticles (AgNPs) were synthesized upon γ-irradiation of AgNO3 precursor suspensions in the presence of diethylaminoethyl-dextran hydrochloride (DEAE-dextran) cationic polymer as a stabilizer. The dose rate of γ-irradiation was 32 kGy h-1, and absorbed doses were 30 and 60 kGy. The γ-irradiation of the precursor suspension at acidic or neutral pH conditions produced predominantly the silver(I) chloride (AgCl) particles, because of the poor solubility of AgCl already present in the precursor suspension. The origin of AgCl in the precursor suspension was due to the presence of chloride ions in DEAE-dextran hydrochloride polymer. The addition of ammonia to the precursor suspension dissolved the AgCl precipitate, and the γ-irradiation of such colourless suspension at alkali pH produced a stable aqueous suspension with rather uniform spherical AgNPs of approximately 30 nm in size. The size of AgNPs was controlled by varying the AgNO3/DEAE-dextran concentration in the suspensions. The surface-enhanced Raman scattering (SERS) activities of synthesized AgNPs were examined using organic molecules rhodamine 6G, pyridine and 4-mercaptobenzoic acid (4-MBA). The NaBH4 was used as SERS aggregation agent. The SERS results have shown that in the presence of synthesized AgNPs, it was possible to detect low concentration of tested compounds.

Material State Awareness for Composites Part II: Precursor Damage Analysis and Quantification of Degraded Material Properties Using Quantitative Ultrasonic Image Correlation (QUIC)

PubMed Central

Patra, Subir; Banerjee, Sourav

2017-01-01

Material state awareness of composites using conventional Nondestructive Evaluation (NDE) method is limited by finding the size and the locations of the cracks and the delamination in a composite structure. To aid the progressive failure models using the slow growth criteria, the awareness of the precursor damage state and quantification of the degraded material properties is necessary, which is challenging using the current NDE methods. To quantify the material state, a new offline NDE method is reported herein. The new method named Quantitative Ultrasonic Image Correlation (QUIC) is devised, where the concept of microcontinuum mechanics is hybrid with the experimentally measured Ultrasonic wave parameters. This unique combination resulted in a parameter called Nonlocal Damage Entropy for the precursor awareness. High frequency (more than 25 MHz) scanning acoustic microscopy is employed for the proposed QUIC. Eight woven carbon-fiber-reinforced-plastic composite specimens were tested under fatigue up to 70% of their remaining useful life. During the first 30% of the life, the proposed nonlocal damage entropy is plotted to demonstrate the degradation of the material properties via awareness of the precursor damage state. Visual proofs for the precursor damage states are provided with the digital images obtained from the micro-optical microscopy, the scanning acoustic microscopy and the scanning electron microscopy. PMID:29258256

Review of the fate and transformation of per- and polyfluoroalkyl substances (PFASs) in landfills.

PubMed

Hamid, Hanna; Li, Loretta Y; Grace, John R

2018-04-01

A critical review of existing publications is presented i) to summarize the occurrence of various classes of per- and polyfluoroalkyl substances (PFASs) and their sources in landfills, ii) to identify temporal and geographical trends of PFASs in landfills; iii) to delineate the factors affecting PFASs in landfills; and iv) to identify research gaps and future research directions. Studies have shown that perfluoroalkyl acids (PFAAs) are routinely detected in landfill leachate, with short chain (C4-C7) PFAAs being most abundant, possibly indicating their greater mobility, and reflecting the industrial shift towards shorter-chain compounds. Despite its restricted use, perfluorooctanoic acid (PFOA) remains one of the most abundant PFAAs in landfill leachates. Recent studies have also documented the presence of PFAA-precursors (e.g., saturated and unsaturated fluorotelomer carboxylic acids) in landfill leachates at concentrations comparable to, or higher than, the most frequently detected PFAAs. Landfill ambient air also contains elevated concentrations of PFASs, primarily semi-volatile precursors (e.g., fluorotelomer alcohols) compared to upwind control sites, suggesting that landfills are potential sources of atmospheric PFASs. The fate of PFASs inside landfills is controlled by a combination of biological and abiotic processes, with biodegradation releasing most of the PFASs from landfilled waste to leachate. Biodegradation in simulated anaerobic reactors has been found to be closely related to the methanogenic phase. The methane-yielding stage also results in higher pH (>7) of leachates, correlated with higher mobility of PFAAs. Little information exists regarding PFAA-precursors in landfills. To avoid significant underestimation of the total PFAS released from landfills, PFAA-precursors and their degradation products should be determined in future studies. Owing to the semi-volatile nature of some precursor compounds and their degradation products, future studies also need to include landfill gas to clarify degradation pathways and the overall fate of PFASs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Evaluation of geophysical properties of the lunar regolith for the design of precursor scientific missions for the space exploration initiative

NASA Technical Reports Server (NTRS)

Morgan, Paul

1990-01-01

The following topics are addressed: (1) the frequency of encountering boulders that represent hazards to lunar operations; (2) the ease of lunar soil excavation; (3) the use of explosives in excavation operation; (4) the trafficability of the regolith; (5) problems encountered in mining (probably strip mining) of the regolith; (6) the stable angle(s) of repose in excavation of the regolith; (7) the layering to be encountered in the subsurface; (8) knowledge of the regolith site and the possibility of its general application to any site on the lunar surface; (9) the data needed to characterize a site for a lunar base; (10) the influence of regolith properties on the design of geophysical experiments from the lunar base; and (11) terrestrial analogues for the geophysical properties of the lunar regolith.

Adaptor protein 2–mediated endocytosis of the β-secretase BACE1 is dispensable for amyloid precursor protein processing

PubMed Central

Prabhu, Yogikala; Burgos, Patricia V.; Schindler, Christina; Farías, Ginny G.; Magadár, Javier G.; Bonifacino, Juan S.

2012-01-01

The β-site amyloid precursor protein (APP)–cleaving enzyme 1 (BACE1) is a transmembrane aspartyl protease that catalyzes the proteolytic processing of APP and other plasma membrane protein precursors. BACE1 cycles between the trans-Golgi network (TGN), the plasma membrane, and endosomes by virtue of signals contained within its cytosolic C-terminal domain. One of these signals is the DXXLL-motif sequence DISLL, which controls transport between the TGN and endosomes via interaction with GGA proteins. Here we show that the DISLL sequence is embedded within a longer [DE]XXXL[LI]-motif sequence, DDISLL, which mediates internalization from the plasma membrane by interaction with the clathrin-associated, heterotetrameric adaptor protein 2 (AP-2) complex. Mutation of this signal or knockdown of either AP-2 or clathrin decreases endosomal localization and increases plasma membrane localization of BACE1. Remarkably, internalization-defective BACE1 is able to cleave an APP mutant that itself cannot be delivered to endosomes. The drug brefeldin A reversibly prevents BACE1-catalyzed APP cleavage, ruling out that this reaction occurs in the endoplasmic reticulum (ER) or ER–Golgi intermediate compartment. Taken together, these observations support the notion that BACE1 is capable of cleaving APP in late compartments of the secretory pathway. PMID:22553349

Crystal structure of human lysyl oxidase-like 2 (hLOXL2) in a precursor state.

PubMed

Zhang, Xi; Wang, Qifan; Wu, Jianping; Wang, Jiawei; Shi, Yigong; Liu, Minhao

2018-04-10

Lysyl oxidases (LOXs), a type of copper- and lysyl tyrosylquinone (LTQ) -dependent amine oxidase, catalyze the oxidative deamination of lysine residues of extracellular matrix (ECM) proteins such as elastins and collagens and generate aldehyde groups. The oxidative deamination of lysine represents the foundational step for the cross-linking of elastin and collagen and thus is crucial for ECM modeling. Despite their physiological significance, the structure of this important family of enzymes remains elusive. Here we report the crystal structure of human lysyl oxidase-like 2 (hLOXL2) at 2.4-Å resolution. Unexpectedly, the copper-binding site of hLOXL2 is occupied by zinc, which blocks LTQ generation and the enzymatic activity of hLOXL2 in our in vitro assay. Biochemical analysis confirms that copper loading robustly activates hLOXL2 and supports LTQ formation. Furthermore, the LTQ precursor residues in the structure are distanced by 16.6 Å, corroborating the notion that the present structure may represent a precursor state and that pronounced conformational rearrangements would be required for protein activation. The structure presented here establishes an important foundation for understanding the structure-function relationship of LOX proteins and will facilitate LOX-targeting drug discovery. Copyright © 2018 the Author(s). Published by PNAS.

Effects of cobalt precursor on pyrolyzed carbon-supported cobalt-polypyrrole as electrocatalyst toward oxygen reduction reaction

PubMed Central

2013-01-01

A series of non-precious metal electrocatalysts, namely pyrolyzed carbon-supported cobalt-polypyrrole, Co-PPy-TsOH/C, are synthesized with various cobalt precursors, including cobalt acetate, cobalt nitrate, cobalt oxalate, and cobalt chloride. The catalytic performance towards oxygen reduction reaction (ORR) is comparatively investigated with electrochemical techniques of cyclic voltammogram, rotating disk electrode and rotating ring-disk electrode. The results are analyzed and discussed employing physiochemical techniques of X-ray diffraction, transmission electron microscopy, Raman spectroscopy, X-ray photoelectron spectroscopy, inductively coupled plasma, elemental analysis, and extended X-ray absorption fine structure. It shows that the cobalt precursor plays an essential role on the synthesis process as well as microstructure and performance of the Co-PPy-TsOH/C catalysts towards ORR. Among the studied Co-PPy-TsOH/C catalysts, that prepared with cobalt acetate exhibits the best ORR performance. The crystallite/particle size of cobalt and its distribution as well as the graphitization degree of carbon in the catalyst greatly affects the catalytic performance of Co-PPy-TsOH/C towards ORR. Metallic cobalt is the main component in the active site in Co-PPy-TsOH/C for catalyzing ORR, but some other elements such as nitrogen are probably involved, too. PMID:24229351

cDNAs encoding [D-Ala2]deltorphin precursors from skin of Phyllomedusa bicolor also contain genetic information for three dermorphin-related opioid peptides.

PubMed

Richter, K; Egger, R; Negri, L; Corsi, R; Severini, C; Kreil, G

1990-06-01

We present the structure of four precursors for [D-Ala2]deltorphins I and II as deduced from cDNAs cloned from skin of the frog Phyllomedusa bicolor. These contain the genetic information for one copy of [D-Ala2]deltorphin II and zero, one, or three copies of [D-Ala2]deltorphin I. In each case, the D-alanine of the end product is encoded by a normal GCG codon for L-alanine. In addition, the existence of three peptides related to dermorphin was predicted from the amino acid sequence of the precursors. These peptides were synthesized with a D-alanine in position 2 and their pharmacological properties were tested. Two of them, [Lys7]dermorphin-OH and [Trp4,Asn7]dermorphin-OH, were found to have roughly the same affinity and selectivity for mu-type opioid receptors as dermorphin.

cDNAs encoding [D-Ala2]deltorphin precursors from skin of Phyllomedusa bicolor also contain genetic information for three dermorphin-related opioid peptides.

PubMed Central

Richter, K; Egger, R; Negri, L; Corsi, R; Severini, C; Kreil, G

1990-01-01

We present the structure of four precursors for [D-Ala2]deltorphins I and II as deduced from cDNAs cloned from skin of the frog Phyllomedusa bicolor. These contain the genetic information for one copy of [D-Ala2]deltorphin II and zero, one, or three copies of [D-Ala2]deltorphin I. In each case, the D-alanine of the end product is encoded by a normal GCG codon for L-alanine. In addition, the existence of three peptides related to dermorphin was predicted from the amino acid sequence of the precursors. These peptides were synthesized with a D-alanine in position 2 and their pharmacological properties were tested. Two of them, [Lys7]dermorphin-OH and [Trp4,Asn7]dermorphin-OH, were found to have roughly the same affinity and selectivity for mu-type opioid receptors as dermorphin. PMID:2352951

Investigation of photocalalytic activity of ZnO prepared by spray pyrolis with various precursors

NASA Astrophysics Data System (ADS)

Bourfaa, F.; Lamri Zeggar, M.; A, A.; Aida, M. S.; Attaf, N.

2016-03-01

Semiconductor photocatalysts such as ZnO has attracted much attention in recent years due to their various applications for the degradation of organic pollutants in water, air and in dye sensitized photovoltaic solar cell. In the present work, ZnO thin films were prepared by ultrasonic spray pyrolysis by using different precursors namely: acetate, chloride and zinc nitrate in order to investigate their influence on ZnO photocatalytic activity. The films crystalline structure was studied by mean of X- ray diffraction measurements (XRD) and the films surface morphology by Scanning Electron Microscopy (SEM). The films optical properties were studied by mean of UV-visible spectroscopy. The prepared films were tested for the degradation of the red reactive dye largely used in textile industry. As a result, we found that the zinc nitrate is the best precursor to prepare ZnO thin films suitable for a good photocatalytic activity.

The Chemistry of Inorganic Precursors during the Chemical Deposition of Films on Solid Surfaces.

PubMed

Barry, Seán T; Teplyakov, Andrew V; Zaera, Francisco

2018-03-20

The deposition of thin solid films is central to many industrial applications, and chemical vapor deposition (CVD) methods are particularly useful for this task. For one, the isotropic nature of the adsorption of chemical species affords even coverages on surfaces with rough topographies, an increasingly common requirement in microelectronics. Furthermore, by splitting the overall film-depositing reactions into two or more complementary and self-limiting steps, as it is done in atomic layer depositions (ALD), film thicknesses can be controlled down to the sub-monolayer level. Thanks to the availability of a vast array of inorganic and metalorganic precursors, CVD and ALD are quite versatile and can be engineered to deposit virtually any type of solid material. On the negative side, the surface chemistry that takes place in these processes is often complex, and can include undesirable side reactions leading to the incorporation of impurities in the growing films. Appropriate precursors and deposition conditions need to be chosen to minimize these problems, and that requires a proper understanding of the underlying surface chemistry. The precursors for CVD and ALD are often designed and chosen based on their known thermal chemistry from inorganic chemistry studies, taking advantage of the vast knowledge developed in that field over the years. Although a good first approximation, however, this approach can lead to wrong choices, because the reactions of these precursors at gas-solid interfaces can be quite different from what is seen in solution. For one, solvents often aid in the displacement of ligands in metalorganic compounds, providing the right dielectric environment, temporarily coordinating to the metal, or facilitating multiple ligand-complex interactions to increase reaction probabilities; these options are not available in the gas-solid reactions associated with CVD and ALD. Moreover, solid surfaces act as unique "ligands", if these reactions are to be viewed from the point of view of the metalorganic complexes used as precursors: they are bulky and rigid, can provide multiple binding sites for a single reaction, and can promote unique bonding modes, especially on metals, which have delocalized electronic structures. The differences between the molecular and surface chemistry of CVD and ALD precursors can result in significant variations in their reactivity, ultimately leading to unpredictable properties in the newly grown films. In this Account, we discuss some of the main similarities and differences in chemistry that CVD/ALD precursors follow on surfaces when contrasted against their known behavior in solution, with emphasis on our own work but also referencing other key contributions. Our approach is unique in that it combines expertise from the inorganic, surface science, and quantum-mechanics fields to better understand the mechanistic details of the chemistry of CVD and ALD processes and to identify new criteria to consider when designing CVD/ALD precursors.

Identification and tissue distribution of mRNAs encoding salmon-type calcitonins-IV and -V in the rainbow trout.

PubMed

Hidaka, Yoshie; Suzuki, Masakazu

2004-06-01

Four types of calcitonin are produced in salmonid fish, although their functional diversity is almost unknown. To explore the significance of these isoforms, we have characterized salmon-type calcitonin (sCT) mRNAs in the rainbow trout (Oncorhynchus mykiss), and examined their tissue distribution. In addition to the previously isolated sCT-I cDNAs, two new forms of sCT cDNA were cloned from the ultimobranchial gland, and one of them (sCT-IV cDNA) was predicted to encode an N-terminal peptide of 80 amino acid residues, a putative cleavage site Lys-Arg, sCT-IV, a cleavage and amidation sequence Gly-Lys-Lys-Arg, and a C-terminal peptide of 18 amino acids. The sCT-IV precursor was 78% identical with the rainbow trout sCT-I precursors. The other cloned cDNA encoded a precursor for a novel CT, sCT-V. The sCT-V peptide was different from sCT-IV by only one amino acid residue: Val at position 8 in the latter was replaced by Met. The sCT-V precursor had 80 and 90% identity with the sCT-I and -IV precursors respectively. No cDNA clones were obtained for sCTs-II or -III.Tissue distribution of sCT-I, -IV and -V mRNAs was examined by RT-PCR and specific cleavage with restriction enzymes. An amplified fragment from sCT-I mRNA was detected not only in the ultimobranchial gland, but also in the gills, testis and ovary. RT-PCR analysis coupled to restriction digestion further revealed that sCT-IV mRNA was expressed in both the testis and the ultimobranchial gland. The expression sites of sCT-IV mRNA were localized to the Leydig cells of the testis and to the parenchymal cells of the ultimobranchial gland, by in situ hybridization histochemistry. Although the amino acid sequence of sCT-V peptide was nearly the same as that of sCT-IV, the sCT-V gene showed a much wider pattern of expression: the band amplified by RT-PCR was detected in all the tissues examined except the kidney, gills and blood cells. The sCT-V mRNA was shown to be localized in the parenchymal cells of the ultimobranchial gland, but not in other tissues at the cellular level, suggesting very low expression of sCT-V mRNA in those tissues. Our results show different patterns of tissue expression of three types of sCT genes in the rainbow trout, suggesting that sCTs-I, -IV and -V might differ in their local actions.

