Characterization of solution-phase and gas-phase reactions in on-line electrochemistry-thermospray tandem mass spectrometry.

PubMed

Volk, K J; Yost, R A; Brajter-Toth, A

1989-07-14

Electrochemistry was used on-line with high-performance liquid chromatography-thermospray tandem mass spectrometry to provide insight into the solution-phase decomposition reactions of electrochemically generated oxidation products. Products formed during electrooxidation were monitored as the electrode potential was varied. The solution reactions which follow the initial electron transfer at the electrode are affected by the vaporizer tip temperature of the thermospray probe and the composition of the thermospray buffer. Either hydrolysis or ammonolysis reactions of the initial electrochemical oxidation products can occur with pH 7 ammonium acetate buffer. Both the electrochemically generated and the synthesized disulfide of 6-thiopurine decompose under thermospray conditions to produce 6-thiopurine and purine-6-sulfinate. Solution-phase studies indicate that nucleophilic and electrophilic substitution reactions with purine-6-sulfinate result in the formation of purine, adenine, and hypoxanthine. Products were identified and characterized by tandem mass spectrometry. This work shows the first example of high-performance liquid chromatography used on-line with electrochemistry to separate stable oxidation products prior to analysis by thermospray tandem mass spectrometry. In addition, solution-phase and gas-phase studies with methylamine show that the site of the nucleophilic and electrophilic reactions is probably inside the thermospray probe. Most importantly, these results also show that the on-line combination of electrochemistry with thermospray tandem mass spectrometry provides valuable information about redox and associated chemical reactions of biological molecules such as the structures of intermediates or products as well as providing insight into reaction pathways.

Parallel Reaction Monitoring: A Targeted Experiment Performed Using High Resolution and High Mass Accuracy Mass Spectrometry

PubMed Central

Rauniyar, Navin

2015-01-01

The parallel reaction monitoring (PRM) assay has emerged as an alternative method of targeted quantification. The PRM assay is performed in a high resolution and high mass accuracy mode on a mass spectrometer. This review presents the features that make PRM a highly specific and selective method for targeted quantification using quadrupole-Orbitrap hybrid instruments. In addition, this review discusses the label-based and label-free methods of quantification that can be performed with the targeted approach. PMID:26633379

Systematic Identification of Combinatorial Drivers and Targets in Cancer Cell Lines

PubMed Central

Tabchy, Adel; Eltonsy, Nevine; Housman, David E.; Mills, Gordon B.

2013-01-01

There is an urgent need to elicit and validate highly efficacious targets for combinatorial intervention from large scale ongoing molecular characterization efforts of tumors. We established an in silico bioinformatic platform in concert with a high throughput screening platform evaluating 37 novel targeted agents in 669 extensively characterized cancer cell lines reflecting the genomic and tissue-type diversity of human cancers, to systematically identify combinatorial biomarkers of response and co-actionable targets in cancer. Genomic biomarkers discovered in a 141 cell line training set were validated in an independent 359 cell line test set. We identified co-occurring and mutually exclusive genomic events that represent potential drivers and combinatorial targets in cancer. We demonstrate multiple cooperating genomic events that predict sensitivity to drug intervention independent of tumor lineage. The coupling of scalable in silico and biologic high throughput cancer cell line platforms for the identification of co-events in cancer delivers rational combinatorial targets for synthetic lethal approaches with a high potential to pre-empt the emergence of resistance. PMID:23577104

Systematic identification of combinatorial drivers and targets in cancer cell lines.

PubMed

Tabchy, Adel; Eltonsy, Nevine; Housman, David E; Mills, Gordon B

2013-01-01

There is an urgent need to elicit and validate highly efficacious targets for combinatorial intervention from large scale ongoing molecular characterization efforts of tumors. We established an in silico bioinformatic platform in concert with a high throughput screening platform evaluating 37 novel targeted agents in 669 extensively characterized cancer cell lines reflecting the genomic and tissue-type diversity of human cancers, to systematically identify combinatorial biomarkers of response and co-actionable targets in cancer. Genomic biomarkers discovered in a 141 cell line training set were validated in an independent 359 cell line test set. We identified co-occurring and mutually exclusive genomic events that represent potential drivers and combinatorial targets in cancer. We demonstrate multiple cooperating genomic events that predict sensitivity to drug intervention independent of tumor lineage. The coupling of scalable in silico and biologic high throughput cancer cell line platforms for the identification of co-events in cancer delivers rational combinatorial targets for synthetic lethal approaches with a high potential to pre-empt the emergence of resistance.

Direct observation of feedout-related areal mass oscillations in planar plastic targets.

NASA Astrophysics Data System (ADS)

Aglitskiy, Y.; Metzler, N.; Velikovich, A. L.; Karasik, M.; Serlin, V.; Pawley, C.; Mostovych, A. N.; Schmitt, A. J.; Obenschain, S. P.; Gardner, J. H.

2001-10-01

"Feedout" means the transfer of mass perturbations from the rear to the front surface of a driven target. The oscillations are expected if the perturbation wavelength λ is not large compared to 2π L_s, where Ls is the shock-compressed target thickness. We report the first direct experimental observation of areal mass oscillation associated with feedout, followed by the onset of exponential RT growth. Our experiments were performed with the Nike KrF laser at irradiation 50 TW/cm^2. The mass redistribution in the target was observed with the aid of monochromatic x-ray imaging coupled to a streak camera. We used 40 to 60 μm thick CH targets rippled on the rear side with wavelengths of either 30 or 45 μm, the ratio 2π L_s/λ thus being close to 2. Two phase reversals of mass variation predicted by the theory and simulations were consistently observed both on the original images and on the time histories of Fourier amplitudes.

The Effect of Arrow Mass and Shape on Penetration into a Target

NASA Astrophysics Data System (ADS)

Shyam, S.; Gurram, A.; Madireddy, S.

2016-12-01

We conducted an archery experiment in order to quantify how aerodynamic design impacted the depth of arrow impact. Research shows that the smaller the surface area of an object, the more easily it travels through the air and the deeper it penetrates a target (Benson 2014). Momentum also affects how far and fast the arrow will go and therefore, how deep it will penetrate into the target. Therefore, a combination of an arrow with greater momentum and better aerodynamics will help the arrow fly faster and penetrate the target deeper. Mass, velocity, momentum, acceleration, force, and drag are the factors that acted on our experiment and produced its results. We hypothesized that the arrow with a thin shaft and pointed arrowhead would penetrate deepest, as opposed to both arrows with no arrowheads or arrows with thick shafts and blunt arrowheads. We tested our hypothesis by having a well-trained archer shoot different types of arrows into a target. We used arrows with shaft lengths of 7 cm and 5.3 cm, coupled with either pointed, blunt, or no arrowhead. We measured the time to target and arrow penetration (in cm) to see which style reached the target the fastest and penetrated the deepest. The results demonstrated that arrows with thin shafts and pointed arrowheads penetrated our target the deepest, followed by arrows with thick shafts and blunt arrowheads. Arrows with thin shafts and blunt arrowheads came after, and arrows with thick shafts and pointed arrowheads came last in depth of penetration. The arrows with no arrowheads either barely penetrated the target, or bounced back. We were able to conclude that the thinner the shaft and the more pointed the arrowhead, the better the arrow cuts the air. This is because, according to the principles of aerodynamics, it creates less drag since the surface area is smaller. However, mass also plays an important role in force through momentum, which also significantly affected our results.

High-throughput screening for multi-class veterinary drug residues in animal muscle using liquid chromatography/tandem mass spectrometry with on-line solid-phase extraction.

PubMed

Tang, Hubert Po-On; Ho, Clare; Lai, Shirley Sau-Ling

2006-01-01

A rapid qualitative method using on-line column-switching liquid chromatography/tandem mass spectrometry (LC/MS/MS) was developed and validated for screening 13 target veterinary drugs: four macrolides - erythromycin A, josamycin (leucomycin A3), kitasamycin (leucomycin A5), and tylosin A; six (fluoro)quinolones - ciprofloxacin, danofloxacin, enrofloxacin, flumequine, oxolinic acid, and sarafloxacin; and lincomycin, virginiamycin M1, and trimethoprim in different animal muscles. Clindamycin, norfloxacin, nalidixic acid, oleandomycin, ormetoprim, and roxithromycin were used as the internal standards. After simple deproteination and analyte extraction of muscle samples using acetonitrile, the supernatant was subjected to on-line cleanup and direct analysis by LC/MS/MS. On-line cleanup with an extraction cartridge packed with hydrophilic-hydrophobic polymer sorbent followed by fast LC using a short C18 column resulted in a total analysis cycle of 6 min for 19 drugs. This screening method considerably reduced the time and the cost for the quantitative and confirmatory analyses. The application of a control point approach was also introduced and explained. Copyright (c) 2006 John Wiley & Sons, Ltd.

Target sites for the transposition of rat long interspersed repeated DNA elements (LINEs) are not random.

PubMed Central

Furano, A V; Somerville, C C; Tsichlis, P N; D'Ambrosio, E

1986-01-01

The long interspersed repeated DNA family of rats (LINE or L1Rn family) contains about 40,000 6.7-kilobase (kb) long members (1). LINE members may be currently mobile since their presence or absence causes allelic variation at three single copy loci (2, 3): insulin 1, Moloney leukemia virus integration 2 (Mlvi-2) (4), and immunoglobulin heavy chain (Igh). To characterize target sites for LINE insertion, we compared the DNA sequences of the unoccupied Mlvi-2 target site, its LINE-containing allele, and several other LINE-containing sites. Although not homologous overall, the target sites share three characteristics: First, depending on the site, they are from 68% to 86% (A+T) compared to 58% (A+T) for total rat DNA (5). Depending on the site, a 7- to 15-bp target site sequence becomes duplicated and flanks the inserted LINE member. The second is a version (0 or 1 mismatch) of the hexanucleotide, TACTCA, which is also present in the LINE member, in a highly conserved region located just before the A-rich right end of the LINE member. The third is a stretch of alternating purine/pyrimidine (PQ). The A-rich right ends of different LINE members vary in length and composition, and the sequence of a particularly long one suggests that it contains the A-rich target site from a previous transposition. PMID:3012480

Targeted mass media interventions promoting healthy behaviours to reduce risk of non-communicable diseases in adult, ethnic minorities.

PubMed

Mosdøl, Annhild; Lidal, Ingeborg B; Straumann, Gyri H; Vist, Gunn E

2017-02-17

comparable between groups 12 months after the baseline (low quality evidence). Scores on a food habits (fat behaviours) and total leisure activity scores changed favourably for the intervention group (very low quality evidence). Two other studies exposed entire populations in geographical areas to radio advertisements targeted towards African American communities. Authors presented effects on two of our secondary outcomes, use of health promotion services and project costs. The campaign message was to call smoking quit lines. The outcome was the number of calls received. After one year, one study reported 18 calls per estimated 10,000 targeted smokers from the intervention communities (estimated target population 310,500 persons), compared to 0.2 calls per estimated 10,000 targeted smokers from the control communities (estimated target population 331,400 persons) (moderate quality evidence). The ITS study also reported an increase in the number of calls from the target population during campaigns (low quality evidence). The proportion of African American callers increased in both studies (low to very low quality evidence). No study provided data on knowledge and attitudes for change and adverse effects. Information on costs were sparse.The third comparison assessed targeted mass media interventions versus a mass media intervention plus personalised content. Findings are based on three studies (1361 participants). Participants in these comparison groups received personal feedback. Two of the studies recorded weight changes over time. Neither found significant differences between the groups (low quality evidence). Evidence on behavioural changes, and knowledge and attitudes typically found some effects in favour of receiving personalised content or no significant differences between groups (very low quality evidence). No study provided data on adverse effects. Information on costs were sparse. The available evidence is inadequate for understanding whether mass media

Identification and Affinity-Quantification of ß-Amyloid and α-Synuclein Polypeptides Using On-Line SAW-Biosensor-Mass Spectrometry

NASA Astrophysics Data System (ADS)

Slamnoiu, Stefan; Vlad, Camelia; Stumbaum, Mihaela; Moise, Adrian; Lindner, Kathrin; Engel, Nicole; Vilanova, Mar; Diaz, Mireia; Karreman, Christiaan; Leist, Marcel; Ciossek, Thomas; Hengerer, Bastian; Vilaseca, Marta; Przybylski, Michael

2014-08-01

Bioaffinity analysis using a variety of biosensors has become an established tool for detection and quantification of biomolecular interactions. Biosensors, however, are generally limited by the lack of chemical structure information of affinity-bound ligands. On-line bioaffinity-mass spectrometry using a surface-acoustic wave biosensor (SAW-MS) is a new combination providing the simultaneous affinity detection, quantification, and mass spectrometric structural characterization of ligands. We describe here an on-line SAW-MS combination for direct identification and affinity determination, using a new interface for MS of the affinity-isolated ligand eluate. Key element of the SAW-MS combination is a microfluidic interface that integrates affinity-isolation on a gold chip, in-situ sample concentration, and desalting with a microcolumn for MS of the ligand eluate from the biosensor. Suitable MS- acquisition software has been developed that provides coupling of the SAW-MS interface to a Bruker Daltonics ion trap-MS, FTICR-MS, and Waters Synapt-QTOF- MS systems. Applications are presented for mass spectrometric identifications and affinity (KD) determinations of the neurodegenerative polypeptides, ß-amyloid (Aß), and pathophysiological and physiological synucleins (α- and ß-synucleins), two key polypeptide systems for Alzheimer's disease and Parkinson's disease, respectively. Moreover, first in vivo applications of αSyn polypeptides from brain homogenate show the feasibility of on-line affinity-MS to the direct analysis of biological material. These results demonstrate on-line SAW-bioaffinity-MS as a powerful tool for structural and quantitative analysis of biopolymer interactions.

Targeted Quantitation of Proteins by Mass Spectrometry

PubMed Central

2013-01-01

Quantitative measurement of proteins is one of the most fundamental analytical tasks in a biochemistry laboratory, but widely used immunochemical methods often have limited specificity and high measurement variation. In this review, we discuss applications of multiple-reaction monitoring (MRM) mass spectrometry, which allows sensitive, precise quantitative analyses of peptides and the proteins from which they are derived. Systematic development of MRM assays is permitted by databases of peptide mass spectra and sequences, software tools for analysis design and data analysis, and rapid evolution of tandem mass spectrometer technology. Key advantages of MRM assays are the ability to target specific peptide sequences, including variants and modified forms, and the capacity for multiplexing that allows analysis of dozens to hundreds of peptides. Different quantitative standardization methods provide options that balance precision, sensitivity, and assay cost. Targeted protein quantitation by MRM and related mass spectrometry methods can advance biochemistry by transforming approaches to protein measurement. PMID:23517332

Targeted quantitation of proteins by mass spectrometry.

PubMed

Liebler, Daniel C; Zimmerman, Lisa J

2013-06-04

Quantitative measurement of proteins is one of the most fundamental analytical tasks in a biochemistry laboratory, but widely used immunochemical methods often have limited specificity and high measurement variation. In this review, we discuss applications of multiple-reaction monitoring (MRM) mass spectrometry, which allows sensitive, precise quantitative analyses of peptides and the proteins from which they are derived. Systematic development of MRM assays is permitted by databases of peptide mass spectra and sequences, software tools for analysis design and data analysis, and rapid evolution of tandem mass spectrometer technology. Key advantages of MRM assays are the ability to target specific peptide sequences, including variants and modified forms, and the capacity for multiplexing that allows analysis of dozens to hundreds of peptides. Different quantitative standardization methods provide options that balance precision, sensitivity, and assay cost. Targeted protein quantitation by MRM and related mass spectrometry methods can advance biochemistry by transforming approaches to protein measurement.

Target intersection probabilities for parallel-line and continuous-grid types of search

USGS Publications Warehouse

McCammon, R.B.

1977-01-01

elliptically shaped target can be approximated by treating the ellipse as intermediate between a circle and a line. A search conducted along a continuous rectangular grid can be represented as intermediate between a search along parallel lines and along a continuous square grid. On this basis, an upper and lower bound for the probability of intersection of an elliptically shaped target for a continuous rectangular grid can be calculated. Charts have been constructed that permit the values for these probabilities to be obtained graphically. The use of conditional probability allows the explorationist greater flexibility in considering alternate search strategies for locating hidden targets. ?? 1977 Plenum Publishing Corp.

Effects of seed mixture sowing with transgenic Bt rice and its parental line on the population dynamics of target stemborers and leafrollers, and non-target planthoppers.

PubMed

Li, Zhuo; Li, Li-Kun; Liu, Bin; Wang, Long; Parajulee, Megha N; Chen, Fa-Jun

2018-01-24

The widespread planting of insect-resistant crops has caused a dramatic shift in agricultural landscapes, thus raising concerns about the potential impacts on both target and non-target pests. In this study, we examined the potential effects of intra-specific seed mixture sowing with transgenic Bt rice (Bt) and its parental non-transgenic line (Nt) (100% Bt rice [Bt 100 ], 5% Nt+95% Bt [Nt 05 Bt 95 ], 10% Nt+90% Bt [Nt 10 Bt 90 ], 20% Nt+80% Bt [Nt 20 Bt 80 ], 40% Nt+60% Bt [Nt 40 Bt 60 ] and 100% Nt rice [Nt 100 ]) on target and non-target pests in a 2-year field trial in southern China. The occurrence of target pests, Sesamia inferens, Chilo suppressalis and Cnaphalocrocis medinalis, decreased with the increased ratio of Bt rice, and the mixture ratios with more than 90% Bt rice (Bt 100 and Nt 05 Bt 95 ) significantly increased the pest suppression efficiency, with the lowest occurrences of non-target planthoppers, Nilaparvata lugens and Sogatella furcifera in Nt 100 and Nt 05 Bt 95 . Furthermore, there were no significant differences in 1000-grain dry weight and grain dry weight per 100 plants between Bt 100 and Nt 05 Bt 95 . Seed mixture sowing of Bt rice with ≤10% (especially 5%) of its parent line was sufficient to overcome potential compliance issues that exist with the use of block or structured refuge to provide most effective control of both target and non-target pests without compromising the grain yield. It is also expected that the strategy of seed mixture sowing with transgenic Bt rice and the non-transgenic parental line would provide rice yield stability while decreasing the insecticide use frequency in rice production. © 2018 Institute of Zoology, Chinese Academy of Sciences.

[Liquid chromatography-tandem mass spectrometry method for determination of 10 macrolide antibiotics in pork samples using on-line solid phase extraction purification].

PubMed

Zhang, Xiaoguang; Liu, Dong; Liu, Hongran; Li, Qiang; Li, Lili; Wang, Lixia; Zhang, Yan

2017-10-08

A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method based on-line solid phase extraction (SPE) purification was established to determine 10 macrolide antibiotics in pork samples. The samples were extracted with acetonitrile, and the extracts were dried with rotary evaporator at 40℃, then the analytes were dissolved with 2 mL phosphate buffer. The solutions were purified and concentrated by on-line SPE with HLB cartridges. The analytes were eluted with methanol, and then transferred to XBridge BEH C18 column, separated with the mobile phases of 10 mmol/L ammonium acetate aqueous solution and acetonitrile. Finally, the target analytes were detected by tandem mass spectrometry. The results showed that good linearity was obtained in the range of 0.1-200 μg/L for the 10 macrolide antibiotics with correlation coefficients better than 0.990. The limits of detection were in range of 0.05-0.30 μg/kg and the limits of quantitation were in range of 0.10-1.00 μg/kg. The recoveries of the method were in range of 69.6%-115.2% at the spiked levels of 0.10-10.0 μg/kg for all analytes, with the relative standard deviations less than 10%. The developed method can be used for the determination of the 10 macrolide antibiotics in pork samples.

Unbiased and targeted mass spectrometry for the HDL proteome.

PubMed

Singh, Sasha A; Aikawa, Masanori

2017-02-01

Mass spectrometry is an ever evolving technology that is equipped with a variety of tools for protein research. Some lipoprotein studies, especially those pertaining to HDL biology, have been exploiting the versatility of mass spectrometry to understand HDL function through its proteome. Despite the role of mass spectrometry in advancing research as a whole, however, the technology remains obscure to those without hands on experience, but still wishing to understand it. In this review, we walk the reader through the coevolution of common mass spectrometry workflows and HDL research, starting from the basic unbiased mass spectrometry methods used to profile the HDL proteome to the most recent targeted methods that have enabled an unprecedented view of HDL metabolism. Unbiased global proteomics have demonstrated that the HDL proteome is organized into subgroups across the HDL size fractions providing further evidence that HDL functional heterogeneity is in part governed by its varying protein constituents. Parallel reaction monitoring, a novel targeted mass spectrometry method, was used to monitor the metabolism of HDL apolipoproteins in humans and revealed that apolipoproteins contained within the same HDL size fraction exhibit diverse metabolic properties. Mass spectrometry provides a variety of tools and strategies to facilitate understanding, through its proteins, the complex biology of HDL.

Orientation of X Lines in Asymmetric Magnetic Reconnection-Mass Ratio Dependency

NASA Technical Reports Server (NTRS)

Liu, Yi-Hsin; Hesse, M.; Kuznetsova, M.

2015-01-01

Using fully kinetic simulations, we study the X line orientation of magnetic reconnection in an asymmetric configuration. A spatially localized perturbation is employed to induce a single X line, which has sufficient freedom to choose its orientation in three-dimensional systems. The effect of ion to electron mass ratio is investigated, and the X line appears to bisect the magnetic shear angle across the current sheet in the large mass ratio limit. The orientation can generally be deduced by scanning through the corresponding 2-D simulations to find the reconnection plane that maximizes the peak reconnection electric field. The deviation from the bisection angle in the lower mass ratio limit is consistent with the orientation shift of the most unstable linear tearing mode in an electron-scale current sheet.

Geometric Model for Tracker-Target Look Angles and Line of Slight Distance

DTIC Science & Technology

2015-10-20

412TW-PA-15239 Geometric Model for Tracker -Target Look Angles and Line of Slight Distance DANIEL T. LAIRD AIR FORCE TEST CENTER EDWARDS...15 – 23 OCT 15 4. TITLE AND SUBTITLE Geometric Model for Tracker -Target Look Angles and Line of Slight Distance 5a. CONTRACT...include area code) 661-277-8615 Standard Form 298 (Rev. 8-98) Prescribed by ANSI Std. Z39.18 GEOMETRIC MODEL FOR TRACKER -TARGET LOOK ANGLES

Galaxy And Mass Assembly (GAMA): Improved emission lines measurements in four representative samples at 0.07

NASA Astrophysics Data System (ADS)

Rodrigues, M.; Foster, C.; Taylor, E. N.; Wright, A. H.; Hopkins, A. M.; Baldry, I.; Brough, S.; Bland-Hawthorn, J.; Cluver, M. E.; Lara-López, M. A.; Liske, J.; López-Sánchez, Á. R.; Pimbblet, K. A.

2016-05-01

This paper presents a new catalog of emission lines based on the GAMA II data for galaxies between 0.07 mass galaxies down to log M∗> 9.4 at z ~ 0.1 and log M∗> 10.6 at z ~ 0.30. We have developed a dedicated code called MARVIN that automates the main steps of the data analysis, but imposes visual individual quality control of each measurement. We use this catalog to investigate how the sample selection influences the shape of the stellar mass - metallicity relation. We find that commonly used selection criteria on line detections and by AGN rejection could affect the shape and dispersion of the high-mass end of the M - Z relation. For log M∗> 10.6, common selection criteria reject about 65% of the emission-line galaxies. We also find that the relation does not evolve significantly from z = 0.07 to z = 0.34 in the range of stellar mass for which the samples are representative (log M∗> 10.6). For lower stellar masses (log M∗< 10.2) we are able to show that the observed 0.15 dex metallicity decrease in the same redshift range is a consequence of a color bias arising from selecting targets in the r-band. We highlight that this color selection bias affects all samples selected in r-band (e.g., GAMA and SDSS), even those drawn from volume-limited samples. Previously reported evolution of the M - Z relation at various redshifts may need to be revised to evaluate the effect of this selection bias.

On-line supercritical fluid extraction-supercritical fluid chromatography-mass spectrometry of polycyclic aromatic hydrocarbons in soil.

PubMed

Wicker, A Paige; Carlton, Doug D; Tanaka, Kenichiro; Nishimura, Masayuki; Chen, Vivian; Ogura, Tairo; Hedgepeth, William; Schug, Kevin A

2018-06-01

On-line supercritical fluid extraction - supercritical fluid chromatography - mass spectrometry (SFE-SFC-MS) has been applied for the determination of polycyclic aromatic hydrocarbons (PAHs) in soil. The purpose of this study was to develop and validate the first on-line SFE-SFC-MS method for the quantification of PAHs in various types of soil. By coupling the sample extraction on-line with chromatography and detection, sample preparation is minimized, diminishing sample loss and contamination, and significantly decreasing the required extraction time. Parameters for on-line extraction coupled to chromatographic analysis were optimized. The method was validated for concentrations of 10-1500 ng of PAHs per gram of soil in Certified Reference Material (CRM) sediment, clay, and sand with R 2  ≥ 0.99. Limits of detection (LOD) were found in the range of 0.001-5 ng/g, and limits of quantification (LOQ) in the range of 5-15 ng/g. The method developed in this study can be effectively applied to the study of PAHs in the environment, and may lay the foundation for further applications of on-line SFE-SFC-MS. Copyright © 2018 Elsevier B.V. All rights reserved.

Plasma Membrane Proteomics of Human Breast Cancer Cell Lines Identifies Potential Targets for Breast Cancer Diagnosis and Treatment

PubMed Central

Ziegler, Yvonne S.; Moresco, James J.; Tu, Patricia G.; Yates, John R.; Nardulli, Ann M.

2014-01-01

The use of broad spectrum chemotherapeutic agents to treat breast cancer results in substantial and debilitating side effects, necessitating the development of targeted therapies to limit tumor proliferation and prevent metastasis. In recent years, the list of approved targeted therapies has expanded, and it includes both monoclonal antibodies and small molecule inhibitors that interfere with key proteins involved in the uncontrolled growth and migration of cancer cells. The targeting of plasma membrane proteins has been most successful to date, and this is reflected in the large representation of these proteins as targets of newer therapies. In view of these facts, experiments were designed to investigate the plasma membrane proteome of a variety of human breast cancer cell lines representing hormone-responsive, ErbB2 over-expressing and triple negative cell types, as well as a benign control. Plasma membranes were isolated by using an aqueous two-phase system, and the resulting proteins were subjected to mass spectrometry analysis. Overall, each of the cell lines expressed some unique proteins, and a number of proteins were expressed in multiple cell lines, but in patterns that did not always follow traditional clinical definitions of breast cancer type. From our data, it can be deduced that most cancer cells possess multiple strategies to promote uncontrolled growth, reflected in aberrant expression of tyrosine kinases, cellular adhesion molecules, and structural proteins. Our data set provides a very rich and complex picture of plasma membrane proteins present on breast cancer cells, and the sorting and categorizing of this data provides interesting insights into the biology, classification, and potential treatment of this prevalent and debilitating disease. PMID:25029196

Transitioning from Targeted to Comprehensive Mass Spectrometry Using Genetic Algorithms.

PubMed

Jaffe, Jacob D; Feeney, Caitlin M; Patel, Jinal; Lu, Xiaodong; Mani, D R

2016-11-01

Targeted proteomic assays are becoming increasingly popular because of their robust quantitative applications enabled by internal standardization, and they can be routinely executed on high performance mass spectrometry instrumentation. However, these assays are typically limited to 100s of analytes per experiment. Considerable time and effort are often expended in obtaining and preparing samples prior to targeted analyses. It would be highly desirable to detect and quantify 1000s of analytes in such samples using comprehensive mass spectrometry techniques (e.g., SWATH and DIA) while retaining a high degree of quantitative rigor for analytes with matched internal standards. Experimentally, it is facile to port a targeted assay to a comprehensive data acquisition technique. However, data analysis challenges arise from this strategy concerning agreement of results from the targeted and comprehensive approaches. Here, we present the use of genetic algorithms to overcome these challenges in order to configure hybrid targeted/comprehensive MS assays. The genetic algorithms are used to select precursor-to-fragment transitions that maximize the agreement in quantification between the targeted and the comprehensive methods. We find that the algorithm we used provided across-the-board improvement in the quantitative agreement between the targeted assay data and the hybrid comprehensive/targeted assay that we developed, as measured by parameters of linear models fitted to the results. We also found that the algorithm could perform at least as well as an independently-trained mass spectrometrist in accomplishing this task. We hope that this approach will be a useful tool in the development of quantitative approaches for comprehensive proteomics techniques. Graphical Abstract ᅟ.

Transitioning from Targeted to Comprehensive Mass Spectrometry Using Genetic Algorithms

NASA Astrophysics Data System (ADS)

Jaffe, Jacob D.; Feeney, Caitlin M.; Patel, Jinal; Lu, Xiaodong; Mani, D. R.

2016-11-01

Targeted proteomic assays are becoming increasingly popular because of their robust quantitative applications enabled by internal standardization, and they can be routinely executed on high performance mass spectrometry instrumentation. However, these assays are typically limited to 100s of analytes per experiment. Considerable time and effort are often expended in obtaining and preparing samples prior to targeted analyses. It would be highly desirable to detect and quantify 1000s of analytes in such samples using comprehensive mass spectrometry techniques (e.g., SWATH and DIA) while retaining a high degree of quantitative rigor for analytes with matched internal standards. Experimentally, it is facile to port a targeted assay to a comprehensive data acquisition technique. However, data analysis challenges arise from this strategy concerning agreement of results from the targeted and comprehensive approaches. Here, we present the use of genetic algorithms to overcome these challenges in order to configure hybrid targeted/comprehensive MS assays. The genetic algorithms are used to select precursor-to-fragment transitions that maximize the agreement in quantification between the targeted and the comprehensive methods. We find that the algorithm we used provided across-the-board improvement in the quantitative agreement between the targeted assay data and the hybrid comprehensive/targeted assay that we developed, as measured by parameters of linear models fitted to the results. We also found that the algorithm could perform at least as well as an independently-trained mass spectrometrist in accomplishing this task. We hope that this approach will be a useful tool in the development of quantitative approaches for comprehensive proteomics techniques.

Mass balance for on-line alphakLa estimation in activated sludge oxidation ditch.

PubMed

Chatellier, P; Audic, J M

2001-01-01

The capacity of an aeration system to transfer oxygen to a given activated sludge oxidation ditch is characterised by the alphakLa parameter. This parameter is difficult to measure under normal plant working conditions. Usually this measurement involves off-gas techniques or static mass balance. Therefore an on-line technique has been developed and tested in order to evaluate alphakLa. This technique deduces alphakLa from a data analysis of low cost sensor measurement: two flow meters and one oxygen probe. It involves a dynamic mass balance applied to aeration cycles selected according to given criteria. This technique has been applied to a wastewater treatment plant during four years. Significant variations of the alphakLa values have been detected while the number of blowers changes. This technique has been applied to another plant during two months.

Target selection and mass estimation for manned NEO exploration using a baseline mission design

NASA Astrophysics Data System (ADS)

Boden, Ralf C.; Hein, Andreas M.; Kawaguchi, Junichiro

2015-06-01

In recent years Near-Earth Objects (NEOs) have received an increased amount of interest as a target for human exploration. NEOs offer scientifically interesting targets, and at the same time function as a stepping stone for achieving future Mars missions. The aim of this research is to identify promising targets from the large number of known NEOs that qualify for a manned sample-return mission with a maximum duration of one year. By developing a baseline mission design and a mass estimation model, mission opportunities are evaluated based on on-orbit mass requirements, safety considerations, and the properties of the potential targets. A selection of promising NEOs is presented and the effects of mission requirements and restrictions are discussed. Regarding safety aspects, the use of free-return trajectories provides the lowest on-orbit mass, when compared to an alternative design that uses system redundancies to ensure return of the spacecraft to Earth. It is discovered that, although a number of targets are accessible within the analysed time frame, no NEO offers both easy access and high incentive for its exploration. Under the discussed aspects a first human exploration mission going beyond the vicinity of Earth will require a trade off between targets that provide easy access and those that are of scientific interest. This lack of optimal mission opportunities can be seen in the small number of only 4 NEOs that meet all requirements for a sample-return mission and remain below an on-orbit mass of 500 metric Tons (mT). All of them require a mass between 315 and 492 mT. Even less ideal, smaller asteroids that are better accessible require an on-orbit mass that exceeds the launch capability of future heavy lift vehicles (HLV) such as SLS by at least 30 mT. These mass requirements show that additional efforts are necessary to increase the number of available targets and reduce on-orbit mass requirements through advanced mission architectures. The need for on

SHIELD: EVLA HI Spectral Line Observations of Low-mass Dwarfs

NASA Astrophysics Data System (ADS)

Miazzo, Masao; Ruvolo, Elizabeth; Cannon, John M.; McNichols, Andrew; Teich, Yaron; Adams, Elizabeth A.; Giovanelli, Riccardo; Haynes, Martha P.; McQuinn, Kristen B.; Salzer, John Joseph; Skillman, Evan D.; Dolphin, Andrew E.; Elson, Edward C.; Haurberg, Nathalie C.; Huang, Shan; Janowiecki, Steven; Jozsa, Gyula; Leisman, Luke; Ott, Juergen; Papastergis, Emmanouil; Rhode, Katherine L.; Saintonge, Amelie; Van Sistine, Angela; Warren, Steven R.

2017-01-01

The “Survey of HI in Extremely Low-mass Dwarfs” (SHIELD) is a multiwavelength study of local volume low-mass galaxies. Using the now-complete Arecibo Legacy Fast ALFA (ALFALFA) source catalog, 82 systems are identified that meet distance, line width, and HI flux criteria for being gas-rich, low-mass galaxies. These systems harbor neutral gas reservoirs smaller than 3x10^7 M_sun, thus populating the faint end of the HI mass function with statistical confidence for the first time. Here we present new Karl G. Jansky Very Large Array D-configuration HI spectral line observations of 32 previously unobserved galaxies. These low angular resolution (~40" beam) images localize the HI gas; with a few exceptions, the HI gas is co-spatial with the optical centers of the galaxies. These images provide the first glimpse of the neutral interstellar medium in these systems.Support for this work was provided by NSF grant 1211683 to JMC at Macalester College.

The Effects of Parachute System Mass and Suspension-Line Elastic Properties on the LADT #3 Viking Parachute Inflation Load

NASA Technical Reports Server (NTRS)

Talay, Theodore A.; Poole, Lamont R.

1971-01-01

Analytical calculations have considered the effects of 1) varying parachute system mass, 2) suspension-line damping, and 3) alternate suspension-line force-elongation data on the canopy force history. Results indicate the canopy force on the LADT #3 parachute did not substantially exceed the recorded vehicle force reading and that the above factors can have significant effects on the canopy force history. Analytical calculations have considered the effects of i) varying parachute system mass, 2) suspension line damping, and 3) different suspension-line force-elongation data on the canopy force history. Based on the results of this study the following conclusions are drawn: Specifically, 1. At the LADT #3 failure time of 1.70 seconds, the canopy force ranged anywhere from 15.7% below to 2.4% above the vehicle force depending upon the model and data used. Therefore, the canopy force did not substantially exceed the recorded vehicle force reading. 2. At a predicted full inflation time of 1.80 seconds the canopy force would be greater than the vehicle force by from 1.1% to 10.6%, again depending upon the model and data used. Generally, 3. At low altitudes, enclosed and apparent air mass can significantly effect the canopy force calculated and should, therefore, not be neglected. 4. The canopy force calculations are sensitive to decelerator physical properties. In this case changes in the damping and/or force-elongation characteristics produced significant changes in the canopy force histories. Accurate prediction of canopy force histories requires accurate inputs in these areas.

The effects of color cues on typically developing preschoolers' speed of locating a target line drawing: implications for augmentative and alternative communication display design.

PubMed

Thistle, Jennifer J; Wilkinson, Krista

2009-08-01

This research examined how the presence of color in relation to a target within an augmentative and alternative communication array influenced the speed with which typically developing preschoolers located a target line drawing. Fifteen children over the age of 4 years (from 4;2 [years;months] to 5;4) and 15 children under the age of 4 years (2;10-3;11) participated. Participants were asked to find a target line drawing of foods (e.g., banana and tomato) among an array of 12. The reaction time of locating the target was measured across 4 conditions in which the foreground color and the background color of the line drawing were manipulated. For all participants, line drawings featuring foreground color provided greater advantages in the speed of locating the target compared with drawings featuring only background color. Younger participants demonstrated faster reaction times when color was limited to the foreground. Clinicians should consider incorporating color in the foreground of the line drawing when constructing visual displays. Targets that contain only background color but no foreground color appear to have a negative effect on the speed with which younger children can locate a target. Further research is needed to determine the effects in children with disabilities.

Recombinant cell lines expressing shRNA targeting herpes simplex virus 2 VP16 inhibit virus replication.

PubMed

Zhang, Rui; Wang, Yan; Song, Bo; Han, Zhi Qiang; Xu, Yu Ming

2012-01-01

To establish HSV2 VP16 targeting shRNA-expressing cell lines and investigate the antiviral effect of shRNA targeting HSV2 VP16. The cell lines Vero-shRNAs and negative-control Vero-shCON were established. Their inhibition effects on VP16 mRNA expression were tested by real-time fluorescent quantitative polymerase chain reaction (PCR) and their antiviral effects were evaluated by yield reduction assay. The influence of passage numbers on the inhibition ability of cell lines was researched. Vero-shRNA24 targeting the upper stream, Vero-shRNA642 targeting the lower stream and Vero-shCON were established. Vero-shRNA24, Vero-shRNA642 and Vero-shRNA24 + 642 could reduce the VP16 mRNA significantly. Vero-shRNA24 was the most efficient. The HSV2 titers in Vero and Vero-shCON were the highest at 72 h after infection, and started decreasing thereafter. The viral titers of the Vero-shRNA groups reached a peak after 84 h and the highest titers were lower than in the Vero group. The inhibiting effect on VP16 mRNA expression and viral replication of Vero-shRNA24 cell lines of passages 10 and 20 were not significantly different from the primary cell line. Although of no statistical significance, the passage 50 cell line showed decreased inhibiting ability. Recombinant cell lines expressing shRNA targeting HSV2 VP16 were established. They can stably inhibit HSV2 VP16 mRNA expression and viral replication within passage 50. Copyright © 2012 S. Karger AG, Basel.

Determinants for DNA target structure selectivity of the human LINE-1 retrotransposon endonuclease.

PubMed

Repanas, Kostas; Zingler, Nora; Layer, Liliana E; Schumann, Gerald G; Perrakis, Anastassis; Weichenrieder, Oliver

2007-01-01

The human LINE-1 endonuclease (L1-EN) is the targeting endonuclease encoded by the human LINE-1 (L1) retrotransposon. L1-EN guides the genomic integration of new L1 and Alu elements that presently account for approximately 28% of the human genome. L1-EN bears considerable technological interest, because its target selectivity may ultimately be engineered to allow the site-specific integration of DNA into defined genomic locations. Based on the crystal structure, we generated L1-EN mutants to analyze and manipulate DNA target site recognition. Crystal structures and their dynamic and functional analysis show entire loop grafts to be feasible, resulting in altered specificity, while individual point mutations do not change the nicking pattern of L1-EN. Structural parameters of the DNA target seem more important for recognition than the nucleotide sequence, and nicking profiles on DNA oligonucleotides in vitro are less well defined than the respective integration site consensus in vivo. This suggests that additional factors other than the DNA nicking specificity of L1-EN contribute to the targeted integration of non-LTR retrotransposons.

Nebular Line Emission and Stellar Mass of Bright z 8 Galaxies "Super-Eights"

NASA Astrophysics Data System (ADS)

Holwerda, Benne; Bouwens, Rychard; Trenti, Michele; Oesch, Pascal; Labbe, Ivo; Smit, Renske; Roberts-Borsani, Guido; Bernard, Stephanie; Bridge, Joanna

2018-05-01

Searches for the Lyman-alpha emission from the very first galaxies ionizing the Universe have proved to be extremely difficult with limited success beyond z 7 (<3% detections). However, a search of all CANDELS yielded four bright z 8 sources with associated strong Lyman-alpha lines, despite the Universe expected to be 70% neutral at this time. The key to their selection is an extremely red IRAC color ([3.6]-[4.5]> 0.5, Roberts-Borsani+ 2016), indicative of very strong nebular line emission. Do such extreme line emitting galaxies produce most of the photons to reionize the Universe? We propose to expand the sample of bright z 8 galaxies with reliable IRAC colors with seven more Y-band dropouts found with HST and confirmed through HST/Spitzer. The Spitzer observations will test how many of bright z 8 galaxies are IRAC-red and measure both their stellar mass and [OIII]+Hbeta line strength. Together with Keck/VLT spectroscopy, they will address these questions: I) Do all luminous z 8 galaxies show such red IRAC colors ([OIII] emission / hard spectra)? II) Is luminosity or a red IRAC color the dominant predictor for Lyman-alpha emission? III) Or are these sources found along exceptionally transparent sightlines into the early Universe? With 11 bright z 8 sources along different lines-of-sight, all prime targets for JWST, we will aim to determine which of the considered factors (luminosity, color, sight-line) drives the high Lyman-alpha prevalence (100%) and insight into the sources reionizing the Universe.

Simple Monitoring of Gene Targeting Efficiency in Human Somatic Cell Lines Using the PIGA Gene

PubMed Central

Karnan, Sivasundaram; Konishi, Yuko; Ota, Akinobu; Takahashi, Miyuki; Damdindorj, Lkhagvasuren; Hosokawa, Yoshitaka; Konishi, Hiroyuki

2012-01-01

Gene targeting in most of human somatic cell lines has been labor-intensive because of low homologous recombination efficiency. The development of an experimental system that permits a facile evaluation of gene targeting efficiency in human somatic cell lines is the first step towards the improvement of this technology and its application to a broad range of cell lines. In this study, we utilized phosphatidylinositol glycan anchor biosynthesis class A (PIGA), a gene essential for the synthesis of glycosylphosphatidyl inositol (GPI) anchors, as a reporter of gene targeting events in human somatic cell lines. Targeted disruption of PIGA was quantitatively detected with FLAER, a reagent that specifically binds to GPI anchors. Using this PIGA-based reporter system, we successfully detected adeno-associated virus (AAV)-mediated gene targeting events both with and without promoter-trap enrichment of gene-targeted cell population. The PIGA-based reporter system was also capable of reproducing previous findings that an AAV-mediated gene targeting achieves a remarkably higher ratio of homologous versus random integration (H/R ratio) of targeting vectors than a plasmid-mediated gene targeting. The PIGA-based system also detected an approximately 2-fold increase in the H/R ratio achieved by a small negative selection cassette introduced at the end of the AAV-based targeting vector with a promoter-trap system. Thus, our PIGA-based system is useful for monitoring AAV-mediated gene targeting and will assist in improving gene targeting technology in human somatic cell lines. PMID:23056640

Research on infrared dim-point target detection and tracking under sea-sky-line complex background

NASA Astrophysics Data System (ADS)

Dong, Yu-xing; Li, Yan; Zhang, Hai-bo

2011-08-01

Target detection and tracking technology in infrared image is an important part of modern military defense system. Infrared dim-point targets detection and recognition under complex background is a difficulty and important strategic value and challenging research topic. The main objects that carrier-borne infrared vigilance system detected are sea-skimming aircrafts and missiles. Due to the characteristics of wide field of view of vigilance system, the target is usually under the sea clutter. Detection and recognition of the target will be taken great difficulties .There are some traditional point target detection algorithms, such as adaptive background prediction detecting method. When background has dispersion-decreasing structure, the traditional target detection algorithms would be more useful. But when the background has large gray gradient, such as sea-sky-line, sea waves etc .The bigger false-alarm rate will be taken in these local area .It could not obtain satisfactory results. Because dim-point target itself does not have obvious geometry or texture feature ,in our opinion , from the perspective of mathematics, the detection of dim-point targets in image is about singular function analysis .And from the perspective image processing analysis , the judgment of isolated singularity in the image is key problem. The foregoing points for dim-point targets detection, its essence is a separation of target and background of different singularity characteristics .The image from infrared sensor usually accompanied by different kinds of noise. These external noises could be caused by the complicated background or from the sensor itself. The noise might affect target detection and tracking. Therefore, the purpose of the image preprocessing is to reduce the effects from noise, also to raise the SNR of image, and to increase the contrast of target and background. According to the low sea-skimming infrared flying small target characteristics , the median filter is used to

The role of off-line mass spectrometry in nuclear fission.

PubMed

De Laeter, J R

1996-01-01

The role of mass spectrometry in nuclear fission has been invaluable since 1940, when A. O. C. Nier separated microgram quantities of (235) U from (238) U, using a gas source mass spectrometer. This experiment enabled the fissionable nature of (235) U to be established. During the Manhattan Project, the mass spectrometer was used to measure the isotope abundances of uranium after processing in various separation systems, in monitoring the composition of the gaseous products in the Oak Ridge Diffusion Plant, and as a helium leak detector. Following the construction of the first reactor at the University of Chicago, it was necessary to unravel the nuclear systematics of the various fission products produced in the fission process. Off-line mass spectrometry was able to identify stable and long-lived isotopes produced in fission, but more importantly, was used in numerous studies of the distribution of mass of the cumulative fission yields. Improvements in sensitivity enabled off-line mass spectrometric studies to identify fine structure in the mass-yield curve and, hence, demonstrate the importance of shell structure in nuclear fission. Solid-source mass spectrometry was also able to measure the cumulative fission yields in the valley of symmetry in the mass-yield curve, and enabled spontaneous fission yields to be quantified. Apart from the accurate measurement of abundances, the stable isotope mass spectrometric technique has been invaluable in establishing absolute cumulative fission yields for many isotopes making up the mass-yield distribution curve for a variety of fissile nuclides. Extensive mass spectrometric studies of noble gases in primitive meteorites revealed the presence of fission products from the now extinct nuclide (244) Pu, and have eliminated the possibility of fission products from a super-heavy nuclide contributing to isotopic anomalies in meteoritic material. Numerous mass spectrometric studies of the isotopic and elemental abundances of

Targeted Multiplex Imaging Mass Spectrometry in Transmission Geometry for Subcellular Spatial Resolution

PubMed Central

Lavenant, Gwendoline Thiery; Zavalin, Andrey I.; Caprioli, Richard M.

2013-01-01

Targeted multiplex Imaging Mass Spectrometry utilizes several different antigen-specific primary antibodies, each directly labeled with a unique photocleavable mass tag, to detect multiple antigens in a single tissue section. Each photocleavable mass tag bound to an antibody has a unique molecular weight and can be readily ionized by laser desorption ionization mass spectrometry. This manuscript describes a mass spectrometry method that allows imaging of targeted single cells within tissue using transmission geometry laser desorption ionization mass spectrometry. Transmission geometry focuses the laser beam on the back side of the tissue placed on a glass slide, providing a 2 μm diameter laser spot irradiating the biological specimen. This matrix-free method enables simultaneous localization at the sub-cellular level of multiple antigens using specific tagged antibodies. We have used this technology to visualize the co-expression of synaptophysin and two major hormones peptides, insulin and somatostatin, in duplex assays in beta and delta cells contained in a human pancreatic islet. PMID:23397138

Targeted Multiplex Imaging Mass Spectrometry in Transmission Geometry for Subcellular Spatial Resolution

NASA Astrophysics Data System (ADS)

Thiery-Lavenant, Gwendoline; Zavalin, Andre I.; Caprioli, Richard M.

2013-04-01

Targeted multiplex imaging mass spectrometry utilizes several different antigen-specific primary antibodies, each directly labeled with a unique photocleavable mass tag, to detect multiple antigens in a single tissue section. Each photocleavable mass tag bound to an antibody has a unique molecular weight and can be readily ionized by laser desorption ionization mass spectrometry. This article describes a mass spectrometry method that allows imaging of targeted single cells within tissue using transmission geometry laser desorption ionization mass spectrometry. Transmission geometry focuses the laser beam on the back side of the tissue placed on a glass slide, providing a 2 μm diameter laser spot irradiating the biological specimen. This matrix-free method enables simultaneous localization at the sub-cellular level of multiple antigens using specific tagged antibodies. We have used this technology to visualize the co-expression of synaptophysin and two major hormones peptides, insulin and somatostatin, in duplex assays in beta and delta cells contained in a human pancreatic islet.

Impacts of a Stochastic Ice Mass-Size Relationship on Squall Line Ensemble Simulations

NASA Astrophysics Data System (ADS)

Stanford, M.; Varble, A.; Morrison, H.; Grabowski, W.; McFarquhar, G. M.; Wu, W.

2017-12-01

Cloud and precipitation structure, evolution, and cloud radiative forcing of simulated mesoscale convective systems (MCSs) are significantly impacted by ice microphysics parameterizations. Most microphysics schemes assume power law relationships with constant parameters for ice particle mass, area, and terminal fallspeed relationships as a function of size, despite observations showing that these relationships vary in both time and space. To account for such natural variability, a stochastic representation of ice microphysical parameters was developed using the Predicted Particle Properties (P3) microphysics scheme in the Weather Research and Forecasting model, guided by in situ aircraft measurements from a number of field campaigns. Here, the stochastic framework is applied to the "a" and "b" parameters of the unrimed ice mass-size (m-D) relationship (m=aDb) with co-varying "a" and "b" values constrained by observational distributions tested over a range of spatiotemporal autocorrelation scales. Diagnostically altering a-b pairs in three-dimensional (3D) simulations of the 20 May 2011 Midlatitude Continental Convective Clouds Experiment (MC3E) squall line suggests that these parameters impact many important characteristics of the simulated squall line, including reflectivity structure (particularly in the anvil region), surface rain rates, surface and top of atmosphere radiative fluxes, buoyancy and latent cooling distributions, and system propagation speed. The stochastic a-b P3 scheme is tested using two frameworks: (1) a large ensemble of two-dimensional idealized squall line simulations and (2) a smaller ensemble of 3D simulations of the 20 May 2011 squall line, for which simulations are evaluated using observed radar reflectivity and radial velocity at multiple wavelengths, surface meteorology, and surface and satellite measured longwave and shortwave radiative fluxes. Ensemble spreads are characterized and compared against initial condition ensemble spreads

Calculation of stresses in a rock mass and lining in stagewise face drivage

NASA Astrophysics Data System (ADS)

Seryakov, VM; Zhamalova, BR

2018-03-01

Using the method of calculating mechanical state of a rock mass for the conditions of stagewise drivage of a production face in large cross-section excavations, the specific features of stress redistribution in lining of excavations are found. The zones of tensile stresses in the lining are detected. The authors discuss the influence of the initial stress state of rocks on the tension stress zones induced in the lining in course of the heading advance

Selection of Phage Display Peptides Targeting Human Pluripotent Stem Cell-Derived Progenitor Cell Lines.

PubMed

Bignone, Paola A; Krupa, Rachel A; West, Michael D; Larocca, David

2016-01-01

The ability of human pluripotent stem cells (hPS) to both self-renew and differentiate into virtually any cell type makes them a promising source of cells for cell-based regenerative therapies. However, stem cell identity, purity, and scalability remain formidable challenges that need to be overcome for translation of pluripotent stem cell research into clinical applications. Directed differentiation from hPS cells is inefficient and residual contamination with pluripotent cells that have the potential to form tumors remains problematic. The derivation of scalable (self-renewing) embryonic progenitor stem cell lines offers a solution because they are well defined and clonally pure. Clonally pure progenitor stem cell lines also provide a means for identifying cell surface targeting reagents that are useful for identification, tracking, and repeated derivation of the corresponding progenitor stem cell types from additional hPS cell sources. Such stem cell targeting reagents can then be applied to the manufacture of genetically diverse banks of human embryonic progenitor cell lines for drug screening, disease modeling, and cell therapy. Here we present methods to identify human embryonic progenitor stem cell targeting peptides by selection of phage display libraries on clonal embryonic progenitor cell lines and demonstrate their use for targeting quantum dots (Qdots) for stem cell labeling.

Determination of 15 N-nitrosodimethylamine precursors in different water matrices by automated on-line solid-phase extraction ultra-high-performance-liquid chromatography tandem mass spectrometry.

PubMed

Farré, Maria José; Insa, Sara; Mamo, Julian; Barceló, Damià

2016-08-05

A new methodology based on on-line solid-phase extraction (SPE) ultra-high-performance-liquid chromatography coupled to a triple quadrupole mass spectrometer (UHPLC-MS-MS) for the determination of 15 individual anthropogenic N-nitrosodimethylamine (NDMA) precursors was developed. On-line SPE was performed by passing 2mL of the water sample through a Hypersil GOLD aQ column and chromatographic separation was done using a Kinetex Biphenyl column using methanol and 0.1% formic acid aqueous solution as a mobile phase. For unequivocal identification and confirmation, two selected reaction monitoring (SRM) transitions were monitored per compound. Quantification was performed by internal standard approach and matrix match calibration. The main advantages of the developed method are high sensitivity (limits of detection in the sub ng/L range), selectivity due to the use of tandem mass spectrometry, precision and minimum sample manipulation as well as fast analytical response. Process efficiency and recovery were also evaluated for all the target compounds. As part of the validation procedure, the method was applied in a sampling campaign for the analysis of influent and secondary effluent of a wastewater treatment plant (WWTP) in Girona, Spain. Additionally, the effluent from a nanofiltration (NF) membrane system used for water recycling was monitored. The percentage of NDMA formation explained by the measured precursors was also quantified. Copyright © 2016 Elsevier B.V. All rights reserved.

Balance Mass Flux and Velocity Across the Equilibrium Line in Ice Drainage Systems of Greenland

NASA Technical Reports Server (NTRS)

Zwally, H. Jay; Giovinetto, Mario B.; Koblinsky, Chester J. (Technical Monitor)

2001-01-01

Estimates of balance mass flux and the depth-averaged ice velocity through the cross-section aligned with the equilibrium line are produced for each of six drainage systems in Greenland. (The equilibrium line, which lies at approximately 1200 m elevation on the ice sheet, is the boundary between the area of net snow accumulation at higher elevations and the areas of net melting at lower elevations around the ice sheet.) Ice drainage divides and six major drainage systems are delineated using surface topography from ERS (European Remote Sensing) radar altimeter data. The net accumulation rate in the accumulation zone bounded by the equilibrium line is 399 Gt/yr and net ablation rate in the remaining area is 231 Gt/yr. (1 GigaTon of ice is 1090 kM(exp 3). The mean balance mass flux and depth-averaged ice velocity at the cross-section aligned with the modeled equilibrium line are 0.1011 Gt kM(exp -2)/yr and 0.111 km/yr, respectively, with little variation in these values from system to system. The ratio of the ice mass above the equilibrium line to the rate of mass output implies an effective exchange time of approximately 6000 years for total mass exchange. The range of exchange times, from a low of 3 ka in the SE drainage system to 14 ka in the NE, suggests a rank as to which regions of the ice sheet may respond more rapidly to climate fluctuations.

Reverberation Mapping of Optical Emission Lines in Five Active Galaxies

DOE PAGES

Fausnaugh, M. M.; Grier, C. J.; Bentz, M. C.; ...

2017-05-10

We present the first results from an optical reverberation mapping campaign executed in 2014 targeting the active galactic nuclei (AGNs) MCG+08-11-011, NGC 2617, NGC 4051, 3C 382, and Mrk 374. Our targets have diverse and interesting observational properties, including a “changing look” AGN and a broad-line radio galaxy. Based on continuum-Hβ lags, we measure black hole masses for all five targets. We also obtain Hγ and He II λ4686 lags for all objects except 3C 382. The He II λ4686 lags indicate radial stratification of the BLR, and the masses derived from different emission lines are in general agreement. Themore » relative responsivities of these lines are also in qualitative agreement with photoionization models. Finally, these spectra have extremely high signal-to-noise ratios (100–300 per pixel) and there are excellent prospects for obtaining velocity-resolved reverberation signatures.« less

Reverberation Mapping of Optical Emission Lines in Five Active Galaxies

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

Fausnaugh, M. M.; Denney, K. D.; Peterson, B. M.

2017-05-10

We present the first results from an optical reverberation mapping campaign executed in 2014 targeting the active galactic nuclei (AGNs) MCG+08-11-011, NGC 2617, NGC 4051, 3C 382, and Mrk 374. Our targets have diverse and interesting observational properties, including a “changing look” AGN and a broad-line radio galaxy. Based on continuum-H β lags, we measure black hole masses for all five targets. We also obtain H γ and He ii λ 4686 lags for all objects except 3C 382. The He ii λ 4686 lags indicate radial stratification of the BLR, and the masses derived from different emission lines aremore » in general agreement. The relative responsivities of these lines are also in qualitative agreement with photoionization models. These spectra have extremely high signal-to-noise ratios (100–300 per pixel) and there are excellent prospects for obtaining velocity-resolved reverberation signatures.« less

Constraints on Porosity and Mass Loss in O-star Winds from the Modeling of X-ray Emission Line Profile Shapes

NASA Technical Reports Server (NTRS)

Leutenegger, Maurice A.; Cohen, David H.; Sundqvist, Jon O.; Owocki, Stanley P.

2013-01-01

We fit X-ray emission line profiles in high resolution XMM-Newton and Chandra grating spectra of the early O supergiant Zeta Pup with models that include the effects of porosity in the stellar wind. We explore the effects of porosity due to both spherical and flattened clumps. We find that porosity models with flattened clumps oriented parallel to the photosphere provide poor fits to observed line shapes. However, porosity models with isotropic clumps can provide acceptable fits to observed line shapes, but only if the porosity effect is moderate. We quantify the degeneracy between porosity effects from isotropic clumps and the mass-loss rate inferred from the X-ray line shapes, and we show that only modest increases in the mass-loss rate (40%) are allowed if moderate porosity effects (h(sub infinity) less than approximately R(sub *)) are assumed to be important. Large porosity lengths, and thus strong porosity effects, are ruled out regardless of assumptions about clump shape. Thus, X-ray mass-loss rate estimates are relatively insensitive to both optically thin and optically thick clumping. This supports the use of X-ray spectroscopy as a mass-loss rate calibration for bright, nearby O stars

Two-dimensional turbulent flow chromatography coupled on-line to liquid chromatography-mass spectrometry for solution-based ligand screening against multiple proteins.

PubMed

Zhou, Jian-Liang; An, Jing-Jing; Li, Ping; Li, Hui-Jun; Jiang, Yan; Cheng, Jie-Fei

2009-03-20

We present herein a novel bioseparation/chemical analysis strategy for protein-ligand screening and affinity ranking in compound mixtures, designed to increase screening rates and improve sensitivity and ruggedness in performance. The strategy is carried out by combining on-line two-dimensional turbulent flow chromatography (2D-TFC) with liquid chromatography-mass spectrometry (LC-MS), and accomplished through the following steps: (1) a reversed-phase TFC stage to separate the protein/ligand complex from the unbound free molecules, (2) an on-line dissociation process to release the bound ligands from the complexes, and (3) a second mixed-mode cation-exchange/reversed-phase TFC stage to trap the bound ligands and to remove the proteins and salts, followed by LC-MS analysis for identification and determination of the binding affinities. The technique can implement an ultra-fast isolation of protein/ligand complex with the retention time of a complex peak in about 5s, and on-line prepare the "clean" sample to be directly compatible with the LC-MS analysis. The improvement in performance of this 2D-TFC/LC-MS approach over the conventional approach has been demonstrated by determining affinity-selected ligands of the target proteins acetylcholinesterase and butyrylcholinesterase from a small library with known binding affinities and a steroidal alkaloid library composed of structurally similar compounds. Our results show that 2D-TFC/LC-MS is a generic and efficient tool for high-throughput screening of ligands with low-to-high binding affinities, and structure-activity relationship evaluation.

Sensitivity of glacier mass balance and equilibrium line altitude to climatic change on King George Island, Antarctic Peninsula.

NASA Astrophysics Data System (ADS)

Falk, Ulrike; Lopez, Damian; Silva-Busso, Adrian

2017-04-01

The South Shetland Islands are located at the northern tip of the Antarctic Peninsula which is among the fastest warming regions on Earth. Surface air temperature increases (ca. 3 K in 50 years) are concurrent with retreating glacier fronts, an increase in melt areas, ice surface lowering and rapid break-up and disintegration of ice shelves. Observed surface air temperature lapse rates show a high variability during winter months (standard deviations up to ±1.0 K/100 m), and a distinct spatial heterogeneity reflecting the impact of synoptic weather patterns especially during winter glacial mass accumulation periods. The increased mesocyclonic activity during the winter time in the study area results in intensified advection of warm, moist air with high temperatures and rain, and leads to melt conditions on the ice cap, fixating surface air temperatures to the melting point. The impact on winter accumulation results in even more negative mass balance estimates. Six years of glaciological measurements on mass balance stake transects are used with a glacier melt model to assess changes in melt water input to the coastal waters, glacier surface mass balance and the equilibrium line altitude. The average equilibrium line altitude (ELA) calculated from own glaciological observations for KGI over the time period 2010 - 2015 amounts to ELA=330±100 m. Published studies suggest rather stable condition slightly negative glacier mass balance until the mid 80's with an ELA of approx. 150 m. The calculated accumulation area ratio suggests rather dramatic changes in extension of the inland ice cap for the South Shetland Islands until an equilibrium with concurrent climate conditions is reached.

Calibration and Limitations of the Mg II Line-based Black Hole Masses

NASA Astrophysics Data System (ADS)

Woo, Jong-Hak; Le, Huynh Anh N.; Karouzos, Marios; Park, Dawoo; Park, Daeseong; Malkan, Matthew A.; Treu, Tommaso; Bennert, Vardha N.

2018-06-01

We present single-epoch black hole mass ({M}BH}) calibrations based on the rest-frame ultraviolet (UV) and optical measurements of Mg II 2798 Å and Hβ 4861 Å lines and the active galactic nucleus (AGN) continuum, using a sample of 52 moderate-luminosity AGNs at z ∼ 0.4 and z ∼ 0.6 with high-quality Keck spectra. We combine this sample with a large number of luminous AGNs from the Sloan Digital Sky Survey to increase the dynamic range for a better comparison of UV and optical velocity and luminosity measurements. With respect to the reference {M}BH} based on the line dispersion of Hβ and continuum luminosity at 5100 Å, we calibrate the UV and optical mass estimators by determining the best-fit values of the coefficients in the mass equation. By investigating whether the UV estimators show a systematic trend with Eddington ratio, FWHM of Hβ, Fe II strength, or UV/optical slope, we find no significant bias except for the slope. By fitting the systematic difference of Mg II-based and Hβ-based masses with the L 3000/L 5100 ratio, we provide a correction term as a function of the spectral index as ΔC = 0.24 (1 + α λ ) + 0.17, which can be added to the Mg II-based mass estimators if the spectral slope can be well determined. The derived UV mass estimators typically show >∼0.2 dex intrinsic scatter with respect to the Hβ-based {M}BH}, suggesting that the UV-based mass has an additional uncertainty of ∼0.2 dex, even if high-quality rest-frame UV spectra are available.

Setting population targets for mammals using body mass as a predictor of population persistence.

PubMed

Hilbers, Jelle P; Santini, Luca; Visconti, Piero; Schipper, Aafke M; Pinto, Cecilia; Rondinini, Carlo; Huijbregts, Mark A J

2017-04-01

Conservation planning and biodiversity assessments need quantitative targets to optimize planning options and assess the adequacy of current species protection. However, targets aiming at persistence require population-specific data, which limit their use in favor of fixed and nonspecific targets, likely leading to unequal distribution of conservation efforts among species. We devised a method to derive equitable population targets; that is, quantitative targets of population size that ensure equal probabilities of persistence across a set of species and that can be easily inferred from species-specific traits. In our method, we used models of population dynamics across a range of life-history traits related to species' body mass to estimate minimum viable population targets. We applied our method to a range of body masses of mammals, from 2 g to 3825 kg. The minimum viable population targets decreased asymptotically with increasing body mass and were on the same order of magnitude as minimum viable population estimates from species- and context-specific studies. Our approach provides a compromise between pragmatic, nonspecific population targets and detailed context-specific estimates of population viability for which only limited data are available. It enables a first estimation of species-specific population targets based on a readily available trait and thus allows setting equitable targets for population persistence in large-scale and multispecies conservation assessments and planning. © 2016 The Authors. Conservation Biology published by Wiley Periodicals, Inc. on behalf of Society for Conservation Biology.

On-line characterization of monoclonal antibody variants by liquid chromatography-mass spectrometry operating in a two-dimensional format.

PubMed

Alvarez, Melissa; Tremintin, Guillaume; Wang, Jennifer; Eng, Marian; Kao, Yung-Hsiang; Jeong, Justin; Ling, Victor T; Borisov, Oleg V

2011-12-01

Recombinant monoclonal antibodies (MAbs) have become one of the most rapidly growing classes of biotherapeutics in the treatment of human disease. MAbs are highly heterogeneous proteins, thereby requiring a battery of analytical technologies for their characterization. However, incompatibility between separation and subsequent detection is often encountered. Here we demonstrate the utility of a generic on-line liquid chromatography-mass spectrometry (LC-MS) method operated in a two-dimensional format toward the rapid characterization of MAb charge and size variants. Using a single chromatographic system capable of running two independent gradients, up to six fractions of interest from an ion exchange (IEC) or size exclusion (SEC) separation can be identified by trapping and desalting the fractions onto a series of reversed phase trap cartridges with subsequent on-line analysis by mass spectrometry. Analysis of poorly resolved and low-level peaks in the IEC or SEC profile was facilitated by preconcentrating fractions on the traps using multiple injections. An on-line disulfide reduction step was successfully incorporated into the workflow, allowing more detailed characterization of modified MAbs by providing chain-specific information. The system is fully automated, thereby enabling high-throughput analysis with minimal sample handling. This technology provides rapid data turnaround time, a much needed feature during product characterization and development of multiple biotherapeutic proteins. Copyright © 2011 Elsevier Inc. All rights reserved.

SU-E-T-486: Effect of the Normalized Prescription Isodose Line On Target Dose Deficiency in Lung SBRT Based On Monte Carlo Calculation

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

Zheng, D; Zhang, Q; Zhou, S

Purpose: To investigate the impact of normalized prescription isodose line on target dose deficiency calculated with Monte Carlo (MC) vs. pencil Beam (PB) in lung SBRT. RTOG guidelines recommend prescription lines between 60% and 90% for lung SBRT. How this affects the magnitude of MC-calculated target dose deficiency has never been studied. Methods: Under an IRB-approved protocol, four lung SBRT patients were replanned following RTOG0813 by a single physicist. For each patient, four alternative plans were generated based on PB calculation prescribing to 60–90% isodose lines, respectively. Each plan consisted of 360o coplanar dynamic conformal arcs with beam apertures manuallymore » optimized to achieve similar dose coverage and conformity for all plans of the same patient. Dose distribution was calculated with MC and compared to that with PB. PTV dose-volume endpoints were compared, including Dmin, D5, Dmean, D95, and Dmax. PTV V100 coverage, conformity index (CI), and heterogeneity index (HI) were also evaluated. Results: For all 16 plans, median (range) PTV V100 and CI were 99.7% (97.5–100%) and 1.27 (1.20–1.41), respectively. As expected, lower prescription line resulted in higher target dose heterogeneity, yielding median (range) HI of 1.26 (1.05–1.51) for all plans. Comparing MC to PB, median (range) D95, Dmean, D5 PTV dose deficiency were 18.9% (11.2–23.2%), 15.6% (10.0–22.7%), and 9.4%(5.5–13.6%) of the prescription dose, respectively. The Dmean, D5, and Dmax deficiency was found to monotonically increase with decreasing prescription line from 90% to 60%, while the Dmin deficiency monotonically decreased. D95 deficiency exhibited more complex trend, reaching the largest deficiency at 80% for all patients. Conclusion: Dependence on prescription isodose line was found for MC-calculated PTV dose deficiency of lung SBRT. When comparing reported MC dose deficiency values from different institutions, their individual selections of prescription

Combining targeted and nontargeted data analysis for liquid chromatography/high-resolution mass spectrometric analyses.

PubMed

Croley, Timothy R; White, Kevin D; Wong, Jon; Callahan, John H; Musser, Steven M; Antler, Margaret; Lashin, Vitaly; McGibbon, Graham A

2013-03-01

Increasing importation of food and the diversity of potential contaminants have necessitated more analytical testing of these foods. Historically, mass spectrometric methods for testing foods were confined to monitoring selected ions (SIM or MRM), achieving sensitivity by focusing on targeted ion signals. A limiting factor in this approach is that any contaminants not included on the target list are not typically identified and retrospective data mining is limited. A potential solution is to utilize high-resolution MS to acquire accurate mass full-scan data. Based on the instrumental resolution, these data can be correlated to the actual mass of a contaminant, which would allow for identification of both target compounds and compounds that are not on a target list (nontargets). The focus of this research was to develop software algorithms to provide rapid and accurate data processing of LC/MS data to identify both targeted and nontargeted analytes. Software from a commercial vendor was developed to process LC/MS data and the results were compared to an alternate, vendor-supplied solution. The commercial software performed well and demonstrated the potential for a fully automated processing solution. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Absorption line profiles in a companion spectrum of a mass losing cool supergiant

NASA Technical Reports Server (NTRS)

Rodrigues, Liliya L.; Boehm-Vitense, Erika

1990-01-01

Cool star winds can best be observed in resonance absorption lines seen in the spectrum of a hot companion, due to the wind passing in front of the blue star. We calculated absorption line profiles that would be seen in the ultraviolet part of the blue companion spectrum. Line profiles are derived for different radial dependences of the cool star wind and for different orbital phases of the binary. Bowen and Wilson find theoretically that stellar pulsations drive mass loss. We therefore apply our calculations to the Cepheid binary S Muscae which has a B5V companion. We find an upper limit for the Cepheid mass loss of M less than or equal to 7 x 10(exp -10) solar mass per year provided that the stellar wind of the companion does not influence the Cepheid wind at large distances.

Locating the optimal internal jugular target site for central venous line placement.

PubMed

Giordano, Chris R; Murtagh, Kevin R; Mills, Jaime; Deitte, Lori A; Rice, Mark J; Tighe, Patrick J

2016-09-01

Historically, the placement of internal jugular central venous lines has been accomplished by using external landmarks to help identify target-rich locations in order to steer clear of dangerous structures. This paradigm is largely being displaced, as ultrasound has become routine practice, raising new considerations regarding target locations and risk mitigation. Most human anatomy texts depict the internal jugular vein as a straight columnar structure that exits the cranial vault the same size that it enters the thoracic cavity. We dispute the notion that the internal jugulars are cylindrical columns that symmetrically descend into the thoracic cavity, and purport that they are asymmetric conical structures. The primary aim of this study was to evaluate 100 consecutive adult chest and neck computed tomography exams that were imaged at an inpatient hospital. We measured the internal jugular on the left and right sides at three different levels to look for differences in size as the internal jugular descends into the thoracic cavity. We revealed that as the internal jugular descends into the thorax, the area of the vessel increases and geometrically resembles a conical structure. We also reconfirmed that the left internal jugular is smaller than the right internal jugular. Understanding that the largest target area for central venous line placement is the lower portion of the right internal jugular vein will help to better target vascular access for central line placement. This is the first study the authors are aware of that depicts the internal jugular as a conical structure as opposed to the commonly depicted symmetrical columnar structure frequently illustrated in anatomy textbooks. This target area does come with additional risk, as the closer you get to the thoracic cavity, the greater the chances for lung injury. Copyright © 2016 Elsevier Inc. All rights reserved.

Faint CO Line Wings in Four Star-forming (Ultra)luminous Infrared Galaxies

NASA Astrophysics Data System (ADS)

Leroy, Adam K.; Walter, Fabian; Decarli, Roberto; Bolatto, Alberto; Zschaechner, Laura; Weiss, Axel

2015-09-01

We report the results of a search for large velocity width, low-intensity line wings—a commonly used signature of molecular outflows—in four low redshift (ultra)luminous infrared galaxies that appear to be dominated by star formation. The targets were drawn from a sample of fourteen targets presented in Chung et al., who showed the stacked CO spectrum of the sample to exhibit 1000 km s-1-wide line wings. We obtained sensitive, wide bandwidth imaging of our targets using the IRAM Plateau de Bure Interferometer. We detect each target at very high significance but do not find the claimed line wings in these four targets. Instead, we constrain the flux in the line wings to be only a few percent. Casting our results as mass outflow rates following Cicone et al. we show them to be consistent with a picture in which very high mass loading factors preferentially occur in systems with high active galactic nucleus contributions to their bolometric luminosity. We identify one of our targets, IRAS 05083 (VII Zw 31), as a candidate molecular outflow.

Beam Transport of 4 GeV Protons from AGS to the Proton Interrogation Target of the Neutrino Line (Z_line) and Effect of the Air on the Transported Beam

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

Tsoupas,N.; Ahrens, L.; Pile, P.

2008-10-01

As part of the preparation for the Proton Interrogation Experiment, we have calculated the beam optics for the transport of 4 GeV protons, from the AGS extraction point, to the 'Cross-Section Target Wheel 1' and to the 'Proton Interrogation Target'. In this technical note we present three possible beam-transports each corresponding to a particular Fast Extracted Beam W B setup of the AGS. In addition we present results on the effect of the atmospheric air, (which fills the drift space of the last 100 [m] of the transport line), on the size of the beam, at two locations along themore » drift space, one location at the middle of the drift space and the other at the end where the 'Proton Interrogation Target' is placed. All the beam transports mentioned above require the removal of the WD1 dipole magnet, which is the first magnet of the W-line, because it acts as a limiting beam aperture, and the magnet is not used in the beam transport. An alternative solution of a beam transport, which does not require the removal of the WD1 magnet, is also presented. In this solution, which models the transport line using the TURTLE computer code[7], the vertical beam sizes at the location of the WD1 magnet is minimized to allow 'lossless' beam transport at the location of the WD1 magnet. A similar solution, but using a MAD model of the line, is also presented.« less

Evaluation of on-line concentration coupled to liquid chromatography tandem mass spectrometry for the quantification of neonicotinoids and fipronil in surface water and tap water.

PubMed

Montiel-León, Juan Manuel; Duy, Sung Vo; Munoz, Gabriel; Amyot, Marc; Sauvé, Sébastien

2018-04-01

A study was initiated to investigate a fast and reliable method for the determination of selected systemic insecticides in water matrixes and to evaluate potential sources of bias in their analysis. Acetamiprid, clothianidin, desnitro-imidacloprid, dinotefuran, fipronil, imidacloprid, nitenpyram, thiacloprid, and thiamethoxam were amenable to analysis via on-line sample enrichment hyphenated to ultra-high-performance liquid chromatography tandem mass spectrometry. The selection of on-line solid-phase extraction parameters was dictated by a multicriterion desirability approach. A 2-mL on-line injection volume with a 1500 μL min -1 loading flow rate met the objectives sought in terms of chromatographic requirements, extraction efficiency, sensitivity, and precision. A total analysis time of 8 min per sample was obtained with method limits of detection in the range of 0.1-5 ng L -1 for the scope of targeted analytes. Automation at the sample concentration step yielded intraday and interday precisions in the range of 1-23 and 2-26%, respectively. Factors that could affect the whole method accuracy were further evaluated in matrix-specific experiments. The impact of the initial filtration step on analyte recovery was evaluated in ultra-pure water, tap water, and surface water. Out of the nine membranes tested, glass fiber filters and polyester filters appeared as the most appropriate materials. Sample storage stability was also investigated across the three matrix types; the targeted analytes displayed suitable stability during 28 days at either 4 °C or - 20 °C, with little deviations (± 10%) with respect to the initial T 0 concentration. Method applicability was demonstrated in a range of tap water and surface water samples from the province of Québec, Canada. Results from the present survey indicated a predominance of thiamethoxam (< 0.5-10 and 3-61 ng L -1 in tap water and river water, respectively), clothianidin (< 0.5-6 and 2-88 ng L -1 in

Mass loss from inhomogeneous hot star winds. I. Resonance line formation in 2D models

NASA Astrophysics Data System (ADS)

Sundqvist, J. O.; Puls, J.; Feldmeier, A.

2010-01-01

Context. The mass-loss rate is a key parameter of hot, massive stars. Small-scale inhomogeneities (clumping) in the winds of these stars are conventionally included in spectral analyses by assuming optically thin clumps, a void inter-clump medium, and a smooth velocity field. To reconcile investigations of different diagnostics (in particular, unsaturated UV resonance lines vs. Hα/radio emission) within such models, a highly clumped wind with very low mass-loss rates needs to be invoked, where the resonance lines seem to indicate rates an order of magnitude (or even more) lower than previously accepted values. If found to be realistic, this would challenge the radiative line-driven wind theory and have dramatic consequences for the evolution of massive stars. Aims: We investigate basic properties of the formation of resonance lines in small-scale inhomogeneous hot star winds with non-monotonic velocity fields. Methods: We study inhomogeneous wind structures by means of 2D stochastic and pseudo-2D radiation-hydrodynamic wind models, constructed by assembling 1D snapshots in radially independent slices. A Monte-Carlo radiative transfer code, which treats the resonance line formation in an axially symmetric spherical wind (without resorting to the Sobolev approximation), is presented and used to produce synthetic line spectra. Results: The optically thin clumping limit is only valid for very weak lines. The detailed density structure, the inter-clump medium, and the non-monotonic velocity field are all important for the line formation. We confirm previous findings that radiation-hydrodynamic wind models reproduce observed characteristics of strong lines (e.g., the black troughs) without applying the highly supersonic “microturbulence” needed in smooth models. For intermediate strong lines, the velocity spans of the clumps are of central importance. Current radiation-hydrodynamic models predict spans that are too large to reproduce observed profiles unless a very

[Building Mass Spectrometry Spectral Libraries of Human Cancer Cell Lines].

PubMed

Faktor, J; Bouchal, P

Cancer research often focuses on protein quantification in model cancer cell lines and cancer tissues. SWATH (sequential windowed acquisition of all theoretical fragment ion spectra), the state of the art method, enables the quantification of all proteins included in spectral library. Spectral library contains fragmentation patterns of each detectable protein in a sample. Thorough spectral library preparation will improve quantitation of low abundant proteins which usually play an important role in cancer. Our research is focused on the optimization of spectral library preparation aimed at maximizing the number of identified proteins in MCF-7 breast cancer cell line. First, we optimized the sample preparation prior entering the mass spectrometer. We examined the effects of lysis buffer composition, peptide dissolution protocol and the material of sample vial on the number of proteins identified in spectral library. Next, we optimized mass spectrometry (MS) method for spectral library data acquisition. Our thorough optimized protocol for spectral library building enabled the identification of 1,653 proteins (FDR < 1%) in 1 µg of MCF-7 lysate. This work contributed to the enhancement of protein coverage in SWATH digital biobanks which enable quantification of arbitrary protein from physically unavailable samples. In future, high quality spectral libraries could play a key role in preparing of patient proteome digital fingerprints.Key words: biomarker - mass spectrometry - proteomics - digital biobanking - SWATH - protein quantificationThis work was supported by the project MEYS - NPS I - LO1413.The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.Submitted: 7. 5. 2016Accepted: 9. 6. 2016.

Efficacy and safety of third-line molecular-targeted therapy in metastatic renal cell carcinoma resistant to first-line vascular endothelial growth factor receptor tyrosine kinase inhibitor and second-line therapy.

PubMed

Ishihara, Hiroki; Takagi, Toshio; Kondo, Tsunenori; Tachibana, Hidekazu; Yoshida, Kazuhiko; Omae, Kenji; Iizuka, Junpei; Kobayashi, Hirohito; Tanabe, Kazunari

2018-06-01

The number of studies evaluating the efficacy and safety of third-line molecular-targeted therapy for metastatic renal cell carcinoma (mRCC) is limited. The data for 48 patients with disease progression after first-line vascular endothelial growth factor receptor tyrosine kinase inhibitor (TKI) and second-line targeted therapy were evaluated. Patients with prior cytokine therapy were excluded. Overall survival (OS) after first- and second-line therapy initiation was compared between patients with and without third-line therapy. In addition, dose-limiting toxicities (DLTs) were evaluated. Twenty-two of 48 patients (45.8%) received third-line therapy, and TKI and mammalian target of rapamycin inhibitor were each administered in 11 patients (50%). Patients with third-line therapy had significantly longer median OS after first-line therapy (26.6 vs. 14.6 months, p = 0.0010) and second-line therapy (18.2 vs. 7.4 months, p < 0.0001) compared to those without third-line therapy. Multivariate analysis showed that the use of third-line therapy following second-line therapy was an independent prognosticator for longer OS (hazard ratio 0.29, 95% confidence interval 0.14-0.58, p = 0.0005). The median progression-free survival and OS after third-line therapy was 2.76 and 8.71 months, respectively. Although a high frequency of DLTs was observed (n = 10, 45.5%), the frequencies were similar among the sequential therapies. Third-line therapy has a beneficial therapeutic effect in patients with mRCC that is resistant to previous therapies. However, there is a need to evaluate in detail the high frequency of adverse events, including DLTs.

The link between quasar broad-line region and galaxy-scale outflows and accurate CIV-based black hole masses

NASA Astrophysics Data System (ADS)

Coatman, Liam; Hewett, Paul C.; Banerji, Manda; Richards, Gordon T.; Hennawi, Joseph F.; Prochaska, Jason X.

2017-01-01

Accurate black-hole (BH) mass estimates for high-redshift (z>2) quasars are essential for better understanding the relationship between super-massive BH accretion and star formation. Progress is currently limited by the large systematic errors in virial BH-masses derived from the CIV broad emission line, which is often significantly blueshifted relative to systemic, most likely due to outflowing gas in the quasar broad-line region. We have assembled Balmer-line based BH masses for a large sample of 230 high-luminosity (1045.5-1048 ergs-1), redshift 1.5masses to be larger than the corresponding Balmer line-based masses by almost an order of magnitude at the most extreme blueshifts (˜5000 kms-1). An empirical correction to the CIV BH-masses is derived, which depends only on the properties of the CIV line itself (i.e. blueshift and FWHM). We show that this new correction now enables the derivation of un-biased CIV-based virial BH masses for the majority of high-luminosity, high-redshift quasars.In the same high-luminosity quasar sample, we find the narrow [OIII] emission to be weaker and more asymmetric than is generally found in lower-luminosity AGN and that a significant fraction of our quasars have exceptionally broad (FWHM > 3000 kms-1), blueshifted [OIII] emission. We find a strong correlation between the CIV and [OIII] blueshifts. This correlation holds even for quasars at fixed luminosity and suggests that broad line region outflows in quasars are connected to galaxy-scale winds.

Identification of potential target genes of ROR-alpha in THP1 and HUVEC cell lines.

PubMed

Gulec, Cagri; Coban, Neslihan; Ozsait-Selcuk, Bilge; Sirma-Ekmekci, Sema; Yildirim, Ozlem; Erginel-Unaltuna, Nihan

2017-04-01

ROR-alpha is a nuclear receptor, activity of which can be modulated by natural or synthetic ligands. Due to its possible involvement in, and potential therapeutic target for atherosclerosis, we aimed to identify ROR-alpha target genes in monocytic and endothelial cell lines. We performed chromatin immunoprecipitation (ChIP) followed by tiling array (ChIP-on-chip) for ROR-alpha in monocytic cell line THP1 and endothelial cell line HUVEC. Following bioinformatic analysis of the array data, we tested four candidate genes in terms of dependence of their expression level on ligand-mediated ROR-alpha activity, and two of them in terms of promoter occupancy by ROR-alpha. Bioinformatic analyses of ChIP-on-chip data suggested that ROR-alpha binds to genomic regions near the transcription start site (TSS) of more than 3000 genes in THP1 and HUVEC. Potential ROR-alpha target genes in both cell types seem to be involved mainly in membrane receptor activity, signal transduction and ion transport. While SPP1 and IKBKA were shown to be direct target genes of ROR-alpha in THP1 monocytes, inflammation related gene HMOX1 and heat shock protein gene HSPA8 were shown to be potential target genes of ROR-alpha. Our results suggest that ROR-alpha may regulate signaling receptor activity, and transmembrane transport activity through its potential target genes. ROR-alpha seems also to play role in cellular sensitivity to environmental substances like arsenite and chloroprene. Although, the expression analyses have shown that synthetic ROR-alpha ligands can modulate some of potential ROR-alpha target genes, functional significance of ligand-dependent modulation of gene expression needs to be confirmed with further analyses. Copyright © 2017 Elsevier Inc. All rights reserved.

Molecular line tracers of high-mass star forming regions

NASA Astrophysics Data System (ADS)

Nagy, Zsofia; Van der Tak, Floris; Ossenkopf, Volker; Bergin, Edwin; Black, John; Faure, Alexandre; Fuller, Gary; Gerin, Maryvonne; Goicoechea, Javier; Joblin, Christine; Le Bourlot, Jacques; Le Petit, Franck; Makai, Zoltan; Plume, Rene; Roellig, Markus; Spaans, Marco; Tolls, Volker

2013-07-01

High-mass stars influence their environment in different ways including feedback via their FUV radiation. The penetration of FUV photons into molecular clouds creates Photon Dominated Regions (PDRs) with different chemical layers where the mainly ionized medium changes into mainly molecular. Different chemical layers in PDRs are traced by different species observable at sub-mm and Far Infrared wavelengths. In this poster we present results from two molecular line surveys. One of them is the James Clerk Maxwell Telescope (JCMT) Spectral Legacy Survey (SLS) toward the luminous (>10^7 L_Sun), massive (~10^6 M_Sun), and distant (11.4 kpc) star-forming region W49A. The SLS images a 2x2 arcminute field toward W49A in the 330-373 GHz frequency range. The detected molecular lines reveal a complex chemistry and the importance of FUV-irradiation in the heating and chemistry of the region. The other line survey presented in the poster is part of the HEXOS (Herschel observations of EXtra-Ordinary Sources, PI: E. Bergin) key program using the Herschel Space Observatory and is toward the nearby (~420 pc) prototypical edge-on Orion Bar PDR and the dense molecular condensation Orion S. Reactive ions, such as CH+, SH+, and CO+, detected as a part of this line survey trace the warm (~500-1000 K) surface region of PDRs. Spectrally resolved HIFI and spectrally unresolved PACS spectra give constraints on the chemistry and excitation of reactive ions in these regions.

MS/MS studies on the selective on-line detection of sesquiterpenes using a Flowing Afterglow-Tandem Mass Spectrometer (FA-TMS)

NASA Astrophysics Data System (ADS)

Rimetz-Planchon, J.; Dhooghe, F.; Schoon, N.; Vanhaecke, F.; Amelynck, C.

2011-04-01

A Flowing Afterglow-Tandem Mass Spectrometer (FA-TMS) was used to investigate the feasibility of selective on-line detection of a series of seven sesquiterpenes (SQTs). These SQTs were chemically ionized by either H3O+ or NO+ reagent ions in the FA, resulting among others in protonated SQT and SQT molecular ions, respectively. These and other Chemical Ionization (CI) product ions were subsequently subjected to dissociation by collisions with Ar atoms in the collision cell of the tandem mass spectrometer. The fragmentation spectra show similarities with mass spectra obtained for these compounds with other instruments such as a Proton Transfer Reaction-Linear Ion Trap (PTR-LIT), a Proton Transfer Reaction-Mass Spectrometer (PTR-MS), a Triple Quadrupole-Mass Spectrometer (QqQ-MS) and a Selected Ion Flow Tube-Mass Spectrometer (SIFT-MS). Fragmentation of protonated SQT is characterized by fragment ions at the same masses but with different intensities for the individual SQT. Distinction of SQTs is based on well-chosen intensity ratios and collision energies. The fragmentation patterns of SQT molecular ions show specific fragment ion tracers at m/z 119, m/z162, m/z 137 and m/z 131 for α-cedrene, δ-neoclovene, isolongifolene and α-humulene, respectively. Consequently, chemical ionization of SQT by NO+, followed by MS/MS of SQT+ seems to open a way for selective quantification of SQTs in mixtures.

Mass Media Strategies Targeting High Sensation Seekers: What Works and Why

ERIC Educational Resources Information Center

Stephenson, Michael T.

2003-01-01

Objectives: To examine strategies for using the mass media effectively in drug prevention campaigns targeting high sensation seekers. Methods: Both experimental lab and field studies were used to develop a comprehensive audience segmentation strategy targeting high sensation seekers. Results: A 4-pronged targeting strategy employed in an…

The SPES High Power ISOL production target

NASA Astrophysics Data System (ADS)

Andrighetto, A.; Corradetti, S.; Ballan, M.; Borgna, F.; Manzolaro, M.; Scarpa, D.; Monetti, A.; Rossignoli, M.; Silingardi, R.; Mozzi, A.; Vivian, G.; Boratto, E.; De Ruvo, L.; Sattin, N.; Meneghetti, G.; Oboe, R.; Guerzoni, M.; Margotti, A.; Ferrari, M.; Zenoni, A.; Prete, G.

2016-11-01

SPES (Selective Production of Exotic Species) is a facility under construction at INFN-LNL (Istituto Nazionale di Fisica Nucleare - Laboratori Nazionali di Legnaro), aimed to produce intense neutron-rich radioactive ion beams (RIBs). These will be obtained using the ISOL (Isotope Separation On-Line) method, bombarding a uranium carbide target with a proton beam of 40MeV energy and currents up to 200μA. The target configuration was designed to obtain a high number of fissions, up to 1013 per second, low power deposition and fast release of the produced isotopes. The exotic isotopes generated in the target are ionized, mass separated and re-accelerated by the ALPI superconducting LINAC at energies of 10AMeV and higher, for masses in the region of A = 130 amu , with an expected rate on the secondary target up to 109 particles per second. In this work, recent results on the R&D activities regarding the SPES RIB production target-ion source system are reported.

Quantification of proteins in urine samples using targeted mass spectrometry methods.

PubMed

Khristenko, Nina; Domon, Bruno

2015-01-01

Numerous clinical proteomics studies are focused on the development of biomarkers to improve either diagnostics for early disease detection or the monitoring of the response to the treatment. Although, a wealth of biomarker candidates are available, their evaluation and validation in a true clinical setup remains challenging. In biomarkers evaluation studies, a panel of proteins of interest are systematically analyzed in a large cohort of samples. However, in spite of the latest progresses in mass spectrometry, the consistent detection of pertinent proteins in high complex biological samples is still a challenging task. Thus, targeted LC-MS/MS methods are better suited for the systematic analysis of biomarkers rather than shotgun approaches. This chapter describes the workflow used to perform targeted quantitative analyses of proteins in urinary samples. The peptides, as surrogates of the protein of interest, are commonly measured using a triple quadrupole mass spectrometers operated in selected reaction monitoring (SRM) mode. More recently, the advances in targeted LC-MS/MS analysis based on parallel reaction monitoring (PRM) performed on a quadrupole-orbitrap instrument have allowed to increase the specificity and selectivity of the measurements.

Molecular line tracers of high-mass star forming regions

NASA Astrophysics Data System (ADS)

Nagy, Zsofia

2013-09-01

High-mass stars influence their environment in different ways including feedback via their far-UV radiation and mechanical feedback via shocks and stellar winds. The penetration of FUV photons into molecular clouds creates Photon Dominated Regions (PDRs) with different chemical layers where the mainly ionized medium changes into mainly molecular. Different chemical layers in PDRs are traced by different species observable at sub-mm and far-infrared wavelengths. In this thesis we present results from two molecular line surveys. One of them is the James Clerk Maxwell Telescope (JCMT) Spectral Legacy Survey (SLS) toward the luminous (>10^7 L_Sun), massive (~10^6 M_Sun), and distant (11.4 kpc) star-forming region W49A. The SLS images a 2x2 arcminute field around W49A in the 330-373 GHz frequency range. The detected molecular lines reveal a complex chemistry and the importance of FUV-irradiation and shocks in the heating and chemistry of the region. The other line survey presented in this thesis is part of the HEXOS (Herschel observations of EXtra-Ordinary Sources) key program using the Herschel Space Observatory and is toward the nearby (~420 pc) prototypical edge-on Orion Bar PDR and the dense molecular condensation Orion S. Reactive ions, such as CH+, SH+, and CO+, detected as a part of this line survey trace the warm (~500-1000 K) surface region of PDRs. Spectroscopic data from the HIFI and PACS instruments of Herschel give constraints on the chemistry and excitation of reactive ions in these regions.

Integrated configurable equipment selection and line balancing for mass production with serial-parallel machining systems

NASA Astrophysics Data System (ADS)

Battaïa, Olga; Dolgui, Alexandre; Guschinsky, Nikolai; Levin, Genrikh

2014-10-01

Solving equipment selection and line balancing problems together allows better line configurations to be reached and avoids local optimal solutions. This article considers jointly these two decision problems for mass production lines with serial-parallel workplaces. This study was motivated by the design of production lines based on machines with rotary or mobile tables. Nevertheless, the results are more general and can be applied to assembly and production lines with similar structures. The designers' objectives and the constraints are studied in order to suggest a relevant mathematical model and an efficient optimization approach to solve it. A real case study is used to validate the model and the developed approach.

Targeted mass treatment for syphilis with oral azithromycin.

PubMed

Rekart, Michael L; Patrick, David M; Chakraborty, Bubli; Maginley, Juanita J L; Jones, H D; Bajdik, Chris D; Pourbohloul, Babak; Brunham, Robert C

2003-01-25

From mid 1997 to end of 1999, there was a sexually-transmitted infectious syphilis outbreak mainly in heterosexual people in British Columbia, Canada, that was concentrated in Vancouver. The rate across the province increased from less than 0.5 to 3.4 per 100000, and the rate in Vancouver reached 12.9 per 100000. We aimed to eliminate the syphillis outbreak by treating people at risk of infection. In 2000, a targeted mass treatment programme provided azithromycin (1.8 g orally) to 4384 at-risk residents in this city. After the programme, syphilis frequency fell significantly for 6 months (p=0.016), but rose again in 2001. Results from curve fitting analyses showed that the number of cases in 2001 (177) was higher than expected (0.0001targeted mass treatment for syphilis, even though feasible, should not be done routinely.

Obscurin Targets Ankyrin-B and Protein Phosphatase 2A to the Cardiac M-line*

PubMed Central

Cunha, Shane R.; Mohler, Peter J.

2008-01-01

Ankyrin-B targets ion channels and transporters in excitable cells. Dysfunction in ankyrin-B-based pathways results in defects in cardiac physiology. Despite a wealth of knowledge regarding the role of ankyrin-B for cardiac function, little is known regarding the mechanisms underlying ankyrin-B regulation. Moreover, the pathways underlying ankyrin-B targeting in heart are unclear. We report that alternative splicing regulates ankyrin-B localization and function in cardiomyocytes. Specifically, we identify a novel exon (exon 43′) in the ankyrin-B regulatory domain that mediates interaction with the Rho-GEF obscurin. Ankyrin-B transcripts harboring exon 43′ represent the primary cardiac isoform in human and mouse. We demonstrate that ankyrin-B and obscurin are co-localized at the M-line of myocytes and co-immunoprecipitate from heart. We define the structural requirements for ankyrin-B/obscurin interaction to two motifs in the ankyrin-B regulatory domain and demonstrate that both are critical for obscurin/ankyrin-B interaction. In addition, we demonstrate that interaction with obscurin is required for ankyrin-B M-line targeting. Specifically, both obscurin-binding motifs are required for the M-line targeting of a GFP-ankyrin-B regulatory domain. Moreover, this construct acts as a dominant-negative by competing with endogenous ankyrin-B for obscurin-binding at the M-line, thus providing a powerful new tool to evaluate the function of obscurin/ankyrin-B interactions. With this new tool, we demonstrate that the obscurin/ankyrin-B interaction is critical for recruitment of PP2A to the cardiac M-line. Together, these data provide the first evidence for the molecular basis of ankyrin-B and PP2A targeting and function at the cardiac M-line. Finally, we report that ankyrin-B R1788W is localized adjacent to the ankyrin-B obscurin-binding motif and increases binding activity for obscurin. In summary, our new findings demonstrate that ANK2 is subject to alternative splicing

Identifying protein kinase target preferences using mass spectrometry

PubMed Central

Douglass, Jacqueline; Gunaratne, Ruwan; Bradford, Davis; Saeed, Fahad; Hoffert, Jason D.; Steinbach, Peter J.; Pisitkun, Trairak

2012-01-01

A general question in molecular physiology is how to identify candidate protein kinases corresponding to a known or hypothetical phosphorylation site in a protein of interest. It is generally recognized that the amino acid sequence surrounding the phosphorylation site provides information that is relevant to identification of the cognate protein kinase. Here, we present a mass spectrometry-based method for profiling the target specificity of a given protein kinase as well as a computational tool for the calculation and visualization of the target preferences. The mass spectrometry-based method identifies sites phosphorylated in response to in vitro incubation of protein mixtures with active recombinant protein kinases followed by standard phosphoproteomic methodologies. The computational tool, called “PhosphoLogo,” uses an information-theoretic algorithm to calculate position-specific amino acid preferences and anti-preferences from the mass-spectrometry data (http://helixweb.nih.gov/PhosphoLogo/). The method was tested using protein kinase A (catalytic subunit α), revealing the well-known preference for basic amino acids in positions −2 and −3 relative to the phosphorylated amino acid. It also provides evidence for a preference for amino acids with a branched aliphatic side chain in position +1, a finding compatible with known crystal structures of protein kinase A. The method was also employed to profile target preferences and anti-preferences for 15 additional protein kinases with potential roles in regulation of epithelial transport: CK2, p38, AKT1, SGK1, PKCδ, CaMK2δ, DAPK1, MAPKAPK2, PKD3, PIM1, OSR1, STK39/SPAK, GSK3β, Wnk1, and Wnk4. PMID:22723110

Analysis of hydroxamate siderophores in soil solution using liquid chromatography with mass spectrometry and tandem mass spectrometry with on-line sample preconcentration.

PubMed

Olofsson, Madelen A; Bylund, Dan

2015-10-01

A liquid chromatography with electrospray ionization mass spectrometry method was developed to quantitatively and qualitatively analyze 13 hydroxamate siderophores (ferrichrome, ferrirubin, ferrirhodin, ferrichrysin, ferricrocin, ferrioxamine B, D1 , E and G, neocoprogen I and II, coprogen and triacetylfusarinine C). Samples were preconcentrated on-line by a switch-valve setup prior to analyte separation on a Kinetex C18 column. Gradient elution was performed using a mixture of an ammonium formate buffer and acetonitrile. Total analysis time including column conditioning was 20.5 min. Analytes were fragmented by applying collision-induced dissociation, enabling structural identification by tandem mass spectrometry. Limit of detection values for the selected ion monitoring method ranged from 71 pM to 1.5 nM with corresponding values of two to nine times higher for the multiple reaction monitoring method. The liquid chromatography with mass spectrometry method resulted in a robust and sensitive quantification of hydroxamate siderophores as indicated by retention time stability, linearity, sensitivity, precision and recovery. The analytical error of the methods, assessed through random-order, duplicate analysis of soil samples extracted with a mixture of 10 mM phosphate buffer and methanol, appears negligible in relation to between-sample variations. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

The Partition Between Terminal Speed and Mass Loss: Thin, Thick, and Rotating Line-Driven Winds

NASA Astrophysics Data System (ADS)

Gayley, K. G.; Onifer, A. J.

2003-01-01

Steady-state supersonic line-driven winds are important contributors to wind-blown bubbles in star forming regions. The key input to the bubble in the energy-conserving phase is the wind kinetic-energy flux, which involves both the mass-loss rate and the terminal speed. However, these quantities are themselves self-consistent parameters of the line-driving process, so relate to each other and to the resulting wind optical depth. This complex interrelation between optical depth, mass-loss, and wind speed lies at the heart of line-driven wind theory. Drawing on the successes and insights of ``CAK'' theory, I will convey a simplified view of how to unite these processes using the concept of effective opacity, with attention to the ramifications for nonspherical nebular and wind-blown structures. Recent extensions to nongray optically thick environments such as Wolf-Rayet winds and supernovae are also discussed.

A targeted neuroglial reporter line generated by homologous recombination in human embryonic stem cells.

PubMed

Xue, Haipeng; Wu, Sen; Papadeas, Sophia T; Spusta, Steve; Swistowska, Anna Maria; MacArthur, Chad C; Mattson, Mark P; Maragakis, Nicholas J; Capecchi, Mario R; Rao, Mahendra S; Zeng, Xianmin; Liu, Ying

2009-08-01

In this study, we targeted Olig2, a basic helix-loop-helix transcription factor that plays an important role in motoneuron and oligodendrocyte development, in human embryonic stem cell (hESC) line BG01 by homologous recombination. One allele of Olig2 locus was replaced by a green fluorescent protein (GFP) cassette with a targeting efficiency of 5.7%. Targeted clone R-Olig2 (like the other clones) retained pluripotency, typical hESC morphology, and a normal parental karyotype 46,XY. Most importantly, GFP expression recapitulated endogenous Olig2 expression when R-Olig2 was induced by sonic hedgehog and retinoic acid, and GFP-positive cells could be purified by fluorescence-activated cell sorting. Consistent with previous reports on rodents, early GFP-expressing cells appeared biased to a neuronal fate, whereas late GFP-expressing cells appeared biased to an oligodendrocytic fate. This was corroborated by myoblast coculture, transplantation into the rat spinal cords, and whole genome expression profiling. The present work reports an hESC reporter line generated by homologous recombination targeting a neural lineage-specific gene, which can be differentiated and sorted to obtain pure neural progenitor populations.

Modelling supernova line profile asymmetries to determine ejecta dust masses: SN 1987A from days 714 to 3604

NASA Astrophysics Data System (ADS)

Bevan, Antonia; Barlow, M. J.

2016-02-01

The late-time optical and near-IR line profiles of many core-collapse supernovae exhibit a red-blue asymmetry as a result of greater extinction by internal dust of radiation emitted from the receding parts of the supernova ejecta. We present here a new code, DAMOCLES, that models the effects of dust on the line profiles of core-collapse supernovae in order to determine newly formed dust masses. We find that late-time dust-affected line profiles may exhibit an extended red scattering wing (as noted by Lucy et al. 1989) and that they need not be flux-biased towards the blue, although the profile peak will always be blueshifted. We have collated optical spectra of SN 1987A from a variety of archival sources and have modelled the Hα line from days 714 to 3604 and the [O I] 6300,6363 Å doublet between days 714 and 1478. Our line profile fits rule out day 714 dust masses >3 × 10-3 M⊙ for all grain types apart from pure magnesium silicates, for which no more than 0.07 M⊙ can be accommodated. Large grain radii ( ≥ 0.6 μm) are generally required to fit the line profiles even at the earlier epochs. We find that a large dust mass (≥0.1 M⊙) had formed by day 3604 and infer that the majority of the present dust mass must have formed after this epoch. Our findings agree with recent estimates from spectral energy distribution fits for the dust mass evolution of SN 1987A and support the inference that the majority of SN 1987A's dust formed many years after the initial explosion.

Leak detection by mass balance effective for Norman Wells line

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

Liou, J.C.P.

Mass-balance calculations for leak detection have been shown as effective as a leading software system, in a comparison based on a major Canadian crude-oil pipeline. The calculations and NovaCorp`s Leakstop software each detected 4% (approximately) or greater leaks on Interprovincial Pipe Line (IPL) Inc.`s Norman Wells pipeline. Insufficient data exist to assess performances of the two methods for leaks smaller than 4%. Pipeline leak detection using such software-based systems are common. Their effectiveness is measured by how small and how quickly a leak can be detected. Algorithms used and measurement uncertainties determine leak detectability.

Targeting ceramide metabolic pathway induces apoptosis in human breast cancer cell lines

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

Vethakanraj, Helen Shiphrah; Babu, Thabraz Ahmed; Sudarsanan, Ganesh Babu

2015-08-28

The sphingolipid ceramide is a pro apoptotic molecule of ceramide metabolic pathway and is hydrolyzed to proliferative metabolite, sphingosine 1 phosphate by the action of acid ceramidase. Being upregulated in the tumors of breast, acid ceramidase acts as a potential target for breast cancer therapy. We aimed at targeting this enzyme with a small molecule acid ceramidase inhibitor, Ceranib 2 in human breast cancer cell lines MCF 7 and MDA MB 231. Ceranib 2 effectively inhibited the growth of both the cell lines in dose and time dependant manner. Morphological apoptotic hallmarks such as chromatin condensation, fragmented chromatin were observedmore » in AO/EtBr staining. Moreover, ladder pattern of fragmented DNA observed in DNA gel electrophoresis proved the apoptotic activity of Ceranib 2 in breast cancer cell lines. The apoptotic events were associated with significant increase in the expression of pro-apoptotic genes (Bad, Bax and Bid) and down regulation of anti-apoptotic gene (Bcl 2). Interestingly, increase in sub G1 population of cell cycle phase analysis and elevated Annexin V positive cells after Ceranib 2 treatment substantiated its apoptotic activity in MCF 7 and MDA MB 231 cell lines. Thus, we report Ceranib 2 as a potent therapeutic agent against both ER{sup +} and ER{sup −} breast cancer cell lines. - Highlights: • Acid Ceramidase inhibitor, Ceranib 2 induced apoptosis in Breast cancer cell lines (MCF 7 and MDA MB 231 cell lines). • Apoptosis is mediated by DNA fragmentation and cell cycle arrest. • Ceranib 2 upregulated the expression of pro-apoptotic genes and down regulated anti-apoptotic gene expression. • More potent compared to the standard drug Tamoxifen.« less

Potential of capillary-column-switching liquid chromatography-tandem mass spectrometry for the quantitative trace analysis of small molecules. Application to the on-line screening of drugs in water.

PubMed

Pitarch, Elena; Hernandez, Felix; ten Hove, Jan; Meiring, Hugo; Niesing, Willem; Dijkman, Ellen; Stolker, Linda; Hogendoorn, Elbert

2004-03-26

We have investigated the potential of capillary-column-switching liquid chromatography coupled to tandem mass spectrometry (cLC-MS-MS) for the quantitative on-line trace analysis of target compounds in aqueous solutions. The technical design of the nano-scale cLC system developed at our Institute for peptide and protein identification has been tested and evaluated for the direct trace analysis of drugs in water samples. Sulphametoxazole, bezafibrate, metoprolol, carbamazepine and bisoprolol occurring frequently in Dutch waters, were selected as test compounds. Adequate conditions for trapping, elution and MS-MS detection were investigated by employing laboratory made 200 microm i.d. capillary columns packed with 5 microm aqua C18 material. In the final cLC-MS-MS conditions, a 1 cm length trapping column and a 4 cm length analytical column were selected. Under these conditions, the target compounds could be directly determined in water down to a level of around 50 ng/l employing only 25 microl of water sample. Validation was done by recovery experiments in ground-, surface- and drinking-water matrices as well as by the analysis of water samples with incurred residues and previously analyzed with a conventional procedure involving off-line solid-phase extraction and narrow-bore LC with MS-MS detection. The new methodology provided recoveries (50-500 ng/l level) between 50 and 114% with RSDs (n = 3, each level) below 20% for most of the compounds. Despite the somewhat less analytical performance in comparison to the conventional procedure, the on-line approach of the new methodology is very suitable for screening of drugs in aqueous samples.

On the Doppler Velocity of Emission Line Profiles Formed in the "Coronal Contraflow" that Is the Chromosphere-Corona Mass Cycle

NASA Astrophysics Data System (ADS)

McIntosh, Scott W.; Tian, Hui; Sechler, Marybeth; De Pontieu, Bart

2012-04-01

This analysis begins to explore the complex chromosphere-corona mass cycle using a blend of imaging and spectroscopic diagnostics. Single Gaussian fits (SGFs) to hot emission line profiles (formed above 1 MK) at the base of coronal loop structures indicate material blueshifts of 5-10 km s-1, while cool emission line profiles (formed below 1 MK) yield redshifts of a similar magnitude—indicating, to zeroth order, that a temperature-dependent bifurcating flow exists on coronal structures. Image sequences of the same region reveal weakly emitting upward propagating disturbances in both hot and cool emission with apparent speeds of 50-150 km s-1. Spectroscopic observations indicate that these propagating disturbances produce a weak emission component in the blue wing at commensurate speed, but that they contribute only a few percent to the (ensemble) emission line profile in a single spatio-temporal resolution element. Subsequent analysis of imaging data shows material "draining" slowly (~10 km s-1) out of the corona, but only in the cooler passbands. We interpret the draining as the return flow of coronal material at the end of the complex chromosphere-corona mass cycle. Further, we suggest that the efficient radiative cooling of the draining material produces a significant contribution to the red wing of cool emission lines that is ultimately responsible for their systematic redshift as derived from an SGF when compared to those formed in hotter (conductively dominated) domains. The presence of counterstreaming flows complicates the line profiles, their interpretation, and asymmetry diagnoses, but allows a different physical picture of the lower corona to develop.

Imaging Ultrasound Guidance and on-line Estimation of Thermal Behavior in HIFU Exposed Targets

NASA Astrophysics Data System (ADS)

Chauhan, Sunita; Haryanto, Amir

2006-05-01

Elevated temperatures have been used for many years to combat several diseases including treatment of certain types of cancers/tumors. High Intensity Focused Ultrasound (HIFU) has emerged as a potential non-invasive modality for trackless targeting of deep-seated cancers of human body. For the procedures which require thermal elevation such as hyperthermia and tissue ablation, temperature becomes a parameter of vital importance in order to monitor the treatment on-line. Also, embedding invasive temperature probes for this purpose beats the supremacy of the non-invasive ablating modality. In this paper, we describe the use of a non-invasive and inexpensive conventional imaging ultrasound modality for lesion positioning and estimation of thermal behavior of the tissue on exposure to HIFU. Representative results of our online lesion tracking algorithm for discerning lesioning behavior using image capture, processing and phase-shift measurements are presented.

Canine histiocytic sarcoma presenting as a target lesion on brain magnetic resonance imaging and as a solitary pulmonary mass.

PubMed

Hicks, Jill; Barber, Renee; Childs, Bronwen; Kirejczyk, Shannon Gm; Uhl, Elizabeth W

2017-04-17

A 6-year-old spayed female miniature schnauzer presented with generalized seizures and progressive multifocal intracranial neurologic disease. Thoracic radiographs and computed tomography (CT) revealed a large solitary pulmonary mass within the right cranial lung lobe. On brain magnetic resonance imaging (MRI), a solitary intraparenchymal mass within the left piriform lobe had a "target" appearance on both pre- and postcontrast sequences. Cerebrospinal fluid was unremarkable and histopathology indicated both masses represented histiocytic sarcoma. This case represents an uncommonly reported MRI appearance of histiocytic sarcoma in the canine brain and a large, solitary-appearing pulmonary histiocytic sarcoma in the same dog. © 2017 American College of Veterinary Radiology.

Low-dose non-targeted radiation effects in human esophageal adenocarcinoma cell lines.

PubMed

Hanu, Christine; Wong, Raimond; Sur, Ranjan K; Hayward, Joseph E; Seymour, Colin; Mothersill, Carmel

2017-02-01

To investigate non-targeted radiation effects in esophageal adenocarcinoma cell lines (OE19 and OE33) using human keratinocyte and colorectal cancer cell reporters following γ-ray exposure. Both clonogenic assays and ratiometric calcium endpoints were used to check for the occurrence of bystander signals in reporter cells. We report data suggesting that γ-irradiation increases cell killing over the expected linear quadratic (LQ) model levels in the OE19 cell line exposed to doses below 1 Gy, i.e. which may be suggestive to be a low hyper-radiosensitive (HRS) response to direct irradiation. Both EAC cell lines (OE19 and OE33) have the ability to produce bystander signals when irradiated cell conditioned medium (ICCM) is placed onto human keratinocyte reporters, but do not seem to be capable of responding to bystander signals when placed on their autologous reporters. Further work with human keratinocyte reporter models showed statistically significant intracellular calcium fluxes following exposure of the reporters to ICCM harvested from both EAC cell lines exposed to 0.5 Gy. These experiments suggest that the OE19 and OE33 cell lines produce bystander signals in human keratinocyte reporter cells. However, the radiosensitivity of the EAC cell lines used in this study cannot be enhanced by the bystander response since both cell lines could not respond to bystander signals.

Target-guided separation of Bougainvillea glabra betacyanins by direct coupling of preparative ion-pair high-speed countercurrent chromatography and electrospray ionization mass-spectrometry.

PubMed

Jerz, Gerold; Wybraniec, Sławomir; Gebers, Nadine; Winterhalter, Peter

2010-07-02

In this study, preparative ion-pair high-speed countercurrent chromatography was directly coupled to an electrospray ionization mass-spectrometry device (IP-HSCCC/ESI-MS-MS) for target-guided fractionation of high molecular weight acyl-oligosaccharide linked betacyanins from purple bracts of Bougainvillea glabra (Nyctaginaceae). The direct identification of six principal acyl-oligosaccharide linked betacyanins in the mass range between m/z 859 and m/z 1359 was achieved by positive ESI-MS ionization and gave access to the genuine pigment profile already during the proceeding of the preparative separation. Inclusively, all MS/MS-fragmentation data were provided during the chromatographic run for a complete analysis of substitution pattern. On-line purity evaluation of the recovered fractions is of high value in target-guided screening procedures and for immediate decisions about suitable fractions used for further structural analysis. The applied preparative hyphenation was shown to be a versatile screening method for on-line monitoring of countercurrent chromatographic separations of polar crude pigment extracts and also traced some minor concentrated compounds. For the separation of 760mg crude pigment extract the biphasic solvent system tert.-butylmethylether/n-butanol/acetonitrile/water 2:2:1:5 (v/v/v/v) was used with addition of ion-pair forming reagent trifluoroacetic acid. The preparative HSCCC-eluate had to be modified by post-column addition of a make-up solvent stream containing formic acid to reduce ion-suppression caused by trifluoroacetic acid and later significantly maximized response of ESI-MS/MS detection of target substances. A variable low-pressure split-unit guided a micro-eluate to the ESI-MS-interface for sensitive and direct on-line detection, and the major volume of the effluent stream was directed to the fraction collector for preparative sample recovery. The applied make-up solvent mixture significantly improved smoothness of the continuously

Studies of uranium carbide targets of a high density

NASA Astrophysics Data System (ADS)

Panteleev, V. N.; Alyakrinskiy, O.; Barbui, M.; Barzakh, A. E.; Dubois, M.; Eleon, C.; Essabaa, S.; Fedorov, D. V.; Gaubert, G.; Ionan, A. M.; Ivanov, V. S.; Jardin, P.; Lau, C.; Leroy, R.; Lhersonneau, G.; Mezilev, K. A.; Mhamed, C.; Molkanov, P. L.; Moroz, F. V.; Orlov, S. Yu.; Saint Laurent, M. G.; Stroe, L.; Tecchio, L. B.; Tonezzer, M.; Villari, A. C. C.; Volkov, Yu. M.

2008-10-01

Production of Cs and Fr isotopes from uranium carbide targets of a high density has been investigated at IRIS (Investigation Radioactive Isotopes at Synchrocyclotron), Gatchina. The UC target material with a density of 12 g/cm3 was prepared in a form of pellets. Two targets were tested on-line under the same temperature conditions: (a) a reference small target with a thickness of 4.5 g/cm2; (b) a heavier (so called intermediate) target with a thickness of 91 g/cm2. Yields and release efficiencies of nuclides with half-lives from some minutes to some milliseconds produced by 1 GeV protons in these targets are presented. It is remarkable that yields, even those of very short-lived isotopes such as 214Fr (T1/2 = 5 ms) and 219Fr (T1/2 = 20 ms), increase proportionally to the target thickness. A one month off-line heating test of the 91 g/cm2 target at a temperature of 2000 °C has been carried out successfully. The yields and release efficiencies of Cs and Fr measured on-line before and after the heating test coincided within the limits of measurement errors, thereby demonstrating the conservation of the target unit parameters. Based on these very promising results, a heavier target with a mass about 0.7 kg is prepared presently at IRIS.

Determining Black Hole Mass of AGN using FWHM of H-beta Emission Line and Luminosity Relations

NASA Astrophysics Data System (ADS)

Cameron, Thomas Jacob; Burris, Debra L.

2017-01-01

At the center of some active galaxies are super-massive black holes and for some time the accepted method of measuring the mass of such galaxies has been the method used by Vestergaard and Peterson, among others. By using the luminosity function which is related to H-β emission spectra from these black holes, both for cosmic redshift and for Fe-II emissions using IRAF. From there, H-β can accurately measure the full width half max of the H-beta line in these spectrum as well as the luminosity and these paired with the O-III lines give us an estimate on the mass of the black hole. The purpose of this is to compare it to the values obtained from the Mass-Pitch Angle relation being proposed by Kennefick et al. (2016 in preparation)

Role of target thickness in proton acceleration from near-critical mass-limited plasmas

NASA Astrophysics Data System (ADS)

Kuri, Deep Kumar; Das, Nilakshi; Patel, Kartik

2017-07-01

The role played by the target thickness in generating high energetic protons by a circularly polarized laser from near-critical mass-limited targets (MLT) has been investigated with the help of three-dimensional (3D) particle-in-cell (PIC) simulations. The radiation pressure accelerates protons from the front side of the target. Due to hole boring, the target front side gets deformed resulting in a change in the effective angle of incidence which causes vacuum heating and hence generates hot electrons. These hot electrons travel through the target at an angle with the laser axis and hence get more diverged along transverse directions for large target thickness. The hot electrons form sheath fields on the target rear side which accelerates protons via target normal sheath acceleration (TNSA). It is observed that the collimation of radiation pressure accelerated protons gets degraded on reaching the target rear side due to TNSA. The effect of transverse hot electron recirculations gets suppressed and the energetic protons get highly collimated on decreasing target thickness as the radiation pressure acceleration (RPA) starts dominating the acceleration process.

A General Method for Targeted Quantitative Cross-Linking Mass Spectrometry.

PubMed

Chavez, Juan D; Eng, Jimmy K; Schweppe, Devin K; Cilia, Michelle; Rivera, Keith; Zhong, Xuefei; Wu, Xia; Allen, Terrence; Khurgel, Moshe; Kumar, Akhilesh; Lampropoulos, Athanasios; Larsson, Mårten; Maity, Shuvadeep; Morozov, Yaroslav; Pathmasiri, Wimal; Perez-Neut, Mathew; Pineyro-Ruiz, Coriness; Polina, Elizabeth; Post, Stephanie; Rider, Mark; Tokmina-Roszyk, Dorota; Tyson, Katherine; Vieira Parrine Sant'Ana, Debora; Bruce, James E

2016-01-01

Chemical cross-linking mass spectrometry (XL-MS) provides protein structural information by identifying covalently linked proximal amino acid residues on protein surfaces. The information gained by this technique is complementary to other structural biology methods such as x-ray crystallography, NMR and cryo-electron microscopy[1]. The extension of traditional quantitative proteomics methods with chemical cross-linking can provide information on the structural dynamics of protein structures and protein complexes. The identification and quantitation of cross-linked peptides remains challenging for the general community, requiring specialized expertise ultimately limiting more widespread adoption of the technique. We describe a general method for targeted quantitative mass spectrometric analysis of cross-linked peptide pairs. We report the adaptation of the widely used, open source software package Skyline, for the analysis of quantitative XL-MS data as a means for data analysis and sharing of methods. We demonstrate the utility and robustness of the method with a cross-laboratory study and present data that is supported by and validates previously published data on quantified cross-linked peptide pairs. This advance provides an easy to use resource so that any lab with access to a LC-MS system capable of performing targeted quantitative analysis can quickly and accurately measure dynamic changes in protein structure and protein interactions.

Proton transfer reaction mass spectrometry: on-line trace gas analysis at the ppb level

NASA Astrophysics Data System (ADS)

Hansel, A.; Jordan, A.; Holzinger, R.; Prazeller, P.; Vogel, W.; Lindinger, W.

1995-11-01

A system for trace gas analysis using proton transfer reaction mass spectrometry (PTR-MS) has been developed which allows for on-line measurements of components with concentrations as low as 1 ppb. The method is based on reactions of H3O+ ions, which perform non-dissociative proton transfer to most of the common organic trace constituents but do not react with any of the components present in clean air. Examples of analysis of breath taken from smokers and non-smokers as well as from patients suffering from cirrhosis of the liver, and of air in buildings as well as of ambient air taken at a road crossing demonstrate the wide range of applicability of this method. An enhanced level of acetonitrile in the breath is a most suitable indicator that a person is a smoker. Enhanced levels of propanol strongly indicate that a person has a severe liver deficiency.

Mass spectrometry of atmospheric aerosols--recent developments and applications. Part II: On-line mass spectrometry techniques.

PubMed

Pratt, Kerri A; Prather, Kimberly A

2012-01-01

Many of the significant advances in our understanding of atmospheric particles can be attributed to the application of mass spectrometry. Mass spectrometry provides high sensitivity with fast response time to probe chemically complex particles. This review focuses on recent developments and applications in the field of mass spectrometry of atmospheric aerosols. In Part II of this two-part review, we concentrate on real-time mass spectrometry techniques, which provide high time resolution for insight into brief events and diurnal changes while eliminating the potential artifacts acquired during long-term filter sampling. In particular, real-time mass spectrometry has been shown recently to provide the ability to probe the chemical composition of ambient individual particles <30 nm in diameter to further our understanding of how particles are formed through nucleation in the atmosphere. Further, transportable real-time mass spectrometry techniques are now used frequently on ground-, ship-, and aircraft-based studies around the globe to further our understanding of the spatial distribution of atmospheric aerosols. In addition, coupling aerosol mass spectrometry techniques with other measurements in series has allowed the in situ determination of chemically resolved particle effective density, refractive index, volatility, and cloud activation properties. Copyright © 2011 Wiley Periodicals, Inc.

[Genetic characteristics associated with drought tolerance of plant height and thousand-grain mass of recombinant inbred lines of wheat].

PubMed

Yang, De-Long; Zhang, Guo-Hong; Li, Xing-Mao; Xing, Hua; Cheng, Hong-Bo; Ni, Sheng-Li; Chen, Xiao-Ping

2012-06-01

A total of 120 recombinant inbred lines (RIL) derived from Chinese winter wheat cultivars Longjian 19xQ9086 and the two parents were taken as test materials to study the quantitative genetics characteristics of their plant height at different development stages, thousand-grain mass, as well as the correlations between the two traits under rainfed (drought stress) and well-watered conditions, and evaluate the genetic variation of the RIL. Under the two water conditions, the target traits of the RIL showed substantial transgressive segregation and great sensitivity to water condition. The drought stress coefficient of the plant height was higher at jointing stage, being up to 0.851. There was a significant positive correlation between the plant height at different development stages and the thousand-grain mass, and comparing with that at other growth stages, the plant height at jointing stage had a higher correlation coefficient with the thousand-grain mass (R2DS = 0.32, R2WW = 0.28). The plant height at both jointing and flowering stages had significant positive and direct effect but negative and indirect gross effect on the thousand-grain mass, while the plant height at heading and maturing stages was in adverse. The target traits showed a lower heritability ranged from 0.27 to 0.60. The numbers of the gene pairs controlling the thousand-grain mass were 10 under rainfed and 13 under well-watered conditions, while those of the gene pairs controlling the plant height at different development stages were 3-7 under rainfed and 4-14 under well-watered conditions, respectively. According to the clustering of the drought stress coefficient of plant height, the RIL could be classified into five subgroups, showing the abundant variation of the RIL in their phe- notypes and in the sensitivity to water condition. It was considered that the test RIL were appropriate for the study of the quantitative genetics of wheat drought resistance.

Animal models for medications development targeting alcohol abuse using selectively bred rat lines: Neurobiological and pharmacological validity

PubMed Central

Bell, Richard L.; Sable, Helen J.K.; Colombo, Giancarlo; Hyytia, Petri; Rodd, Zachary A.; Lumeng, Lawrence

2012-01-01

The purpose of this review paper is to present evidence that rat animal models of alcoholism provide an ideal platform for developing and screening medications that target alcohol abuse and dependence. The focus is on the 5 oldest international rat lines that have been selectively bred for a high alcohol-consumption phenotype. The behavioral and neurochemical phenotypes of these rat lines are reviewed and placed in the context of the clinical literature. The paper presents behavioral models for assessing the efficacy of pharmaceuticals for the treatment of alcohol abuse and dependence in rodents, with particular emphasis on rats. Drugs that have been tested for their effectiveness in reducing alcohol/ethanol consumption and/or self-administration by these rat lines and their putative site of action are summarized. The paper also presents some current and future directions for developing pharmacological treatments targeting alcohol abuse and dependence. PMID:22841890

In-Line Reactions and Ionizations of Vaporized Diphenylchloroarsine and Diphenylcyanoarsine in Atmospheric Pressure Chemical Ionization Mass Spectrometry

NASA Astrophysics Data System (ADS)

Okumura, Akihiko; Takada, Yasuaki; Watanabe, Susumu; Hashimoto, Hiroaki; Ezawa, Naoya; Seto, Yasuo; Takayama, Yasuo; Sekioka, Ryoji; Yamaguchi, Shintaro; Kishi, Shintaro; Satoh, Takafumi; Kondo, Tomohide; Nagashima, Hisayuki; Nagoya, Tomoki

2016-07-01

We propose detecting a fragment ion (Ph2As+) using counter-flow introduction atmospheric pressure chemical ionization ion trap mass spectrometry for sensitive air monitoring of chemical warfare vomiting agents diphenylchloroarsine (DA) and diphenylcyanoarsine (DC). The liquid sample containing of DA, DC, and bis(diphenylarsine)oxide (BDPAO) was heated in a dry air line, and the generated vapor was mixed into the humidified air flowing through the sampling line of a mass spectrometer. Humidity effect on the air monitoring was investigated by varying the humidity of the analyzed air sample. Evidence of the in-line conversion of DA and DC to diphenylarsine hydroxide (DPAH) and then BDPAO was obtained by comparing the chronograms of various ions from the beginning of heating. Multiple-stage mass spectrometry revealed that the protonated molecule (MH+) of DA, DC, DPAH, and BDPAO could produce Ph2As+ through their in-source fragmentation. Among the signals of the ions that were investigated, the Ph2As+ signal was the most intense and increased to reach a plateau with the increased air humidity, whereas the MH+ signal of DA decreased. It was suggested that DA and DC were converted in-line into BDPAO, which was a major source of Ph2As+.