Sulfate and Pb-210 Simulated in a Global Model Using Assimilated Meteorological Fields

NASA Technical Reports Server (NTRS)

Chin, Mian; Rood, Richard; Lin, S.-J.; Jacob, Daniel; Muller, Jean-Francois

1999-01-01

This report presents the results of distributions of tropospheric sulfate, Pb-210 and their precursors from a global 3-D model. This model is driven by assimilated meteorological fields generated by the Goddard Data Assimilation Office. Model results are compared with observations from surface sites and from multiplatform field campaigns of Pacific Exploratory Missions (PEM) and Advanced Composition Explorer (ACE). The model generally captures the seasonal variation of sulfate at the surface sites, and reproduces well the short-term in-situ observations. We will discuss the roles of various processes contributing to the sulfate levels in the troposphere, and the roles of sulfate aerosol in regional and global radiative forcing.

Mechanical performance and thermal stability of glass fiber reinforced silica aerogel composites based on co-precursor method by freeze drying

NASA Astrophysics Data System (ADS)

Zhou, Ting; Cheng, Xudong; Pan, Yuelei; Li, Congcong; Gong, Lunlun; Zhang, Heping

2018-04-01

In order to maintain the integrity, glass fiber (GF) reinforced silica aerogel composites were synthesized using methltrimethoxysilane (MTMS) and water glass co-precursor by freeze drying method. The composites were characterized by scanning electron microscopy, Brunauer-Emmett-Teller analysis, uniaxial compressive test, three-point bending test, thermal conductivity analysis, contact angle test, TG-DSC analysis. It was found that the molar ratio of MTMS/water glass could significantly affect the properties of composites. The bulk density and thermal conductivity first decreased and then increased with the increasing molar ratio. The composites showed remarkable mechanical strength and flexibility compared with pure silica aerogel. Moreover, when the molar ratio is 1.8, the composites showed high specific surface area (870.9 m2/g), high contact angle (150°), great thermal stability (560 °C) and low thermal conductivity (0.0248 W/m·K). These outstanding properties indicate that GF/aerogels have broad prospects in the field of thermal insulation.

Precursor medications as a source of methamphetamine and/or amphetamine positive drug testing results.

PubMed

Cody, John T

2002-05-01

Medical Review Officer interpretation of laboratory results is an important component of drug testing programs. The clinical evaluation of laboratory results to assess the possibility of appropriate medical use of a drug is a task with many different facets, depending on the drug class considered. This intercession prevents the reporting of positive results unless it is apparent that drugs were used illicitly. In addition to the commonly encountered prescribed drugs that yield positive drug testing results, other sources of positive results must be considered. This review describes a series of compounds referred to as "precursor" drugs that are metabolized by the body to amphetamine and/or methamphetamine. These compounds lead to positive results for amphetamines even though neither amphetamine nor methamphetamine were used, a possibility that must be considered in the review of laboratory results. Description of the drugs, their clinical indications, and results seen following administration are provided. This information allows for the informed evaluation of results with regard to the potential involvement of these drugs.

Multiresolution imaging of mantle reflectivity structure using SS and P'P' precursors

NASA Astrophysics Data System (ADS)

Schultz, Ryan; Gu, Yu J.

2013-10-01

Knowledge of the mantle reflectivity structure is highly dependent on our ability to efficiently extract, and properly interpret, small seismic arrivals. Among the various data types and techniques, long-period SS/PP precursors and high-frequency receiver functions are routinely utilized to increase the confidence of the recovered mantle stratifications at distinct spatial scales. However, low resolution and a complex Fresnel zone are glaring weaknesses of SS precursors, while over-reliance on receiver distribution is a formidable challenge for the analysis of converted waves from oceanic regions. A promising high frequency alternative to receiver functions is P'P' precursors, which are capable of resolving mantle structures at vertical and lateral resolution of ˜5 and ˜200 km, respectively, owing to their spectral content, shallow angle of incidence and near-symmetric Fresnel zones. This study presents a novel processing method for both SS (or PP) and P'P' precursors based on deconvolution, stacking, Radon transform and depth migration. A suite of synthetic tests is performed to quantify the fidelity and stability of this method under different data conditions. Our multiresolution survey of the mantle at targeted areas near Nazca-South America subduction zone reveal both olivine and garnet related transitions at depths below 400 km. We attribute a depressed 660 to thermal variations, whereas compositional variations atop the upper-mantle transition zone are needed to explain the diminished or highly complex reflected/scattered signals from the 410 km discontinuity. We also observe prominent P'P' reflections within the transition zone, and the anomalous amplitudes near the plate boundary zone indicate a sharp (˜10 km thick) transition that likely resonates with the frequency content of P'P' precursors. The migration of SS precursors in this study shows no evidence of split 660 reflections, but potential majorite-ilmenite (590-640 km) and ilmenite-perovskite transitions (740-750 km) are identified based on similarly processed high-frequency P'P' precursors. Additional findings of severely scattered energy in the lithosphere and distinct lower mantle reflections at ˜800 km could be potentially important but require further verifications. Overall, our improved imaging methods and the strong sensitivity of P'P' precursors to the existence, depth, sharpness and strength of reflective structures offer significant future promise for the understanding of mantle mineralogy and dynamics.

Determinants of disinfectant pretreatment efficacy for nitrosamine control in chloraminated drinking water.

PubMed

McCurry, Daniel L; Krasner, Stuart W; von Gunten, Urs; Mitch, William A

2015-11-01

Utilities using chloramines need strategies to mitigate nitrosamine formation to meet potential future nitrosamine regulations. The ability to reduce NDMA formation under typical post-chloramination conditions of pretreatment with ultraviolet light from a low pressure mercury lamp (LPUV), free chlorine (HOCl), ozone (O3), and UV light from a medium pressure mercury lamp (MPUV) were compared at exposures relevant to drinking water treatment. The order of efficacy after application to waters impacted by upstream wastewater discharges was O3 > HOCl ≈ MPUV > LPUV. NDMA precursor abatement generally did not correlate well between oxidants, and waters exhibited different behaviors with respect to pH and temperature, suggesting a variety of source-dependent NDMA precursors. For wastewater-impacted waters, the observed pH dependence for precursor abatement suggested the important role of secondary or tertiary amine precursors. Although hydroxyl radicals did not appear to be important for NDMA precursor abatement during O3 or MPUV pretreatment, the efficacy of MPUV correlated strongly with dissolved organic carbon concentration (p = 0.01), suggesting alternative indirect photochemical pathways. The temperature dependences during pre- and post-disinfection indicated that NDMA formation is likely to increase during warm seasons for O3 pretreatment, decrease for HOCl pretreatment, and remain unchanged for MPUV treatment, although seasonal changes in source water quality may counteract the temperature effects. For two waters impacted by relatively high polyDADMAC coagulant doses, pretreatment with HOCl, O3, and MPUV increased NDMA formation during post-chloramination. For O3 pretreatment, hydroxyl radicals likely led to precursor formation from the polymer in the latter tests. MPUV treatment of polymer-impacted water increased subsequent NDMA formation through an indirect photochemical process. Many factors may mitigate the importance of this increased NDMA formation, including the low polyDADMAC doses typically applied, and simultaneous degradation of watershed-associated precursors. Copyright © 2015 Elsevier Ltd. All rights reserved.

Encapsulating Metal Clusters and Acid Sites within Small Voids: Synthetic Strategies and Catalytic Consequences

NASA Astrophysics Data System (ADS)

Goel, Sarika

The selective encapsulation of metal clusters within zeolites can be used to prepare clusters that are uniform in diameter and to protect them against sintering and contact with feed impurities, while concurrently allowing active sites to select reactants based on their molecular size, thus conferring enzyme-like specificity to chemical catalysis. The apertures in small and medium-pore zeolites preclude the use of post-synthetic protocols to encapsulate the relevant metal precursors because cationic or anionic precursors with their charge-balancing double layer and gaseous complexes cannot diffuse through their windows or channels. We have developed general strategies to encapsulate metal clusters within small-pore zeolites by using metal precursors stabilized by ammonia or organic amine ligands, which stabilize metal precursors against their premature precipitation at the high temperature and pH conditions required for the hydrothermal synthesis of the target zeolite structures and favor interactions between metal precursors and incipient aluminosilicate nuclei during the self-assembly of microporous frameworks. When synthesis temperatures were higher than 400 K, available ligands were unable to prevent the premature precipitation of the metal precursors. In such cases, encapsulation was achieved instead via interzeolite transformations after successfully encapsulating metal precursors or clusters via post-synthesis exchange or ligand protection into parent zeolites and subsequently converting them into the target structures while retaining the encapsulated clusters or precursors. Such strategies led to the successful selective encapsulation of a wide range of metal clusters (Pt, Pd, Ru, Rh, Ir, Re, and Ag) within small-pore (SOD (sodalite), LTA (Linde type A (zeolite A)), GIS (gismondine), and ANA (analcime)) and medium-pore (MFI (ZSM-5)) zeolites. These protocols provide novel and diverse mechanism-based strategies for the design of catalysts with protected active sites. We have demonstrated the selectivity of the encapsulation processes by combining transmission electron microscopy and chemisorptive titrations with rigorous catalytic assessments of the ability of these materials to catalyze reactions of small molecules, which can access the intracrystalline voids, but not of larger molecules that cannot access the metal clusters within such voids. The selective confinement of clusters also prevented their contact with sulfur compounds (e.g., thiophene and H2S), thus allowing reactions to occur at conditions that otherwise render unconfined clusters unreactive. We have also developed synthetic protocols and guiding principles, inspired by mechanistic considerations, for the synthesis of zeolites via interzeolite transformations without the use of organic structure-directing agents (OSDA). More specifically, we have synthesized high-silica MFI (ZSM-5), CHA (chabazite), STF (SSZ-35) and MTW (ZSM-12) zeolites from FAU (faujasite) or BEA (beta) parent materials. Structures with lower framework densities (FAU or BEA) were successfully transformed into thermodynamically-favored, more stable structures with higher framework densities (MFI, CHA, STF, and MTW); to date, target materials with higher Si/Al ratios (Si/Al >10) have not been synthesized via interzeolite transformations without the aid of the OSDA species used to discover these zeolite structures and deemed essential up until now for their successful synthesis. Overcoming kinetic hurdles in such transformations required either the presence of common composite building units (CBU) between parent and target structures or, in their absence, the introduction of small amount of seeds of the daughter structures. The NaOH/SiO2 ratio, H2O/SiO2 ratio and Al content in reagents are used to enforce synchronization between the swelling and local restructuring within parent zeolite domains with the spalling of fragments or building units from seeds of the target structure. The pseudomorphic nature of these seed-mediated transformations, which conserve the volume occupied by the parent crystals and lead to similar size and crystal shape in products, reflect incipient nucleation of target structures occurring at the outer regions of the parent domains and lead to the formation of mesoporosity as a natural consequence of the space-conserving nature of these structural changes and of the higher density of the daughter frameworks. The synthesis mechanism and the guidelines developed enable us to enforce conditions required for the formation of zeolites that previously required OSDA species for their synthesis, thus expanding to a significant extent the diversity of zeolite frameworks that are accessible via these synthesis protocols and providing potential savings in the time and cost involved in the synthesis of some of these zeolite structures.

Foundations of reading comprehension in children with intellectual disabilities.

PubMed

van Wingerden, Evelien; Segers, Eliane; van Balkom, Hans; Verhoeven, Ludo

2017-01-01

Knowledge about predictors for reading comprehension in children with intellectual disabilities (ID) is still fragmented. This study compared reading comprehension, word decoding, listening comprehension, and reading related linguistic and cognitive precursor measures in children with mild ID and typically developing controls. Moreover, it was explored how the precursors related to reading achievement. Children with mild ID and typical controls were assessed on reading comprehension, decoding, language comprehension, and linguistic (early literacy skills, vocabulary, grammar) and cognitive (rapid naming, phonological short-term memory, working memory, temporal processing, nonverbal reasoning) precursor measures. It was tested to what extent variations in reading comprehension could be explained from word decoding, listening comprehension and precursor measures. The ID group scored significantly below typical controls on all measures. Word decoding was at or above first grade level in half the ID group. Reading comprehension in the ID group was related to word decoding, listening comprehension, early literacy skills, and temporal processing. The reading comprehension profile of children with mild ID strongly resembles typical early readers. The simple view of reading pertains to children with mild ID, with additional influence of early literacy skills and temporal processing. Copyright © 2016 Elsevier Ltd. All rights reserved.

Fibrous selective emitter structures from sol-gel process

NASA Astrophysics Data System (ADS)

Chen, K. C.

1999-03-01

Selective emitters have the potential benefit of high efficiency due to the matching of emission spectra to the response of photovoltaic (PV) cells. Continuous uniform rare-earth oxide selective emitter fibers were successfully fabricated using a viscous solution made from metal organic precursors. Cylindrical- and planar configuration emitter structures were made by direct cross-winding or stacking of precursor fiber layers. The combustion and optical performance of the planar emitter structures were tested. The results indicates that both the designing of the fiber packing density and the thickness is critical for high photon and power output.

High energy neutrinos from gamma-ray bursts with precursor supernovae.

PubMed

Razzaque, Soebur; Mészáros, Peter; Waxman, Eli

2003-06-20

The high energy neutrino signature from proton-proton and photo-meson interactions in a supernova remnant shell ejected prior to a gamma-ray burst provides a test for the precursor supernova, or supranova, model of gamma-ray bursts. Protons in the supernova remnant shell and photons entrapped from a supernova explosion or a pulsar wind from a fast-rotating neutron star remnant provide ample targets for protons escaping the internal shocks of the gamma-ray burst to interact and produce high energy neutrinos. We calculate the expected neutrino fluxes, which can be detected by current and future experiments.

The Prevalence and Management of Systemic Amyloidosis in Western Countries.

PubMed

Nienhuis, Hans L A; Bijzet, Johan; Hazenberg, Bouke P C

2016-04-01

Amyloidosis has been a mystery for centuries, but research of the last decennia has clarified many of the secrets of this group of diseases. A protein-based classification of amyloidosis helps to understand problems that were part of the obsolete clinical classification in primary, secondary, and familial amyloidosis. All types of amyloid are secondary to some underlying precursor-producing process: each type is caused by a misfolded soluble precursor protein that becomes deposited as insoluble amyloid fibrils. The incidence of amyloidosis is not well documented, but probably falls between 5 and 13 per million per year. Prevalence data are scarce, but one UK study indicates about 20 per million inhabitants. Amyloidosis can be localized (amyloid deposited in the organ or tissue of precursor production) or systemic (amyloid at one or more sites distant from the site of precursor production). The major systemic types of amyloidosis are AL (associated with a light chain-producing plasma cell dyscrasia), AA (associated with longstanding inflammation), wild-type ATTR (associated with normal transthyretin and old age), and hereditary ATTR (associated with a transthyretin mutation) amyloidosis. Imaging techniques, such as cardiac ultrasound, magnetic resonance imaging, bone scintigraphy, and serum amyloid P component scintigraphy, are useful both for diagnosing amyloidosis and for assessing disease severity. Serologic markers are useful for detecting organ disease and disease monitoring during follow-up. Current treatment modalities are directed against the ongoing supply of precursor proteins and thereby aim to stop further accumulation of amyloid. Novel treatment modalities, such as interference with amyloid formation and even removal of amyloid, are being studied. A well-thought and planned monitoring during follow-up helps to assess the effect of treatment and to early detect possible progression of amyloidosis. Clinical management comprises histologic proof of amyloid, evidence of systemic deposition, reliable typing, precursor assessment, severity of organ disease, risk assessment and prognosis, choice of treatment, and planned monitoring during follow-up. (1) AL amyloidosis is the most prevalent type of amyloidosis accounting for 65% of the amyloidosis-diagnosed patients in the UK and for 93% of the amyloidosis-diagnosed patients in China. The predisposition of men over women to develop AL amyloidosis might be higher in China than in Western countries (2:1 vs. 1.3:1). Both in the East and West, incidence increases with age. At the time of diagnosis, edema is twice as frequent and the proportion of renal involvement is higher in Chinese compared to Western patients. (2) Melphalan followed by autologous stem cell transplantation (ASCT) is the current standard therapy but is restricted to eligible patients. The efficacy and safety of bortezomib combined with dexamethasone were proven in Western patients and recently confirmed in a Chinese cohort. Recent studies in China and the US indicate that bortezomib induction prior to ASCT increases the response rate. Thalidomide and lenalidomide have shown benefit, but toxicity and lack of clinical evidence exclude these agents from first-line therapy. The green tea extract epigallocatechin-3-gallate is under investigation as an inhibitor of AL amyloid formation and a compound that might dissolve amyloid.