Liquid Chromatography Mass Spectrometry Analysis and Cytotoxicity of Asparagus adscendens Roots against Human Cancer Cell Lines.

PubMed

Khan, Kashif Maqbool; Nahar, Lutfun; Mannan, Abdul; Arfan, Muhammad; Khan, Ghazanfar Ali; Al-Groshi, Afaf; Evans, Andrew; Dempster, Nicola M; Ismail, Fyaz M D; Sarker, Satyajit D

2018-01-01

Asparagus adscendens Roxb. (Asparagaceae), is native to the Himalayas. This plant has been used in the prevention and effective treatment of various forms of cancers. This paper reports, for the first time, on the cytotoxicity of the methanol (MeOH) extract of the roots of A. adscendens and its solid-phase extraction (SPE) fractions against four human carcinoma cell lines and LC-ESI-QTOF-MS analysis of the SPE fractions. Finely powdered roots of A. adscendens were macerated in methanol and extracted through SPE using gradient solvent system (water: methanol) proceeded for analysis on LC-ESI-QTOF-MS and cytotoxicity against four human carcinoma cell lines: breast (MCF7), liver (HEPG2), lung (A549), and urinary bladder (EJ138), using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide assay. The MeOH extract and four SPE fractions exhibited cytotoxicity against all cell lines with the IC 50 values ranging from 6 to 79 μg/mL. As observed in other Asparagus species, the presence of saponins and sapogenins in the SPE fractions was evident in the liquid chromatography-mass spectrometry data. It is reasonable to assume that the cytotoxicity of the MeOH extract of the roots of A. adscendens and its SPE fractions, at least partly, due to the presence of saponins and their aglycones. This suggests that A. adscendens could be exploited as a potential source of cytotoxic compounds with putative anticancer potential. The MeOH extract and all solid-phase extraction (SPE) fractions exhibited various levels of cytotoxicity against all cell lines with the IC 50 values ranging from 6 to 79 μg/mLThe presence of saponins and sapogenins in the SPE fractions was evident in the Liquid chromatography-mass spectrometry dataDue to the presence of saponins and their aglycones, suggest that A. adscendens could be exploited as a potential source of cytotoxic compounds with putative anticancer potential. Abbreviation used: SPE: Solid-phase extraction, MCF7: Breast cancer cell line

A New Black Hole Mass Estimate for Obscured Active Galactic Nuclei

NASA Astrophysics Data System (ADS)

Minezaki, Takeo; Matsushita, Kyoko

2015-04-01

We propose a new method for estimating the mass of a supermassive black hole, applicable to obscured active galactic nuclei (AGNs). This method estimates the black hole mass using the width of the narrow core of the neutral FeKα emission line in X-rays and the distance of its emitting region from the black hole based on the isotropic luminosity indicator via the luminosity scaling relation. Assuming the virial relation between the locations and the velocity widths of the neutral FeKα line core and the broad Hβ emission line, the luminosity scaling relation of the neutral FeKα line core emitting region is estimated. We find that the velocity width of the neutral FeKα line core falls between that of the broad Balmer emission lines and the corresponding value at the dust reverberation radius for most of the target AGNs. The black hole mass {{M}BH,FeKα } estimated with this method is then compared with other black hole mass estimates, such as the broad emission-line reverberation mass {{M}BH,rev} for type 1 AGNs, the mass {{M}BH,{{H2}O}} based on the H2O maser, and the single-epoch mass estimate {{M}BH,pol} based on the polarized broad Balmer lines for type 2 AGNs. We find that {{M}BH,FeKα } is consistent with {{M}BH,rev} and {{M}BH,pol}, and find that {{M}BH,FeKα } correlates well with {{M}BH,{{H2}O}}. These results suggest that {{M}BH,FeKα } is a potential indicator of the black hole mass for obscured AGNs. In contrast, {{M}BH,FeKα } is systematically larger than {{M}BH,{{H2}O}} by about a factor of 5, and the possible origins are discussed.

Focused transport of energetic particles along magnetic field lines draped around a coronal mass ejection

NASA Technical Reports Server (NTRS)

Tan, L. C.; Mason, G. M.; Lee, M. A.; Klecker, B.; Ipavich, F. M.

1992-01-01

Evidence is presented for focused transport of energetic particles along magnetic field lines draped around a coronal mass ejection. This evidence was obtained with the University of Maryland/Max-Planck-Institute experiment on the ISEE-3 spacecraft during the decay phase of the June 6, 1979, solar particle event. During the early portion of the decay phase of this event, interplanetary magnetic field lines were apparently draped around a coronal mass ejection, leading to a small focusing length on the western flank where ISEE 3 was located. A period of very slow decrease of particle intensity was observed, along with large sunward anisotropy in the solar wind frame, which is inconsistent with predictions of the standard Fokker-Planck equation models for diffusive transport. It was found possible to fit the observations, assuming that focused transport dominates and that the particle pitch angle scattering is isotropic.

CRISPR/Cas9 mediated generation of stable chondrocyte cell lines with targeted gene knockouts; analysis of an aggrecan knockout cell line.

PubMed

Yang, Maozhou; Zhang, Liang; Stevens, Jeff; Gibson, Gary

2014-12-01

The Swarm rat chondrosarcoma (RCS) cell lines derived from a spontaneous neoplasm in a rat spine several decades ago have provided excellent models of chondrosarcoma tumor development. In addition the robust chondrocyte phenotype (expression of a large panel of genes identical to that seen in normal rat cartilage) and the ability to generate cell clones have facilitated their extensive use in the identification of chondrocyte proteins and genes. The clustered regularly interspersed short palindromic repeat (CRISPR) technology employing the RNA-guided nuclease Cas9 has rapidly dominated the genome engineering field as a unique and powerful gene editing tool. We have generated a stable RCS cell line (RCS Cas9) expressing the nuclease Cas9 that enables the editing of any target gene or non-coding RNA by simple transfection with a guide RNA. As proof of principle, stable cell lines with targeted ablation of aggrecan expression (Acan KO) were generated and characterized. The studies show that stable chondrocyte cell lines with targeted genome editing can be quickly generated from RCS Cas9 cells using this system. The Acan KO cell lines also provided a tool for characterizing the response of chondrocytes to aggrecan loss and the role of aggrecan in chondrosarcoma development. Loss of aggrecan expression while not affecting the chondrocyte phenotype resulted in a much firmer attachment of cells to their substrate in culture. Large changes in the expression of several genes were observed in response to the absence of the proteoglycan matrix, including those for several small leucine rich proteoglycans (SLRPs), transcription factors and membrane transporters. Acan KO cells failed to form a substantial chondrosarcoma when injected subcutaneously in nude mice consistent with previous suggestions that the glycosaminoglycan-rich matrix surrounding the chondrosarcoma protects it from destruction by the host immune system. The studies provide new understanding of aggrecan

At-Line Cellular Screening Methodology for Bioactives in Mixtures Targeting the α7-Nicotinic Acetylcholine Receptor.

PubMed

Otvos, Reka A; Mladic, Marija; Arias-Alpizar, Gabriela; Niessen, Wilfried M A; Somsen, Govert W; Smit, August B; Kool, Jeroen

2016-06-01

The α7-nicotinic acetylcholine receptor (α7-nAChR) is a ligand-gated ion channel expressed in different regions of the central nervous system (CNS). The α7-nAChR has been associated with Alzheimer's disease, epilepsy, and schizophrenia, and therefore is extensively studied as a drug target for the treatment of these diseases. Important sources for new compounds in drug discovery are natural extracts. Since natural extracts are complex mixtures, identification of the bioactives demands the use of analytical techniques to separate a bioactive from inactive compounds. This study describes screening methodology for identifying bioactive compounds in mixtures acting on the α7-nAChR. The methodology developed combines liquid chromatography (LC) coupled via a split with both an at-line calcium (Ca(2+))-flux assay and high-resolution mass spectrometry (MS). This allows evaluation of α7-nAChR responses after LC separation, while parallel MS enables compound identification. The methodology was optimized for analysis of agonists and positive allosteric modulators, and was successfully applied to screening of the hallucinogen mushroom Psilocybe Mckennaii The crude mushroom extract was analyzed using both reversed-phase and hydrophilic interaction liquid chromatography. Matching retention times and peak shapes of bioactives found with data from the parallel MS measurements allowed rapid pinpointing of accurate masses corresponding to the bioactives. © 2016 Society for Laboratory Automation and Screening.

The clustering of Hβ +[OIII] and [OII] emitters since z ˜ 5: dependencies with line luminosity and stellar mass

NASA Astrophysics Data System (ADS)

Khostovan, A. A.; Sobral, D.; Mobasher, B.; Best, P. N.; Smail, I.; Matthee, J.; Darvish, B.; Nayyeri, H.; Hemmati, S.; Stott, J. P.

2018-04-01

We investigate the clustering properties of ˜7000 Hβ +[OIII] and [OII] narrowband-selected emitters at z ˜ 0.8 - 4.7 from the High-z Emission Line Survey. We find clustering lengths, r0, of 1.5 - 4.0 h-1 Mpc and minimum dark matter halo masses of 1010.7 - 12.1 M⊙ for our z = 0.8 - 3.2 Hβ +[OIII] emitters and r0˜2.0 - 8.3 h-1 Mpc and halo masses of 1011.5 - 12.6 M⊙ for our z = 1.5 - 4.7 [OII] emitters. We find r0 to strongly increase both with increasing line luminosity and redshift. By taking into account the evolution of the characteristic line luminosity, L⋆(z), and using our model predictions of halo mass given r0, we find a strong, redshift-independent increasing trend between L/L⋆(z) and minimum halo mass. The faintest Hβ +[OIII] emitters are found to reside in 109.5 M⊙ halos and the brightest emitters in 1013.0 M⊙ halos. For [OII] emitters, the faintest emitters are found in 1010.5 M⊙ halos and the brightest emitters in 1012.6 M⊙ halos. A redshift-independent stellar mass dependency is also observed where the halo mass increases from 1011 M⊙ to 1012.5 M⊙ for stellar masses of 108.5 M⊙ to 1011.5 M⊙, respectively. We investigate the interdependencies of these trends by repeating our analysis in a Lline - Mstar grid space for our most populated samples (Hβ +[OIII] z = 0.84 and [OII] z = 1.47) and find that the line luminosity dependency is stronger than the stellar mass dependency on halo mass. For L > L⋆ emitters at all epochs, we find a relatively flat trend with halo masses of 1012.5 - 13 M⊙ which may be due to quenching mechanisms in massive halos which is consistent with a transitional halo mass predicted by models.

Areal Mass Oscillations in Planar Targets Due to Feedout: Theory and Simulations.

NASA Astrophysics Data System (ADS)

Velikovich, A. L.; Schmitt, A. J.; Karasik, M.; Obenschain, S. P.; Serlin, V.; Pawley, C. J.; Gardner, J. H.; Aglitskiy, Y.; Metzler, N.

2001-10-01

When a planar shock wave breaks out at a rippled rear surface of a laser-driven target, the lateral pressure gradient in a rippled rarefaction wave propagating back to the front surface causes a lateral mass redistribution that reverses the phase of mass variation. If the driving laser pulse has no foot, then the RT growth, starting when the rarefaction wave reaches the front surface, causes the second phase reversal of mass variation, and continues at the initial phase, as consistently observed in feedout experiments on Nike. A foot of the laser pulse can cause an early phase reversal of mass variation, making the strong shock wave driven by the main pulse interact with a density variation in a rippled rarefaction wave rather than with static rear surface ripples. Theory and simulations predict that this interaction can make the phase of mass variation reverse one or three times. Then the phase of the RT growing mode would be opposite to that of the initial mass variation.

Confirmation of Small Dynamical and Stellar Masses for Extreme Emission Line Galaxies at z Approx. 2

NASA Technical Reports Server (NTRS)

Maseda, Michael V.; van Der Wel, Arjen; da Cunha, Elisabete; Rix, Hans-Walter; Pacifici, Camilla; Momcheva, Ivelina; Brammer, Gabriel B.; Franx, Marijn; van Dokkum, Pieter; Bell, Eric F.;

An off-line method to characterize the fission product release from uranium carbide-target prototypes developed for SPIRAL2 project

NASA Astrophysics Data System (ADS)

Hy, B.; Barré-Boscher, N.; Özgümüs, A.; Roussière, B.; Tusseau-Nenez, S.; Lau, C.; Cheikh Mhamed, M.; Raynaud, M.; Said, A.; Kolos, K.; Cottereau, E.; Essabaa, S.; Tougait, O.; Pasturel, M.

2012-10-01

In the context of radioactive ion beams, fission targets, often based on uranium compounds, have been used for more than 50 years at isotope separator on line facilities. The development of several projects of second generation facilities aiming at intensities two or three orders of magnitude higher than today puts an emphasis on the properties of the uranium fission targets. A study, driven by Institut de Physique Nucléaire d'Orsay (IPNO), has been started within the SPIRAL2 project to try and fully understand the behavior of these targets. In this paper, we have focused on five uranium carbide based targets. We present an off-line method to characterize their fission product release and the results are examined in conjunction with physical characteristics of each material such as the microstructure, the porosity and the chemical composition.

Application of a haematopoetic progenitor cell-targeted adeno-associated viral (AAV) vector established by selection of an AAV random peptide library on a leukaemia cell line

PubMed Central

Stiefelhagen, Marius; Sellner, Leopold; Kleinschmidt, Jürgen A; Jauch, Anna; Laufs, Stephanie; Wenz, Frederik; Zeller, W Jens; Fruehauf, Stefan; Veldwijk, Marlon R

2008-01-01

Background For many promising target cells (e.g.: haematopoeitic progenitors), the susceptibility to standard adeno-associated viral (AAV) vectors is low. Advancements in vector development now allows the generation of target cell-selected AAV capsid mutants. Methods To determine its suitability, the method was applied on a chronic myelogenous leukaemia (CML) cell line (K562) to obtain a CML-targeted vector and the resulting vectors tested on leukaemia, non-leukaemia, primary human CML and CD34+ peripheral blood progenitor cells (PBPC); standard AAV2 and a random capsid mutant vector served as controls. Results Transduction of CML (BV173, EM3, K562 and Lama84) and AML (HL60 and KG1a) cell lines with the capsid mutants resulted in an up to 36-fold increase in CML transduction efficiency (K562: 2-fold, 60% ± 2% green fluorescent protein (GFP)+ cells; BV173: 9-fold, 37% ± 2% GFP+ cells; Lama84: 36-fold, 29% ± 2% GFP+ cells) compared to controls. For AML (KG1a, HL60) and one CML cell line (EM3), no significant transduction (<1% GFP+ cells) was observed for any vector. Although the capsid mutant clone was established on a cell line, proof-of-principle experiments using primary human cells were performed. For CML (3.2-fold, mutant: 1.75% ± 0.45% GFP+ cells, p = 0.03) and PBPC (3.5-fold, mutant: 4.21% ± 3.40% GFP+ cells) a moderate increase in gene transfer of the capsid mutant compared to control vectors was observed. Conclusion Using an AAV random peptide library on a CML cell line, we were able to generate a capsid mutant, which transduced CML cell lines and primary human haematopoietic progenitor cells with higher efficiency than standard recombinant AAV vectors. PMID:18789140

AssayR: A Simple Mass Spectrometry Software Tool for Targeted Metabolic and Stable Isotope Tracer Analyses.

PubMed

Wills, Jimi; Edwards-Hicks, Joy; Finch, Andrew J

2017-09-19

Metabolic analyses generally fall into two classes: unbiased metabolomic analyses and analyses that are targeted toward specific metabolites. Both techniques have been revolutionized by the advent of mass spectrometers with detectors that afford high mass accuracy and resolution, such as time-of-flights (TOFs) and Orbitraps. One particular area where this technology is key is in the field of metabolic flux analysis because the resolution of these spectrometers allows for discrimination between 13 C-containing isotopologues and those containing 15 N or other isotopes. While XCMS-based software is freely available for untargeted analysis of mass spectrometric data sets, it does not always identify metabolites of interest in a targeted assay. Furthermore, there is a paucity of vendor-independent software that deals with targeted analyses of metabolites and of isotopologues in particular. Here, we present AssayR, an R package that takes high resolution wide-scan liquid chromatography-mass spectrometry (LC-MS) data sets and tailors peak detection for each metabolite through a simple, iterative user interface. It automatically integrates peak areas for all isotopologues and outputs extracted ion chromatograms (EICs), absolute and relative stacked bar charts for all isotopologues, and a .csv data file. We demonstrate several examples where AssayR provides more accurate and robust quantitation than XCMS, and we propose that tailored peak detection should be the preferred approach for targeted assays. In summary, AssayR provides easy and robust targeted metabolite and stable isotope analyses on wide-scan data sets from high resolution mass spectrometers.

AssayR: A Simple Mass Spectrometry Software Tool for Targeted Metabolic and Stable Isotope Tracer Analyses

PubMed Central

2017-01-01

Metabolic analyses generally fall into two classes: unbiased metabolomic analyses and analyses that are targeted toward specific metabolites. Both techniques have been revolutionized by the advent of mass spectrometers with detectors that afford high mass accuracy and resolution, such as time-of-flights (TOFs) and Orbitraps. One particular area where this technology is key is in the field of metabolic flux analysis because the resolution of these spectrometers allows for discrimination between 13C-containing isotopologues and those containing 15N or other isotopes. While XCMS-based software is freely available for untargeted analysis of mass spectrometric data sets, it does not always identify metabolites of interest in a targeted assay. Furthermore, there is a paucity of vendor-independent software that deals with targeted analyses of metabolites and of isotopologues in particular. Here, we present AssayR, an R package that takes high resolution wide-scan liquid chromatography–mass spectrometry (LC-MS) data sets and tailors peak detection for each metabolite through a simple, iterative user interface. It automatically integrates peak areas for all isotopologues and outputs extracted ion chromatograms (EICs), absolute and relative stacked bar charts for all isotopologues, and a .csv data file. We demonstrate several examples where AssayR provides more accurate and robust quantitation than XCMS, and we propose that tailored peak detection should be the preferred approach for targeted assays. In summary, AssayR provides easy and robust targeted metabolite and stable isotope analyses on wide-scan data sets from high resolution mass spectrometers. PMID:28850215

Suspected-target pesticide screening using gas chromatography-quadrupole time-of-flight mass spectrometry with high resolution deconvolution and retention index/mass spectrum library.

PubMed

Zhang, Fang; Wang, Haoyang; Zhang, Li; Zhang, Jing; Fan, Ruojing; Yu, Chongtian; Wang, Wenwen; Guo, Yinlong

2014-10-01

A strategy for suspected-target screening of pesticide residues in complicated matrices was exploited using gas chromatography in combination with hybrid quadrupole time-of-flight mass spectrometry (GC-QTOF MS). The screening workflow followed three key steps of, initial detection, preliminary identification, and final confirmation. The initial detection of components in a matrix was done by a high resolution mass spectrum deconvolution; the preliminary identification of suspected pesticides was based on a special retention index/mass spectrum (RI/MS) library that contained both the first-stage mass spectra (MS(1) spectra) and retention indices; and the final confirmation was accomplished by accurate mass measurements of representative ions with their response ratios from the MS(1) spectra or representative product ions from the second-stage mass spectra (MS(2) spectra). To evaluate the applicability of the workflow in real samples, three matrices of apple, spinach, and scallion, each spiked with 165 test pesticides in a set of concentrations, were selected as the models. The results showed that the use of high-resolution TOF enabled effective extractions of spectra from noisy chromatograms, which was based on a narrow mass window (5 mDa) and suspected-target compounds identified by the similarity match of deconvoluted full mass spectra and filtering of linear RIs. On average, over 74% of pesticides at 50 ng/mL could be identified using deconvolution and the RI/MS library. Over 80% of pesticides at 5 ng/mL or lower concentrations could be confirmed in each matrix using at least two representative ions with their response ratios from the MS(1) spectra. In addition, the application of product ion spectra was capable of confirming suspected pesticides with specificity for some pesticides in complicated matrices. In conclusion, GC-QTOF MS combined with the RI/MS library seems to be one of the most efficient tools for the analysis of suspected-target pesticide residues

Using Prominence Mass Inferences in Different Coronal Lines to Obtain the He/H Abundance

NASA Technical Reports Server (NTRS)

Gilbert, Holly; Kilper, Gary; Alexander, David; Kucera, Therese

2008-01-01

In a previous study we developed a new technique for deriving prominence mass by observing how much coronal radiation in the Fe XI1 (lambda 195) spectral line is absorbed by prominence material. In the present work we apply this method, which allows us to consider the effects of both foreground and background radiation in our calculations, to a sample of prominences absorbing in a coronal line that ionizes both H and He (h < 504 Angstroms), and a line that ionizes only H (504 Angstroms < lambda < 911 Angstroms). This approach, first suggested by Kucera et al. (1998), permits the determination of the abundance ratio [He I]/[H I] of neutral helium and hydrogen in the prominence. This ratio should depend on how the prominence is formed, on its current thermodynamic state, and on its dynamical evolution. Thus, it may provide useful insights into the formation and evolution of prominences.

Using Prominence Mass Inferences in Different Coronal Lines to Obtain the He/H Abundance

NASA Technical Reports Server (NTRS)

Gilbert, Holly; Kilper, Gary; Alexander, David; Kucera, Therese

2009-01-01

In a previous study we developed a new technique for deriving prominence mass by observing how much coronal radiation in the Fe XII (lambda195) spectral Line is absorbed by prominence material. In the present work we apply this method. which allows us to consider the effects of both foreground and background radiation in our calculations, to a sample of prominences absorbing in a coronal line that ionizes both H and He (lambda < 504 Angstroms), and a line that ionizes only H (504 Angstroms < lambda < 911 Angstroms). This approach, first suggested by Mucera et al. (1998). permits the determination of the abundance ratio [He I]/[H I] of neutral helium and hydrogen in the prominence. This ratio should depend on how the prominence is formed, on its current thermodynamic state, and on its dynamical evolution. Thus, it may provide useful insights into the formation and evolution of prominences.

On-line double isotope dilution laser ablation inductively coupled plasma mass spectrometry for the quantitative analysis of solid materials.

PubMed

Fernández, Beatriz; Rodríguez-González, Pablo; García Alonso, J Ignacio; Malherbe, Julien; García-Fonseca, Sergio; Pereiro, Rosario; Sanz-Medel, Alfredo

2014-12-03

We report on the determination of trace elements in solid samples by the combination of on-line double isotope dilution and laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). The proposed method requires the sequential analysis of the sample and a certified natural abundance standard by on-line IDMS using the same isotopically-enriched spike solution. In this way, the mass fraction of the analyte in the sample can be directly referred to the certified standard so the previous characterization of the spike solution is not required. To validate the procedure, Sr, Rb and Pb were determined in certified reference materials with different matrices, including silicate glasses (SRM 610, 612 and 614) and powdered samples (PACS-2, SRM 2710a, SRM 1944, SRM 2702 and SRM 2780). The analysis of powdered samples was carried out both by the preparation of pressed pellets and by lithium borate fusion. Experimental results for the analysis of powdered samples were in agreement with the certified values for all materials. Relative standard deviations in the range of 6-21% for pressed pellets and 3-21% for fused solids were obtained from n=3 independent measurements. Minimal sample preparation, data treatment and consumption of the isotopically-enriched isotopes are the main advantages of the method over previously reported approaches. Copyright © 2014 Elsevier B.V. All rights reserved.

A Fully Redundant On-Line Mass Spectrometer System Used to Monitor Cryogenic Fuel Leaks on the Space Shuttle

NASA Technical Reports Server (NTRS)

Griffin, Timothy P.; Naylor, Guy R.; Haskell, William D.; Breznik, Greg S.; Mizell, Carolyn A.; Helms, William R.; Voska, N. (Technical Monitor)

2002-01-01

An on-line gas monitoring system was developed to replace the older systems used to monitor for cryogenic leaks on the Space Shuttles before launch. The system uses a mass spectrometer to monitor multiple locations in the process, which allows the system to monitor all gas constituents of interest in a nearly simultaneous manner. The system is fully redundant and meets all requirements for ground support equipment (GSE). This includes ruggedness to withstand launch on the Mobile Launcher Platform (MLP), ease of operation, and minimal operator intervention. The system can be fully automated so that an operator is notified when an unusual situation or fault is detected. User inputs are through personal computer using mouse and keyboard commands. The graphical user for detecting cryogenic leaks, many other gas constituents could be monitored using the Hazardous Gas Detection System (HGDS) 2000.

MiRNA-Target Interaction Reveals Cell-Specific Post-Transcriptional Regulation in Mammalian Cell Lines

PubMed Central

Kulkarni, Varun; Naqvi, Afsar Raza; Uttamani, Juhi Raju; Nares, Salvador

2016-01-01

MicroRNAs are 18–22 nucleotides long, non-coding RNAs that bind transcripts with complementary sequences leading to either mRNA degradation or translational suppression. However, the inherent differences in preferred mode of miRNA regulation among cells of different origin have not been examined. In our previous transcriptome profiling studies, we observed that post-transcriptional regulation can differ substantially depending on the cell in context. Here we examined mechanistic differences in the regulation of a let-7a targeted (wild type) or resistant (mutant) engineered renilla transcript across various mammalian cell lines of diverse origin. Dual luciferase assays show that compared to mutant (mut), the reporter gene containing wild type (wt) let-7a binding sites was efficiently suppressed upon transfection in various cell lines. Importantly, the strength of miRNA regulation varied across the cell lines. Total RNA analysis demonstrates that wt renilla mRNA was expressed to similar or higher levels compared to mut suggesting that translation repression is a predominant mode of miRNA regulation. Nonetheless, transcript degradation was observed in some cell lines. Ago-2 immunoprecipitation show that miRNA repressed renilla mRNA are associated with functional mi-RISC (miRNA-RNA induced silencing complex). Given the immense potential of miRNA as a therapeutic option, these findings highlight the necessity to thoroughly examine the mode of mRNA regulation in order to achieve the beneficial effects in targeting cells. PMID:26761000

Development of a Plutonium Ceramic Target for the MASHA Separator

NASA Astrophysics Data System (ADS)

Shaughnessy, D. A.; Moody, K. J.; Kenneally, J. M.; Wild, J. F.; Stoyer, M. A.; Lougheed, R. W.; Yeremin, A. V.; Oganessian, Yu. Ts.

2004-04-01

We are participating in the development of the target for the MASHA (Mass Analyzer of Super Heavy Atoms) on-line mass separator in Dubna. Along with recent upgrades of the U400 cyclotron, MASHA will provide for at least a ten-fold increase in the production- and-detection rate for element 114 atoms, and will allow us to measure their atomic masses precisely. The MASHA separator will employ a thick Pu ceramic target capa- ble of tolerating temperatures in the vicinity of 2000 C without vaporizing the actinide compound. Reaction products will diffuse out of the target and will drift to an ECR ion source after which they will be transported through the separator and will impinge on a position-sensitive focal-plane detector array. Furthermore, operation of the MASHA hot target/ion source combination will provide chemical volatility information that will support our assignment of an atomic number of 114 to these nuclei. Taken together, these experiments on MASHA will allow us to make measurements that will cement our identification of element 114 and provide for future experiments in which the chemical properties of the heaviest elements are studied.

Gas chromatography-mass spectrometric analysis of products from on-line pyrolysis/silylation of plant gums used as binding media

NASA Astrophysics Data System (ADS)

Chiantore, Oscar; Riedo, Chiara; Scalarone, Dominique

2009-07-01

Plant gums are complex polysaccharides used in the field of cultural heritage especially as binding media. Classification of polysaccharides may be achieved on the basis of monosaccharides composition after cleavage of glycosidic bond. Characterization of plant gums in works of art is complicated by the necessity of to use a method minimally invasive and requiring a small mount of sample. Pyrolisys is an useful method to obtain polysaccharides decomposition and generally pyrolysis products can be identified by the use of gas chromatography-mass spectrometry. This paper describes a method where two plant gums, arabic and tragacanth, were pyrolized in presence of silylating agents (HMDS e BSTFA alone and with TMCS as catalyst) using an on-line Py-GC/MS apparatus. Some characteristic trimethylsilyl derivatives of monosaccharides were identified on the basis of mass spectra. The presence of characteristic pyrolysis products of sugars allows to distinguish the two gums.

Metabolomics by Gas Chromatography-Mass Spectrometry: the combination of targeted and untargeted profiling

PubMed Central

Fiehn, Oliver

2016-01-01

Gas chromatography-mass spectrometry (GC-MS)-based metabolomics is ideal for identifying and quantitating small molecular metabolites (<650 daltons), including small acids, alcohols, hydroxyl acids, amino acids, sugars, fatty acids, sterols, catecholamines, drugs, and toxins, often using chemical derivatization to make these compounds volatile enough for gas chromatography. This unit shows that on GC-MS- based metabolomics easily allows integrating targeted assays for absolute quantification of specific metabolites with untargeted metabolomics to discover novel compounds. Complemented by database annotations using large spectral libraries and validated, standardized standard operating procedures, GC-MS can identify and semi-quantify over 200 compounds per study in human body fluids (e.g., plasma, urine or stool) samples. Deconvolution software enables detection of more than 300 additional unidentified signals that can be annotated through accurate mass instruments with appropriate data processing workflows, similar to liquid chromatography-MS untargeted profiling (LC-MS). Hence, GC-MS is a mature technology that not only uses classic detectors (‘quadrupole’) but also target mass spectrometers (‘triple quadrupole’) and accurate mass instruments (‘quadrupole-time of flight’). This unit covers the following aspects of GC-MS-based metabolomics: (i) sample preparation from mammalian samples, (ii) acquisition of data, (iii) quality control, and (iv) data processing. PMID:27038389

Identification of glyceollin metabolites derived from conjugation with glutathione and glucuronic acid in rats by on-line liquid chromatography-electrospray ionization tandem mass spectrometry

USDA-ARS?s Scientific Manuscript database

Glyceollin-related metabolites produced in rats following oral glyceollin administration were screened and identified by precursor and product ion scanning using liquid chromatography, coupled on-line with electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS), to identify all glyceollin me...

Targeted genome editing in a quail cell line using a customized CRISPR/Cas9 system.

PubMed

Ahn, Jinsoo; Lee, Joonbum; Park, Ju Yeon; Oh, Keon Bong; Hwang, Seongsoo; Lee, Chang-Won; Lee, Kichoon

2017-05-01

Soon after RNA-guided Cas9 (CRISPR-associated protein 9) endonuclease opened a new era of targeted genome editing, the CRISPR/Cas9 platform began to be extensively used to modify genes in various types of cells and organisms. However, successful CRISPR/Cas9-mediated insertion/deletion (indel) mutation remains to be demonstrated in avian cell lines. The objective of this study was to design a poultry-specific CRISPR/Cas9 system to efficiently introduce targeted deletion mutation in chromosomes of the quail muscle clone 7 (QM7) cell line using a customized quail CRISPR vector. In this study, two avian-specific promoters, quail 7SK (q7SK) promoter and CBh promoter, the hybrid form of cytomegalovirus and chicken β-actin promoters, were cloned into a CRISPR vector for the expression of guide RNA and Cas9 protein, respectively. Then, guide RNA, which was designed to target 20-base pair (bp) nucleotides in the quail melanophilin (MLPH) locus, was ligated to the modified CRISPR vector and transfected to QM7 cells. Our results showed multiple indel mutations in the quail MLPH locus in nearly half of the alleles being tested, suggesting the high efficiency of the system for targeted gene modification. The new CRISPR vector developed from this study has the potential application to generate knockout avian cell lines and knockout poultry. © 2016 Poultry Science Association Inc.

Single-epoch black hole mass estimators for broad-line active galactic nuclei: recalibrating Hβ with a new approach

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

Feng, Hua; Li, Hong; Shen, Yue

2014-10-10

Based on an updated Hβ reverberation mapping (RM) sample of 44 nearby active galactic nuclei (AGNs), we propose a novel approach for black hole (BH) mass estimation using two filtered luminosities computed from single-epoch (SE) AGN spectra around the Hβ region. We found that the two optimal-filter luminosities extract virial information (size and virial velocity of the broad-line region, BLR) from the spectra, justifying their usage in this empirical BH mass estimator. The major advantages of this new recipe over traditional SE BH mass estimators utilizing continuum luminosity and broad-line width are (1) it has a smaller intrinsic scatter ofmore » 0.28 dex calibrated against RM masses, (2) it is extremely simple to use in practice, without any need to decompose the spectrum, and (3) it produces unambiguous and highly repeatable results even with low signal-to-noise spectra. The combination of the two luminosities can also cancel out, to some extent, systematic luminosity errors potentially introduced by uncertainties in distance or flux calibration. In addition, we recalibrated the traditional SE mass estimators using broad Hβ FWHM and monochromatic continuum luminosity at 5100 Å (L {sub 5100}). We found that using the best-fit slopes on FWHM and L {sub 5100} (derived from fitting the BLR radius-luminosity relation and the correlation between rms line dispersion and SE FWHM, respectively) rather than simple assumptions (e.g., 0.5 for L {sub 5100} and 2 for FWHM) leads to more precise SE mass estimates, improving the intrinsic scatter from 0.41 dex to 0.36 dex with respect to the RM masses. We compared different estimators and discussed their applications to the Sloan Digital Sky Survey quasar sample. Due to the limitations of the current RM sample, application of any SE recipe calibrated against RM masses to distant quasars should be treated with caution.« less

3D printing of graphene-doped target for "matrix-free" laser desorption/ionization mass spectrometry.

PubMed

Wang, Dingyi; Huang, Xiu; Li, Jie; He, Bin; Liu, Qian; Hu, Ligang; Jiang, Guibin

2018-03-13

We report a graphene-doped resin target fabricated via a 3D printing technique for laser desorption/ionization mass spectrometry analysis. The graphene doped in the target acts as an inherent laser absorber and ionization promoter, thus permitting the direct analysis of samples without adding matrix. This work reveals a new strategy for easy designing and fabrication of functional mass spectrometry devices.

Simulation of dependence of the cross section of deuterons beam fragmentation into cumulative pions and protons on the mass of the target nucleus

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

Litvinenko, A. G., E-mail: alitvin@jinr.ru; Litvinenko, E. I.

2015-03-15

We have studied the mechanisms influencing production of cumulative pions and protons in the fragmentation of the incident deuterons into cumulative pions and protons emitted at zero angle. We argue that the peripheral dependence on the atomic mass of the target nucleus, which was obtained in the experiments for medium and heavy nuclei, can be explained by scattering on target nucleons without introducing additional parameters.

On-Line Fringe Tracking and Prediction at IOTA

NASA Technical Reports Server (NTRS)

Wilson, Edward; Mah, Robert; Lau, Sonie (Technical Monitor)

1999-01-01

The Infrared/Optical Telescope Array (IOTA) is a multi-aperture Michelson interferometer located on Mt. Hopkins near Tucson, Arizona. To enable viewing of fainter targets, an on-line fringe tracking system is presently under development at NASA Ames Research Center. The system has been developed off-line using actual data from IOTA, and is presently undergoing on-line implementation at IOTA. The system has two parts: (1) a fringe tracking system that identifies the center of a fringe packet by fitting a parametric model to the data; and (2) a fringe packet motion prediction system that uses characteristics of past fringe packets to predict fringe packet motion. Combined, this information will be used to optimize on-line the scanning trajectory, resulting in improved visibility of faint targets. Fringe packet identification is highly accurate and robust (99% of the 4000 fringe packets were identified correctly, the remaining 1% were either out of the scan range or too noisy to be seen) and is performed in 30-90 milliseconds on a Pentium II-based computer. Fringe packet prediction, currently performed using an adaptive linear predictor, delivers a 10% improvement over the baseline of predicting no motion.

On-line approaches for the determination of residues and contaminants in complex samples.

PubMed

Fumes, Bruno Henrique; Andrade, Mariane Aissa; Franco, Maraíssa Silva; Lanças, Fernando Mauro

2017-01-01

The determination of residues and contaminants in complex matrices such as in the case of food, environmental, and biological samples requires a combination of several steps to succeed in the aimed goal. At least three independent steps are integrated to provide the best available situation to deal with such matrices: (1) a sample preparation technique is employed to isolate the target compounds from the rest of the matrix; (2) a chromatographic (second) step further "purifies" the isolated compounds from the co-extracted matrix interferences; (3) a spectroscopy-based device acts as chromatographic detector (ideally containing a tandem high-resolution mass analyzer) for the qualitative and quantitative analysis. These techniques can be operated in different modes including the off-line and the on-line modes. The present report focus the on-line coupling techniques aiming the determination of analytes present in complex matrices. The fundamentals of these approaches as well as the most common set ups are presented and discussed, as well as a review on the recent applications of these two approaches to the fields of bioanalytical, environmental, and food analysis are critically discussed. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quantitative targeted and retrospective data analysis of relevant pesticides, antibiotics and mycotoxins in bakery products by liquid chromatography-single-stage Orbitrap mass spectrometry.

PubMed

De Dominicis, Emiliano; Commissati, Italo; Gritti, Elisa; Catellani, Dante; Suman, Michele

2015-01-01

In addition to 'traditional' multi-residue and multi-contaminant multiple reaction monitoring (MRM) mass spectrometric techniques devoted to quantifying a list of targeted compounds, the global food industry requires non-targeted methods capable of detecting other possible potentially hazardous compounds. Ultra-high-performance liquid chromatography combined with a single-stage Orbitrap high-resolution mass spectrometer (UHPLC-HRMS Exactive™-Orbitrap Technology) was successfully exploited for the complete selective and quantitative determination of 33 target compounds within three major cross categories (pesticides, antibiotics and mycotoxins) in bakery matrices (specifically milk, wheat flour and mini-cakes). Resolution was set at 50 000 full width at half maximum (FWHM) to achieve the right compromise between an adequate scan speed and selectivity, allowing for the limitations related to the necessary generic sample preparation approach. An exact mass with tolerance of 5 ppm and minimum peak threshold of 10 000 units were fixed as the main identification conditions, including retention time and isotopic pattern as additional criteria devoted to greatly reducing the risk of false-positive findings. The full validation for all the target analytes was performed: linearity, intermediate repeatability and recovery (28 analytes within 70-120%) were positively assessed; furthermore, limits of quantification between 5 and 100 µg kg(-1) (with most of the analytes having a limit of detection below 6 µg kg(-1)) indicate good performance, which is compatible with almost all the regulatory needs. Naturally contaminated and fortified mini-cakes, prepared through combined use of industrial and pilot plant production lines, were analysed at two different concentration levels, obtaining good overall quantitative results and providing preliminary indications of the potential of full-scan HRMS cluster analysis. The effectiveness of this analytical approach was also tested in

33 CFR 334.60 - Cape Cod Bay south of Wellfleet Harbor, Mass.; naval aircraft bombing target area.

Code of Federal Regulations, 2010 CFR

2010-07-01

... Harbor, Mass.; naval aircraft bombing target area. 334.60 Section 334.60 Navigation and Navigable Waters... REGULATIONS § 334.60 Cape Cod Bay south of Wellfleet Harbor, Mass.; naval aircraft bombing target area. (a... bombing target hulk James Longstreet in Cape Cod Bay at latitude 41°49′46″, longitude 70°02′54″. (b) The...

33 CFR 334.60 - Cape Cod Bay south of Wellfleet Harbor, Mass.; naval aircraft bombing target area.

Code of Federal Regulations, 2011 CFR

2011-07-01

... Harbor, Mass.; naval aircraft bombing target area. 334.60 Section 334.60 Navigation and Navigable Waters... REGULATIONS § 334.60 Cape Cod Bay south of Wellfleet Harbor, Mass.; naval aircraft bombing target area. (a... bombing target hulk James Longstreet in Cape Cod Bay at latitude 41°49′46″, longitude 70°02′54″. (b) The...

Stringent Constraints on Fundamental Constant Evolution Using Conjugate 18 cm Satellite OH Lines

NASA Astrophysics Data System (ADS)

Kanekar, Nissim; Ghosh, Tapasi; Chengalur, Jayaram N.

2018-02-01

We have used the Arecibo Telescope to carry out one of the deepest-ever integrations in radio astronomy, targeting the redshifted conjugate satellite OH 18 cm lines at z ≈0.247 towards PKS 1413 +135 . The satellite OH 1720 and 1612 MHz lines are, respectively, in emission and absorption, with exactly the same line shapes due to population inversion in the OH ground state levels. Since the 1720 and 1612 MHz line rest frequencies have different dependences on the fine structure constant α and the proton-electron mass ratio μ , a comparison between their measured redshifts allows one to probe changes in α and μ with cosmological time. In the case of conjugate satellite OH 18 cm lines, the predicted perfect cancellation of the sum of the line optical depths provides a strong test for the presence of systematic effects that might limit their use in probing fundamental constant evolution. A nonparametric analysis of our new Arecibo data yields [Δ X /X ] =(+0.97 ±1.52 )×10-6 , where X ≡μ α2 . Combining this with our earlier results from the Arecibo Telescope and the Westerbork Synthesis Radio Telescope, we obtain [Δ X /X ] =(-1.0 ±1.3 )×10-6 , consistent with no changes in the quantity μ α2 over the last 2.9 Gyr. This is the most stringent present constraint on fractional changes in μ α2 from astronomical spectroscopy, and with no evidence for systematic effects.

Ablation mass features in multi-pulses femtosecond laser ablate molybdenum target

NASA Astrophysics Data System (ADS)

Zhao, Dongye; Gierse, Niels; Wegner, Julian; Pretzler, Georg; Oelmann, Jannis; Brezinsek, Sebastijan; Liang, Yunfeng; Neubauer, Olaf; Rasinski, Marcin; Linsmeier, Christian; Ding, Hongbin

2018-03-01

In this study, the ablation mass features related to reflectivity of bulk Molybdenum (Mo) were investigated by a Ti: Sa 6 fs laser pulse at central wavelength 790 nm. The ablated mass removal was determined using Confocal Microscopy (CM) technique. The surface reflectivity was calibrated and measured by a Lambda 950 spectrophotometer as well as a CCD camera during laser ablation. The ablation mass loss per pulse increase with the increasing of laser shots, meanwhile the surface reflectivity decrease. The multi-pulses (100 shots) ablation threshold of Mo was determined to be 0.15 J/cm2. The incubation coefficient was estimated as 0.835. The reflectivity change of the Mo target surface following multi-pulses laser ablation were studied as a function of laser ablation shots at various laser fluences from 1.07 J/cm2 to 36.23 J/cm2. The results of measured reflectivity indicate that surface reflectivity of Mo target has a significant decline in the first 3-laser pulses at the various fluences. These results are important for developing a quantitative analysis model for laser induced ablation and laser induced breakdown spectroscopy for the first wall diagnosis of EAST tokamak.

Seismic constraints on rotation of Sun-like star and mass of exoplanet.

PubMed

Gizon, Laurent; Ballot, Jérome; Michel, Eric; Stahn, Thorsten; Vauclair, Gérard; Bruntt, Hans; Quirion, Pierre-Olivier; Benomar, Othman; Vauclair, Sylvie; Appourchaux, Thierry; Auvergne, Michel; Baglin, Annie; Barban, Caroline; Baudin, Fréderic; Bazot, Michaël; Campante, Tiago; Catala, Claude; Chaplin, William; Creevey, Orlagh; Deheuvels, Sébastien; Dolez, Noël; Elsworth, Yvonne; García, Rafael; Gaulme, Patrick; Mathis, Stéphane; Mathur, Savita; Mosser, Benoît; Régulo, Clara; Roxburgh, Ian; Salabert, David; Samadi, Réza; Sato, Kumiko; Verner, Graham; Hanasoge, Shravan; Sreenivasan, Katepalli R

2013-08-13

Rotation is thought to drive cyclic magnetic activity in the Sun and Sun-like stars. Stellar dynamos, however, are poorly understood owing to the scarcity of observations of rotation and magnetic fields in stars. Here, inferences are drawn on the internal rotation of a distant Sun-like star by studying its global modes of oscillation. We report asteroseismic constraints imposed on the rotation rate and the inclination of the spin axis of the Sun-like star HD 52265, a principal target observed by the CoRoT satellite that is known to host a planetary companion. These seismic inferences are remarkably consistent with an independent spectroscopic observation (rotational line broadening) and with the observed rotation period of star spots. Furthermore, asteroseismology constrains the mass of exoplanet HD 52265b. Under the standard assumption that the stellar spin axis and the axis of the planetary orbit coincide, the minimum spectroscopic mass of the planet can be converted into a true mass of 1.85(-0.42)(+0.52)M(Jupiter), which implies that it is a planet, not a brown dwarf.

Seismic constraints on rotation of Sun-like star and mass of exoplanet

PubMed Central

Gizon, Laurent; Ballot, Jérome; Michel, Eric; Stahn, Thorsten; Vauclair, Gérard; Bruntt, Hans; Quirion, Pierre-Olivier; Benomar, Othman; Vauclair, Sylvie; Appourchaux, Thierry; Auvergne, Michel; Baglin, Annie; Barban, Caroline; Baudin, Fréderic; Bazot, Michaël; Campante, Tiago; Catala, Claude; Chaplin, William; Creevey, Orlagh; Deheuvels, Sébastien; Dolez, Noël; Elsworth, Yvonne; García, Rafael; Gaulme, Patrick; Mathis, Stéphane; Mathur, Savita; Mosser, Benoît; Régulo, Clara; Roxburgh, Ian; Salabert, David; Samadi, Réza; Sato, Kumiko; Verner, Graham; Hanasoge, Shravan; Sreenivasan, Katepalli R.

2013-01-01

Rotation is thought to drive cyclic magnetic activity in the Sun and Sun-like stars. Stellar dynamos, however, are poorly understood owing to the scarcity of observations of rotation and magnetic fields in stars. Here, inferences are drawn on the internal rotation of a distant Sun-like star by studying its global modes of oscillation. We report asteroseismic constraints imposed on the rotation rate and the inclination of the spin axis of the Sun-like star HD 52265, a principal target observed by the CoRoT satellite that is known to host a planetary companion. These seismic inferences are remarkably consistent with an independent spectroscopic observation (rotational line broadening) and with the observed rotation period of star spots. Furthermore, asteroseismology constrains the mass of exoplanet HD 52265b. Under the standard assumption that the stellar spin axis and the axis of the planetary orbit coincide, the minimum spectroscopic mass of the planet can be converted into a true mass of , which implies that it is a planet, not a brown dwarf. PMID:23898183

Reagent Precoated Targets for Rapid In-Tissue Derivatization of the Anti-Tuberculosis Drug Isoniazid Followed by MALDI Imaging Mass Spectrometry

NASA Astrophysics Data System (ADS)

Manier, M. Lisa; Reyzer, Michelle L.; Goh, Anne; Dartois, Veronique; Via, Laura E.; Barry, Clifton E.; Caprioli, Richard M.

2011-08-01

Isoniazid (INH) is an important component of front-line anti-tuberculosis therapy with good serum pharmacokinetics but unknown ability to penetrate tuberculous lesions. However, endogenous background interferences hinder our ability to directly analyze INH in tissues. Chemical derivatization has been successfully used to measure isoniazid directly from tissue samples using matrix-assisted laser desorption/ionization (MALDI) imaging mass spectrometry (IMS). MALDI targets were pretreated with trans-cinnamaldehyde (CA) prior to mounting tissue slices. Isoniazid present in the tissues was efficiently derivatized and the INH-CA product measured by MS/MS. Precoating of MALDI targets allows the tissues to be directly thaw-mounted and derivatized, thus simplifying the preparation. A time-course series of tissues from tuberculosis infected/INH dosed animals were assayed and the MALDI MS/MS response correlates well with the amount of INH determined to be in the tissues by high-performance liquid chromatography (HPLC)-MS/MS.

microMS: A Python Platform for Image-Guided Mass Spectrometry Profiling

NASA Astrophysics Data System (ADS)

Comi, Troy J.; Neumann, Elizabeth K.; Do, Thanh D.; Sweedler, Jonathan V.

2017-09-01

Image-guided mass spectrometry (MS) profiling provides a facile framework for analyzing samples ranging from single cells to tissue sections. The fundamental workflow utilizes a whole-slide microscopy image to select targets of interest, determine their spatial locations, and subsequently perform MS analysis at those locations. Improving upon prior reported methodology, a software package was developed for working with microscopy images. microMS, for microscopy-guided mass spectrometry, allows the user to select and profile diverse samples using a variety of target patterns and mass analyzers. Written in Python, the program provides an intuitive graphical user interface to simplify image-guided MS for novice users. The class hierarchy of instrument interactions permits integration of new MS systems while retaining the feature-rich image analysis framework. microMS is a versatile platform for performing targeted profiling experiments using a series of mass spectrometers. The flexibility in mass analyzers greatly simplifies serial analyses of the same targets by different instruments. The current capabilities of microMS are presented, and its application for off-line analysis of single cells on three distinct instruments is demonstrated. The software has been made freely available for research purposes. [Figure not available: see fulltext.

microMS: A Python Platform for Image-Guided Mass Spectrometry Profiling.

PubMed

Comi, Troy J; Neumann, Elizabeth K; Do, Thanh D; Sweedler, Jonathan V

2017-09-01

Image-guided mass spectrometry (MS) profiling provides a facile framework for analyzing samples ranging from single cells to tissue sections. The fundamental workflow utilizes a whole-slide microscopy image to select targets of interest, determine their spatial locations, and subsequently perform MS analysis at those locations. Improving upon prior reported methodology, a software package was developed for working with microscopy images. microMS, for microscopy-guided mass spectrometry, allows the user to select and profile diverse samples using a variety of target patterns and mass analyzers. Written in Python, the program provides an intuitive graphical user interface to simplify image-guided MS for novice users. The class hierarchy of instrument interactions permits integration of new MS systems while retaining the feature-rich image analysis framework. microMS is a versatile platform for performing targeted profiling experiments using a series of mass spectrometers. The flexibility in mass analyzers greatly simplifies serial analyses of the same targets by different instruments. The current capabilities of microMS are presented, and its application for off-line analysis of single cells on three distinct instruments is demonstrated. The software has been made freely available for research purposes. Graphical Abstract ᅟ.

Solvent system selectivities in countercurrent chromatography using Salicornia gaudichaudiana metabolites as practical example with off-line electrospray mass-spectrometry injection profiling.

PubMed

Costa, Fernanda das Neves; Jerz, Gerold; Figueiredo, Fabiana de Souza; Winterhalter, Peter; Leitão, Gilda Guimarães

2015-03-13

For the development of an efficient two-stage isolation process for high-speed countercurrent chromatography (HSCCC) with focus on principal metabolites from the ethyl acetate extract of the halophyte plant Salicornia gaudichaudiana, separation selectivities of two different biphasic solvent systems with similar polarities were evaluated using the elution and extrusion approach. Efficiency in isolation of target compounds is determined by the solvent system selectivity and their chronological use in multiple separation steps. The system n-hexane-ethyl acetate-methanol-water (0.5:6:0.5:6, v/v/v/v) resulted in a comprehensive separation of polyphenolic glycosides. The system n-hexane-n-butanol-water (1:1:2, v/v/v) was less universal but was highly efficient in the fractionation of positional isomers such as di-substituted cinnamic acid quinic acid derivatives. Multiple metabolite detection performed on recovered HSCCC tube fractions was done with rapid mass-spectrometry profiling by sequential off-line injections to electrospray mass-spectrometry (ESI-MS/MS). Selective ion traces of metabolites delivered reconstituted preparative HSCCC runs. Molecular weight distribution of target compounds in single HSCCC tube fractions and MS/MS fragment data were available. Chromatographic areas with strong co-elution effects and fractions of pure recoverable compounds were visualized. In total 11 metabolites have been identified and monitored. Result of this approach was a fast isolation protocol for S. gaudichaudiana metabolites using two solvent systems in a strategic sequence. The process could easily be scaled-up to larger lab-scale or industrial recovery. Copyright © 2015 Elsevier B.V. All rights reserved.

Improved methods of AAV-mediated gene targeting for human cell lines using ribosome-skipping 2A peptide

PubMed Central

Karnan, Sivasundaram; Ota, Akinobu; Konishi, Yuko; Wahiduzzaman, Md; Hosokawa, Yoshitaka; Konishi, Hiroyuki

2016-01-01

The adeno-associated virus (AAV)-based targeting vector has been one of the tools commonly used for genome modification in human cell lines. It allows for relatively efficient gene targeting associated with 1–4-log higher ratios of homologous-to-random integration of targeting vectors (H/R ratios) than plasmid-based targeting vectors, without actively introducing DNA double-strand breaks. In this study, we sought to improve the efficiency of AAV-mediated gene targeting by introducing a 2A-based promoter-trap system into targeting constructs. We generated three distinct AAV-based targeting vectors carrying 2A for promoter trapping, each targeting a GFP-based reporter module incorporated into the genome, PIGA exon 6 or PIGA intron 5. The absolute gene targeting efficiencies and H/R ratios attained using these vectors were assessed in multiple human cell lines and compared with those attained using targeting vectors carrying internal ribosome entry site (IRES) for promoter trapping. We found that the use of 2A for promoter trapping increased absolute gene targeting efficiencies by 3.4–28-fold and H/R ratios by 2–5-fold compared to values obtained with IRES. In CRISPR-Cas9-assisted gene targeting using plasmid-based targeting vectors, the use of 2A did not enhance the H/R ratios but did upregulate the absolute gene targeting efficiencies compared to the use of IRES. PMID:26657635

Target prices for mass production of tyrosine kinase inhibitors for global cancer treatment

PubMed Central

Hill, Andrew; Gotham, Dzintars; Fortunak, Joseph; Meldrum, Jonathan; Erbacher, Isabelle; Martin, Manuel; Shoman, Haitham; Levi, Jacob; Powderly, William G; Bower, Mark

2016-01-01

Objective To calculate sustainable generic prices for 4 tyrosine kinase inhibitors (TKIs). Background TKIs have proven survival benefits in the treatment of several cancers, including chronic myeloid leukaemia, breast, liver, renal and lung cancer. However, current high prices are a barrier to treatment. Mass production of low-cost generic antiretrovirals has led to over 13 million people being on HIV/AIDS treatment worldwide. This analysis estimates target prices for generic TKIs, assuming similar methods of mass production. Methods Four TKIs with patent expiry dates in the next 5 years were selected for analysis: imatinib, erlotinib, lapatinib and sorafenib. Chemistry, dosing, published data on per-kilogram pricing for commercial transactions of active pharmaceutical ingredient (API), and quotes from manufacturers were used to estimate costs of production. Analysis included costs of excipients, formulation, packaging, shipping and a 50% profit margin. Target prices were compared with current prices. Global numbers of patients eligible for treatment with each TKI were estimated. Results API costs per kg were $347–$746 for imatinib, $2470 for erlotinib, $4671 for lapatinib, and $3000 for sorafenib. Basing on annual dose requirements, costs of formulation/packaging and a 50% profit margin, target generic prices per person-year were $128–$216 for imatinib, $240 for erlotinib, $1450 for sorafenib, and $4020 for lapatinib. Over 1 million people would be newly eligible to start treatment with these TKIs annually. Conclusions Mass generic production of several TKIs could achieve treatment prices in the range of $128–$4020 per person-year, versus current US prices of $75161–$139 138. Generic TKIs could allow significant savings and scaling-up of treatment globally, for over 1 million eligible patients. PMID:26817636

Target prices for mass production of tyrosine kinase inhibitors for global cancer treatment.

PubMed

Hill, Andrew; Gotham, Dzintars; Fortunak, Joseph; Meldrum, Jonathan; Erbacher, Isabelle; Martin, Manuel; Shoman, Haitham; Levi, Jacob; Powderly, William G; Bower, Mark

2016-01-27

To calculate sustainable generic prices for 4 tyrosine kinase inhibitors (TKIs). TKIs have proven survival benefits in the treatment of several cancers, including chronic myeloid leukaemia, breast, liver, renal and lung cancer. However, current high prices are a barrier to treatment. Mass production of low-cost generic antiretrovirals has led to over 13 million people being on HIV/AIDS treatment worldwide. This analysis estimates target prices for generic TKIs, assuming similar methods of mass production. Four TKIs with patent expiry dates in the next 5 years were selected for analysis: imatinib, erlotinib, lapatinib and sorafenib. Chemistry, dosing, published data on per-kilogram pricing for commercial transactions of active pharmaceutical ingredient (API), and quotes from manufacturers were used to estimate costs of production. Analysis included costs of excipients, formulation, packaging, shipping and a 50% profit margin. Target prices were compared with current prices. Global numbers of patients eligible for treatment with each TKI were estimated. API costs per kg were $347-$746 for imatinib, $2470 for erlotinib, $4671 for lapatinib, and $3000 for sorafenib. Basing on annual dose requirements, costs of formulation/packaging and a 50% profit margin, target generic prices per person-year were $128-$216 for imatinib, $240 for erlotinib, $1450 for sorafenib, and $4020 for lapatinib. Over 1 million people would be newly eligible to start treatment with these TKIs annually. Mass generic production of several TKIs could achieve treatment prices in the range of $128-$4020 per person-year, versus current US prices of $75161-$139,138. Generic TKIs could allow significant savings and scaling-up of treatment globally, for over 1 million eligible patients. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Ga2O3 photocatalyzed on-line tagging of cysteine to facilitate peptide mass fingerprinting.

PubMed

Qiao, Liang; Su, Fangzheng; Bi, Hongyan; Girault, Hubert H; Liu, Baohong

2011-09-01

β-Ga(2)O(3) is a wide-band-gap semiconductor having strong oxidation ability under light irradiation. Herein, the steel target plates modified with β-Ga(2)O(3) nanoparticles have been developed to carry out in-source photo-catalytic oxidative reactions for online peptide tagging during laser desorption/ionization mass spectrometry (LDI-MS) analysis. Under UV laser irradiation, β-Ga(2)O(3) can catalyze the photo-oxidation of 2-methoxyhydroquinone added to a sample mixture to 2-methoxy benzoquinone that can further react with the thiol groups of cysteine residues by Michael addition reaction. The tagging process leads to appearance of pairs of peaks with an m/z shift of 138.1Th. This online labelling strategy is demonstrated to be sensitive and efficient with a detection-limit at femtomole level. Using the strategy, the information on cysteine content in peptides can be obtained together with peptide mass, therefore constraining the database searching for an advanced identification of cysteine-containing proteins from protein mixtures. The current peptide online tagging method can be important for specific analysis of cysteine-containing proteins especially the low-abundant ones that cannot be completely isolated from other high-abundant non-cysteine-proteins. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Dynamic evolution of recurrent mass ejections observed in H-alpha and C IV lines

NASA Technical Reports Server (NTRS)

Schmieder, B.; Mein, P.; Martres, M. J.; Tandberg-Hanssen, E.

1984-01-01

The mass ejections of 1 September, 1980 are studied from observations obtained with the MSDP spectrograph and with the Ultraviolet Spectrometer and Polarimeter aboard the Solar Maximum Mission satellite. The analysis is focused on observations in the chromospheric H-alpha line and the transition region C IV 1548 A line. It is noted that cold and hot material had the same projection, although the upward C IV velocity structure was more extended than the H-alpha one. It is shown that the observed contrast of the H-alpha absorbing structure can be interpreted in terms of a dynamic cloud model overlying the chromosphere. Radial velocities of 25-30 km/s and -40 km/s are estimated for the first and second phases of ejection, respectively.

BEAM ON TARGET MODEL Produces All Gamma Ray Burst Phenomena Including Afterglow

NASA Astrophysics Data System (ADS)

Greyber, H.

2000-12-01

While one must applaud the splendid research by L. Piro et al and L. Amati et al reported in SCIENCE recently, one must question, as M. Rees and S. Woolsey have done, their conclusion that a ``supranova model" is the only explanation for these new X-ray observations. In fact L. Piro was quoted as saying, ``Our data helps rule out the scenario where two neutron stars or black holes collide. We think GRBs result from something similar to a supernova explosion, but much more powerful." A relatively unknown physical model for GRBs, Greyber's Beam On Target model (BOT), dating back to the first CGRO observations, can plausibly explain the iron emission lines observed for GRB991216, and also the mass of the dense medium within a light-day of the GRB being roughly equivalent to at least one-tenth solar mass, as well as the initial shedding of material followed by the GRB event. When a galaxy forms under gravitational collapse in the presence of a primordial magnetic field, Mestel and Strittmatter demonstrated that, for finite Ohmic diffusion, a growing equatorial current loop is formed. Even if this stable ``Storage Ring" has only 10exp-9 of the total energy released during a typical galaxy's formation, the relativistic beam can possess 10exp58 ergs. The GRB ``fireball" occurs when a target star races across the powerful beam, blowing off target material as a hot, rapidly expanding plasma cloud, simulating an explosion. Since currents in space are known to be sometimes filamentary, sharp millisecond spikes can be expected in some GRBs. Proton and alpha particle nuclear reactions produce a gamma ray beam. Beam particles impinging on denser cloud material create an electromagnetic shower, producing X-ray, optical and radio radiation. Since the Storage Ring has an intense magnetic field around it, synchrotron radiation is expected. The beam, striking a highly evolved massive target star, produces the iron emission lines. H. D. Greyber, in ``After the Dark Ages:When Galaxies

Continuous-flow liquid microjunction surface sampling probe connected on-line with high-performance liquid chromatography/mass spectrometry for spatially resolved analysis of small molecules and proteins.

PubMed

Van Berkel, Gary J; Kertesz, Vilmos

2013-06-30

A continuous-flow liquid microjunction surface sampling probe extracts soluble material from surfaces for direct ionization and detection by mass spectrometry. Demonstrated here is the on-line coupling of such a probe with high-performance liquid chromatography/mass spectrometry (HPLC/MS) enabling extraction, separation and detection of small molecules and proteins from surfaces in a spatially resolved (~0.5 mm diameter spots) manner. A continuous-flow liquid microjunction surface sampling probe was connected to a six-port, two-position valve for extract collection and injection to an HPLC column. A QTRAP® 5500 hybrid triple quadrupole linear ion trap equipped with a Turbo V™ ion source operated in positive electrospray ionization (ESI) mode was used for all experiments. The system operation was tested with the extraction, separation and detection of propranolol and associated metabolites from drug dosed tissues, caffeine from a coffee bean, cocaine from paper currency, and proteins from dried sheep blood spots on paper. Confirmed in the tissue were the parent drug and two different hydroxypropranolol glucuronides. The mass spectrometric response for these compounds from different locations in the liver showed an increase with increasing extraction time (5, 20 and 40 s). For on-line separation and detection/identification of extracted proteins from dried sheep blood spots, two major protein peaks dominated the chromatogram and could be correlated with the expected masses for the hemoglobin α and β chains. Spatially resolved sampling, separation, and detection of small molecules and proteins from surfaces can be accomplished using a continuous-flow liquid microjunction surface sampling probe coupled on-line with HPLC/MS detection. Published in 2013. This article is a U.S. Government work and is in the public domain in the USA.