Synergistic Interactions of Eugenol-tosylate and Its Congeners with Fluconazole against Candida albicans.

PubMed

Ahmad, Aijaz; Wani, Mohmmad Younus; Khan, Amber; Manzoor, Nikhat; Molepo, Julitha

2015-01-01

We previously reported the antifungal properties of a monoterpene phenol "Eugenol" against different Candida strains and have observed that the addition of methyl group to eugenol drastically increased its antimicrobial potency. Based on the results and the importance of medicinal synthetic chemistry, we synthesized eugenol-tosylate and its congeners (E1-E6) and tested their antifungal activity against different clinical fluconazole (FLC)- susceptible and FLC- resistant C. albicans isolates alone and in combination with FLC by determining fractional inhibitory concentration indices (FICIs) and isobolograms calculated from microdilution assays. Minimum inhibitory concentration (MIC) results confirmed that all the tested C. albicans strains were variably susceptible to the semi-synthetic derivatives E1-E6, with MIC values ranging from 1-62 μg/ml. The test compounds in combination with FLC exhibited either synergy (36%), additive (41%) or indifferent (23%) interactions, however, no antagonistic interactions were observed. The MICs of FLC decreased 2-9 fold when used in combination with the test compounds. Like their precursor eugenol, all the derivatives showed significant impairment of ergosterol biosynthesis in all C. albicans strains coupled with down regulation of the important ergosterol biosynthesis pathway gene-ERG11. The results were further validated by docking studies, which revealed that the inhibitors snugly fitting the active site of the target enzyme, mimicking fluconazole, may well explain their excellent inhibitory activity. Our results suggest that these compounds have a great potential as antifungals, which can be used as chemosensitizing agents with the known antifungal drugs.

Two key polymorphisms in a newly discovered allele of the Vitis vinifera TPS24 gene are responsible for the production of the rotundone precursor α-guaiene.

PubMed

Drew, Damian Paul; Andersen, Trine Bundgaard; Sweetman, Crystal; Møller, Birger Lindberg; Ford, Christopher; Simonsen, Henrik Toft

2016-02-01

Rotundone was initially identified as a grape-derived compound responsible for the peppery aroma of Shiraz wine varieties. It has subsequently been found in black and white pepper and several other spices. Because of its potent aroma, the molecular basis for rotundone formation is of particular relevance to grape and wine scientists and industry. We have identified and functionally characterized in planta a sesquiterpene synthase, VvGuaS, from developing grape berries, and have demonstrated that it produces the precursor of rotundone, α-guaiene, as its main product. The VvGuaS enzyme is a novel allele of the sesquiterpene synthase gene, VvTPS24, which has previously been reported to encode VvPNSeInt, an enzyme that produces a variety of selinene-type sesquiterpenes. This newly discovered VvTPS24 allele encodes an enzyme 99.5% identical to VvPNSeInt, with the differences comprising just 6 out of the 561 amino acid residues. Molecular modelling of the enzymes revealed that two of these residues, T414 and V530, are located in the active site of VvGuaS within 4 Å of the binding-site of the substrate, farnesyl pyrophosphate. Mutation of these two residues of VvGuaS into the corresponding polymorphisms in VvPNSeInt results in a complete functional conversion of one enzyme into the other, while mutation of each residue individually produces an intermediate change in the product profile. We have therefore demonstrated that VvGuaS, an enzyme responsible for production of the rotundone precursor, α-guaiene, is encoded by a novel allele of the previously characterized grapevine gene VvTPS24 and that two specific polymorphisms are responsible for functional differences between VvTPS24 alleles. © The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology.

First demonstration of cerebrospinal fluid and plasma A beta lowering with oral administration of a beta-site amyloid precursor protein-cleaving enzyme 1 inhibitor in nonhuman primates.

PubMed

Sankaranarayanan, Sethu; Holahan, Marie A; Colussi, Dennis; Crouthamel, Ming-Chih; Devanarayan, Viswanath; Ellis, Joan; Espeseth, Amy; Gates, Adam T; Graham, Samuel L; Gregro, Allison R; Hazuda, Daria; Hochman, Jerome H; Holloway, Katharine; Jin, Lixia; Kahana, Jason; Lai, Ming-tain; Lineberger, Janet; McGaughey, Georgia; Moore, Keith P; Nantermet, Philippe; Pietrak, Beth; Price, Eric A; Rajapakse, Hemaka; Stauffer, Shaun; Steinbeiser, Melissa A; Seabrook, Guy; Selnick, Harold G; Shi, Xiao-Ping; Stanton, Matthew G; Swestock, John; Tugusheva, Katherine; Tyler, Keala X; Vacca, Joseph P; Wong, Jacky; Wu, Guoxin; Xu, Min; Cook, Jacquelynn J; Simon, Adam J

2009-01-01

beta-Site amyloid precursor protein (APP)-cleaving enzyme (BACE) 1 cleavage of amyloid precursor protein is an essential step in the generation of the potentially neurotoxic and amyloidogenic A beta 42 peptides in Alzheimer's disease. Although previous mouse studies have shown brain A beta lowering after BACE1 inhibition, extension of such studies to nonhuman primates or man was precluded by poor potency, brain penetration, and pharmacokinetics of available inhibitors. In this study, a novel tertiary carbinamine BACE1 inhibitor, tertiary carbinamine (TC)-1, was assessed in a unique cisterna magna ported rhesus monkey model, where the temporal dynamics of A beta in cerebrospinal fluid (CSF) and plasma could be evaluated. TC-1, a potent inhibitor (IC(50) approximately 0.4 nM), has excellent passive membrane permeability, low susceptibility to P-glycoprotein transport, and lowered brain A beta levels in a mouse model. Intravenous infusion of TC-1 led to a significant but transient lowering of CSF and plasma A beta levels in conscious rhesus monkeys because it underwent CYP3A4-mediated metabolism. Oral codosing of TC-1 with ritonavir, a potent CYP3A4 inhibitor, twice daily over 3.5 days in rhesus monkeys led to sustained plasma TC-1 exposure and a significant and sustained reduction in CSF sAPP beta, A beta 40, A beta 42, and plasma A beta 40 levels. CSF A beta 42 lowering showed an EC(50) of approximately 20 nM with respect to the CSF [TC-1] levels, demonstrating excellent concordance with its potency in a cell-based assay. These results demonstrate the first in vivo proof of concept of CSF A beta lowering after oral administration of a BACE1 inhibitor in a nonhuman primate.

The maternal genes Ci-p53/p73-a and Ci-p53/p73-b regulate zygotic ZicL expression and notochord differentiation in Ciona intestinalis embryos.

PubMed

Noda, Takeshi

2011-12-01

I isolated a Ciona intestinalis homolog of p53, Ci-p53/p73-a, in a microarray screen of rapidly degraded maternal mRNA by comparing the transcriptomes of unfertilized eggs and 32-cell stage embryos. Higher expression of the gene in eggs and lower expression in later embryonic stages were confirmed by whole-mount in situ hybridization (WISH) and quantitative reverse transcription-PCR (qRT-PCR); expression was ubiquitous in eggs and early embryos. Knockdown of Ci-p53/p73-a by injection of antisense morpholino oligonucleotides (MOs) severely perturbed gastrulation cell movements and expression of notochord marker genes. A key regulator of notochord differentiation in Ciona embryos is Brachyury (Ci-Bra), which is directly activated by a zic-like gene (Ci-ZicL). The expression of Ci-ZicL and Ci-Bra in A-line notochord precursors was downregulated in Ci-p53/p73-a knockdown embryos. Maternal expression of Ci-p53/p73-b, a homolog of Ci-p53/p73-a, was also detected. In Ci-p53/p73-b knockdown embryos, gastrulation cell movements, expression of Ci-ZicL and Ci-Bra in A-line notochord precursors, and expression of notochord marker gene at later stages were perturbed. The upstream region of Ci-ZicL contains putative p53-binding sites. Cis-regulatory analysis of Ci-ZicL showed that these sites are involved in expression of Ci-ZicL in A-line notochord precursors at the 32-cell and early gastrula stages. These results suggest that p53 genes are maternal factors that play a crucial role in A-line notochord differentiation in C. intestinalis embryos by regulating Ci-ZicL expression. Copyright © 2011 Elsevier Inc. All rights reserved.

Maturation of the Hepatitis A Virus Capsid Protein VP1 Is Not Dependent on Processing by the 3Cpro Proteinase

PubMed Central

Martin, Annette; Bénichou, Danièle; Chao, Shih-Fong; Cohen, Lisette M.; Lemon, Stanley M.

1999-01-01

Most details of the processing of the hepatitis A virus (HAV) polyprotein are known. Unique among members of the family Picornaviridae, the primary cleavage of the HAV polyprotein is mediated by 3Cpro, the only proteinase known to be encoded by the virus, at the 2A/2B junction. All other cleavages of the polyprotein have been considered to be due to 3Cpro, although the precise location and mechanism responsible for the VP1/2A cleavage have been controversial. Here we present data that argue strongly against the involvement of the HAV 3Cpro proteinase in the maturation of VP1 from its VP1-2A precursor. Using a heterologous expression system based on recombinant vaccinia viruses directing the expression of full-length or truncated capsid protein precursors, we show that the C terminus of the mature VP1 capsid protein is located near residue 764 of the polyprotein. However, a proteolytically active HAV 3Cpro that was capable of directing both VP0/VP3 and VP3/VP1 cleavages in vaccinia virus-infected cells failed to process the VP1-2A precursor. Using site-directed mutagenesis of an infectious molecular clone of HAV, we modified potential VP1/2A cleavage sites that fit known 3Cpro recognition criteria and found that a substitution that ablates the presumed 3Cpro dipeptide recognition sequence at Glu764-Ser765 abolished neither infectivity nor normal VP1 maturation. Altered electrophoretic mobility of VP1 from a viable mutant virus with an Arg764 substitution indicated that this residue is present in VP1 and that the VP1/2A cleavage occurs downstream of this residue. These data indicate that maturation of the HAV VP1 capsid protein is not dependent on 3Cpro processing and may thus be uniquely dependent on a cellular proteinase. PMID:10400711

Measurements of ozone and its precursors in Beijing in summer

NASA Astrophysics Data System (ADS)

Lee, J. D.; Squires, F. A.; Dunmore, R.; Hamilton, J. F.; Hopkins, J. R.; Rickard, A. R.

2017-12-01

Over the past few years there have been substantial reductions in emission of primary pollutants (e.g. PM, NOx) in Beijing. However, levels of ozone (O3), which is produced from VOCs and NOxin the presence of sunlight, frequently break recommended exposure limits in Beijing and other large conurbations in China. In fact, it is suggested that ozone is likely to become the major air pollutant effecting human health in Beijing over the next 5-10 years. For 5 weeks in May and June 2017 O3 was measured, along with NOx, CO and a large range of VOCs (C2 - C13) at the Institute of Atmospheric Physics of the Chinese Academy of Sciences site, close to the 4th ring road in central Beijing. Elevated levels of O3 were regularly observed, with maximum concentrations of 180 ppbv. On 75% of days during this period, O3 breached the recommended WHO 8 hour exposure limit of 60 ppbv. Data will be presented showing the effect of different levels of precursor species and photolysis rates on O3. The peak concentration of O3 on each day seemed to have little correlation with NOx. Typically NO concentrations were elevated during the morning but often decreased to below <0.05 ppbv during the afternoon hours when the O3 concentrations peaked. The highest levels of O3 were observed on days when CO, VOC and SO2 concentrations were highest, showing the potential importance of industrial emissions of precursor VOCs for O3 formation. Temperatures often peaked at >35oC meaning biogenic emissions also influenced the chemistry at the site, with several ppbv of isoprene measured during the afternoons. The importance of different VOCs for in-situ O3 formation is investigated using a simple steady state analysis of OH reactivity, along with a more detailed analysis using the Master Chemical Mechanism.

Water quality following extensive beetle-induced tree mortality: Interplay of aromatic carbon loading, disinfection byproducts, and hydrologic drivers.

PubMed

Brouillard, Brent M; Dickenson, Eric R V; Mikkelson, Kristin M; Sharp, Jonathan O

2016-12-01

The recent bark beetle epidemic across western North America may impact water quality as a result of elevated organic carbon release and hydrologic shifts associated with extensive tree dieback. Analysis of quarterly municipal monitoring data from 2004 to 2014 with discretization of six water treatment facilities in the Rocky Mountains by extent of beetle impact revealed a significant increasing trend in total organic carbon (TOC) and total trihalomethane (TTHM) production within high (≳50% areal infestation) beetle-impacted watersheds while no or insignificant trends were found in watersheds with lower impact levels. Alarmingly, the TTHM concentration trend in the high impact sites exceeded regulatory maximum contaminant levels during the most recent two years of analysis (2013-14). To evaluate seasonal differences, explore the interplay of water quality and hydrologic processes, and eliminate variability associated with municipal reporting, these treatment facilities were targeted for more detailed surface water sampling and characterization. Surface water samples collected from high impact watersheds exhibited significantly higher TOC, aromatic signatures, and disinfection byproduct (DBP) formation potential than watersheds with lower infestation levels. Spectroscopic analyses of surface water samples indicated that these heightened DBP precursor levels are a function of both elevated TOC loading and increased aromatic character. This association was heightened during precipitation and runoff events in high impact sites, supporting the hypothesis that altered hydrologic flow paths resulting from tree mortality mobilize organic carbon and elevate DBP formation potential for several months after runoff ceases. The historical trends found here likely underestimate the full extent of TTHM shifts due to monitoring biases with the extended seasonal release of DBP precursors increasing the potential for human exposure. Collectively, our analysis suggests that while water quality impacts continue to rise nearly one decade after infestation, significant increases in TOC mobilization and DBP precursors are limited to watersheds that experience extensive tree mortality. Copyright © 2016 Elsevier B.V. All rights reserved.

Understanding the synthesis, performance, and passivation of metal oxide photocathodes

NASA Astrophysics Data System (ADS)

Flynn, Cory James

Metal oxides are ubiquitous in semiconductor technologies for their ease of synthesis, chemical stability, and tunable optical/electronic properties. These properties are especially important to fabricating efficient photoelectrodes for solar-energy applications. To counter inherent problems in these materials, new strategies were developed and successfully implemented on the widely-utilized p-type semiconductor, NiO. As the size of semiconductor materials shrink, the surface-to-volume ratio increases and surface defects dominate the performance of the materials. Surface defects can alter the optical and electronic characteristics of materials by changing the Fermi level, charge-carrier mobility, and surface reactivity. We first present a strategy to increase the electrical mobility of mesoporous metal oxide electrode materials by optimizing shape morphology. Transitioning from nanospheres to hexagonal nanoplatelets increased the charge-carrier mobility by one order of magnitude. We then employed this improved material with a new vapor-phase deposition method termed targeted atomic deposition (TAD) to selectively passivate defect sites in semiconductor nanomaterials. We demonstrated the capabilities of this passivation method by applying a TAD of aluminum onto NiO. By exploiting a temperature-dependent deposition process, we selectively passivated the highly reactive sites in NiO: oxygen dangling bonds associated with Ni vacancies. The TAD treatment completely passivated all measurable surface defects, optically bleached the material, and significantly improved all photovoltaic performance metrics in dye-sensitized solar cells. The technique was proven to be generic to numerous forms of NiO. While the implementation of TAD of Al was successful, the process involved pulsing two precursors to passivate the material. Ideally, the TAD process should require only a single precursor and continuous exposure. We utilized a continuous flow of diborane to perform a TAD of B onto NiO. The TAD process was successfully implemented in a simplified manner. The treatment moderately increased DSSC performance and proved viability with a different vapor-phase precursor.

Luminescent sensors for tracking spatial particle distributions in an explosion

NASA Astrophysics Data System (ADS)

Anderson, Benjamin R.; Gunawidjaja, Ray; Diez-y-Riega, Helena; Eilers, Hergen; Svingala, Forrest R.; Daniels, Amber; Lightstone, James M.