D 2 and DT Liquid-Layer Target Shots on NIF

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

Walters, Curtis; Alger, Ethan; Bhandarkar, Suhas

Experiments at the National Ignition Facility (NIF) using targets containing a Deuterium-Tritium (DT) fuel layer have, until recently, required that a high-quality layer of solid deuterium-tritium (herein referred to as an "ice-layer") be formed in the capsule. The development of a process to line the inner surface of a target capsule with a foam layer of a thickness that is typical of icelayers has resulted in the ability to field targets with liquid layers wetting the foam. Successful fielding of liquid-layer targets on NIF required not only a foam lined capsule, but also changes to the capsule filling process andmore » the manner with which the inventory is maintained in the capsule. Additionally, changes to target heater power and the temperature drops across target components were required in order to achieve the desired range of shot temperatures. These changes, and the target's performance during four target shots on NIF will be discussed.« less

Third-line Targeted Therapy in Metastatic Renal Cell Carcinoma: Results from the International Metastatic Renal Cell Carcinoma Database Consortium.

PubMed

Wells, J Connor; Stukalin, Igor; Norton, Craig; Srinivas, Sandy; Lee, Jae Lyun; Donskov, Frede; Bjarnason, Georg A; Yamamoto, Haru; Beuselinck, Benoit; Rini, Brian I; Knox, Jennifer J; Agarwal, Neeraj; Ernst, D Scott; Pal, Sumanta K; Wood, Lori A; Bamias, Aristotelis; Alva, Ajjai S; Kanesvaran, Ravindran; Choueiri, Toni K; Heng, Daniel Y C

2017-02-01

The use of third-line targeted therapy (TTT) in metastatic renal cell carcinoma (mRCC) is not well characterized and varies due to the lack of robust data to guide treatment decisions. This study examined the use of third-line therapy in a large international population. To evaluate the use and efficacy of targeted therapy in a third-line setting. Twenty-five international cancer centers provided consecutive data on 4824 mRCC patients who were treated with an approved targeted therapy. One thousand and twelve patients (21%) received TTT and were included in the analysis. Patients were analyzed for overall survival (OS) and progression-free survival using Kaplan-Meier curves, and were evaluated for overall response. Cox regression analyses were used to determine the statistical association between OS and the six factors included in the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) prognostic model. Subgroup analysis was performed on patients stratified by their IMDC prognostic risk status. Everolimus was the most prevalent third-line therapy (27.5%), but sunitinib, sorafenib, pazopanib, temsirolimus, and axitinib were all utilized in over ≥9% of patients. Patients receiving any TTT had an OS of 12.4 mo, a progression-free survival of 3.9 mo, and 61.1% of patients experienced an overall response of stable disease or better. Patients not receiving TTT had an OS of 2.1 mo. Patients with favorable- (7.2%) or intermediate-risk (65.3%) disease had the highest OS with TTT, 29.9 mo and 15.5 mo, respectively, while poor-risk (27.5%) patients survived 5.5 mo. Results are limited by the retrospective nature of the study. TTT remains highly heterogeneous. The IMDC prognostic criteria can be used to stratify third-line patients. TTT use in favorable- and intermediate-risk patients was associated with the greatest OS. Patients with favorable- and intermediate-prognostic criteria disease treated with third-line targeted therapy have an associated

Planning an effective anti-smoking mass media campaign targeting adolescents.

PubMed

Pechmann, C; Reibling, E T

2000-05-01

This article addresses the following issues: Can an anti-smoking campaign that depends largely on mass media vehicles effectively reduce adolescent tobacco use? Why is an integrated campaign recommended and what are the steps in designing such a campaign? How should the campaign be evaluated? Specific topics include recommended campaign expenditures, target audience identification, selection of persuasive message content, executional (stylistic) considerations, media buying decisions, the use of focus group research and advertising copy-testing research, and outcome evaluations. It is concluded that comprehensive strategic planning and extensive research at all phases of the campaign are essential to success.

THE LICK AGN MONITORING PROJECT: BROAD-LINE REGION RADII AND BLACK HOLE MASSES FROM REVERBERATION MAPPING OF Hbeta

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

Bentz, Misty C.; Walsh, Jonelle L.; Barth, Aaron J.

2009-11-01

We have recently completed a 64-night spectroscopic monitoring campaign at the Lick Observatory 3-m Shane telescope with the aim of measuring the masses of the black holes in 12 nearby (z < 0.05) Seyfert 1 galaxies with expected masses in the range approx10{sup 6}-10{sup 7} M {sub sun} and also the well-studied nearby active galactic nucleus (AGN) NGC 5548. Nine of the objects in the sample (including NGC 5548) showed optical variability of sufficient strength during the monitoring campaign to allow for a time lag to be measured between the continuum fluctuations and the response to these fluctuations in themore » broad Hbeta emission. We present here the light curves for all the objects in this sample and the subsequent Hbeta time lags for the nine objects where these measurements were possible. The Hbeta lag time is directly related to the size of the broad-line region (BLR) in AGNs, and by combining the Hbeta lag time with the measured width of the Hbeta emission line in the variable part of the spectrum, we determine the virial mass of the central supermassive black hole in these nine AGNs. The absolute calibration of the black hole masses is based on the normalization derived by Onken et al., which brings the masses determined by reverberation mapping into agreement with the local M {sub BH}-sigma{sub *}relationship for quiescent galaxies. We also examine the time lag response as a function of velocity across the Hbeta line profile for six of the AGNs. The analysis of four leads to rather ambiguous results with relatively flat time lags as a function of velocity. However, SBS 1116+583A exhibits a symmetric time lag response around the line center reminiscent of simple models for circularly orbiting BLR clouds, and Arp 151 shows an asymmetric profile that is most easily explained by a simple gravitational infall model. Further investigation will be necessary to fully understand the constraints placed on the physical models of the BLR by the velocity

Modular cell-internalizing aptamer nanostructure enables targeted delivery of large functional RNAs in cancer cell lines.

PubMed

Porciani, David; Cardwell, Leah N; Tawiah, Kwaku D; Alam, Khalid K; Lange, Margaret J; Daniels, Mark A; Burke, Donald H

2018-06-11

Large RNAs and ribonucleoprotein complexes have powerful therapeutic potential, but effective cell-targeted delivery tools are limited. Aptamers that internalize into target cells can deliver siRNAs (<15 kDa, 19-21 nt/strand). We demonstrate a modular nanostructure for cellular delivery of large, functional RNA payloads (50-80 kDa, 175-250 nt) by aptamers that recognize multiple human B cell cancer lines and transferrin receptor-expressing cells. Fluorogenic RNA reporter payloads enable accelerated testing of platform designs and rapid evaluation of assembly and internalization. Modularity is demonstrated by swapping in different targeting and payload aptamers. Both modules internalize into leukemic B cell lines and remained colocalized within endosomes. Fluorescence from internalized RNA persists for ≥2 h, suggesting a sizable window for aptamer payloads to exert influence upon targeted cells. This demonstration of aptamer-mediated, cell-internalizing delivery of large RNAs with retention of functional structure raises the possibility of manipulating endosomes and cells by delivering large aptamers and regulatory RNAs.

Supercritical fluid extraction (SFE) of ketamine metabolites from dried urine and on-line quantification by supercritical fluid chromatography and single mass detection (on-line SFE-SFC-MS).

PubMed

Hofstetter, Robert; Fassauer, Georg M; Link, Andreas

2018-02-15

On-line solid-phase supercritical fluid extraction (SFE) and chromatography (SFC) coupled to mass spectrometry (MS) has been evaluated for its usefulness with respect to metabolic profiling and pharmacological investigations of ketamine in humans. The aim of this study was to develop and validate a rapid, highly selective and sensitive SFE-SFC-MS method for the quantification of ketamine and its metabolites in miniature amounts in human urine excluding liquid-liquid extraction (LLE). Several conditions were optimized systematically following the requirements of the European Medicines Agency: selectivity, carry-over, calibration curve parameters (LLOQ, range and linearity), within- and between-run accuracy and precision, dilution integrity, matrix effect, and stability. The method, which required a relatively small volume of human urine (20 μL per sample), was validated for pharmacologically and toxicologically relevant concentrations ranging from 25.0 to 1000 ng/mL (r 2  > 0.995). The lower limit of quantification (LLOQ) for all compounds was found to be as low as 0.5 ng. In addition, stability of analytes during removal of water from the urine samples using different conditions (filter paper or ISOLUTE® HM-N) was studied. In conclusion, the method developed in this study can be successfully applied to studies of ketamine metabolites in humans, and may pave the way for routine application of on-line SFE-SFC-MS in clinical investigations. Copyright © 2018 Elsevier B.V. All rights reserved.

False-positive rate determination of protein target discovery using a covalent modification- and mass spectrometry-based proteomics platform.

PubMed

Strickland, Erin C; Geer, M Ariel; Hong, Jiyong; Fitzgerald, Michael C

2014-01-01

Detection and quantitation of protein-ligand binding interactions is important in many areas of biological research. Stability of proteins from rates of oxidation (SPROX) is an energetics-based technique for identifying the proteins targets of ligands in complex biological mixtures. Knowing the false-positive rate of protein target discovery in proteome-wide SPROX experiments is important for the correct interpretation of results. Reported here are the results of a control SPROX experiment in which chemical denaturation data is obtained on the proteins in two samples that originated from the same yeast lysate, as would be done in a typical SPROX experiment except that one sample would be spiked with the test ligand. False-positive rates of 1.2-2.2% and <0.8% are calculated for SPROX experiments using Q-TOF and Orbitrap mass spectrometer systems, respectively. Our results indicate that the false-positive rate is largely determined by random errors associated with the mass spectral analysis of the isobaric mass tag (e.g., iTRAQ®) reporter ions used for peptide quantitation. Our results also suggest that technical replicates can be used to effectively eliminate such false positives that result from this random error, as is demonstrated in a SPROX experiment to identify yeast protein targets of the drug, manassantin A. The impact of ion purity in the tandem mass spectral analyses and of background oxidation on the false-positive rate of protein target discovery using SPROX is also discussed.

Cryogenic Hydrogen Fuel for Controlled Inertial Confinement Fusion (Cryogenic Target Factory Concept Based on FST-Layering Method)

NASA Astrophysics Data System (ADS)

Aleksandrova, I. V.; Koresheva, E. R.; Koshelev, I. E.; Krokhin, O. N.; Nikitenko, A. I.; Osipov, I. E.

2017-12-01

A central element of a power plant based on inertial confinement fusion (ICF) is a target with cryogenic hydrogen fuel that should be delivered to the center of a reactor chamber with a high accuracy and repetition rate. Therefore, a cryogenic target factory (CTF) is an integral part of any ICF reactor. A promising way to solve this problem consists in the FST layering method developed at the Lebedev Physical Institute (LPI). This method (rapid fuel layering inside moving free-standing targets) is unique, having no analogs in the world. The further development of FST-layering technologies is implemented in the scope of the LPI program for the creation of a modular CTF and commercialization of the obtained results. In this report, we discuss our concept of CTF (CTF-LPI) that exhibits the following distinctive features: using a FST-layering technology for the elaboration of an in-line production of cryogenic targets, using an effect of quantum levitation of high-temperature superconductors (HTSCs) in magnetic field for noncontacting manipulation, transport, and positioning of the free-standing cryogenic targets, as well as in using a Fourier holography technique for an on-line characterization and tracking of the targets flying into the reactor chamber. The results of original experimental and theoretical investigations performed at LPI indicate that the existing and developing target fabrication capabilities and technologies can be applied to ICF target production. The unique scientific, engineering, and technological base developed in Russia at LPI allows one to make a CTFLPI prototype for mass production of targets and delivery thereof at the required velocity into the ICF reactor chamber.

HERACLES: THE HERA CO LINE EXTRAGALACTIC SURVEY

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

Leroy, Adam K.; Walter, Fabian; Bigiel, Frank

2009-06-15

We present the Heterodyne Receiver Array CO Line Extragalactic Survey, an atlas of CO emission from 18 nearby galaxies that are also part of The H I Nearby Galaxy Survey and the Spitzer Infrared Nearby Galaxies Survey. We used the HERA multipixel receiver on the IRAM 30-m telescope to map the CO J = 2 {yields} 1 line over the full optical disk (defined by the isophotal radius r {sub 25}) of each target, at 13'' angular resolution and 2.6 km s{sup -1} velocity resolution. Here we describe the observations and reduction of the data and show channel maps, azimuthallymore » averaged profiles, integrated intensity maps, and peak intensity maps. The implied H{sub 2} masses range from 7 x 10{sup 6} to 6 x 10{sup 9} M {sub sun}, with four low metallicity dwarf irregular galaxies yielding only upper limits. In the cases where CO is detected, the integrated H{sub 2}-to-H I ratios range from 0.02 to 1.13 and H{sub 2}-to-stellar mass ratios from 0.01 to 0.25. Exponential scale lengths of the CO emission for our targets are in the range 0.8-3.2 kpc, or 0.2 {+-} 0.05r {sub 25}. The intensity-weighted mean velocity of CO matches that of H I very well, with a 1{sigma} scatter of only 6 km s{sup -1}. The CO J = 2 {yields} 1/J = 1 {yields} 0 line ratio varies over a range similar to that found in the Milky Way and other nearby galaxies, {approx}0.6-1.0, with higher values found in the centers of galaxies. The typical line ratio, {approx}0.8, could be produced by optically thick gas with an excitation temperature of {approx}10 K.« less

Atomic mass measurements with radioactive beams and/or targets: Where to start

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

Haustein, P.E.

1989-01-01

Radioactive beams or radioactive targets (or both) can significantly increase the yields of exotic isotopes, allowing studies to be performed in regions which are currently inaccessible. An important goal to pursue with these exotic species is a broad program of nuclidic mass measurements. This is motivated by the observation that mass model predictions generally diverge from one another in regions far from beta-decay stability where well measured masses are sparse or nonexistent. Stringent tests of mass models are therefore possible and these can highlight important features in the mass models that affect the quality of their short-range and long-range extrapolationmore » properties. Selection of systems to study can be guided, in part, by a desire to probe those regions where distinctions among mass models are most apparent and where exotic isotope yields will be optimal. Several examples will be presented to highlight future opportunities in this area. 10 refs., 5 figs.« less

Hybrid adaptive radiotherapy with on-line MRI in cervix cancer IMRT.

PubMed

Oh, Seungjong; Stewart, James; Moseley, Joanne; Kelly, Valerie; Lim, Karen; Xie, Jason; Fyles, Anthony; Brock, Kristy K; Lundin, Anna; Rehbinder, Henrik; Milosevic, Michael; Jaffray, David; Cho, Young-Bin

2014-02-01

Substantial organ motion and tumor shrinkage occur during radiotherapy for cervix cancer. IMRT planning studies have shown that the quality of radiation delivery is influenced by these anatomical changes, therefore the adaptation of treatment plans may be warranted. Image guidance with off-line replanning, i.e. hybrid-adaptation, is recognized as one of the most practical adaptation strategies. In this study, we investigated the effects of soft tissue image guidance using on-line MR while varying the frequency of off-line replanning on the adaptation of cervix IMRT. 33 cervical cancer patients underwent planning and weekly pelvic MRI scans during radiotherapy. 5 patients of 33 were identified in a previous retrospective adaptive planning study, in which the coverage of gross tumor volume/clinical target volume (GTV/CTV) was not acceptable given single off-line IMRT replan using a 3mm PTV margin with bone matching. These 5 patients and a randomly selected 10 patients from the remaining 28 patients, a total of 15 patients of 33, were considered in this study. Two matching methods for image guidance (bone to bone and soft tissue to dose matrix) and three frequencies of off-line replanning (none, single, and weekly) were simulated and compared with respect to target coverage (cervix, GTV, lower uterus, parametrium, upper vagina, tumor related CTV and elective lymph node CTV) and OAR sparing (bladder, bowel, rectum, and sigmoid). Cost (total process time) and benefit (target coverage) were analyzed for comparison. Hybrid adaptation (image guidance with off-line replanning) significantly enhanced target coverage for both 5 difficult and 10 standard cases. Concerning image guidance, bone matching was short of delivering enough doses for 5 difficult cases even with a weekly off-line replan. Soft tissue image guidance proved successful for all cases except one when single or more frequent replans were utilized in the difficult cases. Cost and benefit analysis preferred

Proteomic validation of protease drug targets: pharmacoproteomics of matrix metalloproteinase inhibitor drugs using isotope-coded affinity tag labelling and tandem mass spectrometry.

PubMed

Butler, G S; Overall, C M

2007-01-01

We illustrate the use of quantitative proteomics, namely isotope-coded affinity tag labelling and tandem mass spectrometry, to assess the targets and effects of the blockade of matrix metalloproteinases by an inhibitor drug in a breast cancer cell culture system. Treatment of MT1-MMP-transfected MDA-MB-231 cells with AG3340 (Prinomastat) directly affected the processing a multitude of matrix metalloproteinase substrates, and indirectly altered the expression of an array of other proteins with diverse functions. Therefore, broad spectrum blockade of MMPs has wide-ranging biological consequences. In this human breast cancer cell line, secreted substrates accumulated uncleaved in the conditioned medium and plasma membrane protein substrates were retained on the cell surface, due to reduced processing and shedding of these proteins (cell surface receptors, growth factors and bioactive molecules) to the medium in the presence of the matrix metalloproteinase inhibitor. Hence, proteomic investigation of drug-perturbed cellular proteomes can identify new protease substrates and at the same time provides valuable information for target validation, drug efficacy and potential side effects prior to commitment to clinical trials.

Dust masses for SN 1980K, SN1993J and Cassiopeia A from red-blue emission line asymmetries

NASA Astrophysics Data System (ADS)

Bevan, Antonia; Barlow, M. J.; Milisavljevic, D.

2017-03-01

We present Monte Carlo line transfer models that investigate the effects of dust on the very late time emission line spectra of the core-collapse supernovae SN 1980K and SN 1993J and the young core collapse supernova remnant Cassiopeia A. Their blueshifted emission peaks, resulting from the removal by dust of redshifted photons emitted from the far sides of the remnants, and the presence of extended red emission wings are used to constrain dust compositions and radii and to determine the masses of dust in the remnants. We estimate dust masses of between 0.08 and 0.15 M⊙ for SN 1993J at year 16, 0.12 and 0.30 M⊙ for SN 1980K at year 30 and ∼1.1 M⊙ for Cas A at year ∼330. Our models for the strong oxygen forbidden lines of Cas A require the overall modelled profiles to be shifted to the red by between 700 and 1000 km s-1, consistent with previous estimates for the shift of the dynamical centroid of this remnant.

On-line capillary electrophoresis/laser-induced fluorescence/mass spectrometry analysis of glycans labeled with Teal™ fluorescent dye using an electrokinetic sheath liquid pump-based nanospray ion source.

PubMed

Khan, Shaheer; Liu, Jenkuei; Szabo, Zoltan; Kunnummal, Baburaj; Han, Xiaorui; Ouyang, Yilan; Linhardt, Robert J; Xia, Qiangwei

2018-06-15

N-linked glycan analysis of recombinant therapeutic proteins, such as monoclonal antibodies, Fc-fusion proteins, and antibody-drug conjugates, provides valuable information regarding protein therapeutics glycosylation profile. Both qualitative identification and quantitative analysis of N-linked glycans on recombinant therapeutic proteins are critical analytical tasks in the biopharma industry during the development of a biotherapeutic. Currently, such analyses are mainly carried out using capillary electrophoresis/laser-induced fluorescence (CE/LIF), liquid chromatography/fluorescence (LC/FLR), and liquid chromatography/fluorescence/mass spectrometry (LC/FLR/MS) technologies. N-linked glycans are first released from glycoproteins by enzymatic digestion, then labeled with fluorescence dyes for subsequent CE or LC separation, and LIF or MS detection. Here we present an on-line CE/LIF/MS N-glycan analysis workflow that incorporates the fluorescent Teal™ dye and an electrokinetic pump-based nanospray sheath liquid capillary electrophoresis/mass spectrometry (CE/MS) ion source. Electrophoresis running buffer systems using ammonium acetate and ammonium hydroxide were developed for the negative ion mode CE/MS analysis of fluorescence-labeled N-linked glycans. Results show that on-line CE/LIF/MS analysis can be readily achieved using this versatile CE/MS ion source on common CE/MS instrument platforms. This on-line CE/LIF/MS method using Teal™ fluorescent dye and electrokinetic pump-based nanospray sheath liquid CE/MS coupling technology holds promise for on-line quantitation and identification of N-linked glycans on recombinant therapeutic proteins. Copyright © 2018 John Wiley & Sons, Ltd.

An On-Line Solid Phase Extraction-Liquid Chromatography-Tandem Mass Spectrometry Method for the Determination of Perfluoroalkyl Acids in Drinking and Surface Waters

PubMed Central

Mazzoni, Michela; Rusconi, Marianna; Valsecchi, Sara; Martins, Claudia P. B.; Polesello, Stefano

2015-01-01

An UHPLC-MS/MS multiresidue method based on an on-line solid phase extraction (SPE) procedure was developed for the simultaneous determination of 9 perfluorinated carboxylates (from 4 to 12 carbon atoms) and 3 perfluorinated sulphonates (from 4 to 8 carbon atoms). This work proposes using an on-line solid phase extraction before chromatographic separation and analysis to replace traditional methods of off-line SPE before direct injection to LC-MS/MS. Manual sample preparation was reduced to sample centrifugation and acidification, thus eliminating several procedural errors and significantly reducing time-consuming and costs. Ionization suppression between target perfluorinated analytes and their coeluting SIL-IS were detected for homologues with a number of carbon atoms less than 9, but the quantitation was not affected. Total matrix effect corrected by SIL-IS, inclusive of extraction efficacy, and of ionization efficiency, ranged between −34 and +39%. The percentage of recoveries, between 76 and 134%, calculated in different matrices (tap water and rivers impacted by different pollutions) was generally satisfactory. LODs and LOQs of this on-line SPE method, which also incorporate recovery losses, ranged from 0.2 to 5.0 ng/L and from 1 to 20 ng/L, respectively. Validated on-line SPE-LC/MS/MS method has been applied in a wide survey for the determination of perfluoroalkyl acids in Italian surface and ground waters. PMID:25834752

Magnetic confinement, Alfven wave reflection, and the origins of X-ray and mass-loss 'dividing lines' for late-type giants and supergiants

NASA Technical Reports Server (NTRS)

Rosner, R.; An, C.-H.; Musielak, Z. E.; Moore, R. L.; Suess, S. T.

1991-01-01

A simple qualitative model for the origin of the coronal and mass-loss dividing lines separating late-type giants and supergiants with and without hot, X-ray-emitting corona, and with and without significant mass loss is discussed. The basic physical effects considered are the necessity of magnetic confinement for hot coronal material on the surface of such stars and the large reflection efficiency for Alfven waves in cool exponential atmospheres. The model assumes that the magnetic field geometry of these stars changes across the observed 'dividing lines' from being mostly closed on the high effective temperature side to being mostly open on the low effective temperature side.

Mass loss from alpha Cyg /A2Ia/ derived from the profiles of low excitation Fe II lines

NASA Technical Reports Server (NTRS)

Hensberge, H.; De Loore, C.; Lamers, H. J. G. L. M.; Bruhweiler, F. C.

1982-01-01

The low-excitation Fe II lines in the spectral region 2000-3000 A are studied in the spectrum of alpha-Cyg. The profiles of the resonance lines are described by four representative parameters, and a preliminary model is derived from the dependence of these parameters on theoretical line strength, taking into account the influence of blending photospheric lines in an overall and qualitative way. At least 11% of all iron in the wind is once ionized, unless a non-thermal heating source enhances the fraction Fe(++) without destroying much Al(+). It is shown that the contribution of blending photospheric absorption lines to weaker P Cygni profiles has been previously largely underestimated. The mass loss rate corresponding to the model is derived, and is smaller by a factor of 500 than the one derived from the infrared excess by Barlow and Cohen (1977).

Identification of liver protein targets modified by tienilic acid metabolites using a two-dimensional Western blot-mass spectrometry approach

NASA Astrophysics Data System (ADS)

Methogo, Ruth Menque; Dansette, Patrick M.; Klarskov, Klaus

2007-12-01

A combined approach based on two-dimensional electrophoresis-immuno-blotting and nanoliquid chromatography coupled on-line with electrospray ionization mass spectrometry (nLC-MS/MS) was used to identify proteins modified by a reactive intermediate of tienilic acid (TA). Liver homogenates from rats exposed to TA were fractionated using ultra centrifugation; four fractions were obtained and subjected to 2D electrophoresis. Following transfer to PVDF membranes, modified proteins were visualized after India ink staining, using an anti-serum raised against TA and ECL detection. Immuno-reactive spots were localized on the PVDF membrane by superposition of the ECL image, protein spots of interest were excised, digested on the membrane with trypsin followed by nLC-MS/MS analysis and protein identification. A total of 15 proteins were identified as likely targets modified by a TA reactive metabolite. These include selenium binding protein 2, senescence marker protein SMP-30, adenosine kinase, Acy1 protein, adenosylhomocysteinase, capping protein (actin filament), protein disulfide isomerase, fumarylacetoacetase, arginase chain A, ketohexokinase, proteasome endopeptidase complex, triosephosphate isomerase, superoxide dismutase, dna-type molecular chaperone hsc73 and malate dehydrogenase.

The Effects of Color Cues on Typically Developing Preschoolers' Speed of Locating a Target Line Drawing: Implications for Augmentative and Alternative Communication Display Design

ERIC Educational Resources Information Center

Thistle, Jennifer J.; Wilkinson, Krista

2009-01-01

Purpose: This research examined how the presence of color in relation to a target within an augmentative and alternative communication array influenced the speed with which typically developing preschoolers located a target line drawing. Method: Fifteen children over the age of 4 years (from 4;2 [years;months] to 5;4) and 15 children under the age…

Improving panicle exsertion of rice cytoplasmic male sterile line by combination of artificial microRNA and artificial target mimic.

PubMed

Chen, Hao; Jiang, Shan; Zheng, Jie; Lin, Yongjun

2013-04-01

The adoption of hybrid rice caused the second leap in rice yield after the 'green revolution' and contributes substantially to food security of China and the world. However, almost all cytoplasmic male sterile lines (A lines) as females of hybrid rice have a natural deficiency of 'panicle enclosure', which blocks pollination between the A line and the fertility restorer line as the male (R line) of hybrid rice and decreases seed yield. In hybrid rice seed production, exogenous '920' (the active ingredient is gibberellin A3 ) must be applied to eliminate or alleviate panicle enclosure of the A line; however, this not only increases production cost and pollutes the environment, it also decreases seed quality. In this study, we designed a transgenic approach to improve plant height and panicle exsertion of the A line to facilitate hybrid rice production and maintain the semi-dwarf plant type of the hybrid. This approach comprising two components-artificial microRNA (amiRNA) and artificial target mimicry-can manipulate the differential expression of the endogenous Eui1 gene that is associated with rice internode elongation in the A line and the hybrid. amiRNA is a recently developed gene silencing method with high specificity, while target mimicry is a natural mechanism inhibiting the miRNA function that was also recently characterized. This approach provides a paradigm to tune the expression of endogenous genes to achieve the desired phenotype by combining amiRNA and artificial target mimicry technologies. © 2012 The Authors Plant Biotechnology Journal © 2012 Society for Experimental Biology, Association of Applied Biologists and Blackwell Publishing Ltd.

Impact of an Australian mass media campaign targeting physical activity in 1998.

PubMed

Bauman, A E; Bellew, B; Owen, N; Vita, P

2001-07-01

Physical activity is now a public health priority, but there is only limited evidence on the effectiveness of mass-reach campaigns. Paid and unpaid television and print-media advertising, physician mail-outs, and community-level support programs and strategies. A mass-media statewide campaign to promote regular moderate-intensity activity was conducted during February 1998. The target group was adults aged 25 to 60 who were motivated but insufficiently active. Cohort and independent-sample, cross-sectional representative population surveys, before and after the campaign. The intervention was conducted in the state of New South Wales, with the other states of Australia as the comparison region. Telephone survey items on physical activity, media message awareness, physical activity knowledge, self-efficacy, and intentions. Unprompted recall of the activity messages in the campaign state increased substantially from 2.1% to 20.9% (p<0.01), with small changes elsewhere in Australia (1.2% to 2.6%). There were large changes in prompted awareness from 12.9% to 50.7% (p<0.0001), much larger than changes elsewhere (14.1% to 16%, p=0.06). Knowledge of appropriate moderate-intensity activity and physical activity self-efficacy increased significantly and only in the campaign state. Compared to all others, those in the target group who recalled the media message were 2.08 times more likely to increase their activity by at least an hour per week (95% confidence interval = 1.51-2.86). This integrated campaign positively influenced short-term physical activity message recall, knowledge, and behavior of the target population, compared to the population in the region who were not exposed.

Multi-decadal mass balance series of three Kyrgyz glaciers inferred from modelling constrained with repeated snow line observations

NASA Astrophysics Data System (ADS)

Barandun, Martina; Huss, Matthias; Usubaliev, Ryskul; Azisov, Erlan; Berthier, Etienne; Kääb, Andreas; Bolch, Tobias; Hoelzle, Martin

2018-06-01

Glacier surface mass balance observations in the Tien Shan and Pamir are relatively sparse and often discontinuous. Nevertheless, glaciers are one of the most important components of the high-mountain cryosphere in the region as they strongly influence water availability in the arid, continental and intensely populated downstream areas. This study provides reliable and continuous surface mass balance series for selected glaciers located in the Tien Shan and Pamir-Alay. By cross-validating the results of three independent methods, we reconstructed the mass balance of the three benchmark glaciers, Abramov, Golubin and Glacier no. 354 for the past 2 decades. By applying different approaches, it was possible to compensate for the limitations and shortcomings of each individual method. This study proposes the use of transient snow line observations throughout the melt season obtained from satellite optical imagery and terrestrial automatic cameras. By combining modelling with remotely acquired information on summer snow depletion, it was possible to infer glacier mass changes for unmeasured years. The model is initialized with daily temperature and precipitation data collected at automatic weather stations in the vicinity of the glacier or with adjusted data from climate reanalysis products. Multi-annual mass changes based on high-resolution digital elevation models and in situ glaciological surveys were used to validate the results for the investigated glaciers. Substantial surface mass loss was confirmed for the three studied glaciers by all three methods, ranging from -0.30 ± 0.19 to -0.41 ± 0.33 m w.e. yr-1 over the 2004-2016 period. Our results indicate that integration of snow line observations into mass balance modelling significantly narrows the uncertainty ranges of the estimates. Hence, this highlights the potential of the methodology for application to unmonitored glaciers at larger scales for which no direct measurements are available.

Simultaneous Proteomic Discovery and Targeted Monitoring using Liquid Chromatography, Ion Mobility Spectrometry, and Mass Spectrometry

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

Burnum-Johnson, Kristin E.; Nie, Song; Casey, Cameron P.

Current proteomics approaches are comprised of both broad discovery measurements as well as more quantitative targeted measurements. These two different measurement types are used to initially identify potentially important proteins (e.g., candidate biomarkers) and then enable improved quantification for a limited number of selected proteins. However, both approaches suffer from limitations, particularly the lower sensitivity, accuracy, and quantitation precision for discovery approaches compared to targeted approaches, and the limited proteome coverage provided by targeted approaches. Herein, we describe a new proteomics approach that allows both discovery and targeted monitoring (DTM) in a single analysis using liquid chromatography, ion mobility spectrometrymore » and mass spectrometry (LC-IMS-MS). In DTM, heavy labeled peptides for target ions are spiked into tryptic digests and both the labeled and unlabeled peptides are broadly detected using LC-IMS-MS instrumentation, allowing the benefits of discovery and targeted approaches. To understand the possible improvement of the DTM approach, it was compared to LC-MS broad measurements using an accurate mass and time tag database and selected reaction monitoring (SRM) targeted measurements. The DTM results yielded greater peptide/protein coverage and a significant improvement in the detection of lower abundance species compared to LC-MS discovery measurements. DTM was also observed to have similar detection limits as SRM for the targeted measurements indicating its potential for combining the discovery and targeted approaches.« less

Estimation of Mass-Loss Rate for M Giants from UV Emission Line Profiles

NASA Technical Reports Server (NTRS)

Carpenter, Kenneth G.; Robinson, R. D.; Fisher, Richard R. (Technical Monitor)

2001-01-01

The photon-scattering winds of M giants produce absorption features in the strong chromospheric emission lines. These provide us with an opportunity to assess important parameters of the wind, including flow and turbulent velocities, the optical depth of the wind above the region of photon creation, and the star's mass-loss rate. We have used the Lamers et al. (1987) Sobolev with Exact Integration (SET) radiative transfer code, along with simple models of the outer atmospheric structure and wind, to determine the wind characteristics of two M-giant stars, gamma Cru (M3.4) and mu Gem (M3IIIab). The SET code has the advantage of being computationally fast and allows a great number of possible wind models to be examined. The analysis procedure involves specifying wind parameters and then using the program to calculate line profiles for the Mg II (UV1) lines and a range of unblended Fe II lines. These lines have a wide range of wind opacities and therefore probe different heights in the atmosphere. The assumed wind properties are iterated until the predicted profiles match the observations over as many lines as possible. We present estimates of the wind parameters for these stars and offer a comparison to wind properties previously-derived for low-gravity K stars using the same technique.

Cyclotron Line and Wind studies of Galactic High Mass X-ray Binaries

NASA Astrophysics Data System (ADS)

Suchy, Slawomir

High mass X-ray binaries are rotating neutron stars with very strong magnetic fields that channel accreting matter from their companion star onto the magnetic poles with subsequent collimated X-ray emission. The stars are fed either by a strong stellar wind of the optical companion or by an accretion disk, where material follows the magnetic field lines, emitting X-rays throughout this process either in the accretion column or directly from the neutron star surface. The fast rotation and the narrow collimation of the X-ray emission creates an observed pulsation, forming the concept of a pulsar. Some of the key questions of these thesis are the emission processes above the magnetic pole, including the influence of the magnetic field, the formation of the X-ray beam, and the structure of the stellar wind. An important process is the effect of the teraGauss magnetic field. Cyclotron resonance scattering creates spectral features similar to broad absorption lines (CRSFs or cyclotron lines) that are directly related to the magnetic field. The discovery of cyclotron lines ˜ 35 years ago allows for the only direct method to measure the magnetic field strength in neutron star systems. Variations in the line parameters throughout the pulse phase, and a dependence in the observed luminosity can also aid in the understanding of these processes. In this thesis I present the results of phase averaged and phase resolved analysis of the three high mass X-ray binaries CenX-3, 1A 1118--61, and GX301--2. The data used for this work were obtained with NASA's Rossi X-ray Timing Explorer and the Japanese Suzaku mission. Both satellites are ideal to cover the broad energy band, where CRSFs occur and are necessary for understanding the continuum as a whole. In the process of investigating the 3 sources, I discovered a CRSF at ˜ 55 keV in the transient binary 1A 1118--61, which indicates one of the strongest magnetic fields known in these objects. I used the variations of the CRSF in GX

Stringent Constraints on Fundamental Constant Evolution Using Conjugate 18 cm Satellite OH Lines.

PubMed

Kanekar, Nissim; Ghosh, Tapasi; Chengalur, Jayaram N

2018-02-09

We have used the Arecibo Telescope to carry out one of the deepest-ever integrations in radio astronomy, targeting the redshifted conjugate satellite OH 18 cm lines at z≈0.247 towards PKS 1413+135. The satellite OH 1720 and 1612 MHz lines are, respectively, in emission and absorption, with exactly the same line shapes due to population inversion in the OH ground state levels. Since the 1720 and 1612 MHz line rest frequencies have different dependences on the fine structure constant α and the proton-electron mass ratio μ, a comparison between their measured redshifts allows one to probe changes in α and μ with cosmological time. In the case of conjugate satellite OH 18 cm lines, the predicted perfect cancellation of the sum of the line optical depths provides a strong test for the presence of systematic effects that might limit their use in probing fundamental constant evolution. A nonparametric analysis of our new Arecibo data yields [ΔX/X]=(+0.97±1.52)×10^{-6}, where X≡μα^{2}. Combining this with our earlier results from the Arecibo Telescope and the Westerbork Synthesis Radio Telescope, we obtain [ΔX/X]=(-1.0±1.3)×10^{-6}, consistent with no changes in the quantity μα^{2} over the last 2.9 Gyr. This is the most stringent present constraint on fractional changes in μα^{2} from astronomical spectroscopy, and with no evidence for systematic effects.

Comprehensive identification and structural characterization of target components from Gelsemium elegans by high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry based on accurate mass databases combined with MS/MS spectra.

PubMed

Liu, Yan-Chun; Xiao, Sa; Yang, Kun; Ling, Li; Sun, Zhi-Liang; Liu, Zhao-Ying

2017-06-01

This study reports an applicable analytical strategy of comprehensive identification and structure characterization of target components from Gelsemium elegans by using high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QqTOF MS) based on the use of accurate mass databases combined with MS/MS spectra. The databases created included accurate masses and elemental compositions of 204 components from Gelsemium and their structural data. The accurate MS and MS/MS spectra were acquired through data-dependent auto MS/MS mode followed by an extraction of the potential compounds from the LC-QqTOF MS raw data of the sample. The same was matched using the databases to search for targeted components in the sample. The structures for detected components were tentatively characterized by manually interpreting the accurate MS/MS spectra for the first time. A total of 57 components have been successfully detected and structurally characterized from the crude extracts of G. elegans, but has failed to differentiate some isomers. This analytical strategy is generic and efficient, avoids isolation and purification procedures, enables a comprehensive structure characterization of target components of Gelsemium and would be widely applicable for complicated mixtures that are derived from Gelsemium preparations. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Rapid high-throughput characterisation, classification and selection of recombinant mammalian cell line phenotypes using intact cell MALDI-ToF mass spectrometry fingerprinting and PLS-DA modelling.

PubMed

Povey, Jane F; O'Malley, Christopher J; Root, Tracy; Martin, Elaine B; Montague, Gary A; Feary, Marc; Trim, Carol; Lang, Dietmar A; Alldread, Richard; Racher, Andrew J; Smales, C Mark

2014-08-20

Despite many advances in the generation of high producing recombinant mammalian cell lines over the last few decades, cell line selection and development is often slowed by the inability to predict a cell line's phenotypic characteristics (e.g. growth or recombinant protein productivity) at larger scale (large volume bioreactors) using data from early cell line construction at small culture scale. Here we describe the development of an intact cell MALDI-ToF mass spectrometry fingerprinting method for mammalian cells early in the cell line construction process whereby the resulting mass spectrometry data are used to predict the phenotype of mammalian cell lines at larger culture scale using a Partial Least Squares Discriminant Analysis (PLS-DA) model. Using MALDI-ToF mass spectrometry, a library of mass spectrometry fingerprints was generated for individual cell lines at the 96 deep well plate stage of cell line development. The growth and productivity of these cell lines were evaluated in a 10L bioreactor model of Lonza's large-scale (up to 20,000L) fed-batch cell culture processes. Using the mass spectrometry information at the 96 deep well plate stage and phenotype information at the 10L bioreactor scale a PLS-DA model was developed to predict the productivity of unknown cell lines at the 10L scale based upon their MALDI-ToF fingerprint at the 96 deep well plate scale. This approach provides the basis for the very early prediction of cell lines' performance in cGMP manufacturing-scale bioreactors and the foundation for methods and models for predicting other mammalian cell phenotypes from rapid, intact-cell mass spectrometry based measurements. Copyright © 2014 Elsevier B.V. All rights reserved.

On-line range prediction system, part 2

NASA Technical Reports Server (NTRS)

Levan, Nhan

1988-01-01

The on-line range prediction system is designed for providing a prediction of the target range in the case of a laser data dropout. It consists of real time implementation of a Kalman filter on an IBM PC/AT equipped with necessary hardware. The system was set up and tested at Crows Landing in the Fall of 1987. The improvements made on the on-line range prediction system during 1988 are examined. Solutions are proposed and discussed to the several problems encountered during system tests. Then, the improvements made on the filter software are explained, namely, accounting for the time lag and providing data continously. Finally, the ideas are mentioned that can be considered in the future.

Stellar Absorption Line Analysis of Local Star-forming Galaxies: The Relation between Stellar Mass, Metallicity, Dust Attenuation, and Star Formation Rate

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

Jabran Zahid, H.; Kudritzki, Rolf-Peter; Ho, I-Ting

We analyze the optical continuum of star-forming galaxies in the Sloan Digital Sky Survey by fitting stacked spectra with stellar population synthesis models to investigate the relation between stellar mass, stellar metallicity, dust attenuation, and star formation rate. We fit models calculated with star formation and chemical evolution histories that are derived empirically from multi-epoch observations of the stellar mass–star formation rate and the stellar mass–gas-phase metallicity relations, respectively. We also fit linear combinations of single-burst models with a range of metallicities and ages. Star formation and chemical evolution histories are unconstrained for these models. The stellar mass–stellar metallicity relationsmore » obtained from the two methods agree with the relation measured from individual supergiant stars in nearby galaxies. These relations are also consistent with the relation obtained from emission-line analysis of gas-phase metallicity after accounting for systematic offsets in the gas-phase metallicity. We measure dust attenuation of the stellar continuum and show that its dependence on stellar mass and star formation rate is consistent with previously reported results derived from nebular emission lines. However, stellar continuum attenuation is smaller than nebular emission line attenuation. The continuum-to-nebular attenuation ratio depends on stellar mass and is smaller in more massive galaxies. Our consistent analysis of stellar continuum and nebular emission lines paves the way for a comprehensive investigation of stellar metallicities of star-forming and quiescent galaxies.« less

Analysis of chlorophenoxy acid herbicides in water by large-volume on-line derivatization and gas chromatography-mass spectrometry.

PubMed

Ding, W H; Liu, C H; Yeh, S P

2000-10-27

This work presents a modified method to analyze chlorophenoxy acid herbicides in water samples. The herbicides 2,4-D (2,4-dichlorophenoxyacetic acid). Silvex (2,4,5-trichlorophenoxypropionic acid) and 2,4,5-T (2,4,5-trichlorophenoxyacetic acid) were used to evaluate the method. The method involves extraction of samples by a graphitized carbon black cartridge, and on-line derivatization in the GC injection port using a large-volume (10-20 microl) direct sample introduction (DSI) device with tetraalkylammonium salts. The analytes were then identified and quantitated by ion-trap gas chromatography-mass spectrometry. The large-volume DSI injection-port derivatization technique provides sensitivity, fast and reproducible results for chlorophenoxy acid herbicides residues, to quantitation at 0.1 to 0.2 microg/l in 500-ml water samples. An enhanced characteristic mass chromatogram of molecular ions of butylated chlorophenoxy acid herbicides with a significant chlorine isotope pattern by electron impact ionization MS allows us to determine herbicides residues at trace levels in aqueous samples. Recovery of the herbicide residues in spiked various water samples ranged from 70 to 99% while RSDs ranged from 1 to 13%.

Mechanistic and Kinetic Study of Singlet O2 Oxidation of Methionine by On-Line Electrospray Ionization Mass Spectrometry.

PubMed

Liu, Fangwei; Lu, Wenchao; Yin, Xunlong; Liu, Jianbo

2016-01-01

We report a reaction apparatus developed to monitor singlet oxygen ((1)O2) reactions in solution using on-line ESI mass spectrometry and spectroscopy measurements. (1)O2 was generated in the gas phase by the reaction of H2O2 with Cl2, detected by its emission at 1270 nm, and bubbled into aqueous solution continuously. (1)O2 concentrations in solution were linearly related to the emission intensities of airborne (1)O2, and their absolute scales were established based on a calibration using 9,10-anthracene dipropionate dianion as an (1)O2 trapping agent. Products from (1)O2 oxidation were monitored by UV-Vis absorption and positive/negative ESI mass spectra, and product structures were elucidated using collision-induced dissociation-tandem mass spectrometry. To suppress electrical discharge in negative ESI of aqueous solution, methanol was added to electrospray via in-spray solution mixing using theta-glass ESI emitters. Capitalizing on this apparatus, the reaction of (1)O2 with methionine was investigated. We have identified methionine oxidation intermediates and products at different pH, and measured reaction rate constants. (1)O2 oxidation of methionine is mediated by persulfoxide in both acidic and basic solutions. Persulfoxide continues to react with another methionine, yielding methionine sulfoxide as end-product albeit with a much lower reaction rate in basic solution. Density functional theory was used to explore reaction potential energy surfaces and establish kinetic models, with solvation effects simulated using the polarized continuum model. Combined with our previous study of gas-phase methionine ions with (1)O2, evolution of methionine oxidation pathways at different ionization states and in different media is described.

O Star Wind Mass-Loss Rates and Shock Physics from X-ray Line Profiles in Archival XMM RGS Data

NASA Astrophysics Data System (ADS)

Cohen, David

in order to determine the values of physically meaningful model parameters, and to place confidence limits on them. We have incorporated second-order effects into our models, including resonance scattering. We have also developed tools for modeling the X-ray opacity of the cold, X-ray absorbing wind component, which is a crucial ingredient of the technique we have developed for determining wind mass-loss rates from analyzing the ensemble of emission lines from a given star's X-ray spectrum. In addition to testing state-of-the-art wind shock models and measuring O star mass-loss rates, an important component of our proposed research program is the education of talented undergraduates. Swarthmore undergraduates have made significant contributions to the development of our line profile modeling, the wind opacity modeling, and related research topics such as laboratory astrophysics before going on to PhD programs. Two have been named as finalists for the APS's Apker prize. The research we propose here will involve two undergraduates and will likely lead to honors theses, refereed papers, and the opportunity to present their research results at national and international meetings. By measuring mass-loss rates for all the O stars for which high-resolution X-ray spectra exist and by constraining X-ray production mechanisms, we will address issues important to our understanding of stellar and galactic evolution: including the frequency of core collapse supernovae, the energetics of the Galactic interstellar medium, and the radiation conditions in star formation regions where not only new, solar-type stars form, but also where their planetary systems form and are subject to effects of high-energy emission from nearby stars. In this way, the work we are proposing in this project will make a contribution to NASA's mission to understand cosmic evolution and the conditions for generating and sustaining life in the Universe.

LINE-1 methylation is positively associated with healthier lifestyle but inversely related to body fat mass in healthy young individuals

PubMed Central

Marques-Rocha, José Luiz; Milagro, Fermin I.; Mansego, Maria Luisa; Mourão, Denise Machado; Martínez, J. Alfredo; Bressan, Josefina

2016-01-01

Abstract With the goal of investigating if epigenetic biomarkers from white blood cells (WBC) are associated with dietary, anthropometric, metabolic, inflammatory and oxidative stress parameters in young and apparently healthy individuals. We evaluated 156 individuals (91 women, 65 men; age: 23.1±3.5 years; body mass index: 22.0±2.9 kg/m2) for anthropometric, biochemical and clinical markers, including some components of the antioxidant defense system and inflammatory response. DNA methylation of LINE-1, TNF-α and IL-6 and the expression of some genes related to the inflammatory process were analyzed in WBC. Adiposity was lower among individuals with higher LINE-1 methylation. On the contrary, body fat-free mass was higher among those with higher LINE-1 methylation. Individuals with higher LINE-1 methylation had higher daily intakes of calories, iron and riboflavin. However, those individuals who presented lower percentages of LINE-1 methylation reported higher intakes of copper, niacin and thiamin. Interestingly, the group with higher LINE-1 methylation had a lower percentage of current smokers and more individuals practicing sports. On the other hand, TNF-α methylation percentage was negatively associated with waist girth, waist-to-hip ratio and waist-to-stature ratio. Plasma TNF-α levels were lower in those individuals with higher TNF-α methylation. This study suggests that higher levels of LINE-1 and TNF-α methylation are associated with better indicators of adiposity status in healthy young individuals. In addition, energy and micronutrient intake, as well as a healthy lifestyle, may have a role in the regulation of DNA methylation in WBC and the subsequent metabolic changes may affect epigenetic biomarkers. PMID:26786189

The Planets Around Low-Mass Stars (PALMS) Direct Imaging Survey

NASA Astrophysics Data System (ADS)

Bowler, Brendan P.; Liu, M. C.; Shkolnik, E.; Mann, A.; Tamura, M.

2013-01-01

Direct imaging is the only method to study the outer architecture (>10 AU) of extrasolar planetary systems in a targeted fashion. Previous imaging surveys have primarily focused on intermediate- and high-mass stars because of the relative dearth of known nearby young M dwarfs. As a result, even though M dwarfs make up 70% of stars in our galaxy, there are few constraints on the population of giant planets at moderate separations (10-100 AU) in this stellar mass regime. We present results from an ongoing high-contrast adaptive optics imaging survey targeting newly identified nearby (<35 pc) young (<300 Myr) M dwarfs with Keck-2/NIRC2 and Subaru/HiCIAO. We have already discovered four young brown dwarf companions with masses between 30-70 Mjup; two of these are members of the ~120 Myr AB Dor moving group, and another one will yield a dynamical mass in the near future. Follow-up optical and near-infrared spectroscopy of these companions reveal spectral types of late-M to early-L and spectroscopic indicators of youth such as angular H-band morphologies, weak J-band alkali lines, and Li absorption and Halpha emission in one target. Altogether our survey is sensitive to planet masses a few times that of Jupiter at separations down to ~10 AU. With a sample size of roughly 80 single M dwarfs, this program represents the deepest and most extensive imaging search for planets around young low-mass stars to date.

Nike Experiment to Observe Strong Areal Mass Oscillations in a Rippled Target Hit by a Short Laser Pulse

NASA Astrophysics Data System (ADS)

Aglitskiy, Y.; Karasik, M.; Velikovich, A. L.; Serlin, V.; Weaver, J. L.; Kessler, T. J.; Schmitt, A. J.; Obenschain, S. P.; Metzler, N.; Oh, J.

2010-11-01

When a short (sub-ns) laser pulse deposits finite energy in a target, the shock wave launched into it is immediately followed by a rarefaction wave. If the irradiated surface is rippled, theory and simulations predict strong oscillations of the areal mass perturbation amplitude in the target [A. L. Velikovich et al., Phys. Plasmas 10, 3270 (2003).] The first experiment designed to observe this effect has become possible by adding short-driving-pulse capability to the Nike laser, and has been scheduled for the fall of 2010. Simulations show that while the driving pulse of 0.3 ns is on, the areal mass perturbation amplitude grows by a factor ˜2 due to ablative Richtmyer-Meshkov instability. It then decreases, reverses phase, and reaches another maximum, also about twice its initial value, shortly after the shock breakout at the rear target surface. This signature behavior is observable with the monochromatic x-ray imaging diagnostics fielded on Nike.

Classification of cancer cell lines using matrix-assisted laser desorption/ionization time‑of‑flight mass spectrometry and statistical analysis.

PubMed

Serafim, Vlad; Shah, Ajit; Puiu, Maria; Andreescu, Nicoleta; Coricovac, Dorina; Nosyrev, Alexander; Spandidos, Demetrios A; Tsatsakis, Aristides M; Dehelean, Cristina; Pinzaru, Iulia

2017-10-01

Over the past decade, matrix-assisted laser desorption/ionization time‑of‑flight mass spectrometry (MALDI‑TOF MS) has been established as a valuable platform for microbial identification, and it is also frequently applied in biology and clinical studies to identify new markers expressed in pathological conditions. The aim of the present study was to assess the potential of using this approach for the classification of cancer cell lines as a quantifiable method for the proteomic profiling of cellular organelles. Intact protein extracts isolated from different tumor cell lines (human and murine) were analyzed using MALDI‑TOF MS and the obtained mass lists were processed using principle component analysis (PCA) within Bruker Biotyper® software. Furthermore, reference spectra were created for each cell line and were used for classification. Based on the intact protein profiles, we were able to differentiate and classify six cancer cell lines: two murine melanoma (B16‑F0 and B164A5), one human melanoma (A375), two human breast carcinoma (MCF7 and MDA‑MB‑231) and one human liver carcinoma (HepG2). The cell lines were classified according to cancer type and the species they originated from, as well as by their metastatic potential, offering the possibility to differentiate non‑invasive from invasive cells. The obtained results pave the way for developing a broad‑based strategy for the identification and classification of cancer cells.

High temperature ion source for an on-line isotope separator

DOEpatents

Mlekodaj, Ronald L.

1979-01-01

A reduced size ion source for on-line use with a cyclotron heavy-ion beam is provided. A sixfold reduction in source volume while operating with similar input power levels results in a 2000.degree. C. operating temperature. A combined target/window normally provides the reaction products for ionization while isolating the ion source plasma from the cyclotron beam line vacuum. A graphite felt catcher stops the recoiling reaction products and releases them into the plasma through diffusion and evaporation. Other target arrangements are also possible. A twenty-four hour lifetime of unattended operation is achieved, and a wider range of elements can be studied than was heretofore possible.

Quantitative on-line preconcentration-liquid chromatography coupled with tandem mass spectrometry method for the determination of pharmaceutical compounds in water.

PubMed

Idder, Salima; Ley, Laurent; Mazellier, Patrick; Budzinski, Hélène

2013-12-17

One of the current environmental issues concerns the presence and fate of pharmaceuticals in water bodies as these compounds may represent a potential environmental problem. The characterization of pharmaceutical contamination requires powerful analytical method able to quantify these pollutants at very low concentration (few ng L(-1)). In this work, a multi-residue analytical methodology (on-line solid phase extraction-liquid chromatography-triple quadrupole mass spectrometry using positive and negative electrospray ionization) has been developed and validated for 40 multi-class pharmaceuticals and metabolites for tap and surface waters. This on-line SPE method was very convenient and efficient compared to classical off-line SPE method because of its shorter total run time including sample preparation and smaller sample volume (1 mL vs up to 1 L). The optimized method included several therapeutic classes as lipid regulators, antibiotics, beta-blockers, non-steroidal anti-inflammatories, antineoplastic, etc., with various physicochemical properties. Quantification has been achieved with the internal standards. The limits of detection are between 0.7 and 15 ng L(-1) for drinking waters and 2-15 ng L(-1) for surface waters. The inter-day precision values are below 20% for each studied level. The improvement and strength of the analytical method has been verified along a monitoring of these 40 pharmaceuticals in Isle River, a French stream located in the South West of France. During this survey, 16 pharmaceutical compounds have been detected. Copyright © 2013 Elsevier B.V. All rights reserved.

MAGNETIC FIELD-LINE LENGTHS IN INTERPLANETARY CORONAL MASS EJECTIONS INFERRED FROM ENERGETIC ELECTRON EVENTS

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

Kahler, S. W.; Haggerty, D. K.; Richardson, I. G., E-mail: AFRL.RVB.PA@hanscom.af.mil

About one quarter of the observed interplanetary coronal mass ejections (ICMEs) are characterized by enhanced magnetic fields that smoothly rotate in direction over timescales of about 10-50 hr. These ICMEs have the appearance of magnetic flux ropes and are known as 'magnetic clouds' (MCs). The total lengths of MC field lines can be determined using solar energetic particles of known speeds when the solar release times and the 1 AU onset times of the particles are known. A recent examination of about 30 near-relativistic (NR) electron events in and near 8 MCs showed no obvious indication that the field-line lengthsmore » were longest near the MC boundaries and shortest at the MC axes or outside the MCs, contrary to the expectations for a flux rope. Here we use the impulsive beamed NR electron events observed with the Electron Proton and Alpha Monitor instrument on the Advanced Composition Explorer spacecraft and type III radio bursts observed on the Wind spacecraft to determine the field-line lengths inside ICMEs included in the catalog of Richardson and Cane. In particular, we extend this technique to ICMEs that are not MCs and compare the field-line lengths inside MCs and non-MC ICMEs with those in the ambient solar wind outside the ICMEs. No significant differences of field-line lengths are found among MCs, ICMEs, and the ambient solar wind. The estimated number of ICME field-line turns is generally smaller than those deduced for flux-rope model fits to MCs. We also find cases in which the electron injections occur in solar active regions (ARs) distant from the source ARs of the ICMEs, supporting CME models that require extensive coronal magnetic reconnection with surrounding fields. The field-line lengths are found to be statistically longer for the NR electron events classified as ramps and interpreted as shock injections somewhat delayed from the type III bursts. The path lengths of the remaining spike and pulse electron events are compared with model

Magnetic Field-Line Lengths in Interplanetary Coronal Mass Ejections Inferred from Energetic Electron Events

NASA Technical Reports Server (NTRS)

Kahler, S. W.; Haggerty, D. K.; Richardson, I. G.

2011-01-01

About one quarter of the observed interplanetary coronal mass ejections (ICMEs) are characterized by enhanced magnetic fields that smoothly rotate in direction over timescales of about 10-50 hr. These ICMEs have the appearance of magnetic flux ropes and are known as "magnetic clouds" (MCs). The total lengths of MC field lines can be determined using solar energetic particles of known speeds when the solar release times and the I AU onset times of the particles are known. A recent examination of about 30 near-relativistic (NR) electron events in and near 8 MCs showed no obvious indication that the field-line lengths were longest near the MC boundaries and shortest at the MC axes or outside the MCs, contrary to the expectations for a flux rope. Here we use the impulsive beamed NR electron events observed with the Electron Proton and Alpha Monitor instrument on the Advanced Composition Explorer spacecraft and type III radio bursts observed on the Wind spacecraft to determine the field-line lengths inside ICMEs included in the catalog of Richardson & Cane. In particular, we extend this technique to ICMEs that are not MCs and compare the field-line lengths inside MCs and non-MC ICMEs with those in the ambient solar wind outside the ICMEs. No significant differences of field-line lengths are found among MCs, ICMEs, and the ambient solar wind. The estimated number of ICME field-line turns is generally smaller than those deduced for flux-rope model fits to MCs. We also find cases in which the electron injections occur in solar active regions CARs) distant from the source ARs of the ICMEs, supporting CME models that require extensive coronal magnetic reconnection with surrounding fields. The field-line lengths are found to be statistically longer for the NR electron events classified as ramps and interpreted as shock injections somewhat delayed from the type III bursts. The path lengths of the remaining spike and pulse electron events are compared with model calculations of

C II forbidden-line 158 micron mapping in Sagittarius A Rotation curve and mass distribution in the galactic center

NASA Technical Reports Server (NTRS)

Lugten, J. B.; Genzel, R.; Crawford, M. K.; Townes, C. H.

1986-01-01

Based on data obtained with the NASA Kuiper Airborne Observatory 91.4 cm telescope, the 158-micron fine structure line emission of C(+) is mapped near the galactic center. The strongest emission comes from a 10-pc FWHM diameter disk centered on Sgr A West whose dominant motion is rotation. Extended C(+) emission is also found from the +50 km/s galactic center molecular cloud, and a second cloud at v(LSR) of about -35 km/s. The rotation curve and mass distribution within 10 pc of the galactic center are derived, and the C(+) profiles show a drop-off of rotation velocity between 2 and 10 pc. A mass model is suggested with 2-4 million solar masses in a central point mass, and a M/L ratio of the central stellar cluster of 0.5 solar masses/solar luminosities, suggesting a large abundance of giants and relatively recent star formation in the center.

Mass Spectrometry Based Ultrasensitive DNA Methylation Profiling Using Target Fragmentation Assay.

PubMed

Lin, Xiang-Cheng; Zhang, Ting; Liu, Lan; Tang, Hao; Yu, Ru-Qin; Jiang, Jian-Hui

2016-01-19

Efficient tools for profiling DNA methylation in specific genes are essential for epigenetics and clinical diagnostics. Current DNA methylation profiling techniques have been limited by inconvenient implementation, requirements of specific reagents, and inferior accuracy in quantifying methylation degree. We develop a novel mass spectrometry method, target fragmentation assay (TFA), which enable to profile methylation in specific sequences. This method combines selective capture of DNA target from restricted cleavage of genomic DNA using magnetic separation with MS detection of the nonenzymatic hydrolysates of target DNA. This method is shown to be highly sensitive with a detection limit as low as 0.056 amol, allowing direct profiling of methylation using genome DNA without preamplification. Moreover, this method offers a unique advantage in accurately determining DNA methylation level. The clinical applicability was demonstrated by DNA methylation analysis using prostate tissue samples, implying the potential of this method as a useful tool for DNA methylation profiling in early detection of related diseases.

Use of consumer survey data to target cessation messages to smokers through mass media.

PubMed

Nelson, David E; Gallogly, Meg; Pederson, Linda L; Barry, Matthew; McGoldrick, Daniel; Maibach, Edward W

2008-03-01

We identified the mass media channels that reach the most cigarette smokers in an attempt to more effectively target smoking cessation messages. Reach estimates and index scores for smokers were taken from 2002-2003 ConsumerStyles and HealthStyles national surveys of adults (N=11660) to estimate overall and demographic-specific exposure measures for television, radio, newspapers, and magazines. Smokers viewed more television, listened to more radio, and read fewer magazines and newspapers than did nonsmokers. Nearly one third of smokers were regular daytime or late-night television viewers. Selected cable television networks (USA, Lifetime, and Discovery Channel) and selected radio genres, such as classic rock and country, had high reach and were cost-efficient channels for targeting smokers. Certain mass media channels offer efficient opportunities to target smoking cessation messages so they reach relatively large audiences of smokers at relatively low cost. The approach used in this study can be applied to other types of health risk factors to improve health communication planning and increase efficiency of program media expenditures.

Targeted erlotinib for first-line treatment of advanced non-small cell lung cancer: a budget impact analysis.

PubMed

Bajaj, Preeti S; Veenstra, David L; Goertz, Hans-Peter; Carlson, Josh J

2014-08-01

A recent phase III trial showed that patients with advanced non-small cell lung cancer (NSCLC) whose tumors harbor specific EGFR mutations significantly benefit from first-line treatment with erlotinib compared to chemotherapy. This study sought to estimate the budget impact if coverage for EGFR testing and erlotinib as first-line therapy were provided in a hypothetical 500,000-member managed care plan. The budget impact model was developed from a US health plan perspective to evaluate administration of the EGFR test and treatment with erlotinib for EGFR-positive patients, compared to non-targeted treatment with chemotherapy. The eligible patient population was estimated from age-stratified SEER incidence data. Clinical data were derived from key randomized controlled trials. Costs related to drug, administration, and adverse events were included. Sensitivity analyses were conducted to assess uncertainty. In a plan of 500,000 members, it was estimated there would be 91 newly diagnosed advanced NSCLC patients annually; 11 are expected to be EGFR-positive. Based on the testing and treatment assumptions, it was estimated that 3 patients in Scenario 1 and 6 patients in Scenario 2 receive erlotinib. Overall health plan expenditures would increase by $0.013 per member per month (PMPM). This increase is largely attributable to erlotinib drug costs, in part due to lengthened progression-free survival and treatment periods experienced in erlotinib-treated patients. EGFR testing contributes slightly, whereas adverse event costs mitigate the budget impact. The budget impact did not exceed $0.019 PMPM in sensitivity analyses. Coverage for targeted first-line erlotinib therapy in NSCLC likely results in a small budget impact for US health plans. The estimated impact may vary by plan, or if second-line or maintenance therapy, dose changes/interruptions, or impact on patients' quality-of-life were included.

Genetic variation assessed with microsatellites in mass selection lines of the Pacific oyster ( Crassostrea gigas) in China

NASA Astrophysics Data System (ADS)

Wang, Xubo; Li, Qi; Yu, Hong; Kong, Lingfeng

2016-12-01

Four successive mass selection lines of the Pacific oyster, Crassostrea gigas, selected for faster growth in breeding programs in China were examined at ten polymorphic microsatellite loci to assess the level of allelic diversity and estimate the effective population size. These data were compared with those of their base population. The results showed that the genetic variation of the four generations were maintained at high levels with an average allelic richness of 18.8-20.6, and a mean expected heterozygosity of 0.902-0.921. They were not reduced compared with those of their base population. Estimated effective population sizes based on temporal variances in microsatellite frequencies were smaller to that of sex ratio-corrected broodstock count estimates. Using a relatively large number of broodstock and keeping an equal sex ratio in the broodstock each generation may have contributed to retaining the original genetic diversity and maintaining relatively large effective population size. The results obtained in this study showed that the genetic variation was not affected greatly by mass selection progress and high genetic variation still existed in the mass selection lines, suggesting that there is still potential for increasing the gains in future generations of C. gigas. The present study provided important information for future genetic improvement by selective breeding, and for the design of suitable management guidelines for genetic breeding of C. gigas.

Direct identification of prohibited substances in cosmetics and foodstuffs using ambient ionization on a miniature mass spectrometry system.

PubMed

Ma, Qiang; Bai, Hua; Li, Wentao; Wang, Chao; Li, Xinshi; Cooks, R Graham; Ouyang, Zheng

2016-03-17

Significantly simplified work flows were developed for rapid analysis of various types of cosmetic and foodstuff samples by employing a miniature mass spectrometry system and ambient ionization methods. A desktop Mini 12 ion trap mass spectrometer was coupled with paper spray ionization, extraction spray ionization and slug-flow microextraction for direct analysis of Sudan Reds, parabens, antibiotics, steroids, bisphenol and plasticizer from raw samples with complex matrices. Limits of detection as low as 5 μg/kg were obtained for target analytes. On-line derivatization was also implemented for analysis of steroid in cosmetics. The developed methods provide potential analytical possibility for outside-the-lab screening of cosmetics and foodstuff products for the presence of illegal substances. Copyright © 2016 Elsevier B.V. All rights reserved.

Multiresidue analysis of 24 Water Framework Directive priority substances by on-line solid phase extraction-liquid chromatography tandem mass spectrometry in environmental waters.

PubMed

Rubirola, Adrià; Boleda, Mª Rosa; Galceran, Mª Teresa

2017-04-14

This paper reports the development of a fully multiresidue and automated on-line solid phase extraction (SPE) - liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the determination of 24 priority substances (PS) belonging to different classes (pesticides, hormones or pharmaceuticals) included in the Directive 2013/39/UE and the recent Watch List (Decision 2015/495) in water samples (drinking water, surface water, and effluent wastewaters). LC-MS/MS conditions and on-line SPE parameters such as sorbent type, sample and wash volumes were optimized. The developed method is highly sensitive (limits of detection between 0.1 and 1.4ngL -1 ) and precise (relative standard deviations lower than 8%). As part of the method validation studies, linearity, accuracy and matrix effects were assessed. The main advantage of this method over traditional off-line procedures is the minimization of tedious sample preparation increasing productivity and sample throughput. The optimized method was applied to the analysis of water samples and the results revealed the presence of 16 PS in river water and effluent water of wastewater treatment plants. Copyright © 2017 Elsevier B.V. All rights reserved.

Neurotoxicity fingerprinting of venoms using on-line microfluidic AChBP profiling.

PubMed

Slagboom, Julien; Otvos, Reka A; Cardoso, Fernanda C; Iyer, Janaki; Visser, Jeroen C; van Doodewaerd, Bjorn R; McCleary, Ryan J R; Niessen, Wilfried M A; Somsen, Govert W; Lewis, Richard J; Kini, R Manjunatha; Smit, August B; Casewell, Nicholas R; Kool, Jeroen

2018-06-15

Venoms from snakes are rich sources of highly active proteins with potent affinity towards a variety of enzymes and receptors. Of the many distinct toxicities caused by envenomation, neurotoxicity plays an important role in the paralysis of prey by snakes as well as by venomous sea snails and insects. In order to improve the analytical discovery component of venom toxicity profiling, this paper describes the implementation of microfluidic high-resolution screening (HRS) to obtain neurotoxicity fingerprints from venoms that facilitates identification of the neurotoxic components of envenomation. To demonstrate this workflow, 47 snake venoms were profiled using the acetylcholine binding protein (AChBP) to mimic the target of neurotoxic proteins, in particular nicotinic acetylcholine receptors (nAChRs). In the microfluidic HRS system, nanoliquid chromatographic (nanoLC) separations were on-line connected to both AChBP profiling and parallel mass spectrometry (MS). For virtually all neurotoxic elapid snake venoms tested, we obtained bioactivity fingerprints showing major and minor bioactive zones containing masses consistent with three-finger toxins (3FTxs), whereas, viperid and colubrid venoms showed little or no detectable bioactivity. Our findings demonstrate that venom interactions with AChBP correlate with the severity of neurotoxicity observed following human envenoming by different snake species. We further, as proof of principle, characterized bioactive venom peptides from a viperid (Daboia russelli) and an elapid (Aspidelaps scutatus scutatus) snake by nanoLC-MS/MS, revealing that different toxin classes interact with the AChBP, and that this binding correlates with the inhibition of α7-nAChR in calcium-flux cell-based assays. The on-line post-column binding assay and subsequent toxin characterization methodologies described here provide a new in vitro analytic platform for rapidly investigating neurotoxic snake venom proteins. Copyright © 2018 The Author

In situ Proteomic Profiling of Curcumin Targets in HCT116 Colon Cancer Cell Line.

PubMed

Wang, Jigang; Zhang, Jianbin; Zhang, Chong-Jing; Wong, Yin Kwan; Lim, Teck Kwang; Hua, Zi-Chun; Liu, Bin; Tannenbaum, Steven R; Shen, Han-Ming; Lin, Qingsong

2016-02-26

To date, the exact targets and mechanism of action of curcumin, a natural product with anti-inflammatory and anti-cancer properties, remain elusive. Here we synthesized a cell permeable curcumin probe (Cur-P) with an alkyne moiety, which can be tagged with biotin for affinity enrichment, or with a fluorescent dye for visualization of the direct-binding protein targets of curcumin in situ. iTRAQ(TM) quantitative proteomics approach was applied to distinguish the specific binding targets from the non-specific ones. In total, 197 proteins were confidently identified as curcumin binding targets from HCT116 colon cancer cell line. Gene Ontology analysis showed that the targets are broadly distributed and enriched in the nucleus, mitochondria and plasma membrane, and they are involved in various biological functions including metabolic process, regulation, response to stimulus and cellular process. Ingenuity Pathway Analysis(TM) (IPA) suggested that curcumin may exert its anticancer effects over multiple critical biological pathways including the EIF2, eIF4/p70S6K, mTOR signaling and mitochondrial dysfunction pathways. Functional validations confirmed that curcumin downregulates cellular protein synthesis, and induces autophagy, lysosomal activation and increased ROS production, thus leading to cell death.

In situ Proteomic Profiling of Curcumin Targets in HCT116 Colon Cancer Cell Line

PubMed Central

Wang, Jigang; Zhang, Jianbin; Zhang, Chong-Jing; Wong, Yin Kwan; Lim, Teck Kwang; Hua, Zi-Chun; Liu, Bin; Tannenbaum, Steven R.; Shen, Han-Ming; Lin, Qingsong

2016-01-01

To date, the exact targets and mechanism of action of curcumin, a natural product with anti-inflammatory and anti-cancer properties, remain elusive. Here we synthesized a cell permeable curcumin probe (Cur-P) with an alkyne moiety, which can be tagged with biotin for affinity enrichment, or with a fluorescent dye for visualization of the direct-binding protein targets of curcumin in situ. iTRAQTM quantitative proteomics approach was applied to distinguish the specific binding targets from the non-specific ones. In total, 197 proteins were confidently identified as curcumin binding targets from HCT116 colon cancer cell line. Gene Ontology analysis showed that the targets are broadly distributed and enriched in the nucleus, mitochondria and plasma membrane, and they are involved in various biological functions including metabolic process, regulation, response to stimulus and cellular process. Ingenuity Pathway AnalysisTM (IPA) suggested that curcumin may exert its anticancer effects over multiple critical biological pathways including the EIF2, eIF4/p70S6K, mTOR signaling and mitochondrial dysfunction pathways. Functional validations confirmed that curcumin downregulates cellular protein synthesis, and induces autophagy, lysosomal activation and increased ROS production, thus leading to cell death. PMID:26915414

Liquid chromatography mass spectrometry determination of perfluoroalkyl acids in environmental solid extracts after phospholipid removal and on-line turbulent flow chromatography purification.

PubMed

Mazzoni, M; Polesello, S; Rusconi, M; Valsecchi, S

2016-07-01

An on-line TFC (Turbulent Flow Chromatography) clean up procedures coupled with UHPLC-MS/MS (Ultra High Performance Liquid Chromatography Mass Spectrometry) multi-residue method was developed for the simultaneous determination of 8 perfluroalkyl carboxylic acids (PFCA, from 5 to 12 carbon atoms) and 3 perfluoroalkyl sulfonic acids (PFSA, from 4 to 8 carbon atoms) in environmental solid matrices. Fast sample preparation procedure was based on a sonication-assisted extraction with acetonitrile. Phospholipids in biological samples were fully removed by an off-line SPE purification before injection, using HybridSPE(®) Phospholipid Ultra cartridges. The development of the on-line TFC clean-up procedure regarded the choice of the stationary phase, the optimization of the mobile phase composition, flow rate and injected volume. The validation of the optimized method included the evaluation of matrix effects, accuracy and reproducibility. Signal suppression in the analysis of fortified extracts ranged from 1 to 60%, and this problem was overcome by using isotopic dilution. Since no certified reference materials were available for PFAS in these matrices, accuracy was evaluated by recoveries on spiked clam samples which were 98-133% for PFCAs and 40-60% for PFSAs. MLDs and MLQs ranged from 0.03 to 0.3ngg(-1) wet weight and from 0.1 to 0.9ngg(-1) wet weight respectively. Repeatability (intra-day precision) and reproducibility (inter-day precision) showed RSD from 3 to 13% and from 4 to 27% respectively. Validated on-line TFC/UHPLC-MS/MS method has been applied for the determination of perfluoroalkyl acids in different solid matrices (sediment, fish, bivalves and bird yolk). Copyright © 2016 Elsevier B.V. All rights reserved.

MicroRNA-218 inhibits the proliferation of human choriocarcinoma JEG-3 cell line by targeting Fbxw8

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

Shi, Dazun; Tan, Zhihui; Lu, Rong

2014-08-08

Highlights: • The miR-218 expression was decreased in choriocarcinoma cell lines. • The Fbxw8 protein expression was increased in choriocarcinoma cell lines. • We show that Fbxw8 is bona-fide target of miR-218 in JEG-3. • Ectopic miR-218 expression inhibits the proliferation of JEG-3 via Fbxw8. • Overexpression of miR-218 affected cyclin A and p27 expression via Fbxw8. - Abstract: MicroRNAs (miRNAs) are endogenous 19–25 nucleotide noncoding single-stranded RNAs that regulate gene expression by blocking the translation or decreasing the stability of mRNAs. In this study, we showed that miR-218 expression levels were decreased while Fbxw8 expression levels were increased inmore » human choriocarcinoma cell lines, and identified Fbxw8 as a novel direct target of miR-218. Overexpression of miR-218 inhibited cell growth arrest at G2/M phase, suppressed the protein levels of cyclin A and up-regulated the expression levels of p27 through decreasing the levels of Fbxw8. On the other hand, forced expression of Fbxw8 partly rescued the effect of miR-218 in the cells, attenuated cell proliferation decrease the percentage of cells at G2/M phase, induced cyclin A protein expression and suppressed the protein level of p27 through up-regulating the levels of Fbxw8. Taken together, these findings will shed light the role to mechanism of miR-218 in regulating JEG-3 cells proliferation via miR-218/Fbxw8 axis, and miR-218 may serve as a novel potential therapeutic target in human choriocarcinoma in the future.« less

Estimation of Mass-Loss Rates from Emission Line Profiles in the UV Spectra of Cool Stars

NASA Technical Reports Server (NTRS)

Carpenter, K. G.; Robinson, R. D.; Harper, G. M.

1999-01-01

The photon-scattering winds of cool, low-gravity stars (K-M giants and supergiants) produce absorption features in the strong chromospheric emission lines. This provides us with an opportunity to assess important parameters of the wind, including flow and turbulent velocities, the optical depth of the wind above the region of photon creation, and the star's mass-loss rate. We have used the Lamers et al. Sobolev with Exact Integration (SEI) radiative transfer code along with simple models of the outer atmospheric structure to compute synthetic line profiles for comparison with the observed line profiles. The SEI code has the advantage of being computationally fast and allows a great number of possible wind models to be examined. We therefore use it here to obtain initial first-order estimates of the wind parameters. More sophisticated, but more time-consuming and resource intensive calculations will be performed at a later date, using the SEI-deduced wind parameters as a starting point. A comparison of the profiles over a range of wind velocity laws, turbulence values, and line opacities allows us to constrain the wind parameters, and to estimate the mass-loss rates. We have applied this analysis technique (using lines of Mg II, 0 I, and Fe II) so far to four stars: the normal K5-giant alpha Tau, the hybrid K-giant gamma Dra, the K5 supergiant lambda Vel, and the M-giant gamma Cru. We present in this paper a description of the technique, including the assumptions which go into its use, an assessment of its robustness, and the results of our analysis.

SU-C-303-04: Evaluation of On- and Off-Line Bioluminescence Tomography System for Focal Irradiation Guidance

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

Zhang, B; Wang, K; Reyes, J

Purpose: We have developed offline and on-board bioluminescence tomography(BLT) systems for the small animal radiation research platform(SARRP) for radiation guidance of soft tissue targets. We investigated the effectiveness of offline BLT guidance. Methods: CBCT is equipped on both the offline BLT system and SARRP that are 10 ft. apart. To evaluate the setup error during animal transport between the two systems, we implanted a luminescence source in the abdomen of anesthetized mice. Five mice were studied. After CBCT was acquired on both systems, source centers and correlation coefficients were calculated. CBCT was also used to generate object mesh for BLTmore » reconstruction. To assess target localization, we compared the localization of the luminescence source based on (1)on-board SARRP BLT and CBCT, (2)offline BLT and CBCT, and (3)offline BLT and SARRP CBCT. The 3rd comparison examines if an offline BLT system can be used to guide radiation when there is minimal target contrast in CBCT. Results: Our CBCT results show the offset of the light source center can be maintained within 0.2 mm during animal transport. The center of mass(CoM) of the light source reconstructed by the offline BLT has an offset of 1.0 ± 0.4 mm from the ‘true’ CoM as derived from the SARRP CBCT. The results compare well with the offset of 1.0 ± 0.2 mm using on-line BLT. Conclusion: With CBCT information provided by the SARRP and effective animal immobilization during transport, these findings support the use of offline BLT in close vicinity for accurate soft tissue target localization for irradiation. However, the disadvantage of the off-line system is reduced efficiency as care is required to maintain stable animal transport. We envisage a dual use system where the on-board arrangement allows convenient access to CBCT and avoids disturbance of animal setup. The off-line capability would support standalone longitudinal imaging studies. The work is supported by NIH R01CA158100 and

Mass spectrometry-based targeted quantitative proteomics: achieving sensitive and reproducible detection of proteins.

PubMed

Boja, Emily S; Rodriguez, Henry

2012-04-01

Traditional shotgun proteomics used to detect a mixture of hundreds to thousands of proteins through mass spectrometric analysis, has been the standard approach in research to profile protein content in a biological sample which could lead to the discovery of new (and all) protein candidates with diagnostic, prognostic, and therapeutic values. In practice, this approach requires significant resources and time, and does not necessarily represent the goal of the researcher who would rather study a subset of such discovered proteins (including their variations or posttranslational modifications) under different biological conditions. In this context, targeted proteomics is playing an increasingly important role in the accurate measurement of protein targets in biological samples in the hope of elucidating the molecular mechanism of cellular function via the understanding of intricate protein networks and pathways. One such (targeted) approach, selected reaction monitoring (or multiple reaction monitoring) mass spectrometry (MRM-MS), offers the capability of measuring multiple proteins with higher sensitivity and throughput than shotgun proteomics. Developing and validating MRM-MS-based assays, however, is an extensive and iterative process, requiring a coordinated and collaborative effort by the scientific community through the sharing of publicly accessible data and datasets, bioinformatic tools, standard operating procedures, and well characterized reagents. © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

On-line Field Measurements of Speciated PM1 Emission Factors from Common South Asian Combustion Sources

NASA Astrophysics Data System (ADS)

DeCarlo, P. F.; Goetz, J. D.; Giordano, M.; Stockwell, C.; Maharjan, R.; Adhikari, S.; Bhave, P.; Praveen, P. S.; Panday, A. K.; Jayarathne, T. S.; Stone, E. A.; Yokelson, R. J.

2017-12-01

Characterization of aerosol emissions from prevalent but under sampled combustion sources in South Asia was performed as part of the Nepal Ambient Monitoring and Source Testing Experiment (NAMaSTE) in April 2015. Targeted emission sources included cooking stoves with a variety of solid fuels, brick kilns, garbage burning, crop-residue burning, diesel irrigation pumps, and motorcycles. Real-time measurements of submicron non-refractory particulate mass concentration and composition were obtained using an Aerodyne mini Aerosol Mass Spectrometer (mAMS). Speciated PM1 mass emission factors were calculated for all particulate species (e.g. organics, sulfates, nitrates, chlorides, ammonium) and for each source type using the carbon mass balance approach. Size resolved emission factors were also acquired using a novel high duty cycle particle time-of-flight technique (ePTOF). Black carbon and brown carbon absorption emission factors and absorption Angström exponents were measured using filter loading and scattering corrected attenuation at 370 nm and 880 nm with a dual spot aethalometer (Magee Scientific AE-33). The results indicate that open garbage burning is a strong emitter of organic aerosol, black carbon, and internally mixed particle phase hydrogen chloride (HCl). Emissions of HCl were attributed to the presence chlorinated plastics. The primarily coal fired brick kilns were found to be large emitters of sulfate but large differences in the organic and light absorbing component of emissions were observed between the two kiln types investigated (technologically advanced vs. traditional). These results, among others, bring on-line and field-tested aerosol emission measurements to an area of atmoshperic research dominated by off-line or laboratory based measurements.

New Evidence for Mass Loss from δ Cephei from H I 21 cm Line Observations

NASA Astrophysics Data System (ADS)

Matthews, L. D.; Marengo, M.; Evans, N. R.; Bono, G.

2012-01-01

Recently published Spitzer Space Telescope observations of the classical Cepheid archetype δ Cephei revealed an extended dusty nebula surrounding this star and its hot companion HD 213307. At far-infrared wavelengths, the emission resembles a bow shock aligned with the direction of space motion of the star, indicating that δ Cephei is undergoing mass loss through a stellar wind. Here we report H I 21 cm line observations with the Very Large Array (VLA) to search for neutral atomic hydrogen associated with this wind. Our VLA data reveal a spatially extended H I nebula (~13' or 1 pc across) surrounding the position of δ Cephei. The nebula has a head-tail morphology, consistent with circumstellar ejecta shaped by the interaction between a stellar wind and the interstellar medium (ISM). We directly measure a mass of circumstellar atomic hydrogen M_H I ≈ 0.07 M_{⊙}, although the total H I mass may be larger, depending on the fraction of circumstellar material that is hidden by Galactic contamination within our band or that is present on angular scales too large to be detected by the VLA. It appears that the bulk of the circumstellar gas has originated directly from the star, although it may be augmented by material swept from the surrounding ISM. The H I data are consistent with a stellar wind with an outflow velocity V o = 35.6 ± 1.2 km s-1 and a mass-loss rate of {\\dot{M}}≈ (1.0+/- 0.8)× 10^{-6} M_{⊙} yr-1. We have computed theoretical evolutionary tracks that include mass loss across the instability strip and show that a mass-loss rate of this magnitude, sustained over the preceding Cepheid lifetime of δ Cephei, could be sufficient to resolve a significant fraction of the discrepancy between the pulsation and evolutionary masses for this star.

Stability analyses of the mass abrasive projectile high-speed penetrating into a concrete target Part III: Terminal ballistic trajectory analyses

NASA Astrophysics Data System (ADS)

Wu, H.; Chen, X. W.; Fang, Q.; Kong, X. Z.; He, L. L.

2015-08-01

During the high-speed penetration of projectiles into concrete targets (the impact velocity ranges from 1.0 to 1.5 km/s), important factors such as the incident oblique and attacking angles, as well as the asymmetric abrasions of the projectile nose induced by the target-projectile interactions, may lead to obvious deviation of the terminal ballistic trajectory and reduction of the penetration efficiency. Based on the engineering model for the mass loss and nose-blunting of ogive-nosed projectiles established, by using the Differential Area Force Law (DAFL) method and semi-empirical resistance function, a finite differential approach was programmed (PENTRA2D) for predicting the terminal ballistic trajectory of mass abrasive high-speed projectiles penetrating into concrete targets. It accounts for the free-surface effects on the drag force acting on the projectile, which are attributed to the oblique and attacking angles, as well as the asymmetric nose abrasion of the projectile. Its validation on the prediction of curvilinear trajectories of non-normal high-speed penetrators into concrete targets is verified by comparison with available test data. Relevant parametric influential analyses show that the most influential factor for the stability of terminal ballistic trajectories is the attacking angle, followed by the oblique angle, the discrepancy of asymmetric nose abrasion, and the location of mass center of projectile. The terminal ballistic trajectory deviations are aggravated as the above four parameters increase.

Determination of active components of Ginkgo biloba in human urine by capillary high-performance liquid chromatography/mass spectrometry with on-line column-switching purification.

PubMed

Ding, Shujing; Dudley, Ed; Chen, Lijuan; Plummer, Sue; Tang, Jiandong; Newton, Russell P; Brenton, A Gareth

2006-01-01

Ginkgo biloba is one of the most popular herbal nutritional supplements, with terpene lactones and flavonoids being the two major active components. An on-line purification high-performance liquid chromatography/mass spectrometry (HPLC/MS) method was successfully developed for the quantitative determination of flavonoids and terpene lactones excreted in human urine after ingesting the herbal supplement. Satisfactory separation was obtained using a C18 capillary column made in-house with sample clean-up and pre-concentration achieved using a C18 pre-column with column switching. High selectivity and limits of detection of 1-18 ng/mL were achieved using a selected ion monitoring (SIM) scan in negative ion mode; the on-line solid-phase extraction (SPE) recovery of the active components in Ginkgo biloba determined in this study was greater than 75%. Copyright 2006 John Wiley & Sons, Ltd.

A mass filter based on an accelerating traveling wave.

PubMed

Wiedenbeck, Michael; Kasemset, Bodin; Kasper, Manfred

2008-01-01

We describe a novel mass filtering concept based on the acceleration of a pulsed ion beam through a stack of electrostatic plates. A precisely controlled traveling wave generated within such an ion guide will induce a mass-selective ion acceleration, with mass separation ultimately accomplished via a simple energy-filtering system. Crucial for successful filtering is that the velocity with which the traveling wave passes through the ion guide must be dynamically controlled in order to accommodate the acceleration of the target ion species. Mass selection is determined by the velocity and acceleration with which the wave traverses the ion guide, whereby the target species will acquire a higher kinetic energy than all other lighter as well as heaver species. Finite element simulations of this design demonstrate that for small masses a mass resolution M/DeltaM approximately 1000 can be achieved within an electrode stack containing as few as 20 plates. Some of the possible advantages and drawbacks which distinguish this concept from established mass spectrometric technologies are discussed.

Tracing early evolutionary stages of high-mass star formation with molecular lines

NASA Astrophysics Data System (ADS)

Marseille, M. G.; van der Tak, F. F. S.; Herpin, F.; Jacq, T.

2010-11-01

Context. Despite its major role in the evolution of the interstellar medium, the formation of high-mass stars (M ≥ 10 M_⊙) remains poorly understood. Two types of massive star cluster precursors, the so-called massive dense cores (MDCs), have been observed, which differ in terms of their mid-infrared brightness. The origin of this difference has not yet been established and may be the result of evolution, density, geometry differences, or a combination of these. Aims: We compare several molecular tracers of physical conditions (hot cores, shocks) observed in a sample of mid-IR weakly emitting MDCs with previous results obtained in a sample of exclusively mid-IR bright MDCs. We attempt to understand the differences between these two types of object. Methods: We present single-dish observations of HDO, H_218O, SO2, and CH3OH lines at λ = 1.3-3.5 mm. We study line profiles and estimate abundances of these molecules, and use a partial correlation method to search for trends in the results. Results: The detection rates of thermal emission lines are found to be very similar for both mid-IR quiet and bright objects. The abundances of H2O, HDO (10-13 to 10-9 in the cold outer envelopes), SO2 and CH3OH differ from source to source but independently of their mid-IR flux. In contrast, the methanol class I maser emission, a tracer of outflow shocks, is found to be strongly anti-correlated with the 12 μm source brightnesses. Conclusions: The enhancement of the methanol maser emission in mid-IR quiet MDCs may be indicative of a more embedded nature. Since total masses are similar between the two samples, we suggest that the matter distribution is spherical around mid-IR quiet sources but flattened around mid-IR bright ones. In contrast, water emission is associated with objects containing a hot molecular core, irrespective of their mid-IR brightness. These results indicate that the mid-IR brightness of MDCs is an indicator of their evolutionary stage.

Differential screening and mass mapping of proteins from premalignant and cancer cell lines using nonporous reversed-phase HPLC coupled with mass spectrometric analysis.

PubMed

Chong, B E; Hamler, R L; Lubman, D M; Ethier, S P; Rosenspire, A J; Miller, F R

2001-03-15

Nonporous (NPS) RP-HPLC has been used to rapidly separate proteins from whole cell lysates of human breast cell lines. The nonporous separation involves the use of hard-sphere silica beads of 1.5-microm diameter coated with C18, which can be used to separate proteins ranging from 5 to 90 kDa. Using only 30-40 microg of total protein, the protein molecular weights are detectable on-line using an ESI-oaTOF MS. Of hundreds of proteins detected in this mass range, approxinately 75-80 are more highly expressed. The molecular weight profiles can be displayed as a mass map analogous to a virtual "1-D gel" and differentially expressed proteins can be compared by image analysis. The separated proteins can also be detected by UV absorption and differentially expressed proteins quantified. The eluting proteins can be collected in the liquid phase and the molecular weight and peptide maps determined by MALDI-TOF MS for identification. It is demonstrated that the expressed protein profiles change during neoplastic progression and that many oncoproteins are readily detected. It is also shown that the response of premalignant cancer cells to estradiol can be rapidly screened by this method, demonstrating significant changes in response to an external agent. Ultimately, the proteins can be studied by peptide mapping to search for posttranslational modifications of the oncoproteins accompanying progression.

Multi-year analysis of distributed glacier mass balance modelling and equilibrium line altitude on King George Island, Antarctic Peninsula

NASA Astrophysics Data System (ADS)

Falk, Ulrike; López, Damián A.; Silva-Busso, Adrián

2018-04-01

The South Shetland Islands are located at the northern tip of the Antarctic Peninsula (AP). This region was subject to strong warming trends in the atmospheric surface layer. Surface air temperature increased about 3 K in 50 years, concurrent with retreating glacier fronts, an increase in melt areas, ice surface lowering and rapid break-up and disintegration of ice shelves. The positive trend in surface air temperature has currently come to a halt. Observed surface air temperature lapse rates show a high variability during winter months (standard deviations up to ±1.0 K (100 m)-1) and a distinct spatial heterogeneity reflecting the impact of synoptic weather patterns. The increased mesocyclonic activity during the wintertime over the past decades in the study area results in intensified advection of warm, moist air with high temperatures and rain and leads to melt conditions on the ice cap, fixating surface air temperatures to the melting point. Its impact on winter accumulation results in the observed negative mass balance estimates. Six years of continuous glaciological measurements on mass balance stake transects as well as 5 years of climatological data time series are presented and a spatially distributed glacier energy balance melt model adapted and run based on these multi-year data sets. The glaciological surface mass balance model is generally in good agreement with observations, except for atmospheric conditions promoting snow drift by high wind speeds, turbulence-driven snow deposition and snow layer erosion by rain. No drift in the difference between simulated mass balance and mass balance measurements can be seen over the course of the 5-year model run period. The winter accumulation does not suffice to compensate for the high variability in summer ablation. The results are analysed to assess changes in meltwater input to the coastal waters, specific glacier mass balance and the equilibrium line altitude (ELA). The Fourcade Glacier catchment drains

Performance Analysis of GFDL's GCM Line-By-Line Radiative Transfer Model on GPU and MIC Architectures

NASA Astrophysics Data System (ADS)

Menzel, R.; Paynter, D.; Jones, A. L.

2017-12-01

Due to their relatively low computational cost, radiative transfer models in global climate models (GCMs) run on traditional CPU architectures generally consist of shortwave and longwave parameterizations over a small number of wavelength bands. With the rise of newer GPU and MIC architectures, however, the performance of high resolution line-by-line radiative transfer models may soon approach those of the physical parameterizations currently employed in GCMs. Here we present an analysis of the current performance of a new line-by-line radiative transfer model currently under development at GFDL. Although originally designed to specifically exploit GPU architectures through the use of CUDA, the radiative transfer model has recently been extended to include OpenMP in an effort to also effectively target MIC architectures such as Intel's Xeon Phi. Using input data provided by the upcoming Radiative Forcing Model Intercomparison Project (RFMIP, as part of CMIP 6), we compare model results and performance data for various model configurations and spectral resolutions run on both GPU and Intel Knights Landing architectures to analogous runs of the standard Oxford Reference Forward Model on traditional CPUs.

Measuring the scatter in the cluster optical richness-mass relation with machine learning

NASA Astrophysics Data System (ADS)

Boada, Steven Alvaro

The distribution of massive clusters of galaxies depends strongly on the total cosmic mass density, the mass variance, and the dark energy equation of state. As such, measures of galaxy clusters can provide constraints on these parameters and even test models of gravity, but only if observations of clusters can lead to accurate estimates of their total masses. Here, we carry out a study to investigate the ability of a blind spectroscopic survey to recover accurate galaxy cluster masses through their line-of- sight velocity dispersions (LOSVD) using probability based and machine learning methods. We focus on the Hobby Eberly Telescope Dark Energy Experiment (HETDEX), which will employ new Visible Integral-Field Replicable Unit Spectrographs (VIRUS), over 420 degree2 on the sky with a 1/4.5 fill factor. VIRUS covers the blue/optical portion of the spectrum (3500 - 5500 A), allowing surveys to measure redshifts for a large sample of galaxies out to z < 0.5 based on their absorption or emission (e.g., [O II], Mg II, Ne V) features. We use a detailed mock galaxy catalog from a semi-analytic model to simulate surveys observed with VIRUS, including: (1) Survey, a blind, HETDEX-like survey with an incomplete but uniform spectroscopic selection function; and (2) Targeted, a survey which targets clusters directly, obtaining spectra of all galaxies in a VIRUS-sized field. For both surveys, we include realistic uncertainties from galaxy magnitude and line-flux limits. We benchmark both surveys against spectroscopic observations with perfect" knowledge of galaxy line-of-sight velocities. With Survey observations, we can recover cluster masses to ˜ 0.1 dex which can be further improved to < 0.1 dex with Targeted observations. This level of cluster mass recovery provides important measurements of the intrinsic scatter in the optical richness-cluster mass relation, and enables constraints on the key cosmological parameter, sigma 8, to < 20%. As a demonstration of the methods

Genetic effects on bone mass and turnover-relevance to black/white differences.

PubMed

Parfitt, A M

1997-08-01

The mass of a bone is given by its volume and its apparent density--mass per unit external volume. Most measurements of so-called density are of mass incompletely normalized by some index of bone size. Genes control about 60% to 75% of the variance of peak bone mass/density and a much smaller proportion of the variance in rate of loss. Genetic influence on bone mass/density are mediated in large part by body size, bone size, and muscle mass. Most of the fifty-fold increase in bone mass from birth to maturity is due to bone growth, which is linked to muscle growth and bodily growth. Three-D apparent bone density in the vertebrae increases about 15% during the pubertal growth spurt. The genetic potential for bone accumulation can be frustrated by insufficient calcium intake, disruption of the calendar of puberty and inadequate physical activity. The growing skeleton is much more responsive than the mature skeleton to the osteotrophic effect of exercise, which is mediated by the detection of deviations from a target value for strain, and orchestration of cellular responses that restore the target value, processes collectively termed the mechanostat. Production of metaphyseal cancellous bone and growth in length are both linked to endochondral ossification, which is driven by growth plate cartilage cell proliferation. Production of diaphyseal cortical bone and growth in width are both linked to periosteal apposition, which is driven by osteoblast precursor proliferation. During adolescence trabeculae and cortices become thicker by net endosteal apposition, which increases apparent density. Two lines of evidence support a genetic basis for black/white differences in bone mass. First, the magnitude (10% to 40%) is incommensurate with known nongenetic factors. Second, the difference is already evident in the fetus and increases progressively during growth, especially in adolescence; the difference in peak bone mass persists throughout life. The genetic determination of

Condensed Phase Membrane Introduction Mass Spectrometry with Direct Electron Ionization: On-line Measurement of PAHs in Complex Aqueous Samples

NASA Astrophysics Data System (ADS)

Termopoli, Veronica; Famiglini, Giorgio; Palma, Pierangela; Cappiello, Achille; Vandergrift, Gregory W.; Krogh, Erik T.; Gill, Chris G.

2016-02-01

Polycyclic aromatic hydrocarbons (PAHs) are USEPA regulated priority pollutants. Their low aqueous solubility requires very sensitive analytical methods for their detection, typically involving preconcentration steps. Presented is the first demonstrated `proof of concept' use of condensed phase membrane introduction mass spectrometry (CP-MIMS) coupled with direct liquid electron ionization (DEI) for the direct, on-line measurement of PAHs in aqueous samples. DEI is very well suited for the ionization of PAHs and other nonpolar compounds, and is not significantly influenced by the co-elution of matrix components. Linear calibration data for low ppb levels of aqueous naphthalene, anthracene, and pyrene is demonstrated, with measured detection limits of 4 ppb. Analytical response times (t10%-90% signal rise) ranged from 2.8 min for naphthalene to 4.7 min for pyrene. Both intra- and interday reproducibility has been assessed (<3% and 5% RSD, respectively). Direct measurements of ppb level PAHs spiked in a variety of real, complex environmental sample matrices is examined, including natural waters, sea waters, and a hydrocarbon extraction production waste water sample. For these spiked, complex samples, direct PAH measurement by CP-MIMS-DEI yielded minimal signal suppression from sample matrix effects (81%-104%). We demonstrate the use of this analytical approach to directly monitor real-time changes in aqueous PAH concentrations with potential applications for continuous on-line monitoring strategies and binding/adsorption studies in heterogeneous samples.

Identify Fractions and Decimals on a Number Line

ERIC Educational Resources Information Center

Shaughnessy, Meghan M.

2011-01-01

Tasks that ask students to label rational number points on a number line are common not only in curricula in the upper elementary school grades but also on state assessments. Such tasks target foundational rational number concepts: A fraction (or a decimal) is more than a shaded part of an area, a part of a pizza, or a representation using…

Orion Exploration Mission Entry Interface Target Line

NASA Technical Reports Server (NTRS)

Rea, Jeremy R.

2016-01-01

The Orion Multi-Purpose Crew Vehicle is required to return to the continental United States at any time during the month. In addition, it is required to provide a survivable entry from a wide range of trans-lunar abort trajectories. The Entry Interface (EI) state must be targeted to ensure that all requirements are met for all possible return scenarios, even in the event of no communication with the Mission Control Center to provide an updated EI target. The challenge then is to functionalize an EI state constraint manifold that can be used in the on-board targeting algorithm, as well as the ground-based trajectory optimization programs. This paper presents the techniques used to define the EI constraint manifold and to functionalize it as a set of polynomials in several dimensions.

A Fully Redundant On-Line Mass Spectrometer System Used to Monitor Cryogenic Fuel Leaks on the Space Shuttle

NASA Technical Reports Server (NTRS)

Griffin, Timothy P.; Naylor, Guy R.; Haskell, William D.; Breznik, Greg S.; Mizell, Carolyn A.; Helms, William R.; Steinrock, T. (Technical Monitor)

2001-01-01

An on-line gas monitoring system was developed to replace the older systems used to monitor for cryogenic leaks on the Space Shuttles before launch. The system uses a mass spectrometer to monitor multiple locations in the process, which allows the system to monitor all gas constituents of interest in a nearly simultaneous manner. The system is fully redundant and meets all requirements for ground support equipment (GSE). This includes ruggedness to withstand launch on the Mobile Launcher Platform (MLP), ease of operation, and minimal operator intervention. The system can be fully automated so that an operator is notified when an unusual situation or fault is detected. User inputs are through personal computer using mouse and keyboard commands. The graphical user interface is very intuitive and easy to operate. The system has successfully supported four launches to date. It is currently being permanently installed as the primary system monitoring the Space Shuttles during ground processing and launch operations. Time and cost savings will be substantial over the current systems when it is fully implemented in the field. Tests were performed to demonstrate the performance of the system. Low limits-of-detection coupled with small drift make the system a major enhancement over the current systems. Though this system is currently optimized for detecting cryogenic leaks, many other gas constituents could be monitored using the Hazardous Gas Detection System (HGDS) 2000.

BLACK HOLE MASS AND EDDINGTON RATIO DISTRIBUTION FUNCTIONS OF X-RAY-SELECTED BROAD-LINE AGNs AT z {approx} 1.4 IN THE SUBARU XMM-NEWTON DEEP FIELD

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

Nobuta, K.; Akiyama, M.; Ueda, Y.

2012-12-20

In order to investigate the growth of supermassive black holes (SMBHs), we construct the black hole mass function (BHMF) and Eddington ratio distribution function (ERDF) of X-ray-selected broad-line active galactic nuclei (AGNs) at z {approx} 1.4 in the Subaru XMM-Newton Deep Survey (SXDS) field. A significant part of the accretion growth of SMBHs is thought to take place in this redshift range. Black hole masses of X-ray-selected broad-line AGNs are estimated using the width of the broad Mg II line and 3000 A monochromatic luminosity. We supplement the Mg II FWHM values with the H{alpha} FWHM obtained from our NIRmore » spectroscopic survey. Using the black hole masses of broad-line AGNs at redshifts between 1.18 and 1.68, the binned broad-line AGN BHMFs and ERDFs are calculated using the V{sub max} method. To properly account for selection effects that impact the binned estimates, we derive the corrected broad-line AGN BHMFs and ERDFs by applying the maximum likelihood method, assuming that the ERDF is constant regardless of the black hole mass. We do not correct for the non-negligible uncertainties in virial BH mass estimates. If we compare the corrected broad-line AGN BHMF with that in the local universe, then the corrected BHMF at z = 1.4 has a higher number density above 10{sup 8} M{sub Sun} but a lower number density below that mass range. The evolution may be indicative of a downsizing trend of accretion activity among the SMBH population. The evolution of broad-line AGN ERDFs from z = 1.4 to 0 indicates that the fraction of broad-line AGNs with accretion rates close to the Eddington limit is higher at higher redshifts.« less

Simultaneous screening of targeted and non-targeted contaminants using an LC-QTOF-MS system and automated MS/MS library searching.

PubMed

Herrera-Lopez, S; Hernando, M D; García-Calvo, E; Fernández-Alba, A R; Ulaszewska, M M

2014-09-01

Simultaneous high-resolution full-scan and tandem mass spectrometry (MS/MS) analysis using time of flight mass spectrometry brings an answer for increasing demand of retrospective and non-targeted data analysis. Such analysis combined with spectral library searching is a promising tool for targeted and untargeted screening of small molecules. Despite considerable extension of the panel of compounds of tandem mass spectral libraries, the heterogeneity of spectral data poses a major challenge against the effective usage of spectral libraries. Performance evaluation of available LC-MS/MS libraries will significantly increase credibility in the search results. The present work was aimed to evaluate fluctuation of MS/MS pattern, in the peak intensities distribution together with mass accuracy measurements, and in consequence, performance compliant with ion ratio and mass error criteria as principles in identification processes for targeted and untargeted contaminants at trace levels. Matrix effect and ultra-trace levels of concentration (from 50 ng l(-1) to 1000 ng l(-1) were evaluated as potential source of inaccuracy in the performance of spectral matching. Matrix-matched samples and real samples were screened for proof of applicability. By manual review of data and application of ion ratio and ppm error criteria, false negatives were obtained; this number diminished when in-house library was used, while with on-line MS/MS databases 100% of positive samples were found. In our experience, intensity of peaks across spectra was highly correlated to the concentration effect and matrix complexity. In turn, analysis of spectra acquired at trace concentrations and in different matrices results in better performance in providing correct and reliable identification. Copyright © 2014 John Wiley & Sons, Ltd.

A novel, volumizing cosmetic formulation significantly improves the appearance of target Glabellar lines, nasolabial folds, and crow's feet in a double-blind, vehicle-controlled clinical trial.

PubMed

Farris, Patricia K; Edison, Brenda L; Weinkauf, Ronni L; Green, Barbara A

2014-01-01

Facial lines and wrinkles are caused by many factors including constant exposure to external elements, such as UV rays, as well as the dynamic nature of facial expression. Many cosmetic products and procedures provide global improvement to aging skin, whereas injectable therapies are frequently utilized to diminish specific, target wrinkles. Despite their broad availability, some patients are unwilling to undergo injectables and would benefit from an effective topical option. A noninvasive option to volumize target wrinkle areas could also extend benefits of commonly used cosmetic anti-aging products. To this end, a two-step formulation containing the novel, cosmetic anti-aging ingredient, N-acetyl tyrosinamide, was developed for use on targeted wrinkle areas. The tolerability and efficacy of the serum plus cream were tested for 16 weeks in women with moderate facial photodamage on predetermined wrinkle areas (glabellar lines, nasolabial folds, under eye lines, and lateral canthal (crow's feet) wrinkles) in a single-center, randomized, double-blind, vehicle-controlled, clinical trial. Seventy women (47 Active group, 23 Vehicle group) completed the study. Digital photography, clinical grading, ultrasound and self-assessment scores confirmed improvement to wrinkle areas. The topical cosmetic formulation was statistically superior (P<0.05) to its vehicle in visually improving nasolabial folds, glabellar lines, crow's feet, and under eye wrinkles and in reducing pinch recoil time. Both the test formulation and its vehicle were tolerated well. The novel, two-step cosmetic formulation reduced the appearance of wrinkles and increased skin elasticity thus providing an effective anti-aging option for target wrinkle areas. This study suggests that in addition to its use as monotherapy for reducing targeted lines and wrinkles this cosmetic formulation may be also serve as an adjuvant to injectable therapies.

Mass and Charge Measurements on Heavy Ions

PubMed Central

Sugai, Toshiki

2017-01-01

The relationship between mass and charge has been a crucial topic in mass spectrometry (MS) because the mass itself is typically evaluated based on the m/z ratio. Despite the fact that this measurement is indirect, a precise mass can be obtained from the m/z value with a high m/z resolution up to 105 for samples in the low mass and low charge region under 10,000 Da and 20 e, respectively. However, the target of MS has recently been expanded to the very heavy region of Mega or Giga Da, which includes large particles and biocomplexes, with very large and widely distributed charge from kilo to Mega range. In this region, it is necessary to evaluate charge and mass simultaneously. Recent studies for simultaneous mass and charge observation and related phenomena are discussed in this review. PMID:29302406

Characterization of on-target generated tryptic peptides from Giberella zeae conidia spore proteins by means of matrix-assisted laser desorption/ionization mass spectrometry.

PubMed

Dong, Hongjuan; Marchetti-Deschmann, Martina; Allmaier, Günter

2014-01-01

Traditionally characterization of microbial proteins is performed by a complex sequence of steps with the final step to be either Edman sequencing or mass spectrometry, which generally takes several weeks or months to be complete. In this work, we proposed a strategy for the characterization of tryptic peptides derived from Giberella zeae (anamorph: Fusarium graminearum) proteins in parallel to intact cell mass spectrometry (ICMS) in which no complicated and time-consuming steps were needed. Experimentally, after a simple washing treatment of the spores, the aliquots of the intact G. zeae macro conidia spores solution, were deposited two times onto one MALDI (matrix-assisted laser desorption ionization) mass spectrometry (MS) target (two spots). One spot was used for ICMS and the second spot was subject to a brief on-target digestion with bead-immobilized or non-immobilized trypsin. Subsequently, one spot was analyzed immediately by MALDI MS in the linear mode (ICMS) whereas the second spot containing the digested material was investigated by MALDI MS in the reflectron mode ("peptide mass fingerprint") followed by protonated peptide selection for MS/MS (post source decay (PSD) fragment ion) analysis. Based on the formed fragment ions of selected tryptic peptides a complete or partial amino acid sequence was generated by manual de novo sequencing. These sequence data were used for homology search for protein identification. Finally four different peptides of varying abundances have been identified successfully allowing the verification that our desorbed/ionized surface compounds were indeed derived from proteins. The presence of three different proteins could be found unambiguously. Interestingly, one of these proteins is belonging to the ribosomal superfamily which indicates that not only surface-associated proteins were digested. This strategy minimized the amount of time and labor required for obtaining deeper information on spore preparations within the

Surrogate Endpoints in Second-Line Trials of Targeted Agents in Metastatic Colorectal Cancer: A Literature-Based Systematic Review and Meta-Analysis.

PubMed

Cremolini, Chiara; Antoniotti, Carlotta; Pietrantonio, Filippo; Berenato, Rosa; Tampellini, Marco; Baratelli, Chiara; Salvatore, Lisa; Marmorino, Federica; Borelli, Beatrice; Nichetti, Federico; Bironzo, Paolo; Sonetto, Cristina; Bartolomeo, Maria Di; Braud, Filippo de; Loupakis, Fotios; Falcone, Alfredo; Di Maio, M

2017-07-01

The purpose of this study was to evaluate progression-free survival (PFS) and objective response rate (ORR) as surrogate endpoints of overall survival (OS) in modern clinical trials investigating the efficacy of targeted agents in the second-line treatment of metastatic colorectal cancer (mCRC). A systematic search of literature pertaining to randomized phase II and III trials evaluating targeted agents as second-line treatments for mCRC was performed. The strength of the correlation between both PFS and ORR and OS was assessed based on the Pearson's correlation coefficient (R) and the coefficient of determination (R 2 ). Twenty trials, including a total of 7,571 patients, met the search criteria. The median duration of post-progression survival (PPS) was 7.6 months. The median differences between experimental and control arms were 0.65 months (range, -2.4 to 3.4) for the median PFS and 0.7 months (range, -5.8 to 3.9) for the median OS. PFS and ORR showed moderate (R=0.734, R 2 =0.539, p < 0.001) and poor correlation (R=0.169, R 2 =0.029, p=0.476) with OS, respectively. No differences between anti-angiogenic agents and other drugs were evident. Targeted agents investigated in the second-line treatment of mCRC provided minimal PFS gains translating into modest OS improvements. Considering both the moderate correlation between PFS and OS and the short duration of PPS, the OS should remain the preferred primary endpoint for randomized clinical trials in the second-line treatment of mCRC.

Quantification of mutant SPOP proteins in prostate cancer using mass spectrometry-based targeted proteomics

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

Wang, Hui; Barbieri, Christopher E.; He, Jintang

Speckle-type POZ protein (SPOP) is an E3 ubiquitin ligase adaptor protein that functions as a potential tumor suppressor, and SPOP mutations have been identified in ~10% of human prostate cancers. However, it remains unclear if mutant SPOP proteins can be utilized as biomarkers for early detection, diagnosis, prognosis or targeted therapy of prostate cancer. Moreover, the SPOP mutation sites are distributed in a relatively short region where multiple lysine residues, posing significant challenges for bottom-up proteomics analysis of the SPOP mutations. To address this issue, PRISM (high-pressure, high-resolution separations coupled with intelligent selection and multiplexing)-SRM (selected reaction monitoring) mass spectrometrymore » assays have been developed for quantifying wild-type SPOP protein and 11 prostate cancer-derived SPOP mutations. Despite inherent limitations due to amino acid sequence constraints, all the PRISM-SRM assays developed using Arg-C digestion showed a linear dynamic range of at least two orders of magnitude, with limits of quantification range from 0.1 to 1 fmol/μg of total protein in the cell lysate. Applying these SRM assays to analyze HEK293T cells with and without expression of the three most frequent SPOP mutations in prostate cancer (Y87N, F102C or F133V) led to confident detection of all three SPOP mutations in corresponding positive cell lines but not in the negative cell lines. Expression of the F133V mutation and wild-type SPOP was at much lower levels compared to that of F102C and Y87N mutations; however, at present it is unknown if this also affects the activity of the SPOP protein. In summary, PRISM-SRM enables multiplexed, isoform-specific detection of mutant SPOP proteins in cell lysates, which holds great potential in biomarker development for prostate cancer.« less

A system for the measurement of gene targeting efficiency in human cell lines using an antibiotic resistance-GFP fusion gene.

PubMed

Konishi, Yuko; Karnan, Sivasundaram; Takahashi, Miyuki; Ota, Akinobu; Damdindorj, Lkhagvasuren; Hosokawa, Yoshitaka; Konishi, Hiroyuki

2012-09-01

Gene targeting in a broad range of human somatic cell lines has been hampered by inefficient homologous recombination. To improve this technology and facilitate its widespread application, it is critical to first have a robust and efficient research system for measuring gene targeting efficiency. Here, using a fusion gene consisting of hygromycin B phosphotransferase and 3'-truncated enhanced GFP (HygR-5' EGFP) as a reporter gene, we created a molecular system monitoring the ratio of homologous to random integration (H/R ratio) of targeting vectors into the genome. Cell clones transduced with a reporter vector containing HygR-5' EGFP were efficiently established from two human somatic cell lines. Established HygR-5' EGFP reporter clones retained their capacity to monitor gene targeting efficiency for a longer duration than a conventional reporter system using an unfused 5' EGFP gene. With the HygR-5' EGFP reporter system, we reproduced previous findings of gene targeting frequency being up-regulated by the use of an adeno-associated viral (AAV) backbone, a promoter-trap system, or a longer homology arm in a targeting vector, suggesting that this system accurately monitors H/R ratio. Thus, our HygR-5' EGFP reporter system will assist in the development of an efficient AAV-based gene targeting technology.

THE AKARI 2.5-5.0 μm SPECTRAL ATLAS OF TYPE-1 ACTIVE GALACTIC NUCLEI: BLACK HOLE MASS ESTIMATOR, LINE RATIO, AND HOT DUST TEMPERATURE

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

Kim, Dohyeong; Im, Myungshin; Kim, Ji Hoon

2015-01-01

We present 2.5-5.0 μm spectra of 83 nearby (0.002 < z < 0.48) and bright (K < 14 mag) type-1 active galactic nuclei (AGNs) taken with the Infrared Camera on board AKARI. The 2.5-5.0 μm spectral region contains emission lines such as Brβ (2.63 μm), Brα (4.05 μm), and polycyclic aromatic hydrocarbons (3.3 μm), which can be used for studying the black hole (BH) masses and star formation activity in the host galaxies of AGNs. The spectral region also suffers less dust extinction than in the ultra violet (UV) or optical wavelengths, which may provide an unobscured view of dusty AGNs. Our sample is selectedmore » from bright quasar surveys of Palomar-Green and SNUQSO, and AGNs with reverberation-mapped BH masses from Peterson et al. Using 11 AGNs with reliable detection of Brackett lines, we derive the Brackett-line-based BH mass estimators. We also find that the observed Brackett line ratios can be explained with the commonly adopted physical conditions of the broad line region. Moreover, we fit the hot and warm dust components of the dust torus by adding photometric data of SDSS, 2MASS, WISE, and ISO to the AKARI spectra, finding hot and warm dust temperatures of ∼1100 K and ∼220 K, respectively, rather than the commonly cited hot dust temperature of 1500 K.« less

The Mass-Metallicity Relation with the Direct Method on Stacked Spectra of SDSS Galaxies

NASA Astrophysics Data System (ADS)

Andrews, Brett H.; Martini, Paul

2013-03-01

The relation between galaxy stellar mass and gas-phase metallicity is a sensitive diagnostic of the main processes that drive galaxy evolution, namely cosmological gas inflow, metal production in stars, and gas outflow via galactic winds. We employed the direct method to measure the metallicities of ~200,000 star-forming galaxies from the Sloan Digital Sky Survey that were stacked in bins of (1) stellar mass and (2) both stellar mass and star formation rate (SFR) to significantly enhance the signal-to-noise ratio of the weak [O III] λ4363 and [O II] λλ7320, 7330 auroral lines required to apply the direct method. These metallicity measurements span three decades in stellar mass from log(M sstarf/M ⊙) = 7.4-10.5, which allows the direct method mass-metallicity relation to simultaneously capture the high-mass turnover and extend a full decade lower in mass than previous studies that employed more uncertain strong line methods. The direct method mass-metallicity relation rises steeply at low mass (O/H vprop M sstarf 1/2) until it turns over at log(M sstarf/M ⊙) = 8.9 and asymptotes to 12 + log(O/H) = 8.8 at high mass. The direct method mass-metallicity relation has a steeper slope, a lower turnover mass, and a factor of two to three greater dependence on SFR than strong line mass-metallicity relations. Furthermore, the SFR-dependence appears monotonic with stellar mass, unlike strong line mass-metallicity relations. We also measure the N/O abundance ratio, an important tracer of star formation history, and find the clear signature of primary and secondary nitrogen enrichment. N/O correlates tightly with oxygen abundance, and even more so with stellar mass.

Targeted Multiplex Imaging Mass Spectrometry with Single Chain Fragment Variable (scfv) Recombinant Antibodies

NASA Astrophysics Data System (ADS)

Thiery, Gwendoline; Mernaugh, Ray L.; Yan, Heping; Spraggins, Jeffrey M.; Yang, Junhai; Parl, Fritz F.; Caprioli, Richard M.

2012-10-01

Recombinant scfv antibodies specific for CYP1A1 and CYP1B1 P450 enzymes were combined with targeted imaging mass spectrometry to simultaneously detect the P450 enzymes present in archived, paraffin-embedded, human breast cancer tissue sections. By using CYP1A1 and CYP1B1 specific scfv, each coupled to a unique reporter molecule (i.e., a mass tag) it was possible to simultaneously detect multiple antigens within a single tissue sample with high sensitivity and specificity using mass spectrometry. The capability of imaging multiple antigens at the same time is a significant advance that overcomes technical barriers encountered when using present day approaches to develop assays that can simultaneously detect more than a single antigen in the same tissue sample.

The recommendation of line-balancing improvement on MCM product line 1 using genetics algorithm and moodie young at XYZ Company, Co.

NASA Astrophysics Data System (ADS)

Sriwana, I. K.; Marie, I. A.; Mangala, D.

2017-12-01

Kencana Gemilang, Co. is one electronics industry engaging in the manufacture sector. This company manufactures and assembles household electronic products, such as rice cooker, fan, iron, blender, etc. The company deals with an issue of underachievement of an established production target on MCM products line 1. This study aimed to calculate line efficiencies, delay times, and initial line smoothness indexes. The research was carried out by means of depicting a precedence diagram and gathering time data of each work element followed by examination and calculation of standard time as well as line balancing using methods of Moodie Young and Generics Algorithm. Based on results of calculation, better line balancing than the existing initial conditions, i.e. improvement in the line efficiency by 18.39%, deterioration in balanced delay by 28.39%, and deterioration of a smoothness index by 23.85% was obtained.

Review of in situ derivatization techniques for enhanced bioanalysis using liquid chromatography with mass spectrometry.

PubMed

Baghdady, Yehia Z; Schug, Kevin A

2016-01-01

Accurate and specific analysis of target molecules in complex biological matrices remains a significant challenge, especially when ultra-trace detection limits are required. Liquid chromatography with mass spectrometry is often the method of choice for bioanalysis. Conventional sample preparation and clean-up methods prior to the analysis of biological fluids such as liquid-liquid extraction, solid-phase extraction, or protein precipitation are time-consuming, tedious, and can negatively affect target recovery and detection sensitivity. An alternative or complementary strategy is the use of an off-line or on-line in situ derivatization technique. In situ derivatization can be incorporated to directly derivatize target analytes in their native biological matrices, without any prior sample clean-up methods, to substitute or even enhance the extraction and preconcentration efficiency of these traditional sample preparation methods. Designed appropriately, it can reduce the number of sample preparation steps necessary prior to analysis. Moreover, in situ derivatization can be used to enhance the performance of the developed liquid chromatography with mass spectrometry-based bioanalysis methods regarding stability, chromatographic separation, selectivity, and ionization efficiency. This review presents an overview of the commonly used in situ derivatization techniques coupled to liquid chromatography with mass spectrometry-based bioanalysis to guide and to stimulate future research. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Tandem Mass Spectrometry on a Miniaturized Laser Desorption Time-of-Flight Mass Spectrometer

NASA Technical Reports Server (NTRS)

Li, Xiang; Cornish, Timothy; Getty, Stephanie A.; Brinckerhoff, William B.

2016-01-01

Tandem mass spectrometry (MSMS) is a powerful and widely-used technique for identifying the molecular structure of organic constituents of a complex sample. Application of MSMS to the study of unknown planetary samples on a remote space mission would contribute to our understanding of the origin, evolution, and distribution of extraterrestrial organics in our solar system. Here we report on the realization of MSMS on a miniaturized laser desorption time-of-flight mass spectrometer (LD-TOF-MS), which is one of the most promising instrument types for future planetary missions. This achievement relies on two critical components: a curved-field reflectron and a pulsed-pin ion gate. These enable use of the complementary post-source decay (PSD) and laser-assisted collision induced dissociation (L-CID) MSMS methods on diverse measurement targets with only modest investment in instrument resources such as volume and weight. MSMS spectra of selected molecular targets in various organic standards exhibit excellent agreement when compared with results from a commercial, laboratory-scale TOF instrument, demonstrating the potential of this powerful technique in space and planetary environments.

Dynamics of periodic spring-mass chain coupled with an electric transmission line

NASA Astrophysics Data System (ADS)

Belloni, Edoardo; Cenedese, Mattia; Braghin, Francesco

2017-04-01

Periodic structures have received large interest due to their peculiar behavior: they have band gaps, that is portions of the frequency response along with any wave incoming in the structure is reflected. Numerous are the applications, like metamaterials and locally resonant structures. Nowadays, new possibilities could come from mechanical periodic structures that are connected to an electrical transmission line, periodic in turn. Starting from this idea, this paper analyses ideal a mono-atomic spring-mass chain, considering the springs connected to a periodic electric network, composed by inductances (and resistors): these simple examples will show how the frequency response is affected. In particular, the mutual influence between the electric and mechanical domain is highlighted, and the contribution of parameters on band gap positioning and design is explored. Details are provided about vibration modes and wave transmission.

Infrared small target tracking based on SOPC

NASA Astrophysics Data System (ADS)

Hu, Taotao; Fan, Xiang; Zhang, Yu-Jin; Cheng, Zheng-dong; Zhu, Bin

2011-01-01

The paper presents a low cost FPGA based solution for a real-time infrared small target tracking system. A specialized architecture is presented based on a soft RISC processor capable of running kernel based mean shift tracking algorithm. Mean shift tracking algorithm is realized in NIOS II soft-core with SOPC (System on a Programmable Chip) technology. Though mean shift algorithm is widely used for target tracking, the original mean shift algorithm can not be directly used for infrared small target tracking. As infrared small target only has intensity information, so an improved mean shift algorithm is presented in this paper. How to describe target will determine whether target can be tracked by mean shift algorithm. Because color target can be tracked well by mean shift algorithm, imitating color image expression, spatial component and temporal component are advanced to describe target, which forms pseudo-color image. In order to improve the processing speed parallel technology and pipeline technology are taken. Two RAM are taken to stored images separately by ping-pong technology. A FLASH is used to store mass temp data. The experimental results show that infrared small target is tracked stably in complicated background.

Mass spectrometry-based proteomics: from cancer biology to protein biomarkers, drug targets, and clinical applications.

PubMed

Jimenez, Connie R; Verheul, Henk M W

2014-01-01

Proteomics is optimally suited to bridge the gap between genomic information on the one hand and biologic functions and disease phenotypes at the other, since it studies the expression and/or post-translational modification (especially phosphorylation) of proteins--the major cellular players bringing about cellular functions--at a global level in biologic specimens. Mass spectrometry technology and (bio)informatic tools have matured to the extent that they can provide high-throughput, comprehensive, and quantitative protein inventories of cells, tissues, and biofluids in clinical samples at low level. In this article, we focus on next-generation proteomics employing nanoliquid chromatography coupled to high-resolution tandem mass spectrometry for in-depth (phospho)protein profiling of tumor tissues and (proximal) biofluids, with a focus on studies employing clinical material. In addition, we highlight emerging proteogenomic approaches for the identification of tumor-specific protein variants, and targeted multiplex mass spectrometry strategies for large-scale biomarker validation. Below we provide a discussion of recent progress, some research highlights, and challenges that remain for clinical translation of proteomic discoveries.

Observations of the Ca II K line in Hel0830A dark points on August 3, 1985

NASA Technical Reports Server (NTRS)

Holt, Rush D.; Park, Albert H.; Thompson, Joseph C.; Mullan, D. M.

1986-01-01

Spectroheliograms taken in the light of He I 10830 A at the National Solar Observatory Vacuum Telescope on Kitt Peak were used to identify coronal holes and bright points (BPs). Target points were identified, coordinates calculated, and spectra recorded. For each spectrum, the difference in wavelength between the Ca II K minimum and the FeI reference line was calculated. It was noteworthy that the overall effect is a blueshift. It should be noted that if material of chromospheric density moves outward at this velocity, it could supply the mass flux of the solar wind if this chromospheric flow was concentrated in a few dozen sources, each of a diameter of a few arc seconds.