2017-01-01

We previously developed and tested thermally sensitive particles that, when seeded into an explosive event, flow with the expanding post-detonation fireball and provide ex-situ measurements of this thermal environment. This current work presents the development and testing of tracking particles that are used in concert with the thermally sensitive particles to encode the initial positions of materials recovered for ex-situ analysis. These tracking sensors consist of fully-crystallized (c) rare-earth-doped yttria particles such as c-Dy:Y2O3, c-Sm:Y2O3, and c-Er,Yb:Y2O3. The temperature sensors consist of mixtures of precursor (p) and fully crystallized materials such as p-Eu:Y2O3/c-Tb:Y2O3 or p-Eu:ZrO2. Three mixtures containing one of the tracking sensors and one of the temperature sensing mixtures are placed at different locations within the chamber. Post-detonation, the tracking particles in the debris are excited by 355 nm light, resulting in different color luminescence, and allowing for potential visual inspection of the particle distribution originating from the different locations. Meanwhile, the temperature is determined from spectral changes of the precursor sensor materials or by comparison of the precursor sensor materials with the Tb:Y2O3 intensity reference.

Development of an activated carbon filter to remove NO2 and HONO in indoor air.

PubMed

Yoo, Jun Young; Park, Chan Jung; Kim, Ki Yeong; Son, Youn-Suk; Kang, Choong-Min; Wolfson, Jack M; Jung, In-Ha; Lee, Sung-Joo; Koutrakis, Petros

2015-05-30

To obtain the optimum removal efficiency of NO2 and HONO by coated activated carbon (ACs), the influencing factors, including the loading rate, metal and non-metal precursors, and mixture ratios, were investigated. The NOx removal efficiency (RE) for K, with the same loading (1.0 wt.%), was generally higher than for those loaded with Cu or Mn. The RE of NO2 was also higher when KOH was used as the K precursor, compared to other K precursors (KI, KNO3, and KMnO4). In addition, the REs by the ACs loaded with K were approximately 38-55% higher than those by uncoated ACs. Overall, the REs (above 95%) of HONO and NOx with 3% KOH were the highest of the coated AC filters that were tested. Additionally, the REs of NOx and HONO using a mixing ratio of 6 (2.5% PABA (p-aminobenzoic acid)+6% H3PO4):4 (3% KOH) were the highest of all the coatings tested (both metal and non-metal). The results of this study show that AC loaded with various coatings has the potential to effectively reduce NO2 and HONO levels in indoor air. Copyright © 2015 Elsevier B.V. All rights reserved.

A simplified calculation procedure for mass isotopomer distribution analysis (MIDA) based on multiple linear regression.

PubMed

Fernández-Fernández, Mario; Rodríguez-González, Pablo; García Alonso, J Ignacio

2016-10-01

We have developed a novel, rapid and easy calculation procedure for Mass Isotopomer Distribution Analysis based on multiple linear regression which allows the simultaneous calculation of the precursor pool enrichment and the fraction of newly synthesized labelled proteins (fractional synthesis) using linear algebra. To test this approach, we used the peptide RGGGLK as a model tryptic peptide containing three subunits of glycine. We selected glycine labelled in two 13 C atoms ( 13 C 2 -glycine) as labelled amino acid to demonstrate that spectral overlap is not a problem in the proposed methodology. The developed methodology was tested first in vitro by changing the precursor pool enrichment from 10 to 40% of 13 C 2 -glycine. Secondly, a simulated in vivo synthesis of proteins was designed by combining the natural abundance RGGGLK peptide and 10 or 20% 13 C 2 -glycine at 1 : 1, 1 : 3 and 3 : 1 ratios. Precursor pool enrichments and fractional synthesis values were calculated with satisfactory precision and accuracy using a simple spreadsheet. This novel approach can provide a relatively rapid and easy means to measure protein turnover based on stable isotope tracers. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Preliminary Analysis of Aircraft Loss of Control Accidents: Worst Case Precursor Combinations and Temporal Sequencing

NASA Technical Reports Server (NTRS)

Belcastro, Christine M.; Groff, Loren; Newman, Richard L.; Foster, John V.; Crider, Dennis H.; Klyde, David H.; Huston, A. McCall

2014-01-01

Aircraft loss of control (LOC) is a leading cause of fatal accidents across all transport airplane and operational classes, and can result from a wide spectrum of hazards, often occurring in combination. Technologies developed for LOC prevention and recovery must therefore be effective under a wide variety of conditions and uncertainties, including multiple hazards, and their validation must provide a means of assessing system effectiveness and coverage of these hazards. This requires the definition of a comprehensive set of LOC test scenarios based on accident and incident data as well as future risks. This paper defines a comprehensive set of accidents and incidents over a recent 15 year period, and presents preliminary analysis results to identify worst-case combinations of causal and contributing factors (i.e., accident precursors) and how they sequence in time. Such analyses can provide insight in developing effective solutions for LOC, and form the basis for developing test scenarios that can be used in evaluating them. Preliminary findings based on the results of this paper indicate that system failures or malfunctions, crew actions or inactions, vehicle impairment conditions, and vehicle upsets contributed the most to accidents and fatalities, followed by inclement weather or atmospheric disturbances and poor visibility. Follow-on research will include finalizing the analysis through a team consensus process, defining future risks, and developing a comprehensive set of test scenarios with correlation to the accidents, incidents, and future risks. Since enhanced engineering simulations are required for batch and piloted evaluations under realistic LOC precursor conditions, these test scenarios can also serve as a high-level requirement for defining the engineering simulation enhancements needed for generating them.

Analog Testing of Operations Concepts for Mitigation of Communication Latency During Human Space Exploration

NASA Technical Reports Server (NTRS)

Chappell, Steven P.; Abercromby, Andrew F.; Miller, Matthew J.; Halcon, Christopher; Gernhardt, Michael L.

2016-01-01

OBJECTIVES: NASA Extreme Environment Mission Operations (NEEMO) is an underwater spaceflight analog that allows a true mission-like operational environment and uses buoyancy effects and added weight to simulate different gravity levels. Three missions were undertaken from 2014-2015, NEEMO's 18-20. All missions were performed at the Aquarius undersea research habitat. During each mission, the effects of varying operations concepts and tasks type and complexity on representative communication latencies associated with Mars missions were studied. METHODS: 12 subjects (4 per mission) were weighed out to simulate near-zero or partial gravity extravehicular activity (EVA) and evaluated different operations concepts for integration and management of a simulated Earth-based science backroom team (SBT) to provide input and direction during exploration activities. Exploration traverses were planned in advance based on precursor data collected. Subjects completed science-related tasks including presampling surveys, geologic-based sampling, and marine-based sampling as a portion of their tasks on saturation dives up to 4 hours in duration that were to simulate extravehicular activity (EVA) on Mars or the moons of Mars. One-way communication latencies, 5 and 10 minutes between space and mission control, were simulated throughout the missions. Objective data included task completion times, total EVA times, crew idle time, translation time, SBT assimilation time (defined as time available for SBT to discuss data/imagery after it has been collected, in addition to the time taken to watch imagery streaming over latency). Subjective data included acceptability, simulation quality, capability assessment ratings, and comments. RESULTS: Precursor data can be used effectively to plan and execute exploration traverse EVAs (plans included detailed location of science sites, high-fidelity imagery of the sites, and directions to landmarks of interest within a site). Operations concepts that allow for presampling surveys enable efficient traverse execution and meaningful Mission Control Center (MCC) interaction across long communication latencies and can be done with minimal crew idle time. Imagery and information from the EVA crew that is transmitted real-time to the intravehicular (IV) crewmember(s) can be used to verify that exploration traverse plans are being executed correctly. That same data can be effectively used by MCC (across comm latency) to provide further instructions to the crew from a SBT on sampling priorities, additional tasks, and changes to the plan. Text / data capabilities are preferred over voice capabilities between MCC and IV when executing exploration traverse plans over communication latency. Autonomous crew planning tools can be effective at modifying existing plans if the objectives and constraints are clearly defined.

Agreement between the 'point of care' tests for microalbuminuria and HbA1c performed in mexican family medicine units and the results of standard laboratory tests.

PubMed

Valdez-González, Leticia A; Méndez-Padrón, Araceli; Gómez-Díaz, Rita A; Valladares-Salgado, Adán; Sánchez-Becerra, Martha Catalina; Mondragón-González, Rafael; Hernández-Rubí, Jaime; González-Hermosillo, Arturo; Cruz, Miguel; Borja, Víctor; Wacher, Niels H

The albumin-creatinine ratio is considered an indicator of microalbuminuria, precursor to chronic kidney disease, while HbA1c is used to measure glycemic control. Given the prevalence of diabetes-related nephropathy, spot testing of albumin has long been recommended as a preventative measure, for the timely detection of microalbuminuria. However, many countries do not have this testing available in primary care, and sometimes not even in second- and third-level care. The objective of this study was to compare agreement of the microalbuminuria and HbA1c results obtained in the laboratory with 'gold standard' techniques, with those obtained on site with a 'Point of Care' DCA Vantage™ device by Siemens. Results for the albumin-creatinine ratio and HbA1c from the Siemens DCA Vantage™ point of care device were compared with those from standard laboratory tests in 25 family medicine units in Mexico City and Toluca, State of Mexico, in patients diagnosed with type-2 diabetes. Agreement between the albumin values of the 2 tests was 0.745 (CI 95% 0.655-0.812). Agreement between the two measurement techniques for HbA1c was 0.970 (CI 95% 0.966-0.973). The results obtained were sufficiently comparative (R i = 0.74 for albumin-creatinine ratio and R i  = 0.97 for HbA1c) to justify the use of the point of care device. Given the high agreement between the point of care device and laboratory tests, this device could be used to identify chronic kidney disease and glycemic control for more adequate treatment in patients with diabetes, especially in remote areas.

Wetlands receiving water treated with coagulants improve water quality by removing dissolved organic carbon and disinfection byproduct precursors.

PubMed

Hansen, Angela M; Kraus, Tamara E C; Bachand, Sandra M; Horwath, William R; Bachand, Philip A M

2018-05-01

Constructed wetlands are used worldwide to improve water quality while also providing critical wetland habitat. However, wetlands have the potential to negatively impact drinking water quality by exporting dissolved organic carbon (DOC) that upon disinfection can form disinfection byproducts (DBPs) like trihalomethanes (THMs) and haloacetic acids (HAAs). We used a replicated field-scale study located on organic rich soils in California's Sacramento-San Joaquin Delta to test whether constructed flow-through wetlands which receive water high in DOC that is treated with either iron- or aluminum-based coagulants can improve water quality with respect to DBP formation. Coagulation alone removed DOC (66-77%) and THM (67-70%) precursors, and was even more effective at removing HAA precursors (77-90%). Passage of water through the wetlands increased DOC concentrations (1.5-7.5mgL -1 ), particularly during the warmer summer months, thereby reversing some of the benefits from coagulant addition. Despite this addition, water exiting the wetlands treated with coagulants had lower DOC and DBP precursor concentrations relative to untreated source water. Benefits of the coagulation-wetland systems were greatest during the winter months (approx. 50-70% reduction in DOC and DBP precursor concentrations) when inflow water DOC concentrations were higher and wetland DOC production was lower. Optical properties suggest DOC in this system is predominantly comprised of high molecular weight, aromatic compounds, likely derived from degraded peat soils. Published by Elsevier B.V.

Current challenges for pre-earthquake electromagnetic emissions: shedding light from micro-scale plastic flow, granular packings, phase transitions and self-affinity notion of fracture process

NASA Astrophysics Data System (ADS)

Eftaxias, K.; Potirakis, S. M.

2013-10-01

Are there credible electromagnetic (EM) potential earthquake (EQ) precursors? This a question debated in the scientific community and there may be legitimate reasons for the critical views. The negative view concerning the existence of EM potential precursors is enhanced by features that accompany their observation which are considered as paradox ones, namely, these signals: (i) are not observed at the time of EQs occurrence and during the aftershock period, (ii) are not accompanied by large precursory strain changes, (iii) are not accompanied by simultaneous geodetic or seismological precursors and (iv) their traceability is considered problematic. In this work, the detected candidate EM potential precursors are studied through a shift in thinking towards the basic science findings relative to granular packings, micron-scale plastic flow, interface depinning, fracture size effects, concepts drawn from phase transitions, self-affine notion of fracture and faulting process, universal features of fracture surfaces, recent high quality laboratory studies, theoretical models and numerical simulations. We try to contribute to the establishment of strict criteria for the definition of an emerged EM anomaly as a possibly EQ-related one, and to the explanation of potential precursory EM features which have been considered as paradoxes. A three-stage model for EQ generation by means of pre-EQ fracture-induced EM emissions is proposed. The claim that the observed EM potential precursors may permit a real-time and step-by-step monitoring of the EQ generation is tested.

Functional electrical stimulation-facilitated proliferation and regeneration of neural precursor cells in the brains of rats with cerebral infarction

PubMed Central

Xiang, Yun; Liu, Huihua; Yan, Tiebin; Zhuang, Zhiqiang; Jin, Dongmei; Peng, Yuan

2014-01-01

Previous studies have shown that proliferation of endogenous neural precursor cells cannot alone compensate for the damage to neurons and axons. From the perspective of neural plasticity, we observed the effects of functional electrical stimulation treatment on endogenous neural precursor cell proliferation and expression of basic fibroblast growth factor and epidermal growth factor in the rat brain on the infarct side. Functional electrical stimulation was performed in rat models of acute middle cerebral artery occlusion. Simultaneously, we set up a placebo stimulation group and a sham-operated group. Immunohistochemical staining showed that, at 7 and 14 days, compared with the placebo group, the numbers of nestin (a neural precursor cell marker)-positive cells in the subgranular zone and subventricular zone were increased in the functional electrical stimulation treatment group. Western blot assays and reverse-transcription PCR showed that total protein levels and gene expression of epidermal growth factor and basic fibroblast growth factor were also upregulated on the infarct side. Prehensile traction test results showed that, at 14 days, prehension function of rats in the functional electrical stimulation group was significantly better than in the placebo group. These results suggest that functional electrical stimulation can promote endogenous neural precursor cell proliferation in the brains of acute cerebral infarction rats, enhance expression of basic fibroblast growth factor and epidermal growth factor, and improve the motor function of rats. PMID:25206808

Design of a Mars rover and sample return mission

NASA Technical Reports Server (NTRS)

Bourke, Roger D.; Kwok, Johnny H.; Friedlander, Alan

1990-01-01

The design of a Mars Rover Sample Return (MRSR) mission that satisfies scientific and human exploration precursor needs is described. Elements included in the design include an imaging rover that finds and certifies safe landing sites and maps rover traverse routes, a rover that operates the surface with an associated lander for delivery, and a Mars communications orbiter that allows full-time contact with surface elements. A graph of MRSR candidate launch vehice performances is presented.

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

Agnew, Douglas W.; DiMucci, Ida M.; Arroyave, Alejandra

A permanently porous, three-dimensional metal–organic material formed from zero-valent metal nodes is presented. Combination of ditopic m-terphenyl diisocyanide, [CNAr Mes2] 2, and the d 10 Ni(0) precursor Ni(COD) 2, produces a porous metal–organic material featuring tetrahedral [Ni(CNAr Mes2) 4] n structural sites. X-ray absorption spectroscopy provides firm evidence for the presence of Ni(0) centers, whereas gas-sorption and thermogravimetric analysis reveal the characteristics of a robust network with a microdomain N 2-adsorption profile.

Rational Design of N- S- Fe- Doped Nanoporous Carbon Catalysts from Covalent Triazine Framework for High Efficient ORR.

PubMed

Zhu, Yuanzhi; Chen, Xifan; Liu, Jing; Zhang, Junfeng; Xu, Danyun; Peng, Wenchao; Li, Yang; Zhang, Guoliang; Zhang, Fengbao; Fan, Xiaobin

2018-05-15

Porous organic polymers (POFs) are promising precursors for developing high performance transition metal-nitrogen-carbon (M-N/C) catalysts towards ORR. But the rational design of POFs precursors remain a great challenge, because of the elusive structural association between the sacrificial POFs and the final M-N/C catalysts. Based on covalent triazine frameworks (CTFs), we developed a series of sulfur-doped Fe-N/C catalysts by selecting six different aromatic nitriles as building blocks. A new mixed solvent of molten FeCl3 and S was used for CTF polymerization, which benefit the formation of Fe-Nx site and make the subsequent pyrolysis process more convenient. Comprehensive study on these CTF-derived catalysts shows their ORR activities are not directly dependent on the theoretical N/C ratio of the building block, but closely correlated to the ratios of the nitrile group to benzene ring (Nnitrile/Nbenzene) and geometries of the building blocks. The high ratios of the Nnitrile/Nbenzene are crucial for ORR activity of the final catalysts due to the formation of more N-doped microporous and Fe-Nx sites in pyrolysis possess. The optimized catalyst shows high ORR performances in acid and superior ORR activity to the Pt/C catalysts under alkaline conditions. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Wastewater-based epidemiology generated forensic information: Amphetamine synthesis waste and its impact on a small sewage treatment plant.