Inferring the Composition of Super-Jupiter Mass Companions of Pulsars with Radio Line Spectroscopy

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

Ray, Alak; Loeb, Abraham, E-mail: akr@tifr.res.in, E-mail: aloeb@cfa.harvard.edu

We propose using radio line spectroscopy to detect molecular absorption lines (such as OH at 1.6–1.7 GHz) before and after the total eclipse of black widow and other short orbital period binary pulsars with low-mass companions. The companion in such a binary may be ablated away by energetic particles and high-energy radiation produced by the pulsar wind. The observations will probe the eclipsing wind being ablated by the pulsar and constrain the nature of the companion and its surroundings. Maser emission from the interstellar medium stimulated by a pulsar beam might also be detected from the intrabinary medium. The shortmore » temporal resolution allowed by the millisecond pulsars can probe this medium with the high angular resolution of the pulsar beam.« less

Multiple-hypothesis multiple-model line tracking

NASA Astrophysics Data System (ADS)

Pace, Donald W.; Owen, Mark W.; Cox, Henry

2000-07-01

Passive sonar signal processing generally includes tracking of narrowband and/or broadband signature components observed on a Lofargram or on a Bearing-Time-Record (BTR) display. Fielded line tracking approaches to date have been recursive and single-hypthesis-oriented Kalman- or alpha-beta filters, with no mechanism for considering tracking alternatives beyond the most recent scan of measurements. While adaptivity is often built into the filter to handle changing track dynamics, these approaches are still extensions of single target tracking solutions to multiple target tracking environment. This paper describes an application of multiple-hypothesis, multiple target tracking technology to the sonar line tracking problem. A Multiple Hypothesis Line Tracker (MHLT) is developed which retains the recursive minimum-mean-square-error tracking behavior of a Kalman Filter in a maximum-a-posteriori delayed-decision multiple hypothesis context. Multiple line track filter states are developed and maintained using the interacting multiple model (IMM) state representation. Further, the data association and assignment problem is enhanced by considering line attribute information (line bandwidth and SNR) in addition to beam/bearing and frequency fit. MHLT results on real sonar data are presented to demonstrate the benefits of the multiple hypothesis approach. The utility of the system in cluttered environments and particularly in crossing line situations is shown.

The Bivariate Luminosity--HI Mass Distribution Function of Galaxies based on the NIBLES Survey

NASA Astrophysics Data System (ADS)

Butcher, Zhon; Schneider, Stephen E.; van Driel, Wim; Lehnert, Matt

2016-01-01

We use 21cm HI line observations for 2610 galaxies from the Nançay Interstellar Baryons Legacy Extragalactic Survey (NIBLES) to derive a bivariate luminosity--HI mass distribution function. Our HI survey was selected to randomly probe the local (900 < cz < 12,000 km/s) galaxy population in each 0.5 mag wide bin for the absolute z-band magnitude range of -13.5 < Mz < -24 without regard to morphology or color. This targeted survey allowed more on-source integration time for weak and non-detected sources, enabling us to probe lower HI mass fractions and apply lower upper limits for non-detections than would be possible with the larger blind HI surveys. Additionally, we obtained a factor of four higher sensitivity follow-up observations at Arecibo of 90 galaxies from our non-detected and marginally detected categories to quantify the underlying HI distribution of sources not detected at Nançay. Using the optical luminosity function and our higher sensitivity follow up observations as priors, we use a 2D stepwise maximum likelihood technique to derive the two dimensional volume density distribution of luminosity and HI mass in each SDSS band.

Evidence of a Bottom-heavy Initial Mass Function in Massive Early-type Galaxies from Near-infrared Metal Lines

NASA Astrophysics Data System (ADS)

Lagattuta, David J.; Mould, Jeremy R.; Forbes, Duncan A.; Monson, Andrew J.; Pastorello, Nicola; Persson, S. Eric

2017-09-01

We present new evidence for a variable stellar initial mass function (IMF) in massive early-type galaxies, using high-resolution, near-infrared spectroscopy from the Folded-port InfraRed Echellette spectrograph (FIRE) on the Magellan Baade Telescope at Las Campanas Observatory. In this pilot study, we observe several gravity-sensitive metal lines between 1.1 and 1.3 μm in eight highly luminous (L˜ 10{L}* ) nearby galaxies. Thanks to the broad wavelength coverage of FIRE, we are also able to observe the Ca II triplet feature, which helps with our analysis. After measuring the equivalent widths (EWs) of these lines, we notice mild to moderate trends between EW and central velocity dispersion (σ), with some species (K I, Na I, Mn I) showing a positive EW-σ correlation and others (Mg I, Ca II, Fe I) a negative one. To minimize the effects of metallicity, we measure the ratio R = [EW(K I)/EW(Mg I)], finding a significant systematic increase in this ratio with respect to σ. We then probe for variations in the IMF by comparing the measured line ratios to the values expected in several IMF models. Overall, we find that low-mass galaxies (σ ˜ 100 km s-1) favor a Chabrier IMF, while high-mass galaxies (σ ˜ 350 km s-1) are better described with a steeper (dwarf-rich) IMF slope. While we note that our galaxy sample is small and may suffer from selection effects, these initial results are still promising. A larger sample of galaxies will therefore provide an even clearer picture of IMF trends in this regime. This paper includes data gathered with the 6.5 m Magellan Telescopes located at Las Campanas Observatory, Chile.

CONSTRAINTS ON BLACK HOLE GROWTH, QUASAR LIFETIMES, AND EDDINGTON RATIO DISTRIBUTIONS FROM THE SDSS BROAD-LINE QUASAR BLACK HOLE MASS FUNCTION

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

Kelly, Brandon C.; Hernquist, Lars; Siemiginowska, Aneta

2010-08-20

We present an estimate of the black hole mass function of broad-line quasars (BLQSOs) that self-consistently corrects for incompleteness and the statistical uncertainty in the mass estimates, based on a sample of 9886 quasars at 1 < z < 4.5 drawn from the Sloan Digital Sky Survey (SDSS). We find evidence for 'cosmic downsizing' of black holes in BLQSOs, where the peak in their number density shifts to higher redshift with increasing black hole mass. The cosmic mass density for black holes seen as BLQSOs peaks at z {approx} 2. We estimate the completeness of the SDSS as a functionmore » of the black hole mass and Eddington ratio, and find that at z > 1 it is highly incomplete at M {sub BH} {approx}< 10{sup 9} M {sub sun} and L/L{sub Edd} {approx}< 0.5. We estimate a lower limit on the lifetime of a single BLQSO phase to be t {sub BL} > 150 {+-} 15 Myr for black holes at z = 1 with a mass of M {sub BH} = 10{sup 9} M{sub sun}, and we constrain the maximum mass of a black hole in a BLQSO to be {approx}3 x 10{sup 10} M{sub sun}. Our estimated distribution of BLQSO Eddington ratios peaks at L/L {sub Edd} {approx} 0.05 and has a dispersion of {approx}0.4 dex, implying that most BLQSOs are not radiating at or near the Eddington limit; however, the location of the peak is subject to considerable uncertainty. The steep increase in number density of BLQSOs toward lower Eddington ratios is expected if the BLQSO accretion rate monotonically decays with time. Furthermore, our estimated lifetime and Eddington ratio distributions imply that the majority of the most massive black holes spend a significant amount of time growing in an earlier obscured phase, a conclusion which is independent of the unknown obscured fraction. These results are consistent with models for self-regulated black hole growth, at least for massive systems at z > 1, where the BLQSO phase occurs at the end of a fueling event when black hole feedback unbinds the accreting gas, halting the accretion flow.« less

Rapid detection of proteins in transgenic crops without protein reference standards by targeted proteomic mass spectrometry.

PubMed

Schacherer, Lindsey J; Xie, Weiping; Owens, Michaela A; Alarcon, Clara; Hu, Tiger X

2016-09-01

Liquid chromatography coupled with tandem mass spectrometry is increasingly used for protein detection for transgenic crops research. Currently this is achieved with protein reference standards which may take a significant time or efforts to obtain and there is a need for rapid protein detection without protein reference standards. A sensitive and specific method was developed to detect target proteins in transgenic maize leaf crude extract at concentrations as low as ∼30 ng mg(-1) dry leaf without the need of reference standards or any sample enrichment. A hybrid Q-TRAP mass spectrometer was used to monitor all potential tryptic peptides of the target proteins in both transgenic and non-transgenic samples. The multiple reaction monitoring-initiated detection and sequencing (MIDAS) approach was used for initial peptide/protein identification via Mascot database search. Further confirmation was achieved by direct comparison between transgenic and non-transgenic samples. Definitive confirmation was provided by running the same experiments of synthetic peptides or protein standards, if available. A targeted proteomic mass spectrometry method using MIDAS approach is an ideal methodology for detection of new proteins in early stages of transgenic crop research and development when neither protein reference standards nor antibodies are available. © 2016 Society of Chemical Industry. © 2016 Society of Chemical Industry.

Ultra-trace levels analysis of microcystins and nodularin in surface water by on-line solid-phase extraction with high-performance liquid chromatography tandem mass spectrometry.

PubMed

Balest, Lydia; Murgolo, Sapia; Sciancalepore, Lucia; Montemurro, Patrizia; Abis, Pier Paolo; Pastore, Carlo; Mascolo, Giuseppe

2016-06-01

An on-line solid phase extraction coupled with high-performance liquid chromatography in tandem with mass spectrometry (on-line SPE/HPLC/MS-MS) method for the determination of five microcystins and nodularin in surface waters at submicrogram per liter concentrations has been optimized. Maximum recoveries were achieved by carefully optimizing the extraction sample volume, loading solvent, wash solvent, and pH of the sample. The developed method was also validated according to both UNI EN ISO IEC 17025 and UNICHIM guidelines. Specifically, ten analytical runs were performed at three different concentration levels using a reference mix solution containing the six analytes. The method was applied for monitoring the concentrations of microcystins and nodularin in real surface water during a sampling campaign of 9 months in which the ELISA method was used as standard official method. The results of the two methods were compared showing good agreement when the highest concentration values of MCs were found. Graphical abstract An on-line SPE/HPLC/MS-MS method for the determination of five microcystins and nodularin in surface waters at sub μg L(-1) was optimized and compared with ELISA assay method for real samples.

On-Line and Off-Line Assessment of Metacognition

ERIC Educational Resources Information Center

Saraç, Seda; Karakelle, Sema

2012-01-01

The study investigates the interrelationships between different on-line and off-line measures for assessing metacognition. The participants were 47 fifth grade elementary students. Metacognition was assessed through two off-line and two on-line measures. The off-line measures consisted of a teacher rating scale and a self-report questionnaire. The…

Targeted silver nanoparticles for ratiometric cell phenotyping

NASA Astrophysics Data System (ADS)

Willmore, Anne-Mari A.; Simón-Gracia, Lorena; Toome, Kadri; Paiste, Päärn; Kotamraju, Venkata Ramana; Mölder, Tarmo; Sugahara, Kazuki N.; Ruoslahti, Erkki; Braun, Gary B.; Teesalu, Tambet

2016-04-01

Affinity targeting is used to deliver nanoparticles to cells and tissues. For efficient targeting, it is critical to consider the expression and accessibility of the relevant receptors in the target cells. Here, we describe isotopically barcoded silver nanoparticles (AgNPs) as a tool for auditing affinity ligand receptors in cells. Tumor penetrating peptide RPARPAR (receptor: NRP-1) and tumor homing peptide GKRK (receptor: p32) were used as affinity ligands on the AgNPs. The binding and uptake of the peptide-functionalized AgNPs by cultured PPC-1 prostate cancer and M21 melanoma cells was dependent on the cell surface expression of the cognate peptide receptors. Barcoded peptide-functionalized AgNPs were synthesized from silver and palladium isotopes. The cells were incubated with a cocktail of the barcoded nanoparticles [RPARPAR (R), GKRK (K), and control], and cellular binding and internalization of each type of nanoparticle was assessed by inductively coupled plasma mass spectrometry. The results of isotopic analysis were in agreement with data obtained using optical methods. Using ratiometric measurements, we were able to classify the PPC-1 cell line as mainly NRP-1-positive, with 75 +/- 5% R-AgNP uptake, and the M21 cell line as only p32-positive, with 89 +/- 9% K-AgNP uptake. The isotopically barcoded multiplexed AgNPs are useful as an in vitro ratiometric phenotyping tool and have potential uses in functional evaluation of the expression of accessible homing peptide receptors in vivo.Affinity targeting is used to deliver nanoparticles to cells and tissues. For efficient targeting, it is critical to consider the expression and accessibility of the relevant receptors in the target cells. Here, we describe isotopically barcoded silver nanoparticles (AgNPs) as a tool for auditing affinity ligand receptors in cells. Tumor penetrating peptide RPARPAR (receptor: NRP-1) and tumor homing peptide GKRK (receptor: p32) were used as affinity ligands on the AgNPs. The

Expanding Academic Vocabulary with an Interactive On-Line Database

ERIC Educational Resources Information Center

Horst, Marlise; Cobb, Tom; Nicolae, Ioana

2005-01-01

University students used a set of existing and purpose-built on-line tools for vocabulary learning in an experimental ESL course. The resources included concordance, dictionary, cloze-builder, hypertext, and a database with interactive self-quizzing feature (all freely available at www.lextutor.ca). The vocabulary targeted for learning consisted…

Incomplete mass transfer processes in 28Si +93Nb reaction

NASA Astrophysics Data System (ADS)

Tripathi, R.; Sodaye, S.; Ramachandran, K.; Sharma, S. K.; Pujari, P. K.

Cross sections of reaction products were measured in 28Si +93Nb reaction using recoil catcher technique involving by off-line gamma-ray spectrometry at beam energies of 105 and 155MeV. At Elab = 155MeV, the contribution from different incomplete mass transfer processes is investigated. Results of the present studies show the contribution from deep inelastic collision (DIC), massive transfer or incomplete fusion (ICF) and quasi-elastic transfer (QET). The contribution from massive transfer reactions was confirmed from the fractional yield of the reaction products in the forward catcher foil. The present results are different from those from the reactions with comparatively higher entrance channel mass asymmetry with lighter projectiles, for which dominant transfer processes are ICF and QET which involve mass transfer predominantly from projectile to target. The N/Z values of the products close to the target mass were observed to be in a wide range, starting from N/Z of the target (93Nb) and extending slightly below the N/Z of the composite system, consistent with the contribution from DIC and QET reactions. At Elab = 105MeV, a small contribution from QET was observed in addition to complete fusion.

A Reverberation-based Black Hole Mass for MCG-06-30-15

NASA Astrophysics Data System (ADS)

Bentz, Misty C.; Cackett, Edward M.; Crenshaw, D. Michael; Horne, Keith; Street, Rachel; Ou-Yang, Benjamin

2016-10-01

We present the results of a reverberation campaign targeting MGC-06-30-15. Spectrophotometric monitoring and broad-band photometric monitoring over the course of four months in spring 2012 allowed a determination of a time delay in the broad Hβ emission line of τ = 5.3 ± 1.8 days in the rest frame of the active galactic nucleus (AGN). Combined with the width of the variable portion of the emission line, we determine a black hole mass of M BH = (1.6 ± 0.4) × 106 M ⊙. Both the Hβ time delay and the black hole mass are in good agreement with expectations from the R BLR-L and M BH-σ ⋆ relationships for other reverberation-mapped AGNs. The Hβ time delay is also in good agreement with the relationship between Hβ and broad-band near-IR delays, in which the effective size of the broad-line region is ˜4-5 times smaller than the inner edge of the dust torus. Additionally, the reverberation-based mass is in good agreement with estimates from the scaling relationship of the break in the X-ray power spectral density, and with constraints based on stellar kinematics derived from integral field spectroscopy of the inner ˜0.5 kpc of the galaxy.

Targeted and untargeted high resolution mass approach for a putative profiling of glycosylated simple phenols in hybrid grapes.

PubMed

Barnaba, Chiara; Dellacassa, Eduardo; Nicolini, Giorgio; Giacomelli, Mattia; Roman Villegas, Tomas; Nardin, Tiziana; Larcher, Roberto

2017-08-01

Vitis vinifera is one of the most widespread grapevines around the world representing the raw material for high quality wine production. The availability of more resistant interspecific hybrid vine varieties, developed from crosses between Vitis vinifera and other Vitis species, has generated much interest, also due to the low environmental effect of production. However, hybrid grape wine composition and varietal differences between interspecific hybrids have not been well defined, particularly for the simple phenols profile. The dynamic of these phenols in wines, where the glycosylated forms can be transformed into the free ones during winemaking, also raises an increasing health interest by their role as antoxidants in wine consumers. In this work an on-line SPE clean-up device, to reduce matrix interference, was combined with ultra-high liquid chromatography-high resolution mass spectrometry in order to increase understanding of the phenolic composition of hybrid grape varieties. Specifically, the phenolic composition of 4 hybrid grape varieties (red, Cabernet Cantor and Prior; white, Muscaris and Solaris) and 2 European grape varieties (red, Merlot; white, Chardonnay) was investigated, focusing on free and glycosidically bound simple phenols and considering compound distribution in pulp, skin, seeds and wine. Using a targeted approach 53 free simple phenols and 7 glycosidic precursors were quantified with quantification limits ranging from 0.001 to 2mgKg -1 and calibration R 2 of 0.99 for over 86% of compounds. The untargeted approach made it possible to tentatively identify 79 glycosylated precursors of selected free simple phenols in the form of -hexoside (N=30), -pentoside (21), -hexoside-hexoside (17), -hexoside-pentoside (4), -pentoside-hexoside (5) and -pentoside-pentoside (2) derivatives on the basis of accurate mass, isotopic pattern and MS/MS fragmentation. Copyright © 2017 Elsevier Ltd. All rights reserved.

Fragment-Based Screening of a Natural Product Library against 62 Potential Malaria Drug Targets Employing Native Mass Spectrometry

PubMed Central

2018-01-01

Natural products are well known for their biological relevance, high degree of three-dimensionality, and access to areas of largely unexplored chemical space. To shape our understanding of the interaction between natural products and protein targets in the postgenomic era, we have used native mass spectrometry to investigate 62 potential protein targets for malaria using a natural-product-based fragment library. We reveal here 96 low-molecular-weight natural products identified as binding partners of 32 of the putative malarial targets. Seventy-nine (79) fragments have direct growth inhibition on Plasmodium falciparum at concentrations that are promising for the development of fragment hits against these protein targets. This adds a fragment library to the published HTS active libraries in the public domain. PMID:29436819

Fragment-Based Screening of a Natural Product Library against 62 Potential Malaria Drug Targets Employing Native Mass Spectrometry.

PubMed

Vu, Hoan; Pedro, Liliana; Mak, Tin; McCormick, Brendan; Rowley, Jessica; Liu, Miaomiao; Di Capua, Angela; Williams-Noonan, Billy; Pham, Ngoc B; Pouwer, Rebecca; Nguyen, Bao; Andrews, Katherine T; Skinner-Adams, Tina; Kim, Jessica; Hol, Wim G J; Hui, Raymond; Crowther, Gregory J; Van Voorhis, Wesley C; Quinn, Ronald J

2018-04-13

Natural products are well known for their biological relevance, high degree of three-dimensionality, and access to areas of largely unexplored chemical space. To shape our understanding of the interaction between natural products and protein targets in the postgenomic era, we have used native mass spectrometry to investigate 62 potential protein targets for malaria using a natural-product-based fragment library. We reveal here 96 low-molecular-weight natural products identified as binding partners of 32 of the putative malarial targets. Seventy-nine (79) fragments have direct growth inhibition on Plasmodium falciparum at concentrations that are promising for the development of fragment hits against these protein targets. This adds a fragment library to the published HTS active libraries in the public domain.

BEAM TRANSPORT LINES FOR THE BSNS.

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

WEI, J.

2006-06-26

This paper presents the design of two beam transport lines at the BSNS: one is the injection line from the Linac to the RCS and the other is the target line from the RCS to the target station. In the injection beam line, space charge effects, transverse halo collimation, momentum tail collimation and debunching are the main concerned topics. A new method of using triplet cells and stripping foils is used to collimate transverse halo. A long straight section is reserved for the future upgrading linac and debuncher. In the target beam line, large halo emittance, beam stability at themore » target due to kicker failures and beam jitters, shielding of back-scattering neutrons from the target are main concerned topics. Special bi-gap magnets will be used to reduce beam losses in the collimators in front of the target.« less

On-line liquid chromatography/tandem mass spectrometry simultaneous determination of opiates, cocainics and amphetamines in dried blood spots.

PubMed

Saussereau, E; Lacroix, C; Gaulier, J M; Goulle, J P

2012-02-15

A novel approach has been developed for the illicit drugs quantitative determination using dried blood spots (DBS) on filter paper. The illicit drugs tested were opiates (morphine and its 3- and 6-glucuronide metabolites, codeine, 6-monoacetylmorphine), cocainics (ecgonine methylester, benzoylecgonine, cocaine, cocaethylene) and amphetamines (amphetamine, methamphetamine, MDA, MDMA, MDEA). The described method, requiring a small blood volume, is based on high performance liquid chromatography coupled to tandem mass spectrometry using on-line extraction. A Whatman card 903 was spotted with 30μL of whole blood and left overnight to dry at room temperature. A 3-mm diameter disk was removed using a manual punch, suspended in 150μL of water for 10min with ultrasonication, and then 100μL was injected in the on-line LC-MS/MS system. An Oasis HLB was used as an extraction column and a C18 Atlantis as an analytical column. The chromatographic cycle was performed with 20mM ammonium formate buffer (pH 2.8) (solvent A) and acetonitrile/solvent A (90:10, v/v) gradient in 16min. Detection was performed in positive electrospray ionization mode (ESI+) with a Quattro Micro (Waters). Recoveries of all analytes were up to 80%. DBS were stored in duplicate at 4°C and -20°C for up to 6 months. Illicit drugs seemed to be much more stabled at -20°C. Furthermore, it was tested whether analysis of DBS may be as reliable as that of whole blood investigating authentic samples; significant correlations were obtained. This DBS assay has potential as rapid, sensitive and inexpensive option for the illicit drugs determination in small blood volumes, which seems of great interest in suspected cases of driving under the influence of drugs. Copyright © 2011 Elsevier B.V. All rights reserved.

P39-T Analysis of Oligosaccharides by Capillary-Scale High-Performance Anion-Exchange Chromatography with Pulsed Amperometric Detection (CHPAEC-PAD) and On-Line Electrospray-Ionization Ion-Trap Mass Spectrometry (CHPAEC-ITMS)

PubMed Central

Bruggink, C.; Koeleman, C.; Barreto, V.; Lui, Y.; Pohl, C.; Ingendoh, A.; Wuhrer, M.; Hokke, C.; Deelder, A.

2007-01-01

High-pH anion-exchange chromatography with pulsed amperometric detection (HPAEC-PAD) is an established technique for selective separation and analysis of underivatized carbohydrates. The miniaturization of chromatographic techniques by means of capillary columns, and on-line coupling to mass spectrometry are critical to the further development of glycan analysis methods that are compatible with the current requirements in clinical settings. A system has been developed based on the Dionex BioLC equipped with a microbore gradient pump with PEEK flow splitter, a FAMOS micro autosampler, a modified electrochemical cell for on-line capillary PAD, and a capillary column (380 μm i.d.) packed with a new type of anion-exchange resin. This system operates with sensitivity in the low femtomol range. In addition, an on-line capillary desalter has been developed to allow direct coupling to the Bruker Esquire 3000 ion-trap mass spectrometer with electrospray ionization interface (ESI-IT-MS). Both systems have been evaluated using oligosaccharide standards as well as urine samples exhibiting various lysosomal oligosaccharide storage diseases. Initial data indicate that the robust and selective anion-exchange system, in combination with ESI-IT-MS for structure confirmation and analysis, provides a powerful platform that complements existing nano/capillary LC-MS methods for analytical determination of oligosaccharides in biological matrices.

Potential role for mammalian target of rapamycin inhibitors as first-line therapy in hormone receptor–positive advanced breast cancer

PubMed Central

Beck, J Thaddeus

2015-01-01

Despite advances in cytotoxic chemotherapy and targeted therapies, 5-year survival rates remain low for patients with advanced breast cancer at diagnosis. This highlights the limited effectiveness of current treatment options. An improved understanding of cellular functions associated with the development and progression of breast cancer has resulted in the creation of a number of novel targeted molecular therapies. However, more work is needed to improve outcomes, particularly in the first-line recurrent or metastatic hormone receptor–positive breast cancer setting. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) pathway is a major intracellular signaling pathway that is often upregulated in breast cancer, and overactivation of this pathway has been associated with primary or developed resistance to endocrine treatment. Clinical data from the Phase III Breast Cancer Trials of Oral Everolimus-2 (BOLERO-2) study of the mTOR inhibitor everolimus combined with exemestane in hormone receptor–positive advanced breast cancer were very promising, highlighting the potential role of mTOR inhibitors in combination with endocrine therapies as a first-line treatment option for these patients. It is hoped that the use of mTOR inhibitors combined with current standard-of-care endocrine therapies, such as aromatase inhibitors, in the first-line advanced breast cancer setting may result in greater antitumor effects and also delay or reverse treatment resistance. PMID:26675495

At-line nanofractionation with parallel mass spectrometry and bioactivity assessment for the rapid screening of thrombin and factor Xa inhibitors in snake venoms.

PubMed

Mladic, Marija; Zietek, Barbara M; Iyer, Janaki Krishnamoorthy; Hermarij, Philip; Niessen, Wilfried M A; Somsen, Govert W; Kini, R Manjunatha; Kool, Jeroen

2016-02-01

Snake venoms comprise complex mixtures of peptides and proteins causing modulation of diverse physiological functions upon envenomation of the prey organism. The components of snake venoms are studied as research tools and as potential drug candidates. However, the bioactivity determination with subsequent identification and purification of the bioactive compounds is a demanding and often laborious effort involving different analytical and pharmacological techniques. This study describes the development and optimization of an integrated analytical approach for activity profiling and identification of venom constituents targeting the cardiovascular system, thrombin and factor Xa enzymes in particular. The approach developed encompasses reversed-phase liquid chromatography (RPLC) analysis of a crude snake venom with parallel mass spectrometry (MS) and bioactivity analysis. The analytical and pharmacological part in this approach are linked using at-line nanofractionation. This implies that the bioactivity is assessed after high-resolution nanofractionation (6 s/well) onto high-density 384-well microtiter plates and subsequent freeze drying of the plates. The nanofractionation and bioassay conditions were optimized for maintaining LC resolution and achieving good bioassay sensitivity. The developed integrated analytical approach was successfully applied for the fast screening of snake venoms for compounds affecting thrombin and factor Xa activity. Parallel accurate MS measurements provided correlation of observed bioactivity to peptide/protein masses. This resulted in identification of a few interesting peptides with activity towards the drug target factor Xa from a screening campaign involving venoms of 39 snake species. Besides this, many positive protease activity peaks were observed in most venoms analysed. These protease fingerprint chromatograms were found to be similar for evolutionary closely related species and as such might serve as generic snake protease

Application of Targeted Mass Spectrometry for the Quantification of Sirtuins in the Central Nervous System

NASA Astrophysics Data System (ADS)

Jayasena, T.; Poljak, A.; Braidy, N.; Zhong, L.; Rowlands, B.; Muenchhoff, J.; Grant, R.; Smythe, G.; Teo, C.; Raftery, M.; Sachdev, P.

2016-10-01

Sirtuin proteins have a variety of intracellular targets, thereby regulating multiple biological pathways including neurodegeneration. However, relatively little is currently known about the role or expression of the 7 mammalian sirtuins in the central nervous system. Western blotting, PCR and ELISA are the main techniques currently used to measure sirtuin levels. To achieve sufficient sensitivity and selectivity in a multiplex-format, a targeted mass spectrometric assay was developed and validated for the quantification of all seven mammalian sirtuins (SIRT1-7). Quantification of all peptides was by multiple reaction monitoring (MRM) using three mass transitions per protein-specific peptide, two specific peptides for each sirtuin and a stable isotope labelled internal standard. The assay was applied to a variety of samples including cultured brain cells, mammalian brain tissue, CSF and plasma. All sirtuin peptides were detected in the human brain, with SIRT2 being the most abundant. Sirtuins were also detected in human CSF and plasma, and guinea pig and mouse tissues. In conclusion, we have successfully applied MRM mass spectrometry for the detection and quantification of sirtuin proteins in the central nervous system, paving the way for more quantitative and functional studies.

Charged derivatization and on-line solid phase extraction to measure extremely low cortisol and cortisone levels in human saliva with liquid chromatography-tandem mass spectrometry.

PubMed

Magda, Balázs; Dobi, Zoltán; Mészáros, Katalin; Szabó, Éva; Márta, Zoltán; Imre, Tímea; Szabó, Pál T

2017-06-05

The aim of this study was to develop a sensitive, reliable and high-throughput liquid chromatography - electrospray ionization - mass spectrometric (LC-ESI-MS/MS) method for the simultaneous quantitation of cortisol and cortisone in human saliva. Derivatization with 2-hydrazino-1-methylpyridine (HMP) was one of the most challenging aspects of the method development. The reagent was reacting with cortisol and cortisone at 60°C within 1h, giving mono- and bis-hydrazone derivatives. Investigation of derivatization reaction and sample preparation was detailed and discussed. Improvement of method sensitivity was achieved with charged derivatization and use of on-line solid phase extraction (on-line SPE). The lower limit of quantitation (LLOQ) was 5 and 10pg/ml for cortisol and cortisone, respectively. The developed method was subsequently applied to clinical laboratory measurement of cortisol and cortisone in human saliva. Copyright © 2017 Elsevier B.V. All rights reserved.

Spatial and Foveal Biases, Not Perceived Mass or Heaviness, Explain the Effect of Target Size on Representational Momentum and Representational Gravity

ERIC Educational Resources Information Center

De Sá Teixeira, Nuno; Oliveira, Armando Mónica

2014-01-01

The spatial memory for the last position occupied by a moving target is usually displaced forward in the direction of motion. Interpreted as a mental analogue of physical momentum, this phenomenon was coined "representational momentum" (RM). As momentum is given by the product of an object's velocity and mass, both these factors came to…

Advances in targeted proteomics and applications to biomedical research

PubMed Central

Shi, Tujin; Song, Ehwang; Nie, Song; Rodland, Karin D.; Liu, Tao; Qian, Wei-Jun; Smith, Richard D.

2016-01-01

Targeted proteomics technique has emerged as a powerful protein quantification tool in systems biology, biomedical research, and increasing for clinical applications. The most widely used targeted proteomics approach, selected reaction monitoring (SRM), also known as multiple reaction monitoring (MRM), can be used for quantification of cellular signaling networks and preclinical verification of candidate protein biomarkers. As an extension to our previous review on advances in SRM sensitivity herein we review recent advances in the method and technology for further enhancing SRM sensitivity (from 2012 to present), and highlighting its broad biomedical applications in human bodily fluids, tissue and cell lines. Furthermore, we also review two recently introduced targeted proteomics approaches, parallel reaction monitoring (PRM) and data-independent acquisition (DIA) with targeted data extraction on fast scanning high-resolution accurate-mass (HR/AM) instruments. Such HR/AM targeted quantification with monitoring all target product ions addresses SRM limitations effectively in specificity and multiplexing; whereas when compared to SRM, PRM and DIA are still in the infancy with a limited number of applications. Thus, for HR/AM targeted quantification we focus our discussion on method development, data processing and analysis, and its advantages and limitations in targeted proteomics. Finally, general perspectives on the potential of achieving both high sensitivity and high sample throughput for large-scale quantification of hundreds of target proteins are discussed. PMID:27302376

Population kinetics on K alpha lines of partially ionized Cl atoms.

PubMed

Kawamura, Tohru; Nishimura, Hiroaki; Koike, Fumihiro; Ochi, Yoshihiro; Matsui, Ryoji; Miao, Wen Yong; Okihara, Shinichiro; Sakabe, Shuji; Uschmann, Ingo; Förster, Eckhart; Mima, Kunioki

2002-07-01

A population kinetics code was developed to analyze K alpha emission from partially ionized chlorine atoms in hydrocarbon plasmas. Atomic processes are solved under collisional-radiative equilibrium for two-temperature plasmas. It is shown that the fast electrons dominantly contribute to ionize the K-shell bound electrons (i.e., inner-shell ionization) and the cold electrons to the outer-shell bound ones. Ratios of K alpha lines of partially ionized atoms are presented as a function of cold-electron temperature. The model was validated by observation of the K alpha lines from a chlorinated plastic target irradiated with 1 TW Ti:sapphire laser pulses at 1.5 x 10(17) W/cm(2), inferring a plasma temperature of about 100 eV on the target surface.

Tailored first-line and second-line CDK4-targeting treatment combinations in mouse models of pancreatic cancer.

PubMed

Chou, Angela; Froio, Danielle; Nagrial, Adnan M; Parkin, Ashleigh; Murphy, Kendelle J; Chin, Venessa T; Wohl, Dalia; Steinmann, Angela; Stark, Rhys; Drury, Alison; Walters, Stacey N; Vennin, Claire; Burgess, Andrew; Pinese, Mark; Chantrill, Lorraine A; Cowley, Mark J; Molloy, Timothy J; Waddell, Nicola; Johns, Amber; Grimmond, Sean M; Chang, David K; Biankin, Andrew V; Sansom, Owen J; Morton, Jennifer P; Grey, Shane T; Cox, Thomas R; Turchini, John; Samra, Jaswinder; Clarke, Stephen J; Timpson, Paul; Gill, Anthony J; Pajic, Marina

2017-10-28

Extensive molecular heterogeneity of pancreatic ductal adenocarcinoma (PDA), few effective therapies and high mortality make this disease a prime model for advancing development of tailored therapies. The p16-cyclin D-cyclin-dependent kinase 4/6-retinoblastoma (RB) protein (CDK4) pathway, regulator of cell proliferation, is deregulated in PDA. Our aim was to develop a novel personalised treatment strategy for PDA based on targeting CDK4. Sensitivity to potent CDK4/6 inhibitor PD-0332991 (palbociclib) was correlated to protein and genomic data in 19 primary patient-derived PDA lines to identify biomarkers of response. In vivo efficacy of PD-0332991 and combination therapies was determined in subcutaneous, intrasplenic and orthotopic tumour models derived from genome-sequenced patient specimens and genetically engineered model. Mechanistically, monotherapy and combination therapy were investigated in the context of tumour cell and extracellular matrix (ECM) signalling. Prognostic relevance of companion biomarker, RB protein, was evaluated and validated in independent PDA patient cohorts (>500 specimens). Subtype-specific in vivo efficacy of PD-0332991-based therapy was for the first time observed at multiple stages of PDA progression: primary tumour growth, recurrence (second-line therapy) and metastatic setting and may potentially be guided by a simple biomarker (RB protein). PD-0332991 significantly disrupted surrounding ECM organisation, leading to increased quiescence, apoptosis, improved chemosensitivity, decreased invasion, metastatic spread and PDA progression in vivo. RB protein is prevalent in primary operable and metastatic PDA and may present a promising predictive biomarker to guide this therapeutic approach. This study demonstrates the promise of CDK4 inhibition in PDA over standard therapy when applied in a molecular subtype-specific context. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights

Enhanced tumor targeting of cRGD peptide-conjugated albumin nanoparticles in the BxPC-3 cell line.

PubMed

Yu, Xinzhe; Song, Yunlong; Di, Yang; He, Hang; Fu, Deliang; Jin, Chen

2016-08-12

The emerging albumin nanoparticle brings new hope for the delivery of antitumor drugs. However, a lack of robust tumor targeting greatly limits its application. In this paper, cyclic arginine-glycine-aspartic-conjugated, gemcitabine-loaded human serum albumin nanoparticles (cRGD-Gem-HSA-NPs) were successfully prepared, characterized, and tested in vitro in the BxPC-3 cell line. Initially, 4-N-myristoyl-gemcitabine (Gem-C14) was formed by conjugating myristoyl to the 4-amino group of gemcitabine. Then, cRGD-HSA was synthesized using sulfosuccinimidyl-(4-N-maleimidomethyl)cyclohexane-1-carboxylate (Sulfo-SMCC) cross-linkers. Finally, cRGD-Gem-HSA-NPs were formulated based on the nanoparticle albumin-bound (nab) technology. The resulting NPs were characterized for particle size, zeta potential, morphology, encapsulation efficiency, and drug loading efficiency. In vitro cellular uptake and inhibition studies were conducted to compare Gem-HSA-NPs and cRGD-Gem-HSA-NPs in a human pancreatic cancer cell line (BxPC-3). The cRGD-Gem-HSA-NPs exhibited an average particle size of 160 ± 23 nm. The encapsulation rate and drug loading rate were approximately 83 ± 5.6% and 11 ± 4.2%, respectively. In vitro, the cRGD-anchored NPs exhibited a significantly greater affinity for the BxPC-3 cells compared to non-targeted NPs and free drug. The cRGD-Gem-HSA-NPs also showed the strongest inhibitory effect in the BxPC-3 cells among all the analyzed groups. The improved efficacy of cRGD-Gem-HSA-NPs in the BxPC-3 cell line warrants further in vivo investigations.

Quality of Graphite Target for Biological/Biomedical/Environmental Applications of 14C-Accelerator Mass Spectrometry

PubMed Central

2010-01-01

Catalytic graphitization for 14C-accelerator mass spectrometry (14C-AMS) produced various forms of elemental carbon. Our high-throughput Zn reduction method (C/Fe = 1:5, 500 °C, 3 h) produced the AMS target of graphite-coated iron powder (GCIP), a mix of nongraphitic carbon and Fe3C. Crystallinity of the AMS targets of GCIP (nongraphitic carbon) was increased to turbostratic carbon by raising the C/Fe ratio from 1:5 to 1:1 and the graphitization temperature from 500 to 585 °C. The AMS target of GCIP containing turbostratic carbon had a large isotopic fractionation and a low AMS ion current. The AMS target of GCIP containing turbostratic carbon also yielded less accurate/precise 14C-AMS measurements because of the lower graphitization yield and lower thermal conductivity that were caused by the higher C/Fe ratio of 1:1. On the other hand, the AMS target of GCIP containing nongraphitic carbon had higher graphitization yield and better thermal conductivity over the AMS target of GCIP containing turbostratic carbon due to optimal surface area provided by the iron powder. Finally, graphitization yield and thermal conductivity were stronger determinants (over graphite crystallinity) for accurate/precise/high-throughput biological, biomedical, and environmental14C-AMS applications such as absorption, distribution, metabolism, elimination (ADME), and physiologically based pharmacokinetics (PBPK) of nutrients, drugs, phytochemicals, and environmental chemicals. PMID:20163100

Near-infrared line-strengths in elliptical galaxies: evidence for initial mass function variations?

NASA Astrophysics Data System (ADS)

Cenarro, A. J.; Gorgas, J.; Vazdekis, A.; Cardiel, N.; Peletier, R. F.

2003-02-01

We present new relations between recently defined line-strength indices in the near-infrared (CaT*, CaT, PaT, MgI and sTiO) and central velocity dispersion (σ0) for a sample of 35 early-type galaxies, showing evidence for significant anti-correlations between CaII triplet indices (CaT* and CaT) and log σ0. These relations are interpreted in the light of our recent evolutionary synthesis model predictions, suggesting the existence of important Ca underabundances with respect to Fe and/or an increase of the dwarf to giant stars ratio along the mass sequence of elliptical galaxies.

High-fidelity Glucagon-CreER mouse line generated by CRISPR-Cas9 assisted gene targeting.

PubMed

Ackermann, Amanda M; Zhang, Jia; Heller, Aryel; Briker, Anna; Kaestner, Klaus H

2017-03-01

α-cells are the second most prominent cell type in pancreatic islets and are responsible for producing glucagon to increase plasma glucose levels in times of fasting. α-cell dysfunction and inappropriate glucagon secretion occur in both type 1 and type 2 diabetes. Thus, there is growing interest in studying both normal function and pathophysiology of α-cells. However, tools to target gene ablation or activation specifically of α-cells have been limited, compared to those available for β-cells. Previous Glucagon-Cre and Glucagon-CreER transgenic mouse lines have suffered from transgene silencing, and the only available Glucagon-CreER "knock-in" mouse line results in glucagon haploinsufficiency, which can confound the interpretation of gene deletion analyses. Therefore, we sought to develop a Glucagon-CreER T2 mouse line that would maintain normal glucagon expression and would be less susceptible to transgene silencing. We utilized CRISPR-Cas9 technology to insert an IRES-CreER T2 sequence into the 3' UTR of the Glucagon ( Gcg ) locus in mouse embryonic stem cells (ESCs). Targeted ESC clones were then injected into mouse blastocysts to obtain Gcg-CreER T2 mice. Recombination efficiency in GCG + pancreatic α-cells and glucagon-like peptide 1 positive (GLP1 + ) enteroendocrine L-cells was measured in Gcg-CreER T2 ; Rosa26-LSL-YFP mice injected with tamoxifen during fetal development and adulthood. Tamoxifen injection of Gcg-CreER T2 ; Rosa26-LSL-YFP mice induced high recombination efficiency of the Rosa26-LSL-YFP locus in perinatal and adult α-cells (88% and 95%, respectively), as well as in first-wave fetal α-cells (36%) and adult enteroendocrine L-cells (33%). Mice homozygous for the Gcg-CreER T2 allele were phenotypically normal. We successfully derived a Gcg-CreER T2 mouse line that expresses CreER T2 in pancreatic α-cells and enteroendocrine L-cells without disrupting preproglucagon gene expression. These mice will be a useful tool for performing

An Analytical Means of Determining Mass Loss from High Velocity Rigid Penetrators based on the Thermodynamic and Mechanical Properties of the Penetrator and Target

NASA Astrophysics Data System (ADS)

Foster, Joseph C., Jr.; Jones, S. E.; Rule, William; Toness, Odin

1999-06-01

Sub-scale experimentation is commonly used as a cost-effective means of conducting terminal ballistics research. Analytical models of the penetration process focus on calculating the depth of penetration based on target density, target strength represented by the unconfined compressive-strength (f”c), the areal density of the penetrator (W/A), and the impact velocity.1 Forrestal, et. al. have documented the mass loss from the penetrator during the penetration process and employed improved equations of motion.2 Various researchers have investigated the upper limits of rigid body penetration and identified the onset of instabilities.3 In an effort to better understand the physical processes associated with this instability, experimental techniques have been developed to capture the details of the penetrator and target and subject them to microscopic analysis.4 These results have served as motivation to explore new forms for the physics included in the penetration equation as a means of identifying the processes associated with high velocity instability. We have included target shear and nose friction in the formulation of the fundamental load function expressions.5 When the resulting equations of motion are integrated and combined with the thermodynamics indicated by microscopic analysis, methods are identified to calculated penetrator mass loss. A comparison of results with experimental data serves as an indicator of the thermodynamic state variables associated with the quasi-steady state penetrator target interface conditions. 1 Young, C. W. , “Depth Predictions for Earth Penetrating Projectiles,” Journal of Soil Mechanics and Foundations, Division of ASCE, May 1998 pp 803-817 2. M.J. Forrestal, D.J. Frew, S.J. Hanchak, amd Brar, “ Pentration of Grout and Concrete Targets with Ogive-Nose Steel Projectiles,” Inrt. J. Impact Engng. Vol 18, pp. 465-476,1996 3. Andrew J. Piekutowski, Michael J. Forrestal, Kevin L. Poormon, and Thomas L. Warren, �

Effect of verteporfin-PDT on epithelial growth factor receptor (EGFR) signaling pathway in cholangiocarcinoma cell lines

NASA Astrophysics Data System (ADS)

Andreola, Fausto; Cerec, Virginie; Pereira, Stephen P.

2009-06-01

EGFR, a member of the ERBB family, plays a pivotal role in carcinogenesis. EGFR overexpression is implicated in DNA repair and synergistic interactions between EGFR-targeting drugs and conventional chemo/radiotherapy have been reported in preclinical studies for different cancers but not cholangiocarcinoma (CCA). To date there are no in vitro data available on the cellular response and effect of either photodynamic therapy (PDT) or EGFR-targeting drugs on CCA. Therefore, we aimed to study the: (i) response to Verteporfin PDT and to EGFR-targeting drugs, as single agents; (ii) effect of PDT on ERBBs expression, phosporylation status and activation of its signaling pathways; (iii) response to combination of PDT and EGFR-targeting agents. We showed that two cholangiocarcinoma cell lines (HuCCT1 and TFK1 cells, intra- and extrahepatic, respectively) differentially respond to verteporfin-PDT treatment and are resistant to EGFR-targeting agents. A constitutive activation of EGFR in both cell lines was also observed, which could partly account for the observed resistance to EGFR-targeting drugs. In addition, verteporfin-PDT induced further phosphorylation of both EGFR and other Receptor Tyrosine Kinases. Mitochondria-independent apoptosis was induced by PDT in both CCA cell lines; in particular, PDT modulated the expression of members of the Inhibitor of Apoptosis (IAP) family of proteins. Interestingly, there was a PDT-induced EGFR nuclear translocation in both cell lines; co-treatment with either an EGFR-inhibitor (Cetuximab) or a nuclear import blocking agent (Wheat Germ Agglutinin) had an additive effect on PDT cell killing, thus implying a role of EGFR in repairing the potential PDT-induced DNA damage.

On-line solid-phase extraction coupled to liquid chromatography tandem mass spectrometry for the analysis of cyanotoxins in algal blooms.

PubMed

Fayad, Paul B; Roy-Lachapelle, Audrey; Duy, Sung Vo; Prévost, Michèle; Sauvé, Sébastien

2015-12-15

An analytical method based on on-line SPE-LC-HESI-MS/MS has been developed for the detection and quantification of eight selected cyanotoxins in algal bloom waters that include mycrocystins, anatoxin-a and cylindrospermopsin. The injection volume was 2 mL according to the expected concentration of cyanotoxins in matrix. The method provides an analysis time of 7 min per sample, acceptable recovery values (91-101%), good precision (RSD < 13%) and method limits of detection at the sub-microgram per liter levels (0.01-0.02 μg L(-1)). A detailed discussion on optimization parameters that have an impact on the overall performance of the method are presented. In particular, method optimization permitted the chromatographic separation of anatoxin-a and phenylalanine, an isobaric interference with a similar chromatographic characteristics. All optimization and validation experiments for the on-line SPE method and chromatographic separation were performed in environmentally relevant algal bloom water matrices. The applicability of the method was tested on several algal bloom water samples from monitored lakes across the province of Québec (Québec, Canada) known to produce cyanotoxins. All of the targeted cyanotoxins were detected with the exception of cylindrospermopsin. In addition, it was found that total microcystin concentrations in several surface water samples exceeded the proposed guidelines established by the province of Québec in Canada of 1.5 μg L(-1) as well as the World Health Organization of 1 μg L(-1) for both free and cell-bound microcystin-LR equivalent. Copyright © 2015 Elsevier Ltd. All rights reserved.

A study of electric transmission lines for use on the lunar surface

NASA Technical Reports Server (NTRS)

Gaustad, Krista L.; Gordon, Lloyd B.; Weber, Jennifer R.

1994-01-01

The sources for electrical power on a lunar base are said to include solar/chemical, nuclear (static conversion), and nuclear (dynamic conversion). The transmission of power via transmission lines is more practical than power beaming or superconducting because of its low cost and reliable, proven technology. Transmission lines must have minimum mass, maximum efficiency, and the ability to operate reliably in the lunar environment. The transmission line design includes conductor material, insulator material, conductor geometry, conductor configuration, line location, waveform, phase selection, and frequency. This presentation oulines the design. Liquid and gaseous dielectrics are undesirable for long term use in the lunar vacuum due to a high probability of loss. Thus, insulation for high voltage transmission line will most likely be solid dielectric or vacuum insulation.

Simultaneous Proteomic Discovery and Targeted Monitoring using Liquid Chromatography, Ion Mobility Spectrometry, and Mass Spectrometry*

PubMed Central

Burnum-Johnson, Kristin E.; Nie, Song; Casey, Cameron P.; Monroe, Matthew E.; Orton, Daniel J.; Ibrahim, Yehia M.; Gritsenko, Marina A.; Clauss, Therese R. W.; Shukla, Anil K.; Moore, Ronald J.; Purvine, Samuel O.; Shi, Tujin; Qian, Weijun; Liu, Tao; Baker, Erin S.; Smith, Richard D.

2016-01-01

Current proteomic approaches include both broad discovery measurements and quantitative targeted analyses. In many cases, discovery measurements are initially used to identify potentially important proteins (e.g. candidate biomarkers) and then targeted studies are employed to quantify a limited number of selected proteins. Both approaches, however, suffer from limitations. Discovery measurements aim to sample the whole proteome but have lower sensitivity, accuracy, and quantitation precision than targeted approaches, whereas targeted measurements are significantly more sensitive but only sample a limited portion of the proteome. Herein, we describe a new approach that performs both discovery and targeted monitoring (DTM) in a single analysis by combining liquid chromatography, ion mobility spectrometry and mass spectrometry (LC-IMS-MS). In DTM, heavy labeled target peptides are spiked into tryptic digests and both the labeled and unlabeled peptides are detected using LC-IMS-MS instrumentation. Compared with the broad LC-MS discovery measurements, DTM yields greater peptide/protein coverage and detects lower abundance species. DTM also achieved detection limits similar to selected reaction monitoring (SRM) indicating its potential for combined high quality discovery and targeted analyses, which is a significant step toward the convergence of discovery and targeted approaches. PMID:27670688

Characterization of core–shell MOF particles by depth profiling experiments using on-line single particle mass spectrometry

DOE PAGES

Cahill, J. F.; Fei, H.; Cohen, S. M.; ...

2015-01-05

Materials with core-shell structures have distinct properties that lend themselves to a variety of potential applications. Characterization of small particle core-shell materials presents a unique analytical challenge. Herein, single particles of solid-state materials with core-shell structures were measured using on-line aerosol time-of-flight mass spectrometry (ATOFMS). Laser 'depth profiling' experiments verified the core-shell nature of two known core-shell particle configurations (< 2 mu m diameter) that possessed inverted, complimentary core-shell compositions (ZrO2@SiO2 versus SiO2@ZrO2). The average peak area ratios of Si and Zr ions were calculated to definitively show their core-shell composition. These ratio curves acted as a calibrant for anmore » uncharacterized sample - a metal-organic framework (MOF) material surround by silica (UiO-66(Zr)@SiO2; UiO = University of Oslo). ATOFMS depth profiling was used to show that these particles did indeed exhibit a core-shell architecture. The results presented here show that ATOFMS can provide unique insights into core-shell solid-state materials with particle diameters between 0.2-3 mu m.« less

P41IDENTIFICATION OF GLIOMA SPECIFIC APTAMER TARGETS

PubMed Central

Arora, Mohit; Alder, Jane; Lawrence, Clare; Davis, Charles; Dawson, Tim; Hall, Greg; Shaw, Lisa

2014-01-01

INTRODUCTION: Aptamers are in vitro generated DNA and RNA sequences which are randomly created as a library, with multiple permutations and combinations. These are then exposed to the target structure against which we want an aptamer ‘selected’ using Sequential Enumeration of Ligands by Exponential enrichment (SELEX). METHOD: Commercially available glioma and glial cell lines and in-house generated primary glioma cultures were used. Modified aptamers based on published sequences against glioma cell lines and newly generated sequences were used in the project to identify their binding targets. Cy3 or biotin- conjugated aptamers were incubated with live glioma cell cultures and imaged using confocal or light microscopy.To determine the target ligand, aptamers were then reacted with glial cell lysate and subjected to precipitation using streptavidin agarose beads and SDS polyacrylamide electrophoresis. Proteins were analysed by mass spectroscopy. RESULTS: Known and unknown aptamer protein ligands were co-precipitated. Ku70, Ku80 were precipitated along with nucleolin and related proteins. CONCLUSION: The aptamer has shown preferential binding to glioma cells and could act as a delivery system for therapeutic payloads. The aptamer targets Ku70 and Ku80, which are known to be over expressed in other forms of cancer but their role in gliomagenesis has not been fully elucidated. Other novel proteins have also been identified. Thus the aptamer co-precipitation technique has identified potential glioma biomarkers that may be of clinical significance.

Mixture model normalization for non-targeted gas chromatography/mass spectrometry metabolomics data.

PubMed

Reisetter, Anna C; Muehlbauer, Michael J; Bain, James R; Nodzenski, Michael; Stevens, Robert D; Ilkayeva, Olga; Metzger, Boyd E; Newgard, Christopher B; Lowe, William L; Scholtens, Denise M

2017-02-02

Metabolomics offers a unique integrative perspective for health research, reflecting genetic and environmental contributions to disease-related phenotypes. Identifying robust associations in population-based or large-scale clinical studies demands large numbers of subjects and therefore sample batching for gas-chromatography/mass spectrometry (GC/MS) non-targeted assays. When run over weeks or months, technical noise due to batch and run-order threatens data interpretability. Application of existing normalization methods to metabolomics is challenged by unsatisfied modeling assumptions and, notably, failure to address batch-specific truncation of low abundance compounds. To curtail technical noise and make GC/MS metabolomics data amenable to analyses describing biologically relevant variability, we propose mixture model normalization (mixnorm) that accommodates truncated data and estimates per-metabolite batch and run-order effects using quality control samples. Mixnorm outperforms other approaches across many metrics, including improved correlation of non-targeted and targeted measurements and superior performance when metabolite detectability varies according to batch. For some metrics, particularly when truncation is less frequent for a metabolite, mean centering and median scaling demonstrate comparable performance to mixnorm. When quality control samples are systematically included in batches, mixnorm is uniquely suited to normalizing non-targeted GC/MS metabolomics data due to explicit accommodation of batch effects, run order and varying thresholds of detectability. Especially in large-scale studies, normalization is crucial for drawing accurate conclusions from non-targeted GC/MS metabolomics data.

Simultaneous determination of metolazone and valsartan in plasma by on-line SPE coupled with liquid chromatography/tandem mass spectrometry.

PubMed

Zhou, Jiezhao; Chen, Meiling; Li, Ying; Yu, Fanglin; Cheng, Xiaohui; Yang, Yang; Liu, Yan; Xie, Xiangyang; Li, Zhiping; Zhang, Hui; Mei, Xingguo

2017-10-01

Combination of metolazone (0.5 mg) and valsartan (80 mg) has been verified as a promising therapy treatment for hypertension. In order to facilitate to pharmacokinetic research, it needs a method for the simultaneously determination of metolazone and valsartan in biological samples. However, there are no relative reports so far. In order to facilitate to pharmacokinetic research, an on-line solid phase extraction coupled with liquid chromatography-tandem mass spectrometry method for the simultaneous determination of metolazone and valsartan in beagle dog plasma was developed and validated in this study. An on-line solid phase extraction column Retain PEP Javelin (10 mm × 2.1 mm) was used to remove impurities in plasma samples. The metolazone, valsartan and internal standard (losartan) were separated on a Poroshell 120 SB-C18 column (4.6 mm × 50 mm × 2.7 µm) with a gradient elution procedure. Acidified acetonitrile/water mixture was used as a mobile phase. The selected multiple-reaction monitoring mode in positive ion was performed and the parent to the product transitions m/z 366/259, m/z 436.2/291 and m/z 423.4/207 were used to measure the metolazone, valsartan and losartan. The method was linear over the range of 0.1-100 ng/mL and 1-1000 ng/mL for metolazone and valsartan, respectively. This method was validated in terms of specificity, linearity, sensitivity, precision, accuracy, matrix effect, and stability and then successfully applied to pharmacokinetic studies of the metolazone and valsartan combination tablets in beagle dogs.

[Target and non-target screening of volatile organic compounds in industrial exhaust gas using thermal desorption-gas chromatography-mass spectrometry].

PubMed

Ma, Huilian; Jin, Jing; Li, Yun; Chen, Jiping

2017-10-08

A method of comprehensive screening of the target and non-target volatile organic compounds (VOCs) in industrial exhaust gas using thermal desorption-gas chromatography-mass spectrometry (TD-GC-MS) has been developed. In this paper, two types of solid phase adsorption column were compared, and the Tenex SS TD Tube was selected. The analytes were enriched into the adsorption tube by constant flow sampling, and detected by TD-GC-MS in full scan mode. Target compounds were quantified by internal standard method, and the quantities of non-target compounds were calculated by response coefficient of toluene. The method detection limits (MDLs) for the 24 VOCs were 1.06 to 5.44 ng, and MDLs could also be expressed as 0.004 to 0.018 mg/m 3 assuming that the sampling volume was 300 mL. The average recoveries were in the range of 78.4% to 89.4% with the relative standard deviations (RSDs) of 3.9% to 14.4% ( n =7). The established analytical method was applied for the comprehensive screening of VOCs in a waste incineration power plant in Dalian city. Twenty-nine VOCs were identified. In these compounds, only five VOCs were the target compounds set in advance, which accounted for 26.7% of the total VOCs identified. Therefore, this study further proved the importance of screening non-target compounds in the analysis of VOCs in industrial exhaust gas, and has certain reference significance for the complete determination of VOCs distribution.

Targeted screening of pesticides, veterinary drugs and mycotoxins in bakery ingredients and food commodities by liquid chromatography-high-resolution single-stage Orbitrap mass spectrometry.

PubMed

De Dominicis, Emiliano; Commissati, Italo; Suman, Michele

2012-09-01

In the food industry, it is frequently necessary to check the quality of an ingredient to decide whether to use it in production and/or to have an idea of the final possible contamination of the finished product. The current need to quickly separate and identify relevant contaminants within different classes, often with legal residue limits on the order of 1-100 µg kg(-1), has led to the need for more effective analytical methods. With thousands of organic compounds present in complex food matrices, the development of new analytical solutions leaned towards simplified extraction/clean-up procedures and chromatography coupled with mass spectrometry. Efforts must also be made regarding the instrumental phase to overcome sensitivity/selectivity limits and interferences. For this purpose, high-resolution full scan analysis in mass spectrometry is an interesting alternative to the traditional tandem mass approach. A fast method for extracting and purifying bakery matrices was therefore developed and combined with the exploitation of ultra-high-pressure liquid chromatography (UHPLC) coupled to a Orbitrap Exactive™ high-resolution mass spectrometer (HRMS). Extracts of blank, naturally contaminated and fortified minicakes, prepared through a combined use of industrial and pilot plant production lines, were analyzed at different concentration levels (1-100 µg kg(-1)) of various contaminants: a limit of detection at 10 µg kg(-1) was possible for most of the analytes within all the categories analyzed, including pesticides, aflatoxins, trichothecene toxins and veterinary drugs. The application of accurate mass targeted screening described in this article demonstrates that current single-stage HRMS analytical instrumentation is well equipped to meet the challenges posed by chemical contaminants in the screening of both bakery raw materials and finished products. Copyright © 2012 John Wiley & Sons, Ltd.

Killing of targets by effector CD8 T cells in the mouse spleen follows the law of mass action

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

Ganusov, Vitaly V

2009-01-01

In contrast with antibody-based vaccines, it has been difficult to measure the efficacy of T cell-based vaccines and to correlate the efficacy of CD8 T cell responses with protection again viral infections. In part, this difficulty is due to poor understanding of the in vivo efficacy of CD8 T cells produced by vaccination. Using a: recently developed experimental method of in vivo cytotoxicity we have investigated quantitative aspects of killing of peptide-pulsed targets by effector and memory CD8 T cells, specific to three epitopes of lymphocytic choriomeningitis virus (LCMV), in the mouse spleen. By analyzing data on killing of targetsmore » with varying number of epitope-specific effector and memory CD8 T cells, we find that killing of targets by effectors follows the law of mass-action, that is the death rate of peptide-pulsed targets is proportional to the frequency of CTLs in the spleen. In contrast, killing of targets by memory CD8 T cells does not follow the mass action law because the death rate of targets saturates at high frequencies of memory CD8 T cells. For both effector and memory cells, we also find little support for the killing term that includes the decrease of the death rate of targets with target cell density. Interestingly, our analysis suggests that at low CD8 T cell frequencies, memory CD8 T cells on the per capita basis are more efficient at killing peptide-pulsed targets than effectors, but at high frequencies, effectors are more efficient killers than memory T cells. Comparison of the estimated killing efficacy of effector T cells with the value that is predicted from theoretical physics and based on motility of T cells in lymphoid tissues, suggests that limiting step in the killing of peptide-pulsed targets is delivering the lethal hit and not finding the target. Our results thus form a basis for quantitative understanding of the process of killing of virus-infected cells by T cell responses in tissues and can be used to correlate the

On-Line, Gyro-Based, Mass-Property Identification for Thruster-Controlled Spacecraft Using Recursive Least Squares

NASA Technical Reports Server (NTRS)

Wilson, Edward; Lages, Chris; Mah, Robert; Clancy, Daniel (Technical Monitor)

2002-01-01

Spacecraft control, state estimation, and fault-detection-and-isolation systems are affected by unknown v aerations in the vehicle mass properties. It is often difficult to accurately measure inertia terms on the ground, and mass properties can change on-orbit as fuel is expended, the configuration changes, or payloads are added or removed. Recursive least squares -based algorithms that use gyro signals to identify the center of mass and inverse inertia matrix are presented. They are applied in simulation to 3 thruster-controlled vehicles: the X-38 and Mini-AERCam under development at NASA-JSC, and the SAM, an air-bearing spacecraft simulator at the NASA-Ames Smart Systems Research Lab (SSRL).

First Responder Weapons of Mass Destruction Training Using Massively Multiplayer On-Line Gaming

DTIC Science & Technology

2004-06-01

Training Using Massively Multiplayer On-Line Gaming 6. AUTHOR(S) Thomas J. Richardson 5. FUNDING NUMBERS 7. PERFORMING ORGANIZATION NAME(S) AND...ADDRESS(ES) Naval Postgraduate School Monterey, CA 93943-5000 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING /MONITORING AGENCY NAME...37 1. Transitioning from Hierarchical to Networked Control................37 2. Compliance with Government Performance and Results Act

Mass spectrometry-based metabolomics: Targeting the crosstalk between gut microbiota and brain in neurodegenerative disorders.