PubMed

Emke, Erik; Vughs, Dennis; Kolkman, Annemieke; de Voogt, Pim

2018-05-01

Chemical analysis of domestic wastewater can reveal the presence of illicit drugs either consumed by a population or directly discharged into the sewer system. In the search for causes of a recent malfunctioning of a small domestic wastewater treatment plant aberrantly high loads of amphetamine were observed in the influent of the plant. Direct discharges of chemical waste from illegal production sites were suspected to be the cause. Illegal manufacturing of amphetamines creates substantial amounts of chemical waste. Here we show that fly-tipping of chemical waste originating from an amphetamine synthesis in the catchment of a small sewage treatment plant resulted in failure of the treatment process. Target analysis of drugs of abuse and non-target screening using high resolution mass spectrometry provided evidence for the presence of amphetamine produced from the precursor 1-phenylpropan-2-one by the Leuckart process through specific synthesis markers. Furthermore the identity and presence of the pre-precursor 3-oxo-2-phenylbutanamide was confirmed and a route specific marker was proposed. This is the first study that demonstrates that non-target screening of wastewater can identify intermediates, impurities and by products of the synthesis routes used in illegal manufacturing of amphetamine. The profiles of chemicals thus obtained can be used in tracking productions sites within the corresponding sewer catchment. Copyright © 2018 Elsevier B.V. All rights reserved.

Identification of specific posttranslational O-mycoloylations mediating protein targeting to the mycomembrane.

PubMed

Carel, Clément; Marcoux, Julien; Réat, Valérie; Parra, Julien; Latgé, Guillaume; Laval, Françoise; Demange, Pascal; Burlet-Schiltz, Odile; Milon, Alain; Daffé, Mamadou; Tropis, Maryelle G; Renault, Marie A M

2017-04-18

The outer membranes (OMs) of members of the Corynebacteriales bacterial order, also called mycomembranes, harbor mycolic acids and unusual outer membrane proteins (OMPs), including those with α-helical structure. The signals that allow precursors of such proteins to be targeted to the mycomembrane remain uncharacterized. We report here the molecular features responsible for OMP targeting to the mycomembrane of Corynebacterium glutamicum , a nonpathogenic member of the Corynebacteriales order. To better understand the mechanisms by which OMP precursors were sorted in C. glutamicum , we first investigated the partitioning of endogenous and recombinant PorA, PorH, PorB, and PorC between bacterial compartments and showed that they were both imported into the mycomembrane and secreted into the extracellular medium. A detailed investigation of cell extracts and purified proteins by top-down MS, NMR spectroscopy, and site-directed mutagenesis revealed specific and well-conserved posttranslational modifications (PTMs), including O -mycoloylation, pyroglutamylation, and N -formylation, for mycomembrane-associated and -secreted OMPs. PTM site sequence analysis from C. glutamicum OMP and other O -acylated proteins in bacteria and eukaryotes revealed specific patterns. Furthermore, we found that such modifications were essential for targeting to the mycomembrane and sufficient for OMP assembly into mycolic acid-containing lipid bilayers. Collectively, it seems that these PTMs have evolved in the Corynebacteriales order and beyond to guide membrane proteins toward a specific cell compartment.

Identification of specific posttranslational O-mycoloylations mediating protein targeting to the mycomembrane

PubMed Central

Carel, Clément; Réat, Valérie; Parra, Julien; Latgé, Guillaume; Laval, Françoise; Burlet-Schiltz, Odile; Milon, Alain; Daffé, Mamadou; Tropis, Maryelle G.; Renault, Marie A. M.

2017-01-01

The outer membranes (OMs) of members of the Corynebacteriales bacterial order, also called mycomembranes, harbor mycolic acids and unusual outer membrane proteins (OMPs), including those with α-helical structure. The signals that allow precursors of such proteins to be targeted to the mycomembrane remain uncharacterized. We report here the molecular features responsible for OMP targeting to the mycomembrane of Corynebacterium glutamicum, a nonpathogenic member of the Corynebacteriales order. To better understand the mechanisms by which OMP precursors were sorted in C. glutamicum, we first investigated the partitioning of endogenous and recombinant PorA, PorH, PorB, and PorC between bacterial compartments and showed that they were both imported into the mycomembrane and secreted into the extracellular medium. A detailed investigation of cell extracts and purified proteins by top-down MS, NMR spectroscopy, and site-directed mutagenesis revealed specific and well-conserved posttranslational modifications (PTMs), including O-mycoloylation, pyroglutamylation, and N-formylation, for mycomembrane-associated and -secreted OMPs. PTM site sequence analysis from C. glutamicum OMP and other O-acylated proteins in bacteria and eukaryotes revealed specific patterns. Furthermore, we found that such modifications were essential for targeting to the mycomembrane and sufficient for OMP assembly into mycolic acid-containing lipid bilayers. Collectively, it seems that these PTMs have evolved in the Corynebacteriales order and beyond to guide membrane proteins toward a specific cell compartment. PMID:28373551

Analysis of cardiomyocyte movement in the developing murine heart

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

Hashimoto, Hisayuki; Yuasa, Shinsuke, E-mail: yuasa@a8.keio.jp; Tabata, Hidenori

The precise assemblage of several types of cardiac precursors controls heart organogenesis. The cardiac precursors show dynamic movement during early development and then form the complicated heart structure. However, cardiomyocyte movements inside the newly organized mammalian heart remain unclear. We previously established the method of ex vivo time-lapse imaging of the murine heart to study cardiomyocyte behavior by using the Fucci (fluorescent ubiquitination-based cell cycle indicator) system, which can effectively label individual G1, S/G2/M, and G1/S-transition phase nuclei in living cardiomyocytes as red, green, and yellow, respectively. Global analysis of gene expression in Fucci green positive ventricular cardiomyocytes confirmed that cellmore » cycle regulatory genes expressed in G1/S, S, G2/M, and M phase transitions were upregulated. Interestingly, pathway analysis revealed that many genes related to the cell cycle were significantly upregulated in the Fucci green positive ventricular cardiomyocytes, while only a small number of genes related to cell motility were upregulated. Time-lapse imaging showed that murine proliferating cardiomyocytes did not exhibit dynamic movement inside the heart, but stayed on site after entering the cell cycle. - Highlights: • We directly visualized cardiomyocyte movement inside the developing murine heart. • Cell cycle related genes were upregulated in the proliferating cardiomyocytes. • Time-lapse imaging revealed that proliferating murine cardiomyocytes stayed in place. • Murine ventricular cardiomyocytes proliferate on site during development.« less

Hes repressors are essential regulators of hematopoietic stem cell development downstream of Notch signaling

PubMed Central

Guiu, Jordi; Shimizu, Ritsuko; D’Altri, Teresa; Fraser, Stuart T.; Hatakeyama, Jun; Bresnick, Emery H.; Kageyama, Ryoichiro; Dzierzak, Elaine; Yamamoto, Masayuki; Espinosa, Lluis

2013-01-01

Previous studies have identified Notch as a key regulator of hematopoietic stem cell (HSC) development, but the underlying downstream mechanisms remain unknown. The Notch target Hes1 is widely expressed in the aortic endothelium and hematopoietic clusters, though Hes1-deficient mice show no overt hematopoietic abnormalities. We now demonstrate that Hes is required for the development of HSC in the mouse embryo, a function previously undetected as the result of functional compensation by de novo expression of Hes5 in the aorta/gonad/mesonephros (AGM) region of Hes1 mutants. Analysis of embryos deficient for Hes1 and Hes5 reveals an intact arterial program with overproduction of nonfunctional hematopoietic precursors and total absence of HSC activity. These alterations were associated with increased expression of the hematopoietic regulators Runx1, c-myb, and the previously identified Notch target Gata2. By analyzing the Gata2 locus, we have identified functional RBPJ-binding sites, which mutation results in loss of Gata2 reporter expression in transgenic embryos, and functional Hes-binding sites, which mutation leads to specific Gata2 up-regulation in the hematopoietic precursors. Together, our findings show that Notch activation in the AGM triggers Gata2 and Hes1 transcription, and next HES-1 protein represses Gata2, creating an incoherent feed-forward loop required to restrict Gata2 expression in the emerging HSCs. PMID:23267012

Investigating the Formation Mechanisms and Inorganic Precursors of Formate and Acetate in Lost City Hydrothermal Fluids

NASA Astrophysics Data System (ADS)

Lang, S. Q.; Bernasconi, S. M.; Früh-Green, G.

2010-12-01

Fluids from the Lost City Hydrothermal Field are rich in hydrogen and methane, with high pHs (9 - 11), as a result of serpentinization reactions at moderate temperatures of approximately 120-200°C. It has been predicted that organic carbon compounds would form abiologically under these chemical and thermal conditions from inorganic precursors, in the form of hydrocarbons and organic acids. Previous work has demonstrated the presence of high concentrations of both formate and acetate in the Lost City fluids [Lang et al., 2010, GCA]. Formate is the second most prevalent carbon species in the fluids and may provide local microbial communities with a necessary carbon source in the face of low dissolved inorganic carbon concentrations. The goals of this study are to constrain the formation mechanisms of these organic acids (abiotic vs. biotic) and to identify their inorganic precursors. Formate and acetate were isolated from multiple fluid samples by preparative high-performance liquid chromatography for isotopic analysis. The δ13C of formate is similar to that of Lost City methane, and consistent with an abiological origin. The isotopic signature of acetate is significantly different from these values, and may be indicative of a biological source. Radiocarbon measurements of the isolated formate are in progress and should allow us to determine if the precursor carbon is derived from a mantle or deep-seawater source. Alkaline hydrothermal systems have been proposed as potential sites to the origin of life and formate has been proposed as a critical intermediate towards the kinds of reduced carbon species found in biochemistry. Evidence of an abiological formation mechanism of formate at Lost City may significantly further our understanding of prebiotic chemistry.

Identification of an miRNA candidate reflects the possible significance of transcribed microsatellites in the hairpin precursors of black pepper.

PubMed

Joy, Nisha; Soniya, Eppurathu Vasudevan

2012-06-01

Plant miRNAs (18-24nt) are generated by the RNase III-type Dicer endonuclease from the endogenous hairpin precursors ('pre-miRNAs') with significant regulatory functions. The transcribed regions display a higher frequency of microsatellites, when compared to other regions of the genomic DNA. Simple sequence repeats (SSRs) resulting from replication slippage occurring in transcripts affect the expression of genes. The available experimental evidence for the incidence of SSRs in the miRNA precursors is limited. Considering the potential significance of SSRs in the miRNA genes, we carried out a preliminary analysis to verify the presence of SSRs in the pri-miRNAs of black pepper (Piper nigrum L.). We isolated a (CT) dinucleotide SSR bearing transcript using SMART strategy. The transcript was predicted to be a 'pri-miRNA candidate' with Dicer sites based on miRNA prediction tools and MFOLD structural predictions. The presence of this 'miRNA candidate' was confirmed by real-time TaqMan assays. The upstream sequence of the 'miRNA candidate' by genome walking when subjected to PlantCARE showed the presence of certain promoter elements, and the deduced amino acid showed significant similarity with NAP1 gene, which affects the transcription of many genes. Moreover the hairpin-like precursor overlapped the neighbouring NAP1 gene. In silico analysis revealed distinct putative functions for the 'miRNA candidate', of which majority were related to growth. Hence, we assume that this 'miRNA candidate' may get activated during transcription of NAP gene, thereby regulating the expression of many genes involved in developmental processes.

High resolution biogeochemistry in the Upper Cenomanian black shales of the Umbria-Marche Basin (central Italy)

NASA Astrophysics Data System (ADS)

Bombardiere, L.; Farrimond, P.; Tyson, R. V.; Forster, A.; Sinninghe-Damsté, J.

2003-04-01

The uppermost Cenomanian "anoxic event" (i.e. OAE2) in the Umbria-Marche Basin is recorded by a 0.7-1.2 metre thick interval (the Bonarelli Level) consisting of black, organic-rich laminated mudstones ("black shales"), radiolarian layers and grey-greenish, organic-poor claystones. The occurrence of the radiolarian layers and the organic-poor claystones defines three lithological sub-units which can be correlated at basin scale. In addition, a number of thin black shales ("Bonarelli precursors") has been observed in the limestones underlying the Bonarelli Level; their occurrence appears to be tuned with Milankovitch cycles. This study investigates palaeoproductivity and preservation in the Bonarelli Level and in the precursors using a high resolution molecular biomarker analysis. The onset of the Bonarelli deposition (i.e. the lower sub-unit) is characterized by a drastic increase in the relative abundance of compounds associated with algal precursors (e.g. steranes and phytane). Equally, the same interval shows an increase in the biomarker proxies related to the intensity of oxygen depletion (e.g. homohopane index). The other two Bonarelli sub-units also reflect fluctuations in oxic-anoxic conditions and palaeoproductivity. As the molecular compounds thought to reflect qualitative changes in palaeoproductivity and anoxia do not exhibit any significant differencies between the precursor black shales and the Bonarelli Level, the palaeoenvironmental conditions leading to organic-rich sediments were presumably similar. The results from the Italian sites have been compared with two other OAE2 localities, both characterized by proximal depositional settings: Oued Bahloul (Tunisia) and Tarfaya (Morocco). This work is supported by the European Community's Improving Human Potential Programme under contract HPRN-CT-1999-00055, C/T-NET.

Anaplasia in pilocytic astrocytoma predicts aggressive behavior.

PubMed

Rodriguez, Fausto J; Scheithauer, Bernd W; Burger, Peter C; Jenkins, Sarah; Giannini, Caterina

2010-02-01

The clinical significance of anaplastic features, a rare event in pilocytic astrocytoma (PA), is not fully established. We reviewed 34 PA with anaplastic features (Male = 21, Female = 13; median age 35 y, 5 to 75) among approximately 2200 PA cases (1.7%). Tumors were included which demonstrated brisk mitotic activity [at least 4 mitoses/10 high power fields (400 x )], in addition to hypercellularity and moderate-to-severe cytologic atypia, with or without necrosis. The tumors either had a PA precursor, coexistent (n = 14) (41%) or documented by previous biopsy (n = 10) (29%), or exhibited typical pilocytic features in an otherwise anaplastic astrocytoma (n = 10) (29%). Clinical features of neurofibromatosis type-1 were present in 24% and a history of radiation for PA precursor in 12%. Histologically, the anaplastic component was classified as pilocytic like (41%), small cell (32%), epithelioid (15%), or fibrillary (12%). Median MIB1 labeling index was 24.7% in the anaplastic component and 2.6% in the precursor, although overlapping values were present. Strong p53 staining (3+) was limited to areas with anaplasia (19%), with overlapping values for 1 and 2+ in areas without anaplasia. Median overall and progression-free survivals after diagnosis for the entire study group were 24 and 14 months, respectively. Overall and progression-free survivals were shorter in the setting of prior radiation for a PA precursor (P = 0.007, 0.028), increasing mitotic activity (P = 0.03, 0.02), and presence of necrosis (P = 0.02, 0.02), after adjusting for age and site. The biologic behavior of PAs with high-mitotic rates and those with necrosis paralleled that of St Anne-Mayo grades 2 and 3 diffuse astrocytomas, respectively. In summary, PA with anaplastic features exhibits a spectrum of morphologies and is associated with decreased survival when compared with typical PA.

Diurnally resolved particulate and VOC measurements at a rural site: indication of significant biogenic secondary organic aerosol formation

NASA Astrophysics Data System (ADS)

Sjostedt, S. J.; Slowik, J. G.; Brook, J. R.; Chang, R. Y.-W.; Mihele, C.; Stroud, C. A.; Vlasenko, A.; Abbatt, J. P. D.

2011-06-01

We report simultaneous measurements of volatile organic compound (VOC) mixing ratios including C6 to C8 aromatics, isoprene, monoterpenes, acetone and organic aerosol mass loadings at a rural location in southwestern Ontario, Canada by Proton-Transfer-Reaction Mass Spectrometry (PTR-MS) and Aerosol Mass Spectrometry (AMS), respectively. During the three-week-long Border Air Quality and Meteorology Study in June-July 2007, air was sampled from a range of sources, including aged air from the polluted US Midwest, direct outflow from Detroit 50 km away, and clean air with higher biogenic input. After normalization to the diurnal profile of CO, a long-lived tracer, diurnal analyses show clear photochemical loss of reactive aromatics and production of oxygenated VOCs and secondary organic aerosol (SOA) during the daytime. Biogenic VOC mixing ratios increase during the daytime in accord with their light- and temperature-dependent sources. Long-lived species, such as hydrocarbon-like organic aerosol and benzene show little to no photochemical reactivity on this timescale. From the normalized diurnal profiles of VOCs, an estimate of OH concentrations during the daytime, measured O3 concentrations, and laboratory SOA yields, we calculate integrated local organic aerosol production amounts associated with each measured SOA precursor. Under the assumption that biogenic precursors are uniformly distributed across the southwestern Ontario location, we conclude that such precursors contribute significantly to the total amount of SOA formation, even during the period of Detroit outflow. The importance of aromatic precursors is more difficult to assess given that their sources are likely to be localized and thus of variable impact at the sampling location.

New Methods for the Site-Selective Placement of Peptides on a Microelectrode Array: Probing VEGF-v107 Binding as Proof of Concept.

PubMed

Graaf, Matthew D; Marquez, Bernadette V; Yeh, Nai-Hua; Lapi, Suzanne E; Moeller, Kevin D

2016-10-21

Cu(I)-catalyzed "click" reactions cannot be performed on a borate ester derived polymer coating on a microelectrode array because the Cu(II) precursor for the catalyst triggers background reactions between both acetylene and azide groups with the polymer surface. Fortunately, the Cu(II)-background reaction can itself be used to site-selectively add the acetylene and azide nucleophiles to the surface of the array. In this way, molecules previously functionalized for use in "click" reactions can be added directly to the array. In a similar fashion, activated esters can be added site-selectively to a borate ester coated array. The new chemistry can be used to explore new biological interactions on the arrays. Specifically, the binding of a v107 derived peptide with both human and murine VEGF was probed using a functionalized microelectrode array.

Mutations of RNA splicing factors in hematological malignancies.

PubMed

Shukla, Girish C; Singh, Jagjit

2017-11-28

Systematic large-scale cancer genomic studies have produced numerous significant findings. These studies have not only revealed new cancer-promoting genes, but they also have identified cancer-promoting functions of previously known "housekeeping" genes. These studies have identified numerous mutations in genes which play a fundamental role in nuclear precursor mRNA splicing. Somatic mutations and copy number variation in many of the splicing factors which participate in the formation of multiple spliceosomal complexes appear to play a role in many cancers and in particular in myelodysplastic syndromes (MDS). Mutated proteins seem to interfere with the recognition of the authentic splice sites (SS) leading to utilization of suboptimal alternative splicing sites generating aberrantly spliced mRNA isoforms. This short review is focusing on the function of the splice factors involved in the formation of splicing complexes and potential mechanisms which affect usage of the authentic splice site recognition. Copyright © 2017 Elsevier B.V. All rights reserved.

Airborne precursor missions in support of SIR-C/X-SAR

NASA Technical Reports Server (NTRS)

Evans, D.; Oettl, H.; Pampaloni, P.

1991-01-01

The NASA DC-8 and DLR E-SAR airborne imaging radars have been deployed over several sites in Europe and the U.S. in support of SIR-C/X-SAR (Shuttle Imaging Radar-C/X-Synthetic Aperture Radar) science team investigations. To date, data have been acquired in support of studies of alpine glaciers, forests, geology, oceanography, and calibration. An experimental campaign with airborne sensors will take place in Europe in June to July 1991 which will allow multitemporal surveys of several Europeans sites. Current plans are for calibration and ecology experiments to be undertaken in Germany, the Netherlands, Italy, France, and the United Kingdom. Coordinated multitemporal aircraft and ground campaigns are planned in support of hydrology experiments in Italy, the United Kingdom, and Austria. Data will also be acquired in support of oceanogrqhy in the Gulf of Genova, North Atlantic, Straits of Messina and the North Sea. Geology sites will include Campi Flegrei and Vesuvio, Italy.

Environmental Aspects of Sites Like America's Stonehenge, (AS), Florida's Miami Tequesta Site, and Lowell's A.D. 1069

NASA Astrophysics Data System (ADS)

Ochs, Michael Ann; Mc Leod, Roger D.

2002-04-01

Subtle ``instrumentation" is often unnoticed. Stone-chamber transponder-receivers are principle and secondary wave detectors, part of the ``technologic" arsenal of men like Passaconaway/Metacomen of colonial-era Massachusetts, or the earthquake-predicting Shawnee Tecumseh of the Ohio Valley region, during 1811-1813. An Ohio stone-effigy ``serpent" is a thunderstorm precursor signal indicator. The Hopi require similar ``equipment," when duping gullible ``rain-dance" patrons. Tornado/waterspout activity is documented right in the Tequesta site at the river in Miami, Florida, which generates detectable signals. Columbus could have used similar ``secret sacred science" previously learned from American Indians, and thereby successfully predicted an anomalous hurricane on a subsequent trip. These, and the Hawaiian volcano goddess Pelee, seem to be a mythic equivalent of electromagnetically generated signals, i.e., a metaphor for ``environmental applied physics" we detect at A.S.

Ozone, carbon monoxide and nitrogen oxides time series at four alpine GAW mountain stations in central Europe

NASA Astrophysics Data System (ADS)

Gilge, S.; Plass-Duelmer, C.; Fricke, W.; Kaiser, A.; Ries, L.; Buchmann, B.; Steinbacher, M.

2010-12-01

Long-term, ground based in-situ observations of ozone (O3) and its precursor gases nitrogen dioxide (NO2) and carbon monoxide (CO) from the four sites Hohenpeissenberg and Zugspitze (D), Sonnblick (A) and Jungfraujoch (CH) are presented for the period 1995-2007. These Central European alpine mountain observatories cover an altitude range of roughly 1000 to 3500 m. Comparable analytical methods and common quality assurance (QA) procedures are used at all sites. For O3 and CO, calibration is linked to primary calibrations (O3) or CO standards provided by the Central Calibration Laboratory (CCL) at NOAA/ESRL. All stations have been audited by the World Calibration Centre (WCC) for CO and O3 (WCC-Empa; CH). Data from long-term measurements of NO2 and CO are only available from Hohenpeissenberg and Jungfraujoch. Both sites show slightly decreasing mixing ratios of the primarily emitted NO2 and the partly anthropogenically emitted CO between 1995 and 2007. The findings are generally consistent with shorter observation periods at Zugspitze and Sonnblick and thus are considered to represent regional changes in Central European atmospheric composition at this altitude range. Over the same period, 1995-2007, the O3 mixing ratios have slightly increased at three of the four sites independent of wind sector. Trends are often more pronounced in winter and less in summer; highest declines of NO2 and CO are observed in winter and the lowest in summer, whereas the strongest O3 increase was detected in winter and lowest or even decline in summer, respectively. Weekly cycles demonstrate anthropogenic impact at all elevations with enhanced NO2 on working days compared to weekends. Enhanced O3 values on working days indicating photochemical production from anthropogenic precursors are only observed in summer, whereas in all other seasons anti-correlation with NO2 was found due to reduced O3 values on working days. Trends are discussed with respect to anthropogenic impacts and vertical mixing. The observed trends for NO2 at the alpine mountain sites are less pronounced than trends estimated based on emission inventories.

Analysis of ozone precursor data from Baton Rouge, Houston, El Paso, and Dallas

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

Sather, M.E.; Kemp, M.G.

1998-12-31

Ongoing analyses of ozone precursor data continue to be performed for Baton Rouge, Louisiana, and Houston, El Paso, and Dallas, Texas. All four areas have collected ambient monitoring data for ozone, nitrogen oxides (NO{sub x}), and over 50 volatile organic compound (VOC) species in accordance with the Photochemical Assessment Monitoring Stations (PAMS) requirements. The PAMS program was initiated to provide more detailed VOC, NO{sub x}, and meteorological data for scientists, modelers, and managers working toward eliminating violations of the ozone National Ambient Air Quality Standards (NAAQS). This paper will focus on several useful analyses of PAMS data for the fourmore » study areas including: (1) a trends analysis of Total Non-Methane Organic Compounds (TNMOC), NO{sub x}, and ozone data from two Baton Rouge sites, (2) results of TNMOC/NO{sub x} ratio analyses for the three Baton Rouge PAMS sites which can provide a starting point for evaluating specific site sensitivity to changes in VOC or NO{sub x} ambient concentrations, (3) results of benzene/toluene ratio analyses which supply information on aged/fresh air masses, and (4) results of ethylene/acetylene ratio analyses which are useful in determining the impacts of catalytic/noncatalytic vehicles. This paper will also discuss the continuing maturation of the PAMS program in Baton Rouge, Houston, and El Paso. The Dallas area is expected to formally begin implementing a PAMS program in 1998 after the area is reclassified to a serious status for ozone pollution. In addition, the Beaumont, Texas area is currently scheduled to be reclassified to a serious status for ozone pollution in the 1998/1999 time period, and thus would also need to begin implementing a PAMS program.« less

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

Thornburg, Nicholas E.; Nauert, Scott L.; Thompson, Anthony B.

Many industrially significant selective oxidation reactions are catalyzed by supported and bulk transition metal oxides. Catalysts for the synthesis of oxygenates, and especially for epoxidation, have predominantly focused on TiO x supported on or co-condensed with SiO 2, whereas much of the rest of Groups 4 and 5 have been less studied. We have recently demonstrated through periodic trends using a uniform molecular precursor that niobium(V)-silica catalysts reveal the highest activity and selectivity for efficient utilization of H 2O 2 for epoxidation across all of Groups 4 and 5. In this work, we graft a wide range of Nb(V) precursors,more » spanning surface densities of 0.07–1.6 Nb groups nm –2 on mesoporous silica, and we characterize these materials with UV–visible spectroscopy and Nb K-edge XANES. Further, we apply in situ chemical titration with phenylphosphonic acid (PPA) in the epoxidation of cis-cyclooctene by H 2O 2 to probe the numbers and nature of the active sites across this series and in a set of related Ti-, Zr-, Hf-, and Ta-SiO2 catalysts. By this method, the fraction of kinetically relevant NbO x species ranges from ~15% to ~65%, which correlates with spectroscopic evaluation of the NbO x sites. This titration leads to a single value for the average turnover frequency, on a per active site basis rather than a per Nb atom basis, of 1.4 ± 0.52 min –1 across the 21 materials in the series. These quantitative maps of structural properties and kinetic consequences link key catalyst descriptors of supported Nb-SiO 2 to enable rational design for next-generation oxidation catalysts.« less

Thiol–ene click hydrogels for therapeutic delivery

PubMed Central

Kharkar, Prathamesh M.; Rehmann, Matthew S.; Skeens, Kelsi M.; Maverakis, Emanual; Kloxin, April M.

2016-01-01

Hydrogels are of growing interest for the delivery of therapeutics to specific sites in the body. For use as a delivery vehicle, hydrophilic precursors are usually laden with bioactive moieties and then directly injected to the site of interest for in situ gel formation and controlled release dictated by precursor design. Hydrogels formed by thiol–ene click reactions are attractive for local controlled release of therapeutics owing to their rapid reaction rate and efficiency under mild aqueous conditions, enabling in situ formation of gels with tunable properties often responsive to environmental cues. Herein, we will review the wide range of applications for thiol–ene hydrogels, from the prolonged release of anti-inflammatory drugs in the spine to the release of protein-based therapeutics in response to cell-secreted enzymes, with a focus on their clinical relevance. We will also provide a brief overview of thiol–ene click chemistry and discuss the available alkene chemistries pertinent to macromolecule functionalization and hydrogel formation. These chemistries include functional groups susceptible to Michael type reactions relevant for injection and radically-mediated reactions for greater temporal control of formation at sites of interest using light. Additionally, mechanisms for the encapsulation and controlled release of therapeutic cargoes are reviewed, including i) tuning the mesh size of the hydrogel initially and temporally for cargo entrapment and release and ii) covalent tethering of the cargo with degradable linkers or affinity binding sequences to mediate release. Finally, myriad thiol–ene hydrogels and their specific applications also are discussed to give a sampling of the current and future utilization of this chemistry for delivery of therapeutics, such as small molecule drugs, peptides, and biologics. PMID:28361125

Evidence of Intermediate Hydrogen States in the Formation of a Complex Hydride

DOE PAGES

Sato, Toyoto; Ramirez-Cuesta, Anibal J.; Daemen, Luke L.; ...

2017-12-26

A complex hydride (LaMg 2NiH 7) composed of La 3+, two Mg 2+, [NiH 4] 4– with a covalently bonded hydrogen, and three H – was formed from an intermetallic LaMg 2Ni via an intermediate phase (LaMg 2NiH 4.6) composed of La, Mg, NiH 2, NiH 3 units, and H atoms at tetrahedral sites. The NiH 2 and NiH 3 units in LaMg 2NiH 4.6 were reported as precursors for [NiH 4] 4– in LaMg 2NiH 7 [Miwa et al. J. Phys. Chem. C 2016, 120, 5926–5931]. To further understand the hydrogen states in the precursors (the NiH 2 andmore » NiH 3 units) and H atoms at the tetrahedral sites in the intermediate phase, LaMg 2NiH 4.6, we observed the hydrogen vibrations in LaMg 2NiH 4.6 and LaMg 2NiH 7 by using inelastic neutron scattering. A comparison of the hydrogen vibrations of the NiH 2 and NiH 3 units with that of [NiH 4] 4– shows that the librational modes of the NiH 2 and NiH 3 units were nonexistent; librational modes are characteristic modes for complex anions, such as [NiH 4] 4–. Furthermore, the hydrogen vibrations for the H atoms in the tetrahedral sites showed a narrower wavenumber range than that for H – and a wider range than that for typical interstitial hydrogen. The results indicated the presence of intermediate hydrogen states before the formation of [NiH 4] 4– and H –.« less

Anti-amyloid precursor protein antibodies inhibit amyloid-β production by steric hindrance

PubMed Central

Thomas, Rhian S.; Liddell, J. Eryl; Kidd, Emma J.

2015-01-01

Summary Cleavage of amyloid precursor protein (APP) by β- and γ-secretases results in the production of amyloid-β (Aβ) in Alzheimer’s disease (AD). We raised two monoclonal antibodies, 2B3 and 2B12, that recognise the β-secretase cleavage site on APP but not Aβ. We hypothesised that these antibodies would reduce Aβ levels via steric hindrance of β-secretase. Both antibodies decreased extracellular Aβ levels from astrocytoma cells, but 2B3 was more potent than 2B12. Levels of soluble sAPPα from the non-amyloidogenic α-secretase pathway and intracellular APP were not affected by either antibody nor were there any effects on cell viability. 2B3 exhibited a higher affinity for APP than 2B12 and its epitope appeared to span the cleavage site while 2B12 bound slightly upstream. Both of these factors probably contribute to its greater effect on Aβ levels. After 60 minutes incubation at pH 4.0, most 2B3 and 2B12 remained bound to their antigen, suggesting that the antibodies will remain bound to APP in the acidic endosomes where β-secretase cleavage probably occurs. Only 2B3 and 2B12, but not control antibodies, inhibited the cleavage of sAPPα by β-secretase in a cell-free assay where effects of antibody internalisation and intracellular degradation were excluded. 2B3 virtually abolished this cleavage. In addition, levels of C-terminal APP fragments, βCTF, generated following β-secretase cleavage, were significantly reduced in cells after incubation with 2B3. These results strongly suggest that anti-cleavage site antibodies can generically reduce Aβ levels via inhibition of β-secretase by steric hindrance and may provide a novel alternative therapy for AD. PMID:21122073

Wintertime vertical variations in particulate matter (PM) and precursor concentrations in the San Joaquin Valley during the California Regional Coarse PM/Fine PM Air Quality Study.

PubMed

Brown, Steven G; Roberts, Paul T; McCarthy, Michael C; Lurmann, Frederick W; Hyslop, Nicole P

2006-09-01

Air quality monitoring was conducted at a rural site with a tower in the middle of California's San Joaquin Valley (SJV) and at elevated sites in the foothills and mountains surrounding the SJV for the California Regional PM10/ PM2.5 Air Quality Study. Measurements at the surface and n a tower at 90 m were collected in Angiola, CA, from December 2000 through February 2001 and included hourly black carbon (BC), particle counts from optical particle counters, nitric oxide, ozone, temperature, relative humidity, wind speed, and direction. Boundary site measurements were made primarily using 24-hr integrated particulate matter (PM) samples. These measurements were used to understand the vertical variations of PM and PM precursors, the effect of stratification in the winter on concentrations and chemistry aloft and at the surface, and the impact of aloft-versus-surface transport on PM concentrations. Vertical variations of concentrations differed among individual species. The stratification may be important to atmospheric chemistry processes, particularly nighttime nitrate formation aloft, because NO2 appeared to be oxidized by ozone in the stratified aloft layer. Additionally, increases in accumulation-mode particle concentrations in the aloft layer during a fine PM (PM2.5) episode corresponded with increases in aloft nitrate, demonstrating the likelihood of an aloft nighttime nitrate formation mechanism. Evidence of local transport at the surface and regional transport aloft was found; transport processes also varied among the species. The distribution of BC appeared to be regional, and BC was often uniformly mixed vertically. Overall, the combination of time-resolved tower and surface measurements provided important insight into PM stratification, formation, and transport.