PubMed

Luan, Hemi; Wang, Xian; Cai, Zongwei

2017-11-12

Metabolomics seeks to take a "snapshot" in a time of the levels, activities, regulation and interactions of all small molecule metabolites in response to a biological system with genetic or environmental changes. The emerging development in mass spectrometry technologies has shown promise in the discovery and quantitation of neuroactive small molecule metabolites associated with gut microbiota and brain. Significant progress has been made recently in the characterization of intermediate role of small molecule metabolites linked to neural development and neurodegenerative disorder, showing its potential in understanding the crosstalk between gut microbiota and the host brain. More evidence reveals that small molecule metabolites may play a critical role in mediating microbial effects on neurotransmission and disease development. Mass spectrometry-based metabolomics is uniquely suitable for obtaining the metabolic signals in bidirectional communication between gut microbiota and brain. In this review, we summarized major mass spectrometry technologies including liquid chromatography-mass spectrometry, gas chromatography-mass spectrometry, and imaging mass spectrometry for metabolomics studies of neurodegenerative disorders. We also reviewed the recent advances in the identification of new metabolites by mass spectrometry and metabolic pathways involved in the connection of intestinal microbiota and brain. These metabolic pathways allowed the microbiota to impact the regular function of the brain, which can in turn affect the composition of microbiota via the neurotransmitter substances. The dysfunctional interaction of this crosstalk connects neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease and Huntington's disease. The mass spectrometry-based metabolomics analysis provides information for targeting dysfunctional pathways of small molecule metabolites in the development of the neurodegenerative diseases, which may be valuable for the

A targeted drug delivery system based on dopamine functionalized nano graphene oxide

NASA Astrophysics Data System (ADS)

Masoudipour, Elham; Kashanian, Soheila; Maleki, Nasim

2017-01-01

The cellular targeting property of a biocompatible drug delivery system can widely increase the therapeutic effect against various diseases. Here, we report a dopamine conjugated nano graphene oxide (DA-nGO) carrier for cellular delivery of the anticancer drug, Methotrexate (MTX) into DA receptor positive human breast adenocarcinoma cell line. The material was characterized using scanning electron microscopy, atomic force microscopy, Fourier transform infrared spectroscopy and UV-vis spectroscopy. Furthermore, the antineoplastic action of MTX loaded DA-nGO against DA receptor positive and negative cell lines were explored. The results presented in this article demonstrated that the application of DA functionalized GO as a targeting drug carrier can improve the drug delivery efficacy for DA receptor positive cancer cell lines and promise future designing of carrier conjugates based on it.

Quantitation of triacylglycerols in edible oils by off-line comprehensive two-dimensional liquid chromatography-atmospheric pressure chemical ionization mass spectrometry using a single column.

PubMed

Wei, Fang; Hu, Na; Lv, Xin; Dong, Xu-Yan; Chen, Hong

2015-07-24

In this investigation, off-line comprehensive two-dimensional liquid chromatography-atmospheric pressure chemical ionization mass spectrometry using a single column has been applied for the identification and quantification of triacylglycerols in edible oils. A novel mixed-mode phenyl-hexyl chromatographic column was employed in this off-line two-dimensional separation system. The phenyl-hexyl column combined the features of traditional C18 and silver-ion columns, which could provide hydrophobic interactions with triacylglycerols under acetonitrile conditions and can offer π-π interactions with triacylglycerols under methanol conditions. When compared with traditional off-line comprehensive two-dimensional liquid chromatography employing two different chromatographic columns (C18 and silver-ion column) and using elution solvents comprised of two phases (reversed-phase/normal-phase) for triacylglycerols separation, the novel off-line comprehensive two-dimensional liquid chromatography using a single column can be achieved by simply altering the mobile phase between acetonitrile and methanol, which exhibited a much higher selectivity for the separation of triacylglycerols with great efficiency and rapid speed. In addition, an approach based on the use of response factor with atmospheric pressure chemical ionization mass spectrometry has been developed for triacylglycerols quantification. Due to the differences between saturated and unsaturated acyl chains, the use of response factors significantly improves the quantitation of triacylglycerols. This two-dimensional liquid chromatography-mass spectrometry system was successfully applied for the profiling of triacylglycerols in soybean oils, peanut oils and lord oils. A total of 68 triacylglycerols including 40 triacylglycerols in soybean oils, 50 triacylglycerols in peanut oils and 44 triacylglycerols in lord oils have been identified and quantified. The liquid chromatography-mass spectrometry data were analyzed

An open workflow to generate “MS Ready” structures and improve non-targeted mass spectrometry (ACS Fall 1 of 3)

EPA Science Inventory

High-throughput non-targeted analyses (NTA) rely on chemical reference databases for tentative identification of observed chemical features. Many of these databases and online resources incorporate chemical structure data not in a form that is readily observed by mass spectromet...

A replaceable microreactor for on-line protein digestion in a two-dimensional capillary electrophoresis system with tandem mass spectrometry detection

PubMed Central

Li, Yihan; Wojcik, Roza; Dovichi, Norman J.

2010-01-01

We describe a two-dimensional capillary electrophoresis system that incorporates a replaceable enzymatic microreactor for on-line protein digestion. In this system, trypsin is immobilized on magnetic beads. At the start of each experiment, old beads are flushed to waste and replaced with a fresh plug of beads, which is captured by a pair of magnets at the distal tip of the first capillary. For analysis, proteins are separated in the first capillary. A fraction is then parked in the reactor to create peptides. Digested peptides are periodically transferred to the second capillary for separation; a fresh protein fraction is simultaneously moved to the reactor for digestion. An electrospray interface is used to introduce peptides into a mass spectrometer for analysis. This procedure is repeated for several dozen fractions under computer control. The system was demonstrated by the separation and digestion of insulin chain b oxidized and β-casein as model proteins. PMID:21030030

Comparison of a modern broiler line and a heritage line unselected since the 1950s.

PubMed

Schmidt, C J; Persia, M E; Feierstein, E; Kingham, B; Saylor, W W

2009-12-01

Selecting chicken for improved meat production has altered the relative growth of organs in modern broiler lines compared with heritage lines. In this study, we compared the growth and feed efficiency of a heritage line, UIUC, with a modern production line, Ross 708, for 5 wk posthatch. During this period, the BW and feed efficiency of the modern strain was higher than that of the heritage line, indicating that the Ross 708 birds were more efficient than the UIUC birds at converting feed to body mass. The relative growth of the breast, heart, liver, and intestine were also compared during these 5 wk. The breast muscle of the heritage line constituted 9% of the total body mass at 5 wk, whereas in the modern line, the breast muscle was 18% of the total mass of the bird. In contrast, the relative size of the heart decreased after d 14 in the modern line, suggesting that selection for increased breast muscle has translated into relatively less weight of the heart muscle. The liver matured earlier in modern lines, possibly improving nutrient utilization as the birds shift from lipid- to carbohydrate-rich feed. Finally, jejunal and ileal sections of the intestine were 20% longer in the modern line, perhaps allowing for increased nutrient absorption.

Address substrates as promising targets for laser histochemical surgery as a nontraditional line in medicine

NASA Astrophysics Data System (ADS)

Piruzyan, L. A.; Mikhailovskiy, Ye. M.; Piruzyan, A. L.

1999-12-01

The priority concept of the laser histochemical surgery as a potentially novel line in medicine is presented. The histochemical stains, selectively coloring some targets (address substrates), that are cells or their biochemical ingredients, sensitize them to the laser irradiation. Such sensitization to laser irradiation by staining turns the colored targets into targets for the laser beam. The action of the irradiation onto its specific targets beats out of the cell its ingredients which participate in a pathology process. In particular, the beating of a stained ferment out of the general stage of biochemical processes characteristic for the pathology interrupts their currence. The laser beam, when beating out its stained targets without any damage of the unstained tissues, acts like a scalpel that cuts off affected tissues not brushing healthy ones. A scheme for testing stains as sensitizers of the `address substrates' to the laser irradiation is presented. As the criterion of the stain sensitization the fact was chosen of absence or weakness of pathomorphologic and biochemical signs of the disease in an experimental model of the pathology irradiated with laser after a stain use, while the pathology signs are present in a control sample. The basis is done for study of the histochemical stains as potential means for the laser histochemical surgery of disseminated sclerosis, mucopolysaccharidosis, hypercholesterolemia, myocardial infarction, cardiosclerosis, caries and parodontosis.

Impurity profiling of liothyronine sodium by means of reversed phase HPLC, high resolution mass spectrometry, on-line H/D exchange and UV/Vis absorption.

PubMed

Ruggenthaler, M; Grass, J; Schuh, W; Huber, C G; Reischl, R J

2017-09-05

For the first time, a comprehensive investigation of the impurity profile of the synthetic thyroid API (active pharmaceutical ingredient) liothyronine sodium (LT 3 Na) was performed by using reversed phase HPLC and advanced structural elucidation techniques including high resolution tandem mass spectrometry (HRMS/MS) and on-line hydrogen-deuterium (H/D) exchange. Overall, 39 compounds were characterized and 25 of these related substances were previously unknown to literature. The impurity classification system recently developed for the closely related API levothyroxine sodium (LT 4 Na) could be applied to the newly characterized liothyronine sodium impurities resulting in a wholistic thyroid API impurity classification system. Furthermore, the mass-spectrometric CID-fragmentation of specific related substances was discussed and rationalized by detailed fragmentation pathways. Moreover, the UV/Vis absorption characteristics of the API and selected impurities were investigated to corroborate chemical structure assignments derived from MS data. Copyright © 2017 Elsevier B.V. All rights reserved.

Advances in targeted proteomics and applications to biomedical research

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

Shi, Tujin; Song, Ehwang; Nie, Song

Targeted proteomics technique has emerged as a powerful protein quantification tool in systems biology, biomedical research, and increasing for clinical applications. The most widely used targeted proteomics approach, selected reaction monitoring (SRM), also known as multiple reaction monitoring (MRM), can be used for quantification of cellular signaling networks and preclinical verification of candidate protein biomarkers. As an extension to our previous review on advances in SRM sensitivity (Shi et al., Proteomics, 12, 1074–1092, 2012) herein we review recent advances in the method and technology for further enhancing SRM sensitivity (from 2012 to present), and highlighting its broad biomedical applications inmore » human bodily fluids, tissue and cell lines. Furthermore, we also review two recently introduced targeted proteomics approaches, parallel reaction monitoring (PRM) and data-independent acquisition (DIA) with targeted data extraction on fast scanning high-resolution accurate-mass (HR/AM) instruments. Such HR/AM targeted quantification with monitoring all target product ions addresses SRM limitations effectively in specificity and multiplexing; whereas when compared to SRM, PRM and DIA are still in the infancy with a limited number of applications. Thus, for HR/AM targeted quantification we focus our discussion on method development, data processing and analysis, and its advantages and limitations in targeted proteomics. Finally, general perspectives on the potential of achieving both high sensitivity and high sample throughput for large-scale quantification of hundreds of target proteins are discussed.« less

Testing the white dwarf mass-radius relation and comparing optical and far-UV spectroscopic results with Gaia DR2, HST and FUSE

NASA Astrophysics Data System (ADS)

Joyce, S. R. G.; Barstow, M. A.; Casewell, S. L.; Burleigh, M. R.; Holberg, J. B.; Bond, H. E.

2018-05-01

Observational tests of the white dwarf mass-radius relationship have always been limited by the uncertainty in the available distance measurements. Most studies have focused on Balmer line spectroscopy because these spectra can be obtained from ground based observatories, while the Lyman lines are only accessible to space based UV telescopes. We present results using parallax data from Gaia DR2 combined with space based spectroscopy from HST and FUSE covering the Balmer and Lyman lines. We find that our sample supports the theoretical relation, although there is at least one star which is shown to be inconsistent. Comparison of results between Balmer and Lyman line spectra shows they are in agreement when the latest broadening tables are used. We also assess the factors which contribute to the error in the mass-radius calculations and confirm the findings of other studies which show that the spread in results for targets where multiple spectra are available is larger than the statistical error. The uncertainty in the spectroscopically derived log g parameter is now the main source of error rather than the parallax. Finally, we present new results for the radius and spectroscopic mass of Sirius B which agree with the dynamical mass and mass-radius relation within 1σ.

SPECIATION OF SELENIUM AND ARSENIC COMPOUNDS BY CAPILLARY ELECTROPHORESIS WITH HYDRODYNAMICALLY MODIFIED ELECTROOSMOTIC FLOW AND ON-LINE REDUCTION OF SELENIUM(VI) TO SELENIUM(IV) WITH HYDRIDE GENERATION INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRIC DETECTION

EPA Science Inventory

Capillary electrophoresis (CE) with hydride generation inductively coupled plasma mass spectrometry was used to determine four arsenicals and two selenium species. Selenate (SeVI) was reduced on-line to selenite (SeIV') by mixing the CE effluent with concentrated HCl. A microporo...

The Survey of HI in Extremely Low-mass Dwarfs: A Multi-Wavelength Perspective on Low-Mass Galaxy Evolution

NASA Astrophysics Data System (ADS)

Cannon, John M.; McNichols, Andrew; Teich, Yaron; Adams, Elizabeth A.; Giovanelli, Riccardo; Haynes, Martha P.; McQuinn, Kristen B.; Salzer, John Joseph; Skillman, Evan D.; Dolphin, Andrew E.; Elson, Edward C.; Haurberg, Nathalie C.; Huang, Shan; Janowiecki, Steven; Jozsa, Gyula; Leisman, Luke; Ott, Juergen; Papastergis, Emmanouil; Rhode, Katherine L.; Saintonge, Amelie; Van Sistine, Angela; Warren, Steven R.

2017-01-01

The “Survey of HI in Extremely Low-mass Dwarfs” (SHIELD) is a multiwavelength study of local volume low-mass galaxies drawn from the Arecibo Legacy Fast ALFA (ALFALFA) catalog. HST/Spitzer joint program GO-12658 revealed the stellar populations of the first 12 SHIELD galaxies (Cannon et al. 2011), allowing accurate distance measurements (McQuinn et al. 2014) and detailed studies of the patterns of recent star formation in each galaxy (McQuinn et al. 2015). These HST and Spitzer images are a critical interpretive benchmark for ground-based optical imaging and spectroscopy (Haurberg et al. 2015), as well as for sensitive VLA HI spectral line imaging of the SHIELD galaxies (McNichols et al. 2016; Teich et al. 2016). These results have furthered our understanding of the evolution of galaxies in a mass regime that was previously only sparsely populated. With the low-redshift ALFALFA catalog now complete, the scope of the SHIELD program has been expanded to include all 82 galaxies that meet distance, line width, and HI flux criteria for being gas-rich, low-mass galaxies. In HST program 13750, images of 18 more SHIELD galaxies have again set the physical scales for supporting HI spectral line imaging with both the VLA and the WSRT (Gordon et al. 2016). Taken as a whole, the ongoing SHIELD program is one of the most comprehensive multiwavelength studies of the physical properties of low-mass galaxies outside of the Local Group.

A Systematic Search and Review of Adult-Targeted Overweight and Obesity Prevention Mass Media Campaigns and Their Evaluation: 2000-2017.

PubMed

Kite, James; Grunseit, Anne; Bohn-Goldbaum, Erika; Bellew, Bill; Carroll, Tom; Bauman, Adrian

2018-01-01

Mass media campaigns are a commonly used strategy in public health. However, no review has assessed whether the design and evaluation of overweight and obesity campaigns meets best practice recommendations. This study aimed to fill this gap. We systematically searched five databases for peer-reviewed articles describing adult-targeted obesity mass media campaigns published between 2000 and 2017, complemented by reference list searches and contact with authors and agencies responsible for the campaigns. We extracted data on campaign design, implementation, and evaluation from eligible publications and conducted a qualitative review of 29 publications reporting on 14 campaigns. We found a need for formative research with target audiences to ensure campaigns focus on the most salient issues. Further, we noted that most campaigns targeted individual behaviors, despite calls for campaigns to also focus upstream and to address social determinants of obesity. Television was the dominant communication channel but, with the rapid advance of digital media, evaluation of other channels, such as social media, is increasingly important. Finally, although evaluation methods varied in quality, the evidence suggests that campaigns can have an impact on intermediate outcomes, such as knowledge and attitudes. However, evidence is still limited as to whether campaigns can influence behavior change.

Simultaneous Proteomic Discovery and Targeted Monitoring using Liquid Chromatography, Ion Mobility Spectrometry, and Mass Spectrometry.

PubMed

Burnum-Johnson, Kristin E; Nie, Song; Casey, Cameron P; Monroe, Matthew E; Orton, Daniel J; Ibrahim, Yehia M; Gritsenko, Marina A; Clauss, Therese R W; Shukla, Anil K; Moore, Ronald J; Purvine, Samuel O; Shi, Tujin; Qian, Weijun; Liu, Tao; Baker, Erin S; Smith, Richard D

2016-12-01

Current proteomic approaches include both broad discovery measurements and quantitative targeted analyses. In many cases, discovery measurements are initially used to identify potentially important proteins (e.g. candidate biomarkers) and then targeted studies are employed to quantify a limited number of selected proteins. Both approaches, however, suffer from limitations. Discovery measurements aim to sample the whole proteome but have lower sensitivity, accuracy, and quantitation precision than targeted approaches, whereas targeted measurements are significantly more sensitive but only sample a limited portion of the proteome. Herein, we describe a new approach that performs both discovery and targeted monitoring (DTM) in a single analysis by combining liquid chromatography, ion mobility spectrometry and mass spectrometry (LC-IMS-MS). In DTM, heavy labeled target peptides are spiked into tryptic digests and both the labeled and unlabeled peptides are detected using LC-IMS-MS instrumentation. Compared with the broad LC-MS discovery measurements, DTM yields greater peptide/protein coverage and detects lower abundance species. DTM also achieved detection limits similar to selected reaction monitoring (SRM) indicating its potential for combined high quality discovery and targeted analyses, which is a significant step toward the convergence of discovery and targeted approaches. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Vesicle-associated membrane protein 7 (VAMP-7) is essential for target cell killing in a natural killer cell line

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

Marcet-Palacios, Marcelo; Odemuyiwa, Solomon O.; Coughlin, Jason J.

2008-02-15

Natural killer cells recognize and induce apoptosis in foreign, transformed or virus-infected cells through the release of perforin and granzymes from secretory lysosomes. Clinically, NK-cell mediated killing is a major limitation to successful allo- and xenotransplantation. The molecular mechanisms that regulate the fusion of granzyme B-containing secretory lysosomes to the plasma membrane in activated NK cells, prior to target cell killing, are not fully understood. Using the NK cell line YT-Indy as a model, we have investigated the expression of SNAP REceptors (SNAREs), both target (t-) and vesicular (v-) SNAREs, and their function in granzyme B-mediated target cell killing. Ourmore » data showed that YT-Indy cells express VAMP-7 and SNAP-23, but not VAMP-2. VAMP-7 was associated with granzyme B-containing lysosomal granules. Using VAMP-7 small interfering RNA (siRNA), we successfully knocked down the expression of VAMP-7 protein in YT-Indy to less than 10% of untreated cells in 24 h. VAMP7-deficient YT-Indy cells activated via co-culture with Jurkat cells released <1 ng/mL of granzyme B, compared to 1.5-2.5 {mu}g/mL from controls. Using Jurkat cells as targets, we showed a 7-fold reduction in NK cell-mediated killing by VAMP-7 deficient YT-Indy cells. Our results show that VAMP-7 is a crucial component of granzyme B release and target cell killing in the NK cell line YT-Indy. Thus, targeting VAMP-7 expression specifically with siRNA, following transplantation, may be a viable strategy for preventing NK cell-mediated transplant rejection, in vivo.« less

ULTRAVIOLET SPECTROSCOPY OF RAPIDLY ROTATING SOLAR-MASS STARS: EMISSION-LINE REDSHIFTS AS A TEST OF THE SOLAR-STELLAR CONNECTION

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

Linsky, Jeffrey L.; Bushinsky, Rachel; Ayres, Tom

2012-07-20

We compare high-resolution ultraviolet spectra of the Sun and thirteen solar-mass main-sequence stars with different rotational periods that serve as proxies for their different ages and magnetic field structures. In this, the second paper in the series, we study the dependence of ultraviolet emission-line centroid velocities on stellar rotation period, as rotation rates decrease from that of the Pleiades star HII314 (P{sub rot} = 1.47 days) to {alpha} Cen A (P{sub rot} = 28 days). Our stellar sample of F9 V to G5 V stars consists of six stars observed with the Cosmic Origins Spectrograph on the Hubble Space Telescopemore » (HST) and eight stars observed with the Space Telescope Imaging Spectrograph on HST. We find a systematic trend of increasing redshift with more rapid rotation (decreasing rotation period) that is similar to the increase in line redshift between quiet and plage regions on the Sun. The fastest-rotating solar-mass star in our study, HII314, shows significantly enhanced redshifts at all temperatures above log T = 4.6, including the corona, which is very different from the redshift pattern observed in the more slowly rotating stars. This difference in the redshift pattern suggests that a qualitative change in the magnetic-heating process occurs near P{sub rot} = 2 days. We propose that HII314 is an example of a solar-mass star with a magnetic heating rate too large for the physical processes responsible for the redshift pattern to operate in the same way as for the more slowly rotating stars. HII314 may therefore lie above the high activity end of the set of solar-like phenomena that is often called the 'solar-stellar connection'.« less

The Discrepancy between Einstein Mass and Dynamical Mass for SIS and Power-law Mass Models

NASA Astrophysics Data System (ADS)

Li, Rui; Wang, Jiancheng; Shu, Yiping; Xu, Zhaoyi

2018-03-01

We investigate the discrepancy between the two-dimensional projected lensing mass and the dynamical mass for an ensemble of 97 strong gravitational lensing systems discovered by the Sloan Lens ACS Survey, the BOSS Emission-Line Lens Survey (BELLS), and the BELLS for GALaxy-Lyα EmitteR sYstems Survey. We fit the lensing data to obtain the Einstein mass and use the velocity dispersion of the lensing galaxies provided by the Sloan Digital Sky Survey to get the projected dynamical mass within the Einstein radius by assuming the power-law mass approximation. The discrepancy is found to be obvious and quantified by Bayesian analysis. For the singular isothermal sphere mass model, we obtain that the Einstein mass is 20.7% more than the dynamical mass, and the discrepancy increases with the redshift of the lensing galaxies. For the more general power-law mass model, the discrepancy still exists within a 1σ credible region. We suspect the main reason for this discrepancy is mass contamination, including all invisible masses along the line of sight. In addition, the measurement errors and the approximation of the mass models could also contribute to the discrepancy.

Measurements of Laser Imprint with High-Z Coated targets on Omega EP

NASA Astrophysics Data System (ADS)

Karasik, Max; Oh, J.; Stoeckl, C.; Aglitskiy, Y.; Schmitt, A. J.; Bates, J. W.; Obenschain, S. P.

2015-11-01

Previous experiments on Nike KrF laser (λ = 248nm) at NRL found that a thin (400-800 Å) high-Z (Au or Pd) overcoat on the laser side of the target is effective in suppressing broadband imprint and reducing ablative Richtmyer-Meshkov growth. The overcoat initially absorbs the laser and emits soft x-rays that ablate the target, forming a large stand-off distance between laser absorption and ablation and driving the target at higher mass ablation rate. Implementation of this technique on the frequency-tripled Nd:glass (351 nm) NIF would enable a wider range direct drive experiments there. To this end, we are carrying out experiments using the NIF-like beams of Omega EP. Analogous to experiments on Nike, areal mass perturbations due to RT-amplified laser imprint are measured using curved crystal imaging coupled to a streak camera. High-Z coating dynamics and target trajectory are imaged side-on. First results indicate that imprint suppression is observed, albeit with thicker coatings. Work supported by the Department of Energy/NNSA.

Modelling the line-of-sight contribution in substructure lensing

NASA Astrophysics Data System (ADS)

Despali, Giulia; Vegetti, Simona; White, Simon D. M.; Giocoli, Carlo; van den Bosch, Frank C.

2018-04-01

We investigate how Einstein rings and magnified arcs are affected by small-mass dark-matter haloes placed along the line of sight to gravitational lens systems. By comparing the gravitational signature of line-of-sight haloes with that of substructures within the lensing galaxy, we derive a mass-redshift relation that allows us to rescale the detection threshold (i.e. lowest detectable mass) for substructures to a detection threshold for line-of-sight haloes at any redshift. We then quantify the line-of-sight contribution to the total number density of low-mass objects that can be detected through strong gravitational lensing. Finally, we assess the degeneracy between substructures and line-of-sight haloes of different mass and redshift to provide a statistical interpretation of current and future detections, with the aim of distinguishing between cold dark matter and warm dark matter. We find that line-of-sight haloes statistically dominate with respect to substructures, by an amount that strongly depends on the source and lens redshifts, and on the chosen dark-matter model. Substructures represent about 30 percent of the total number of perturbers for low lens and source redshifts (as for the SLACS lenses), but less than 10 per cent for high-redshift systems. We also find that for data with high enough signal-to-noise ratio and angular resolution, the non-linear effects arising from a double-lens-plane configuration are such that one is able to observationally recover the line-of-sight halo redshift with an absolute error precision of 0.15 at the 68 per cent confidence level.

Two-Step Single Particle Mass Spectrometry for On-Line Monitoring of Polycyclic Aromatic Hydrocarbons Bound to Ambient Fine Particulate Matter

NASA Astrophysics Data System (ADS)

Zimmermann, R.; Bente, M.; Sklorz, M.

2007-12-01

Polycyclic aromatic hydrocarbons (PAH) are formed as trace products in combustion processes and are emitted to the atmosphere. Larger PAH have low vapour pressure and are predominantly bound to the ambient fine particulate matter (PM). Upon inhalation, PAH show both, chronic human toxicity (i.e. many PAH are potent carcinogens) as well as acute human toxicity (i.e. inflammatory effects due to oxi-dative stress) and are discussed to be relevant for the observed health effect of ambient PM. Therefore a better understanding of the occurrence, dynamics and particle size dependence of particle bound-PAH is of great interest. On-line aerosol mass spectrometry in principle is the method of choice to investigate the size resolved changes in the chemical speciation of particles as well the status of internal vs. external mixing of chemical constituents. However the present available aerosol mass spectrometers (ATOFMS and AMS) do not allow detection of PAH from ambient air PM. In order to allow a single particle based monitoring of PAH from ambient PM a new single particle laser ionisation mass spectrometer was built and applied. The system is based on ATOFMS principle but uses a two- step photo-ionization. A tracked and sized particle firstly is laser desorbed (LD) by a IR-laser pulse (CO2-laser, λ=10.2 μm) and subsequently the released PAH are selectively ionized by an intense UV-laser pulse (ArF excimer, λ=248 nm) in a resonance enhanced multiphoton ionisation process (REMPI). The PAH-ions are detected in a time of flight mass spectrometer (TOFMS). A virtual impactor enrichment unit is used to increase the detection frequency of the ambient particles. With the current inlet system particles from about 400 nm to 10 μm are accessible. Single particle based temporal profiles of PAH containing particles ion (size distribution and PAH speciation) have been recorded in Oberschleissheim, Germany from ambient air. Furthermore profiles of relevant emission sources (e

piRNA pathway targets active LINE1 elements to establish the repressive H3K9me3 mark in germ cells

PubMed Central

Pezic, Dubravka; Manakov, Sergei A.; Sachidanandam, Ravi; Aravin, Alexei A.

2014-01-01

Transposable elements (TEs) occupy a large fraction of metazoan genomes and pose a constant threat to genomic integrity. This threat is particularly critical in germ cells, as changes in the genome that are induced by TEs will be transmitted to the next generation. Small noncoding piwi-interacting RNAs (piRNAs) recognize and silence a diverse set of TEs in germ cells. In mice, piRNA-guided transposon repression correlates with establishment of CpG DNA methylation on their sequences, yet the mechanism and the spectrum of genomic targets of piRNA silencing are unknown. Here we show that in addition to DNA methylation, the piRNA pathway is required to maintain a high level of the repressive H3K9me3 histone modification on long interspersed nuclear elements (LINEs) in germ cells. piRNA-dependent chromatin repression targets exclusively full-length elements of actively transposing LINE families, demonstrating the remarkable ability of the piRNA pathway to recognize active elements among the large number of genomic transposon fragments. PMID:24939875

Process Analytical Technology for High Shear Wet Granulation: Wet Mass Consistency Reported by In-Line Drag Flow Force Sensor Is Consistent With Powder Rheology Measured by At-Line FT4 Powder Rheometer.

PubMed

Narang, Ajit S; Sheverev, Valery; Freeman, Tim; Both, Douglas; Stepaniuk, Vadim; Delancy, Michael; Millington-Smith, Doug; Macias, Kevin; Subramanian, Ganeshkumar

2016-01-01

Drag flow force (DFF) sensor that measures the force exerted by wet mass in a granulator on a thin cylindrical probe was shown as a promising process analytical technology for real-time in-line high-resolution monitoring of wet mass consistency during high shear wet granulation. Our previous studies indicated that this process analytical technology tool could be correlated to granulation end point established independently through drug product critical quality attributes. In this study, the measurements of flow force by a DFF sensor, taken during wet granulation of 3 placebo formulations with different binder content, are compared with concurrent at line FT4 Powder Rheometer characterization of wet granules collected at different time points of the processing. The wet mass consistency measured by the DFF sensor correlated well with the granulation's resistance to flow and interparticulate interactions as measured by FT4 Powder Rheometer. This indicated that the force pulse magnitude measured by the DFF sensor was indicative of fundamental material properties (e.g., shear viscosity and granule size/density), as they were changing during the granulation process. These studies indicate that DFF sensor can be a valuable tool for wet granulation formulation and process development and scale up, as well as for routine monitoring and control during manufacturing. Copyright © 2016. Published by Elsevier Inc.

Tetrahydrofuran-water extraction, in-line clean-up and selective liquid chromatography/tandem mass spectrometry for the quantitation of perfluorinated compounds in food at the low picogram per gram level.

PubMed

Ballesteros-Gómez, Ana; Rubio, Soledad; van Leeuwen, Stefan

2010-09-17

A new solvent extraction system was developed for extraction of PFCs from food. The extraction is carried out with 75:25 (v/v) tetrahydrofuran:water, a solvent mixture that provides an appropriate balance of hydrogen bonding, dispersion and dipole-dipole interactions to efficiently extract PFCs with chains containing 4-14 carbon atoms from foods. This mixture provided recoveries above 85% from foods including vegetables, fruits, fish, meat and bread; and above 75% from cheese. Clean-up with a weak anion exchange resin and Envi-carb SPE, which were coupled in line for simplicity, was found to minimize matrix effects (viz. enhancement or suppression of electrospray ionization). The target analytes (PFCs) were resolved on a perfluorooctyl phase column that proved effective in separating mass interferences for perfluorooctane sulfonate (PFOS) in fish and meat samples. The mass spectrometer was operated in the negative electrospray ionization mode and used to record two transitions per analyte and one per mass-labeled method internal standard. The target PFCs were quantified from solvent based calibration curves. The limits of detection (LODs) were as low as 1-5 pg analyte g(-1) food; by exception, those for C(4) and C(5) PFCs were somewhat higher (25-30 pg g(-1)) owing to their less favourable mass response. To the best of our knowledge these are among the best LODs for PFCs in foods reported to date. The analysis of a variety of foods revealed contamination with PFCs at levels from 4.5 to 75 pg g(-1) in 25% of samples (fish and packaged spinach). C(10)-C(14) PFCs were found in fish, which testifies to the need to control long-chain PFCs in this type of food. The proposed method is a useful tool for the development of a large-scale database for the presence of PFCs in foods. 2010 Elsevier B.V. All rights reserved.

Quantifying Feedback from Narrow Line Region Outflows in Nearby Active Galaxies. I. Spatially Resolved Mass Outflow Rates for the Seyfert 2 Galaxy Markarian 573

NASA Astrophysics Data System (ADS)

Revalski, M.; Crenshaw, D. M.; Kraemer, S. B.; Fischer, T. C.; Schmitt, H. R.; Machuca, C.

2018-03-01

We present the first spatially resolved mass outflow rate measurements ({\\dot{M}}out}) of the optical emission line gas in the narrow line region (NLR) of a Seyfert 2 galaxy, Markarian 573. Using long slit spectra and [O III] imaging from the Hubble Space Telescope and Apache Point Observatory in conjunction with emission line diagnostics and Cloudy photoionization models, we find a peak outflow rate of {\\dot{M}}out}≈ 3.4 +/- 0.5 {M}ȯ {yr}}-1 at a distance of 210 pc from the central supermassive black hole (SMBH). The outflow extends to distances of 600 pc from the nucleus with a total mass and kinetic energy of M ≈ 2.2 × 106 M ⊙ and E ≈ 5.1 × 1054 erg, revealing the outflows to be more energetic than those in the lower luminosity Seyfert 1 galaxy NGC 4151. The peak outflow rate is an order of magnitude larger than the mass accretion and nuclear outflow rates, indicating local in situ acceleration of the circumnuclear NLR gas. We compare these results to global techniques that quantify an average outflow rate across the NLR, and find the latter are subject to larger uncertainties. These results indicate that spatially resolved observations are critical for probing AGN feedback on scales where circumnuclear star formation occurs.

New Results on Cepheid Masses

NASA Astrophysics Data System (ADS)

Evans, N. R.; Bohm-Vitense, E.; Carpenter, K.; Robinson, R.; Beck-Winchatz, B.

1996-12-01

Masses for Cepheid variable stars can be measured by combining the orbital velocity amplitude for the Cepheid (from a ground-based orbit) with the orbital velocity amplitude of a hot main sequence companion (observed in the ultraviolet from satellites such as IUE and HST) and the mass of the companion (inferred from from the ultraviolet energy distribution). Observations of 5 binary systems are now completed or in progress with the Goddard High Resolution Spectrograph on the Hubble Space Telescope. Recently completed observations of U Aql lead to a mass of 5.1 +/- 1.1 Msun . We will discuss the results for S Mus, V350 Sgr, U Aql, and Y Car, and the constraints they place on stellar evolution calculations. As would be expected, some of the B companions have high rotational velocities, decreasing the accuracy with which their orbital velocities can be measured. The preliminary conclusion from the 4 HST targets and SU Cyg (mass from IUE observations) is that a weighted mean indicates no convective overshoot but the mode (which reflects the HST results better) agrees with the modest overshoot used in the Geneva evolutionary calculations. Financial Support was provided by a NASA grant GO-4541-01 to EB--V and GO-4541.02 to KGC, a grant from the Natural Sciences and Engineering Council, Canada to NRE, from the AXAF Science Center NASA Contract NAS8-39073.

Emission line models for the lowest mass core-collapse supernovae - I. Case study of a 9 M⊙ one-dimensional neutrino-driven explosion

NASA Astrophysics Data System (ADS)

Jerkstrand, A.; Ertl, T.; Janka, H.-T.; Müller, E.; Sukhbold, T.; Woosley, S. E.

2018-03-01

A large fraction of core-collapse supernovae (CCSNe), 30-50 per cent, are expected to originate from the low-mass end of progenitors with MZAMS = 8-12 M⊙. However, degeneracy effects make stellar evolution modelling of such stars challenging, and few predictions for their supernova light curves and spectra have been presented. Here, we calculate synthetic nebular spectra of a 9 M⊙ Fe CCSN model exploded with the neutrino mechanism. The model predicts emission lines with FWHM ˜ 1000 km s-1, including signatures from each deep layer in the metal core. We compare this model to the observations of the three subluminous IIP SNe with published nebular spectra; SN 1997D, SN 2005cs and SN 2008bk. The predictions of both line profiles and luminosities are in good agreement with SN 1997D and SN 2008bk. The close fit of a model with no tuning parameters provides strong evidence for an association of these objects with low-mass Fe CCSNe. For SN 2005cs, the interpretation is less clear, as the observational coverage ended before key diagnostic lines from the core had emerged. We perform a parametrized study of the amount of explosively made stable nickel, and find that none of these three SNe show the high 58Ni/56Ni ratio predicted by current models of electron capture SNe (ECSNe) and ECSN-like explosions. Combined with clear detection of lines from O and He shell material, these SNe rather originate from Fe core progenitors. We argue that the outcome of self-consistent explosion simulations of low-mass stars, which gives fits to many key observables, strongly suggests that the class of subluminous Type IIP SNe is the observational counterpart of the lowest mass CCSNe.

Metabolic profiling for the identification of Huntington biomarkers by on-line solid-phase extraction capillary electrophoresis mass spectrometry combined with advanced data analysis tools.

PubMed

Pont, Laura; Benavente, Fernando; Jaumot, Joaquim; Tauler, Romà; Alberch, Jordi; Ginés, Silvia; Barbosa, José; Sanz-Nebot, Victoria

2016-03-01

In this work, an untargeted metabolomic approach based on sensitive analysis by on-line solid-phase extraction capillary electrophoresis mass spectrometry (SPE-CE-MS) in combination with multivariate data analysis is proposed as an efficient method for the identification of biomarkers of Huntington's disease (HD) progression in plasma. For this purpose, plasma samples from wild-type (wt) and HD (R6/1) mice of different ages (8, 12, and 30 weeks), were analyzed by C18 -SPE-CE-MS in order to obtain the characteristic electrophoretic profiles of low molecular mass compounds. Then, multivariate curve resolution alternating least squares (MCR-ALS) was applied to the multiple full scan MS datasets. This strategy permitted the resolution of a large number of metabolites being characterized by their electrophoretic peaks and their corresponding mass spectra. A total number of 29 compounds were relevant to discriminate between wt and HD plasma samples, as well as to follow-up the HD progression. The intracellular signaling was found to be the most affected metabolic pathway in HD mice after 12 weeks of birth, when mice already showed motor coordination deficiencies and cognitive decline. This fact agreed with the atrophy and dysfunction of specific neurons, loss of several types of receptors, and changed expression of neurotransmitters. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Highly abundant defense proteins in human sweat as revealed by targeted proteomics and label-free quantification mass spectrometry.

PubMed

Csősz, É; Emri, G; Kalló, G; Tsaprailis, G; Tőzsér, J

2015-10-01

The healthy human skin with its effective antimicrobial defense system forms an efficient barrier against invading pathogens. There is evidence suggesting that the composition of this chemical barrier varies between diseases, making the easily collected sweat an ideal candidate for biomarker discoveries. Our aim was to provide information about the normal composition of the sweat, and to study the chemical barrier found at the surface of skin. Sweat samples from healthy individuals were collected during sauna bathing, and the global protein panel was analysed by label-free mass spectrometry. SRM-based targeted proteomic methods were designed and stable isotope labelled reference peptides were used for method validation. Ninety-five sweat proteins were identified, 20 of them were novel proteins. It was shown that dermcidin is the most abundant sweat protein, and along with apolipoprotein D, clusterin, prolactin-inducible protein and serum albumin, they make up 91% of secreted sweat proteins. The roles of these highly abundant proteins were reviewed; all of which have protective functions, highlighting the importance of sweat glands in composing the first line of innate immune defense system, and maintaining the epidermal barrier integrity. Our findings with regard to the proteins forming the chemical barrier of the skin as determined by label-free quantification and targeted proteomics methods are in accordance with previous studies, and can be further used as a starting point for non-invasive sweat biomarker research. © 2015 European Academy of Dermatology and Venereology.

An automated on-line turbulent flow liquid-chromatography technology coupled to a high resolution mass spectrometer LTQ-Orbitrap for suspect screening of antibiotic transformation products during microalgae wastewater treatment.

PubMed

Jaén-Gil, Adrián; Hom-Diaz, Andrea; Llorca, Marta; Vicent, Teresa; Blánquez, Paqui; Barceló, Damià; Rodríguez-Mozaz, Sara

2018-06-11

The evaluation of wastewater treatment capabilities in terms of removal of water pollutants is crucial when assessing water mitigation issues. Not only the monitoring of target pollutants becomes a critical point, but also the transformation products (TPs) generated. Since these TPs are very often unknown compounds, their study in both wastewater and natural environment is currently recognized as a tedious task and challenging research field. In this study, a novel automated suspect screening methodology was developed for a comprehensive assessment of the TPs generated from nine antibiotics during microalgae water treatment. Three macrolides (azithromycin, erythromycin, clarithromycin), three fluoroquinolones (ofloxacin, ciprofloxacin, norfloxacin) and three additional antibiotics (trimethoprim, pipemidic acid, sulfapyridine) were selected as target pollutants. The analysis of samples was carried out by direct injection in an on-line turbulent flow liquid chromatography-high resolution mass spectrometry (TFC-LC-LTQ-Orbitrap-MS/MS) system, followed by automatic data processing for compound identification. The screening methodology allowed the identification of 40 tentative TPs from a list of software predicted intermediates created automatically. Once known and unknown TPs were identified, degradation pathways were suggested considering the different mechanisms involved on their formation (biotic and abiotic). Results reveal microalgae ability for macrolide biotransformation, but not for other antibiotics such as for fluoroquinolones. Finally, the intermediates detected were included into an in-house library and applied to the identification of tentative TPs in real toilet wastewater treated in a microalgae based photobioreactor (PBR). The overall approach allowed a comprehensive overview of the performance of microalgae water treatment in a fast and reliable manner: it represents a useful tool for the rapid screening of wide range of compounds, reducing time

A hand and a field effect in on-line motor control in unilateral optic ataxia.

PubMed

Blangero, Annabelle; Gaveau, Valérie; Luauté, Jacques; Rode, Gilles; Salemme, Romeo; Guinard, Marine; Boisson, Dominique; Rossetti, Yves; Pisella, Laure

2008-05-01

Patients with bilateral optic ataxia fail to show rapid perturbation-induced corrections during manual aiming movements. Based on this, it has been proposed that this pathology results from a disruption of processes of on-line motor control in the posterior parietal cortex (PPC). Here, we show that on-line motor control performance in a patient with unilateral optic ataxia is similar to that of pointing towards stationary targets in peripheral vision, showing the same combination of hand and field effects. We also show that in the patient, manual correction towards his ataxic field was possible only when a preceding saccade (100msec earlier) rapidly provides foveal information about the new target location. In control subjects, manual correction was often, but not necessarily preceded by a saccade. These results allow us to put forward a model of visuo-manual transformation, which involves updating of the reach plan based on the target-eye error, and rely upon two dissociated spatial representations (of the hand and of the target, respectively) within the PPC.

On-line identification of fermentation processes for ethanol production.

PubMed

Câmara, M M; Soares, R M; Feital, T; Naomi, P; Oki, S; Thevelein, J M; Amaral, M; Pinto, J C

2017-07-01

A strategy for monitoring fermentation processes, specifically, simultaneous saccharification and fermentation (SSF) of corn mash, was developed. The strategy covered the development and use of first principles, semimechanistic and unstructured process model based on major kinetic phenomena, along with mass and energy balances. The model was then used as a reference model within an identification procedure capable of running on-line. The on-line identification procedure consists on updating the reference model through the estimation of corrective parameters for certain reaction rates using the most recent process measurements. The strategy makes use of standard laboratory measurements for sugars quantification and in situ temperature and liquid level data. The model, along with the on-line identification procedure, has been tested against real industrial data and have been able to accurately predict the main variables of operational interest, i.e., state variables and its dynamics, and key process indicators. The results demonstrate that the strategy is capable of monitoring, in real time, this complex industrial biomass fermentation. This new tool provides a great support for decision-making and opens a new range of opportunities for industrial optimization.

The Ca II V/R ratio and mass loss. [stellar spectral emission lines

NASA Technical Reports Server (NTRS)

Stencel, R. E.

1978-01-01

High-dispersion coude spectrograms of 181 MK standards of types early F through late M, including luminosity classes Ia, Ib, II, and III, are analyzed. It is shown that the brightness ratio of the V and R self-reversed emission peaks (denoted V/R) in the center of the Ca II K line is correlated with spectral type as well as with certain other spectral-type and luminosity-sensitive parameters, including indicators of mass loss and the H-K wing emission lines. The observations indicate that V/R varies smoothly from less than unity in late K and M giants to greater than unity for G giants. This trend appears to be true for bright giants as well but not necessarily for supergiants and seems to hold for the average V/R for a given star, although short-term variations in V/R occur. It is suggested that the V/R values, which can be interpreted in terms of atmospheric motions, may indirectly relate to effects of evolutionary changes in stellar structure and that V/R among late-type stars could be useful as an indicator of both chromospheric activity and the state of stellar evolution.

Multivariate Calibration Approach for Quantitative Determination of Cell-Line Cross Contamination by Intact Cell Mass Spectrometry and Artificial Neural Networks.

PubMed

Valletta, Elisa; Kučera, Lukáš; Prokeš, Lubomír; Amato, Filippo; Pivetta, Tiziana; Hampl, Aleš; Havel, Josef; Vaňhara, Petr

2016-01-01

Cross-contamination of eukaryotic cell lines used in biomedical research represents a highly relevant problem. Analysis of repetitive DNA sequences, such as Short Tandem Repeats (STR), or Simple Sequence Repeats (SSR), is a widely accepted, simple, and commercially available technique to authenticate cell lines. However, it provides only qualitative information that depends on the extent of reference databases for interpretation. In this work, we developed and validated a rapid and routinely applicable method for evaluation of cell culture cross-contamination levels based on mass spectrometric fingerprints of intact mammalian cells coupled with artificial neural networks (ANNs). We used human embryonic stem cells (hESCs) contaminated by either mouse embryonic stem cells (mESCs) or mouse embryonic fibroblasts (MEFs) as a model. We determined the contamination level using a mass spectra database of known calibration mixtures that served as training input for an ANN. The ANN was then capable of correct quantification of the level of contamination of hESCs by mESCs or MEFs. We demonstrate that MS analysis, when linked to proper mathematical instruments, is a tangible tool for unraveling and quantifying heterogeneity in cell cultures. The analysis is applicable in routine scenarios for cell authentication and/or cell phenotyping in general.

Multivariate Calibration Approach for Quantitative Determination of Cell-Line Cross Contamination by Intact Cell Mass Spectrometry and Artificial Neural Networks

PubMed Central

Prokeš, Lubomír; Amato, Filippo; Pivetta, Tiziana; Hampl, Aleš; Havel, Josef; Vaňhara, Petr

2016-01-01

Cross-contamination of eukaryotic cell lines used in biomedical research represents a highly relevant problem. Analysis of repetitive DNA sequences, such as Short Tandem Repeats (STR), or Simple Sequence Repeats (SSR), is a widely accepted, simple, and commercially available technique to authenticate cell lines. However, it provides only qualitative information that depends on the extent of reference databases for interpretation. In this work, we developed and validated a rapid and routinely applicable method for evaluation of cell culture cross-contamination levels based on mass spectrometric fingerprints of intact mammalian cells coupled with artificial neural networks (ANNs). We used human embryonic stem cells (hESCs) contaminated by either mouse embryonic stem cells (mESCs) or mouse embryonic fibroblasts (MEFs) as a model. We determined the contamination level using a mass spectra database of known calibration mixtures that served as training input for an ANN. The ANN was then capable of correct quantification of the level of contamination of hESCs by mESCs or MEFs. We demonstrate that MS analysis, when linked to proper mathematical instruments, is a tangible tool for unraveling and quantifying heterogeneity in cell cultures. The analysis is applicable in routine scenarios for cell authentication and/or cell phenotyping in general. PMID:26821236

Constructing Proteome Reference Map of the Porcine Jejunal Cell Line (IPEC-J2) by Label-Free Mass Spectrometry.

PubMed

Kim, Sang Hoon; Pajarillo, Edward Alain B; Balolong, Marilen P; Lee, Ji Yoon; Kang, Dae-Kyung

2016-06-28

In this study, the global proteome of the IPEC-J2 cell line was evaluated using ultra-high performance liquid chromatography coupled to a quadrupole Q Exactive™ Orbitrap mass spectrometer. Proteins were isolated from highly confluent IPEC-J2 cells in biological replicates and analyzed by label-free mass spectrometry prior to matching against a porcine genomic dataset. The results identified 1,517 proteins, accounting for 7.35% of all genes in the porcine genome. The highly abundant proteins detected, such as actin, annexin A2, and AHNAK nucleoprotein, are involved in structural integrity, signaling mechanisms, and cellular homeostasis. The high abundance of heat shock proteins indicated their significance in cellular defenses, barrier function, and gut homeostasis. Pathway analysis and annotation using the Kyoto Encyclopedia of Genes and Genomes database resulted in a putative protein network map of the regulation of immunological responses and structural integrity in the cell line. The comprehensive proteome analysis of IPEC-J2 cells provides fundamental insights into overall protein expression and pathway dynamics that might be useful in cell adhesion studies and immunological applications.

Structure identification by Mass Spectrometry Non-Targeted Analysis using the US EPA’s CompTox Chemistry Dashboard

EPA Science Inventory

Identification of unknowns in mass spectrometry based non-targeted analyses (NTA) requires the integration of complementary pieces of data to arrive at a confident, consensus structure. Researchers use chemical reference databases, spectral matching, fragment prediction tools, r...

Feasibility of on-line temperature-based hyperthermia treatment planning to improve tumour temperatures during locoregional hyperthermia.

PubMed

Kok, H P; Korshuize-van Straten, L; Bakker, A; de Kroon-Oldenhof, R; Westerveld, G H; Versteijne, E; Stalpers, L J A; Crezee, J

2017-11-16

The effectiveness of hyperthermia is strongly dependent on the achieved tumour temperatures. Phased-array systems allow flexible power steering to realise good tumour heating while avoiding excessive heating in normal tissue, but the limited quantitative accuracy of pre-treatment planning complicates realising optimal tumour heating. On-line hyperthermia treatment planning could help to improve the heating quality. This paper demonstrates the feasibility of using on-line temperature-based treatment planning to improve the heating quality during hyperthermia in three patients. Hyperthermia treatment planning was performed using the Plan2Heat software package combined with a dedicated graphical user interface for on-line application. Electric fields were pre-calculated to allow instant update and visualisation of the predicted temperature distribution for user-selected phase-amplitude settings during treatment. On-line treatment planning using manual variation of system settings for the AMC-8 hyperthermia system was applied in one patient with a deep-seated pelvic melanoma metastasis and two cervical cancer patients. For a clinically relevant improvement the increase in average target temperature should be at least 0.2 °C. With the assistance of on-line treatment planning a substantial improvement in tumour temperatures was realised for all three patients. In the melanoma patient, the average measured target temperature increased from 38.30 °C to 39.15 °C (i.e. +0.85 °C). In the cervical cancer patients, the average measured target temperature increased from 41.30 °C to 42.05 °C (i.e. +0.75 °C) and from 41.70 °C to 42.80 °C (i.e. +1.1 °C), respectively. On-line temperature-based treatment planning is clinically feasible to improve tumour temperatures. A next, worthwhile step is automatic optimisation for a larger number of patients.

Analysis of biogenic carbonates by inductively coupled plasma-mass spectrometry (ICP-MS). Flow injection on-line solid-phase preconcentration for trace element determination in fish otoliths.

PubMed

Arslan, Z; Paulson, A J

2002-04-01

The aragonite deposits within the ear bones (otoliths) of teleost fish retain a chemical signal reflecting the life history of fish (similar to rings of trees) and the nature of fish habitats. Otoliths dissolved in acid solutions contain high concentrations of calcium and a variety of proteins. Elimination of matrix salts and organic interferences during preconcentration is essential for accurate determination of trace elements in otolith solutions by inductively coupled plasma-quadrupole mass spectrometry. An iminodiacetate-based chelating resin (Toyopearl AF-Chelate 650 M) has been used for on-line preconcentration and matrix separation for the determination of 31 transition and rare elements. Successful preconcentration of the elements was achieved at pH 5 by on-line buffering, except Mn which required pH 8.8. Sample solutions were loaded on to the column for 1 min at 3.2 mL min(-1), and then eluted directly into the mass spectrometer with 4% v/v nitric acid. This procedure enabled up to 25-fold preconcentration with successful removal of the calcium matrix. The effect of heat-assisted oxidation with concentrated nitric acid was investigated to eliminate the organic matrix. It was found that heating to dryness after dissolution and further mineralization with the acid significantly improved the retention of the transition elements. The method was validated by analysis of a certified reference material produced from saggittal otoliths of emperor snapper ( Lutjanus sebae), and then applied to the determination of trace metal concentrations in juvenile bluefin tuna ( Thunnus thynnus) from the Western Pacific Ocean.

Analysis of particulate polycyclic aromatic hydrocarbons by on-line coupled supercritical fluid extraction-liquid chromatography-gas chromatography-mass spectrometry

NASA Astrophysics Data System (ADS)

Shimmo, Masahiko; Adler, Heidi; Hyötyläinen, Tuulia; Hartonen, Kari; Kulmala, Markku; Riekkola, Marja-Liisa

An on-line supercritical fluid extraction-liquid chromatography-gas chromatography-mass spectrometry (SFE-LC-GC-MS) method was developed for the analysis of the particulate polycyclic aromatic hydrocarbons (PAHs). The limits of detection of the system for the quantification standards were in the range of 0.25-0.57 ng, while the limits of determinations for filter samples varied from 0.02 to 0.04 ng m -3 (24 h sampling). The linearity was excellent from 5 to 300 ng ( R2>0.967). The analysis could be carried out in a closed system without tedious manual sample pretreatment and with no risk of errors by contamination or loss of the analytes. The results of the SFE-LC-GC-MS method were comparable with those for Soxhlet and shake-flask extractions with GC-MS. The new method was applied to the analysis of PAHs collected by high-volume filter in the Helsinki area to study the seasonal trend of the concentrations. The individual PAH concentrations varied from 0.015 to more than 1 ng m -3, while total PAH concentrations varied from 0.81 to 5.68 ng m -3. The concentrations were generally higher in winter than in summer. The mass percentage of the total PAHs in total suspended particulates ranged from 2.85×10 -3% in July to 15.0×10 -3% in December. Increased emissions in winter, meteorological conditions, and more serious artefacts during the sampling in summer season may explain the concentration profiles.

Multiplexed Liquid Chromatography-Multiple Reaction Monitoring Mass Spectrometry Quantification of Cancer Signaling Proteins

PubMed Central

Chen, Yi; Fisher, Kate J.; Lloyd, Mark; Wood, Elizabeth R.; Coppola, Domenico; Siegel, Erin; Shibata, David; Chen, Yian A.; Koomen, John M.

2017-01-01

Quantitative evaluation of protein expression across multiple cancer-related signaling pathways (e.g. Wnt/β-catenin, TGF-β, receptor tyrosine kinases (RTK), MAP kinases, NF-κB, and apoptosis) in tumor tissues may enable the development of a molecular profile for each individual tumor that can aid in the selection of appropriate targeted cancer therapies. Here, we describe the development of a broadly applicable protocol to develop and implement quantitative mass spectrometry assays using cell line models and frozen tissue specimens from colon cancer patients. Cell lines are used to develop peptide-based assays for protein quantification, which are incorporated into a method based on SDS-PAGE protein fractionation, in-gel digestion, and liquid chromatography-multiple reaction monitoring mass spectrometry (LC-MRM/MS). This analytical platform is then applied to frozen tumor tissues. This protocol can be broadly applied to the study of human disease using multiplexed LC-MRM assays. PMID:28808993

Theoretical investigation on the mass loss impact on asteroseismic grid-based estimates of mass, radius, and age for RGB stars

NASA Astrophysics Data System (ADS)

Valle, G.; Dell'Omodarme, M.; Prada Moroni, P. G.; Degl'Innocenti, S.

2018-01-01

Aims: We aim to perform a theoretical evaluation of the impact of the mass loss indetermination on asteroseismic grid based estimates of masses, radii, and ages of stars in the red giant branch (RGB) phase. Methods: We adopted the SCEPtER pipeline on a grid spanning the mass range [0.8; 1.8] M⊙. As observational constraints, we adopted the star effective temperatures, the metallicity [Fe/H], the average large frequency spacing Δν, and the frequency of maximum oscillation power νmax. The mass loss was modelled following a Reimers parametrization with the two different efficiencies η = 0.4 and η = 0.8. Results: In the RGB phase, the average random relative error (owing only to observational uncertainty) on mass and age estimates is about 8% and 30% respectively. The bias in mass and age estimates caused by the adoption of a wrong mass loss parameter in the recovery is minor for the vast majority of the RGB evolution. The biases get larger only after the RGB bump. In the last 2.5% of the RGB lifetime the error on the mass determination reaches 6.5% becoming larger than the random error component in this evolutionary phase. The error on the age estimate amounts to 9%, that is, equal to the random error uncertainty. These results are independent of the stellar metallicity [Fe/H] in the explored range. Conclusions: Asteroseismic-based estimates of stellar mass, radius, and age in the RGB phase can be considered mass loss independent within the range (η ∈ [0.0,0.8]) as long as the target is in an evolutionary phase preceding the RGB bump.

Proton-transfer reaction mass spectrometry (PTRMS) in combination with thermal desorption (TD) for sensitive off-line analysis of volatiles.

PubMed

Crespo, Elena; Devasena, Samudrala; Sikkens, Cor; Centeno, Raymund; Cristescu, Simona M; Harren, Frans J M

2012-04-30

When performing trace gas analysis, it is not always possible to bring the source of volatiles and the gas analyzer together. In these cases, volatile storage containers, such as thermal desorption (TD) tubes, can be used for off-line measurement. TD is routinely combined with gas chromatography/mass spectrometry (GC/MS), but so far not with proton-transfer reaction mass spectrometry (PTRMS), which has a faster response. A PTR-quadrupole-MS instrument and a PTR-ion-trap-MS instrument were separately coupled to a TD unit for off-line analysis of trace volatiles in air. Carbograph 1TD/Carbopack X sorbent tubes were filled with different concentrations of a trace gas mixture containing low molecular weight volatiles (32 g/mol up to 136 g/mol) and measured with the above-mentioned combinations. The carrier gas in the TD unit was changed from helium to nitrogen to be able to combine this instrument with the mass spectrometer. Good linearity and reproducibility with the amount of gas stored were obtained. The storage capacity over time (up to 14 days) showed larger variability (<11% for all compounds, except for acetone 27%). Several tubes were filled with breath of different persons, and the breath of a smoker showed increased levels of acetonitrile and benzene. The combination of the PTR ion-trap instrument with the TD unit was also investigated. Due to its higher sampling rate, the ion-trap system showed higher throughput capabilities than the quadrupole system. The combination of TD with PTRMS using both a quadrupole and an ion trap for off-line volatile analysis has been validated. TD tubes can be a robust and compact volatile storage method when the mass spectrometry and the sampling cannot be performed in the same place, for example in large screening studies. In addition, a higher measurement throughput than with GC/MS could be obtained. Copyright © 2012 John Wiley & Sons, Ltd.

Transmission line design for the lunar environment

NASA Technical Reports Server (NTRS)

Gaustad, Krista L.; Gordon, Lloyd B.

1990-01-01

How the mass, operating temperature, and efficiency of a transmission line operating on the moon are affected by its operating parameters, the lunar environment, and the choice of materials is examined. The key transmission line parameters which have an effect on mass, operating temperature, and efficiency are voltage, power loss, and waveform. The choice of waveform for transmission will be influenced by the waveform of the source and load, and therefore an analysis of both DC and AC transmission is necessary for a complete understanding of lunar power transmission. The data presented are for the DC case only; however, the discussion of the environmental effects and of material selection is pertinent to both AC and DC transmission. The operating voltage is shown to be a key parameter in transmission line design. The role efficiency plays in transmission line design is also examined. The analyses include above- and below-the-surface operation for both a vacuum-insulated, two-wire, transmission line, and a solid-dielectric-insulated, coaxial, transmission line.

Estimation of the bio-accessible fraction of Cr, As, Cd and Pb in locally available bread using on-line continuous leaching method coupled to inductively coupled plasma mass spectrometry.

PubMed

Lamsal, Ram P; Beauchemin, Diane

2015-03-31

A previously developed, efficient and simple on-line leaching method was used to assess the maximum bio-accessible fraction (assuming no synergistic effect from other food and beverage) of potentially toxic elements (Cr, As, Cd and Pb) in whole wheat brown and white bread samples. Artificial saliva, gastric juice and intestinal juice were successively pumped into a mini-column, packed with bread (maintained at 37 °C) connected on-line to the nebulizer of an inductively coupled plasma mass spectrometry (ICP-MS) instrument equipped with a collision-reaction interface (CRI) using hydrogen as reaction gas to minimize carbon- and chlorine-based polyatomic interferences. In contrast to the conventional batch method to which it was compared, this approach provides real-time monitoring of potentially toxic elements that are continuously released during leaching. Mass balance for both methods was verified at the 95% confidence level. Results obtained from the whole wheat brown and white bread showed that the majority of Cr, Cd and Pb was leached by gastric juice but, in contrast, the majority of As was leached by saliva. While there was higher total content for elements in whole wheat bread than in white bread, a higher percentage of elements were bio-accessible in white bread than in whole wheat bread. Both the on-line and batch methods indicate that 40-98% of toxic elements in bread samples are bio-accessible. While comparison of total analyte concentrations with provisional tolerable daily intake values may indicate some serious health concern for children, when accounting for the bio-accessibility of these elements, bread consumption is found to be safe for all ages. Copyright © 2015 Elsevier B.V. All rights reserved.

On-line solid phase extraction using the Prospekt-2 coupled with a liquid chromatography/tandem mass spectrometer for the determination of dextromethorphan, dextrorphan and guaifenesin in human plasma.

PubMed

Kuhlenbeck, Debbie L; Eichold, Thomas H; Hoke, Steven H; Baker, Timothy R; Mensen, Robert; Wehmeyer, Kenneth R

2005-01-01

An on-line liquid chromatography/tandem mass spectrometry (LC-MS/MS) procedure, using the Prospekt- 2 system, was developed and used for the determination of the levels of the active ingredients of cough/cold medications in human plasma matrix. The experimental configuration allows direct plasma injection by performing on- line solid phase extraction (SPE) on small cartridge columns prior to elution of the analyte(s) onto the analytical column and subsequent MS/MS detection. The quantitative analysis of three analytes with differing polarities, dextromethorphan (DEX), dextrorphan (DET) and guaifenesin (GG) in human plasma presented a significant challenge. Using stable-isotope-labeled internal standards for each analyte, the Prospekt-2 on-line methodology was evaluated for sensitivity, suppression, accuracy, precision, linearity, analyst time, analysis time, cost, carryover and ease of use. The lower limit of quantitation for the on-line SPE procedure for DEX, DET and GG was 0.05, 0.05 and 5.0 ng mL(-1), respectively, using a 0.1 mL sample volume. The linear range for DEX and DET was 0.05-50 ng mL(-1) and was 5-5,000 ng mL(-1) for GG. Accuracy and precision data for five different levels of QC samples were collected over three separate days. Accuracy ranged from 90% to 112% for all three analytes, while the precision, as measured by the %RSD, ranged from 1.5% to 16.0%

A REVERBERATION-BASED BLACK HOLE MASS FOR MCG-06-30-15

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

Bentz, Misty C.; Crenshaw, D. Michael; Ou-Yang, Benjamin

2016-10-20

We present the results of a reverberation campaign targeting MGC-06-30-15. Spectrophotometric monitoring and broad-band photometric monitoring over the course of four months in spring 2012 allowed a determination of a time delay in the broad H β emission line of τ = 5.3 ± 1.8 days in the rest frame of the active galactic nucleus (AGN). Combined with the width of the variable portion of the emission line, we determine a black hole mass of M {sub BH} = (1.6 ± 0.4) × 10{sup 6} M {sub ⊙}. Both the H β time delay and the black hole mass aremore » in good agreement with expectations from the R {sub BLR}– L and M {sub BH}– σ {sub ⋆} relationships for other reverberation-mapped AGNs. The H β time delay is also in good agreement with the relationship between H β and broad-band near-IR delays, in which the effective size of the broad-line region is ∼4–5 times smaller than the inner edge of the dust torus. Additionally, the reverberation-based mass is in good agreement with estimates from the scaling relationship of the break in the X-ray power spectral density, and with constraints based on stellar kinematics derived from integral field spectroscopy of the inner ∼0.5 kpc of the galaxy.« less

Research on the Test of Transmission Line Galloping

NASA Astrophysics Data System (ADS)

Zhang, Lichun; Li, Qing; lv, Zhongbin; Ji, Kunpeng; Liu, Bin

2018-03-01

The load of iced transmission line and the load generated by galloping after the conductor are covered by ice all may cause severe circuit faults, such as tripping, conductor breaking, armor clamp damage and even tower collapse, thus severely threatening running safety of power system. The generation and development processes of galloping of power transmission line is very complicated, and numerous factors may influence the galloping excitation, such as environmental factors, terrain factors and structural parameters of power transmission line; in which, the ice covering of conductor is one of necessary factors causing galloping. Therefore, researches on ice covering increasing test of different types of conductors under different meteorological conditions have been conducted in large-sized multi-functional phytotron, thus obtaining the relation curve of ice covering increasing of conductor along with time under different conditions, and analyzing factors influencing increasing of ice covering. The research result shows that under the same ice covering conditions, the increasing of ice covering of conductor with small diameter is relatively rapid; both environmental temperature and wind speed have obvious influence on increasing of ice covering of conductor, and the environmental temperature will decide the type of ice covering of conductor surface. Meanwhile, after wind tunnel tests targeting conductors with different ice covering shapes, pneumatic stability loss characteristics of conductors with different ice shapes have been obtained. Research results have important scientific reference value for revealing the mechanism of galloping of iced power transmission line, and have relatively high engineering practicability value for promoting realization of early warning system for galloping of iced power transmission line.