Evidence of Intermediate Hydrogen States in the Formation of a Complex Hydride

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

Sato, Toyoto; Ramirez-Cuesta, Anibal J.; Daemen, Luke L.

A complex hydride (LaMg 2NiH 7) composed of La 3+, two Mg 2+, [NiH 4] 4– with a covalently bonded hydrogen, and three H – was formed from an intermetallic LaMg 2Ni via an intermediate phase (LaMg 2NiH 4.6) composed of La, Mg, NiH 2, NiH 3 units, and H atoms at tetrahedral sites. The NiH 2 and NiH 3 units in LaMg 2NiH 4.6 were reported as precursors for [NiH 4] 4– in LaMg 2NiH 7 [Miwa et al. J. Phys. Chem. C 2016, 120, 5926–5931]. To further understand the hydrogen states in the precursors (the NiH 2 andmore » NiH 3 units) and H atoms at the tetrahedral sites in the intermediate phase, LaMg 2NiH 4.6, we observed the hydrogen vibrations in LaMg 2NiH 4.6 and LaMg 2NiH 7 by using inelastic neutron scattering. A comparison of the hydrogen vibrations of the NiH 2 and NiH 3 units with that of [NiH 4] 4– shows that the librational modes of the NiH 2 and NiH 3 units were nonexistent; librational modes are characteristic modes for complex anions, such as [NiH 4] 4–. Furthermore, the hydrogen vibrations for the H atoms in the tetrahedral sites showed a narrower wavenumber range than that for H – and a wider range than that for typical interstitial hydrogen. The results indicated the presence of intermediate hydrogen states before the formation of [NiH 4] 4– and H –.« less

[In situ diffuse reflectance FTIR spectroscopy study of CO adsorption on Ni2P/mesoporous molecule sieve catalysts].

PubMed

Liu, Qian-qian; Ji, Sheng-fu; Wu, Ping-yi; Hu, Lin-hua; Huang, Xiao-fan; Zhu, Ji-qin; Li, Cheng-yue

2009-05-01

Abstract The supported nickel phosphate precursors were prepared by incipient wetness impregnation using nickel nitrate as nickel source, diammonium hydrogen phosphate as phosphorus source, and MCM-41, MCM-48, SBA-15 and SBA-16 as supports, respectively. Then, the supported Ni2 P catalysts were prepared by temperature-programmed reduction in flowing Hz from their nickel phosphate precursors. The in situ diffuse reflectance FTIR spectroscopy (DRIFTS) analysis with the probe molecule CO was carried out to characterize the surface properties. The results indicated that there were significant differences in the spectral features of the samples. The upsilon(CO) absorbances observed for adsorbed CO on mesoporous molecule sieve was attributed to weak physical adsorption. There are four different kinds of upsilon(CO) absorbances observed for adsorbed CO on Ni2 P/MCM-41 catalyst with the following assignments: (1) the formation of Ni(CO)4 at 2055 cm(-1). (2) CO terminally bonded to cus Ni(delta+) (0

Influence of catalyst synthesis method on selective catalytic reduction (SCR) of NO by NH 3 with V 2O 5-WO 3/TiO 2 catalysts

DOE PAGES

He, Yuanyuan; Ford, Michael E.; Zhu, Minghui; ...

2016-04-14

We compared the molecular structures, surface acidity and catalytic activity for NO/NH 3/O 2 SCR of V 2O 5-WO 3/TiO 2 catalysts for two different synthesis methods: co-precipitation of aqueous vanadium and tungsten oxide precursors with TiO(OH) 2 and by incipient wetness impregnation of the aqueous precursors on a reference crystalline TiO 2 support (P25; primarily anatase phase). Bulk analysis by XRD showed that co-precipitation results in small and/or poorly ordered TiO 2(anatase) particles and that VO x and WO x do not form solid solutions with the bulk titania lattice. Surface analysis of the co-precipitated catalyst by High Sensitivity-Lowmore » Energy Ion Scattering (HS-LEIS) confirms that the VO x and WO x are surface segregated for the co-precipitated catalysts. In situ Raman and IR spectroscopy revealed that the vanadium and tungsten oxide components are present as surface mono-oxo O = VO 3 and O = WO 4 sites on the TiO 2 supports. Co-precipitation was shown for the first time to also form new mono-oxo surface VO 4 and WO 4 sites that appear to be anchored at surface defects of the TiO 2 support. IR analysis of chemisorbed ammonia showed the presence of both surface NH 3 * on Lewis acid sites and surface NH 4 +* on Brønsted acid sites. TPSR spectroscopy demonstrated that the specific SCR kinetics was controlled by the redox surface VO 4 species and that the surface kinetics was independent of TiO 2 synthesis method or presence of surface WO 5 sites. SCR reaction studies revealed that the surface WO5 sites possess minimal activity below ~325 °C and their primary function is to increase the adsorption capacity of ammonia. A relationship between the SCR activity and surface acidity was not found. The SCR reaction is controlled by the surface VO 4 sites that initiate the reaction at ~200 °C. The co-precipitated catalysts were always more active than the corresponding impregnated catalysts. Finally, we ascribe the higher activity of the co-precipitated catalysts to the presence of the new surface WO x sites associated surface defects on the TiO 2 support that increase the ammonia adsorption capacity.« less

Human Mars Landing Site and Impacts on Mars Surface Operations

NASA Technical Reports Server (NTRS)

Bussey, Ben; Hoffman, Stephen J.

2016-01-01

NASA has begun a process to identify and discuss candidate locations where humans could land, live and work on the Martian surface. These locations are referred to as Exploration Zones (EZs). Given current mission concepts, an EZ is a collection of Regions of Interest (ROIs) that are located within approximately 100 kilometers of a centralized landing site. ROIs are areas that are relevant for scientific investigation and/or development/maturation of capabilities and resources necessary for a sustainable human presence. The EZ also contains a landing site and a habitation site that will be used by multiple human crews during missions to explore and utilize the ROIs within the EZ. These candidate EZs will be used by NASA as part of a multi-year process of determining where and how humans could explore Mars. In the near term this process includes: (a) identifying locations that would maximize the potential science return from future human exploration missions, (b) identifying locations with the potential for resources required to support humans, (c) developing concepts and engineering systems needed by future human crews to conduct operations within an EZ, and (d) identifying key characteristics of the proposed candidate EZs that cannot be evaluated using existing data sets, thus helping to define precursor measurements needed in advance of human missions. Existing and future robotic spacecraft will be tasked to gather data from specific Mars surface sites within the representative EZs to support these NASA activities. The proposed paper will describe NASA's initial steps for identifying and evaluating candidate EZs and ROIs. This includes plans for the "First Landing Site/Exploration Zone Workshop for Human Missions to the Surface of Mars" to be held in October 2015 at which proposals for EZs and ROIs will be presented and discussed. It will also include a discussion of how these considerations are (or will be) taken into account as future robotic Mars missions are defined and developed. One or more representative EZs, drawn from similar previous studies involving Mars sites, will be used in the proposed paper to illustrate the process NASA envisions for gathering additional data from robotic precursor missions to assist in making a final selection of an EZ for human crews as well as the steps likely to occur during the buildup of a habitation site. Examples of the systems and operations likely to be used by human crews, assisted by robotic vehicles, to explore the scientific ROIs as well as developing the resource ROIs within the example EZs will be discussed.

Analysis of the seasonal and inter-annual variations, and long-term trends of ozone in the metropolitan area of Monterrey, Mexico

NASA Astrophysics Data System (ADS)

Yassmany Hernández Paniagua, Iván; Clemitshaw, Kevin C.; Mendoza, Alberto

2016-04-01

Since 1993, high-precision and high-frequency measurements of ambient O3 have been recorded at 5 sites within the metropolitan area of Monterrey, the third largest city in Mexico. O3was measured by the Integral Environmental Monitoring System of the Nuevo Leon State Government using commercially available, conventional UV photometry instrumentation (precision better than ±1 ppb). The datasets exhibit variations on differing time-scales of minutes to hours, with evidence of seasonal cycles and inter-annual variability. The O3 diurnal cycles vary with length of daylight, which influences its formation and loss via photochemistry. No apparent influence is observed in the amplitudes of O3 diurnal cycles recorded during weekdays with higher emissions from fossil fuel combustion than at weekends, although larger amplitudes occur at sites with polluted air from industrial areas. Seasonal cycles are driven by the variation in solar radiation and changes in emissions of primary precursors, VOCs and NOX. Maximum O3 mixing ratios were recorded in spring, and minimum values in winter, with a secondary trough during summer due to the advection of clean air masses from the Gulf of Mexico. The largest spring maxima are recorded downwind of an industrial area likely due photochemical processing of VOCs and NOx, with the lowest recorded in a highly populated area due to reaction of O3 and NO. At all sites, decreasing seasonal amplitudes were observed during 1993-1998, followed by persistent increases from 1998 to 2014. Wind sector analyses were carried out by splitting the wind direction into 8 categories (45°). At all sites, the highest O3 mixing ratios were recorded from the E and SE sectors, with lowest values recorded in air masses from the W and NW. Wind sector analysis of primary precursors (such as VOCs, CO, NOX) reveal that sources are dominated by emissions from industrial regions in Monterrey and surrounding areas. The largest annual growth rates for the E and SE sectors and for all sites are 0.50 and 0.66 ppb O3 yr-1, whereas the lowest are 0.36 and 0.25 ppb O3 yr-1,respectively. In the metropolitan area of Monterrey, O3has increased at an average annual rate of 0.20 ppb O3 yr-1 (p <0.001), which is in marked contrast with the decline of 0.71 ppb O3 yr-1 (p <0.001) observed at Mexico City during the same period and the variable levels at Guadalajara from 1996 to 2014. The analysed O3 records imply that controls on primary precursor emissions have been successful in Mexico City, whereas more measures to improve air quality should be introduced in Guadalajara and Monterrey.

Dynamic model evaluation for secondary inorganic aerosol and its precursors over Europe between 1990 and 2009

NASA Astrophysics Data System (ADS)

Banzhaf, S.; Schaap, M.; Kranenburg, R.; Manders, A. M. M.; Segers, A. J.; Visschedijk, A. J. H.; Denier van der Gon, H. A. C.; Kuenen, J. J. P.; van Meijgaard, E.; van Ulft, L. H.; Cofala, J.; Builtjes, P. J. H.

2015-04-01

In this study we present a dynamic model evaluation of chemistry transport model LOTOS-EUROS (LOng Term Ozone Simulation - EURopean Operational Smog) to analyse the ability of the model to reproduce observed non-linear responses to emission changes and interannual variability of secondary inorganic aerosol (SIA) and its precursors over Europe from 1990 to 2009. The 20 year simulation was performed using a consistent set of meteorological data provided by RACMO2 (Regional Atmospheric Climate MOdel). Observations at European rural background sites have been used as a reference for the model evaluation. To ensure the consistency of the used observational data, stringent selection criteria were applied, including a comprehensive visual screening to remove suspicious data from the analysis. The LOTOS-EUROS model was able to capture a large part of the seasonal and interannual variability of SIA and its precursors' concentrations. The dynamic evaluation has shown that the model is able to simulate the declining trends observed for all considered sulfur and nitrogen components following the implementation of emission abatement strategies for SIA precursors over Europe. Both the observations and the model show the largest part of the decline in the 1990s, while smaller concentration changes and an increasing number of non-significant trends are observed and modelled between 2000 and 2009. Furthermore, the results confirm former studies showing that the observed trends in sulfate and total nitrate concentrations from 1990 to 2009 are lower than the trends in precursor emissions and precursor concentrations. The model captured well these non-linear responses to the emission changes. Using the LOTOS-EUROS source apportionment module, trends in the formation efficiency of SIA have been quantified for four European regions. The exercise has revealed a 20-50% more efficient sulfate formation in 2009 compared to 1990 and an up to 20% more efficient nitrate formation per unit nitrogen oxide emission, which added to the explanation of the non-linear responses. However, we have also identified some weaknesses in the model and the input data. LOTOS-EUROS underestimates the observed nitrogen dioxide concentrations throughout the whole time period, while it overestimates the observed nitrogen dioxide concentration trends. Moreover, model results suggest that the emission information of the early 1990s used in this study needs to be improved concerning magnitude and spatial distribution.

Dynamic model evaluation for secondary inorganic aerosol and its precursors over Europe between 1990 and 2009

NASA Astrophysics Data System (ADS)

Banzhaf, S.; Schaap, M.; Kranenburg, R.; Manders, A. M. M.; Segers, A. J.; Visschedijk, A. H. J.; Denier van der Gon, H. A. C.; Kuenen, J. J. P.; van Meijgaard, E.; van Ulft, L. H.; Cofala, J.; Builtjes, P. J. H.

2014-07-01

In this study we present a dynamic model evaluation of the chemistry transport model LOTOS-EUROS to analyse the ability of the model to reproduce observed non-linear responses to emission changes and interannual variability of secondary inorganic aerosol (SIA) and its precursors over Europe from 1990 to 2009. The 20 year simulation was performed using a consistent set of meteorological data provided by the regional climate model RACMO2. Observations at European rural background sites have been used as reference for the model evaluation. To ensure the consistency of the used observational data stringent selection criteria were applied including a comprehensive visual screening to remove suspicious data from the analysis. The LOTOS-EUROS model was able to capture a large part of the day-to-day, seasonal and interannual variability of SIA and its precursors' concentrations. The dynamic evaluation has shown that the model is able to simulate the declining trends observed for all considered sulphur and nitrogen components following the implementation of emission abatement strategies for SIA precursors over Europe. Both, the observations and the model show the largest part of the decline in the 1990's while smaller concentration changes and an increasing number of non-significant trends are observed and modelled between 2000-2009. Furthermore, the results confirm former studies showing that the observed trends in sulphate and total nitrate concentrations from 1990 to 2009 are significantly lower than the trends in precursor emissions and precursor concentrations. The model captured these non-linear responses to the emission changes well. Using the LOTOS-EUROS source apportionment module trends in formation efficiency of SIA have been quantified for four European regions. The exercise has revealed a 20-50% more efficient sulphate formation in 2009 compared to 1990 and an up to 20% more efficient nitrate formation per unit nitrogen oxide emission, which added to the explanation of the non-linear responses. However, we have also identified some weaknesses to the model and the input data. LOTOS-EUROS underestimates the observed nitrogen dioxide concentrations throughout the whole time period, while it overestimates the observed nitrogen dioxide concentration trends. Moreover, model results suggest that the emission information of the early 1990's used in this study needs to be improved concerning magnitude and spatial distribution.

Sources and characteristics of organic matter in the Clackamas River, Oregon, related to the formation of disinfection by-products in treated drinking water

USGS Publications Warehouse

Carpenter, Kurt D.; Kraus, Tamara E.C.; Goldman, Jami H.; Saraceno, John Franco; Downing, Bryan D.; Bergamaschi, Brian A.; McGhee, Gordon; Triplett, Tracy

2013-01-01

This study characterized the amount and quality of organic matter in the Clackamas River, Oregon, to gain an understanding of sources that contribute to the formation of chlorinated and brominated disinfection by-products (DBPs), focusing on regulated DBPs in treated drinking water from two direct-filtration treatment plants that together serve approximately 100,000 customers. The central hypothesis guiding this study was that natural organic matter leaching out of the forested watershed, in-stream growth of benthic algae, and phytoplankton blooms in the reservoirs contribute different and varying proportions of organic carbon to the river. Differences in the amount and composition of carbon derived from each source affects the types and concentrations of DBP precursors entering the treatment plants and, as a result, yield varying DBP concentrations and species in finished water. The two classes of DBPs analyzed in this study-trihalomethanes (THMs) and haloacetic acids (HAAs)-form from precursors within the dissolved and particulate pools of organic matter present in source water. The five principal objectives of the study were to (1) describe the seasonal quantity and character of organic matter in the Clackamas River; (2) relate the amount and composition of organic matter to the formation of DBPs; (3) evaluate sources of DBP precursors in the watershed; (4) assess the use of optical measurements, including in-situ fluorescence, for estimating dissolved organic carbon (DOC) concentrations and DBP formation; and (5) assess the removal of DBP precursors during treatment by conducting treatability "jar-test" experiments at one of the treatment plants. Data collection consisted of (1) monthly sampling of source and finished water at two drinking-water treatment plants; (2) event-based sampling in the mainstem, tributaries, and North Fork Reservoir; and (3) in-situ continuous monitoring of fluorescent dissolved organic matter (FDOM), turbidity, chlorophyll-a, and other constituents to continuously track source-water conditions in near real-time. Treatability tests were conducted during the four event-based surveys to determine the effectiveness of coagulant and powdered activated carbon (PAC) on the removal of DBP precursors. Sample analyses included DOC, total particulate carbon (TPC), total and dissolved nutrients, absorbance and fluorescence spectroscopy, and, for regulated DBPs, concentrations of THMs and HAAs in finished water and laboratory-based THM and HAA formation potentials (THMFP and HAAFP, respectively) for source water and selected locations throughout the watershed. The results of this study may not be typical given the record and near record amounts of precipitation that occurred during spring that produced streamflow much higher than average in 2010-11. Although there were algal blooms, lower concentrations of chlorophyll-a were observed in the water column during the study period compared to historical data. Concentrations of DBPs in finished (treated) water averaged 0.024 milligrams per liter (mg/L) for THMs and 0.022 mg/L for HAAs; maximum values were about 0.040 mg/L for both classes of DBPs. Although DBP concentrations were somewhat higher within the distribution system, none of the samples collected for this study or for the quarterly compliance monitoring by the water utilities exceeded levels permissible under existing U.S. Environmental Protection Agency (USEPA) regulations: 0.080 mg/L for THMs and 0.060 mg/L for HAAs. DOC concentrations were generally low in the Clackamas River, typically about 1.0-1.5 mg/L. Concentrations in the mainstem occasionally increased to nearly 2.5 mg/L during storms; DOC concentrations in tributaries were sometimes much higher (up to 7.8 mg/L). The continuous in-situ FDOM measurements indicated sharp rises in DOC concentrations in the mainstem following rainfall events; concentrations were relatively stable during summer base flow. Even though the first autumn storm mobilized appreciable quantities of carbon, higher concentrations of DBPs in finished water were observed 3-weeks later, after the ground was saturated from additional rainfall. The majority of the DOC in the lower Clackamas River appears to originate from the upper basin, suggesting terrestrial carbon was commonly the dominant source. Lower-basin tributaries typically contained the highest concentrations of DOC and DBP precursors and contributed substantially to the overall loads in the mainstem during storms. During low-flow periods, tributaries were not major sources of DOC or DBP precursors to the Clackamas River. Although the dissolved fraction of organic carbon contributed the majority of DBP precursors, at times the particulate fraction (inorganic sediment and organic particles including detritus and algal material) contributed a substantial fraction of DBP precursors. Considering just the main-stem sites, on average, 10 percent of THMFP and 32 percent of HAAFP were attributed to particulate carbon. This finding suggests water-treatment methods that remove particles prior to chlorination would reduce finished-water DBP concentrations to some degree. Overall, concentrations of THM and HAA precursors were closely linked to DOC concentrations; laboratory DBP formation potentials (DBPFPs) clearly showed that THMFP and HAAFP were greatest in the downstream tributaries that contained elevated carbon concentrations. However, carbon-normalized "specific" formation potentials for THMs and HAAs (STHMFP and SHAAFP, respectively) revealed changes in carbon character over time that affected the two types of DBP classes differently. HAA precursors were elevated in waters containing aromatic-rich soil-derived material arising from forested areas. In contrast, THM precursors were associated with carbon having a lower aromatic content; highest STHMFP occurred in autumn 2011 in the mainstem from North Fork Reservoir downstream to LO DWTP. This pattern suggests the potential for a link between THM precursors and algal-derived carbon. The highest STHMFP value was measured within North Fork Reservoir, indicating reservoir derived carbon may be important for this class of DBPs. Weak correlations between STHMFP and SHAAFP emphasize that precursor sources for these types of DBPs may be different. This highlights not only that different locations within the watershed produce carbon with different reactivity (specific DBPFP), but also that different management approaches for each class of DBP precursors could be required for control. Treatability tests conducted on source water during four basin-wide surveys demonstrated that an average of about 40 percent of DOC can be removed by coagulation. While the decrease in THMFP following coagulation was similar to DOC, the decrease in HAAFP was much greater (approximately 70 percent), indicating coagulation is particularly effective at removing HAA precursors'likely because of the aromatic nature of the carbon associated with HAA precursors. Several findings from this study have direct implications for managing drinking-water resources and for providing useful information that may help improve treatment-plant operations. For example, the use of in-situ fluorometers that measure FDOM provided an excellent proxy for DOC concentration in this system and revealed short-term, rapid changes in DOC concentration during storm events. In addition, the strong correlation between FDOM values measured in-situ and HAA5 concentrations in finished water may permit estimation of continuous HAA concentrations, as was done here. As part of this study, multiple in-situ FDOM sensors were deployed continuously and in real-time to characterize the composition of dissolved organic matter. Although the initial results were promising, additional research and engineering developments will be needed to demonstrate the full utility of these sensors for this purpose. In conclusion, although DBPFPs were strongly correlated to DOC concentration, some DBPs formed from particulate carbon, including terrestrial leaf material and algal material such as planktonic species of blue-green algae and sloughed filaments, stalks, and cells of benthic algae. Different precursor sources in the watershed were evident from the data, suggesting specific actions may be available to address some of these sources. In-situ measurements of FDOM proved to be an excellent proxy for DOC concentration as well as HAA formation during treatment, which suggests further development and refinement of these sensors have the potential to provide real-time information about complex watershed processes to operators at the drinking-water treatment plants. Follow-up studies could examine the relative roles that terrestrial and algal sources have on the DBP precursor pool to better understand how watershed-management activities may be affecting the transport of these compounds to Clackamas River drinking-water intakes. Given the low concentrations of algae in the water column during this study, additional surveys during more typical river conditions could provide a more complete understanding of how algae contribute DBP precursors. Further development of FDOM-sensor technology can improve our understanding of carbon dynamics in the river and how concentrations may be trending over time. This study was conducted in collaboration with Clackamas River Water and the City of Lake Oswego water utilities. Other research partners included Oregon Health and Science University in Hillsboro, Oregon, Alexin Laboratory in Tigard, Oregon, U.S. Geological Survey National Research Program Laboratory in Denver, Colorado, and the U.S. Geological Survey Water Science Centers in Portland, Oregon, and Sacramento, California. This project was supported with funding from Clackamas River Water, City of Lake Oswego, the U.S. Geological Survey, and the Water Research Foundation.

Isoprene and its degradation products as strong ozone precursors in Insubria, Northern Italy

NASA Astrophysics Data System (ADS)

Duane, M.; Poma, B.; Rembges, D.; Astorga, C.; Larsen, B. R.

Frequent smog episodes occur during spring, summer, and autumn in Insubria, Northern Italy. On a test site in this area the atmospheric concentration of the photo-oxidants ozone and peroxyacetyl nitrate has been monitored over a year (2000) together with ozone precursors listed in the European Union Air Quality Directive 2002/3/EC, such as nitrous oxides (NO X) and volatile organic compounds (VOC) including hydrocarbons and carbonyls. The results of this study revealed a strong impact of biogenic isoprene on the air quality. In winter isoprene was detected at the ppt level and correlated with anthropogenic VOC. However, during the growing season isoprene exhibited a distinct diurnal variation with maximum concentrations late in the afternoon reaching up 70 ppbC attributed to strong emissions from the abundant vegetation of broad-leaf deciduous trees in this area. A new HPLC-MS method was developed for the determination of isoprene's primary atmospheric oxidation products methacrolein as its 2,4-dinitrophenylhydrazone and methyl vinyl ketone as an unusual double derivative with 2,4-dinitrophenylhydrazine. Methacrolein and methyl vinyl ketone followed the same diurnal and annual trends as isoprene. The average monthly concentration of isoprene and these products ranged from around 10 ppbC in June, July and September to 20 ppbC in August, which constitutes 15-30% of C 3-C 9 VOCs. The contribution from isoprene photo-oxidation to the ambient air formaldehyde concentrations was also found to be high during this period ranging from 30% to 60% in May, June, July and August. From the atmospheric VOC and NO X concentrations the local photochemical ozone formation was estimated by the incremental reactivity approach. The calculations showed that in summer isoprene's contribution to the local ozone formation was as high as 50-75%.

Abscisic Acid Acts as a Blocker of the Bitter Taste G Protein-Coupled Receptor T2R4.

PubMed

Pydi, Sai P; Jaggupilli, Appalaraju; Nelson, Ken M; Abrams, Suzanne R; Bhullar, Rajinder P; Loewen, Michele C; Chelikani, Prashen

2015-04-28

Bitter taste receptors (T2Rs) belong to the G protein-coupled receptor superfamily. In humans, 25 T2Rs mediate bitter taste sensation. In addition to the oral cavity, T2Rs are expressed in many extraoral tissues, including the central nervous system, respiratory system, and reproductive system. To understand the mechanistic roles of the T2Rs in oral and extraoral tissues, novel blockers or antagonists are urgently needed. Recently, we elucidated the binding pocket of T2R4 for its agonist quinine, and an antagonist and inhibitory neurotransmitter, γ-aminobutyric acid. This structure-function information about T2R4 led us to screen the plant hormone abscisic acid (ABA), its precursor (xanthoxin), and catabolite phaseic acid for their ability to bind and activate or inhibit T2R4. Molecular docking studies followed by functional assays involving calcium imaging confirmed that ABA is an antagonist with an IC50 value of 34.4 ± 1.1 μM. However, ABA precursor xanthoxin acts as an agonist on T2R4. Interestingly, molecular model-guided site-directed mutagenesis suggests that the T2R4 residues involved in quinine binding are also predominantly involved in binding to the novel antagonist, ABA. The antagonist ability of ABA was tested using another T2R4 agonist, yohimbine. Our results suggest that ABA does not inhibit yohimbine-induced T2R4 activity. The discovery of natural bitter blockers has immense nutraceutical and physiological significance and will help in dissecting the T2R molecular pathways in various tissues.

Positive Selection on a Regulatory Insertion–Deletion Polymorphism in FADS2 Influences Apparent Endogenous Synthesis of Arachidonic Acid

PubMed Central

Kothapalli, Kumar S. D.; Ye, , Kaixiong; Gadgil, Maithili S.; Carlson, Susan E.; O’Brien, Kimberly O.; Zhang, Ji Yao; Park, Hui Gyu; Ojukwu, Kinsley; Zou, James; Hyon, Stephanie S.; Joshi, Kalpana S.; Gu, Zhenglong; Keinan, Alon; Brenna, J.Thomas

2016-01-01

Long chain polyunsaturated fatty acids (LCPUFA) are bioactive components of membrane phospholipids and serve as substrates for signaling molecules. LCPUFA can be obtained directly from animal foods or synthesized endogenously from 18 carbon precursors via the FADS2 coded enzyme. Vegans rely almost exclusively on endogenous synthesis to generate LCPUFA and we hypothesized that an adaptive genetic polymorphism would confer advantage. The rs66698963 polymorphism, a 22-bp insertion–deletion within FADS2, is associated with basal FADS1 expression, and coordinated induction of FADS1 and FADS2 in vitro. Here, we determined rs66698963 genotype frequencies from 234 individuals of a primarily vegetarian Indian population and 311 individuals from the US. A much higher I/I genotype frequency was found in Indians (68%) than in the US (18%). Analysis using 1000 Genomes Project data confirmed our observation, revealing a global I/I genotype of 70% in South Asians, 53% in Africans, 29% in East Asians, and 17% in Europeans. Tests based on population divergence, site frequency spectrum, and long-range haplotype consistently point to positive selection encompassing rs66698963 in South Asian, African, and some East Asian populations. Basal plasma phospholipid arachidonic acid (ARA) status was 8% greater in I/I compared with D/D individuals. The biochemical pathway product–precursor difference, ARA minus linoleic acid, was 31% and 13% greater for I/I and I/D compared with D/D, respectively. This study is consistent with previous in vitro data suggesting that the insertion allele enhances n-6 LCPUFA synthesis and may confer an adaptive advantage in South Asians because of the traditional plant-based diet practice. PMID:27188529

Defining the carbohydrate specificities of Abrus precatorius agglutinin as T (Gal beta 1----3GalNAc) greater than I/II (Gal beta 1----3/4GlcNAc).

PubMed

Wu, A M; Lin, S R; Chin, L K; Chow, L P; Lin, J Y

1992-09-25

The combining site of the nontoxic carbohydrate binding protein (Abrus precatorius agglutinin, APA) purified from the needs of Abrus precatorius (Jequirity bean), was studied by quantitative precipitin and precipitin-inhibition assays. Of 26 glycoproteins and polysaccharides tested, all, except sialic acid-containing glycoproteins and desialized ovine salivary glycoproteins, reacted strongly with the lectin, and precipitated over 70% of the lectin added, indicating that APA has a broad range of affinity and recognizes (internal) Gal beta 1----sequences of carbohydrate chains. The strong reaction with desialized porcine and rat salivary glycoproteins as well as pneumococcus type XIV polysaccharide suggests that APA has affinity for one or more of the following carbohydrate sequences: Thomsen-Friedenreich (T, Gal beta 1----3GalNAc), blood group precursor type I and/or type II (Gal beta 1----3/4GlcNAc) disaccharide determinants of complex carbohydrates. Among the oligosaccharides tested, the T structure was the best inhibitor; it was 2.4 and 3.2 times more active than type II and type I sequences, respectively. The blood group I Ma-active trisaccharide, Gal beta 1----4GlcNAc beta 1----6Gal, was about as active as the corresponding disaccharide (II). From the above results, we conclude that the size of the combining site of the A. precatorius agglutinin is probably as large as a disaccharide and most strongly complementary to the Gal beta 1----3GalNAc (T determinant) sequence. The carbohydrate specificities of this lectin will be further investigated once the related oligosaccharide structures become available.

Optimizing the deposition of hydrogen evolution sites on suspended semiconductor particles using on-line photocatalytic reforming of aqueous methanol solutions.

PubMed

Busser, G Wilma; Mei, Bastian; Muhler, Martin

2012-11-01

The deposition of hydrogen evolution sites on photocatalysts is a crucial step in the multistep process of synthesizing a catalyst that is active for overall photocatalytic water splitting. An alternative approach to conventional photodeposition was developed, applying the photocatalytic reforming of aqueous methanol solutions to deposit metal particles on semiconductor materials such as Ga₂O₃ and (Ga₀.₆ Zn₀.₄)(N₀.₆O₀.₄). The method allows optimizing the loading of the co-catalysts based on the stepwise addition of their precursors and the continuous online monitoring of the evolved hydrogen. Moreover, a synergetic effect between different co-catalysts can be directly established. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The hppA gene of Helicobacter pylori encodes the class C acid phosphatase precursor.

PubMed

Godlewska, Renata; Bujnicki, Janusz M; Ostrowski, Jerzy; Jagusztyn-Krynicka, Elzbieta K

2002-08-14

Screening of the Helicobacter pylori genomic library with sera from infected humans and from immunized rabbits resulted in identification of the 25 kDa protein cell envelope (HppA) which exhibits acid phosphatase activity. Enzyme activity was demonstrated by specific enzymatic assays with whole-cell protein preparations of H. pylori strain N6 and from Escherichia coli carrying the hppA gene (pUWM192). HppA showed optimum activity at pH 5.6 and was resistant to inhibition by EDTA. Bioinformatics analysis and site-directed mutagenesis of two putative active site residues (D73 and D192) provide further insight into the sequence-structure-function relationships of HppA as a member of the DDDD phosphohydrolase superfamily.

ORP5/ORP8 localize to endoplasmic reticulum-mitochondria contacts and are involved in mitochondrial function.

PubMed

Galmes, Romain; Houcine, Audrey; van Vliet, Alexander R; Agostinis, Patrizia; Jackson, Catherine L; Giordano, Francesca

2016-06-01

The oxysterol-binding protein (OSBP)-related proteins ORP5 and ORP8 have been shown recently to transport phosphatidylserine (PS) from the endoplasmic reticulum (ER) to the plasma membrane (PM) at ER-PM contact sites. PS is also transferred from the ER to mitochondria where it acts as precursor for mitochondrial PE synthesis. Here, we show that, in addition to ER-PM contact sites, ORP5 and ORP8 are also localized to ER-mitochondria contacts and interact with the outer mitochondrial membrane protein PTPIP51. A functional lipid transfer (ORD) domain was required for this localization. Interestingly, ORP5 and ORP8 depletion leads to defects in mitochondria morphology and respiratory function. © 2016 The Authors.