Accuracy of off-line bioluminescence imaging to localize targets in preclinical radiation research.

PubMed

Tuli, Richard; Armour, Michael; Surmak, Andrew; Reyes, Juvenal; Iordachita, Iulian; Patterson, Michael; Wong, John

2013-04-01

In this study, we investigated the accuracy of using off-line bioluminescence imaging (BLI) and tomography (BLT) to guide irradiation of small soft tissue targets on a small animal radiation research platform (SARRP) with on-board cone beam CT (CBCT) capability. A small glass bulb containing BL cells was implanted as a BL source in the abdomen of 11 mouse carcasses. Bioluminescence imaging and tomography were acquired for each carcass. Six carcasses were setup visually without immobilization and 5 were restrained in position with tape. All carcasses were setup in treatment position on the SARRP where the centroid position of the bulb on CBCT was taken as "truth". In the 2D visual setup, the carcass was setup by aligning the point of brightest luminescence with the vertical beam axis. In the CBCT assisted setup, the pose of the carcass on CBCT was aligned with that on the 2D BL image for setup. For both 2D setup methods, the offset of the bulb centroid on CBCT from the vertical beam axis was measured. In the BLT-CBCT fusion method, the 3D torso on BLT and CBCT was registered and the 3D offset of the respective source centroids was calculated. The setup results were independent of the carcass being immobilized or not due to the onset of rigor mortis. The 2D offset of the perceived BL source position from the CBCT bulb position was 2.3 mm ± 1.3 mm. The 3D offset between BLT and CBCT was 1.5 mm ± 0.9 mm. Given the rigidity of the carcasses, the setup results represent the best that can be achieved with off-line 2D BLI and 3D BLT. The setup uncertainty would require the use of undesirably large margin of 4-5 mm. The results compel the implementation of on-board BLT capability on the SARRP to eliminate setup error and to improve BLT accuracy.

Accuracy of Off-Line Bioluminescence Imaging to Localize Targets in Preclinical Radiation Research

PubMed Central

Tuli, Richard; Armour, Michael; Surmak, Andrew; Reyes, Juvenal; Iordachita, Iulian; Patterson, Michael; Wong, John

2013-01-01

In this study, we investigated the accuracy of using off-line bioluminescence imaging (BLI) and tomography (BLT) to guide irradiation of small soft tissue targets on a small animal radiation research platform (SARRP) with on-board cone beam CT (CBCT) capability. A small glass bulb containing BL cells was implanted as a BL source in the abdomen of 11 mouse carcasses. Bioluminescence imaging and tomography were acquired for each carcass. Six carcasses were setup visually without immobilization and 5 were restrained in position with tape. All carcasses were setup in treatment position on the SARRP where the centroid position of the bulb on CBCT was taken as “truth”. In the 2D visual setup, the carcass was setup by aligning the point of brightest luminescence with the vertical beam axis. In the CBCT assisted setup, the pose of the carcass on CBCT was aligned with that on the 2D BL image for setup. For both 2D setup methods, the offset of the bulb centroid on CBCT from the vertical beam axis was measured. In the BLT-CBCT fusion method, the 3D torso on BLT and CBCT was registered and the 3D offset of the respective source centroids was calculated. The setup results were independent of the carcass being immobilized or not due to the onset of rigor mortis. The 2D offset of the perceived BL source position from the CBCT bulb position was 2.3 mm ± 1.3 mm. The 3D offset between BLT and CBCT was 1.5 mm ± 0.9 mm. Given the rigidity of the carcasses, the setup results represent the best that can be achieved with off-line 2D BLI and 3D BLT. The setup uncertainty would require the use of undesirably large margin of 4–5 mm. The results compel the implementation of on-board BLT capability on the SARRP to eliminate setup error and to improve BLT accuracy. PMID:23578189

Disclosing the Parameters Leading to High Productivity of Retroviral Producer Cells Lines: Evaluating Random Versus Targeted Integration.

PubMed

Bandeira, Vanessa S; Tomás, Hélio A; Alici, Evren; Carrondo, Manuel J T; Coroadinha, Ana S

2017-04-01

Gammaretrovirus and lentivirus are the preferred viral vectors to genetically modify T and natural killer cells to be used in immune cell therapies. The transduction efficiency of hematopoietic and T cells is more efficient using gibbon ape leukemia virus (GaLV) pseudotyping. In this context gammaretroviral vector producer cells offer competitive higher titers than transient lentiviral vectors productions. The main aim of this work was to identify the key parameters governing GaLV-pseudotyped gammaretroviral vector productivity in stable producer cells, using a retroviral vector expression cassette enabling positive (facilitating cell enrichment) and negative cell selection (allowing cell elimination). The retroviral vector contains a thymidine kinase suicide gene fused with a ouabain-resistant Na + ,K + -ATPase gene, a potential safer and faster marker. The establishment of retroviral vector producer cells is traditionally performed by randomly integrating the retroviral vector expression cassette codifying the transgene. More recently, recombinase-mediated cassette exchange methodologies have been introduced to achieve targeted integration. Herein we compared random and targeted integration of the retroviral vector transgene construct. Two retroviral producer cell lines, 293 OuaS and 293 FlexOuaS, were generated by random and targeted integration, respectively, producing high titers (on the order of 10 7 infectious particles·ml -1 ). Results showed that the retroviral vector transgene cassette is the key retroviral vector component determining the viral titers notwithstanding, single-copy integration is sufficient to provide high titers. The expression levels of the three retroviral constructs (gag-pol, GaLV env, and retroviral vector transgene) were analyzed. Although gag-pol and GaLV env gene expression levels should surpass a minimal threshold, we found that relatively modest expression levels of these two expression cassettes are required. Their levels of

On-line solid phase extraction-liquid chromatography-tandem mass spectrometry for insect repellent residue analysis in surface waters using atmospheric pressure photoionization.

PubMed

Molins-Delgado, Daniel; García-Sillero, Daniel; Díaz-Cruz, M Silvia; Barceló, Damià

2018-04-06

Insect repellents (IRs) are a group of organic chemicals whose function is to prevent the ability of insects of landing in a surface. These compounds have been found in the environment and may pose a risk to non-target organisms. In this study, an on-line solid phase extraction - high performance liquid chromatography-tandem mass spectrometry multiresidue method was developed using an atmospheric photoionization source (SPE-HPLC-(APPI)-MS/MS). The use of the APPI as an alternative ionization technique to electrospray (ESI) and atmospheric pressure chemical ionization (APCI) allowed expanding the range of analytical techniques suitable for the analysis of IRs, so far relied in gas chromatography. High sensitivity and precision was reached with method limits of quantification between 0.2 and 4.6 ng l -1 and interday and intraday precision equal or below 15%. The validated method was applied to the study of surface water samples from three European river basins with different flow regime (Adige River in Italy, Sava River in the Balkans, and Evrotas River in Greece). The results showed that two IRs (DEET and Bayrepel) were ubiquitous in the Sava and Evrotas basins, reaching concentrations as high as 105 μg l -1 of Bayrepel in the Sava River, and 5 μg l -1 of DEET in the Evrotas River. Densely populated areas and effluent waste waters are pointed out as the responsible for this pollution. In the alpine river Adige, only three samples showed low levels of IRs (6.01-37.8 ng l -1 ). The concentrations measured were used to perform an environmental risk assessment based on the hazard quotients (HQs) estimation approach by using the chronic and acute eco-toxicity data available. The results revealed that despite the high frequency and eventually high concentrations of these IRs determined in the three basins, only few sites were at risk, with 1 < HQs < 3.3. Copyright © 2018 The Author(s). Published by Elsevier B.V. All rights reserved.

Split Flow Online Solid-Phase Extraction Coupled with Inductively Coupled Plasma Mass Spectrometry System for One-Shot Data Acquisition of Quantification and Recovery Efficiency.

PubMed

Furukawa, Makoto; Takagai, Yoshitaka

2016-10-04

Online solid-phase extraction (SPE) coupled with inductively coupled plasma mass spectrometry (ICPMS) is a useful tool in automatic sequential analysis. However, it cannot simultaneously quantify the analytical targets and their recovery percentages (R%) in one-shot samples. We propose a system that simultaneously acquires both data in a single sample injection. The main flowline of the online solid-phase extraction is divided into main and split flows. The split flow line (i.e., bypass line), which circumvents the SPE column, was placed on the main flow line. Under program-controlled switching of the automatic valve, the ICPMS sequentially measures the targets in a sample before and after column preconcentration and determines the target concentrations and the R% on the SPE column. This paper describes the system development and two demonstrations to exhibit the analytical significance, i.e., the ultratrace amounts of radioactive strontium ( 90 Sr) using commercial Sr-trap resin and multielement adsorbability on the SPE column. This system is applicable to other flow analyses and detectors in online solid phase extraction.

Closing in on singlet scalar dark matter: LUX, invisible Higgs decays and gamma-ray lines

DOE PAGES

Feng, Lei; Profumo, Stefano; Ubaldi, Lorenzo

2015-03-10

Here, we study the implications of the Higgs discovery and of recent results from dark matter searches on real singlet scalar dark matter. The phenomenology of the model is defined by only two parameters, the singlet scalar mass m S and the quartic coupling a 2 between the SU(2) Higgs and the singlet scalar. We concentrate on the window 5 < m S /GeV < 300. The most dramatic impact on the viable parameter space of the model comes from direct dark matter searches with LUX, and, for very low masses in the few GeV range, from constraints from themore » invisible decay width of the Higgs. In the resonant region the best constraints come from gamma-ray line searches. We show that they leave only a small region of viable parameter space, for dark matter masses within a few percent of half the mass of the Higgs. We demonstrate that direct and indirect dark matter searches (especially the search for monochromatic gamma-ray lines) will play a key role in closing the residual parameter space in the near future.« less

The effect of on-line position correction on the dose distribution in focal radiotherapy for bladder cancer

PubMed Central

van Rooijen, Dominique C; van de Kamer, Jeroen B; Pool, René; Hulshof, Maarten CCM; Koning, Caro CE; Bel, Arjan

2009-01-01

Background The purpose of this study was to determine the dosimetric effect of on-line position correction for bladder tumor irradiation and to find methods to predict and handle this effect. Methods For 25 patients with unifocal bladder cancer intensity modulated radiotherapy (IMRT) with 5 beams was planned. The requirement for each plan was that 99% of the target volume received 95% of the prescribed dose. Tumor displacements from -2.0 cm to 2.0 cm in each dimension were simulated, using 0.5 cm increments, resulting in 729 simulations per patient. We assumed that on-line correction for the tumor was applied perfectly. We determined the correlation between the change in D99% and the change in path length, which is defined here as the distance from the skin to the isocenter for each beam. In addition the margin needed to avoid underdosage was determined and the probability that an underdosage occurs in a real treatment was calculated. Results Adjustments for tumor displacement with perfect on-line position correction resulted in an altered dose distribution. The altered fraction dose to the target varied from 91.9% to 100.4% of the prescribed dose. The mean D99% (± SD) was 95.8% ± 1.0%. There was a modest linear correlation between the difference in D99% and the change in path length of the beams after correction (R2 = 0.590). The median probability that a systematic underdosage occurs in a real treatment was 0.23% (range: 0 - 24.5%). A margin of 2 mm reduced that probability to < 0.001% in all patients. Conclusion On-line position correction does result in an altered target coverage, due to changes in average path length after position correction. An extra margin can be added to prevent underdosage. PMID:19775479

Looking into individual coffee beans during the roasting process: direct micro-probe sampling on-line photo-ionisation mass spectrometric analysis of coffee roasting gases.

PubMed

Hertz-Schünemann, Romy; Streibel, Thorsten; Ehlert, Sven; Zimmermann, Ralf

2013-09-01

A micro-probe (μ-probe) gas sampling device for on-line analysis of gases evolving in confined, small objects by single-photon ionisation time-of-flight mass spectrometry (SPI-TOFMS) was developed. The technique is applied for the first time in a feasibility study to record the formation of volatile and flavour compounds during the roasting process within (inside) or in the direct vicinity (outside) of individual coffee beans. A real-time on-line analysis of evolving volatile and semi-volatile organic compounds (VOC and SVOC) as they are formed under the mild pyrolytic conditions of the roasting process was performed. The soft-ionisation mass spectra depict a molecular ion signature, which is well corresponding with the existing knowledge of coffee roasting and evolving compounds. Additionally, thereby it is possible to discriminate between Coffea arabica (Arabica) and Coffea canephora (Robusta). The recognized differences in the roasting gas profiles reflect the differences in the precursor composition of the coffee cultivars very well. Furthermore, a well-known set of marker compounds for Arabica and Robusta, namely the lipids kahweol and cafestol (detected in their dehydrated form at m/z 296 and m/z 298, respectively) were observed. If the variation in time of different compounds is observed, distinctly different evolution behaviours were detected. Here, phenol (m/z 94) and caffeine (m/z 194) are exemplary chosen, whereas phenol shows very sharp emission peaks, caffeine do not have this highly transient behaviour. Finally, the changes of the chemical signature as a function of the roasting time, the influence of sampling position (inside, outside) and cultivar (Arabica, Robusta) is investigated by multivariate statistics (PCA). In summary, this pilot study demonstrates the high potential of the measurement technique to enhance the fundamental knowledge of the formation processes of volatile and semi-volatile flavour compounds inside the individual coffee bean.

Apportionment of urban aerosol sources in Chongqing (China) using synergistic on-line techniques

NASA Astrophysics Data System (ADS)

Chen, Yang; Yang, Fumo

2016-04-01

The sources of ambient fine particulate matter (PM2.5) during wintertime at a background urban location in Chongqing (southwestern China) have been determined. Aerosol chemical composition analyses were performed using multiple on-line techniques, such as single particle aerosol mass spectrometer (SPAMS) for single particle chemical composition, on-line elemental carbon-organic carbon analyzer (on-line OC-EC), on-line X-ray fluorescence (XRF) for elements, and in-situ Gas and Aerosol Compositions monitor (IGAC) for water-soluble ions in PM2.5. All the datasets from these techniques have been adjusted to a 1-h time resolution for receptor model input. Positive matrix factorization (PMF) has been used for resolving aerosol sources. At least six sources, including domestic coal burning, biomass burning, dust, traffic, industrial and secondary/aged factors have been resolved and interpreted. The synergistic on-line techniques were helpful for identifying aerosol sources more clearly than when only employing the results from the individual techniques. This results are useful for better understanding of aerosol sources and atmospheric processes.

Intensity Mapping of the [CII] Fine Structure Line during the Epoch of Reionization

NASA Astrophysics Data System (ADS)

Gong, Yan; Cooray, A.; Silva, M.; Santos, M. G.; Bock, J.; Bradford, M.; Zemcov, M.

2012-01-01

The atomic CII fine-structure line is one of the brightest lines in a typical star-forming galaxy spectrum with a luminosity 0.1% to 1% of the bolometric luminosity. It is otentially a reliable tracer of the dense gas distribution at high edshifts and could provide an additional probe to the era of reionization. By taking into account of the spontaneous, stimulated and collisional emission of the CII line, we calculate the spin temperature and the mean intensity as a function of the redshift. When averaged over a cosmologically large volume, we find that the CII emission from ionized carbon in individual galaxies is larger than the signal generated by carbon in the intergalactic medium (IGM). Assuming that the CII luminosity is proportional to the carbon mass in dark matter halos, we also compute the power spectrum of the CII line intensity at various redshifts. In order to avoid the contamination from CO rotational lines at low redshift when targeting a CII survey at high redshifts, we propose the cross-correlation of CII and 21-cm line emission from high redshifts. To explore the detectability of the CII signal from reionization, we also evaluate the expected errors on the CII power spectrum and CII-21 cm cross power spectrum based on the design of the future milimeter surveys. We note that the CII-21 cm cross power spectrum contains interesting features that captures physics during reionization, including the ionized bubble sizes and the mean ionization fraction, which are challenging to measure from 21-cm data alone. We propose an instrumental concept for the reionization CII experiment targeting the frequency range of 200 to 300 GHz with 1, 3 and 10 meter apertures and a bolometric spectrometer array with 64 independent spectral pixels with about 20,000 bolometers.

Simultaneous Detection of Human C-Terminal p53 Isoforms by Single Template Molecularly Imprinted Polymers (MIPs) Coupled with Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS)-Based Targeted Proteomics.

PubMed

Jiang, Wenting; Liu, Liang; Chen, Yun

2018-03-06

Abnormal expression of C-terminal p53 isoforms α, β, and γ can cause the development of cancers including breast cancer. To date, much evidence has demonstrated that these isoforms can differentially regulate target genes and modulate their expression. Thus, quantification of individual isoforms may help to link clinical outcome to p53 status and to improve cancer patient treatment. However, there are few studies on accurate determination of p53 isoforms, probably due to sequence homology of these isoforms and also their low abundance. In this study, a targeted proteomics assay combining molecularly imprinted polymers (MIPs) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed for simultaneous quantification of C-terminal p53 isoforms. Isoform-specific surrogate peptides (i.e., KPLDGEYFTLQIR (peptide-α) for isoform α, KPLDGEYFTLQDQTSFQK (peptide-β) for isoform β, and KPLDGEYFTLQMLLDLR (peptide-γ) for isoform γ) were first selected and used in both MIPs enrichment and mass spectrometric detection. The common sequence KPLDGEYFTLQ of these three surrogate peptides was used as single template in MIPs. In addition to optimization of imprinting conditions and characterization of the prepared MIPs, binding affinity and cross-reactivity of the MIPs for each surrogate peptide were also evaluated. As a result, a LOQ of 5 nM was achieved, which was >15-fold more sensitive than that without MIPs. Finally, the assay was validated and applied to simultaneous quantitative analysis of C-terminal p53 isoforms α, β, and γ in several human breast cell lines (i.e., MCF-10A normal cells, MCF-7 and MDA-MB-231 cancer cells, and drug-resistant MCF-7/ADR cancer cells). This study is among the first to employ single template MIPs and cross-reactivity phenomenon to select isoform-specific surrogate peptides and enable simultaneous quantification of protein isoforms in LC-MS/MS-based targeted proteomics.

Unconscious-thought effects take place off-line, not on-line.

PubMed

Strick, Madelijn; Dijksterhuis, Ap; van Baaren, Rick B

2010-04-01

The unconscious-thought effect refers to an improvement in decision making following distraction from the decision context for a period of time. The dominant explanation for this effect is that unconscious processes continue to deal with the problem during the distraction period. Recently, however, some researchers have proposed that unconscious thinkers may be merely recalling a judgment that was formed on-line (i.e., during information acquisition). We present two experiments that rule out the latter interpretation. In the unconscious-thought condition of the first experiment, participants who reported making their decision after unconscious thought made better decisions than those who reported making their decision on-line. In the second experiment, all participants judged the choice alternatives both on-line and off-line. On-line judgments were predictive of off-line judgments only in the immediate-decision condition, but not in the conscious- and unconscious-thought conditions. These results demonstrate that a period of unconscious thought does improve judgments that were formed earlier on-line.

On-line MR imaging for dose validation of abdominal radiotherapy

NASA Astrophysics Data System (ADS)

Glitzner, M.; Crijns, S. P. M.; de Senneville, B. Denis; Kontaxis, C.; Prins, F. M.; Lagendijk, J. J. W.; Raaymakers, B. W.

2015-11-01

For quality assurance and adaptive radiotherapy, validation of the actual delivered dose is crucial. Intrafractional anatomy changes cannot be captured satisfactorily during treatment with hitherto available imaging modalitites. Consequently, dose calculations are based on the assumption of static anatomy throughout the treatment. However, intra- and interfraction anatomy is dynamic and changes can be significant. In this paper, we investigate the use of an MR-linac as a dose tracking modality for the validation of treatments in abdominal targets where both respiratory and long-term peristaltic and drift motion occur. The on-line MR imaging capability of the modality provides the means to perform respiratory gating of both delivery and acquisition yielding a model-free respiratory motion management under free breathing conditions. In parallel to the treatment, the volumetric patient anatomy was captured and used to calculate the applied dose. Subsequently, the individual doses were warped back to the planning grid to obtain the actual dose accumulated over the entire treatment duration. Ultimately, the planned dose was validated by comparison with the accumulated dose. Representative for a site subject to breathing modulation, two kidney cases (25 Gy target dose) demonstrated the working principle on volunteer data and simulated delivery. The proposed workflow successfully showed its ability to track local dosimetric changes. Integration of the on-line anatomy information could reveal local dose variations  -2.3-1.5 Gy in the target volume of a volunteer dataset. In the adjacent organs at risk, high local dose errors ranging from  -2.5 to 1.9 Gy could be traced back.

Continuous Mass Measurement on Conveyor Belt

NASA Astrophysics Data System (ADS)

Tomobe, Yuki; Tasaki, Ryosuke; Yamazaki, Takanori; Ohnishi, Hideo; Kobayashi, Masaaki; Kurosu, Shigeru

The continuous mass measurement of packages on a conveyor belt will become greatly important. In the mass measurement, the sequence of products is generally random. An interesting possibility of raising throughput of the conveyor line without increasing the conveyor belt speed is offered by the use of two or three conveyor belt scales (called a multi-stage conveyor belt scale). The multi-stage conveyor belt scale can be created which will adjust the conveyor belt length to the product length. The conveyor belt scale usually has maximum capacities of less than 80kg and 140cm, and achieves measuring rates of more than 150 packages per minute and more. The output signals from the conveyor belt scale are always contaminated with noises due to vibrations of the conveyor and the product to be measured in motion. In this paper an employed digital filter is of Finite Impulse Response (FIR) type designed under the consideration on the dynamics of the conveyor system. The experimental results on the conveyor belt scale suggest that the filtering algorithms are effective enough to practical applications to some extent.

Mass communication and development: impact depends on strategies.

PubMed

Wete, F N

1988-01-01

Development scholars are moving toward an emphasis on noneconomic factors (social values, social advancement, equality, individual freedom) and their interactions with labor, capital, and technology. People are now conceptualized as the agents of change, and they in turn must be convinced of the need for change. This new approach implies a need for a review of the role of mass communication in development. A central question is whether development makes possible mass communication development or do improved mass communication facilities--and the resulting increase in the flow of information--make possible economic and social development. Although there have undoubtedly been incidents in which self-serving politicians have used mass communication to oppress the masses, the mass media has the potential to be a powerful force in the education of the society, the sharing of consciousness, the creation of nationhood, and the promotion of socioeconomic development. Mass communication is, for example, vital in the development approach that accords importance to self-sufficiency at the village level. The mass media can be used in such cases to transmit information of a background nature to a group or community about their expressed needs and to disseminate innovations that may need these needs. In the final analysis, mass media's role in development depends on the media's messages reaching the target audiences. This underscores the importance of analyzing in advance who will be the recipients of a mass media campaign and encouraging community involvement in communications planning.

Development of an automated on-line pepsin digestion-liquid chromatography-tandem mass spectrometry configuration for the rapid analysis of protein adducts of chemical warfare agents.

PubMed

Carol-Visser, Jeroen; van der Schans, Marcel; Fidder, Alex; Hulst, Albert G; van Baar, Ben L M; Irth, Hubertus; Noort, Daan

2008-07-01

Rapid monitoring and retrospective verification are key issues in protection against and non-proliferation of chemical warfare agents (CWA). Such monitoring and verification are adequately accomplished by the analysis of persistent protein adducts of these agents. Liquid chromatography-mass spectrometry (LC-MS) is the tool of choice in the analysis of such protein adducts, but the overall experimental procedure is quite elaborate. Therefore, an automated on-line pepsin digestion-LC-MS configuration has been developed for the rapid determination of CWA protein adducts. The utility of this configuration is demonstrated by the analysis of specific adducts of sarin and sulfur mustard to human butyryl cholinesterase and human serum albumin, respectively.

The evaluation of tissue mass loss in the incision line of prostate with benign hyperplasia performed using holmium laser and cutting electrode

PubMed Central

Szewczyk, Mariusz; Jesionek–Kupnicka, Dorota; Lipinski, Piotr; Różański, Waldemar

2014-01-01

Introduction The aim of this study is to compare the changes in the incision line of prostatic adenoma using a monopolar cutting electrode and holmium laser, as well as the assessment of associated tissue mass and volume loss of benign prostatic hyperplasia (BPH). Material and methods The material used in this study consisted of 74 preparations of prostatic adenoma obtained via open retropubic adenomectomy, with an average volume of 120.7 ml. The material obtained cut in vitro before fixation in formaldehyde. One lobe was cut using holmium laser, the other using a monopolar cutting electrode. After the incision was made, tissue mass and volume loss were evaluated. Thermocoagulation changes in the incision line were examinedunder light microscope. Results In the case of the holmium laser incision, the average tissue mass loss was 1.73 g, tissue volume loss 3.57 ml and the depth of thermocoagulation was 1.17 mm. When the monopolar cutting electrode was used average tissue mass loss was 0.807 g, tissue volume loss 2.48 ml and the depth of thermocoagulation was 0.19 mm. Conclusions Where holmium laser was used, it was observed that the layer of tissue with thermocoagulation changes was deeper than in the case of the monopolar cutting electrode. Moreover, it was noticed that holmium laser caused bigger tissue mass and volume loss than the cutting electrode. PMID:25247088

The evaluation of tissue mass loss in the incision line of prostate with benign hyperplasia performed using holmium laser and cutting electrode.

PubMed

Szewczyk, Mariusz; Jesionek-Kupnicka, Dorota; Lipiński, Marek Ireneusz; Lipinski, Piotr; Różański, Waldemar

2014-01-01

The aim of this study is to compare the changes in the incision line of prostatic adenoma using a monopolar cutting electrode and holmium laser, as well as the assessment of associated tissue mass and volume loss of benign prostatic hyperplasia (BPH). The material used in this study consisted of 74 preparations of prostatic adenoma obtained via open retropubic adenomectomy, with an average volume of 120.7 ml. The material obtained cut in vitro before fixation in formaldehyde. One lobe was cut using holmium laser, the other using a monopolar cutting electrode. After the incision was made, tissue mass and volume loss were evaluated. Thermocoagulation changes in the incision line were examinedunder light microscope. In the case of the holmium laser incision, the average tissue mass loss was 1.73 g, tissue volume loss 3.57 ml and the depth of thermocoagulation was 1.17 mm. When the monopolar cutting electrode was used average tissue mass loss was 0.807 g, tissue volume loss 2.48 ml and the depth of thermocoagulation was 0.19 mm. Where holmium laser was used, it was observed that the layer of tissue with thermocoagulation changes was deeper than in the case of the monopolar cutting electrode. Moreover, it was noticed that holmium laser caused bigger tissue mass and volume loss than the cutting electrode.

An on-line high-performance liquid chromatography-diode-array detector-electrospray ionization-ion-trap-time-of-flight-mass spectrometry-total antioxidant capacity detection system applying two antioxidant methods for activity evaluation of the edible flowers from Prunus mume.

PubMed

Zhang, Xiaoxia; Lin, Zongtao; Fang, Jinggui; Liu, Meixian; Niu, Yanyan; Chen, Shizhong; Wang, Hong

2015-10-02

An on-line high-performance liquid chromatography-diode-array detector-electrospray ionization-ion-trap-time-of-flight-mass spectrometry-total antioxidant capacity detection (HPLC-DAD-ESI-IT-TOF-MS-TACD) system was created for identification and evaluation of antioxidants in Prunus (P.) mume flowers. Applying this system, the HPLC fingerprint, ultraviolet (UV) spectra, mass fragmentations, active profiles against 1,1-diphenylpicryl-2-hydrazyl radical (DPPH•) scavenging activity and ferric reducing antioxidant power (FRAP) of each complex sample were obtained simultaneously after one injection. Synchronous structure identification and activities screening of complex samples were thus accomplished. In this study, 78 compounds were identified from P. mume flowers by their chromatographic behaviors, UV spectra and MS data with the assistance of standard compounds and literature reports. The DPPH and FRAP activity of 24 samples (23 different P. mume varieties and 1 related herbal medicine) were then quantified by their detailed activity profiles from the on-line system, and by the total activity of each sample extract from off-line 96-well plate method. As a result, 21 and 32 compounds in the on-line system showed anti-oxidative effects against DPPH and FRAP, respectively. The established on-line system is efficient, sensitive and reliable to tell the DPPH and FRAP antioxidant activities of individual compound in complex samples, and therefore would be a useful and promising technique for antioxidant screening from different food and medicinal matrices. Copyright © 2015 Elsevier B.V. All rights reserved.

Killing effect of TNF-mediated by conditionally replicating adenovirus on esophageal cancer and lung cancer cell lines.

PubMed

Jiang, Yue-Quan; Zhang, Zhi; Cai, Hua-Rong; Zhou, Hong

2015-01-01

The killing effect of TNF mediated by conditionally replicating adenovirus SG502 on human cancer cell lines was assessed by in vivo and in vitro experiments. The recombinant adenovirus SG502-TNF was used to infect human lung cancer cell line A549 and human esophageal cancer cell line TE-1. The expression of the exogenous gene and its inhibitory effect on the tumor cell lines were thus detected. Tumor transplantation experiment was performed in mice with the purpose of assessing the inhibitory effect of the adenovirus on tumor cells and tumor formation. The targeting of the adenovirus and the mechanism of tumor inhibition were discussed by in vivo imaging technology, HE staining and TUNEL assay. Recombinant adenovirus SG502-TNF targeted the tumor cells specifically with stable expression of TNF, which produced a killing effect on tumor cells by regulating the apoptotic signaling pathway. Recombinant adenovirus SG502-TNF possessed significant killing effect on TE-1 cells either in vivo or in vitro. This finding demonstrated the potential clinical application of adenovirus SG502.

Correcting C IV-based virial black hole masses

NASA Astrophysics Data System (ADS)

Coatman, Liam; Hewett, Paul C.; Banerji, Manda; Richards, Gordon T.; Hennawi, Joseph F.; Prochaska, J. Xavier

2017-02-01

The C IVλλ1498,1501 broad emission line is visible in optical spectra to redshifts exceeding z ˜ 5. C IV has long been known to exhibit significant displacements to the blue and these `blueshifts' almost certainly signal the presence of strong outflows. As a consequence, single-epoch virial black hole (BH) mass estimates derived from C IV velocity widths are known to be systematically biased compared to masses from the hydrogen Balmer lines. Using a large sample of 230 high-luminosity (LBol = 1045.5-1048 erg s-1), redshift 1.5 < z < 4.0 quasars with both C IV and Balmer line spectra, we have quantified the bias in C IV BH masses as a function of the C IV blueshift. C IV BH masses are shown to be a factor of 5 larger than the corresponding Balmer-line masses at C IV blueshifts of 3000 km s-1and are overestimated by almost an order of magnitude at the most extreme blueshifts, ≳5000 km s-1. Using the monotonically increasing relationship between the C IV blueshift and the mass ratio BH(C IV)/BH(Hα), we derive an empirical correction to all C IV BH masses. The scatter between the corrected C IV masses and the Balmer masses is 0.24 dex at low C IV blueshifts (˜0 km s-1) and just 0.10 dex at high blueshifts (˜3000 km s-1), compared to 0.40 dex before the correction. The correction depends only on the C IV line properties - i.e. full width at half-maximum and blueshift - and can therefore be applied to all quasars where C IV emission line properties have been measured, enabling the derivation of unbiased virial BH-mass estimates for the majority of high-luminosity, high-redshift, spectroscopically confirmed quasars in the literature.

Combination of atomic force microscopy and mass spectrometry for the detection of target protein in the serum samples of children with autism spectrum disorders

NASA Astrophysics Data System (ADS)

Kaysheva, A. L.; Pleshakova, T. O.; Kopylov, A. T.; Shumov, I. D.; Iourov, I. Y.; Vorsanova, S. G.; Yurov, Y. B.; Ziborov, V. S.; Archakov, A. I.; Ivanov, Y. D.

2017-10-01

Possibility of detection of target proteins associated with development of autistic disorders in children with use of combined atomic force microscopy and mass spectrometry (AFM/MS) method is demonstrated. The proposed method is based on the combination of affine enrichment of proteins from biological samples and visualization of these proteins by AFM and MS analysis with quantitative detection of target proteins.

Mutational analysis of genes coding for cell surface proteins in colorectal cancer cell lines reveal novel altered pathways, druggable mutations and mutated epitopes for targeted therapy

PubMed Central

Correa, Bruna R.; Bettoni, Fabiana; Koyama, Fernanda C.; Navarro, Fabio C.P.; Perez, Rodrigo O.; Mariadason, John; Sieber, Oliver M.; Strausberg, Robert L.; Simpson, Andrew J.G.; Jardim, Denis L.F.; Reis, Luiz Fernando L.; Parmigiani, Raphael B.; Galante, Pedro A.F.; Camargo, Anamaria A.

2014-01-01

We carried out a mutational analysis of 3,594 genes coding for cell surface proteins (Surfaceome) in 23 colorectal cancer cell lines, searching for new altered pathways, druggable mutations and mutated epitopes for targeted therapy in colorectal cancer. A total of 3,944 somatic non-synonymous substitutions and 595 InDels, occurring in 2,061 (57%) Surfaceome genes were catalogued. We identified 48 genes not previously described as mutated in colorectal tumors in the TCGA database, including genes that are mutated and expressed in >10% of the cell lines (SEMA4C, FGFRL1, PKD1, FAM38A, WDR81, TMEM136, SLC36A1, SLC26A6, IGFLR1). Analysis of these genes uncovered important roles for FGF and SEMA4 signaling in colorectal cancer with possible therapeutic implications. We also found that cell lines express on average 11 druggable mutations, including frequent mutations (>20%) in the receptor tyrosine kinases AXL and EPHA2, which have not been previously considered as potential targets for colorectal cancer. Finally, we identified 82 cell surface mutated epitopes, however expression of only 30% of these epitopes was detected in our cell lines. Notwithstanding, 92% of these epitopes were expressed in cell lines with the mutator phenotype, opening new venues for the use of “general” immune checkpoint drugs in this subset of patients. PMID:25193853

Analysis of phenolic compounds from different morphological parts of Helichrysum devium by liquid chromatography with on-line UV and electrospray ionization mass spectrometric detection.

PubMed

Gouveia, Sandra C; Castilho, Paula C

2009-12-01

A simple and rapid method has been used for the screening and identification of the main phenolic compounds from Helichrysum devium using high-performance liquid chromatography with on-line UV and electrospray ionization mass spectrometric detection (LC-DAD/ESI-MS(n)). The total aerial parts and different morphological parts of the plant, namely leaves, flowers and stems, were analyzed separately. A total of 34 compounds present in the methanolic extract from Helichrysum devium were identified or tentatively characterized based on their UV and mass spectra and retention times. Three of these compounds were positively identified by comparison with reference standards. The phenolic compounds included derivatives of quinic acid, O-glycosylated flavonoids, a caffeic acid derivative and a protocatechuic acid derivative. The characteristic loss of 206 Da from malonylcaffeoyl quinic acid was used to confirm the malonyl linkage to the caffeoyl group. This contribution presents one of the first reports on the analysis of phenolic compounds from Helichrysum devium using LC-DAD/ESI-MS(n) and highlights the prominence of quinic acid derivatives as the main group of phenolic compounds present in these extracts. We also provide evidence that the methanolic extract from the flowers was significantly more complex when compared to that of other morphological parts. Copyright 2009 John Wiley & Sons, Ltd.

Oxidative and inert pyrolysis on-line coupled to gas chromatography with mass spectrometric detection: On the pyrolysis products of tobacco additives.

PubMed

Paschke, Meike; Hutzler, Christoph; Henkler, Frank; Luch, Andreas

2016-11-01

According to European legislation, tobacco additives may not increase the toxicity or the addictive potency of the product, but there is an ongoing debate on how to reliably characterize and measure such properties. Further, too little is known on pyrolysis patterns of tobacco additives to assume that no additional toxicological risks need to be suspected. An on-line pyrolysis technique was used and coupled to gas chromatography-mass spectrometry (GC/MS) to identify the pattern of chemical species formed upon thermal decomposition of 19 different tobacco additives like raw cane sugar, licorice or cocoa. To simulate the combustion of a cigarette it was necessary to perform pyrolysis at inert conditions as well as under oxygen supply. All individual additives were pyrolyzed under inert or oxidative conditions at 350, 700 and 1000°C, respectively, and the formation of different toxicants was monitored. We observed the generation of vinyl acrylate, fumaronitrile, methacrylic anhydride, isobutyric anhydride and 3-buten-2-ol exclusively during pyrolysis of tobacco additives. According to the literature, these toxicants so far remained undetectable in tobacco or tobacco smoke. Further, the formation of 20 selected polycyclic aromatic hydrocarbons (PAHs) with molecular weights of up to 278Da was monitored during pyrolysis of cocoa in a semi-quantitative approach. It was shown that the adding of cocoa to tobacco had no influence on the relative amounts of the PAHs formed. Copyright © 2016 Elsevier GmbH. All rights reserved.

Muscle mass and physical recovery in ICU: innovations for targeting of nutrition and exercise.

PubMed

Wischmeyer, Paul E; Puthucheary, Zudin; San Millán, Iñigo; Butz, Daniel; Grocott, Michael P W

2017-08-01

We have significantly improved hospital mortality from sepsis and critical illness in last 10 years; however, over this same period we have tripled the number of 'ICU survivors' going to rehabilitation. Furthermore, as up to half the deaths in the first year following ICU admission occur post-ICU discharge, it is unclear how many of these patients ever returned home or a meaningful quality of life. For those who do survive, recent data reveals many 'ICU survivors' will suffer significant functional impairment or post-ICU syndrome (PICS). Thus, new innovative metabolic and exercise interventions to address PICS are urgently needed. These should focus on optimal nutrition and lean body mass (LBM) assessment, targeted nutrition delivery, anabolic/anticatabolic strategies, and utilization of personalized exercise intervention techniques, such as utilized by elite athletes to optimize preparation and recovery from critical care. New data for novel LBM analysis technique such as computerized tomography scan and ultrasound analysis of LBM are available showing objective measures of LBM now becoming more practical for predicting metabolic reserve and effectiveness of nutrition/exercise interventions. 13C-Breath testing is a novel technique under study to predict infection earlier and predict over-feeding and under-feeding to target nutrition delivery. New technologies utilized routinely by athletes such as muscle glycogen ultrasound also show promise. Finally, the role of personalized cardiopulmonary exercise testing to target preoperative exercise optimization and post-ICU recovery are becoming reality. New innovative techniques are demonstrating promise to target recovery from PICS utilizing a combination of objective LBM and metabolic assessment, targeted nutrition interventions, personalized exercise interventions for prehabilitation and post-ICU recovery. These interventions should provide hope that we will soon begin to create more 'survivors' and fewer victim's post

Circumstellar radio molecular lines

NASA Technical Reports Server (NTRS)

NGUYEN-QUANG-RIEU

1987-01-01

Radio molecular lines appear to be useful probes into the stellar environment. Silicon oxide masers provide information on the physical conditions in the immediate vicinity of the stellar photosphere. Valuable information on the physics operating in the envelope of IRC + 10216 was recently obtained by high sensitivity observations and detailed theoretical analyses. Infrared speckle interferometry in the molecular lines and in the continuum is helpful in the investigation of the inner region of the envelope. These techniques are discussed in terms of late-type star mass loss.

Copernicus ultraviolet observations of mass-loss effects in O and B stars

NASA Technical Reports Server (NTRS)

Snow, T. P., Jr.; Morton, D. C.

1976-01-01

Far-UV spectra of 47 O, B, and A stars obtained with the Copernicus satellite are examined for P Cygni profiles. For all 40 stars with displaced absorption lines, values are given for the velocities of the short-wavelength edge, the line center, and the emission peak (if present). Parts of the spectra of 42 stars are reproduced, evidence for mass motions in ground-based spectra is discussed, and the best available data are summarized on the wavelengths and oscillator strengths of most lines likely to show mass-loss effects in either visual or UV spectra. The main conclusions are that: (1) the far-UV transitions, especially resonance lines, show that mass flow is present over a much wider group of stars than revealed by visible data on subordinate lines; (2) most of the line shifts imply mass motion away from the stars; (3) mass flow occurs in all but one star brighter than a bolometric magnitude of -6.0; and (4) the observed terminal velocities generally exhibit no significant correlation with temperature, luminosity, gravity, rotational velocity, or line strength.

Epidermal growth factor receptor (EGFR) density may not be the only determinant for the efficacy of EGFR-targeted photoimmunotherapy in human head and neck cancer cell lines.

PubMed

Peng, Wei; de Bruijn, Henriette S; Farrell, Eric; Sioud, Mouldy; Mashayekhi, Vida; Oliveira, Sabrina; van Dam, Go M; Roodenburg, Jan L N; Witjes, Max J H; Robinson, Dominic J

2018-05-19

The aim of this study was to investigate the effects of targeted photoimmunotherapy (PIT) in vitro on cell lines with various expression levels of epidermal growth factor receptor (EGFR) using an anti-EGFR targeted conjugate composed of Cetuximab and IR700DX, phthalocyanine dye. Relative EGFR density and cell binding assay was conducted in three human head & neck cancer cell lines (scc-U2, scc-U8, and OSC19) and one reference cell line A431. After incubation with the conjugate for 1 or 24 hours, cellular uptake and localization were investigated by confocal laser scanning microscopy and quantified by image analysis. Cell survival was determined using the MTS assay and alamarBlue assay after PIT with a 690 nm laser to a dose of 7 J.cm -2 (at 5 mW.cm -2 ). The mode of cell death was examined with flow cytometry using apoptosis/necrosis staining by Annexin V/propidium iodide, together with immunoblots of anti-apoptotic Bcl-2 family proteins Bcl-2 and Bcl-xL. A431 cells had the highest EGFR density followed by OSC19, and then scc-U2 and scc-U8. The conjugates were localized both on the surface and in the cytosol of the cells after 1- and 24-hour incubation. After 24-hour incubation the granular pattern was more pronounced and in a similar pattern of a lysosomal probe, suggesting that the uptake of conjugates by cells was via receptor-mediated endocytosis. The results obtained from the quantitative imaging analysis correlate with the level of EGFR expression. Targeted PIT killed scc-U8 and A431 cells efficiently; while scc-U2 and OSC19 were less sensitive to this treatment, despite having similar EGFR density, uptake and localization pattern. Scc-U2 cells showed less apoptotic cell dealth than in A431 after 24-hour targeted PIT. Immunoblots showed significantly higher expression of anti-apoptotic Bcl-2 and Bcl-xL proteins in scc-U2 cell lines compared to scc-U8. Our study suggests that the effectiveness of EGFR targeted PIT is not only dependent upon EGFR density

2MASS J00423991+3017515: An AGN On The Run?

NASA Astrophysics Data System (ADS)

Hogg, James

2016-09-01

We have discovered a peculiar AGN, 2MASS J00423991+3017515, in a local (z=0.14), disturbed galaxy whose optical spectrum has multiple broad lines that are consistently offset from the narrow line emission and host galaxy absorption by 1530 km/s. The morphology of the host galaxy and spectral properties thus suggest this AGN may be a recoiling supermassive black hole (SMBH). We propose high-resolution X-ray imaging and spectral follow-ups with the ACIS camera on Chandra to determine if the source of the kinematically-offset broad line emission is also spatially offset from the nucleus of the host galaxy. If a single, spatially offset AGN is detected, this source will be strongest candidate for a recoiling AGN candidate discovered to date.

Effects of target shape and impact speed on the outcome of catastrophic disruptions

NASA Astrophysics Data System (ADS)

Campo~Bagatin, A.; Durda, D.; Alemañ, R.; Flynn, G.; Strait, M.; Clayton, A.; Patmore, E.

2014-07-01

Because of the propensity of previous laboratory investigations to focus on idealized spherical targets, there is a bit of ambiguity in decoupling the relative importance/influence of low speed or spherical shape in producing the 'onion shell' fragment shape outcomes found in impacts into spherical targets [1,2]. If due primarily to impact speed/energy density as suggested by [3], this could play an important role in main-belt impacts due to the presence of non-spherical targets and non-negligible probability of low-speed (i.e., below about 3-4 km/s, subsonic in rock) impacts [4]. Also, [5] and [6] suggested that the shape of targets may affect the outcome of shattering processes, both in terms of fragment shape and mass distribution. To examine explicitly the effects of target shape in impact outcomes, we chose to conduct impact experiments on both spherical and naturally-occurring irregularly-shaped basalt targets. We impacted a total of six targets (two spheres and four irregular targets). We focused on shots with impact speeds in the ˜4 to 6 km/s range by 3/16th-inch diameter Al-sphere projectiles fired at the NASA AVGR. Following each shot, the debris were recovered (>95 %) and large fragments (>0.20 g) were individually weighed, allowing us to carefully measure the mass-frequency distribution from each impact experiment. The 36 largest fragments of each shot were photographed and their largest axes accurately measured by the program ''ImageJ''. Their shortest axes were measured by means of a digital caliber. High-speed video of each impact was obtained to aid interpretation of the fragmentation mode of the targets. Images clearly show that shell-like fragments can be produced in shattering events not in the target's surface. Instead, those fragments may form around the core, well inside the target structure, independently on the target shape itself. This is a feature not reported to date. In order to understand what the bulk macro-porosity of a non

Clustering Properties of Emission Line Selected Galaxies over the past 12.5 Gyrs

NASA Astrophysics Data System (ADS)

Khostovan, Ali Ahmad; Sobral, David; Mobasher, Bahram; Best, Philip N.; Smail, Ian; Matthee, Jorryt; Darvish, Behnam; Nayyeri, Hooshang; Hemmati, Shoubaneh; Stott, John P.

2018-01-01

In this talk, I will present my latest results on the clustering and dark matter halo (DMH) mass properties of ~7000 narrowband-selected [OIII] and [OII] emitters. I will briefly describe the past work that has been done with our samples (e.g., luminosity functions, evolution of equivalent widths) as motivation of using [OIII] and [OII] emitters to study clustering/halo properties. My talk will focus on our findings regarding the line luminosity and stellar mass dependencies with DMH mass. We find strongly increasing and redshift-independent trends between line luminosity and DMH mass with evidence for a shallower slope at the bright end consistent with halo masses of ~ 1012.5-13 M⊙. Similar, but weaker, trends between stellar mass and halo mass have also been found. We investigate the inter-dependencies of these trends on halo mass and find that the correlation with line luminosity is stronger than with stellar mass. This suggest that active galaxies may be connected with their host DMHs simply based on their emission line luminosity. If time permits, I will briefly present our most recent results using our sample of ~4000 Lyα emitters, where we find similar trends to that seen with the [OIII] and [OII] samples, as well as previous Hα measurements, which suggests galaxies selected based on emission lines may be tracing the same subpopulation of star forming galaxies. I will conclude my talk with an interpretation of this connection and suggest that the shallower slope seen for the brightest emitters is evidence for a transitional halo mass as suggested in models where quenching mechanisms truncate star formation activity and reduce the fraction of star forming galaxies with increasing halo mass.

Isolation of 163Ho from dysprosium target material by HPLC for neutrino mass measurements

DOE PAGES

Mocko, Veronika; Taylor, Wayne  A.; Nortier, Francois M.; ...

2015-04-29

The rare earth isotope 163Ho is of interest for neutrino mass measurements. This report describes the isolation of 163Ho from a proton-irradiated dysprosium target and its purification. A Dy metal target was irradiated with 16 MeV protons for 10 h. After target dissolution, 163Ho was separated from the bulk Dy via cation-exchange high performance liquid chromatography using 70 mmol dm –3 α-hydroxyisobutyric acid as the mobile phase. Subsequent purification of the collected Ho fraction was performed to remove the α-hydroxyisobutyrate chelating agent and to concentrate the Ho in a low ionic strength aqueous matrix. The final solution was characterized bymore » MC-ICP-MS to determine the 163Ho/ 165Ho ratio, 163Ho and the residual Dy content. The HPLC purification process resulted in a decontamination factor 1.4E5 for Dy. As a result, the isolated Ho fraction contained 24.8 ±1.3 ng of 163Ho corresponding to holmium recovery of 72 ± 3%.« less

Isolation of 163Ho from dysprosium target material by HPLC for neutrino mass measurements

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

Mocko, Veronika; Taylor, Wayne  A.; Nortier, Francois M.

The rare earth isotope 163Ho is of interest for neutrino mass measurements. This report describes the isolation of 163Ho from a proton-irradiated dysprosium target and its purification. A Dy metal target was irradiated with 16 MeV protons for 10 h. After target dissolution, 163Ho was separated from the bulk Dy via cation-exchange high performance liquid chromatography using 70 mmol dm –3 α-hydroxyisobutyric acid as the mobile phase. Subsequent purification of the collected Ho fraction was performed to remove the α-hydroxyisobutyrate chelating agent and to concentrate the Ho in a low ionic strength aqueous matrix. The final solution was characterized bymore » MC-ICP-MS to determine the 163Ho/ 165Ho ratio, 163Ho and the residual Dy content. The HPLC purification process resulted in a decontamination factor 1.4E5 for Dy. As a result, the isolated Ho fraction contained 24.8 ±1.3 ng of 163Ho corresponding to holmium recovery of 72 ± 3%.« less

Target CLAB Zero: A national improvement collaborative to reduce central line-associated bacteraemia in New Zealand intensive care units.

PubMed

Gray, Jonathon; Proudfoot, Suzanne; Power, Maxine; Bennett, Brandon; Wells, Sue; Seddon, Mary

2015-09-04

Central line-associated bacteraemia (CLAB) is a preventable cause of patient morbidity and mortality in intensive care units. Target CLAB Zero was a national campaign that ran from October 2011 to March 2013 across all New Zealand ICUs (intensive care units). The campaign aimed to reduce the national CLAB rate to less than one incident per 1,000 line days and to establish a national measurement system for CLAB. We used Institute for Healthcare Improvement (IHI) Breakthrough Series methodology to structure the campaign. IHI bundles of care for catheter insertion and maintenance were implemented across 25 New Zealand ICUs. We collected monthly data on line days, CLAB infections and compliance with the bundles. Data were analysed using run charts. The rate of CLAB per 1,000 line days fell from 3.32 at baseline to an average of 0.28 between April 2012 and March 2013. In the final 3-month period, January to March 2013, average insertion bundle compliance was 80% and average maintenance bundle compliance was 75%. All ICUs participated in the collaborative. Over 90% of those invited attended all three national learning sessions and bi-monthly regional learning sessions. National collaboratives can effect improvement and shared learning in New Zealand. International evidence combined with New Zealand experience, a supportive methodology, partnership, clinical respect and an effective communication plan were keys to successful engagement.

AAVS1-Targeted Plasmid Integration in AAV Producer Cell Lines.

PubMed

Luo, Yuxia; Frederick, Amy; Martin, John M; Scaria, Abraham; Cheng, Seng H; Armentano, Donna; Wadsworth, Samuel C; Vincent, Karen A

2017-06-01

Adeno-associated virus (AAV) producer cell lines are created via transfection of HeLaS3 cells with a single plasmid containing three components (the vector sequence, the AAV rep and cap genes, and a selectable marker gene). As this plasmid contains both the cis (Rep binding sites) and trans (Rep protein encoded by the rep gene) elements required for site-specific integration, it was predicted that plasmid integration might occur within the AAVS1 locus on human chromosome 19 (chr19). The objective of this study was to investigate whether integration in AAVS1 might be correlated with vector yield. Plasmid integration sites within several independent cell lines were assessed via Southern, fluorescence in situ hybridization (FISH) and PCR analyses. In the Southern analyses, the presence of fragments detected by both rep- and AAVS1-specific probes suggested that for several mid- and high-producing lines, plasmid DNA had integrated into the AAVS1 locus. Analysis with puroR and AAVS1-specific probes suggested that integration in AAVS1 was a more widespread phenomenon. High-producing AAV2-secreted alkaline phosphatase (SEAP) lines (masterwell 82 [MW82] and MW278) were evaluated via FISH using probes specific for the plasmid, AAVS1, and a chr19 marker. FISH analysis detected two plasmid integration sites in MW278 (neither in AAVS1), while a total of three sites were identified in MW82 (two in AAVS1). An inverse PCR assay confirmed integration within AAVS1 for several mid- and high-producing lines. In summary, the FISH, Southern, and PCR data provide evidence of site-specific integration of the plasmid within AAVS1 in several AAV producer cell lines. The data also suggest that integration in AAVS1 is a general phenomenon that is not necessarily restricted to high producers. The results also suggest that plasmid integration within the AAVS1 locus is not an absolute requirement for a high vector yield.

Constraints on the neutrino parameters by future cosmological 21 cm line and precise CMB polarization observations

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

Oyama, Yoshihiko; Kohri, Kazunori; Hazumi, Masashi, E-mail: oyamayo@icrr.u-tokyo.ac.jp, E-mail: kohri@post.kek.jp, E-mail: masashi.hazumi@kek.jp

2016-02-01

Observations of the 21 cm line radiation coming from the epoch of reionization have a great capacity to study the cosmological growth of the Universe. Besides, CMB polarization produced by gravitational lensing has a large amount of information about the growth of matter fluctuations at late time. In this paper, we investigate their sensitivities to the impact of neutrino property on the growth of density fluctuations, such as the total neutrino mass, the effective number of neutrino species (extra radiation), and the neutrino mass hierarchy. We show that by combining a precise CMB polarization observation such as Simons Array withmore » a 21 cm line observation such as Square kilometer Array (SKA) phase 1 and a baryon acoustic oscillation observation (Dark Energy Spectroscopic Instrument:DESI) we can measure effects of non-zero neutrino mass on the growth of density fluctuation if the total neutrino mass is larger than 0.1 eV. Additionally, the combinations can strongly improve errors of the bounds on the effective number of neutrino species σ (N{sub ν}) ∼ 0.06−0.09 at 95 % C.L.. Finally, by using SKA phase 2, we can determine the neutrino mass hierarchy at 95 % C.L. if the total neutrino mass is similar to or smaller than 0.1 eV.« less

Organotin speciation in environmental matrices by automated on-line hydride generation-programmed temperature vaporization-capillary gas chromatography-mass spectrometry detection.

PubMed

Serra, H; Nogueira, J M F

2005-11-11

In the present contribution, a new automated on-line hydride generation methodology was developed for dibutyltin and tributyltin speciation at the trace level, using a programmable temperature-vaporizing inlet followed by capillary gas chromatography coupled to mass spectrometry in the selected ion-monitoring mode acquisition (PTV-GC/MS(SIM)). The methodology involves a sequence defined by two running methods, the first one configured for hydride generation with sodium tetrahydroborate as derivatising agent and the second configured for speciation purposes, using a conventional autosampler and data acquisition controlled by the instrument's software. From the method-development experiments, it had been established that injector configuration has a great effect on the speciation of the actual methodology, particularly, the initial inlet temperature (-20 degrees C; He: 150 ml/min), injection volume (2 microl) and solvent characteristics using the solvent venting mode. Under optimized conditions, a remarkable instrumental performance including very good precision (RSD < 4%), excellent linear dynamic range (up to 50 microg/ml) and limits of detection of 0.12 microg/ml and 9 ng/ml, were obtained for dibutyltin and tributyltin, respectively. The feasibility of the present methodology was validated through assays upon in-house spiked water (2 ng/ml) and a certified reference sediment matrix (Community Bureau of Reference, CRM 462, Nr. 330 dibutyltin: 68+/-12 ng/g; tributyltin: 54+/-15 ng/g on dry mass basis), using liquid-liquid extraction (LLE) and solid-phase extraction (SPE) sample enrichment and multiple injections (2 x 5 microl) for sensitivity enhancement. The methodology evidenced high reproducibility, is easy to work-up, sensitive and showed to be a suitable alternative to replace the currently dedicated analytical systems for organotin speciation in environmental matrices at the trace level.

MDI Exposure for Spray-On Truck Bed Lining.

PubMed

Lofgren, Don J; Walley, Terry L; Peters, Phillip M; Weis, Marty L

2003-10-01

Worker exposure to MDI (methylenediphenyl isocyanate) in the sprayed-on truck bed lining industry was assessed by examining Washington State OSHA inspection files and industrial insurance records. The industry uses MDI to form a protective urethane coating on pick-up truck beds. The lining is applied by a worker using a handheld spray gun with application equipment at temperatures and pressures specified by the urethane supplier. Inspections with MDI sampling were initially identified by searching the agency's laboratory database and were further screened for the targeted process. Data for 13 employers was found and extracted from the inspection records. All were small companies with only 1 to 2 workers exposed to MDI; 10 of the 13 employers had started the bed lining service within the last 4 years. The process was found in truck bed lining specialty shops as well as in other truck-related businesses. Six different urethane products were used with reported MDI monomer concentrations of up to 75 percent along with varying concentrations of MDI pre-polymers and other reactants and solvents. Sampling for MDI by inspectors found 7 worksites with worker exposure in excess of the state and OSHA ceiling limit of 0.200 mg/M(3). Deficiencies in respirator programs and engineering controls for MDI were cited. A review of the industrial insurance records found a total of five MDI-related claims at 4 inspected worksites, two for new-onset asthma. It was concluded that workers in the urethane sprayed-on truck bed lining industry are at an increased risk of developing illnesses associated with isocyanate exposure. Interventions are needed to further assess the hazard as well as motivate and assist franchisers, distributors, and retailers to implement effective engineering controls and respiratory protection programs in this nationally emerging small employer industry.

Targeted High Performance Liquid Chromatography Tandem Mass Spectrometry-based Metabolomics differentiates metabolic syndrome from obesity.

PubMed

Zhong, Fanyi; Xu, Mengyang; Bruno, Richard S; Ballard, Kevin D; Zhu, Jiangjiang

2017-04-01

Both obesity and the metabolic syndrome are risk factors for type 2 diabetes and cardiovascular disease. Identification of novel biomarkers are needed to distinguish metabolic syndrome from equally obese individuals in order to direct them to early interventions that reduce their risk of developing further health problems. We utilized mass spectrometry-based targeted metabolic profiling of 221 metabolites to evaluate the associations between metabolite profiles and established metabolic syndrome criteria (i.e. elevated waist circumference, hypertension, elevated fasting glucose, elevated triglycerides, and low high-density lipoprotein cholesterol) in plasma samples from obese men ( n = 29; BMI = 35.5 ± 5.2 kg/m 2 ) and women ( n = 40; 34.9 ± 6.7 kg/m 2 ), of which 26 met the criteria for metabolic syndrome (17 men and 9 women). Compared to obese individuals without metabolic syndrome, univariate statistical analysis and partial least squares discriminant analysis showed that a specific group of metabolites from multiple metabolic pathways (i.e. purine metabolism, valine, leucine and isoleucine degradation, and tryptophan metabolism) were associated with the presence of metabolic syndrome. Receiver operating characteristic curves generated based on the PLS-DA models showed excellent areas under the curve (0.85 and 0.96, for metabolites only model and enhanced metabolites model, respectively), high specificities (0.86 and 0.93), and good sensitivities (0.71 and 0.91). Moreover, principal component analysis revealed that metabolic profiles can be used to further differentiate metabolic syndrome with 3 versus 4-5 metabolic syndrome criteria. Collectively, these findings support targeted metabolomics approaches to distinguish metabolic syndrome from obesity alone, and to stratify metabolic syndrome status based on the number of criteria met. Impact statement We utilized mass spectrometry-based targeted metabolic profiling of 221 metabolites to

Quantum gravitational collapse as a Dirac particle on the half line

NASA Astrophysics Data System (ADS)

Hassan, Syed Moeez; Husain, Viqar; Ziprick, Jonathan

2018-05-01

We show that the quantum dynamics of a thin spherical shell in general relativity is equivalent to the Coulomb-Dirac equation on the half line. The Hamiltonian has a one-parameter family of self-adjoint extensions with a discrete energy spectrum |E |m , where m is the rest mass of the shell and E is the Arnowitt-Deser-Misner mass. For sufficiently large m , the ground state energy level is negative. This suggests that classical positivity of energy does not survive quantization. The scattering states provide a realization of singularity avoidance. We speculate on the consequences of these results for black hole radiation.

Injector design for liner-on-target gas-puff experiments

NASA Astrophysics Data System (ADS)

Valenzuela, J. C.; Krasheninnikov, I.; Conti, F.; Wessel, F.; Fadeev, V.; Narkis, J.; Ross, M. P.; Rahman, H. U.; Ruskov, E.; Beg, F. N.

2017-11-01

We present the design of a gas-puff injector for liner-on-target experiments. The injector is composed of an annular high atomic number (e.g., Ar and Kr) gas and an on-axis plasma gun that delivers an ionized deuterium target. The annular supersonic nozzle injector has been studied using Computational Fluid Dynamics (CFD) simulations to produce a highly collimated (M > 5), ˜1 cm radius gas profile that satisfies the theoretical requirement for best performance on ˜1-MA current generators. The CFD simulations allowed us to study output density profiles as a function of the nozzle shape, gas pressure, and gas composition. We have performed line-integrated density measurements using a continuous wave (CW) He-Ne laser to characterize the liner gas density. The measurements agree well with the CFD values. We have used a simple snowplow model to study the plasma sheath acceleration in a coaxial plasma gun to help us properly design the target injector.